BC

For the week of April 26, 2004
BioCentury 100 Indicators

Week ended 4/23/04
PRICES VOLUME
TM
VOLUME 12, NUMBER 19
BioCentury
THE BERNSTEIN REPORT
1649.29 up 4%
540.9M shrs up 37% P AGE A1 OF 20
ON
B IOBUSINESS
Regulation
Tag team wrestling

BioCentury This Week
Cover Story
As SEC intensifies its scrutiny of biotech with the help of FDA, there is widespread agreement that companies need to rethink old assumptions that the two agencies can be handled independently. development in response to investor deBy Kathryn Calkins mand. That, in turn, is prompting more & Steve Usdin questions, according to Jeffrey Riedler, diSenior Writers Increased collaboration between FDA rector of SECs corporate finance division, and SEC, fallout from the ImClone Systems who described the agencys activity at a Inc. case, and investor demands for more recent meeting of the Food and Drug Law Institute in Washington. information about Elizabeth Gray, a early-stage drug develpartner at Foley & opment, are contribThe assumption Lardner LLP in Washuting to an intensificaington and a former tion of SECs scrutiny of secrecy at FDA assistant director at of public disclosures by SECs division of enb i o p h a r m a c e u t i c a l has been dashed forcement, told BioCencompanies. Biotech explicitly. tury that initiatives like companies are receiv Alan Goldberg of the FDA-SEC MOU ofing more queries from Goulston & Storrs ten result from several SEC, and the questions forces that together creare far more technical, ate the need for faster, according to attorneys who specialize in handling securities is- more informed enforcement. Complexity in the filings could have been a trigger, and sues for biotech companies. The vigilance includes a more rigorous it could have been one reason for the scrutiny for consistency of statements made FDA-SEC agreement, she said Some securities lawyers suggest there to both FDA and the public, as well as the use of trading suspensions in a handful of are other reasons for SECs increased cases related to allegations of misleading surveillance. John Kamp, an attorney at Wiley Rein & Fielding LLP in Washington, disclosures. As a result, corporate attorneys are told the FDLI meeting that biotech and warning that its no longer possible to deal pharma companies are experiencing the fallout from corporate scandals. He sugwith each regulatory agency separately. In February, the agencies exchanged gested SEC is trying to demonstrate that it memos formalizing a route for FDA offi- is aggressively regulating the biotech seccials to report suspected false and mis- tor in response to the media storm created leading statements from companies to SEC, by the trials of former IMCL CEO Samuel and streamlining SEC access to non-pub- Waksal and especially Martha Stewart. Both Gray and Terri Garland, a seculic information from FDA. But while the increased scrutiny might appear to be the rities litigator and partner at Morrison & direct result of the MOU, senior officials at Foerster LLP in San Francisco, also pointed both agencies say thats just coincidence to the IMCL scandal in 2001-2002 as a probable touchstone for SECs apparent (see ABCs of the FDA-SEC MOU, A4). In part, what appears to be happening is interest in biotech. That scandal, Garland that companies are proactively disclosing noted, was rooted in FDA-sponsor comSee next page more information about early-stage drug
Strategy
BioMarins head start/Page A6 ID BioMedical heading south/Page A7
Product Development
Alteon: More or less/Page A8 Anadys: Five is not a crowd/Page A9
Technology Briefing
Mass Listeria/Page A10
Emerging Company Profile

Cancer trifecta: Hudson; Cougar & Gloucester/Page A11
Washington
CMS rationing wars/Page A13 Patents vs. research/Page A14
Ebb & Flow

MEDIs R&D; IPO queue; earnings week; EPO sales, et al./Page A15 Online this week/Page A10 Stock charts & tables/Page A20 Company index/Page A9
BioEquity Europe Update

Europes clinical bellwethers. Please see announcement following A20.
BioCentury,
Regulation, from previous page
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A2 OF 20
clinical trial, for example, the investing public should know whether or not there FDA and the sponsor has been statistical analysis done and the munications. Gray said that the prosecu- might be more guarded, results of the analysis, Reidler said. We tion history in that case probably revealed would like the company to disclose what a need for better coordination between and the interchange the trial is designed to show, he added. FDA and SEC. It also may have sharpened might be less productive Another area of concern is how comSECs awareness of the inherent complexpanies describe their role in the drug develif meetings were ity of biotech filings. opment process, Reidler noted. We would Garland also noted that the sector like companies to be clear and transparent recorded. enjoyed a huge increase in investment about their role. For example, if a company about three years ago, which is resulting Frank Sasinowski primarily licenses intellectual property, we in projects now coming to fruition in the of Hyman, Phelps would like it to say not that it has filed an industry. Investor complaints to SEC probIND with the FDA, but that its collaborator ably have increased as investment has has filed an IND. grown, which she said also can focus the commissions attention. Reidler also cautioned companies about the way they charWhile there is some disagreement about SECs motivation, acterize clinical trials. SEC might question whether a company is there is widespread agreement that companies need to rethink stretching the truth when it says a trial is Phase I/II, he said. Such old assumptions that interactions with SEC and FDA can be questions would go to the FDA. handled independently. Securities filings and press releases must The bottom line is that companies must be consistent in their be crafted with the expectation that FDA officials with access to communications with FDA, SEC and the public, said John INDs and NDAs may review the documents for accuracy, Manthei, a partner at Latham & Watkins LLP in Washington. If, according to senior SEC officials. And FDA filings, as well as in all the communications to FDA, investigators describe a trial public statements about the interactions with the agency, may be as Phase I, even if it has some efficacy endpoints, dont turn the subject of discussion between FDA and SEC, according to around and call it a Phase I/II trial in a press release, Manthei attorneys at both agencies. advised the FDLI audience.
More, and more detailed, questions

The MOU notwithstanding, SEC has a longstanding policy of routinely querying FDA about statements in securities filings on topics such as the status of a companys NDA, and when it has concerns about press releases or other public statements. FDA has provided technical support for SEC enforcement of federal securities law for years, Coleen Klasmeier, special assistant to the FDA Chief Counsel, said at the FDLI meeting. Typically we assess the accuracy of statements in registration and other securities filings with regard to the status of FDAs review of a product or other issues within our purview. SECs Riedler agreed. The SEC and FDA have been talking to each other and sharing information for many, many years, he noted. This agreement is merely a refinement, a modernization of the procedures that we engage in, in order to share information. We hope it will make the process a lot more efficient. Riedler added that the number of such queries has increased in recent months as companies have included more data about FDA-related topics in prospectuses and other documents. Indeed, companies apparent efforts to be proactive on this score seem to have backfired. Instead of decreasing regulatory scrutiny, Riedler said, the trend to increasingly detailed disclosures has led SEC to question whether drug companies are providing sufficient context to allow investors to make informed decisions. We have concerns with regard to several areas of disclosure that drug companies make. We have noticed of late that drug companies are making more disclosures about the drug development process, particularly the preliminary results of drug trials, he said. There certainly is no requirement under federal securities law that companies disclose preliminary results of drug trials, but if they choose to make those disclosures, we feel they should be in the proper context so investors dont make erroneous conclusions. If a company chooses to disclose interim results from a
A different take
While government attorneys are downplaying the scope and novelty of the SEC-FDA MOU, several attorneys told BioCentury that they do see more coordination between FDA and SEC, saying that they have seen increasing numbers of questions from SEC on biotech filings, and that the questions betray specific knowledge about products and the drug approval process that only FDA possesses. They maintain that the playing field thus has changed perceptibly in recent months. In the last four to five months, there has been a real up-tick in IPOs, Manthei said. The quality, the depth and amount of disclosures going into securities statements are much more than a few years ago. At the same time, comments from the SEC have been significantly better and much more specific, leading industry to wonder if they were formulated by someone at FDA. SEC may be seeing a shift in complexity and detail of filings because the companies going public are more mature, and thus have more advanced products, than those that went public in the past, suggested Alan Mendelson, a partner at Latham & Watkins in Palo Alto. The companies that Mendelson has helped to file IPOs this year Corgentech Inc. (South San Francisco, Calif.), Dynavax Technologies Corp. (DVAX, Berkeley, Calif.) and Renovis Inc. (RNVS, South San Francisco, Calif.) have wanted to include detailed data from their clinical trials. To take a company public, bankers say they want a Phase II or Phase III product and good data, so companies are laying that out, he told BioCentury. The level of company maturity demanded by the market also shows the sophistication of investors now, Mendelson added. Corgentechs CGT003 E2F Decoy is in Phase III testing to prevent peripheral bypass graft failure, DVAXs AIC is in Phase II/III studies in allergy, and RNVSs Ceravive is in Phase III trials
See next page
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A3 OF 20
the FDA-sponsor discussion. I imagine that this could lead to a less robust exIt would be ill-advised change, he said. Part of the dialog in for stroke. meetings permits a work-through of opto disclose less. While questions from SEC are not tions. FDA and the sponsor might be more necessarily burdensome, lawyers say the Laura Berezin of guarded, and the interchange might be increasing frequency of such consultaCooley Godward less productive if meetings were recorded. tions makes it more challenging to meet However sponsors handle meetings and the agencys requirement for explaining other interactions with FDA in the future, the risks of a biotech business to investors in plain English. All they will be aware that even if an SEC liaison isnt in the room, this adds to the rising cost of completing public offerings. securities regulators may be made aware of the content of Laura Berezin, a partner at Cooley Godward LLP in Palo Alto, discussions and documents. What you say now has to be noted that her primary concern is not with FDA reviewing analyzed in terms of both agencies. The assumption of secrecy clients disclosures which she said the agency has done for at FDA has been dashed explicitly. What you say to FDA can some time but with the change in the nature and extent of the travel to the SEC, Alan Goldberg, a director at Goulston & comments she sees from SEC. Specifically, Berezin noted that Storrs in Washington, said at the FDLI meeting. disclosures in SEC filings are required to be complete and written in plain English. Theoretically, these are not mutually exclusive, Berezin Enforcement said. One should be able to disclose information completely to SEC enforcement actions against biotech companies have satisfy SEC while making the disclosure understable to the been on the rise since mid-2003, Garland said. She added, average investor. The reality, she noted, is different. however, that it is too early to judge whether this will translate According to Berezin, SEC staff has begun requiring extensive to a greater cost to biotechs in defending such actions. Garland disclaimer language about the preliminary nature of clinical and Gray also noted an increased interest in the sector by the results, potentially in response to comments from FDA. Berezin Private Plaintiffs Bar, attorneys who bring class action lawsuits. said while companies dont have a problem stating that their Recent securities trading suspensions leveled at small cap results are preliminary, SEC has been asking for the same companies also signal a level of scrutiny by SEC that has not been disclosure information to be repeated every time clinical infor- seen before, Gray noted. In separate cases in April, SEC suspended mation is discussed, making language repetitive, cumbersome trading for 10 days in BioCurex Inc. (BOCX, Richmond, B.C.) and and awkward. Vaso Active Pharmaceuticals Inc. (VAPH, Danvers, Mass.). In both In my view, that absolutely violates the principle of plain cases, SEC referred to statements of questionable accuracy made English, Berezin said. Instead of clarity, were getting more in relation to FDA approval of the companies products and/or boilerplate, which confuses the issue. It doesnt help investors in relation to studies intended to demonstrate efficacy. understand the risks better. BOCX develops cancer detection tests and tools. VAPH She suggested that FDAs zeal for caution and lack of concern develops compounds targeted at the OTC market that are about plain English is producing documents not intended for a formulated with transdermal technology from VAPHs parent Wall Street audience. company, BioChemics Inc. (Danvers, Mass.). SECs response to increased disclosure by biotech companies However, the two suspensions did not necessarily result from is not resulting in improved communication to investors, accord- information provided by FDA. ing to Berezin. In my experience, the filings are not different in In the BOCX case, trading volume spiked to 25.8 million substance now, but there is a heightened concern among shares on April 5 from low background volumes. On the same companies about what to disclose, she said. day, the price of BOCX stock increased more than 400%, to $2.38. On April 8, SEC temporarily suspended trading because of questions regarding the accuracy of assertions by BioCurex FDA relations and by others, in press releases and emails to investors concernSome attorneys also worry that the situation will damage ing, among other things, (1) a study confirming the effectiveness relations between companies and FDA. of its primary product and (2) approval of its main product by To illustrate, Frank Sasinowski, a partner at Hyman, Phelps & the Food and Drug Administration. McNamara PC in Washington, noted that an SEC liaison from In a press release, BOCX said it did not send and was not FDAs chief counsels office sat in on a meeting he attended with a responsible for emails touting its stock. client. Both companies released statements saying they would coopAlthough Sasinowski said that SEC liaisons do not attend all erate with SEC to remedy misinformation. Indeed, on April 19, FDA-sponsor meetings, he now advises his clients to document BOCX released a statement clarifying that its Histo-Recaf carefully any discrepancies between their own meeting minutes cancer detection product has been classified by FDA as a Class and those drawn up separately by FDA. Standard procedure is I device exempt from the premarket notification process. The for each party to write its own minutes of meetings. FDA has not approved the Histo-Recaf product for the diagnoWhile Sasinowski previously had not worried about small sis of cancer, the company said. differences, he now believes clients should send letters about BOCXs stock has changed to the Pink Sheets and resumed them to the agency to create a written record of the differences. trading on Friday, when the stock closed at $1.27, down $0.65 Meetings are recorded on rare occasions, Sasinowski said, from the trading halt. but he does not advocate this approach to solving the problem On April 1, SEC announced suspension of trading in VAPH, of discrepancies in minutes, warning that recording could chill See next page
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A4 OF 20
Tag Team Wrestling
ABCs of the FDA-SEC MOU

By Steve Usdin & Kathryn Calkins Senior Writers The FDA-SEC memorandum of understanding (MOU) primarily involves referrals from FDA of possible criminal misconduct, and is unrelated to routine inquiries from SEC about the truthfulness of corporate filings and press releases. FDA employees have been informed of the appropriate people within the agency to contact if they come upon statements of potential interest to SEC. Those people, in turn, contact FDAs chief counsels office, which decides whether any report should be referred to the SEC. There has been no increase in criminal referrals since the memorandum was signed, according to senior FDA officials. Indeed, according to officials at both agencies, there has been only one referral from FDA since the MOU was exchanged in
February (see BioCentury, Feb. 9). The MOU is an incremental step that is intended to remove some of the red tape that made FDA-SEC communications cumbersome, but it does not reflect a major change in policy, according to Coleen Klasmeier, special assistant to the FDA Chief Counsel. We do not view ourselves, nor should we, as the health SEC, she said. Klasmeier added that the MOU does not modify restrictions on the disclosure of proprietary information. We continue to have great respect for all of the statutory restrictions on the disclosure of non-public information, she said. Training of SEC and FDA staff to better understand food and drug and securities law is another aspect of the MOU. I am particularly looking forward to the mutual training our two
See next page
citing concerns related to (1) FDA approval of certain key products and (2) the regulatory consequences of the future application of their primary product. VAPHs stock was delisted from NASDAQ on April 8 at the companys request. VAPH also ceased marketing its three OTC products, which included one for athletes foot and two for pain relief, according to spokesperson Matt Carter.
The cost
While apparent shifts in SECs attention toward biotech have resulted in incremental increases in the time required to complete SEC filings and thus the costs to companies employing securities lawyers such increases are dwarfed by the impact of Sarbanes-Oxley. The law, passed in 2002 to combat corporate and accounting fraud as a result of the Enron and Arthur Andersen scandals, led to changes in the filing process. According to Mendelson, costs of public offerings generally have risen by one-third to one-half in the last three to five years. Berezin agreed, adding that companies are waiting until later in the SEC comment process to print their prospectuses and go on the road, extending the process and making it more expensive. A few years ago, companies would wait for a single set of SEC comments to come back before printing, but now they frequently wait through the third set of comments to assure themselves that no major changes will require them to reprint their documents.
Whats material
A core problem posed by all of these changes or perceived changes is the definition of what is material. Securities attorneys have differing views on whether the FDASEC relationship will clarify which communications with FDA that companies should consider material. SEC regulations covering what is material have not changed, although last December the commission did release a document advising companies on
how to improve the language in the Managements Discussion and Analysis (MD&A) section of filings (see Online Links, A10). However, Berezin said she thinks clients have heightened concerns about being second-guessed by FDA after the fact as a result of the inter-agency collaboration. Neither she nor Mendelson, however, believes that companies will respond by putting less detail in their prospectuses to avoid detailed questioning from the agencies. It would be illadvised to disclose less, Berezin said. Mendelson agreed, adding that one potential stumbling block for biotechs in terms of adequate disclosure is the big company partner. Big pharma, especially European and Asian partners, does not like to disclose more information than is legally required, and does not need to raise money. Therefore, such companies often are unsympathetic to the disclosure needs of their smaller partners. Former SEC attorney Gray said she believes the SEC-FDA communications will change disclosures, but she does not expect companies to clam up. Her best advice to companies is that any disclosure must be put into the context of your entire development program. As an example, Gray cited a Wells Notice received recently by BioPure Corp. (BPUR, Cambridge, Mass.) (see BioCentury, Jan. 5). A Wells Notice alerts a company that an SEC team is going to recommend an enforcement action to the commission and allows the company time to develop a defense. In this case, Gray said, BPUR had not disclosed that FDA had not agreed to a portion of a proposed clinical trial for its lead product, Hemopure hemoglobin glutamer. Although the trial was under a separate IND from the primary trial and was never initiated, SEC argued that the circumstances affected the larger program in a negative way, Gray said. A BLA for Hemopure is under review by FDA. BPUR said it has cooperated with SEC and is waiting for further information from the agency. Press releases appear to receive the most scrutiny from FDA and SEC, Manthei suggested, so companies should take care to ensure that they are accurate and consistent with information they have communicated to both agencies.
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A5 OF 20
BIOCENTURY
PUBLICATIONS INC .
Main Offices PO Box 1246, San Carlos CA 94070-1246 650-595-5333; Fax: 650-595-5589 Website: www.biocentury.com Newsroom: pressreleases@biocentury.com Chicago: 312-755-0798; Fax: 312-755-0658 Washington D.C.: 202-462-9582; Fax: 202-667-2922
We do not view ourselves, nor should we, as the health SEC.

