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BioEquity Europe Update

Europe’s clinical bellwethers. Please see announcement following A20.

For the week of April 26, 2004

BioCenturyBioCentury 100

TM

Indicators

Week ended 4/23/04

PRICES VOLUM

1649.29 540.9M shup 4% up 37

VOLUME 12, NUMBER 19 THE BERNSTEIN R EPORT ON BIOBUSINESS PAGE A1 OF

BioCentury This Week

Cover Story

As SEC intensifies its scrutiny of

biotech with the help of FDA, there iswidespread agreement that companiesneed to rethink old assumptions thatthe two agencies can be handledindependently.

Strategy

BioMarin’s 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 A13Patents vs. research/Page A14

Ebb & Flow

MEDI’s R&D; IPO queue; earningsweek; EPO sales, et al./Page A15

Online this week /Page A10

Stock charts & tables/Page A20

Company index/Page A9

By Kathryn Calkins& Steve UsdinSenior Writers

Increased collaboration between FDAand SEC, fallout from the ImClone SystemsInc. case, and investor demands for more

informat ion aboutearly-stage drug devel-opment, are contrib-uting to an intensifica-tion of SEC’s scrutinyof public disclosures byb iopharmaceut i ca lcompanies. Biotechcompanies are receiv-ing more queries fromSEC, and the questionsare far more technical,according to attorneyswho specialize in handling securities is-

sues for biotech companies.The vigilance includes a more rigorous

scrutiny for consistency of statements madeto both FDA and the public, as well as theuse of trading suspensions in a handful of cases related to allegations of misleadingdisclosures.

As a result, corporate attorneys arewarning that it’s no longer possible to dealwith each regulatory agency separately.

In February, the agencies exchangedmemos formalizing a route for FDA offi-cials to report suspected false and mis-leading statements from companies to SEC,

and streamlining SEC access to non-pub-lic information from FDA. But while theincreased scrutiny might appear to be thedirect result of the MOU, senior officials atboth agencies say that’s just coincidence(see “ABCs of the FDA-SEC MOU,” A4).

In part, what appears to be happening isthat companies are proactively disclosingmore information about early-stage drug

Regulation

Tag team wrestling

‘The assumption

of secrecy at FDA

has been dashed

explicitly.’

— Alan Goldberg of Goulston & Storrs

development in response to investor mand. That, in turn, is prompting moquestions, according to Jeffrey Riedler, rector of SEC’s corporate finance divisiwho described the agency’s activity arecent meeting of the Food and Drug L

Institute in WashingtElizabeth Gray

partner at FoleyLardner LLP in Waington and a formassistant directorSEC’s division of forcement, told BioCtury that initiatives lthe FDA-SEC MOU ten result from seveforces that together cate the need for fast

more informed enforcement. “Complex

in the filings could have been a trigger, ait could have been one reason for tFDA-SEC agreement,” she said

Some securities lawyers suggest thare other reasons for SEC’s increasurveillance. John Kamp, an attorneyWiley Rein & Fielding LLP in Washingttold the FDLI meeting that biotech apharma companies are experiencing tfallout from corporate scandals. He sgested SEC is trying to demonstrate thais aggressively regulating the biotech stor in response to the media storm creaby the trials of former IMCL CEO Sam

Waksal and especially Martha StewartBoth Gray and Terri Garland, a se

rities litigator and partner at MorrisonFoerster LLP in San Francisco, also pointto the IMCL scandal in 2001-2002 aprobable touchstone for SEC’s apparinterest in biotech. That scandal, Garlanoted, was rooted in FDA-sponsor co

See next pa

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BioCentury, THE BERNSTEIN R EPORT ON BIOBUSINESS APRIL 26, 2004 PAG E A2 OF 2

munications. Gray said that the prosecu-tion history in that case probably revealeda need for better coordination betweenFDA and SEC. It also may have sharpenedSEC’s awareness of the inherent complex-ity of biotech filings.

Garland also noted that the sectorenjoyed a huge increase in investmentabout three years ago, which is resultingin projects now coming to fruition in theindustry. Investor complaints to SEC prob-ably have increased as investment hasgrown, which she said also can focus the commission’s attention.

While there is some disagreement about SEC’s motivation,there is widespread agreement that companies need to rethink old assumptions that interactions with SEC and FDA can behandled independently. Securities filings and press releases mustbe crafted with the expectation that FDA officials with access to

INDs and NDAs may review the documents for accuracy,according to senior SEC officials. And FDA filings, as well aspublic statements about the interactions with the agency, may bethe subject of discussion between FDA and SEC, according toattorneys at both agencies.

More, and more detailed, questions

The MOU notwithstanding, SEC has a longstanding policy of routinely querying FDA about statements in securities filings ontopics such as the status of a company’s NDA, and when it hasconcerns 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 registrationand other securities filings with regard to the status of FDA’sreview of a product or other issues within our purview.”

SEC’s Riedler agreed. “The SEC and FDA have been talkingto each other and sharing information for many, many years,” henoted. “This agreement is merely a refinement, a modernizationof the procedures that we engage in, in order to share informa-tion. We hope it will make the process a lot more efficient.”

Riedler added that the number of such queries has increasedin recent months as companies have included more data aboutFDA-related topics in prospectuses and other documents.

Indeed, companies’ apparent efforts to be proactive on thisscore seem to have backfired. Instead of decreasing regulatory

scrutiny, Riedler said, the trend to increasingly detailed disclosureshas led SEC to question whether drug companies are providingsufficient context to allow investors to make informed decisions.

“We have concerns with regard to several areas of disclosurethat drug companies make. We have noticed of late that drugcompanies are making more disclosures about the drug develop-ment process, particularly the preliminary results of drug trials,”he said. “There certainly is no requirement under federalsecurities law that companies disclose preliminary results of drugtrials, but if they choose to make those disclosures, we feel theyshould be in the proper context so investors don’t makeerroneous conclusions.”

If a company chooses to disclose interim results from a

Regulation,

from previous page clinical trial, for example, “the investpublic should know whether or not thehas been statistical analysis done and tresults” of the analysis, Reidler said. “Wwould like the company to disclose wthe trial is designed to show,” he adde

“Another area of concern is how copanies describe their role in the drug devopment process,” Reidler noted. “We wolike companies to be clear and transparabout their role. For example, if a compprimarily licenses intellectual property, would like it to say not that it has filedIND with the FDA, but that its collaborahas filed an IND.”

Reidler also cautioned companies about the way they chacterize clinical trials. SEC might question whether a companstretching the truth when it says a trial is Phase I/II, he said. Suquestions would go to the FDA.

The bottom line is that companies must be consistent in thcommunications with FDA, SEC and the public, said Jo

Manthei, a partner at Latham & Watkins LLP in Washington. in all the communications to FDA, investigators describe a tas Phase I, even if it has some efficacy endpoints, don’t tuaround and call it a Phase I/II trial” in a press release, Mantadvised the FDLI audience.

A different take

While government attorneys are downplaying the scope anovelty of the SEC-FDA MOU, several attorneys told BioCentthat they do see more coordination between FDA and SEsaying that they have seen increasing numbers of questions frSEC on biotech filings, and that the questions betray specknowledge about products and the drug approval process t

only FDA possesses. They maintain that the playing field thus changed perceptibly in recent months.“In the last four to five months, there has been a real up-t

in IPOs,” Manthei said. “The quality, the depth and amountdisclosures going into securities statements are much more ta few years ago.”

At the same time, “comments from the SEC have besignificantly better and much more specific, leading industrywonder if they were formulated by someone at FDA.”

SEC may be seeing a shift in complexity and detail of filibecause the companies going public are more mature, and thhave more advanced products, than those that went public in tpast, suggested Alan Mendelson, a partner at Latham & Watkin Palo Alto.

The companies that Mendelson has helped to file IPOs tyear — Corgentech Inc. (South San Francisco, Calif.), DynaTechnologies Corp. (DVAX, Berkeley, Calif.) and Renovis I(RNVS, South San Francisco, Calif.) — have wanted to includetailed data from their clinical trials. To take a company pub“bankers say they want a Phase II or Phase II I product and godata, so companies are laying that out,” he told BioCentury

The level of company maturity demanded by the market ashows the sophistication of investors now, Mendelson added

Corgentech’s CGT003 E2F Decoy is in Phase III testingprevent peripheral bypass graft failure, DVAX’s AIC is in PhaII/III studies in allergy, and RNVS’s Ceravive is in Phase III tr

‘FDA and the sponsor

might be more guarded,and the interchange

might be less productive

if meetings were recorded.’

— Frank Sasinowskiof Hyman, Phelps

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By Steve Usdin& Kathryn Calkins

Senior WritersThe FDA-SEC memorandum of understanding (MOU) primarily

involves referrals from FDA of possible criminal misconduct, and isunrelated to routine inquiries from SEC about the truthfulness of corporate filings and press releases. FDA employees have beeninformed of the appropriate people within the agency to contact if they come upon statements of potential interest to SEC. Thosepeople, in turn, contact FDA’s chief counsel’s office, which decideswhether any report should be referred to the SEC.

There has been no increase in criminal referrals since thememorandum was signed, according to senior FDA officials.Indeed, according to officials at both agencies, there has beenonly 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 remo

some of the red tape that made FDA-SEC communicatiocumbersome, but it does not reflect a major change in polaccording to Coleen Klasmeier, special assistant to the FDChief Counsel. “We do not view ourselves, nor should we, as thealth SEC,” she said.

Klasmeier added that the MOU does not modify restrictioon the disclosure of propr ietary in formation. “We continuehave great respect for all of the statutory restrictions on tdisclosure of non-public information,” she said.

Training of SEC and FDA staff to better understand food adrug and securities law is another aspect of the MOU.

“I am particularly looking forward to the mutual training our t

Tag Team Wrestling

ABCs of the FDA-SEC MOU

See next pa

Regulation,

from previous page how to improve the language in the Management’s Discussand Analysis (MD&A) section of filings (see “Online Links,” A1However, Berezin said she thinks clients have heightened cocerns about being second-guessed by FDA after the fact aresult of the inter-agency collaboration.

Neither she nor Mendelson, however, believes that comnies will respond by putting less detail in their prospectusesavoid detailed questioning from the agencies. “It would be advised to disclose less,” Berezin said.

Mendelson agreed, adding that one potential stumbling blofor biotechs in terms of adequate disclosure is the big compapartner. Big pharma, especially European and Asian partne

does not like to disclose more information than is legarequired, and does not need to raise money. Therefore, sucompanies often are unsympathetic to the disclosure needstheir smaller partners.

Former SEC attorney Gray said she believes the SEC-FDcommunications will change disclosures, but she does nexpect companies to clam up. Her best advice to companiethat “any disclosure must be put into the context of your entdevelopment program.”

As an example, Gray cited a Wells Notice received recenby BioPure Corp. (BPUR, Cambridge, Mass.) (see BioCentury, J5). A Wells Notice alerts a company that an SEC team is goto recommend an enforcement action to the commission aallows the company time to develop a defense.

In this case, Gray said, BPUR had not disclosed that FDA hnot agreed to a portion of a proposed clinical trial for its leproduct, Hemopure hemoglobin glutamer. Although the twas under a separate IND from the primary trial and was nevinitiated, SEC argued that the circumstances affected the largprogram in a negative way, Gray said.

A BLA for Hemopure is under review by FDA. BPUR saihas cooperated with SEC and is waiting for further informatfrom the agency.