Coleen Klasmeier of FDA
BioCentury International
Hamburg, Germany: +49 (40)41-35-77-60; Fax: +49 (40)41-35-77-62 Oxford, UK: +44 (0)1865-512155; Fax: +44 (0)1865-311195 Corporate KAREN BERNSTEIN, Ph.D./Chairman & Editor-in-Chief DAVID FLORES/President, CEO & Publisher KRIS HALL/Administrative Assistant Editorial ERIC PIERCE/Senior Editor, News STEVE USDIN/Senior Editor, Washington LUDGER WESS, Ph.D./Senior Editor, Europe KATHRYN CALKINS; KEITH HAAN, Ph.D.; CHRISTOPHER MAGGOS/Senior Writers STEVE EDELSON/News Editor; SHAUN BROWN/News Editor, Europe AIMEE R. DINGWELL; MICHAEL FLANAGAN; SUSAN SCHAEFFER; WALTER YANG/ Staff Writers Information Services JULIA KULIKOVA/Director, Information Services; CHARLEY LU/Editor, ePublishing; CONRAD SEELYE/Manager, Information Services JENNY NICHOLS/Production Manager; JULIANA BALESTRIERI, TRACY CORRAL/ Associate Production Managers Subscriber & Business Services TIM TULLOCH/Senior Director, Subscriber Services; MICHELLE ORTEGA/Subscriber Services Associate; JOSEPHINE ASCIUTTO/Manager, Customer Service; SYLVIA D'HAENENS ZIMMERLI/Marketing Manager; BEN AMIWERO, JARROD KLEIN/ Marketing & Sales Associates; ROSY ROGERS/Senior Director, Conferences & Special Projects; WILLIAM WEYENETH/ Manager, Conferences & Special Projects Business Administration BRENDA GEORG/Business Manager Privacy & Advertising BioCentury does NOT sell or rent its customer information or usage data to third parties. BioCentury does NOT sell advertising in any of its publications. BioCentury is pleased to acknowledge its conference partners and sponsors through promotional announcements in its publications and on its Web site, but such announcements do not constitute paid advertising. Letters & Outside Contributors Letters to the Editor and inquiries about Guest Commentary may be submitted to biocentury@biocentury.com. Outside contributions may be accepted based on timeliness, reader interest, and other criteria established at BioCentury's sole discretion. Outside contributors are subject to editing for space and other factors. Unsolicited manuscripts may not be acknowledged or returned.
Tag Team, from previous page
BioCentury
ON BIOBUSINESS
BioCentury; The Bernstein Report on BioBusiness; The BioCentury 100; and The Clear Route to ROI are trademarks of BIOCENTURY PUBLICATIONS INC. All contents Copyright 2004, BIOCENTURY PUBLICATIONS INC. ALL RIGHTS RESERVED. No part of this publication may be copied, reproduced, retransmitted, disseminated, sold, distributed, published, broadcast, circulated, commercially exploited or used to create derivative works without the written consent of BioCentury. Information provided by this publication is gathered from sources that BioCentury believes are reliable; however, BioCentury does not guarantee the accuracy, completeness, or timeliness of the information, nor does BioCentury make any warranties of any kind regarding the information. The contents of this publication are not intended as investment, business, tax or legal advice, and BioCentury is not responsible for any investment, business, tax or legal opinions cited in the publication.
agencies will do, said Jeffrey Riedler, director of SECs corporate finance division. SEC will train FDA staff in terms of the SEC examination procedures and disclosure regulations, while FDA will train us in what the FDAs requirements are and the FDAs examination process, so we can better understand it and understand drug companies, he said. Joint training and streamlined communications suggest that the MOU is only the starting point, and that the two agencies may begin to collaborate more closely in the future, said John Manthei, a partner at Latham & Watkins LLP in Washington. I cant help but look at what they are doing and think that a year or two from now it will lead to a much greater level of activity by FDA in this area, he said. The identification of inter-agency liaisons, increased training, more sharing of confidential information, and the streamlining of communications under the new inter-agency initiative is likely to lead to greater coordination and involvement in the future. On the other hand, the MOUs creation of formal channels for FDA officials to refer potential violations of securities laws to the SEC is likely to protect companies, according to Frank Sasinowski, a partner with FDA specialty firm Hyman, Phelps & McNamara PC in Washington. Referrals will be vetted by FDA attorneys who are familiar with securities laws. You should be relieved by part of this, he told an audience of biotech executives and attorneys attending a recent meeting in Palo Alto. No rogue reviewer can now go straight to SEC with a statement because of this vetting procedure. But Sasinowski believes that, overall, the new relationship is damaging to company-FDA relations. He suggested sponsors may become more circumspect and formal in communicating with FDA as they try to create a paper trail that avoids potential legal liabilities.
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A6 OF 20
Strategy
BioMarins head start

You cant just mention this once and think that there will be By Aimee Dingwell a common understanding. Staff Writer Thus, he argued, if you dont start going to medical BioMarin Pharmaceutical Inc. has been best known for its focus on enzyme replacement therapies for genetic diseases, geneticists and pediatricians one, two, three years before so it came as a surprise last week when the company said it launch, you are going to stumble when the drug is launched. will refocus to become a pediatrics company and partner out And we cant afford to do that. Indeed, sales have been slow for BMRNs first enzyme its non-pediatric products. The transformation is pegged to BMRNs acquisition of replacement therapy, Aldurazyme laronidase to treat MPS-I, the Ascent Pediatrics Inc. business of Medicis Pharmaceutical even though the drug is sold by an experienced partner, Corp (MRX, Phoenix, Ariz.). The deal provides BMRN with Genzyme (GENZ, Cambridge, Mass.). First quarter sales were two key elements that it sees as essential to reaching profit- $7.3 million. At the end of 2003, GENZ provided 2004 sales guidance of $40-$44 million. ability: immediate and growing reveIn addition to providing a foot in the nues from the sale of Ascents main door at pediatricians offices, Price said product, asthma drug Orapred; and a If you dont start going that acquiring Ascent now hedges some 73-person sales and marketing team. of the risk inherent in timing drug apThe sales force currently calls on to medical geneticists provals. Aryplase has completed Phase about 14,000 of the 25,000-30,000 III testing in MPS-VI and BMRN expects board-certified pediatricians in the U.S. and pediatricians one, to file for approval in the fourth quarter. who have an active practice. BMRN plans two, three years before If you buy a sales force with a to increase that number to about 19,000 profitable, growing product, then if there by the time it launches its Aryplase treat- launch, you are going to ment for mucopolysaccharidosis VI (MPS- stumble when the drug is are delays, it is not the end of the world and it doesnt cost you anything, said VI) within the next 18 months. Price. BMRN says the head start is neces- launched. Assuming Aryplase is approved in sary. Chairman and CEO Fredric Price BioMarins Fredric Price October 2005, Price said, that gives us said that commercializing compounds 18 months to not only educate physifor genetic diseases, particularly those cians, but to get the field force comin children, requires significant groundwork prior to launch not only to educate physicians pletely comfortable with the drug, the diseases, the logistical on how to identify and properly diagnose diseases that issues surrounding treatment. Orapred is a liquid corticosteroid. BMRN expects the typically are very rare, but also to prepare for logistical issues drug to have net sales of about $42 million this year, which related to treatment administration and costs. Unlike more common diseases such as bacterial infec- Price said is more than 50% of the liquid oral prednisolone tions, for which diagnostics are readily available and public market. The company also plans to file this year for regulatory awareness exists, Price said physicians spend little time learning about genetic disorders, and parental knowledge is approval of a non-refrigerated version of the drug, and to launch OraPred 2, a quick-dissolve tablet formulation, in nearly nonexistent. MPS-VI is caused by a deficiency of the N-acetylgalac- 2005. BMRN also plans to launch OraPred in markets outside tosamine 4-sulfate enzyme. For an extremely rare disease like the U.S. by early 2006. BMRN (Novato, Calif.) hopes to eventually use the 66MPS-VI, which affects about 1,100 patients in the western world, timely diagnosis also can be hindered by vague symp- person sales force and 7 regional managers to market its toms. Parents of children with the disease often first notice Phenoptin, an oral form of the enzyme cofactor tetrahydrocloudy eyes, coarse facial features, or a slight sway in the back. biopterin that is in Phase I testing to treat mild to moderate Most patients are diagnosed by age five. Most are treated phenylketonuria (PKU), and Phenylase phenylalanine ammosymptomatically, although some younger patients receive bone nia lyase, which is expected to start clinical trials for severe PKU next year. marrow transplants. PKU is a pediatric disease caused by insufficient quantiOnce diagnosis of a lysosomal storage disorder like MPSVI is made, physicians then must describe the treatment to ties of phenylalanine hydroxylase. It results in a variety of neurological complications, including severe mental retardaparents. Explaining to parents that the treatment is a two to three tion and brain damage, mental illness, seizures and tremors, hour infusion that will need to be administered in a medical and cognitive problems. BMRN plans to out-license its Vibrilase topical enzyme geneticists office, which hopefully is not too far away, and, by the way, is going to cost $150,000 to $200,000 a year therapy for burn deridement. Vibrilase is in Phase Ib trials. BMRN will pay MRX (Phoenix, Ariz.) up to $175 million you can imagine the logistical and emotional effects, said Price. This cant be rectified by an ad in one of the journals. in cash and stock over the next five years for Ascent (see B2).
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A7 OF 20
Strategy
Coming to America
By Michael Flanagan Staff Writer ID Biomedical Corp. has two vaccines in development but has lacked an adequate antigen supply. The company solved that problem last week and positioned itself to enter the U.S. vaccine market by announcing that it would buy the vaccine business of Shire Pharmaceuticals Group plc (LSE:SHP; SHPGY, Basingstoke, U.K.). The deal includes one marketed vaccine, Fluviral, which is an intramuscular influenza prophylactic marketed in Canada, as well as a streptococcal pneumonia vaccine that has finished Phase I testing. ID Biomedical (TSE:IDB; IDBE, Vancouver, B.C.) also gets 10 vaccine candidates that are in or near preclinical development (see IDBs Bigger Pipeline). These will complement IDBs FluInsure, which is an intranasal vaccine in nonpivotal Phase III testing, and its StreptAvax group A streptococcus vaccine, which is in Phase I/II studies. SHPs vaccine business posted a 2003 net operating loss of $21.9 million. But, according to IDB CEO Anthony Holler, it is important to note that while Shires vaccine business as a whole was not profitable, the flu business itself was. Indeed, he said, the most important aspect of the deal is the flexibility the antigen supply allows us with our flu vaccines. We previously had to purchase small amounts of antigen from a number of suppliers. Having our own antigen supply means we dont have to deal with a third party, providing us with the flexibility to negotiate our own marketing and distribution deals. Now, said Holler, our main goal is to bring both Fluviral and FluInsure to market in the U.S. by 2007. If successful, IDB would be the fourth entrant into the U.S. flu vaccine market IDBs bigger pipeline
ID Biomedicals acquisition of Shires vaccine business adds a marketed flu vaccine and a Phase I compound to IDBs two clinical candidates, which are in Phase II and III trials. Product Fluviral (intramuscular) FluInsure (intranasal) StreptAvax Pneumococcal vaccine NA NA NA NA NA Indication Influenza Influenza Group A streptococcus Streptococcus pneumoniae Allergy Plague RSV Group B streptococcus Neisseria meningitidis Status Mkt (Canada) Non-pivotal Ph III Ph II Ph I complete Preclin Preclin Preclin Preclin Preclin Originator SHP IDB IDB SHP IDB IDB IDB SHP SHP
occupied by Aventis SA (AVE, Strasbourg, France); Chiron Corp. (CHIR, Emeryville, Calif.); and partners MedImmune Inc. (MEDI, Gaithersburg, Md.) and Wyeth (WYE, Madison, N.J.). Based in St. Foy, Quebec, SHPs vaccine business generated C$36 million (US$26.7 milion) in 2003 sales, of which C$30 million came from sales of Fluviral, a subunit, nonliving vaccine sold to the Canadian government. SHP, the fifth largest flu vaccine manufacturer, in 2001 contracted with the Canadian government to supply up to C$300 million (US$222.8 million) in flu vaccine over the next several years. IDB expects to sell 7 million doses of Fluviral to the Canadian government this year. Along with SHPs vaccine unit, IDB inherits an agreement worth an estimated C$60 million (US$44.6 million) with Technology Partnerships Canada, a government agency that promotes Canadian technology and will help offset some R&D expenses.
IDB also acquires three research and manufacturing facilities in the U.S. and Canada, as well as some 400 employees, most of whom are involved in manufacturing a significant jump from IDBs headcount of 150. SHP will receive $30 million in cash at closing, plus another $30 million on the first anniversary of closing. The U.K. company also receives rights to acquire 5.4 million IDB shares worth another $60 million. SHP also will provide IDB with a $100 million loan facility, of which Holler said $70 million will be written off, while the remainder will be repaid by a percentage of sales of Fluviral outside Canada and any products resulting from SHPs preclinical pipeline. IDB plans to keep Canadian rights for all of its products, and to find partners for StreptAvax in North America, Europe and Asia. The company also will look to out-license, or possibly co-develop, one or more of its preclinical vaccine candidates.
Its the BioCenturyTM

Authoritative. Globally focused. The leading perspective on the strategic issues essential to the formation, development and sustainability of life science ventures into 2005 and beyond.
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A8 OF 20
Product Development
Getting it right, more or less

By Christopher Maggos However, 210 mg of alagebrium twice daily showed signifiSenior Writer cance on the secondary endpoint of reduction in left ventricular Last year, Alteon Inc.s alagebrium (ALT-711) failed in sepa- mass (p=0.04). In DIAMOND we saw that alagebrium could rate Phase II trials in systolic hypertension and diastolic heart remodel the heart in a matter of months. Usually it takes years, failure. The company is now hypothesizing that the two patient Moch said. As blood pressure increases, the heart changes from populations need different dose levels because alagebrium may a cylindrical volume pump to a spherical pressure pump. If you have two separate mechanisms of action, each of which may be give a blood pressure drug, over the course of years patients can triggered at a different dose. ALT is testing that hypothesis in two get back to a cylindrical volume pump. new Phase II trials. ALT also saw a trend toward improved Alagebrium is an oral thiazolium comleft ventricular diastolic filling in DIApound that breaks advanced glycation MOND, and the compound significantly endproduct (AGE) crosslinks. At all dose Data have been improved quality of life as measured by levels, ALT thinks alagebrium may be actthe Minnesota Living with Heart Failure ing to break glucose cross-links, which published showing that (MLHF) questionnaire (p=0.01) (see harden tissues such as artery walls. BioCentury, April 7, 2003). alagebrium reduces the At higher doses, alagebrium also may ALT hypothesizes that the down regube acting to alleviate some of the anatomic expression of cytokines lation of cytokines and growth factors by and functional manifestations of heart dis- such as TGF beta, VEGF high doses of alagebrium may be what ease by altering cell signaling. Data have facilitated the reduction in left ventricle been published showing that alagebrium and growth hormones. mass seen in DIAMOND. ALT expects reduces the expression of cytokines such this would make the hypertrophied heart Alteons Kenneth Moch a better pump because it would lessen as TGF beta, VEGF and growth hormones, said President and CEO Kenneth Moch. stiffness by breaking glucose cross-links ALT (Ramsey, N.J.) thinks a lower dose and decrease mass by reducing the signalcould work for hypertension while a higher dose may be effective ing that causes the heart muscle to bulk up. for heart failure. To understand why, it is necessary to go back Hence, while high dose alagebrium could be efficacious for to the companys two failed Phase IIb trials, SAPPHIRE and heart failure, it could raise blood pressure in hypertension SILVER, as well as to the Phase IIa DIAMOND trial. because it allows the heart to pump more blood. Thus, a lower SAPPHIRE and SILVER both enrolled uncontrolled systolic dose would be desirable in hypertension patients. Conversely, a hypertension patients with or without left ventricular hypertro- higher dose would be better in heart failure patients, where the phy (LVF), and both missed the primary endpoint of an improve- hearts ability to pump is diminished. ment in systolic blood pressure of at least 5 mmHg at the highest More data should come in the next year and a half. Last dose. Doses tested were in the range of 35-210 mg per day (see month, ALT began the U.S. Phase IIb SPECTRA trial in about 390 BioCentury, July 21, 2003). patients with a systolic blood pressure of at least 140 mmHg. What we saw in SAPPHIRE/SILVER was that the best result Patients will receive 10, 50 or 150 mg of alagebrium or placebo was actually at the lower dose of about 35 mg/day and that the for 12 weeks (see BioCentury, March 15). Results are expected in change was about 4 mmHg, Moch said. We saw a good p-value 2005. that was less than 0.05. But that was not a prospectively defined Last week, ALT began PEDESTAL, a U.S. Phase II trial in 20 endpoint. patients with diastolic dysfunction in diastolic heart failure and More analyses of the low dose data will be released in May at impaired ejection fraction. Patients will receive 35 mg/day or 210 the American Society of Hypertension meeting in New York. mg twice daily (see B10). Results are expected in the second half. DIAMOND was a 16-week, open-label U.S. trial in diastolic PEDESTAL is enrolling a different patient population than heart failure patients with normal ejection fractions. Data on the DIAMOND, which was done in patients with normal ejection primary endpoint of exercise tolerance were not reportable fractions. Although ALT saw an effect in patients with normal because of variability attributed to both methods and execution ejection fraction, Moch said the company also wants to study of measurement (see BioCentury, Jan. 27, 2003). patients with abnormal ejection fraction.
All press releases, news announcements and story inquiries should be submitted to our News Room at pressreleases@biocentury.com. Editorial announcements emailed to the Editor-in-Chief and/or the Publisher may not receive immediate attention and potential stories will be delayed.
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A9 OF 20
Product Development
In HBV, five is not a crowd

By Susan Schaeffer Staff Writer With two polymerase inhibitors on the market and two more in Phase III trials, the market for hepatitis B therapeutics is getting crowded. But Anadys Pharmaceuticals Inc. is betting that the shortcomings of all four leave room for it to work on a better mousetrap. ANDS last week exercised its option to co-develop ANA380 (LB80380), a polymerase inhibitor from LG Life Sciences Ltd. that is in Phase II trials. The partners plan to develop the compound for chronic HBV infection as front-line therapy and salvage therapy for lamivudine-resistant patients. According to Kleanthis Xanthopoulos, president and CEO of ANDS (San Diego, Calif.), shortcomings of other polymerase inhibitors include low potency, high toxicity and lack of activity against resistant strains. Although the company has not yet identified how ANA380 produces a different result, he said it has demonstrated high potency, low toxicity and activity against lamivudine-resistant HBV strains in preclinical and early clinical studies. In addition to Epivir lamivudine, a nucleoside analog from Shire Pharmaceuticals Group plc (LSE:SHP; SHPGY, Basingstoke, U.K.) and GlaxoSmithKline plc (LSE:GSK; GSK, London, U.K.), the marketed HBV polymerase inhibitors include Hepsera adefovir dipivoxil, a nucleotide analog from Gilead Sciences Inc. (GILD, Foster City, Calif.). Lamivudines primary drawback is viral resistance. According to Xanthopoulos, in about 25% of HBV patients treated with lamivudine, the virus develops resistance within one year; within four years, that figure increases to 65%. Adefovir has a very low resistance profile, at single-digit percentages within the first year. But the dose must be kept low to avoid nephrotoxicity, which leads to a trade-off in potency. Interferon alpha also is indicated to treat HBV but does not directly inhibit viral replication. Of the up-and-comers, Idenix Pharmaceuticals Inc. (Cambridge, Mass.) is developing telbivudine, a nucleoside analog in Phase III testing, and Bristol-Myers Squibb Co. (BMY, Princeton, N.J.) has restarted development of its entecavir, a nucleoside analog also in Phase III. ANDS reckons ANA380 is about 12-18 months behind telbivudine in development. In a head-to-head Phase IIb trial in 104 patients, telbivudine demonstrated superior antiviral activity compared with lamivudine. Idenix said telbivudine has a favorable safety profile and that it is focusing on developing the compound as a first-line therapy because untreated patients represent the greater unmet medical need. Indeed, Idenix said telbivudine has not been tested in lamivudine-resistant patients. Although ANA380 and adefovir are in the same chemical class both are nucleotide analogs ANDS said ANA380 showed a 20-fold differential in indicators of nephrotoxicity in head-to-head in vitro studies. In addition, the compound has shown no renal or other toxicity in animal models. Such a large difference in vitro, in combination with animal toxicology studies, suggests that well have a very high safety margin, said Devron Averett, senior vice president of drug development. In addition, Averett said that an in vitro assessment of ANA380s potency in lamivudine-resistant strains showed about a two-fold difference in one direction for one mutation, and a two-fold difference in the other direction for another mutation what you see is very similar to adefovir. In humans, the company said interim results from a Phase IIa trial of ANA380 in 28 patients showed potency greater than lamivudine, adefovir and entecavir and comparable to telbivudine. According to Xanthopoulos, after the first four weeks of treatment, ANA380 reduced mean HBV DNA by 4.1 log. Citing data extracted from published sources, he said this compares to a reduction of 1.9 log for adefovir, 3.6 log for telbivudine; 2.9 log for entecavir, and 2.2 log for lamivudine. ANDS expects final data from the trial within the next couple of quarters. ANDS plans to start a Phase II trial of ANA380 in lamivudine-resistant HBV patients within the next six months. Xanthopoulos estimated that there are 8-10 million cases of HBV in the territories licensed by ANDS. Under the deal, LG Life Sciences (Seoul, Korea) has commercialization rights in China, India, Korea and Southeast Asia, and ANDS has rights in North America, Europe, Japan and the rest of the world.
Ascent A6 Astex B2 AstraZeneca (LSE:AZN; AZN) A10, B2 AtheroGenics (AGIX) A16 Auxilium A15, B12 Avant (AVAN) B2 Avecia B7 Aventis (AVE) A7, B5 Axcan (TSE:AXP; AXCA) A10 Barbeau Pharma B5 Beckman Coulter (BEC) B4 Benitec (ASX:BLT) B8 Bertek A10, B6 BioChemics A3 BioCurex (BOCX) A3 Bioenvision (BIV) B8 BioGeneriX B5 Biogen Idec )BIIB) A13 BioInvent (SSE:BINV) B2 BioMarin (BMRN; SWX:BMRN) A6, A18, B2 See page A12
BioCentury Company Index

April 26, 2004
Actlion (SWX:ATLN) A13 Adprotech B2 Advanced Biotherapy (ADVB) B9 Advanced Viral Research (ADVR) B7 Agencourt B7 Agrobiogen B11
Alexion (ALXN) B8 Alkermes (ALKS) A17, B9 Altana (FSE:ALT; AAA) B5 Alteon (ALT) A8, A18, B10 Amgen (AMGN) A13, B13 Anadys (ANDS) A9, B2 Anika (ANIK) B10 Antigenics (AGEN) A17, B5, B13 Antisoma (LSE:ASM) B2 Applied Biosystems (ABI) B6 Array (ARRY) B12
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A10 OF 20
Technology Briefing
Mass Listeria
When MedImmune Inc. licensed rights to EphA2 from Purdue University in 2001, the companys first order of business was to develop antibodies against the cancer target. More recently, the company decided to add a complementary approach by developing EphA2 cancer vaccines, and set about looking for a platform with which to deliver the antigen. Last week, MEDI placed its bet with Cerus Corp.s Listeria technology, which the partners hope will provide a broad immune response and straightforward manufacturing. EphA2 is a receptor tyrosine kinase that, when overexpressed, promotes tumor growth and metastasis. According to MEDI (Gaithersburg, Md.), the target is overexpressed in multiple cancers, including breast, prostate and colon cancer, and metastatic melanoma. EphA2 is an important oncogene, said Michael Kinch, director of biology. Its also been shown to correlate with poor patient outcomes. Last year, MEDI published in Cancer Research that 6 mg/kg of its anti-EphA2 antibodies inhibited tumor growth in mice. Antibodies induce EphA2 internalization and degradation, said Jim Young, president of R&D at MEDI. Following this, youd expect to get antigen presentation. Thus, having a vaccine would help you mop up. MEDI said further research could include studies on the combination of EphA2 antibodies and vaccines. As a vaccine delivery vehicle for its antigen, MEDI chose CERSs Listeria technology, which uses strains of the bacteria that have been engineered to have reduced toxicity. Young told BioCentury that a main reason MEDI opted for this technology is the broad immune stimulation elicited by Listeria. MEDI is responsible for clinical development, manufacturing and commercialization. CERS will participate in development, and will receive an upfront payment and development funding and is eligible for milestones and royalties. Although the deal was officially announced last week, the companies have been working on the project for some time. In March, they presented data at the American Association for Cancer Research meeting in Orlando, Fla., showing that the vaccine significantly improved survival times compared with control in a mouse model of lung cancer. CERS (Concord, Calif.) said the data showed that the technology elicited Class I and II immune responses and stimulated cytokine production from the innate immune system. Stephen Isaacs, president and CEO of CERS, noted that Listeria is an intracellular bacterium. It lives inside host cells and eventually is encapsulated into a vesicle where antigens are processed and presented for CD4 cells. It then enters the cytoplasm, and weve programmed the Listeria to stimulate CD8 cells. In addition, the human immune system is able to, over time, recognize molecular patterns and mount an innate immune response. David Cook, vice president of R&D at CERS, added that Listeria is easy to manufacture and scale up. All youre really doing is fermenting bacterium, he said. You dont have any subsequent purification steps because the bacterium itself is the product. MEDI expects to start clinical trials of an EphA2 antibody next year. The company did not disclose a timeline for getting the vaccine into the clinic. Steve Edelson
Online links this week

Links to the following documents reside online at BioCenturys News Center at www.biocentury.com.
Orphan drugs
of Financial Condition and Results of Operations (MD&A) sections of SEC filings (see Cover Story).
Transparency
Summary of actions taken at the April meeting of the EMEAs Committee for Orphan Medicinal Products (COMP).
Patents
CPMP executive recommendations for improving transparency of information provided to patients.

Product documentation
National Academy of Sciences report, A Patent System for the 21st Century (see A14).
SEC
Guidance regarding the Managements Discussion & Analysis
Apokyn: FDA Talk Paper on the approval of injectable Apokyn apomorphine to treat immobility episodes in patents with Parkinsons disease (PD), from Bertek Pharmaceuticals (Research Park Triangle, N.C.). Faslodex: EPAR for Faslodex fulvestrant to treat breast cancer in postmenopausal women, from AstraZeneca plc (LSE:AZN; AZN, London, U.K.). Paxil: Summary of the CPMPs safety review of Paxil paroxetine to treat depression, from GlaxoSmithKline plc (LSE:GSK; GSK). PhotoBarr: EPAR for PhotoBarr porfimer sodium to treat high-grade dysplasia associated with Barretts esophagus, from Axcan Pharma Inc. (TSE:AXP; AXCA).
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A11 OF 20
Emerging Company Profile
A cancer trifecta
By Keith Haan & Aimee Dingwell Staff Writers The spate of startups built on inlicensing begs the question of whether there are enough compounds to support the model and how each company will differentiate itself. Three newcos built on this model, all of which announced deals in the last few months, have slightly different tacks on how they plan to make the model work in cancer. Hudson Health Sciences Inc. (South San Francisco, Calif.) is in-licensing early-stage compounds from academia. In contrast, Cougar Biotechnology Inc. (Los Angeles, Calif.) and Gloucester Pharmaceuticals Inc. (Cambridge, Mass.) have taken a more conventional approach, licensing their lead compounds from industry.
Hudson Health Sciences Inc.

South San Francisco, Calif. Technology: Small molecule anticancer compounds Disease focus: Cancer Founded: 2002 by Paramount Capital University collaborators: Yale University, Dana Farber Cancer Institute, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Case Western Reserve University Corporate partnerships: NA Number of employees: 8 Funds raised: $5 million Investors: NA CEO: Mark Ahn Patents: NA
analog belonging to a class of radiosensitizing pyrimidine analogs. In addition to having a different route of administration, Hudson believes the compound will side-step the gastrointestinal and myelotoxicities of IUdR. The company plans to start clinical testing in brain cancer by year end. Also by year end, Ahn expects to inlicense at least one additional cancer compound and to nearly double the companys size from 8 to 15 employees. In addition, by the end of summer, Hudson is aiming to reverse-merge into a public shell and raise about $10-$12 million, which would include an equity investment by Rodman & Renshaw. Ahn expects the funds to last for at least two years.
Cougar: Plenty to eat

Cougar, which thus far has taken its compounds from industry, believes there are enough clinical-stage compounds to keep everyone busy. We are looking to find compounds that have some clinical experience, said Cougar CEO Alan Auerbach. There are a lot of players looking for products in this space, but we feel there are enough compounds.
See next page
Hudson: Its academic

Hudson is looking to academia to fuel its engine with early-stage cancer compounds. We believe that there is far more science going on outside companies than inside them, said Hudson CEO Mark Ahn. Time and time again, we come across programs in academia that would have gotten killed inside a company. Ahn noted that identifying preclinical and early-stage compounds in this way is difficult because fewer compounds have gone beyond early preclinical development. The place where development in academia gets hung up is in whole animals, he said. Thats because it gets really pricey when you start to go into animals, and it gets more competitive. But there is a natural attrition process conducted by the institution that picks the winners and losers. Promising leads get grant funding. Indeed, third party research funding is one of about five criteria the company uses to evaluate potential in-licensing opportunities. Specifically, the compounds also should have an established target and/or known mechanism of action, a favorable or improved therapeutic index, clear IP status that ideally allows Hudson to have global rights, and late preclinical or early clinical
development status. According to Ahn, the research leading to the discovery of the companys PT-523 compound took more than 24 years. PT-523 is a non-classical antifolate that is a water-soluble, nonpolyglutamatable analog of aminopterin. The company said PT-523 has shown better selectivity for the target enzyme dihydrofolate reductase (DHFR) in vitro and has significantly better efficacy than methotrexate, a classical antifolate. Hudson believes the compound has potential in multiple cancer indications. PT-523 is in Phase I testing in solid tumors, and Ahn expects the company to start Phase II testing in lung and possibly gastrointestinal cancer by year end or the first quarter of 2005. Hudson in-licensed PT-523 last February from the Dana Farber Cancer Institute at Harvard University. The compound came with an $8 million grant from the Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute. Hudsons second compound, IpdR, was in-licensed from Yale University this February and came with a $4 million NCI grant. At that time, the company also raised $4.7 million in a series A round. IpdR is an oral prodrug of intravenous IUdR, a halogenated nucleoside
Cougar Biotechnology Inc.

Los Angeles, Calif. Technology: Testosterone synthesis inhibitor Disease focus: Cancer Clinical status: Phase I Founded: 2003 by Horizon BioMedical Ventures LLC and Alan Auerbach Corporate partners: BTG International plc University collaborators: NA Employees: NA Funds raised: $5 million Investors: Horizon BioMedical Ventures LLC CEO: Alan Auerbach Patents: NA
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A12 OF 20
The compound is in Phase II trials for renal cell carcinoma (RCC) and Gloucester Pharmaceuticals Inc. hormone-refractory prostate cancer Last week, Cougar acquired exclu- Cambridge, Mass. (HRPC). In addition, the NCI is consive worldwide rights to develop and Technology: Histone deacetylase inhibitors ducting a Phase II trial in cutaneous T commercialize abiraterone acetate to cell lymphoma (CTCL) under a CRADA treat prostate cancer from BTG Inter- Disease focus: Cancer with Fujisawa. Gloucester also gained national plc (LSE:BGC, London, U.K.). Clinical status: Phase II rights to FR135313, the biologically acAbiraterone is an oral inhibitor of Founded: 2003 by Jay Mohr, Gregory Verdine, tive moiety of FK228 that is in preclinical the 17 alpha-hydroxylase/C17-20 lyase Martin Vogelbaum development. enzyme complex, which is involved in Corporate partners: Fujisawa PharmaceutiAccording to Mohr, FK228 was put testosterone synthesis. By blocking cal Co. Ltd. on the block because Fujisawa (Tokyo, testosterone production, the com- University collaborators: NA Japan) was exiting the oncology space. pound would inhibit tumor survival/ From what Fujisawa told us, there Employees: 15 by year end growth signaling through the androwere several companies interested in gen receptor, which often requires Funds raised: NA licensing FK228, Mohr said. Part of Investors: Apple Tree Partners testosterone for activity. what tilted the scale in Gloucesters There is clinical proof of concept CEO: Jay Mohr favor was that it would be focused on the for the idea of inhibiting testosterone Patents: NA compound, he said. Because we are synthesis. According to Auerbach, many small, companies know that their comphysicians prescribe the antifungal kepound will get the attention it needs. toconazole to treat prostate cancer based on its profile as a The company is looking to add one or two more compounds. relatively broad-spectrum steroid synthesis inhibitor. As an Mohr said he is likely to look to a Phase I or preclinical antifungal, ketoconazole is thought to inhibit P450 sterol C-14 compound, although the latter would have to be late in alpha demethylase, blocking synthesis of ergosterol, which is preclinical development with a significant pharm/tox package. an essential component of the fungal cell membrane. Although Gloucester hasnt disclosed how much money it Abiraterone has completed Phase I trials in 26 prostate has raised, Mohr said it has enough to fund ongoing clinical cancer patients, in which it showed the ability to suppress trials to the point where the company will be able to testosterone synthesis. Cougar initially will focus the com- determine which indication it wants to pursue in a registrapound as a second-line treatment for prostate cancer, but did tional study. Later this year, it plans to raise a new round that not provide a timeline for the start of Phase II trials. will fund the registrational trial and enable it to in-license one or two compounds, and add to its clinical and regulatory capabilities. Gloucester: MOA matters Mohr noted that Phase III trials in either RCC or CTCL Though an in-licensor, Gloucester is not looking at would require far fewer patients than cancers such as lung or reprofiling or rescuing old drugs, said CEO Jay Mohr. colorectal. These are niche indications, and would likely Instead, the company is looking for small molecules that have require much smaller trials, perhaps as few as 100 patients, a new mechanism of action and have shown biologic activity he said. on their own, or belong to a class of compounds sharing the Should FK288 reach the market, Gloucester plans to keep same target or MOA that has shown biologic activity. U.S. rights. Our plan is to become an integrated company. Earlier this month, Gloucester acquired worldwide rights The indications we will be pursuing are small enough in the to develop and market FK228, a depsipeptide histone deacety- U.S. that we could market the compound with a focused lase (HDAC) inhibitor from Fujisawa Pharmaceutical Co. Ltd. commercial infrastructure, Mohr said. (see BioCentury, April 19). The company will seek a partner outside the U.S.
Company Index, from page A9 BioPure (BPUR) A4 Bioreason B7 Bioseek B3 Biotica B4 BioTrove B12 Boehringer B6 Boston Biomedica (BBII) B3, B7 Bristol-Myers (BMY) A9, A16, B3, B6 Bruker (BRKR) B12 BTG International (LSE:BGC) A12 Callisto (CLSP) B12 Carolina Pharma B7 Celgene (CELG) A13 Cell Signaling B3 Cell Therap (CTIC; NMerc:CTIC) B10 CeNeS (LSE:CEN) A19, B13 Centocor B6 Cerus (CERS) A10, A19, B3 Chiron (CHIR) A7 co.don (FSE:CNW) B6, B7 Cognia B3 Conforma B7 Corgentech A2, B7 Cougar A11 CuraGen (CRGN) B10 CV Therap (CVTX) B8 CytRx (CYTR) B3 Daiichi Pharma B4 Discovery Partners (DPII) B3 Dow (DOW) B3 Dragon (TSE:DDD; DRUG) B3 DSM B4 DxS B12 Dynavax (DVAX) A2 Dynogen B12 DynPort B2, B9 Echelon B3 Edmond Pharma B5 Edwards Lifesciences (EW) B7 Elan (ELN) A19, B3 Enzo (ENZ) B3 Enzon (ENZN) B2 ESP Pharma B5 Eyetech (EYET) A16 Fujisawa A12 Genelabs (GNLB) B4 Genencor (GCOR) B7 Genentech (DNA) A13 GeneProt B4 Genitope (GTOP) B7 Genta(GNTA) B5 Genzyme (GENZ) A6, B5, B10 Gilead (GILD) A9, A16, B4, B13 GlaxoSmithKline (LSE:GSK; GSK) A9, A10, B5 Gloucester A11 GTx (GTXI) B4 Harvard U B3 See page A19
Emerging Companies, from previous page
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A13 OF 20
Politics & Policy
Zero sum game

CMSs criteria for selecting drugs. By Steve Usdin Washington Editor The decision to exclude off-label indications was attacked by Senior officials of the Centers for Medicare & Medicaid representatives of multiple myeloma (MM) patients, physicians Services got a full dose of rationing warfare last week, as patients, and an aide to Sen. Kay Bailey Hutchison (R-Texas). They their advocates and caregivers made diametrically opposite contended that Celgene Corp.s Thalomid thalidomide, which is demands for their fair share of a $500 million prescription drug not approved for MM, should be covered because it is the de demonstration project mandated by the new Medicare prescrip- facto standard of care. tion drug law. Sol Barer, president and COO of CELG (Warren, N.J.), did note that an sNDA for At a meeting held to receive public MM is pending at FDA, with an October comments about how CMS should manage the program, aides to two senators There will be many more user fee deadline. As to beneficiary selection, reprewarned that the plan the agency is likely to people interested and sentatives of seniors suffering from comimplement bears little resemblance to the benefit Congress intended when lawmak- eligible for this project mon diseases such as RA made a pitch based on numbers. Funds should be ers passed the Medicare Modernization than we can include. apportioned based on prevalence in the Act (MMA) last November. Section 641 of the MMA instructs CMS Stuart Guterman of CMS M e d i c a r e p o p u l a t i o n , s a i d K e v i n Brennan, a lobbyist for the Arthritis to launch a Demonstration Project for Foundation. Coverage of Certain Prescription Drugs and Biologicals within 90 days of enactment. The 90-day Partners Wyeth (WYE, Madison, N.J.) and Amgen Inc. deadline came and went in March, but CMS still is struggling to (AMGN, Thousand Oaks, Calif.) also argued in favor of propordesign the program. It recently announced some tentative tional allocation according to disease prevalence within the nondecisions, and solicited public comments on scope of coverage cancer group. They also reported that 57% of Medicare recipients with RA have incomes below $15,000 per year, and urged and criteria for selecting eligible patients. A few things are clear about the project: the $500 million is CMS to create enrollment criteria weighted toward low-income not nearly enough to cover drugs and biologics for everyone patients who lack drug coverage. The companies market Enbrel who believes they should be eligible, and the 50,000-person etanercept for RA and other indications. MS patient groups, however, strongly opposed proportional enrollment cap is not large enough to accommodate all of the potential participants. And based on last weeks meeting, allocation. It doesnt account for the cost of drugs and therefore however the parameters are defined, elderly patients will not be wont correct access barriers, said Stephanie Simmons, a quiet if they think theyre been excluded from receiving therapies representative of the National Multiple Sclerosis Society. they need. Simmons and other MS advocates said that funds should be A total of 40% of the $500 million will be reserved for cancer set aside to pay for three drugs: Rebif interferon beta-1a, drugs, but to the disappointment of advocates for rheumatoid marketed by Serono SA (SWX:SEO; SRA, Geneva, Switzerland); arthritis (RA) and multiple sclerosis (MS) patients, who felt the Betaseron interferon beta-1b, marketed by Schering AG (FSE:SCH; remainder should be reserved for treatments for these diseases, SHR, Berlin, Germany); and Copaxone glatiramer, marketed by CMS has not yet set limits on the types of other conditions the Teva Pharmaceutical Industries Ltd. (TEVA, Jerusalem, Israel). program will address. The fourth MS biologic, Avonex interferon beta-1a from Biogen CMS announced five criteria for the demonstration program Idec Inc. (BIIB Cambridge, Mass.), is covered by Medicare. Moveover, advocates for patients with pulmonary arterial on April 14: A drug or biological covered under the project must hypertension (PAH) have formed a coalition to lobby CMS to set eliminate the need for a drug or biological currently covered by aside $37 million of the Section 641 funds to pay for Tracleer bosentan from Actelion Ltd. (SWX:ATLN, Allschwil, SwitzerMedicare. Coverage of the drug or biological in the project is limited land), which is marketed in the U.S. by Genentech Inc. (DNA, to approved indications. South San Francisco, Calif.). Putting all patients in a single The drug or biological must be of at least equal efficacy to selection pool would discriminate against orphan diseases, said the covered drug it replaces. Cara Ugolini, a spokesperson for the Pulmonary Hypertension Use of the replacement drug or biological must repre- Association. Many of the concerns about implementation of the demonsent an advantage in terms of access and/or convenience for patients compared to the currently covered drug or biologi- stration program stem from CMSs misinterpretation of the law cal. mandating it, according to Bill Pewin, a staffer for Sen. Olympia The drug or biological is not eligible for coverage Snowe (R-Maine). The bills authors didnt intend replacement under the project if the drug or biological it replaces is not to be a criteria. What we were trying to do is provide a benefit commonly provided incident to a physicians services. broadly for patient-administered drugs, he said. Pewin added that CMSs focus on the word replacement Although last weeks meeting was supposed to focus on See next page criteria for beneficiary selection, participants also criticized
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A14 OF 20
Washington Notebook
Patents vs. research

By Steve Usdin Washington Editor The bar for patenting gene sequences should be raised, steps should be taken to ensure that overly broad biotech patents do not impede medical research, and clear exemptions from patents should be created for academic researchers, according to a National Academy of Sciences report. The NAS report, A Patent System for the 21st Century, also recommends the creation of an open review procedure that would make it easier for third parties to challenge patents. Federal courts have set a low standard of nonobviousness for patenting gene sequence-related inventions, according to the NAS. All other industrialized countries approach the non-obviousness of novel genes by focusing on the technical hurdle the inventors faced cloning the gene, the report notes. For example, according to the report, the European Patent Office has taken a strict stance on the obviousness of recent genomics invention. Thus EPO takes the position that a patent can be awarded to genomics inventions only if obtaining the sequence was a technical achievement or if some new or unexpected property associated with the gene has been discovered. The report also reviews concerns that biomedical biotech patent practice might be impeding medical and scientific progress. In particular, these center on the following fears: broad patents on upstream discoveries could impede follow-on research and development if access to the foundational intellectual property is restricted; assembling rights to a plethora of patents on basic technologies could constitute an insurmountable barrier, causing scientists and companies to avoid or abandon promising areas of R&D; and the high costs associated with biotech patents could put academic researchers at a competitive disadvantage. To assess the validity of these concerns, the NAS commissioned a survey, conducting 70 interviews with IP practitioners, researchers and government officials. With a few exceptions, the study found that patent policies have not impeded research or drug development. This is in part because the number of patents required for most R&D projects remains manageable and in part because the various players have improvised arrangePolitics & Policy, from previous page
ments or followed norms that mitigate the intellectual property complexities that exist, the report says. Tactics for overcoming IP barriers include negotiating licenses and royalty payments, circumventing patents by inventing around them, using substitute research tools, and locating research activity offshore, the report notes. Many university and corporate respondents to the survey reported an even simpler expedient: patent infringement. One of the most pervasive working solutions is infringement of patents, especially on tools of precommercial laboratory research, in some cases on the presumption that research is legally shielded from infringement liability by a research exception, and in other cases on the assumption that patent holders will not sue over research uses, the report says. In particular, there is a widely held belief that private firms will not sue university investigators over patent infringement because there is little to be gained financially and a high risk of adverse publicity. A Federal Circuit Court of Appeals ruling has shaken the confidence of academic researchers that they will be shielded from liability for patent infringement by law or custom. In the October 2002 Madey v. Duke decision, the appeals court ruled that universities are engaged in the business of scientific research, and therefore are not eligible for an exemption from patents. It is not clear, however, whether Madey has a direct bearing on biomedical research, according to the NAS report. The NAS recommended that Congress consider narrow legislation creating some level of protection for noncommercial uses of patented inventions. The report also recommended that Congress consider enacting legislation intended to reduce the time and cost associated with IP litigation. This could be accomplished, the report suggested, by creating a procedure for third parties to challenge patents for a limited period after their issuance in an administrative proceeding before administrative patent judges of the USPTO. The speed, cost, and design details of this proceeding should make it an attractive alternative to litigation to determine patent validity and fair to all parties (see Online Links, A10). people interested and eligible for this project than we can include, said Stuart Guterman, director of CMSs Office of Research, Development and Information. Parameters of the program will be announced when it is launched, which will be some time this summer, according to Guterman. The project sunsets in 2006, when the new Medicare drug benefit is supposed to start.
has created a quagmire that inappropriately limits coverage. He also said that excluding off-label uses goes against the intent of Congress. CMS decided to limit the program to FDA-approved uses because establishing fair criteria for selecting off-label indications would delay starting the program, said CMS Chief Medical Officer Sean Tunis. CMS officials indicated that they will not reconsider the decision to limit the program to replacement products. Whatever criteria CMS adopts, there will be many more
BioCentury Extra: Online every business day.
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A15 OF 20
Ebb & Flow
Pipeline gardening
By Steve Edelson stable formulation of FluMist. Money Raised in 2004 & Shaun Brown Three other compounds are slated for Senior Writers Phase III trials next year: Numax, a nextTotal last week: $130.0M In the best of all possible worlds, generation antibody for RSV; Vitaxin, a IPOs YTD: $1102.4M revenues from the launch of humanized MAb against integrin alpha Follow-on YTD: $1087.3M MedImmunes FluMist intranasal influ(v)beta(3) that is in Phase II trials to treat Venture YTD: $2042.8M enza vaccine would have more than made psoriasis, rheumatoid arthritis (RA), metaOther YTD: $3011.9M up for planned increases in R&D spendstatic melanoma and metastatic prostate Total YTD: $7244.3M ing, thus keeping EPS intact. When that cancer; and an anti-HPV vaccine that also In 2003 a total of $19.5 billion was raised, including didnt happen, MEDI decided to keep is in Phase II trials. $509 million in IPOs, $3.8 billion in follow-ons, spending up anyway. Phase II Vitaxin data are expected this $3.9 billion in venture capital, and $11.3 billion in As a result of that decision, the year. Also this year, the company plans to other fundraising. Totals include overallotments companys first quarter net income grew complete additional analyses of its Phase III and warrants. (Source: BioCentury Financial Center) only 1% quarter over quarter from CAIV-T data. Positive preliminary results $110 to $111 million, despite revenue from two Phase III trials were reported last growth of 13% from $431 million to $489 million. Much of the month (see BioCentury, March 8). difference was in the R&D line, as first quarter R&D spending MEDI plans to launch CAIV-T in 2007 and hopes that the increased 57% to $49.8 million from $31.7 million in the vaccine will rejuvenate its sales. At that time, Young said, the 2003 quarter. trend of higher R&D spending as a percent of sales will reverse For 2004, the company expects sales to grow in the low and could return to around 16%. double digits versus a 26% increase in 2002. The slowing sales In addition to its late-stage products, MEDI filed INDs last growth in part reflects the maturity of Synagis, MEDIs antibody year for three compounds, and plans to continue that pace to prevent respiratory syncytial virus (RSV). through 2006. Young said the company has been filling its early Given slowing revenue growth and rising R&D spending, pipeline in part through more in-licensing. In the front end, the R&D will rise as a percent of total sales, noted Jim Young, R&D spend isnt huge, he noted. Weve used our venture president of R&D. This year, we expect to see R&D investment capital arm to make equity investments in companies, which use at about 20% of product sales, which is up from last years the money to fund the work theyre doing for us its very P&L investment of 16%. friendly. The good news is that MEDIs higher R&D spend correlates MEDI was up $0.41 to $23.95 on the week. with pipeline visibility. MedImmune expects to have four products in Phase III trials next year, including CAIV-T, a refrigerator-
IPO watch
EPO sales watch