Press releases “appear to receive the most scrutiny from FDand SEC,” Manthei suggested, so companies should take careensure that they are accurate and consistent with informatthey have communicated to both agencies.

citing concerns related to “(1) FDA approval of certain keyproducts and (2) the regulatory consequences of the futureapplication of their primary product.”

VAPH’s stock was delisted from NASDAQ on April 8 at thecompany’s request. VAPH also ceased marketing its three OTCproducts, which included one for athlete’s foot and two for painrelief, according to spokesperson Matt Carter.

The cost

While apparent shifts in SEC’s attention toward biotech haveresulted in incremental increases in the time required to com-plete SEC filings — and thus the costs to companies employingsecurities lawyers — such increases are dwarfed by the impactof Sarbanes-Oxley. The law, passed in 2002 to combat corporateand accounting fraud as a result of the Enron and ArthurAndersen scandals, led to changes in the filing process. Accord-ing to Mendelson, costs of public offerings generally have risenby one-third to one-half in the last three to five years.

Berezin agreed, adding that companies are waiting until later inthe SEC comment process to print their prospectuses and go on theroad, extending the process and making it more expensive. A fewyears ago, companies would wait for a single set of SEC comments

to come back before printing, but now they frequently wait throughthe third set of comments to assure themselves that no majorchanges will require them to reprint their documents.

What’s material

A core problem posed by all of these changes — or perceivedchanges — is the definition of what is “material.”

Securities attorneys have differing views on whether the FDA-SEC relationship will clarify which communications with FDAthat companies should consider material. SEC regulations cov-ering what is material have not changed, although last Decemberthe commission did release a document advising companies on

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agencies will do,” said Jeffrey Riedler, dirtor of SEC’s corporate finance division. Swill train FDA staff in terms of the Sexamination procedures and disclosregulations, while FDA “will train us in wthe FDA’s requirements are and the FDexamination process, so we can better derstand it and understand drug com

nies,” he said. Joint training and streamlined commnications suggest that the MOU is only starting point, and that the two agencmay begin to collaborate more closelythe future, said John Manthei, a partnerLatham & Watkins LLP in Washington

“I can’t help but look at what they doing and think that a year or two from nit will lead to a much greater level of activby FDA in this area,” he said. “The idefication of inter-agency liaisons, increatraining, more sharing of confidential infmation, and the streamlining of communi

tions under the new inter-agency initiativlikely to lead to greater coordination ainvolvement in the future.”

On the other hand, the MOU’s creatof formal channels for FDA officials to repotential violations of securities laws to SEC is likely to protect companies, accoing to Frank Sasinowski, a partner with Fspecialty firm Hyman, Phelps & McNamPC in Washington. Referrals will be vetby FDA attorneys who are familiar wsecurities laws.

“You should be relieved by partthis,” he told an audience of biote

executives and attorneys attendingrecent meeting in Pa lo Alto. “No rogreviewer can now go straight to SEC wa statement” because of this vetting pcedure.

But Sasinowski believes that, overthe new relationship is damaging to copany-FDA relations. He suggested sposors may become more circumspect aformal in communicating with FDA they try to create a paper trail that avopotential legal liabilities.

Tag Team,

from previous page

‘We do not view

ourselves, nor should

we, as the health SEC.’

— Coleen Klasmeier of FD

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By Aimee DingwellStaff Writer

BioMarin Pharmaceutical Inc. has been best known for itsfocus on enzyme replacement therapies for genetic diseases,so it came as a surprise last week when the company said itwill refocus to become a pediatric s company and partner outits non-pediatric products.

The transformation is pegged to BMRN’s acquisition of the Ascent Pediatrics Inc. business of Medicis PharmaceuticalCorp (MRX, Phoenix, Ariz.). The deal provides BMRN withtwo key elements that it sees as essential to reaching profit-ability: immediate and growing reve-nues from the sale of Ascent’s mainproduct, asthma drug Orapred; and a73-person sales and marketing team.

The sales force currently calls onabout 14,000 of the 25,000-30,000board-certified pediatricians in the U.S.who have an active practice. BMRN plansto increase that number to about 19,000by the time it launches its Aryplase treat-ment for mucopolysaccharidosis VI (MPS-VI) within the next 18 months.

BMRN says the head start is neces-sary. Chairman and CEO Fredric Pricesaid that commercializing compoundsfor genetic diseases, particularly thosein ch i ldren , requ ires “s ign i f i cantgroundwork” prior to launch not only to educate physicians

on how to identify and properly diagnose diseases thattypically are very rare, but also to prepare for logistical issuesrelated to treatment administration and costs.

Unlike more common diseases such as bacterial infec-tions, for which diagnostics are readily available and publicawareness exists, Price said physicians spend little timelearning about genetic disorders, and parental knowledge isnearly nonexistent.

MPS-VI is caused by a deficiency of the N-acetylgalac-tosamine 4-sulfate enzyme. For an extremely rare disease likeMPS-VI, which affects about 1,100 patients in the westernworld, timely diagnosis also can be hindered by vague symp-toms. Parents of children with the disease often first noticecloudy eyes, coarse facial features, or a slight sway in the back.

Most patients are diagnosed by age five. Most are treatedsymptomatically, although some younger patients receive bonemarrow transplants.

Once diagnosis of a lysosomal storage disorder like MPS-VI is made, physicians then must describe the treatment toparents.

“Explaining to paren ts that the treatment is a two to threehour infusion that will need to be administered in a medicalgeneticist’s office, which hopefully is not too far away, and,by the way, is going to cost $150,000 to $200,000 a year — you can imagine the logistical and emotional effects,” saidPrice. “This can’t be rectified by an ad in one of the journals.

Strategy

BioMarin’s head startYou can’t just mention this once and think that there willa common understanding.”

Thus, he argued, “if you don’t start going to medigeneticists and pediatricians one, two, three years befolaunch, you are going to stumble when the drug is launchAnd we can’t afford to do that.”

Indeed, sales have been slow for BMRN’s first enzyreplacement therapy, Aldurazyme laronidase to treat MPeven though the drug is sold by an experienced partnGenzyme (GENZ, Cambridge, Mass.). First quarter sales we$7.3 million. At the end of 2003, GENZ provided 2004 sa

guidance of $40-$44 million.In addition to providing a foot in t

door at pediatricians’ offices, Price sthat acquiring Ascent now hedges so

of the risk inherent in timing drug provals. Aryplase has completed PhaIII testing in MPS-VI and BMRN expeto file for approval in the fourth quart

“If you buy a sales force withprofitable, growing product, then if theare delays, it is not the end of the woand it doesn’t cost you anything,” sPrice.

Assuming Aryplase is approved October 2005, Price said, “that gives18 months to not only educate phycians, but to get the field force co

pletely comfortable with the drug, the diseases, the logist

issues surrounding treatment.”Orapred is a liquid corticosteroid. BMRN expects tdrug to have net sales of about $42 million this year, whPrice said is more than 50% of the liquid oral prednisolomarket.

The company also plans to file this year for regulatoapproval of a non-refrigerated version of the drug, andlaunch OraPred 2, a quick-dissolve tablet formulation,2005. BMRN also plans to launch OraPred in markets outsthe U.S. by early 2006.

BMRN (Novato, Calif.) hopes to eventually use the 6person sales force and 7 regional managers to market Phenoptin, an oral form of the enzyme cofactor tetrahydbiopterin that is in Phase I test ing to treat mild to moder

phenylketonuria (PKU), and Phenylase phenylalanine ammnia lyase, which is expected to start clinical trials for sevePKU next year.

PKU is a pediatric disease caused by insufficient quanties of phenylalanine hydroxylase. It results in a varietyneurological complications, including severe mental retartion and brain damage, mental illness, seizures and tremoand cognitive problems.

BMRN plans to out-license its Vibrilase topical enzytherapy for burn deridement. Vibrilase is in Phase Ib tria

BMRN will pay MRX (Phoenix, Ariz.) up to $175 milliin cash and stock over the next five years for Ascent (see B

‘If you don’t start going

to medical geneticists and pediatricians one,

two, three years before

launch, you are going to

stumble when the drug is

launched.’

— BioMarin’s Fredric Price

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By Michael FlanaganStaff Writer

ID Biomedical Corp. has two vaccinesin development but has lacked an ad-equate antigen supply. The companysolved that problem last week — andpositioned itself to enter the U.S. vaccinemarket — by announcing that it wouldbuy the vaccine business of Shire Pharma-ceuticals Group plc (LSE:SHP; SHPGY,Basingstoke, U.K.).

The deal includes one marketed vac-cine, Fluviral, which is an intramuscularinfluenza prophylactic marketed in Canada,as well as a streptococcal pneumonia vac-

cine that has finished Phase I testing. IDBiomedical (TSE:IDB; IDBE, Vancouver,B.C.) also gets 10 vaccine candidates thatare in or near preclinical development(see “IDB’s Bigger Pipeline”).

These will complement IDB’s FluInsure,which is an intranasal vaccine in non-pivotal Phase III testing, and its StreptAvaxgroup A streptococcus vaccine, which isin Phase I/II studies.

SHP’s vaccine business posted a 2003net operating loss of $21.9 million. But,according to IDB CEO Anthony Holler, “itis important to note that while Shire’s vac-

cine 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 antigensupply allows us with our flu vaccines. Wepreviously had to purchase small amountsof antigen from a number of suppliers.Having our own antigen supply means wedon’t have to deal with a third party, provid-ing us with the flexibility to negotiate ourown marketing and distribution deals.”

Now, said Holler, “our main goal is tobring both Fluviral and FluInsure to marketin the U.S. by 2007.”

If successful, IDB would be the fourthentrant into the U.S. flu vaccine market

Strategy

Coming to America

IDB’s bigger pipeline

ID Biomedical’s acquisition of Shire’s vaccine business adds a marketed flu vaccine and a

Phase I compound to IDB’s two clinical candidates, which are in Phase II and III trials.

Product Indication Status Originat

Fluviral (intramuscular) Influenza Mkt (Canada) SHP

FluInsure (intranasal) Influenza Non-pivotal Ph III IDB

StreptAvax Group A streptococcus Ph II IDB

Pneumococcal vaccine Streptococcus pneumoniae Ph I complete SHP

NA Allergy Preclin IDB

NA Plague Preclin IDB

NA RSV Preclin IDB

NA Group B streptococcus Preclin SHP

NA Neisseria meningitidis Preclin 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, SHP’s vac-cine business generated C$36 million(US$26.7 milion) in 2003 sales, of whichC$30 million came from sales of Fluviral,a subunit, nonliving vaccine sold to the

Canadian government.SHP, the fifth largest flu vaccinemanufacturer, in 2001 contracted withthe Canadian government to supply upto C$300 million (US$222.8 million) influ vaccine over the next several years.IDB expects to sell 7 million doses of Fluviral to the Canadian governmentthis year.

Along with SHP’s vaccine unit, IDBinherits an agreement worth an estimatedC$60 million (US$44.6 million) with Tech-nology Partnerships Canada, a govern-ment agency that promotes Canadian tech-

nology and will help offset some R&Dexpenses.

IDB also acquires three research amanufacturing facilities in the U.S. aCanada, as well as some 400 employemost of whom are involved in manufacting — a significant jump from IDheadcount of 150.

SHP will receive $30 million in cashclosing, plus another $30 million on tfirst anniversary of closing. The U.K. copany also receives rights to acquire

million IDB shares worth another $million.SHP also will provide IDB with a $

million loan facility, of which Holler s$70 million will be written off, while remainder will be repaid by a percentaof sales of Fluviral outside Canada and aproducts resulting from SHP’s preclinpipeline.