In their respective earnings calls last week, Amgen (AMGN) and Johnson & Johnson (JNJ) fired shots related to their EPO drugs. Two weeks ago, JNJ said its competitor was offering aggressive discounting of up to 40% off list. Last week, AMGN retorted that the price difference between Aranesp and competing drugs was modest, and noted that others also are discounting their EPO drugs. Whether its discounting or old-fashioned competition thats lowering EPO prices, AMGN is still forecasting a solid sales trajectory. ($M) Product 2001 2002 2003 2004 1Q04 guidance
AMGN Epogen Aranesp Total $2,108.5 $41.5 $2,150.0 $2,260.6 $415.6 $2,676.2 $2,434.7 $1,543.8 $3,978.5 JNJ Procrit/ Eprex $3,430.0 $4,269.0 $3,984.0 NA NA $590.0 $543.0 $1,100.0 NA NA $4,600$5,100
Nanotechnology company Nanosys filed to raise $115 million in an IPO underwritten by Merrill Lynch; Lehman; CIBC; and Needham. Among other things, the company is developing a nanowire-array molecular sensing system to detect analytes in real time using low voltage measurement technology. Nanosys has about four years of cash, posting a 2003 operating loss of $9.5 million and ending the year with $38.9 million in cash. Principal stockholders include Arch Venture Partners (14.7% prior to the offering); CW Group (13.6%); Polaris (13.6%); and Venrock (13.6%). Urology company Auxilium also threw its hat into the ring, filing to raise up to $86.3 million in an IPO underwritten by Deutsche Bank; Piper Jaffray; and Thomas Weisel. The company has one marketed product: Testim (AA2500) topical testosterone gel to treat hypogonadism. Last year, Auxilium reported an operating loss of $29.6 million and revenues of $8.8 million. The company had $28.4 million in cash at Dec. 31. Principal stockholders include Perseus-Soros BioPharmaceutical Fund (22.4% prior to the offering); SCP Private Equity (22.1%); Sprout Capital (17.7%); Lehman Brothers (11.1%); Schroder Ventures (10%); Caduceus (9.6%); and Biotech Growth (8.5%).
See next page
BioCentury,
Ebb & Flow, from previous page
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A16 OF 20
Barrons bump
Investors liked what they read in a Barrons article last week that merely stated the obvious: pharma needs drugs and biotech companies have compounds available in late-stage development or on the market. Cardiovascular play AtheroGenics (AGIX), ophthalmic company Eyetech (EYET) and cancer companies Millennium (MLNM), Onyx (ONXX) and OSI (OSIP) were mentioned. AGIX had the smallest gain on Monday a 1% increase despite being the only company listed that holds full rights to its late-stage compound. Its AGI-1067 is in a Phase III trial for secondary prevention of coronary artery disease. The other companies all added at least 3% on the day. OSIP led the way with a 10% pop. On the week, AGIX slipped $0.44 to $24.67; EYET gained $2.21 to $35.70; MLNM added $0.41 to $23.95; ONXX was up $3.90 to $47.15; and OSIP rose $1.94 to $38.14.
allow IMCL and partner Bristol-Myers (BMY) to meet full commercial demand for colorectal cancer drug Erbitux cetuximab. BB36 has FDA approval to manufacture Erbitux for investigational use, and Swiss approval to manufacture commercial product. The partners have met initial Erbitux demand in the U.S. with supplies produced at a Lonza Biologics facility.
Viread sales go up and north

Gilead (GILD) bumped up 2004 guidance for its Viread tenofovir HIV drug on its earnings call after market Thursday. The increase to $725-$775 million from $700-$750 million reflects global demand. In the first quarter, 40% of Vireads $193.1 million in sales came from outside the U.S. The company also said that it has established a national list price in Canada of C$16.25 (US$12.07) per day for Viread. The price is still under negotiation in certain provinces, where discounts to the list price may apply. GILD said it would continue to provide the drug at no cost to patients enrolled in its Extended Access Program until the drug is on the formularies of all the provinces (see BioCentury, Nov. 10, 2003). GILD closed Friday at $60.12, up $0.90 on the day and $2.80 on the week.
Branching out on Erbitux

ImClone (IMCL) jumped $7.03 (12%) to $66.30 on 9.9 million shares on Monday following post-market news the prior Friday that FDA accepted for review a CMC supplemental BLA for IMCLs BB36 manufacturing facility in Branchburg, N.J. The PDUFA date for the sBLA is June 18. Approval would IPO queue update
On the road
Cancer play Pharmexa (CSE:PHARMX) was down DKK1.40
See next page
Although a trio of IPOs have priced this month, the queue has grown, as six companies have filed since the start of the second quarter. The 19 IPOs that have priced in this window had an average post-money valuation of $275.2 million. Excluding the $809 million valuation garnered by Eyetech (EYET), the average is $245.5 million. (A) Assumes proposed shares (excluding overallotment) are sold at mean price. ($M) Company Barrier Cytokinetics Not updated Acadia Alnylam Celldex CoTherix Critical Therapeutics Favrille Icagen Idenix Inhibitex Metabasis Momenta Threshold ViaCell Xenogen NA NA NA NA NA NA NA NA NA NA NA NA NA NA Up to $86.3 Up to $86.3 Up to $50 Up to $70 Up to $103.5 Up to $86.3 Up to $86.3 Up to $100 Up to $86.3 Up to $86.3 Up to $86.3 Up to $86.3 Up to $92 Up to $51.8 NA NA NA NA NA NA NA NA NA NA NA NA NA NA TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD TBD Ph II Preclin Preclin Approved Ph II Ph II completed Ph III Ph II Ph II ANDA submission this year Ph II completed Ph I/II Mkt 2/27/04 3/1/04 4/9/04 3/19/04 4/8/04 4/8/04 12/15/03 3/3/04 2/3/04 3/11/04 4/9/04 4/5/05 4/2/04 S-1 update 4/2 3/11 Original funding goal Up to $86.3 Up to $86.3 New funding goal (A) $75.0 $69.6 Shares 5.0 5.8 Price range $14-$16 $11-$13 Hoped for post-$ (A) $327.0 $310.0 $318.5 Lead program Ph III Ph II Original filing 2/6/04 1/27/04
Hoped for post-$ avg
NDA submission 04 3/11/04
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A17 OF 20
equity research analyst at Stephens, where he covered companies with enabling technologies for discovery research.
to DKK30 on the week after saying it plans to raise about DKK209 million ($33.6 million) through a rights issue of 12.3 million shares at DKK17 each. PHARMXs shareholders will be offered 3 new shares for each share they hold. The subscription period will run from May 3 through May 17. PHARMXs lead programs are HER-2 Protein AutoVac and HER-2 DNA AutoVac, which have both completed Phase I studies in breast cancer. PHARMX estimates that it needs about DKK160 million ($25.8 million) to get through to mid2006 at its current burn rate. The offering is partly underwritten by ING, and ING and Gudme Raaschou are lead managers. The companys market cap is DKK123 million ($20 million).
Clinical milestones
Alkermes (ALKS) was up $0.54 to $15.74 on the week after completing enrollment in a Phase III safety trial of its Vivitrex injectable extended-release naltrexone in about 400 patients who are alcohol- or opiate-dependent. ALKS expects interim safety data after six months and plans to use results to support an NDA submission in the first half of 2005 (see B9). Antigenics (AGEN) fell $0.87 to $9.99 on the week after announcing that FDA wants additional product characterization for the companys Oncophage cancer vaccine to treat renal cell carcinoma (RCC), despite having lifted a partial clinical hold on the Phase III trial last November. AGEN said it will submit the data over the next several weeks. ZymoGenetics (ZGEN) added $0.59 to $16.74 on Monday after starting the first of four double-blind Phase II trials of its recombinant human thrombin (rhThrombin) to control bleeding
See next page
Analyst tracks
John Sullivan joined Leerink Swann as an analyst in the firms biotech group. Previously, Sullivan was vice president and senior EPS watch
There were only two misses in last weeks earnings crush: one biotech and one pharma. Chiron (CHIR) missed the Street by a nickel, but the news didnt faze investors, as the company added $0.27 to $45.30 on the week. CHIR expects to have backloaded EPS due to seasonal sales of its flu vaccine. Schering-Plough (SGP) was nicked after coming in $0.02 shy of the consensus estimate. The company slid $0.13 to $17.21 on the week. Investors likely are looking to 2005, when the company hopes to start reporting sales of potential blockbuster cholesterol drug Zytorin. (A) The Street expects AFFX to be profitable on a full-year basis. (B) FRX results are for fiscal 4Q. 1Q04 EPS est -$0.08 1Q04 EPS actual -$0.03 Growth from 1Q03 NA 4/23 cls $31.39 Wk chg -$3.62 % chg -10% Mcap chg ($M) $(219.1) 4/23 Mcap ($B) $1.9
Company Affymetrix (AFFX) (A)
Outcome Beat by $0.05
For 2Q04, the company expects EPS of $0.03 on revenues of $78M. Analysts had expected EPS of $0.14 in the second quarter. The company also said that certain SG&A expenses that were expected in 1Q04 will now come in 2Q04. Amgen (AMGN) $0.56 $0.57 Beat by $0.01 36% $58.31 -$1.83 -3% $(2,350.7) $74.9
Product sales were $2.2B, up 35% from $1.6B in 1Q03 (see EPO Sales Watch, A15). Celgene (CELG) $0.08 $0.10 Beat by $0.02 900% $56.94 $4.53 9% $366.0 $4.6
1Q revenue rose 69% to $82.9M from $49.1M in 1Q03, driven by sales of Thalomid thalidomide. For the year, CELG increased its EPS guidance to $0.42-$0.52 from $0.40-$0.50. The company also raised its revenue guidance to $365-$385M from $360-$380M. Chiron (CHIR) $0.27 $0.22 Missed by $0.05 -27% $45.43 $0.27 1% $50.5 $8.5 Because of sales seasonality, CHIR said 2H04 will account for 75-80% of full-year EPS. The seasonality in part reflects sales of Fluvirin, an influenza vaccine that CHIR gained through its purchase of PowderJect in 3Q03. CHIR noted that PowderJect revenues are recognized mainly in the second half, but that costs associated with PowderJect are incurred throughout the year. Eli Lilly (LLY) $0.66 $0.70 Beat by $0.04 15% $73.15 $0.70 1% $786.6 $82.2
LLYs EPS guidance for 2Q04 is $0.67-$0.69. The company reiterated full-year EPS guidance of $2.80-$2.85 and sales growth in the low double digits. Forest (FRX) (B) $0.37 $0.38 Beat by $0.01 -21% $66.15 -$6.71 -9% $(2,464.9) $24.3
FRX said the quarter-over-quarter EPS decrease reflects increased selling expenses related to the launches of Namenda for Alzheimers disease (AD) and antidepressant Lexapro for generalized anxiety disorder. Fiscal 2004 EPS came in at $1.95, up from $1.66 in 2003 and higher than the companys guidance of $1.82-$1.92. Gilead (GILD) $0.34 $0.45 Beat by $0.11 88% $60.12 $2.80 5% $600.8 $12.9
GILD raised its 2004 guidance for HIV drug Viread to $725-$775M from $700-$750M and increased its guidance for antifungal AmBisome to $170$190M from $160-$180M. Invitrogen (IVGN) $0.60 $0.63 Beat by $0.03 21% $74.74 $5.20 7% $271.3 $3.9
The pro forma figures exclude acquisition-related amortization. For the full year, IVGN raised its revenue and EPS guidance to $1.04B and $2.88. The Street was expecting 2004 revenue and EPS of $1.02B and $2.85. MedImmune (MEDI) $0.42 $0.44 Beat by $0.02 2% $23.95 $0.41 2% $101.0 $5.9
Expects 2Q04 revenues of $93-$98M, with a loss of $0.13-$0.16. Reiterated 2004 EPS guidance of $0.50-$0.60.
See next page
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A18 OF 20
in surgeries. The company hopes to begin Phase III testing in early 2005 (see B11). ZGEN closed Friday at $16.37, up $0.22 on the week. Neurobiological (NTII) slipped $0.16 on the week to $4.49 after starting the first of two Phase III trials of Xerecept to treat peritumoral cerebral edema. NTII has an SPA with FDA for both trials, and the compound, a synthetic CRH peptide, has Orphan Drug designation (see B10). Rigel (RIGL) added $1.75 on the week to $21.50 after starting a U.S. Phase II trial of its R112 in allergic rhinitis (see B11). Results are expected in the second half. R112 is a nasal spray Syk kinase inhibitor that inhibits mast cell activation. Alteon (ALT) added $0.06 on the week to $1.74 after starting a Phase II trial of its alagebrium (formerly ALT-711) in patients with diastolic dysfunction and impaired ejection fraction (see Product Development, A8). Inspire (ISPH) gained $1.05 on the week to $14.25 after starting a Phase II trial of its INS37217 ophthalmic denufosol as a first-line therapy in patients with rhegmatogenous retinal detachment (RRD) (see B10). Ilex (ILXO) gained $0.26 on the week and closed Friday at $24.20 after completing enrollment in a Phase II multiple sclerosis (MS) trial comparing its Campath alemtuzumab to Rebif interferon beta-1a from Serono (SWX:SEO; SRA) (see B10).
EPS Watch, from previous page
1Q04 EPS est $0.05 1Q04 EPS actual $0.08
Campath is marketed to treat refractory B cell chronic lymphocytic leukemia (B-CLL). Vivus (VVUS) was up $0.22 on the week and closed Friday at $6.38 after starting a Phase II trial of its avanafil (TA-1790) to treat erectile dysfunction (ED). VVUS expects to complete enrollment in the trial by year end and data are expected in the first half of 2005 (see B11).
Ebb & Flow

Trimeris (TRMS) popped $1.64 (13%) to $14.70 on 2.2 million shares on Wednesday following its post-market earnings announcement on Tuesday, in which it said worldwide sales of HIV drug Fuzeon increased 36% to $24 million from $17.6 million in the fourth quarter of 2003. TRMS and partner Roche (SWX:ROCZ) launched the injectable HIV fusion inhibitor last spring, and the drug has had a slow in an indication populated by oral drugs (see BioCentury, Feb. 9). TRMS closed Friday at $15.07, up $1.66 on the week. Investors shrugged off BioMarins news that it will pay a total of $175 million for the Ascent Pediatrics business of Medicis (MRX), as the stock added $0.04 to $6.89 on Wednesdays announcement. BioMarin (BMRN; SWX:BMRN) wants to become a pediatrics-focused biopharmaceutical company, and plans to partner its non-pediatric pipeline products (see Strategy, A6). BMRN closed Friday at $6.92, down $0.17 on
See next page
Company Medicines Co. (MDCO)
Outcome Beat by $0.03
Growth from 1Q03 NA
4/23 cls $34.24
Wk chg $0.47
% chg 1%
Mcap chg ($M) $22.0
4/23 Mcap ($B) $1.6
1Q sales of anticoagulant Angiomax bivalirudin for coronary angioplasty procedures increased 87% to $31.3M from $16.7M in 1Q03. Merck (MRK) $0.72 $0.73 Beat by $0.01 7% $46.76 -$0.32 -1% $(711.7) $104.0
For the year, MRK reiterated its EPS guidance of $3.11-$3.17. The company also provided 2Q EPS guidance of $0.78-$0.82. The Street expects 2Q and full-year EPS of $0.77 and $3.13, respectively. Novartis (NVS; SWX: NOVN) $0.53 $0.52 ($0.57 using U.S. GAAP) NA NA $42.43 -$1.49 -3% $(3,666.2) $104.4
Pharmaceutical sales increased 19% quarter over quarter to $4.3B from $3.6B. Global sales of Gleevec/Glivec imatinib to treat chronic myeloid leukemia and gastrointestinal stromal tumors (GIST) increased 51% to $351M. Pfizer (PFE) $0.51 $0.52 Beat by $0.01 16% $36.42 -$1.20 -3% $(9,149.9) $277.7
Human pharmaceutical sales came in at $11B, a 46% increase compared with 1Q03, which in part reflects PFEs 2003 acquisition of Pharmacia. The company reiterated its full year adjusted EPS guidance of $2.13. PFE expects to spend $7.9B on R&D this year. Schering-Plough (SGP) $0.01 -$0.01 Missed by $0.02 NA $17.21 -$0.13 -1% $(191.1) $25.3
The EPS figure excludes charges for employee termination costs and SGPs exit from a European R&D facility. Next year, the company hopes that cholesterol therapeutic Vytorin, a combination of SGPs Zetia and Mercks Zocor, will drive its turnaround. SGP plans to launch Vytorin in the second half. Serono (SRA) $0.17 $0.17 Met 89% $15.10 -$0.36 -2% $(228.9) $9.6
Global sales of Rebif interferon beta-1a to treat multiple sclerosis (MS) were up 48% to $259.6M from $175.2M in 1Q03. In the U.S., Rebif sales grew 56% to $62.7M. For 2004, SEO expects net income growth of at least 20%. Wyeth (WYE) $0.55 $0.56 Beat by $0.01 4% 39.79 -0.59 -1% $(785.9) $53.0
Human pharmaceutical sales came in at $3.2B, up 8% from 1Q03.
BioCentury,
ON
BIOBUSINESS
APRIL 26, 2004
P AGE A19 OF 20
the week. Cerus (CERS) popped $0.47 (13%) to $4 on 2.3 million shares on Wednesdays news that it partnered with MedImmune (MEDI) to develop and commercialize a vaccine to treat cancers of the breast, prostate and colon, as well as metastatic melanoma. CERSs Listeria vaccine technology will be used to develop a vaccine against MEDIs EphA2 protein (see Technology Briefing, A10). CERS gave back some gains and closed Friday at $3.96, up $0.35 on the week. Isotechnika (TSE:ISA) fell C$0.45 (15%) to C$2.50 on Tuesday after reworking its deal with Roche (SWX:ROCZ) for ISA247, a small molecule immunosuppressant. ISA now will independently develop the trans isomer version of ISA247 for renal transplant and psoriasis, and the companies dropped development of a mixed version of ISA247, which had comCompany Index, from page A12 H. Lundbeck (CSE:LUN) B4 Hudson Health Sci. A11 Icon B11 ID Biomedical (TSE:IDB; IDBE) A7, A19, B4 Idenix A9 Ilex (ILXO) A18, B10 ImClone (IMCL) A1, A16, B6, B13 Immuno-Designed B7 Inamed (IMDC) B5 Incara (ICRA) B12 Inflazyme (TSE:IZP) B2 Inhibox B6 InKine (INKP) B8 Inpharmatica B4 Inspire (ISPH) A18, B10 Integrated Biopharma (INB) B12 Introgen (INGN) B10 Inverness Medical (IMA) B2 Invitrogen (IVGN) B13 Isotechnika (TSE:ISA) A19, B4, B13 J&J (JNJ) B6 Kissei B4 Laboratorios del Dr. Esteve B5 Lexicon (LEXG) B13 LG Life Sci A9, B2 Lonza B6 M.D. Anderson Cancer Ctr B3 Martek (MATK) B4 Medicis (MRX) A6, B2 MedImmune (MEDI) A7, A10, A15, B3, B7, B13
pleted Phase II testing in psoriasis and kidney transplantation. ISA continued to slide, and closed Friday at C$2.22, down C$0.86 (28%) on the week.
London & the Continent