IDB plans to keep Canadian rigfor all of its products, and to find paners for StreptAvax in North AmeriEurope and Asia. The company also wlook to out-license, or possibly co-d

velop, one or more of its preclinivaccine candidates.

‘It’s the BioCentury’TM

Authoritative. Globally focused. The leading perspectiveon the strategic issues essential to the formation, develop-ment and sustainability of life science ventures into 2005and beyond.

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By Christopher MaggosSenior Writer

Last year, Alteon Inc.’s alagebrium (ALT-711) failed in sepa-rate Phase II trials in systolic hypertension and diastolic heartfailure. The company is now hypothesizing that the two patientpopulations need different dose levels because alagebrium mayhave two separate mechanisms of action, each of which may betriggered at a different dose. ALT is testing that hypothesis in twonew Phase II trials.

Alagebrium is an oral thiazolium com-pound that breaks advanced glycationendproduct (AGE) crosslinks. At all doselevels, ALT thinks alagebrium may be act-ing to break glucose cross-links, whichharden tissues such as artery walls.

At higher doses, alagebrium also maybe acting to alleviate some of the anatomicand functional manifestations of heart dis-ease by altering cell signaling. “Data havebeen published showing that alagebriumreduces the expression of cytokines suchas TGF beta, VEGF and growth hormones,”said President and CEO Kenneth Moch.

ALT (Ramsey, N.J.) thinks a lower dosecould work for hypertension while a higher dose may be effectivefor heart failure. To understand why, it is necessary to go back to the company’s two failed Phase IIb trials, SAPPHIRE andSILVER, as well as to the Phase IIa DIAMOND trial.

SAPPHIRE and SILVER both enrolled uncontrolled systolic

hypertension patients with or without left ventricular hypertro-phy (LVF), and both missed the primary endpoint of an improve-ment in systolic blood pressure of at least 5 mmHg at the highestdose. Doses tested were in the range of 35-210 mg per day (seeBioCentury, July 21, 2003).

“What we saw in SAPPHIRE/SILVER was that the best resultwas actually at the lower dose of about 35 mg/day and that thechange was about 4 mmHg,” Moch said. “We saw a good p-valuethat was less than 0.05. But that was not a prospectively definedendpoint.”

More analyses of the low dose data will be released in May atthe American Society of Hypertension meeting in New York.

DIAMOND was a 16-week, open-label U.S. trial in diastolicheart failure patients with normal ejection fractions. Data on the

primary endpoint of exercise tolerance were not reportablebecause of variability attributed to both methods and executionof measurement (see BioCentury, Jan. 27, 2003).

Product Development

Getting it right, more or lessHowever, 210 mg of alagebrium twice daily showed sign

cance on the secondary endpoint of reduction in left ventricumass (p=0.04). “In DIAMOND we saw that alagebrium coremodel the heart in a matter of months. Usually it takes yearMoch said. “As blood pressure increases, the heart changes fra cylindrical volume pump to a spherical pressure pump. If ygive a blood pressure drug, over the course of years patients cget back to a cylindrical volume pump.”

ALT also saw a trend toward improvleft ventricular diastolic filling in DMOND, and the compound significanimproved quality of life as measured the Minnesota Living with Heart Fail(MLHF) questionnaire (p=0.01) (BioCentury, April 7, 2003).

ALT hypothesizes that the down relation of cytokines and growth factorshigh doses of alagebrium may be wfacilitated the reduction in left ventrimass seen in DIAMOND. ALT expethis would make the hypertrophied hea better pump because it would lessstiffness by breaking glucose cross-linand decrease mass by reducing the sign

ing that causes the heart muscle to bulk up.Hence, while high dose alagebrium could be efficacious

heart failure, it could raise blood pressure in hypertensbecause it allows the heart to pump more blood. Thus, a lowdose would be desirable in hypertension patients. Conversel

higher dose would be better in heart failure patients, where heart’s ability to pump is diminished.More data should come in the next year and a half. L

month, ALT began the U.S. Phase IIb SPECTRA trial in about 3patients with a systolic blood pressure of at least 140 mmHPatients will receive 10, 50 or 150 mg of alagebrium or placefor 12 weeks (see BioCentury, March 15). Results are expected2005.

Last week, ALT began PEDESTAL, a U.S. Phase II trial inpatients with diastolic dysfunction in diastolic heart failure aimpaired ejection fraction. Patients will receive 35 mg/day or 2mg twice daily (see B10). Results are expected in the second h

PEDESTAL is enrolling a different patient population thDIAMOND, which was done in patients with normal eject

fractions. Although ALT saw an effect in patients with normejection fraction, Moch said the company also wants to stupatients with abnormal ejection fraction.

‘Data have been

published showing that

alagebrium reduces the

expression of cytokines such as TGF beta, VEGF

and growth hormones.’

— Alteon’s Kenneth Moch

All press releases, news announcements and story inquiries should be submitted to our News Room at [email protected]. Editorial announcements emailed to the Editor-in-Chief

and/or the Publisher may not receive immediate attention and potential stories will be delayed.

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By Susan Schaeffer Staff Writer

With two polymerase inhibitors on the market and twomore in Phase III trials, the market for hepatitis B therapeu-tics is getting crowded. But Anadys Pharmaceuticals Inc. is

betting that the shortcomings of allfour leave room for it to work on abetter mousetrap.

ANDS last week exercised its op-tion to co-develop ANA380 (LB80380),a polymerase inhibitor from LG LifeSciences Ltd. that is in Phase II trials.The partners plan to develop the com-pound for chronic HBV infection asfront-line therapy and salvage therapy

for lamivudine-resistant patients.According to Kleanthis Xanthopou-los, president and CEO of ANDS (San

Diego, Calif.), shortcomings of other polymerase inhibitorsinclude low potency, high toxici ty and lack of activity againstresistant strains. Although the company has not yet identi-fied how ANA380 produces a different result, he said it hasdemonstrated high potency, low toxicity and activity againstlamivudine-resistant HBV strains in preclinical and earlyclinical studies.

In addition to Epivir lamivudine, a nucleoside analog fromShire Pharmaceuticals Group plc (LSE:SHP; SHPGY, Basing-stoke, U.K.) and GlaxoSmithKline plc (LSE:GSK; GSK, Lon-don, U.K.), the marketed HBV polymerase inhibitors include

Hepsera adefovir dipivoxil, a nucleotide analog from GileadSciences Inc. (GILD, Foster City, Calif.).Lamivudine’s primary drawback is viral resistance. According

to Xanthopoulos, in about 25% of HBV patients treated withlamivudine, the virus develops resistance within one year; withinfour years, that figure increases to 65%. Ade fovir has a verylow resistance profile, at single-digit percentages within thefirst year. But the dose must be kept low to avoid nephrotox-icity, which leads to a trade-off in potency.

Interferon alpha also is indicated to treat HBV but doesnot directly inhibit viral replication.

Of the up-and-comers, Idenix Pharmaceuticals Inc. (Cam-bridge, Mass.) is developing telbivudine, a nucleoside analogin Phase III testing, and Bristol-Myers Squibb Co. (BMY,

Product Development

In HBV, five is not a crowdPrinceton, N.J.) has restarted development of its entecavinucleoside analog also in Phase III.

ANDS reckons ANA380 is about 12-18 months behtelbivudine in development.

In a head-to-head Phase IIb trial in 104 patients, telbidine demonstrated superior antiviral activity compared wlamivudine. Idenix said telbivudine has a favorable safprofile and that it is focusing on developing the compounda first-line therapy because untreated patients represent tgreater unmet medical need. Indeed, Idenix said telbivudhas not been tested in lamivudine-resistant patients.

Although ANA380 and adefovir are in the same chemiclass – both are nucleotide analogs – ANDS said ANA3showed a 20-fold differential in indicators of nephrotoxicin head-to-head in vitro studies. In addition, the compou

has shown no renal or other toxicity in animal models.“Such a large difference in vitro, in combination wanimal toxicology studies, suggests that we’ll have a very hsafety margin,” said Devron Averett, senior vice presidentdrug development.

In addition, Averett said that an in vitro assessmentANA380’s potency in lamivudine-resistant strains show“about a two-fold difference in one direction for one mution, and a two-fold difference in the other direction fanother mutation — what you see is very similar to adefov

In humans, the company said interim resul ts from a PhaIIa trial of ANA380 in 28 patients showed potency greathan lamivudine, adefovir and entecavir and comparable telbivudine. According to Xanthopoulos, after the first fo

weeks of treatment, ANA380 reduced mean HBV DNA by log. Citing data extracted from published sources, he sthis compares to a reduction of 1.9 log for adefovir, 3.6 for telbivudine; 2.9 log for entecavi r, and 2.2 log for lamidine. ANDS expects final data from the trial within the necouple of quarters.

ANDS plans to start a Phase II trial of ANA380 lamivudine-resistant HBV patients within the next six mont

Xanthopoulos estimated that there are 8-10 million caof HBV in the territories licensed by ANDS. Under the deLG Life Sciences (Seoul, Korea) has commercialization rigin China, India, Korea and Southeast Asia, and ANDS rights in North America, Europe, Japan and the rest of tworld.

BioCentury

Company IndexApril 26, 2004

Actlion (SWX:ATLN) A13

Adprotech B2

Advanced Biotherapy (ADVB) B9

Advanced Viral Research (ADVR)

B7

Agencourt B7

Agrob iogen 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

Ascent A6

Astex B2

AstraZeneca (LSE:AZN; AZN) A10,

B2

AtheroGenics (AGIX) A16

Auxil ium 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)

A18, B2See page A

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BioCentury, THE BERNSTEIN R EPORT ON BIOBUSINESS APRIL 26, 2004 PAGE A10 OF 2

Technology Briefing

Mass ListeriaWhen MedImmune Inc. licensed rights to EphA2 from Purdue

University in 2001, the company’s first order of business was todevelop antibodies against the cancer target. More recently, thecompany decided to add a complementary approachby developing EphA2 cancer vaccines, and set aboutlooking for a platform with which to deliver the antigen.Last week, MEDI placed its bet with Cerus Corp.’s Listeriatechnology, which the partners hope will provide a broadimmune response and straightforward manufacturing.

EphA2 is a receptor tyrosine kinase that, whenoverexpressed, promotes tumor growth and metastasis.According to MEDI (Gaithersburg, Md.), the target isoverexpressed in multiple cancers, including breast,prostate and colon cancer, and metastatic melanoma.“EphA2 is an important oncogene,” said Michael Kinch,

director of biology. “It’s also been shown to correlate with poorpatient 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, you’dexpect to get antigen presentation. Thus, having a vaccine wouldhelp you mop up.” MEDI said further research could includestudies on the combination of EphA2 antibodies and vaccines.

As a vaccine delivery vehicle for its antigen, MEDI choseCERS’s Listeria technology, which uses strains of the bacteriathat have been engineered to have reduced toxicity. Young toldBioCentury that a main reason MEDI opted for this technologyis the broad immune stimulation elicited by Listeria.

MEDI is responsible for clinical development, manufacturing

and commercialization. CERS will participate in developmeand will receive an upfront payment and development fundand is eligible for milestones and royalties.

Although the deal was officially announced lweek, the companies have been working on the projfor some time. In March, they presented data at tAmerican Association for Cancer Research meetingOrlando, Fla., showing that the vaccine significanimproved survival times compared with control inmouse model of lung cancer.

CERS (Concord, Calif.) said the data showed that technology elic ited Class I and II immune responses astimulated cytokine production from the innate immusystem.

Stephen Isaacs, president and CEO of CERS, no

that Listeria “is an intracellular bacterium. It lives inside host cand eventually is encapsulated into a vesicle where antigens aprocessed and presented for CD4 cells. It then enters tcytoplasm, and we’ve programmed the Listeria to stimulate Ccells. In addition, the human immune system is able to, over timrecognize molecular patterns and mount an innate immuresponse.”

David Cook, vice president of R&D at CERS, added tListeria is easy to manufacture and scale up. “All you’re readoing is fermenting bacterium,” he said. “You don’t have asubsequent purification steps because the bacterium itself is tproduct.”

MEDI expects to start clinical trials of an EphA2 antibonext year. The company did not disclose a timeline for getting

vaccine into the clinic. — Steve Edelson

Online links this week

Links to the following documents reside online at BioCentury’sNews Center at www.biocentury.com.

Orphan drugs

Summary of actions taken at the April meeting of the EMEA’sCommittee for Orphan Medicinal Products (COMP).

Patents

National Academy of Sciences report, “A Patent System forthe 21st Century” (see A14).

SEC

Guidance regarding the Management’s Discussion & Analysis

of Financial Condition and Results of Operations (MD&sections of SEC filings (see Cover Story).

Transparency

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

Product documentation

— Apokyn: FDA Talk Paper on the approval of injectaApokyn apomorphine to treat immobility episodes in patewith Parkinson’s disease (PD), from Bertek Pharmaceutic(Research Park Triangle, N.C.).

— Faslodex: EPAR for Faslodex fulvestrant to treat brecancer in postmenopausal women, from AstraZeneca (LSE:AZN; AZN, London, U.K.).

— Paxil : Summary of the CPMP’s safety review of Paparoxetine to treat depression, from GlaxoSmithKline (LSE:GSK; GSK).

— PhotoBarr: EPAR for PhotoBarr porfimer sodium to trhigh-grade dysplasia associated with Barrett’s esophagus, frAxcan Pharma Inc. (TSE:AXP; AXCA).


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Last week, Cougar acquired exclu-sive worldwide rights to develop andcommercialize abiraterone acetate totreat prostate cancer from BTG Inter-national plc (LSE:BGC, London, U.K.).

Abiraterone is an oral inhibitor of the 17 alpha-hydroxylase/C17-20 lyaseenzyme complex, which is involved intestosterone synthesis. By blockingtestosterone production, the com-pound would inhibit tumor survival/growth signaling through the andro-gen receptor, which often requirestestosterone for activity.

There is clinical proof of conceptfor the idea of inhibiting testosteronesynthesis. According to Auerbach, manyphysicians prescribe the antifungal ke-

toconazole to treat prostate cancer based on its profile as arelatively broad-spectrum steroid synthesis inhibitor. As anantifungal, ketoconazole is thought to inhibit P450 sterol C-14alpha demethylase, blocking synthesi s of ergosterol, which isan essential component of the fungal cell membrane.

Abiraterone has completed Phase I trials in 26 prostatecancer patients, in which it showed the ability to suppresstestosterone synthesis. Cougar initially will focus the com-pound as a second-line treatment for prostate cancer, but didnot provide a timeline for the start of Phase II trials.

Gloucester: MOA matters

Though an in-licensor, Gloucester is “not looking at

reprofiling or rescuing old drugs,” said CEO Jay Mohr.Instead, the company is looking for small molecules that havea new mechanism of action and have shown biologic activityon their own, or belong to a class of compounds sharing thesame target or MOA that has shown biologic activity.

Earlier this month, Gloucester acquired worldwide rightsto develop and market FK228, a depsipeptide histone deacety-lase (HDAC) inhibitor from Fujisawa Pharmaceutical Co. Ltd.(see BioCentury, April 19).

Emerging Companies,

from previous page The compound is in Phase II tr

for renal cell carcinoma (RCC) ahormone-refractory prostate can(HRPC). In addition, the NCI is coducting a Phase II trial in cutaneouscell lymphoma (CTCL) under a CRADwith Fujisawa. Gloucester also gainrights to FR135313, the biologically tive moiety of FK228 that is in preclinidevelopment.

According to Mohr, FK228 was on the block because Fujisawa (Tok

Japan) was exit ing the oncology spac“From what Fujisawa told us, th

were several companies interestedlicensing FK228,” Mohr said. Part what tilted the scale in Gloucestefavor was that it would be focused on compound, he said. “Because we small, companies know that thei r copound will get the attention it need

The company is looking to add one or two more compounMohr said he is likely to look to a Phase I or preclincompound, although the latter “would have to be latepreclinical development with a significant pharm/tox packag

Although Gloucester hasn’t disclo sed how much monehas raised, Mohr said it has enough to fund ongoing clinitrials to the point where the company will be able determine which indication it wants to pursue in a registtional study. Later this year, i t plans to raise a new round twill fund the registrational trial and enable it to in-license oor two compounds, and add to its clinical and regulatocapabilities.

Mohr noted that Phase III trials in either RCC or CTwould require far fewer patients than cancers such as lung

colorectal. “These are niche indications, and would likrequire much smaller trials, perhaps as few as 100 patienthe said.

Should FK288 reach the market, Gloucester plans to keU.S. rights. “Our plan is to become an integrated compaThe indications we will be pursuing are small enough in tU.S. that we could market the compound with a focuscommercial infrastructure,” Mohr said.

The company will seek a partner outside the U.S.

Gloucester Pharmaceuticals Inc.

Cambridge, Mass.

Technology: Histone deacetylase inhibitors

Disease focus: Cancer

Clinical status: Phase II

Founded: 2003 by Jay Mohr, Gregory Verdine,Martin Vogelbaum

Corporate partners: Fujisawa Pharmaceuti-cal Co. Ltd.

University collaborators: NA

Employees: 15 by year end

Funds raised: NA

Investors: Apple Tree Partners

CEO: Jay Mohr

Patents: NA

BioPure (BPUR) A4Bioreason 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

Carol ina Pharma B7

Company Index,

from page A9 Celgene (CELG) A13

Cel l S ignaling B3

Cell Therap (CTIC; NMerc:CTIC)

B10CeNeS (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) B3DSM 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) B7Genentech (DNA) A13

GeneProt B4

Genitope (GTOP) B7

Genta(GNTA) B5

Genzyme (GENZ) A6, B5, B

Gilead (GILD) A9, A16, B4,

GlaxoSmithKline (LSE:GSK; G

A9, A10, B5

Gloucester A11

GTx (GTXI) B4

Harvard U B3

See page A

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By Steve Usdin Washington Editor

Senior officials of the Centers for Medicare & MedicaidServices got a full dose of rationing warfare last week, as patients,their advocates and caregivers made diametrically oppositedemands for their fair share of a $500 million prescription drugdemonstration project mandated by the new Medicare prescrip-tion drug law.

At a meeting held to receive publiccomments about how CMS should man-age the program, aides to two senatorswarned that the plan the agency is likely toimplement bears little resemblance to thebenefit Congress intended when lawmak-ers passed the Medicare Modernization

Act (MMA) last November.Section 641 of the MMA instructs CMSto launch a “Demonstration Project forCoverage of Certain Prescription Drugsand Biologicals” within 90 days of enactment. The 90-daydeadline came and went in March, but CMS still is struggling todesign the program. It recently announced some tentativedecisions, and solicited public comments on scope of coverageand criteria for selecting eligible patients.

A few things are clear about the project: the $500 million isnot nearly enough to cover drugs and biologics for everyonewho believes they should be eligible, and the 50,000-personenrollment cap is not large enough to accommodate all of thepotential participants. And based on last week’s meeting,

however the parameters are defined, elderly patients will not bequiet if they think they’re been excluded from receiving therapiesthey need.

A total of 40% of the $500 million will be reserved for cancerdrugs, but to the disappointment of advocates for rheumatoidarthritis (RA) and multiple sclerosis (MS) patients, who felt theremainder should be reserved for treatments for these diseases,CMS has not yet set limits on the types of other conditions theprogram will address.

CMS announced five criteria for the demonstration programon April 14:

— A drug or biological covered under the project musteliminate the need for a drug or biological currently covered byMedicare.

— Coverage of the drug or biological in the project is limitedto approved indications.

— The drug or biological must be of at least equal efficacy tothe covered drug it replaces.

— Use of the replacement drug or biological must repre-sent an advantage in terms of access and/or convenience forpatients compared to the currently covered drug or biologi-cal.

— The drug or biological is not el ig ib le for coverageunder the project if the drug or biological it replaces is notcommonly provided incident to a physician’s services.

Although last week’s meeting was supposed to focus oncriteria for beneficiary selection, participants also criticized

Politics & Policy

Zero sum game

‘There will be many more

people interested and

eligible for this project

than we can include.’

— Stuart Guterman of CMS

CMS’s criteria for selecting drugs.The decision to exclude off-label indications was attacked

representatives of multiple myeloma (MM) patients, physiciand an aide to Sen. Kay Bailey Hutchison (R-Texas). Thcontended that Celgene Corp.’s Thalomid thalidomide, whicnot approved for MM, should be covered because it is the facto standard of care.

Sol Barer, president and COO of CE(Warren, N.J.) , did note that an sNDA MM is pending at FDA, with an Octouser fee deadline.

As to beneficiary selection, repsentatives of seniors suffering from comon diseases such as RA made a pitbased on numbers. Funds “should

apportioned based on prevalence in tMedicare populat ion,” sa id KeBrennan, a lobbyist for the ArthrFoundation.

Partners Wyeth (WYE, Madison, N.J.) and Amgen I(AMGN, Thousand Oaks, Calif.) also argued in favor of proptional allocation according to disease prevalence within the nocancer group. They also reported that 57% of Medicare recents with RA have incomes below $15,000 per year, and urgCMS to create enrollment criteria weighted toward low-incopatients who lack drug coverage. The companies market Enbetanercept for RA and other indications.

MS patient groups, however, strongly opposed proportioallocation. “It doesn’t account for the cost of drugs and therefo

won’t correct access barriers,” said Stephanie Simmonsrepresentative of the National Multiple Sclerosis Society.Simmons and other MS advocates said that funds should

set aside to pay for three drugs: Rebif interferon beta-marketed by Serono SA (SWX:SEO; SRA, Geneva, SwitzerlanBetaseron interferon beta-1b, marketed by Schering AG (FSE:SCSHR, Berlin, Germany); and Copaxone glatiramer, marketedTeva Pharmaceutical Industries Ltd. (TEVA, Jerusalem, IsraThe fourth MS biologic, Avonex interferon beta-1a from BiogIdec Inc. (BIIB Cambridge, Mass.), is covered by Medicare.

Moveover, advocates for patients with pulmonary artehypertension (PAH) have formed a coalition to lobby CMS to aside $37 million of the Section 641 funds to pay for Traclbosentan from Actelion Ltd. (SWX:ATLN, Allschwil, Switz

land), which is marketed in the U.S. by Genentech Inc. (DNSouth San Francisco, Calif.). “Putting all patients in a sinselection pool would discriminate against orphan diseases,” sCara Ugolini, a spokesperson for the Pulmonary HypertensAssociation.

Many of the concerns about implementation of the demostration program stem from CMS’s misinterpretation of the mandating it, according to Bill Pewin, a staffer for Sen. OlymSnowe (R-Maine). The bill’s authors “didn’t intend replacemto be a criteria. What we were trying to do is provide a benbroadly for patient-administered drugs,” he said.