Shire (LSE:SHP; SHPGY) was off 7.5p to 530.5p on the week after saying it will sell Shire Biologics, its Canada-based vaccine business to ID Biomedical (TSE:IDB; IDBE) for $120 million in cash and shares (see Strategy, A7). The move is SHPs penultimate step before completing its new business model of in-licensing late-stage products and acquiring companies, while dropping early stage R&D (see BioCentury, Aug. 4, 2003). The final step will be to open an office in the U.S. for its R&D and commercial teams. The office is expected to be based near Philadelphia and is slated to open midyear. On NASDAQ, SHPGY was down $0.61 to $28.62 and IDBE was up $0.35
to $10.90 on the week. On TSE, IDB was up C$0.70 to $14.85 on the week. Neurological company CeNes (LSE:CEN) was up 0.8p to 11.9p on the week after Nomura analyst Sam Fazeli began coverage with a buy recommendation and a fair value of 22p (see B16). The company, which had 7.8 million ($14 million) in cash at Dec. 31, enough for about two years, is expecting Phase III results mid-year for its lead program, M6G morphine-6-glucuronide. CEN will be meeting with City investors over the next two weeks to retell its story, now that it has completed the acquisition and integration of CNS company TheraSci (see BioCentury, Dec. 8, 2003). CEN has a market cap of 30 million ($54 million). Elan (ELN) was up $1.53 to $23.53 on the week after licensing its NanoCrystal technology to Roche (SWX:ROCZ) for use with an undisclosed compound (see B3). The technology is used to improve the bioavailability of therapeutics.
Structural GenomiX B8 Suzhou Zhongkai B3 Syn X (TSE:SYY) B5 Tercica (TRCA) B8 Teva (TEVA) A13 TheraSci A19 Tissera (TSSR) B8 Trimeris (TRMS) A18 U of Connecticut B3 Valeant (VRX) B4, B9 Vaso Active (VAPH) A3 Vertex (VRTX) B3 Vical (VICL) B3, B8 Vivus (VVUS) A18, B11 Watson (WPI) B4 Wyeth (WYE) A7, A13 Xenome B11 Yale U B3, B11 Zeptosens B3 ZymoGenetics (ZGEN) A17, B9, B11
Memory (MEMY) B12 Merck (MRK) B3 Metabasis B4 Metaphore B7 Metrika B6 Micromet B2 Millennium (MLNM) A16 MIV Therap (MIVT) B13 MJ Research B6 MP Biomedicals B4 Mylan (MYL) B6 Myriad (MYGN) B9 Nanogen (NGEN) B5 Nanosys A15, B12 Nastech (NSTK) B7 Neoprobe (NEOP) B6 Neose (NTEC) B5 Neurobiological Tech (NTII) A18, B10 Novartis (NVS; SWX:NOVN) B6, B11 NPS (NPSP) B5 Nycomed B5 Onyx (ONXX) A16 Oriental Wave B3 OSI (OSIP) A16, B7 OxiGene (OXGN; SSE:OXGN) B6 Pfizer (PFE) B6 Pharmexa (CSE:PHARMX) A16, B12 Pharming (Euronext:PHARM) B5 Pierre Fabre B3 Porton B2 Prana (ASX:PBT; PRNAY) B9 Prosidion B7 Protherics (LSE:PTI) B8
Provalis (LSE:PRO; PVLS) B5 Purely Proteins B6 QLT (TSE:QLT; QLTI) B6 RegeneRx (RGRX) B8 Renovis (RNVS) A2 Rigel (RIGL) A18, B10, B13 Roche (SWX:ROCZ) A18, B2, B3, B4, B6, B9 Scancell B8 Schering (FSE:SCH; SHR) A13 Schering-Plough (SGP) B6, B9 Scolr (SCLL) B7 Seer Pharma B11 Semafore B8 SeraCare (SRLS) B3 Serono (SWX:SEO; SRA) A13, B10 Shire (LSE:SHP; SHPGY) A7, A9, A19, B4 Southern Research Inst B4 Spectrum (SPPI) B12 State U of New York B3
BioCentury makes people think

We know you have many choices for headlines. But if you need to know what the news means, there is only one journal BioCentury, the Bernstein Report on BioBusiness that is recognized by key decision makers as the best source of perspective, interpretation and analysis for top managers and investors in the biotech community.
BioCentury,
ON
BIOBUSINESS
Price Gains
APRIL 26, 2004
P AGE A20 OF 20
BioCentury 100 Price & Volume Trend

Cumulative weekly performance of 100 bioscience stocks. 12-week period. Line shows Price Level change (Left scale. Index base=1000 on May 10, 1996). Bars show cumulative volume in millions (right scale).
1900 800 700 600 1700 500 1600 400 1500 300 1400 200 1300 100
1800
Stocks with greatest % price increase in the week ended April 23. (Priced above $2.50; 25,000 minimum share volume) Company Ticker $Close $Chg %Chg Vol(00) Zonagen ZONA 3.860 1.030 36% 6913 ImmunoGen IMGN 9.980 2.040 26% 22909 Genta GNTA 13.940 2.600 23% 194400 Avant AVAN 2.770 0.490 21% 63626 Quidel QDEL 8.500 1.420 20% 33424 Illumina ILMN 8.040 1.320 20% 18938 ImClone IMCL 70.300 11.030 19% 253289 DUSA DUSA 12.870 2.010 19% 23401 Cytogen CYTO 14.550 2.200 18% 14603 Iomed IOX 3.000 0.450 18% 2035 GTx GTXI 12.980 1.760 16% 5331 Hollis-Eden HEPH 8.950 1.210 16% 21365
Price Declines
1200 0
BioCentury London Index

Weekly change in the combined market capitalization for 14 bioscience stocks listed on the LSE or AIM, 12-week period. Index base =1000 on May 10, 1996.
700 650 600 550 500 450 400 350 300 250 200 150
Apr 23
Stocks with greatest % price decline (criteria as above). Company Ticker $Close $Chg %Chg Vol(00) Sonus SNUS 5.520 -1.410 -20% 7835 Lynx LYNX 4.210 -0.850 -17% 3410 Medivir MVIR SEK101 -SEK16.5 -14% 1478 november NBX 5.270 - 0.780 -13% 1463 Vernalis 1 VNLS 2.550 -0.350 -12% 42568 Aerogen AEGN 3.281 -0.409 -11% 1497 Affymetrix AFFX 31.390 -3.620 -10% 177914 Cholestech CTEC 8.610 -0.940 -10% 9754 Dynavax DVAX 6.450 -0.700 -10% 1494 Corcept CORT 10.900 -1.100 -9% 5881 Labopharm DDS C5.550 -C0.500 -8% 3063 Antigenics AGEN 9.990 -0.870 -8% 31326 Memory MEMY 8.980 -0.730 -8% 771
Volume Gains
Greatest changes in volume above 25,000 Company Ticker Vol(00) NeuTec NTP 4185 Pharmexa PHARMX 4554 Aeterna 2 AELA 35631 Zonagen ZONA 6913 GPC GPC 11284 november NBX 1463 Cerus CERS 30455 BioVeris BIOV 23883 Nymox NYMX 11567 Affymetrix AFFX 177914 Pharmion PHRM 11416 shares. %Chg 3615% 1005% 937% 852% 561% 490% 465% 435% 427% 396% 395% $Close $Chg 295p 14p DKK30 -DKK1.4 7.350 0.801 3.860 1.030 12.00 - 0.300 5.270 - 0.780 3.960 0.350 12.310 0.550 3.950 -0.310 31.390 -3.620 24.010 -0.110
TFCG Life Sciences Indexes

Weekly change in combined market capitalization. 12-week period. Tier I = market caps>$1B; Tier II <$1B. Base =100 on Dec. 31, 1998.
750 700 650 600 550 500 450 400 350 300 250 200 150 100 50 0
Apr 23 Tier II (180 companies)
1 Includes volume from London Stock Exchange with converted ADSs (ADS = 40 shares) 2 Includes volume from Toronto Stock Exchange Tier I (20 companies)
BioCentury 100 Advance-Decline Trend

Week ended Mar 26 Apr 02 Apr 08 Apr 16 Apr 23 BC100 Price level 1504.63 1605.67 1600.97 1587.16 1649.29 BC100 Stocks gaining 31 94 34 30 75 Gaining vol. (00) 1183073 5320967 1235946 1544595 3688326 BC100 Stocks Declining declining vol. (00) 69 4078787 6 259998 65 2330186 68 2368397 25 1721026
Source: Thomson Financial BioCentury tracks 467 issues that report prices and volume daily. The BioCentury 100 is a subset used to monitor price and volume trends. TFCG Life Sciences Indexes are compiled by Thomson Financial, provider of market intelligence services to publicly held companies.
IO QUITY B EUROPE
2004
Organized by
BioCentury
E.B.D. Group BIO
May 17-18, 2004

Sheraton Grand Hotel Edinburgh, U.K.
INVESTMENT PROFESSIONALS
Register Now & Reserve Your Seat

INTRODUCING
Acknowledging the Support of Gold Equity Sponsor
THE BIOEQUITY EUROPE PRESENTING COMPANIES

Celebrating its 5th anniversary, BioEquity Europe has established itself as the magnet for financial dealmakers and the premier venue for life science companies positioning themselves to attract capital from international investors. The 2004 meeting focuses on Europes growing inventory of companies facing mid- and later-stage clinical milestones, especially in the areas of cancer, neurology, cardiology and metabolic diseases, as well as a special track of companies building next-generation protein therapeutics.
Silver Equity Sponsors

Palmer & Dodge LLP Mayer, Brown, Rowe & Maw Cooley Godward
LLP
Pharma Sponsor
Astra Zeneca
Contributing Sponsors
Techno Venture Management Deutsche Bank DVC Deutsche Venture Capital SOFINNOVA Partners Bank Vontobel 3i Fortis Bank SWX Swiss Exchange CMS Deutsche Boerse
BioEquity Europe also provides a venue explicitly designed to maximize financial networking, with the 2004 program offering small discussion sessions with a faculty of seasoned life science investors from Europe and North America.
Ablynx N.V. Addex Pharmaceuticals S.A. Affibody AB Arakis Ltd. Ardana Bioscience Ltd. Ark Therapeutics Group plc (LSE:AKT) Arpida Ltd. ARYx Therapeutics Inc. AVONTEC GmbH Basilea Pharmaceutica Ltd. (SWX:BSLN) BioMarin Pharmaceutical Inc.
(BMRN; SWX:BMRN)
Regional Host
and Regional Host Members

Ernst & Young Wood Mackenzie Scottish Equity Partners Scottish Widows Investment Partnership BIA ITI Life Sciences
Register Online at www.biocentury.com
Biolipox AB BioVex Ltd. BioXell SpA CareX S.A. Cellectis S.A. CeNeS Pharmaceuticals plc (LSE:CEN) Coley Pharmaceutical Group CombinatoRx Inc. Cyclacel Ltd. deCODE genetics Inc. (DCGN) DeveloGen AG Domantis Ltd. Encysive Pharmaceuticals Inc. (ENCY) Epigenomics AG Evotec OAI AG (FSE:EVT) Exelixis Inc. (EXEL) ExonHit Therapeutics S.A. Faust Pharmaceuticals 4SC AG Gamida-Cell Ltd. Global Genomics AB
GLYCART biotechnology AG IDEA AG igeneon AG Intercell AG Jerini AG Laxdale Ltd. Lorantis Ltd. MediGene AG (FSE:MDG) Micromet AG Myogen Inc. (MYOG) NeuroSearch A/S (CSE:NEUS) Neuro3d S.A. Newron Pharmaceuticals SpA OctoPlus B.V. Onyvax Ltd. Orexo AB Oxxon Pharmaccines Ltd. PAION GmbH PheneX Pharmaceuticals AG PIERIS Proteolab AG Probiodrug AG Serono S.A. (SWX:SEO; SRA) SiRENADE Pharmaceuticals AG Sosei Co. Ltd. Speedel Group SWITCH Biotech AG TeGenero AG Trigen Ltd. U3 Pharma AG VaxGen Inc. (VXGN) Vernalis plc (LSE:VER; VNLS) Wilex AG Ys Therapeutics Co. Ltd.
BioCentury Part II
VOL. 12, N O. 19
THE COMPLETE REPORT
OF
BIOBUSINESS NEWS
APRIL 26, 2004
PAGE B1 OF 13
BioBusiness for the week ended April 23

COMPANY NEWS Deals (Page B2)
Adprotech/Inflazyme (TSE:IZP) Anadys (ANDS)/LG Life Sciences Antisoma (LSE:ASM)/Inverness Medical (IMA) Astex/AstraZeneca (LSE:AZN; AZN) Avant (AVAN)/DynPort BioInvent (SSE:BINV)/Enzon (ENZN)/ Micromet BioMarin (BMRN; SWX:BMRN)/Medicis (MRX) Bioseek/Cognia/Harvard U/State U of New York/Yale U Boston (BBII)/SeraCare (SRLS) Bristol-Myers (BMY)/Dow (DOW) Bristol-Myers (BMY)/Pierre Fabre Cell Signaling Tech/Zeptosens Cerus (CERS)/MedImmune (MEDI) CytRx (CYTR)/Vical (VICL) Discovery Partners (DPII)/Vertex (VRTX) Dragon (TSE:DDD; DRUG)/Suzhou Zhongkai Echelon/M.D. Anderson Cancer Ctr Elan (ELN)/Roche (SWX:ROCZ) Enzo (ENZ)/U of Connecticut Genelabs (GNLB)/MP Biomedicals GeneProt/Lundbeck (CSE:LUN) Gilead (GILD)/Southern Research Inst GTx (GTXI)/Beckman Coulter (BEC) ID Biomedical (TSE:IDB; IDBE)/Shire (LSE:SHP; SHPGY) Inpharmatica/Biotica Isotechnika (TSE:ISA)/Roche (SWX:ROCZ) Kissei/Watson (WPI) Martek (MATK)/DSM Metabasis/Valeant (VRX) Nanogen (NGEN)/Syn X (TSE:SYY) Neose (NTEC)/BioGeneriX NPS (NPSP)/Nycomed Pharming (Euronext:PHARM)/Laboratorios del Dr. Esteve Provalis (LSE:PRO; PVLS)/Edmond
Using BioCentury Part II

BioCentury Part II is a comprehensive compendium of business news for management and investors in bioscience companies. It is organized into three departments: Company News, Clinical News and Financial News. The index on this page lists all the companies covered this week. The news items in each department are organized alphabetically by company. When more than one company is listed, the biotech company is shown first. Each brief is labeled with one or more applicable business categories from the following list: ADMET; Agbio/Environmental; Antibodies; Autoimmune; Bioinformatics; Biomanufacturing; Biopharmaceuticals; Cancer; Cardiovascular; Chemistry; Combinatorial biology; Computational chemistry/biology; Dental; Dermatology; Diagnostic; Drug delivery; Endocrine; Finance; Functional genomics; Gastrointestinal; Gene/Cell therapy; Generics; Genitourinary; Genomics; Hematology; Hepatic; High throughput screening; Infectious; Inflammation; Metabolic; Microarrays; Microfluidics; Musculoskeletal; Neurology; Nutraceuticals; Ophthalmic; Other; Pharmaceuticals; Pharmacogenetics; Proteomics; Pulmonary; Renal; Supply/Service; Transplant; Veterinary
Avecia Benitec (ASX:BLT) Bioreason Boston Biomedica (BBII) Carolina Pharma Conforma Corgentech Edwards Lifesciences (EW) Genencor (GCOR) Genitope (GTOP) MedImmune MEDI) Metaphore Nastech (NSTK) Protherics (LSE:PTI) RegeneRx (RGRX) Scancell Scolr (SCLL) Semafore Structural GenomiX Tercica (TRCA) Tissera (TSSR) Vical (VICL)
CLINICAL NEWS Clinical Results (Page B8)

Alexion (ALXN) Bioenvision (BIV) CV Therap (CVTX) InKine (INKP) Prana (ASX:PBT; PRNAY) Valeant (VRX) ZymoGenetics (ZGEN)
Preclinical Results (Page B9)

QLT; QLTI)/Novartis (NVS; SWX:NOVN) Schering-Plough (SGP) DynPort Myriad (MYGN)
Sales & Marketing (Page B6)

Bristol-Myers (BMY)/Metrika co.don (FSE:CNW) Inhibox/Purely Proteins Roche (SWX:ROCZ)
Clinical Status (Page B9)

Advanced Biotherapy (ADVB) Alkermes (ALKS) Alteon (ALT) Anika (ANIK) Cell Therap (CTIC; NMERC:CTIC) CuraGen (CRGN) Ilex (ILXO) Inspire (ISPH) Introgen (INGN) Neurobiological Tech (NTII) Rigel (RIGL) Vivus (VVUS) Xenome ZymoGenetics (ZGEN) See next page
Regulatory (Page B5)

Altana (FSE:ALT; AAA) Antigenics (AGEN) Barbeau Pharma/ESP Pharma Genta (GNTA)/Aventis (AVE) Genzyme (GENZ)/Inamed (IMDC) GlaxoSmithKline (LSE:GSK; GSK) ImClone (IMCL) J&J (JNJ)/Schering-Plough (SGP) Mylan (MYL) Neoprobe (NEOP) OxiGene (OXGN; SSE:OXGN)/QLT (TSE:
Other News (Page B6)

Applied Biosystems (ABI)/MJ Research/Roche (SWX:ROCZ) co.don (FSE:CNW) Immuno-Designed Molecules OSI (OSIP)
Management Tracks (Page B7)

Advanced Viral Res (ADVR) Agencourt
BioCentury Part II
APRIL 26, 2004
PAGE B2 OF 13
COMPANY NEWS/Deals, Regulatory, Sales & Marketing, Management Tracks

DEALS
Adprotech Ltd., Cambridge, U.K. Inflazyme Pharmaceuticals Ltd. (TSE:IZP), Vancouver, B.C. Business: Inflammation IZP completed its previously announced acquisition of Adprotech for 12.7 million shares, valued at C$18.4 million (US$13.7 million) using IZPs pre-deal closing price of C$1.45 on April 20. The deal was announced earl i er t hi sm ont h (see BioCentury, April 12). Anadys Pharmaceuticals Inc. (ANDS), San Diego, Calif. LG Life Sciences, Seoul, South Korea Business: Infectious ANDS exercised an exclusive option to license LGs LB80380, a nucleotide analog in Phase II testing to treat chronic HBV infection (see BioCentury, March 1). The companies will jointly develop LB80380. ANDS obtains exclusive commercialization rights in North America, Europe, Japan and most countries worldwide excluding China, India, Korea and Southeast Asia. The companies will pay each other royalties on sales in their respective territories. Antisoma plc (LSE:ASM), London, U.K. Inverness Medical Innovations Inc. (IMA), Waltham, Mass. Business: Cancer ASM will pay IMA $300,000 in cash and up to $1.5 million in milestones to acquire IMAs royalty rights to ASMs R1549 and R1550 compounds, which are mouse and humanized variants of the HMFG1 antibody. R1549, a yttrium-90 radiolabeled antibody against PEM, is in Phase III trials for ovarian cancer. R1550, a humanized HMFG1 antibody against MUC1, is in a Phase I trial to treat locally advanced or metastatic breast cancer. Both compounds are being co-developed with Roche (SWX:ROCZ, Basel, Switzerland). Astex Technology Ltd., Cambridge, U.K. AstraZeneca plc (LSE:AZN; AZN), London, U.K. Business: Neurology AZN selected for further development specific molecules from the companies 2003 ADMET deal (see BioCentury, March 10, 2003). The selection triggered a second milestone to Astex. Avant Immunotherapeutics Inc. (AVAN), Needham, Mass. DynPort Vaccine Co. LLC, Frederick, Md. Business: Infectious AVAN received $3 million from DynPort under a subcontract to discover and develop an oral combination vaccine against anthrax and plague for the U.S. Department of Defense (see BioCentury, Jan. 27, 2003). The money will support human clinical trials of AVANs plague vaccine candidate. DynPort, which is a joint venture between DynCorp (Reston, Va.) and Porton International Inc. (Washington, D.C.), has an ongoing 10-year contract with the Department of Defense to develop vaccines against biological warfare agents. BioInvent International AB (SSE:BINV), Malmo, Sweden Enzon Inc. (ENZN), Bridgewater, N.J. Micromet AG, Munich, Germany Business: Antibodies BINV obtained non-exclusive access from Micromet to Micromets and ENZNs shared IP covering single-chain antibody (SCA) technologies. BINV will apply SCA to its antibody library and can use the technologies for both internal programs and development partnerships. BINV also can sublicense the technology to collaboration partners. Micromet receives an upfront payment and annual maintenance fees plus potential sublicensing fees. Micromet and ENZN will share the revenues under their 2002 development and marketing deal (see BioCentury, April 15, 2002). BioMarin Pharmaceutical Inc. (BMRN; SWX:BMRN), Novato, Calif. Medicis Pharmaceutical Corp. (MRX), Phoenix, Ariz. Business: Inflammation BMRN will pay a total of $175 million for Ascent Pediatrics, the pediatrics business of MRX. BMRN said the move will help it become a fully integrated pediatrics-focused biopharmaceutical company. BMRN said it will partner its non-pediatric pipeline products, including Vibrilase in Phase I testing for burns and wounds, and preclinical compounds Chondroitinase for spinal cord injury, and NeuroTrans for delivering proteins across the blood-brain barrier. BMRN will pay MRX $10 million at closing. MRX also will receive $145 million in cash over the next 5 years plus $20 million in stock in 2009. BMRN also will assume $15 million of MRXs debt. Ascent markets Orapred, a corticosteroid to treat asthma in children. The compound is expected to have net sales of about $42 million this year. Two additional formulations of Orapred are in development: Orapred 2, a non-refrigerated formulation that could be launched in 2005, and a rapid-dissolve tablet dose formulation that could be launched in early 2007. BMRN plans to See next page BioTrove Memory (MEMY) MIV (MIVT)
Clinical News, from previous page Other Research News (Page B11)
Agrobiogen Icon Novartis (NVS; SWX:NOVN) Yale U
Callisto (CLSP) DxS Dynogen Incara (ICRA) Integrated (INB) Spectrum (SPPI)
Analysts (Page B13)

Amgen (AMGN) Antigenics (AGEN) CeNeS (LSE:CEN) Gilead (GILD) ImClone (IMCL) Invitrogen (IVGN) Isotechnika (TSE:ISA) Lexicon (LEXG) MedImmune (MEDI) Rigel (RIGL)
Proposed Offerings (Page B12)

Auxilium Nanosys Pharmexa (CSE:PHARMX)
FINANCIAL NEWS Completed Offerings (Page B12)

Bruker (BRKR)
Other Financial News (Page B12)

Array (ARRY)
BioCentury Part II
Deals, from previous page
launch Orapred in markets outside the U.S. by early 2006. The products will be marketed in the U.S. by BMRN through a 73-person sales force that BMRN acquired in the deal. The company plans to use that sales force to market its Aryplase enzyme replacement therapy to treat MPSVI, for which Phase III data are expected this quarter. BMRN expects the acquisition to decrease its estimated 2004 loss of $68-$70 million, but did not provide specific guidance. The company said it will give more specific guidance in the third quarter. Bioseek Inc., Burlingame, Calif. Cognia Corp., New York, N.Y. Harvard University, Cambridge, Mass. State University of New York, Binghamton, N.Y. Yale University, New Haven, Conn. Business: Bioinformatics Cognia licensed its molecular information management system to Bioseek and the universities. Boston Biomedica Inc. (BBII), West Bridgewater, Mass. SeraCare Life Sciences Inc. (SRLS), Oceanside, Calif. Business: Diagnostic, Supply/Service SRLS signed an agreement to purchase BBIIs BBI Diagnostics and BBI Biotech Research Laboratories divisions for $30 million in cash. SRLS, which provides biological material manufacturing services, expects the deal to be accretive to EPS. BBII expects the deal to close by Aug. 15, and said the sale will let it focus on its Pressure Cycling Technology (PCT). Bristol-Myers Squibb Co. (BMY), Princeton, N.J. Dow Chemical Co. (DOW), Midland, Mich. Business: Supply/Service DOWs Dowpharma subsidiary will use its particle engineering technologies to improve the solubility of undisclosed compounds from BMY. BMY will fund feasibility studies, and Dowpharma is eligible for milestones and royalties. Bristol-Myers Squibb Co. (BMY), Princeton, N.J. Pierre Fabre Medicament, Castres Cedex, France Business: Cancer BMY received rights from Pierre Fabre to develop and market Javlor vinflunine, a vinca alkaloid chemotherapeutic, in the U.S., Canada, Japan, Korea and selected Southeast Asian countries. Pierre Fabre will retain development and marketing rights in all other countries. Javlor is in European Phase III trials to treat bladder cancer and non-small cell lung cancer (NSCLC) and Phase II trials to treat breast and ovarian cancer. BMY said it will discuss with FDA whether additional clinical trials in the U.S. will be necessary to submit an NDA. Cell Signaling Technology Inc., Beverly, Mass. Zeptosens AG, Witterswil, Switzerland Business: Antibodies, Supply/Service The companies partnered to combine Cell Signalings reagents, including phospho-specific antibodies, with Zeptosens ZeptoMark protein microarray technology. The combined product will be used for protein expression analysis and protein activation profiling. Cerus Corp. (CERS), Concord, Calif. MedImmune Inc. (MEDI), Gaithersburg, Md. Business: Cancer The companies partnered to develop and commercialize a vaccine
APRIL 26, 2004
PAGE B3 OF 13
to treat cancers of the breast, prostate and colon, and metastatic melanoma. CERSs Listeria vaccine technology will be used to develop a vaccine against MEDIs EphA2 protein. The companies said an antiEphA2 vaccine showed antitumor responses in mice. Under the deal, MEDI is responsible for clinical development, manufacturing and commercialization. CERS will participate in development and will receive an upfront payment and development funding, and is eligible for milestones and royalties. CytRx Corp. (CYTR), Norcross, Ga. Vical Inc. (VICL), San Diego, Calif. Business: Gene/Cell therapy CYTR received a $100,000 milestone from VICL triggered by the start of a Phase I trial of VICLs plasmid DNA vaccine for cytomegalovirus (CMV), which uses CYTRs TranzFect technology. Under a 2001 deal, VICL has exclusive rights to CYTRs TranzFect poloxamer technology to enhance viral or non-viral delivery of polynucleotides, except for prostate-specific membrane antigen and four infectious disease targets that CYTR previously licensed to Merck & Co. Inc. (MRK, Whitehouse Station, N.J.) (see BioCentury, Dec. 24, 2001). Discovery Partners Inc. (DPII), San Diego, Vertex Pharmaceuticals Inc. (VRTX), Cambridge, Mass. Business: Chemistry DPII will use its focused library synthesis and medicinal chemistry capabilities to support VRTXs drug discovery efforts for an undisclosed research program. Dragon Pharmaceuticals Inc. (TSE:DDD; DRUG), Vancouver, B.C. Suzhou Zhongkai Bio-Pharmaceuticals Co. Ltd., Suzhou, China Business: Cancer DDD received exclusive worldwide rights, excluding China, to Zhongkais recombinant human granulocyte colony stimulating factor (G-CSF). Zhongkais product is approved in China to increase white blood cell counts in cancer patients receiving chemotherapy. DDD is merging with Oriental Wave Holding Ltd. (British Virgin Islands), and the combined company plans to offer generics chemical intermediates (see BioCentury, March 29). Echelon Biosciences Inc., Salt Lake City, Utah M.D. Anderson Cancer Center, Austin, Texas Business: Cancer Echelon and the center will collaborate to develop therapeutics against new cancer targets beginning with PI3 kinase. The center will receive warrants to buy Echelon stock, and Echelon will receive an option to market compounds developed under the deal. Elan Corp. plc (ELN), Dublin, Ireland Roche (SWX:ROCZ), Basel, Switzerland Business: Drug delivery ROCZ licensed ELNs NanoCrystal technology for use with an undisclosed compound in development. In exchange for providing formulation services and access to the technology, ELN will receive research revenues and is eligible for milestones and royalties. NanoCrystal technology is used to improve the bioavailability of therapeutics. Enzo Biochem Inc. (ENZ), Farmingdale, N.Y. University of Connecticut Health Center, Farmington, Conn. Business: Musculoskeletal Under two deals with the university, ENZ subsidiary Enzo Therapeutics Inc. will license and co-develop therapeutics to stimulate and See next page
BioCentury Part II
enhance bone formation. The technology relates to the modulation of signaling pathways in cell development and differentiation by signaling proteins and small molecules that act in both osteoblasts and the primitive cells of the hematopoietic system. Under the licensing deal, ENZ holds an exclusive license to the technology and is a co-inventor along with the university. Genelabs Technologies Inc. (GNLB), Redwood City, Calif. MP Biomedicals LLC, Irvine, Calif. Business: Diagnostic GNLB completed the sale of its diagnostics business, selling all shares of Genelabs Asia Pte. Ltd. to MP Biomedicals. GNLB said the sale will allow it to focus on drug discovery and development. GeneProt Inc., Geneva, Switzerland H. Lundbeck A/S (CSE:LUN), Copenhagen, Denmark Business: Proteomics, Neurology GeneProt will use its MicroProt process to study the proteomics of fluid samples taken from a rodent model of CNS disease. LUN will have exclusive rights to commercialize results. Gilead Sciences Inc. (GILD), Foster City, Calif. Southern Research Institute, Birmingham, Ala. Business: Chemistry The institute will provide chemistry and screening services to GILD for an undisclosed early drug discovery program. GTx Inc. (GTXI), Memphis, Tenn. Beckman Coulter Inc. (BEC), Fullerton, Calif. Business: Genitourinary GTXI and BECs Hybritech Inc. unit partnered to develop assays for prostate cancer. GTXI will provide clinical samples from its Phase IIb trial of Acapodene to reduce the incidence of high-grade prostatic intraepithelial neoplasia (PIN). BEC will use the samples to determine whether its panel of proPSA serum markers can help diagnose the presence of PIN. ID Biomedical Corp. (TSE:IDB; IDBE), Vancouver, B.C. Shire Pharmaceuticals Group plc (LSE:SHP; SHPGY), Basingstoke, U.K. Business: Infectious SHP will sell its vaccine business, Shire Biologics, to vaccine company IDB for $120 million. SHP will receive $60 million in cash through two equal payments at closing and 12 months later. The remaining $60 million will be paid in about 5.4 million IDB shares or cash in the first 22 months following closing. In 2003, the vaccines business generated revenues of $24.8 million and a net operating loss of $21.9 million. IDB said the deal gives it an antigen supply for IDBs FluInsure intranasal influenza vaccine. Also included are two products marketed in Canada: Fluviral, an intramuscular influenza prophylactic to treat influenza; and NeisVac-C for meningitis C. Shire Biologics also is developing vaccines for streptococcus pneumonia, neisseria meningitidis, group B streptococcus and group A streptococcus. The business employs 400 in Quebec City and Laval, Quebec, and Northborough, Mass. SHP will provide IDB with a loan facility of $100 million, which IDB can draw down over the next 4 years to fund development of injectible flu and pipeline products within the vaccine business. The loan will be repaid out of income generated by IDBs non-Canadian sales of the
APRIL 26, 2004
PAGE B4 OF 13
injectible flu and other pipeline products. Bear, Stearns advised SHP, and UBS and Canaccord advised IDB. Inpharmatica Ltd., London, U.K. Biotica Technology Ltd., Cambridge, U.K. Business: ADMET Under a two-year deal, Inpharmatica will provide ADME services to improve the pharmacokinetics of rapamycin analogs and other antiproliferatives in development at Biotica. The services include in vitro ADME screening, analysis and interpretation of ADME data, and lead optimization. Isotechnika Inc. (TSE:ISA), Edmonton, Alberta Roche (SWX:ROCZ), Basel, Switzerland Business: Transplant ISA and ROCZ renegotiated a 2002 deal covering ISA247, a mixture of cis and trans isomers of a small molecule immunosuppressant (see BioCentury, April 15, 2002). As amended, ISA will independently develop the trans isomer version of ISA247 for renal transplant and psoriasis. ISA said development of the mixed version of ISA247, which had completed Phase II testing in psoriasis and kidney transplantation, is no longer being pursued. ROCZ has an option to assume development and marketing rights to trans-ISA247 for transplant indications up to 90 days after a planned Phase II renal transplant trial. If exercised, ISA would receive a $75 million payment and milestones, and ROCZ would be responsible for 70% of future development costs. ISA also would be eligible to receive royalties. ISA retains worldwide rights to develop and sell the product for non-transplant indications. ISA said trans-ISA247 is in Phase I doseranging trials. The company plans to begin a Canadian Phase III psoriasis trial by year end, and a Phase IIb renal transplantation trial in the first quarter of 2005. ISA has about $59 million in cash. Kissei Pharmaceutical Co. Ltd., Nagano, Japan Watson Pharmaceuticals Inc. (WPI), Corona, Calif. Business: Genitourinary, Cancer WPI received exclusive rights in the U.S., Canada and Mexico to develop and market Kisseis KMD-3213 silodosin, a selective adrenergic receptor alpha 1a antagonist for benign prostatic hyperplasia (BPH). The compound has completed a U.S. Phase II trial. Kissei is eligible for milestones and royalties. In Japan, Kissei and partner Daiichi Pharmaceutical Co. Ltd. (Tokyo, Japan) are preparing an NDA. Martek Biosciences Corp. (MATK), Columbia, Md. DSM N.V., Heerlen, The Netherlands Business: Nutraceuticals The companies expanded a 1997 manufacturing and supply deal to include cross-licensing of IP relating to arachidonic acid (ARA) and joint R&D to expand applications for ARA. MATK received rights to certain DSM IP, as well as certain ARA production rights. DSM gained access to MATKs IP related to ARA manufacturing, as well as rights to use MATKs technology for non-human applications. DSM, which supplies ARA to MATK, also will expand its manufacturing capacity for ARA. Metabasis Therapeutics Inc., San Diego, Calif. Valeant Pharmaceuticals International (VRX), Costa Mesa, Calif. Business: Infectious Under a 2001 deal, Metabasis received a $1 million milestone payment from VRX triggered by the decision to start a Phase II trial of remofovir (formerly Hepavir B) to treat chronic HBV infection. Under See next page
BioCentury Part II
the original deal, VRX is responsible for clinical development of the compound, an oral prodrug of the antiviral adefovir. Nanogen Inc. (NGEN), San Diego, Calif. Syn X Pharma Inc. (TSE:SYY), Toronto, Ontario Business: Diagnostic, Cardiovascular NGEN completed its previously announced acquisition of point-ofcare diagnostic company SYY for 1.6 million shares, which values the deal at $12.3 million using NGENs close of $7.68 on April 20, the day before the deal closed. NGEN announced the acquisition in February (see BioCentury, Feb. 16). Neose Technologies Inc. (NTEC), Horsham, Penn. BioGeneriX AG, Mannheim, Germany Business: Biomanufacturing, Hematology The companies partnered to use NTECs GlycoPEGylation technology to develop a long-acting version of granulocyte colony stimulating factor (G-CSF) to promote white blood cell production. The companies will share preclinical development expenses, and BioGeneriX is responsible for clinical expenses. NTEC will receive an upfront fee and will have commercialization rights in the U.S., Canada, Mexico and Japan. BioGeneriX will have rights in Europe and the rest of the world. The companies will receive royalties on each others sales. NPS Pharmaceuticals Inc. (NPSP), Salt Lake City, Utah Nycomed Group A/S, Roskilde, Denmark Business: Musculoskeletal NPSP granted development and marketing rights to Nycomed for osteoporosis candidate Preos in Europe, the Commonwealth of Independent States and Turkey. In exchange, Nycomed will purchase $40 million of NPSP stock and assume responsibility for conducting Phase IIIb and IV trials in Europe, representing at least a $25 million investment. NPSP also is eligible for up to $25 million in milestones plus royalties. NPSP plans to submit an NDA by year end for Preos, an injectable full-length recombinant human parathyroid hormone. Pharming Group N.V. (Euronext:PHARM), Leiden the Netheralnds Laboratorios del Dr. Esteve S.A., Barcelona, Spain Business: Cardiovascular The companies signed a letter of intent under which PHARM will license its recombinant human C1 inhibitor (rhC1INH) to Laboratorios del Dr. Esteve. The companies hope to close the deal by June 30. They will partner to develop, market and sell rhC1INH in Spain, Portugal and Greece to treat hereditary angioedema (HAE). rhC1INH has completed Phase II studies, and PHARM expects to begin Phase III trials by mid-year. PHARM will receive R&D contributions, milestone and royalties. Provalis plc (LSE:PRO; PVLS), Deeside, U.K. Edmond Pharma SpA, Paderno dAdda, Italy Business: Diagnostic PRO will distribute Erdotin erdosteine from Edmond Pharma in the U.K. and Ireland for at least 10 years. PRO will be the exclusive distributor for the first 5 years and has the option to acquire Erdotin a mucolytic agent to treat chronic bronchitis or chronic obstructive pulmonary disease (COPD) for a predetermined amount after three years. PRO will pay 200,000 ($239,800) in installments towards development and regulatory costs. Erdotin is undergoing European registration.
APRIL 26, 2004 REGULATORY
PAGE B5 OF 13
Altana AG (FSE:ALT; AAA), Bad Homburg, Germany Product: Alvesco ciclesonide Business: Inflammation The U.K. granted marketing approval for Alvesco inhaled corticosteroid to treat persistent asthma in adults. ALT said the U.K. will serve as the Reference Member State under the European Mutual Recognition Procedure. ALT did not disclose when it plans to launch Alvesco but said it hopes to coordinate launch timing in several European countries. Alvesco was approved in Australia in February. The product is partnered with Aventis SA (AVE, Strasbourg, France) in the U.S., where the partners submitted an NDA in December 2003. Antigenics Inc. (AGEN), New York, N.Y. Product: Oncophage (HSPPC-96) Business: Cancer AGEN plans to submit over the next several weeks additional product characterization data requested by FDA for the companys Oncophage cancer vaccine to treat renal cell carcinoma (RCC). FDA lifted a partial clinical hold on the compound last November. Barbeau Pharma Inc., Northfield, Ill. ESP Pharma Inc., Edison, N.J. Product: Hydralazine Business: Cardiovascular FDA granted Orphan Drug designation for the companies Hydralazine peripheral vasodilator to treat severe intrapartum hypertension associated with severe pre-eclampsia and eclampsia of pregnancy. Genta Inc. (GNTA), Berkeley Heights, N.J. Aventis SA (AVE), Strasbourg, France Product: Genasense oblimersen Business: Cancer The partners began an expanded access program to make GNTAs Genasense available to chemotherapy-naive patients with advanced melanoma. The antisense agent targeting Bcl-2 is under FDA review in combination with dacarbazine for the indication, and has a PDUFA date of June 8. FDAs Oncologic Drugs Advisory Committee will review the Genasense NDA on May 3. Genzyme Corp. (GENZ), Cambridge, Mass. Inamed Corp. (IMDC), Santa Barbara, Calif. Product: Hylaform (Hylan-B gel) Business: Dermatology FDA granted marketing approval to IMDC and GENZ for Hylaform, a hyaluronic acid-based dermal filler for injection into mid- to deep dermis to correct moderate to severe facial wrinkles and folds. The partners said no pre-treatment skin test is required and that they will start shipping the product immediately. GENZ developed and manufactures Hylaform. IMDC holds worldwide marketing and distribution rights. GlaxoSmithKline plc (LSE:GSK; GSK), London, U.K. Product: Advair Diskus 100/50 fluticasone propionate 250 g and salmeterol 50 g inhalation powder Business: Pulmonary FDA granted marketing approval for Advair Diskus to treat children ages 4-11 with asthma who are symptomatic on inhaled corticosteroid monotherapy. See next page
BioCentury Part II
Regulatory, from previous page
ImClone Systems Inc. (IMCL), New York, N.Y. Product: Manufacturing plant Business: Cancer FDA accepted for review a CMC supplemental BLA for IMCLs BB36 manufacturing facility (Branchburg, N.J.). The PDUFA date for the sBLA is June 18. If BB36 is approved, IMCL said it and partner Bristol-Myers Squibb Co. (BMY, Princeton, N.J.) will be able to meet full commercial demand for colorectal cancer drug Erbitux cetuximab. In February, IMCL and BMY said that FDA had approved Lonza Biologics (Slough, U.K.) to manufacture Erbitux for commercial use in the U.S., and that supplies of the drug manufactured at Lonzas facility would be used to meet initial demand. BB36 has FDA approval to manufacture Erbitux for investigational use, and Swiss approval to manufacture commercial product. Boehringer Ingelheim (Ingelheim, Germany) also manufactures the drug in Europe. In February, Erbitux was approved in combination with irinotecan to treat metastatic colorectal cancer. The antibody against epidermal growth factor (EGF) receptor also was approved as monotherapy in patients who cannot tolerate Camptosar irinotecan from Pfizer Inc. (PFE, New York, N.Y.). Johnson & Johnson (JNJ), New Brunswick, N.J. Schering-Plough Corp. (SGP), Kenilworth, N.J. Product: Remicade infliximab monoclonal antibody Business: Autoimmune FDA accepted for filing Centocors sBLA for Remicade to treat ankylosing spondylitis. The combination of Remicade and methotrexate is approved to reduce the signs and symptoms, inhibit the progression of structural damage and improve physical function in patients with moderately to severely active RA who have had an inadequate response to methotrexate alone. The anti-TNF alpha antibody also is approved in the U.S. to treat Crohns disease and in Europe to treat Crohns disease and ankylosing spondylitis. Centocor (Malvern, Penn.) is a subsidiary of JNJ. Remicade is marketed in Europe by SGP. Mylan Laboratories Inc. (MYL), Pittsburgh, Penn. Product: Apokyn apomorphine injection Business: Neurology FDA granted marketing approval to MYLs Bertek Pharmaceuticals Inc. subsidiary (Research Triangle Park, N.C.) for its Apokyn to treat off episodes associated with Parkinsons disease (PD). MYL expects to launch the product by July and said it must perform post-marketing studies. Apokyn has Orphan Drug status. Neoprobe Corp. (NEOP), Dublin, Ohio Product: RIGScan CR49 (125I-CC49 monoclonal antibody) Business: Diagnostic NEOP said FDA told it to run an additional Phase III trial of RIGScan for the intraoperative detection of metastatic colorectal cancer. FDA requested additional clinical data after completing its review of NEOPs BLA, which was submitted in January 1997. OxiGene Inc. (OXGN; SSE:OXGN), Watertown, Mass. Product: Combrestatin A4 Prodrug (CA4P) Phosphatase activated tumor vascular targeting agent Business: Cancer EMEA granted Orphan Medicinal Product designation to CA4P to treat anaplastic thyroid cancer (ATC). The compound is in Phase II testing in the U.S. for the indication.
APRIL 26, 2004
PAGE B6 OF 13
QLT Inc. (TSE:QLT; QLTI), Vancouver, B.C. Novartis AG (NVS; SWX:NOVN), Basel, Switzerland Product: Visudyne verteporfin Business: Ophthalmic The partners Visudyne received reimbursement in Japan to treat wet age-related macular degeneration (AMD). Visudnye was approved in Japan in October 2003. Schering-Plough Corp. (SGP), Kenilworth, N.J. Product: Peg-Intron peginterferon alfa-2b Business: Infectious SGP subsidiary Schering-Plough K.K. submitted an NDA in Japan requesting approval of Peg-Intron in combination with its Rebetol ribavirin to treat chronic HCV. The NDA has priority review.
SALES & MARKETING