Pewin added that CMS’s focus on the word “replacemeSee next p

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By Steve Edelson& Shaun BrownSenior Writers

In the best of all possible worlds,revenues from the launch of MedImmune’s FluMist intranasal influ-enza vaccine would have more than madeup for planned increases in R&D spend-ing, thus keeping EPS intact. When thatdidn’t happen, MEDI decided to keepspending up anyway.

As a result of that decision, thecompany’s first quarter net income grewonly 1% quarter over quarter from$110 to $111 million, despite revenue

growth of 13% from $431 million to $489 million. Much of thedifference was in the R&D line, as first quarter R&D spendingincreased 57% to $49.8 million from $31.7 million in the2003 quarter.

For 2004, the company expects sales to grow in the lowdouble digits versus a 26% increase in 2002. The slowing salesgrowth in part reflects the maturity of Synagis, MEDI’s antibodyto prevent respiratory syncytial virus (RSV).

Given slowing revenue growth and rising R&D spending,R&D will rise as a percent of total sales, noted Jim Young,president of R&D. “This year, we expect to see R&D investmentat about 20% of product sales, which is up from last year’sinvestment of 16%.”

The good news is that MEDI’s higher R&D spend correlates

with pipeline visibility. MedImmune expects to have four prod-ucts in Phase III trials next year, including CAIV-T, a refrigerator-

Ebb & Flow

Pipeline gardeningstable formulation of FluMist.

Three other compounds are slated Phase III trials next year: Numax, a negeneration antibody for RSV; Vitaxinhumanized MAb against integrin alp(v)beta(3) that is in Phase II trials to trpsoriasis, rheumatoid arthritis (RA), mestatic melanoma and metastatic prostcancer; and an anti-HPV vaccine that ais in Phase II trials.

Phase II Vitaxin data are expected tyear. Also this year, the company planscomplete additional analyses of its PhaseCAIV-T data. Positive preliminary resufrom two Phase III trials were reported l

month (see BioCentury, March 8).MEDI plans to launch CAIV-T in 2007 and hopes that tvaccine will rejuvenate its sales. At that time, Young said, “ttrend of higher R&D spending as a percent of sales will reverand could return to around 16%.

In addition to its late-stage products, MEDI filed INDs lyear for three compounds, and plans to continue that pathrough 2006. Young said the company has been filling its eapipeline in part through more in-licensing. “In the front end, tR&D spend isn’t huge,” he noted. “We’ve used our ventcapital arm to make equity investments in companies, which uthe money to fund the work they’re doing for us — it’s very Pfriendly.”

MEDI was up $0.41 to $23.95 on the week.

IPO watch

Nanotechnology company Nanosys filed to raise $1million in an IPO underwritten by Merrill Lynch; LehmCIBC; and Needham. Among other things, the companydeveloping a nanowire-array molecular sensing system detect analytes in real time using low voltage measuremetechnology.

Nanosys has about four years of cash, posting a 20operating loss of $9.5 million and ending the year with $3million in cash. Principal stockholders include Arch VentPartners (14.7% prior to the offering); CW Group (13.6Polaris (13.6%); and Venrock (13.6%).

Urology company Auxilium also threw its hat into tring, filing to raise up to $86.3 million in an IPO underwrit tby Deutsche Bank; Piper Jaffray; and Thomas Weisel. Tcompany has one marketed product: Testim (AA2500) tocal testosterone gel to treat hypogonadism. Last year, Auxil ireported an operating loss of $29.6 million and revenues$8.8 million. The company had $28.4 million in cash at D31 . P r inc ipa l s tockho lders i nc lude Perseus -SorBioPharmaceutical Fund (22.4% prior to the offering); SPrivate Equity (22.1%); Sprout Capital (17.7%); LehmBrothers (11.1%); Schroder Ventures (10%); Caduceus (9.6and Biotech Growth (8.5%).

See next p

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 it’s discounting or old-fashioned competition that’s

lowering EPO prices, AMGN is still forecasting a solid sales

trajectory. ($M)

2004

Product 2001 2002 2003 1Q04 guidance

AMGN

Epogen $2,108.5 $2,260.6 $2,434.7 $590.0 NA

Aranesp $41.5 $415.6 $1,543.8 $543.0 NA

Total $2,150.0 $2,676.2 $3,978.5 $1,100.0 $4,600-

$5,100

JNJ

Procrit/ $3,430.0 $4,269.0 $3,984.0 NA NA

Eprex

Total last week: $130.0M

IPOs YTD: $1102.4M

Follow-on YTD: $1087.3M

Venture YTD: $2042.8M

Other YTD: $3011.9MTotal YTD: $7244.3M

In 2003 a total of $19.5 billion was raised, including

$509 million in IPOs, $3.8 billion in follow-ons,$3.9 billion in venture capital, and $11.3 billion in

other fundraising. Totals include overallotmentsand warrants. (Source: BioCentury Financial Center)

Money Raised in 2004

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Ebb & Flow,

from previous page

Barron’s bump

Investors liked what they read in a Barron’s article last week that merely stated the obvious: pharma needs drugs and biotechcompanies have compounds available in late-stage development

or on the market. Cardiovascular play AtheroGenics (AGIX),ophthalmic company Eyetech (EYET) and cancer companiesMillennium (MLNM), Onyx (ONXX) and OSI (OSIP) werementioned.

AGIX had the smallest gain on Monday — a 1% increase — despite being the only company listed that holds full rights to itslate-stage compound. Its AGI-1067 is in a Phase III trial forsecondary prevention of coronary artery disease.

The other companies all added at least 3% on the day. OSIPled the way with a 10% pop. On the week, AGIX slipped $0.44to $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.

Branching out on ErbituxImClone (IMCL) jumped $7.03 (12%) to $66.30 on 9.9

million shares on Monday following post-market news theprior Friday that FDA accepted for review a CMC supplemen-tal BLA for IMCL’s BB36 manufacturing facility in Branchburg,N.J.

The PDUFA date for the sBLA is June 18. Approval would

allow IMCL and partner Bristol-Myers (BMY) to meet commercial demand for colorectal cancer drug Erbitcetuximab. BB36 has FDA approval to manufacture Erbitfor investigational use, and Swiss approval to manufactucommercial product. The partners have met initial Erbitdemand in the U.S. with supplies produced at a LonBiologics facility.

Viread sales go up… and north

Gilead (GILD) bumped up 2004 guidance for its Viretenofovir HIV drug on its earnings call after market ThursdThe increase to $725-$775 million from $700-$750 millreflects global demand. In the first quarter, 40% of Virea$193.1 million in sales came from outside the U.S.

The company also said that it has established a national price in Canada of C$16.25 (US$12.07) per day for Viread. Tprice is still under negotiation in certain provinces, whediscounts to the list price may apply. GILD said it would continto provide the drug at no cost to patients enrolled in its ExtendAccess Program until the drug is on the formularies of all t

provinces (see BioCentury, Nov. 10, 2003).GILD closed Friday at $60.12, up $0.90 on the day and $2on the week.

On the road

Cancer play Pharmexa (CSE:PHARMX) was down DKK1

IPO queue update

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. T

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)S-1 Original New funding Price Hoped for Lead Origin

Company update funding goal goal (A) Shares range post-$ (A) program filin

Barrier 4/2 Up to $86.3 $75.0 5.0 $14-$16 $327.0 Ph III 2/6/

Cytokinetics 3/11 Up to $86.3 $69.6 5.8 $11-$13 $310.0 Ph II 1/27/

Hoped for post-$ avg $318.5

Not updated

Acadia NA Up to $86.3 NA TBD TBD TBD Ph II 2/27/

Alnylam NA Up to $86.3 NA TBD TBD TBD Preclin 3/1/

Celldex NA Up to $50 NA TBD TBD TBD Preclin 4/9/

CoTherix NA Up to $70 NA TBD TBD TBD NDA submission ‘04 3/11/

Critical Therapeutics NA Up to $103.5 NA TBD TBD TBD Approved 3/19/

Favrille NA Up to $86.3 NA TBD TBD TBD Ph II 4/8/

Icagen NA Up to $86.3 NA TBD TBD TBD Ph II completed 4/8/

Idenix NA Up to $100 NA TBD TBD TBD Ph III 12/15/

Inhibitex NA Up to $86.3 NA TBD TBD TBD Ph II 3/3/

Metabasis NA Up to $86.3 NA TBD TBD TBD Ph II 2/3/

Momenta NA Up to $86.3 NA TBD TBD TBD ANDA submission 3/11/

this year

Threshold NA Up to $86.3 NA TBD TBD TBD Ph II completed 4/9/

ViaCell NA Up to $92 NA TBD TBD TBD Ph I/II 4/5/

Xenogen NA Up to $51.8 NA TBD TBD TBD Mkt 4/2/

See next pa

8/13/2019 042604 Bc



to DKK30 on the week after saying it plans to raise aboutDKK209 million ($33.6 million) through a rights issue of 12.3million shares at DKK17 each. PHARMX’s shareholders will beoffered 3 new shares for each share they hold. The subscriptionperiod will run from May 3 through May 17.

PHARMX’s lead programs are HER-2 Protein AutoVacand HER-2 DNA AutoVac, which have both completed PhaseI studies in breast cancer. PHARMX estimates that it needsabout DKK160 million ($25.8 million) to get through to mid-2006 at its current burn rate. The offering is partly under-written by ING, and ING and Gudme Raaschou are leadmanagers. The company’s market cap is DKK123 million($20 million).

Analyst tracks

John Sullivan joined Leerink Swann as an analyst in the firm’sbiotech group. Previously, Sullivan was vice president and senior

Ebb & Flow,

from previous page

EPS watchThere were only two misses in last week’s earnings crush: one biotech and one pharma. Chiron (CHIR) missed the Street by a nickel, but the news

didn’t 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 Stre

expects AFFX to be profitable on a full-year basis. (B) FRX results are for fiscal 4Q.

1Q04 1Q04 Growth Mcap 4/

EPS EPS from 4/23 Wk % chg Mc

Company est actual Outcome 1Q03 cls chg chg ($M) ($

Affymetrix (AFFX) (A) -$0.08 -$0.03 Beat by $0.05 NA $31.39 -$3.62 -10% $(219.1) $

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 s

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) $74Product 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

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

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

LLY’s 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 digit

Forest (FRX) (B) $0.37 $0.38 Beat by $0.01 -21% $66.15 -$6.71 -9% $(2,464.9) $24

FRX said the quarter-over-quarter EPS decrease reflects increased selling expenses related to the launches of Namenda for Alzheimer’s 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 company

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

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

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. Th

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

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 p

equity research analyst at Stephens, where he covered comnies with enabling technologies for discovery research.

Clinical milestones

Alkermes (ALKS) was up $0.54 to $15.74 on the week afcompleting enrollment in a Phase III safety trial of its Vivitr

injectable extended-release naltrexone in about 400 patiewho are alcohol- or opiate-dependent. ALKS expects intersafety data after six months and plans to use results to suppan NDA submission in the first half of 2005 (see B9).

Antigenics (AGEN) fell $0.87 to $9.99 on the week afannouncing that FDA wants additional product characterizatfor the company’s Oncophage cancer vaccine to treat renal ccarcinoma (RCC), despite having lifted a partial clinical hold the Phase III trial last November. AGEN said it will submit tdata over the next several weeks.