Bristol-Myers Squibb Co. (BMY), Princeton, N.J. Metrika Inc., Sunnyvale, Calif. Business: Diagnostic BMY received exclusive U.S. sales and distribution rights to Metrikas A1cNow diabetes monitor, an OTC product to measure blood sugar control. co.don AG (FSE:CNW), Berlin, Germany Business: Dermatology CNW launched its chondrotransplant Disc, an autologous disc cell transplant to treat disc degeneration. Inhibox Ltd., Oxford, U.K. Purely Proteins Ltd., Cambridge, U.K. Business: Supply/Service The partners launched screening services for phosphatases, kinases and proteases. The discovery services combine computational technologies from Inhibox and laboratory-based screening technologies from Purely Proteins. Roche Ltd. (SWX:ROCZ), Basel, Switzerland Business: Diagnostic ROCZs subsidiary Roche Diagnostics Corp. (Indianapolis, Ind.) launched in Europe its Amplicor human papillomavirus (HPV) PCRbased test kit. The test detects all 13 DNA genotypes of the HPV. The kit has CE mark approval.
OTHER NEWS
Applied Biosystems Group (ABI), Foster City, Calif. MJ Research Inc., Waltham, Mass. Roche (SWX:ROCZ), Basel, Switzerland Business: Supply/Service ABI said that a jury in the U.S. District Court for the District of Connecticut, decided in favor of ABI and ROCZs Roche Molecular Diagnostics unit in a patent infringement suit against MJ Research concerning patents covering PCR and thermal cycler technologies. The jury found that MJ Research infringed the following U.S. patents: 4,683,195; 4,683,202; 4,965,188; 5,656,493; 5,333,675; and 5,475,610. ABI and ROCZ were awarded $19.8 million in damages. ABI said the companies will pursue enhancement of the damages, because the jury found infringement of four of the patents to be willful. The courts decision concludes the first phase of a two-phase trial. The second phase, which will review MJ Researchs counterclaim that See next page
BioCentury Part II
Other News, from previous page
ABI violated antitrust laws, will begin in July. ABI said MJ Research filed for bankruptcy protection in March. co.don AG (FSE:CNW), Berlin, Germany Business: Dermatology The company restructured and reduced its head count by 23% to 24 from 32. The cuts will reduce its annual burn rate by 33% to less than 2 million ($2.4 million). The restructuring follows slower than expected market development for CNWs tissue engineered products. CNW had 2.8 million ($3.4 million) in cash at Dec. 31, 2003. The company said it has enough cash to last until 2005. Immuno-Designed Molecules SA, Paris, France Business: Cancer IDM opened in Irvine, Calif., a cGMP manufacturing center dedicated to the production of its Cell Drugs for clinical trials. IDM said production of Collidem, a therapeutic vaccine containing autologous dendritic cells loaded with peptides, began in January. Collidem is in Phase I/II trials to treat colorectal cancer. OSI Pharmaceuticals Inc. (OSIP), Melville, N.Y. Business: Endocrine, Cancer OSIP will invest a further $40 million in its majority-owned subsidiary, Prosidion Ltd. (Oxford, U.K.). The first installment of $10 million has been invested, which brings to 81% OSIPs stake in the company. OSIP formed Prosidion last year in order to focus on oncology. The subsidiary is developing small molecules targeting glucokinase activation and glycogen phosphorylase inhibition, and expects to begin clinical trials in 2005.
APRIL 26, 2004
PAGE B7 OF 13
Agencourt Bioscience Corp., Beverly, Mass. Business: Genomics Hired: John Linnan as VP of sales, formerly district sales manager for New England at Applied Biosystems Group Avecia Ltd., Manchester, U.K. Business: Supply/Service Hired: Daniel Moore as VP of manufacturing and Avecias Avecia Biotechnology Inc. subsidiary Bioreason Inc., Santa Fe, N.M. Business: Bioinformatics Hired: Andrew DePristo as president and CEO, formerly senior director of research and preclinical development information systems at Amgen Inc. Boston Biomedica Inc. (BBII), West Bridgewater, Mass. Business: Diagnostic, Supply/Service Hired: Richard Schumacher, a director, as CEO Carolina Pharmaceuticals Inc., Cary, N.C. Business: Infectious Hired: Daniel Fisher as VP of business development, formerly president of Strategic Pharmaceutical Solutions Inc. Conforma Therapeutics Corp., San Diego, Calif. Business: Cancer Hired: Christopher LeMasters as VP of corporate development, formerly a corporate business development executive at Eli Lilly and Co. Edwards Lifesciences Corp. (EW), Irvine, Calif. Business: Cardiovascular Hired: John Alexander Martin as president of the North America region, formerly SVP-international at Cordis Corp., a subsidiary of Johnson & Johnson Genencor International Inc. (GCOR), Palo Alto, Calif. Business: Infectious Hired: Philip Haworth as VP of business development for health care, formerly VP of business development at Galileo Pharmaceuticals Inc. Genitope Corp. (GTOP), Redwood City, Calif. Business: Cancer Hired: John Vuko as VP of finance and CFO, formerly EVP and CFO of Incyte Corp. MedImmune Inc. (MEDI), Gaithersburg, Md. Business: Infectious Promoted: Lota Zoth to SVP and CFO from VP and controller; Joan Brandt to VP of corporate quality control from senior director; Michael Cowan to VP of corporate quality assurance from senior director; Christine Dingivan to VP of clinical development and head of strategic operations from director of medical sciences; Lori Weiman to VP of corporate communications from senior director; and Peter Young to VP of information technology from senior director Metaphore Pharmaceuticals Inc., Fort Lee, N.J. Business: Neurology, Autoimmune, Inflammation Hired: Per Lindell as VP of corporate development, formerly VP of business development at Avalon Pharmaceuticals Inc. See next page
MANAGEMENT TRACKS Boards of Directors

Corgentech Inc., South San Francisco, Calif. Business: Cardiovascular Appointed: Richard Brewer, founding partner of Crest Asset Management Nastech Pharmaceutical Co. Inc. (NSTK), Bothell, Wash. Business: Drug delivery Appointed: Myron Holubiak, former president of Roche Laboratories Inc.; Leslie Michelson, vice chairman and CEO of the Prostate Cancer Foundation; and Gerald Stanewick, former institutional bond salesman at Goldman Sachs & Co.s Leeds & Kellogg subsidiary Scolr Inc. (SCLL), Bellevue, Wash. Business: Drug delivery Appointed: Wayne Pines, former chief of consumer education and information, chief of press relations and associate commissioner for public affairs at FDA; and Michael Sorell, managing member of MS Capital
Management
Advanced Viral Research Corp. (ADVR), Yonkers, N.Y. Business: Infectious Departed: Alan Gallantar as CFO and treasurer; Martin Bookman, assistant controller, becomes acting CFO
Take advantage of BioCentury Extra.
BioCentury Part II
CLINICAL NEWS
Clinical activities and selected announcements for the week ended April 23.
APRIL 26, 2004
PAGE B8 OF 13
CLINICAL RESULTS
Alexion Pharmaceuticals Inc. (ALXN), Cheshire, Conn. Product: Eculizumab (5G1.1) Business: Hematology Molecular target: Complement 5 (C5) Description: Humanized monoclonal antibody targeting C5 Indication: Treat Paroxysmal nocturnal hemoglobinuria (PNH) Endpoint: Need for blood transfusion Status: Phase Ib data Milestone: NA Cumulative 12-month results from a previously reported openlabel, U.K. Phase Ib trial in 11 patients showed eculizumab therapy resulted in 76% fewer packed red blood cell transfusions compared to the 12 month clinical history (p=0.001). The number of paroxysm events was reduced 94% from 3.2 days of paroxysms/patient/month to 0.2 days (p<0.001). Patients showed significant improvements in several quality of life parameters. Data were presented at the British Society of Hemotology meeting in Cardiff. Bioenvision Inc. (BIV), New York, N.Y. Product: Clofarabine Business: Cancer Molecular target: DNA polymerase; ribonucleotide reductase Description: Second-generation nucleoside analog Indication: Treat older patients with acute myelogenous leukemia (AML) for whom chemotherapy is not suitable Endpoint: Response rate Status: Phase II data Milestone: NA
Interim data from a Phase II trial of clofarabine as a first-line therapy showed 9 of 14 (64%) evaluable patients have had a complete response. To date, the study has enrolled 18 of an expected 25 patients. Results were presented at the Bristish Society of Hematology meeting in Cardiff. CV Therapeutics Inc. (CVTX), Palo Alto, Calif. Product: Ranexa Business: Cardiovascular Molecular target: Enoyl-CoA-hydratase Description: Partial inhibitor of enoyl-CoA-hydratase Indication: Treat chronic stable angina Endpoint: Exercise duration Status: Phase III data Milestone: NA Previously reported result from the Phase III MARISA trial in 191 angina patients showed Ranexa increased symptom-limited exercise duration (p<0.005). Ranexa also increased the secondary endpoint of time to onset of angina pain during exercise testing and time to electrocardiographic evidence of ischemia (p<0.005). Mean QTc differences for Ranexa vs. placebo were <1.0 msec at 500 mg & 1000 mg doses. Data were published in the Journal of the American College of Cardiology. InKine Pharmaceutical Co. Inc. (INKP), Blue Bell, Penn. Product: Visicol (INKP-100) Business: Gastrointestinal Molecular target: NA Description: Sodium phosphate gastrointestinal cleansing/purging agent Indication: Treat chronic functional constipation or constipationpredominant irritable bowel syndrome (IBS) Endpoint: Safety; laxative effects See next page
Management, from previous page

Protherics plc (LSE:PTI), Macclesfield, U.K. Business: Inflammation, Cancer Hired: Sally Waterman as director of R&D, formerly director of development operations at Xenova Group plc Scancell Ltd., Nottingham, U.K. Business: Cancer Hired: Michael Capaldi as CEO, formerly CEO of Synaptica Ltd. Structural GenomiX Inc., San Diego, Calif. Business: Chemistry Hired: Neill Giese as SVP of drug development, formerly senior director of cancer and cardiovascular biology at Millennium Pharmaceuticals Inc. Tercica Inc. (TRCA), South San Francisco, Calif. Business: Endocrine Hired: Thomas Silberg as COO, formerly EVP and COO of Ligand Pharmaceuticals Inc. Vical Inc. (VICL), San Diego, Calif. Business: Cancer Resigning: Martha Demski as VP, CFO, treasurer and secretary
Scientific Advisory Boards

Benitec Ltd. (ASX:BLT), Queensland, Australia Business: Functional genomics Appointed: Cy Stein, professor of medicine, urology and molecular pharmacology at the Albert Einstein College of Medicine; and David Engelke, professor of biological chemistry at The University of Michigan RegeneRx Biopharmaceuticals Inc. (RGRX), Bethesda, Md. Business: Dermatology Appointed: Jo-David Fine, professor of dermatology at the University of Kentucky School of Medicine; and Claudio De Simone, associate professor of experimental medicine at the University of LAquila Semafore Pharmaceuticals Inc., Indianapolis, Ind. Business: Cancer Appointed: Donald Durden, professor of pediatric oncology and hematology at Emory University School of Medicine Tissera Inc. (TSSR), Tel Aviv, Israel Business: Transplant Appointed: Giuseppe Remuzzi, director of the Mario Negri Institute for Pharmacological Research; Sir Roy Caln, professor of surgery at the National University of Singapore
Try the searchable BioCentury Archives.
BioCentury Part II
Clinical Results, from previous page
Status: Phase IV data Milestone: NA In a dose-ranging, U.S. Phase IV trial in 40 evaluable patients, 88% responded to Visicol treatment during the first week. Patients received either a single 4 tablet dose or an 8 tablet regimen, with 4 tablets dosed twice over 15 minutes. During the last week of therapy (week 4) all patients in the 4 tablet group responded and 92% of those in the 8 tablet group responded. Both groups showed significant improvements in constipation-associated symptoms such as straining, cramping, bloating, and stool consistency when compared to baseline. In the 8 tablet group, 4 patients withdrew from the study due to non-serious adverse events. No patients in the 4 tablet group withdrew due to adverse events. INKP intends to use doses of 2-4 tablets in the future. Prana Biotechnology Ltd. (ASX:PBT; PRNAY), Melbourne, Australia Product: PBT-1 Business: Neurology Molecular target: Cu ion; Zn ion Description: Small molecule that binds copper and zinc to prevent aggregation of amyloid beta Indication: Treat Alzheimers disease (AD) Endpoint: ADAS-Cog; safety, serum amyloid levels Status: Phase II updated data Milestone: NA Results from a 48-week extension of a previously reported 36week Phase II trial showed that PBT-1 slowed decline in cognitive function. The longer-term treatment was well tolerated. Data were presented at the International Springfield/Montreal Symposium on Advances in Alzheimers Disease. Valeant Pharmaceuticals International (VRX), Costa Mesa, Calif. Product: Viramidine Business: Infectious Molecular target: NA Description: Ribavirin prodrug Indication: Treat hepatitis C virus (HCV) Endpoint: HCV RNA levels Status: Phase II data Milestone: NA Interim results from an open-label, U.S. Phase II trial in 180 treatment-nave patients showed 83% of those given Viramidine plus peginterferon alfa-2a had 2 log10 reduction or had non-detectable HCV RNA at 24 weeks, the same proportion as those receiving ribavirin and peginterferon alfa-2a. The Viramidine group had a significantly lower incidence of anemia (2% versus 24%, p<0.001). All 3 tested doses
APRIL 26, 2004
PAGE B9 OF 13
of Viramidine (400 mg, 600 mg and 800 mg, twice daily) were comparable to ribavirin 1000 or 1200 mg/day. Data were presented at the European Association for the Study of the Liver conference in Berlin. The compound is in Phase III testing in combination with pegylated interferon alpha 2b. Roche (SWX:ROCZ; Basel, Switzerland) markets Pegasys peginterferon alfa-2a, while Schering-Plough (SGP, New Brunswick, N.J.) markets Peg-Intron peginterferon alfa-2b. ZymoGenetics Inc. (ZGEN), Seattle, Wash. Product: rhThrombin Business: Hematology Molecular target: NA Description: Recombinant human thrombin Indication: Control blood loss during surgery Endpoint: Safety Status: Phase I data Milestone: Phase I data 2H04 In an ongoing, open-label, U.S. Phase I study in 9 lumbar spinal surgery patients, ZGEN said instances of hemostatic response with rhThrombin were observed. The trial has completed enrollment.
PRECLINICAL RESULTS
DynPort Vaccine Co. LLC, Frederick, Md. Product: rF1V Indication: Prevent Yersinia infection DynPort said that in mice, rF1V protected against both bubonic and pneumonic forms of plague. Myriad Genetics Inc. (MYGN), Salt Lake City, Utah Product: MPC-4505 Indication: Treat chemotherapy-induced nausea and vomiting MYGN said that in a monkey model, MPC-4505 achieved significant blood levels and had peak blood levels about 4 hours after oral dosing.
CLINICAL STATUS
Advanced Biotherapy Inc. (ADVB), Woodland Hills, Calif. Product: TNF alpha inhibitor Business: Infectious Molecular target: NA Description: Tumor necrosis factor (TNF) alpha inhibitor Indication: Treat HIV infection Endpoint: Safety; viral load, increase in CD4 count Status: Phase I started Milestone: Phase I data 2004 ADVB started an open-label, U.S. Phase I trial in about 10 patients who are in virologic failure. Alkermes Inc. (ALKS), Cambridge, Mass. Product: Vivitrex Business: Neurology Molecular target: Opioid receptors Description: Injectable sustained-release formulation of naltrexone in polylactide co-glycolide polymer microspheres Indication: Treat alcohol- and opiate-dependence Endpoint: Safety Status: Phase III completed enrollment Milestone: Complete Phase III 1H05; submit NDA 1H05 ALKS completed enrollment in an open-label, Phase III safety study comparing once-monthly injections of Vivitrex (380 mg) to once-daily oral naltrexone (50 mg) in more than 400 alcohol- and opiate-depenSee next page
BioCentury Part II
BioCentury Part II is published by BIOCENTURY PUBLICATIONS INC., PO Box 1246 San Carlos CA 94070-1246. Phone 650-595-5333. Fax 650-595-5589. David Flores, President & Publisher; Karen Bernstein, Ph.D., Chairman & Editor-in-Chief BioCentury; The Bernstein Report on BioBusiness; The BioCentury 100; and The Clear Route to ROI are trademarks of BIOCENTURY PUBLICATIONS INC. All contents Copyright 2004, BIOCENTURY PUBLICATIONS INC. ALL RIGHTS RESERVED. No part of this publication may be photocopied or reproduced in any form, retransmitted, or stored in a retrieval system without prior written consent of the publisher.
BioCentury Part II
Clinical Status, from previous page
dent patients. ALKS said an interim safety analysis will be complete in about 6 months. Alteon Inc. (ALT), Ramsey, N.J. Product: Alagebrium (ALT-711) Business: Cardiovascular Molecular target: Advanced glycosylation endproduct (AGE) Description: AGE crosslink breaker Indication: Treat diastolic dysfunction in patients with grade II-IV heart failure Endpoint: Quantification of left ventricular mass and diastolic function as measured by Doppler evaluation; quality of life as measured by Minnesota Living with Heart Failure questionnaire Status: Phase II started Milestone: NA ALT began a U.S., open-label Phase II trial in 20 patients. The trial will measure 2 oral doses of alagebrium (35 mg daily or 210 mg twice daily) for a total of 24 weeks. Anika Therapeutics Inc. (ANIK), Woburn, Mass. Product: Incert-S Business: Musculoskeletal Molecular target: NA Description: Bioabsorbable, chemically modified hylauronic acid Indication: Prevent internal adhesions and scarring following spinal surgery Endpoint: NA Status: Pilot trial started Milestone: NA ANIK began a U.K. pilot trial in about 45 patients. Cell Therapeutics Inc. (CTIC; NMerc:CTIC), Seattle, Wash. Product: CT-2106 Business: Cancer Molecular target: Topoisomerase I Description: Camptothecin topoisomerase I inhibitor attached to polyglutamate polymer Indication: Treat colorectal cancer Endpoint: Maximum tolerated dose; safety, antitumor activity Status: Phase I/II started Milestone: NA CTI started an international, open-label Phase I/II trial of CT-2106 plus 5-fluorouracil/folinic acid in about 45 patients with metastatic colorectal cancer who have failed front-line therapy with oxaliplatin. CuraGen Corp. (CRGN), New Haven, Conn. Product: CG53135 Business: Other Molecular target: NA Description: Human fibroblast growth factor 20 (FGF-20) Indication: Treat oral mucositis in patients undergoing bone marrow transplantation Endpoint: Safety; response Status: Phase I started Milestone: Start Phase II 2004 CRGN started an open-label, U.S. Phase I study in 15 cancer patients. Ilex Oncology Inc. (ILXO), San Antonio, Texas Product: Campath alemtuzumab Business: Autoimmune
APRIL 26, 2004
PAGE B10 OF 13
Molecular target: CD52 Description: Humanized monoclonal antibody against CD52 Indication: Treat previously untreated relapsing/remitting multiple sclerosis (MS) Endpoint: Time to sustained accumulative disability (SAD) Status: Phase II completed enrollment Milestone: NA ILXO completed enrollment of 240 patients in an international, open-label Phase II trial comparing Campath to Rebif interferon beta1a from from Serono SA (SWX:SEO; SRA, Geneva, Switzerland). ILEX is being acquired by Genzyme Corp. (GENZ, Cambridge, Mass.). Inspire Pharmaceuticals Inc. (ISPH), Durham, N.C. Product: INS37217 Business: Ophthalmic Molecular target: P2Y(2) receptor Description: Second-generation P2Y(2) agonist Indication: Treat rhegmatogenous retinal detachment Endpoint: Surgery-free retinal attachment Status: Phase II started Milestone: Phase II data 2005 ISPH began a U.S., double-blind, placebo-controlled Phase II trial of INS37217 as first-line therapy in about 160 patients. The protocol allows for up to 2 more injections of INS37217 in patients showing signs of improvement after the first intravitreal injection. Introgen Therapeutics Inc. (INGN), Austin, Texas Product: Advexin (INGN 201) Business: Cancer Molecular target: NA Description: Adenovirus p53 tumor suppressor gene therapy (Ad5CMVp53) Indication: Treat stage III or IV squamous cell carcinoma of the oral cavity Endpoint: Progression-free survival; overall survival, overall response rate Status: Phase II started Milestone: NA The Southwest Oncology Group began a U.S. Phase II trial of INGNs Advexin to treat about 60 patients who will receive Advexin at the time of surgery. Patients will then receive chemotherapy and radiation. Neurobiological Technologies Inc. (NTII), Richmond, Calif. Product: Xerecept Business: Cancer Molecular target: Corticotropin-releasing factor (CRF1) receptor; corticotropin-releasing factor (CRF2) receptor Description: Synthetic human CRF Indication: Treat peritumoral cerebral edema associated with brain tumors Endpoint: 50% reduction in steroid use at 3 weeks Status: Phase III started Milestone: NA NTII began a U.S. and Canadian Phase III trial in about 200 patients who are taking high doses of dexamethasone. NTII said it will start a second Phase III trial this summer in 120 steroid-nave patients who will be given either Xerecept or dexamethasone. Both pivotal trials have been given a Special Protocol Assessment by FDA. Rigel Pharmaceuticals Inc. (RIGL), South San Francisco, Calif. Product: R112 Business: Inflammation Molecular target: Syk See next page
BioCentury Part II
Clinical Status, from previous page
Description: Nasal spray Syk kinase inhibitor that inhibits mast cell activation Indication: Treat allergic rhinitis Endpoint: Change from baseline in global symptom score; time to onset of effect, safety Status: Phase II started Milestone: Phase II data 2H04 RIGL began an outdoor, U.S. placebo-controlled Phase II trial in 300 patients who have had seasonal allergic rhinitis during the spring pollen season for at least 2 years. Vivus Inc. (VVUS), Mountain View, Calif. Product: Avanafil (TA-1790) Business: Genitourinary Molecular target: Phosphodiesterase-5 (PDE-5) Description: Fast-acting oral PDE-5 inhibitor Indication: Treat erectile dysfunction (ED) Endpoint: Optimal dose range Status: Phase II started Milestone: Complete enrollment Phase II 2004; Phase II data 1H05 VVUS began a U.S., at-home, double-blind, crossover Phase II trial in about 250 patients. Xenome Ltd., Brisbane, Australia Product: Xen2174 Business: Neurology Molecular target: Norepinephrine transporter Description: Synthetic peptide modeled on a peptide isolated from the venom of the marine coneshell Indication: Treat severe cancer pain Endpoint: Safety Status: IND filed Milestone: Start Phase I 06/04 Xenome filed an IND to begin a placebo-controlled Phase I trial in 4 groups of 5 healthy volunteers. ZymoGenetics Inc. (ZGEN), Seattle, Wash. Product: rhThrombin Business: Hematology Molecular target: NA Description: Recombinant human thrombin Indication: Control blood loss during surgery Endpoint: Safety as measured by immunogenicity; time-to-hemostasis, rhThrombin antibodies at 28 days
APRIL 26, 2004
PAGE B11 OF 13
Status: Phase II started Milestone: Complete Phase II 2004 ZGEN started a double-blind, placebo-controlled, U.S. Phase II study in 40 patients undergoing liver resection. ZGEN said it plans to start this quarter 3 other identical studies in patients undergoing lumbar spine surgery, lower extremity peripheral artery bypass surgery, and for the formation of vascular access grafts for dialysis. The endpoints in all 4 studies includes safety, time-to-hemostasis, and a 28day follow-up test for antibodies against rhThrombin. ZGEN expects to complete all 4 Phase II studies this year.
OTHER RESEARCH NEWS