ZymoGenetics (ZGEN) added $0.59 to $16.74 on Mondafter starting the first of four double-blind Phase II trials ofrecombinant human thrombin (rhThrombin) to control bleed

See next pa

8/13/2019 042604 Bc



1Q04 1Q04 Growth Mcap 4/2

EPS EPS from 4/23 Wk % chg Mca

Company est actual Outcome 1Q03 cls chg chg ($M) ($B

Medicines Co. $0.05 $0.08 Beat by $0.03 NA $34.24 $0.47 1% $22.0 $1

(MDCO)

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

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; $0.53 $0.52 ($0.57 using NA NA $42.43 -$1.49 -3% $(3,666.2) $104

SWX: NOVN) U.S. GAAP)

Pharmaceutical sales increased 19% quarter over quarter to $4.3B from $3.6B. Global sales of Gleevec/Glivec imatinib to treat chronic myeloid leukem

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

Human pharmaceutical sales came in at $11B, a 46% increase compared with 1Q03, which in part reflects PFE’s 2003 acquisition of Pharmacia. Thecompany reiterated its full year adjusted EPS guidance of $2.13. PFE expects to spend $7.9B on R&D this year.

Schering-Plough $0.01 -$0.01 Missed by $0.02 NA $17.21 -$0.13 -1% $(191.1) $25

(SGP)

The EPS figure excludes charges for employee termination costs and SGP’s exit from a European R&D facility. Next year, the company hopes that

cholesterol therapeutic Vytorin, a combination of SGP’s Zetia and Merck’s 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

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

Human pharmaceutical sales came in at $3.2B, up 8% from 1Q03.

in surgeries. The company hopes to begin Phase III testing inearly 2005 (see B11). ZGEN closed Friday at $16.37, up $0.22on the week.

Neurobiological (NTII) slipped $0.16 on the week to $4.49after starting the first of two Phase III trials of Xerecept to treatperitumoral cerebral edema. NTII has an SPA with FDA for bothtrials, and the compound, a synthetic CRH peptide, has OrphanDrug designation (see B10).

Rigel (RIGL) added $1.75 on the week to $21.50 afterstarting a U.S. Phase II trial of its R112 in allergic rhinitis (seeB11). Results are expected in the second half. R112 is a nasalspray Syk kinase inhibitor that inhibits mast cell activation.

Alteon (ALT) added $0.06 on the week to $1.74 afterstarting a Phase II trial of its alagebrium (formerly ALT-711) inpatients with diastolic dysfunction and impaired ejection fraction(see Product Development, A8).

Inspire (ISPH) gained $1.05 on the week to $14.25 afterstarting a Phase II trial of its INS37217 ophthalmic denufosol as

a first-line therapy in patients with rhegmatogenous retinaldetachment (RRD) (see B10).Ilex (ILXO) gained $0.26 on the week and closed Friday at

$24.20 after completing enrollment in a Phase II multiplesclerosis (MS) trial comparing its Campath alemtuzumab to Rebif interferon beta-1a from Serono (SWX:SEO; SRA) (see B10).

Ebb & Flow,

from previous page Campath is marketed to treat refractory B cell chronic lymphcytic leukemia (B-CLL).

Vivus (VVUS) was up $0.22 on the week and closed Fridat $6.38 after starting a Phase II trial of its avanafil (TA-1790)treat erectile dysfunction (ED). VVUS expects to complenrollment in the trial by year end and data are expected in tfirst half of 2005 (see B11).

Ebb & Flow

Trimeris (TRMS) popped $1.64 (13%) to $14.70 on million shares on Wednesday following its post-market earniannouncement on Tuesday, in which it said worldwide salesHIV drug Fuzeon increased 36% to $24 million from $1million in the fourth quarter of 2003. TRMS and partner Roc(SWX:ROCZ) launched the injectable HIV fusion inhibitor lspring, and the drug has had a slow in an indication populatby oral drugs (see BioCentury, Feb. 9). TRMS closed Friday$15.07, up $1.66 on the week.

Investors shrugged off BioMarin’s news that it will patotal of $175 million for the Ascent Pediatrics business

Medicis (MRX), as the stock added $0.04 to $6.89 Wednesday’s announcement. BioMarin (BMRN; SWX:BMRwants to become a pedia tric s-focused biopharmaceutical copany, and plans to partner its non-pediatric pipeline produ(see Strategy, A6). BMRN closed Friday at $6.92, down $0.17

EPS Watch,

from previous page

See next pa

8/13/2019 042604 Bc



the week.Cerus (CERS) popped $0.47 (13%) to

$4 on 2.3 million shares on Wednesday’snews that it partnered with MedImmune(MEDI) to develop and commercialize avaccine to treat cancers of the breast,prostate and colon, as well as metastaticmelanoma. CERS’s Listeria vaccine tech-nology will be used to develop a vaccineagainst MEDI’s EphA2 protein (see Tech-nology Briefing, A10). CERS gave back somegains and closed Friday at $3.96, up $0.35on the week.

Isotechnika (TSE:ISA) fell C$0.45(15%) to C$2.50 on Tuesday after rework-ing its deal with Roche (SWX:ROCZ) forISA247, a small molecule immunosup-pressant. ISA now will independently de-

velop the trans isomer version of ISA247for renal transplant and psoriasis, and thecompanies dropped development of amixed version of ISA247, which had com-

Ebb & Flow,

from previous page pleted Phase II testing in psoriasis andkidney transplantation. ISA continued toslide, and closed Friday at C$2.22, downC$0.86 (28%) on the week.

London & the Continent

Shire (LSE:SHP; SHPGY) was off 7.5pto 530.5p on the week after saying it willsell Shire Biologics, its Canada-based vac-cine business to ID Biomedical (TSE:IDB;IDBE) for $120 million in cash and shares(see Strategy, A7).

The move is SHP’s penultimate stepbefore completing its new business modelof in-licensing late-stage products andacquiring companies, while dropping earlystage R&D (see BioCentury, Aug. 4, 2003).The final step will be to open an office inthe U.S. for its R&D and commercial teams.The office is expected to be based near

Philadelphia and is slated to open mid-year.On NASDAQ, SHPGY was down

$0.61 to $28.62 and IDBE was up $0.35

to $10.90 on the week. On TSE, Iwas up C$0.70 to $14.85 on the we

Neurological company CeN(LSE:CEN) was up 0.8p to 11.9p on tweek after Nomura analyst Sam Fazbegan coverage with a “buy” recommdation and a fair value of 22p (see B1The company, which had £7.8 mill($14 million) in cash at Dec. 31, enoufor about two years, is expecting Phaseresults mid-year for its lead program, Mmorphine-6-glucuronide.

CEN will be meeting with City invtors over the next two weeks to retellstory, now that it has completed the quisition and integration of CNS compaTheraSci (see BioCentury, Dec. 8, 200CEN has a market cap of £30 million ($million).

Elan (ELN) was up $1.53 to $23.53the week after licensing its NanoCrys

technology to Roche (SWX:ROCZ) use with an undisclosed compound (B3). The technology is used to improthe bioavailability of therapeutics.

Company Index,

from page A12

H. Lundbeck (CSE:LUN) B4

Hudson Health Sci. A11

Icon B11

ID Biomedical (TSE:IDB; IDBE) A7,

A19, B4

Idenix A9I lex (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

Inpharmat ica B4

Inspire (ISPH) A18, B10

Integrated Biopharma (INB) B12

Introgen (INGN) B10

Inverness Medical (IMA) B2

Invitrogen (IVGN) B13Isotechnika (TSE:ISA) A19, B4, B13

J&J ( JNJ) B6

Kissei B4

Laboratorios del Dr. Esteve B5

Lexicon (LEXG) B13

LG Li fe 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

Memory (MEMY) B12

Merck (MRK) B3

Metabasis B4

Metaphore B7

Metrika B6

Micromet B2

Millennium (MLNM) A16

MIV Therap (MIVT) B13

MJ Research B6MP 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 B5Onyx (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 B8Schering (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

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 B3Valeant (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

ZymoGenet ics (ZGEN) A

B9, B11

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.

8/13/2019 042604 Bc



Source: Thomson Financial

Weekly change in combined market capitalization. 12-week period.

Tier I = market caps>$1B; Tier II <$1B. Base =100 on Dec. 31, 1998.

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.

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 May10, 1996). Bars show cumulative volume in millions (right scale).

BioCentury London Index

Weekly change in the combined market capitalization for 14 biosciencestocks listed on the LSE or AIM, 12-week period. Index base =1000 on

May 10, 1996.

Tier I (20 companies)

Apr 23Tier II (180 companies)

BC100 BC100 BC100

Week Price Stocks Gaining Stocks Declini

ended level gaining vol. (00) declining vol. (0

Mar 26 1504.63 31 1183073 69 40787

Apr 02 1605.67 94 5320967 6 2599

Apr 08 1600.97 34 1235946 65 23301

Apr 16 1587.16 30 1544595 68 23683

Apr 23 1649.29 75 3688326 25 17210

TFCG Life Sciences Indexes

Price Gains

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(0

Zonagen ZONA 3.860 1.030 36% 69

ImmunoGen IMGN 9.980 2.040 26% 229

Genta GNTA 13.940 2.600 23% 1944

Avant AVAN 2.770 0.490 21% 636Quidel QDEL 8.500 1.420 20% 334

Illumina ILMN 8.040 1.320 20% 189

ImClone IMCL 70.300 11.030 19% 2532

DUSA DUSA 12.870 2.010 19% 234

Cytogen CYTO 14.550 2.200 18% 146

Iomed IOX 3.000 0.450 18% 20

GTx GTXI 12.980 1.760 16% 53

Hollis-Eden HEPH 8.950 1.210 16% 213

Price Declines

Stocks with greatest % price decline (criteria as above).

Company Ticker $Close $Chg %Chg Vol(0

Sonus SNUS 5.520 -1.410 -20% 78Lynx LYNX 4.210 -0.850 -17% 34

Medivir MVIR SEK101 -SEK16.5 -14% 14

november NBX 5.270 -0.780 -13% 14

Vernalis1 VNLS 2.550 -0.350 -12% 425

Aerogen AEGN 3.281 -0.409 -11% 14

Affymetrix AFFX 31.390 -3.620 -10% 1779

Cholestech CTEC 8.610 -0.940 -10% 97

Dynavax DVAX 6.450 -0.700 -10% 14

Corcept CORT 10.900 -1.100 -9% 58

Labopharm DDS C5.550 -C0.500 -8% 30

Antigenics AGEN 9.990 -0.870 -8% 313

Memory MEMY 8.980 -0.730 -8% 7

Volume Gains

Greatest changes in volume above 25,000 shares.

Company Ticker Vol(00) %Chg $Close $C

NeuTec NTP 4185 3615% 295p 1

Pharmexa PHARMX 4554 1005% DKK30 -DKK

Aeterna2 AELA 35631 937% 7.350 0.8

Zonagen ZONA 6913 852% 3.860 1.0

GPC GPC 11284 561% 12.00 -0.3

november NBX 1463 490% 5.270 -0.7

Cerus CERS 30455 465% 3.960 0.3

BioVeris BIOV 23883 435% 12.310 0.5

Nymox NYMX 11567 427% 3.950 -0.3

Affymetrix AFFX 177914 396% 31.390 -3.6

Pharmion PHRM 11416 395% 24.010 -0.

BioCentury 100 Advance-Decline Trend

Apr 23

1200

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1 Includes volume from London Stock Exchange with converted AD

(ADS = 40 shares)

2 Includes volume from Toronto Stock Exchange

8/13/2019 042604 Bc


BIOQUITY EUROPE2004

Contributing Sponsors

Techno Venture Management

Deutsche Bank

DVC Deutsche Venture Capital

SOFINNOVA Partners

Bank Vontobel

3i

Fortis Bank

SWX Swiss Exchange

CMS

Deutsche Boerse

Organized by

BioCentury

E.B.D. Group

BIO

Acknowledging the Support of

Gold Equity Sponsor

and Regional Host Members

Ernst & Young

Wood Mackenzie

Scottish Equity Partners

Scottish WidowsInvestment Partnership

BIA

ITI Life Sciences

Silver Equity Sponsors

Palmer & Dodge LLP

Mayer, Brown, Rowe & Maw

Cooley Godward LLP

INTRODUCING

THE BIOEQUITY EUROPE PRESENTING COMPANIES

Celebrating its 5th anniversary, BioEquity Europe has established itself as themagnet for financial dealmakers and the premier venue for life science companiespositioning themselves to attract capital from international investors.

The 2004 meeting focuses on Europe’s growing inventory of companies facingmid- and later-stage clinical milestones, especially in the areas of cancer, neurol-

ogy, cardiology and metabolic diseases, as well as a special track of companiesbuilding next-generation protein therapeutics.

BioEquity Europe also provides a venue explicitly designed to maximize financialnetworking, with the 2004 program offering small discussion sessions with a facul

of seasoned life science investors from Europe and North America.

Regional Host

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 GmbHBasilea Pharmaceutica Ltd. (SWX:BSLN)

BioMarin Pharmaceutical Inc.(BMRN; SWX:BMRN)

Biolipox ABBioVex Ltd.

BioXell SpACareX S.A.

Cellectis S.A.

CeNeS Pharmaceuticals plc (LSE:CEN)

Coley Pharmaceutical Group

CombinatoRx Inc.Cyclacel Ltd.

deCODE genetics Inc. (DCGN)

DeveloGen AGDomantis 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 AGigeneon AG

Intercell AGJerini AG

Laxdale Ltd.Lorantis Ltd.

MediGene AG (FSE:MDG)

Micromet AGMyogen Inc. (MYOG)

NeuroSearch A/S (CSE:NEUS)

Neuro3d S.A.

Newron Pharmaceuticals SpAOctoPlus B.V.

Onyvax Ltd.Orexo AB

Oxxon Pharmaccines Ltd.

PAION GmbHPheneX Pharmaceuticals AG

PIERIS Proteolab AGProbiodrug AG

Serono S.A. (SWX:SEO; SRA)

SiRENADE Pharmaceuticals AGSosei Co. Ltd.

Speedel GroupSWITCH Biotech AG

TeGenero AGTrigen Ltd.

U3 Pharma AGVaxGen Inc. (VXGN)

Vernalis plc (LSE:VER; VNLS)

Wilex AG

Y’s Therapeutics Co. Ltd.

May 17-18, 2004Sheraton Grand Hote

Edinburgh, U.K.

Pharma Sponsor

Astra Zeneca

INVESTMENT PROFESSIONALS

Register Now & Reserve Your Seat

Register Online atwww.biocentury.com

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BioCentury Part IIVOL. 12, NO. 19 THE COMPLETE R EPORT OF BIOBUSINESS NEWS APRIL 26, 2004 PAGE B1 OF

BioBusiness for the week ended April 23

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Using BioCentury Part IIBioCentury Part II is a comprehensive

compendium of business news for man-

agement and investors in bioscience com-panies. It is organized into three depart-

ments: Company News, Clinical News andFinancial News.

The index on this page lists all the

companies covered this week. The newsitems in each department are organizedalphabetically by company. When morethan one company is listed, the biotechcompany is shown first. Each brief is la-

beled with one or more applicable busi-ness categories from the following list:

ADMET; Agbio/Environmental; Anti-bodies; Autoimmune; Bioinformatics;Biomanufacturing; Biopharmaceuticals;

Cancer; Cardiovascular; Chemistry; Com-binatorial biology; Computational chem-

istry/biology; Dental; Dermatology; Diag-nostic; Drug delivery; Endocrine; Finance;Functional genomics; Gastrointestinal;

Gene/Cell therapy; Generics; Genitouri-nary; Genomics; Hematology; Hepatic;High throughput screening; Infectious;Inflammation; Metabolic; Microarrays; Mi-

crofluidics; Musculoskeletal; Neurology;Nutraceuticals; Ophthalmic; Other; Phar-maceuticals; Pharmacogenetics; Proteom-

ics; Pulmonary; Renal; Supply/Service;Transplant; Veterinary

COMPANY NEWS

Deals (Page B2)

Adprotech/Inflazyme (TSE:IZP)Anadys (ANDS)/LG Life SciencesAntisoma (LSE:ASM)/Inverness Medical (IMA)

Astex/AstraZeneca (LSE:AZN; AZN)Avant (AVAN)/DynPortBioInvent (SSE:BINV)/Enzon (ENZN)/

MicrometBioMarin (BMRN; SWX:BMRN)/Medicis (MRX)

Bioseek/Cognia/Harvard U/State U of NewYork/Yale U

Boston (BBII)/SeraCare (SRLS)Bristol-Myers (BMY)/Dow (DOW)Bristol-Myers (BMY)/Pierre FabreCell Signaling Tech/ZeptosensCerus (CERS)/MedImmune (MEDI)CytRx (CYTR)/Vical (VICL)Discovery Partners (DPII)/Vertex (VRTX)Dragon (TSE:DDD; DRUG)/Suzhou Zhongkai

Echelon/M.D. Anderson Cancer CtrElan (ELN)/Roche (SWX:ROCZ)Enzo (ENZ)/U of Connecticut

Genelabs (GNLB)/MP BiomedicalsGeneProt/Lundbeck (CSE:LUN)

Gilead (GILD)/Southern Research Inst

GTx (GTXI)/Beckman Coulter (BEC)ID Biomedical (TSE:IDB; IDBE)/Shire (LSE:SHP;

SHPGY)Inpharmatica/BioticaIsotechnika (TSE:ISA)/Roche (SWX:ROCZ)Kissei/Watson (WPI)Martek (MATK)/DSMMetabasis/Valeant (VRX)Nanogen (NGEN)/Syn X (TSE:SYY)

Neose (NTEC)/BioGeneriXNPS (NPSP)/NycomedPharming (Euronext:PHARM)/Laboratorios

del Dr. EsteveProvalis (LSE:PRO; PVLS)/Edmond

Regulatory (Page B5)

Altana (FSE:ALT; AAA)

Antigenics (AGEN)Barbeau Pharma/ESP PharmaGenta (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:

QLT; QLTI)/Novartis (NVS; SWX:NOVN)Schering-Plough (SGP)

Sales & Marketing (Page B6)

Bristol-Myers (BMY)/Metrika

co.don (FSE:CNW)

Inhibox/Purely ProteinsRoche (SWX:ROCZ)

Other News (Page B6)

Applied Biosystems (ABI)/MJ Research/Roche(SWX:ROCZ)

co.don (FSE:CNW)Immuno-Designed MoleculesOSI (OSIP)

Management Tracks (Page B7)

Advanced Viral Res (ADVR)

Agencourt

Avecia

Benitec (ASX:BLT)BioreasonBoston Biomedica (BBII)Carolina Pharma

ConformaCorgentechEdwards Lifesciences (EW)

Genencor (GCOR)Genitope (GTOP)

MedImmune MEDI)MetaphoreNastech (NSTK)

Protherics (LSE:PTI)RegeneRx (RGRX)

ScancellScolr (SCLL)SemaforeStructural GenomiXTercica (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)

DynPortMyriad (MYGN)

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)Neurobiologica l Tech (NTII)Rigel (RIGL)Vivus (VVUS)Xenome

ZymoGenetics (ZGEN)

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BioCentury Part II APRIL 26, 2004 PAGE B3 OF

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Deals,from previous page

launch Orapred in markets outside the U.S. by early 2006. The productswill 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 salesforce to market its Aryplase enzyme replacement therapy to treat MPS-VI, 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 morespecific 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 toBioseek 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 BBII’s BBI Diagnostics andBBI Biotech Research Laboratories divisions for $30 million in cash.SRLS, which provides biological material manufacturing services, ex-pects the deal to be accretive to EPS. BBII expects the deal to close byAug. 15, and said the sale will let it focus on its Pressure CyclingTechnology (PCT).

Bristol-Myers Squibb Co. (BMY), Princeton, N.J.Dow Chemical Co. (DOW), Midland, Mich.

Business: Supply/ServiceDOW’s 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 formilestones and royalties.

Bristol-Myers Squibb Co. (BMY), Princeton, N.J.Pierre Fabre Medicament, Castres Cedex, FranceBusiness: Cancer

BMY received rights from Pierre Fabre to develop and market Javlorvinflunine, a vinca alkaloid chemotherapeutic, in the U.S., Canada, Japan,Korea and selected Southeast Asian countries. Pierre Fabre will retaindevelopment and marketing rights in all other countries. Javlor is inEuropean Phase III trials to treat bladder cancer and non-small cell lungcancer (NSCLC) and Phase II trials to treat breast and ovarian cancer.

BMY said it will discuss with FDA whether additional clinical trials inthe U.S. will be necessary to submit an NDA.

Cell Signaling Technology Inc., Beverly, Mass.Zeptosens AG, Witterswil, Switzerland

Business: Antibodies, Supply/ServiceThe companies partnered to combine Cell Signaling’s reagents,

including phospho-specific antibodies, with Zeptosens’ ZeptoMark

protein microarray technology. The combined product will be used forprotein 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

to treat cancers of the breast, prostate and colon, and metastamelanoma. CERS’s Listeria vaccine technology will be used to devea vaccine against MEDI’s EphA2 protein. The companies said an a

EphA2 vaccine showed antitumor responses in mice. Under the dMEDI is responsible for clinical development, manufacturing and co

mercialization. CERS will participate in development and will recean upfront payment and development funding, and is eligible for mstones 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 start of a Phase I trial of VICL’s plasmid DNA vaccine for cytomegalorus (CMV), which uses CYTR’s TranzFect technology. Under a 20

deal, VICL has exclusive rights to CYTR’s TranzFect poloxamer tenology to enhance viral or non-viral delivery of polynucleotides, excfor prostate-specific membrane antigen and four infectious dise

targets that CYTR previously licensed to Merck & Co. Inc. (MRWhitehouse 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 chemiscapabilities to support VRTX’s drug discovery efforts for an unclosed research program.

Dragon Pharmaceuticals Inc. (TSE:DDD; DRUG), Vancouver, BSuzhou Zhongkai Bio-Pharmaceuticals Co. Ltd., Suzhou, ChiBusiness: Cancer

DDD received exclusive worldwide rights, excluding China,Zhongkai’s recombinant human granulocyte colony stimulating fac

(G-CSF). Zhongkai’s product is approved in China to increase whblood cell counts in cancer patients receiving chemotherapy. DDDmerging with Oriental Wave Holding Ltd. (British Virgin Islands), a

the combined company plans to offer generics chemical intermedia(see BioCentury, March 29).

Echelon Biosciences Inc., Salt Lake City, UtahM.D. Anderson Cancer Center , Austin, TexasBusiness: Cancer

Echelon and the center will collaborate to develop therapeuagainst new cancer targets beginning with PI3 kinase. The center wreceive warrants to buy Echelon stock, and Echelon will receiveoption to market compounds developed under the deal.