Agrobiogen GmbH, Hilgertshausen, Germany, et al. Product: r38M bispecific single-chain antibody Use: Treat cancer Researchers published in the Proceedings of the National Academy of Sciences the production of a bispecific single-chain antibody in the serum of transgenic rabbits and cattle. The antibody, designated r28M, showed antitumor activity in culture. Icon Genetics AG, Munich, Germany Product: Bacterial expression system Use: Biomanufacturing Researchers published in the Proceedings of the National Academy of Sciences the development of a system that uses bacteria to deliver protein expression vectors to plants. Novartis AG (NVS; SWX:NOVN), Basel, Switzerland, et al. Product: CGP76030 Src kinase inhibitor Use: Treat leukemia Researchers published in Nature Genetics that CGP76030 increased survival compared to control in a mouse model of B cell acute lymphoblastic leukemia (B-ALL), but did not significantly increase survival in a mouse model of chronic myelogenous leukemia (CML). In the model of B-ALL, animals given CGP76030 plus imatinib survived longer than animals receiving monotherapy with either agent. NOVN markets Gleevec imatinib to treat CML. Yale University, New Haven, Conn., et al. Product: Curcumin Use: Treat cystic fibrosis (CF) Researchers published in Science that in a mouse model of CF, curcumin restored the nasal membrane potential. Also, the compound promoted the accumulation of the mature CFTR protein in cells grown in culture. Yale has licensed the technology to Seer Pharmaceuticals LLC (Southport, Conn.).
The search for intelligent life

We know you have many choices for headlines. But finding real intelligence is a lot harder. Thats why top managers and investors in the life sciences community depend on BioCentury, the Bernstein Report on BioBusiness for its leading perspective on the strategic issues essential to the formation, development and sustainability of life science ventures in 2005 and beyond.
BioCentury Part II
OFFERINGS & SECURITIES TRANSACTIONS
Week ended 4/23/04. Shares after offering refers to shares outstanding. Proceeds are gross, not net. Shares offered dont include overallotments. Currency rates used in the week: C$=US$0.7427; DKK=$0.1610; =$1.1990; =$1.7967 Dynogen Pharmaceuticals Inc., Boston, Mass. Business: Genitourinary, Gastrointestinal Date completed: 4/19/04 Type: Venture financing Raised: $50 million Investors: Schroder Ventures; Abingworth; Atlas Venture; Medica Holdings; Wellcome Trust; Oxford Bioscience Partners; HealthCare Ventures; A.M. Pappas & Associates Incara Pharmaceuticals Corp. (ICRA), Research Triangle Park, N.C. Business: Neurology Date completed: 4/19/04 Type: Private placement of common stock and warrants Raised: $10.3 million Shares: 41 million Price: $0.25 Shares after offering: 88.4 million Placement agent: SCO Securities Investors: Biotechnology Value Fund; Perceptive Life Sciences Fund; Great Point Partners Note: Investors also received warrants to purchase an additional 16.4 million shares at $0.40. Along with the offering, ICRA announced that Goodnow Capital LLC converted its remaining $2.5 million worth of debentures into shares. Integrated Biopharma Inc. (INB), Hillside, N.J. Business: Cancer Date completed: 4/21/04 Type: Private placement of convertible preferred stock and warrants Raised: $8.5 million Price: $10,000 Shares after offering: 10.6 million Underwriter: NA Shares outstanding prior: 10.6 million Investors: Alexandra Investment Management; and other investors Note: The series B convertible shares have a 7% dividend and are
APRIL 26, 2004
PAGE B12 OF 13
convertible into common shares at $10. Investors also received warrants to purchase an additional 425,000 common shares at $14. Investors may purchase an additional 425 series B convertible preferred shares and related warrants over the next 18 months. Spectrum Pharmaceuticals Inc. (SPPI), Irvine, Calif. Business: Cancer, Generics Date completed: 4/21/04 Type: Private placement of common stock and warrants Raised: $25 million Shares: 3.2 million Price: $7.75 Shares after offering: 13.2 million Note: Investors also received 1year warrants to purchase up to an additional 1.1 million shares at $10
Completed Offerings
Bruker BioSciences Corp. (BRKR), Billerica, Mass. Business: Supply/Service, Proteomics, Computational chemistry/biology Date completed: 4/23/04 Type: Follow-on Raised: $13.5 million Shares: 3 million Price: $4.50 Shares after offering: 89 million Underwriters: Bear Stearns; UBS; SG Cowen Overallotment: 450,000 Note: In conjunction with the follow-on, 4 selling shareholders sold 12 million BRKR shares in a secondary offering. These shareholders are offering an additional 1.8 million shares to cover overallotments. Callisto Pharmaceuticals Inc. (CLSP), New York, N.Y. Business: Cancer, Musculoskeletal Date completed: 4/19/04 Type: Private placement Raised: $4.8 million Shares: 2.2 million Price: $2.25 Shares after offering: 29.2 million Placement agent: Punk Ziegel DxS Ltd., Manchester, U.K. Business: Diagnostic, High throughput screening Date completed: 4/19/04 Type: Venture financing Raised: 10 million ($18 million) Investors: Northern Venture Managers; BioScience VCT; British Smaller Technology Companies VCT2; North West Business Investment Scheme
Pharmexa A/S (CSE:PHARMX), Horsholm, Denmark Business: Cancer, Autoimmune Date announced: 4/20/04 Type: Rights offering To be raised: DKK209 million ($33.6 million) Shares: 12.3 million Underwriter: ING Investment Banking Shares outstanding prior: 4.1 million Note: Existing shareholders may purchase 3 shares for every share held
Other Financial News

Array BioPharma Inc. (ARRY), Boulder, Colo. Business: Cancer, Inflammation, Chemistry Date announced: 4/22/04 ARRY filed a shelf registration covering the sale of up to $70 million of securities, including common stock, preferred stock and warrants. ARRY, which closed Friday at $9.15, has 28.6 million shares outstanding. BioTrove Inc., Woburn, Mass. Business: Microfluidics Date announced: 4/15/04 BioTrove raised $2.8 million in a second tranche of a January financing, bringing to $19 million the total amount raised in the series B round. Investors included Catalyst Health and Technology Partners; Echelon Ventures; Fletcher Spaght; CB Health Ventures; Zero Stage Capital; and BioFrontier Partners. Memory Pharmaceuticals Corp. (MEMY), Montvale, N.J. Business: Neurology Date announced: 4/20/04 MEMY raised an additional $5.3 million through the sale of 750,000 shares at $7 to cover over-allotments from its IPO earlier this month, bringing to $40.3 million the total raised in the offering. See next page
Proposed Offerings
Auxilium Inc. (Proposed:AUXL), East Norriton, Penn. Business: Metabolic, Neurology Date announced: 4/21/04 Type: IPO To be raised: $86.3 million Shares: To be determined Price: To be determined Shares after offering: To be determined Underwriters: Deutsche Bank; Piper Jaffray; Thomas Weisel Partners Nanosys Inc. (Proposed:NNSY), New York, N.Y. Business: Supply/Service Date announced: 4/22/04 Type: IPO To be raised: Up to $115 million Shares: To be determined Price: To be determined Shares after offering: To be determined Underwriters: Merrill Lynch; Lehman; CIBC World Markets; Needham Overallotment: To be determined
BioCentury Part II
ANALYST PICKS & CHANGES
Amgen Inc. (AMGN), Thousand Oaks, Calif. Business: Biopharmaceuticals Deutsche Bank analyst Dennis Harp raised his 2004 EPS estimate to $2.38 from $2.36. Last week, AMGN reported first quarter adjusted EPS of $0.57, beating the Street estimate by a penny and up 36% from EPS of $0.42 in the same period last year. Product sales were $2.2 billion, up 35% from $1.6 billion in the first quarter of 2003. AMGN closed Friday at $58.31. Antigenics Inc. (AGEN), New York, N.Y. Business: Cancer, Infectious Needham & Co. analyst Mark Monane lowered his rating to hold from buy because of a lack of near-term drivers. On Tuesday, the company said that FDA is still seeking additional product characterization for its Oncophage cancer vaccine to treat renal cell carcinoma (RCC). The agency had a partial hold on the compound, but lifted it last November. AGEN closed Friday at $9.99. CeNeS Pharmaceuticals plc (LSE:CEN), Cambridge, U.K. Business: Neurology Nomura analyst Sam Fazeli began coverage with a buy rating. CEN has two products in development: M6G morphine-6-glucuronide is in Phase III testing to treat post-operative pain, and CNS 5161, a glutamate receptor NMDA ion channel blocker, is in Phase II studies to treat neuropathic pain. Fazeli expects positive news flow from these two compounds to drive the stock in the next 6-12 months. CEN closed Friday at 11.9p. Gilead Sciences Inc. (GILD), Foster City, Calif. Business: Infectious Leerink Swann analyst William Tanner raised his 2004 and 2005 revenue estimates to $1.27 billion and $1.68 billion from $1.24 billion and $1.66 billion, respectively. Last week, GILD reported first quarter non-GAAP EPS of $0.45, beating the Streets $0.34 estimate by $0.11. The company also raised its sales guidance for HIV drug Viread and antifungal Ambisome. WR Hambrecht analyst Jason Kantor said GILDs increased guidance is conservative. He expects 2004 Viread sales of $809 million versus the companys new guidance of $725-$775 million. Legg Mason analyst Edward Nash lowered his rating to hold from buy. He said the stock is fairly valued and expects that GILD will have to increase R&D and SG&A expenses in order to improve its top line via new drugs. Deutsche Bank analyst Dennis Harp raised his 2004 and 2005 EPS estimates to $1.55 and $1.96 from $1.38 and $1.84. GILD closed Friday at $60.12. ImClone Systems Inc. (IMCL), New York, N.Y. Business: Cancer WR Hambrecht analyst Jason Kantor began coverage with a buy rating and an $83 price target. He expects the company to turn
APRIL 26, 2004
PAGE B13 OF 13
profitable next year on strong sales of colorectal cancer antibody Ertibux cetuximab. SG Cowen analyst Eric Schmidt began coverage and expects the company to turn profitable this year. His 2004 and 2005 EPS estimates are $0.50 and $1.65. Schmidt said potential upside to sales estimates of Erbitux, plus a strong presence at ASCO, are likely to propel the stock. IMCL closed Friday at $70.30. Invitrogen Corp. (IVGN), Carlsbad, Calif. Business: Supply/Service Pacific Growth analyst Adam Chazan raised his 2004 EPS and revenue estimates to $2.88 and $1.03 billion from $2.84 and $1.01 billion. Last week, the reagent and tool supplier reported first quarter pro forma EPS of $0.63, which was $0.03 better than the consensus estimate of $0.60. For the full year, IVGN raised its revenue and EPS guidance to $1.04 billion and $2.88. IVGN closed Friday at $74.74. Isotechnika Inc. (TSE:ISA), Edmonton, Alberta Business: Transplant, Autoimmune Dundee Securities analyst David Martin lowered his price target to C$2. On Tuesday, ISA and Roche (SWX:ROCZ, Basel, Switzerland) renegotiated a 2002 co-development deal for ISA247, restoring development rights to ISA and giving ROCZ an option to assume development after the start of Phase II transplantation trials. The trans isomer version of ISA247 is in Phase I dose-ranging trials for renal transplant and psoriasis. ISA closed Friday at C$2.22. Lexicon Genetics Inc. (LEXG), The Woodlands, Texas Business: Functional genomics, Genomics WR Hambrecht analyst Jason Kantor began coverage with a buy rating and a $10 price target. Kantor expects new partnerships to be the primary driver for the stock over the next 12 months. LEXG closed Friday $7.06. MedImmune Inc. (MEDI), Gaithersburg, Md. Business: Infectious, Cancer Deutsche Bank analyst Dennis Harp raised his EPS estimates to $0.52 from $0.50 in 2004 and to $0.53 from $0.52 in 2005 based on first quarter 2004 results and company guidance. On Wednesday, MEDI reported first quarter EPS of $0.44, beating Street expectations by $0.02. The company reiterated 2004 EPS guidance of $0.50-$0.60. MEDI closed Friday at $23.95. Rigel Pharmaceuticals Inc. (RIGL), South San Francisco, Calif. Business: Autoimmune Needham analyst Mark Monane began coverage with a buy rating and a $33 price target. He said a value driver for the company will be partnerships for its clinical compounds, including R112, an intranasal mast cell activation inhibitor that is in Phase II testing for allergic rhinitis. RIGL closed Friday at $21.50.
Other Financial News, from previous page

Underwriters included UBS; SG Cowen; Banc of America Securi-
ties; and Fortis. MEMY has 20.2 million shares outstanding. MIV Therapeutics Inc. (MIVT), Vancouver, British Columbia
Business: Cardiovascular Date announced: 4/21/04 MIVT raised an additional C$700,000 through the sale of 1.6 million shares at C$0.44 to cover
BioCentury Extra: Online every business day.
overallotments from a March private placement, bringing to C$3 million the total raised in the offering. Ducan Capital LLC served as the placement agent. MIVT has 43.2 million shares outstanding.

BC

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

BC

Uploaded by

Copyright:

Available Formats

For the week of April 26, 2004

BioCentury 100 Indicators

VOLUME 12, NUMBER 19

540.9M shrs up 37% P AGE A1 OF 20

Tag team wrestling

Emerging Company Profile

Ebb & Flow

BioEquity Europe Update

THE BERNSTEIN REPORT

APRIL 26, 2004

More, and more detailed, questions

THE BERNSTEIN REPORT

APRIL 26, 2004

THE BERNSTEIN REPORT

APRIL 26, 2004

Tag Team Wrestling

ABCs of the FDA-SEC MOU

THE BERNSTEIN REPORT

APRIL 26, 2004

We do not view ourselves, nor should we, as the health SEC.

Tag Team, from previous page

THE BERNSTEIN REPORT

APRIL 26, 2004

BioMarins head start

THE BERNSTEIN REPORT

APRIL 26, 2004

Its the BioCenturyTM

THE BERNSTEIN REPORT

APRIL 26, 2004

Getting it right, more or less

THE BERNSTEIN REPORT

APRIL 26, 2004

In HBV, five is not a crowd

BioCentury Company Index

THE BERNSTEIN REPORT

APRIL 26, 2004

Online links this week

CPMP executive recommendations for improving transparency of information provided to patients.

Guidance regarding the Managements Discussion & Analysis

Its the BioCenturyTM

THE BERNSTEIN REPORT

APRIL 26, 2004

Emerging Company Profile

Hudson Health Sciences Inc.

Cougar: Plenty to eat

Hudson: Its academic

Cougar Biotechnology Inc.

THE BERNSTEIN REPORT

APRIL 26, 2004

Emerging Companies, from previous page

THE BERNSTEIN REPORT

APRIL 26, 2004

Politics & Policy

Zero sum game

THE BERNSTEIN REPORT

APRIL 26, 2004

Patents vs. research

BioCentury Extra: Online every business day.

THE BERNSTEIN REPORT

APRIL 26, 2004

Ebb & Flow

EPO sales watch

THE BERNSTEIN REPORT