Elan Corp. plc (ELN), Dublin, IrelandRoche (SWX:ROCZ), Basel, SwitzerlandBusiness: Drug delivery

ROCZ licensed ELN’s NanoCrystal technology for use with

undisclosed compound in development. In exchange for providformulation services and access to the technology, ELN will rece

research revenues and is eligible for milestones and royaltNanoCrystal technology is used to improve the bioavailabilitytherapeutics.

Enzo Biochem Inc. (ENZ), Farmingdale, N.Y.University of Connecticut Health Center , Farmington, ConnBusiness: Musculoskeletal

Under two deals with the university, ENZ subsidiary Enzo Thepeutics Inc. will license and co-develop therapeutics to stimulate

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Deals,from previous page

the original deal, VRX is responsible for clinical development of thecompound, an oral prodrug of the antiviral adefovir.

Nanogen Inc. (NGEN), San Diego, Calif.Syn X Pharma Inc. (TSE:SYY), Toronto, Ontario

Business: Diagnostic, CardiovascularNGEN completed its previously announced acquisition of point-of-

care diagnostic company SYY for 1.6 million shares, which values thedeal at $12.3 million using NGEN’s close of $7.68 on April 20, the daybefore the deal closed. NGEN announced the acquisition in February(see BioCentury, Feb. 16).

Neose Technologies Inc. (NTEC), Horsham, Penn.BioGeneriX AG, Mannheim, GermanyBusiness: Biomanufacturing, Hematology

The companies partnered to use NTEC’s GlycoPEGylation technol-ogy to develop a long-acting version of granulocyte colony stimulating

factor (G-CSF) to promote white blood cell production. The companieswill share preclinical development expenses, and BioGeneriX is re-

sponsible for clinical expenses. NTEC will receive an upfront fee andwill have commercialization rights in the U.S., Canada, Mexico and Japan.BioGeneriX will have rights in Europe and the rest of the world. Thecompanies will receive royalties on each other’s sales.

NPS Pharmaceuticals Inc. (NPSP), Salt Lake City, UtahNycomed Group A/S, Roskilde, Denmark Business: Musculoskeletal

NPSP granted development and marketing rights to Nycomed forosteoporosis candidate Preos in Europe, the Commonwealth of Inde-pendent States and Turkey. In exchange, Nycomed will purchase $40

million of NPSP stock and assume responsibility for conducting PhaseIIIb and IV trials in Europe, representing at least a $25 million invest-ment. NPSP also is eligible for up to $25 million in milestones plus

royalties. NPSP plans to submit an NDA by year end for Preos, aninjectable full-length recombinant human parathyroid hormone.

Pharming Group N.V. (Euronext:PHARM), Leiden the NetheralndsLaboratorios del Dr. Esteve S.A., Barcelona, SpainBusiness: Cardiovascular

The companies signed a letter of intent under which PHARM willlicense its recombinant human C1 inhibitor (rhC1INH) to Laboratoriosdel Dr. Esteve. The companies hope to close the deal by June 30. Theywill partner to develop, market and sell rhC1INH in Spain, Portugal andGreece to treat hereditary angioedema (HAE). rhC1INH has completedPhase 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 d’Adda, ItalyBusiness: Diagnostic

PRO will distribute Erdotin erdosteine from Edmond Pharma in theU.K. and Ireland for at least 10 years. PRO will be the exclusive distributorfor the first 5 years and has the option to acquire Erdotin — a mucolytic

agent to treat chronic bronchitis or chronic obstructive pulmonarydisease (COPD) — for a predetermined amount after three years. PROwill pay 200,000 ($239,800) in installments towards development andregulatory costs. Erdotin is undergoing European registration.

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REGULATORY

Altana AG (FSE:ALT; AAA), Bad Homburg, GermanyProduct: Alvesco ciclesonide

Business: InflammationThe U.K. granted marketing approval for Alvesco inhaled cortic

teroid to treat persistent asthma in adults. ALT said the U.K. will se

as the Reference Member State under the European Mutual RecognitProcedure. ALT did not disclose when it plans to launch Alvesco said it hopes to coordinate launch timing in several European countrAlvesco was approved in Australia in February. The product is partnewith Aventis SA (AVE, Strasbourg, France) in the U.S., where 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 additioproduct characterization data requested by FDA for the compan

Oncophage cancer vaccine to treat renal cell carcinoma (RCC). Flifted a partial clinical hold on the compound last November.

Barbeau Pharma Inc., Northfield, Ill.ESP Pharma Inc., Edison, N.J.Product: HydralazineBusiness: Cardiovascular

FDA granted Orphan Drug designation for the companies’ Hydlazine peripheral vasodilator to treat severe intrapartum hypertensassociated with severe pre-eclampsia and eclampsia of pregnancy.

Genta Inc. (GNTA), Berkeley Heights, N.J.Aventis SA (AVE), Strasbourg, France

Product: Genasense oblimersenBusiness: Cancer

The partners began an expanded access program to make GNT

Genasense available to chemotherapy-naive patients with advanmelanoma. The antisense agent targeting Bcl-2 is under FDA review

combination with dacarbazine for the indication, and has a PDUFA dof June 8. FDA’s Oncologic Drugs Advisory Committee will review 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 Hylafoa hyaluronic acid-based dermal filler for injection into mid- to deep der

to correct moderate to severe facial wrinkles and folds. The partners sno pre-treatment skin test is required and that they will start shippingproduct immediately. GENZ developed and manufactures Hylafo

IMDC holds worldwide marketing and distribution rights.

GlaxoSmithKline plc (LSE:GSK; GSK), London, U.K.Product: Advair Diskus 100/50 fluticasone propionate 250 µg asalmeterol 50 µg inhalation powder

Business: PulmonaryFDA granted marketing approval for Advair Diskus to treat child

ages 4-11 with asthma who are symptomatic on inhaled corticostermonotherapy.

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Regulatory,from previous page

ImClone Systems Inc. (IMCL), New York, N.Y.Product: Manufacturing plant

Business: CancerFDA accepted for review a CMC supplemental BLA for IMCL’s 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-MyersSquibb Co. (BMY, Princeton, N.J.) will be able to meet “full commercialdemand” 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 thatsupplies of the drug manufactured at Lonza’s facility would be used tomeet initial demand. BB36 has FDA approval to manufacture Erbitux for

investigational use, and Swiss approval to manufacture commercialproduct. Boehringer Ingelheim (Ingelheim, Germany) also manufac-tures the drug in Europe.

In February, Erbitux was approved in combination with irinotecanto treat metastatic colorectal cancer. The antibody against epidermal

growth factor (EGF) receptor also was approved as monotherapy inpatients 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: AutoimmuneFDA accepted for filing Centocor’s sBLA for Remicade to treat

ankylosing spondylitis. The combination of Remicade and methotrexateis approved to reduce the signs and symptoms, inhibit the progressionof structural damage and improve physical function in patients withmoderately to severely active RA who have had an inadequate response

to methotrexate alone. The anti-TNF alpha antibody also is approvedin the U.S. to treat Crohn’s disease and in Europe to treat Crohn’sdisease 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 injectionBusiness: Neurology

FDA granted marketing approval to MYL’s Bertek PharmaceuticalsInc. subsidiary (Research Triangle Park, N.C.) for its Apokyn to treat“off” episodes associated with Parkinson’s disease (PD). MYL expectsto launch the product by July and said it must perform post-marketingstudies. 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. FDArequested additional clinical data after completing its review of NEOP’s

BLA, which was submitted in January 1997.

OxiGene Inc. (OXGN; SSE:OXGN), Watertown, Mass.

Product: Combrestatin A4 Prodrug (CA4P) Phosphatase activatedtumor vascular targeting agentBusiness: Cancer

EMEA granted Orphan Medicinal Product designation to CA4P totreat anaplastic thyroid cancer (ATC). The compound is in Phase IItesting in the U.S. for the indication.

QLT Inc. (TSE:QLT; QLTI), Vancouver, B.C.Novartis AG (NVS; SWX:NOVN), Basel, SwitzerlandProduct: Visudyne verteporfin

Business: OphthalmicThe partners’ Visudyne received reimbursement in Japan to tr

wet age-related macular degeneration (AMD). Visudnye was approin Japan in October 2003.

Schering-Plough Corp. (SGP), Kenilworth, N.J.Product: Peg-Intron peginterferon alfa-2bBusiness: Infectious

SGP subsidiary Schering-Plough K.K. submitted an NDA in Japrequesting approval of Peg-Intron in combination with its Reberibavirin 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 MetriA1cNow diabetes monitor, an OTC product to measure blood su

control.

co.don AG (FSE:CNW), Berlin, GermanyBusiness: Dermatology

CNW launched its chondrotransplant Disc, an autologous disc 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,

nases and proteases. The discovery services combine computatiotechnologies from Inhibox and laboratory-based screening technogies from Purely Proteins.

Roche Ltd. (SWX:ROCZ), Basel, Switzerland

Business: DiagnosticROCZ’s subsidiary Roche Diagnostics Corp. (Indianapolis, In

launched in Europe its Amplicor human papillomavirus (HPV) PCbased test kit. The test detects all 13 DNA genotypes of the HPV. Tkit has CE mark approval.

OTHER NEWS

Applied Biosystems Group (ABI), Foster City, Calif.MJ Research Inc., Waltham, Mass.Roche (SWX:ROCZ), Basel, SwitzerlandBusiness: Supply/Service

ABI said that a jury in the U.S. District Court for the Distric

Connecticut, decided in favor of ABI and ROCZ’s Roche MolecuDiagnostics unit in a patent infringement suit against MJ Resea

concerning patents covering PCR and thermal cycler technologThe jury found that MJ Research infringed the following Upatents: 4,683,195; 4,683,202; 4,965,188; 5,656,493; 5,333,6

and 5,475,610. ABI and ROCZ were awarded $19.8 milliondamages. ABI said the companies will pursue enhancement of damages, because the jury found infringement of four of the pateto be willful.

The court’s decision concludes the first phase of a two-phase trThe second phase, which will review MJ Research’s counterclaim t

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Other News,from previous page

ABI violated antitrust laws, will begin in July. ABI said MJ Research filedfor bankruptcy protection in March.

co.don AG (FSE:CNW), Berlin, GermanyBusiness: Dermatology

The company restructured and reduced its head count by 23% to 24from 32. The cuts will reduce its annual burn rate by 33% to less than2 million ($2.4 million). The restructuring follows slower thanexpected market development for CNW’s tissue engineered products.CNW had 2.8 million ($3.4 million) in cash at Dec. 31, 2003. Thecompany said it has enough cash to last until 2005.

Immuno-Designed Molecules SA, Paris, FranceBusiness: Cancer

IDM opened in Irvine, Calif., a cGMP manufacturing center dedicated

to the production of its Cell Drugs for clinical trials. IDM said produc-tion of Collidem, a therapeutic vaccine containing autologous dendritic

cells loaded with peptides, began in January. Collidem is in Phase I/IItrials 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 subsid-iary, Prosidion Ltd. (Oxford, U.K.). The first installment of $10 millionhas been invested, which brings to 81% OSIP’s stake in the company.OSIP formed Prosidion last year in order to focus on oncology. Thesubsidiary is developing small molecules targeting glucokinase activa-tion and glycogen phosphorylase inhibition, and expects to beginclinical trials in 2005.

MANAGEMENT TRACKS

Boards of DirectorsCorgentech Inc., South San Francisco, Calif.Business: Cardiovascular

Appointed: Richard Brewer, founding partner of Crest Asset Manage-ment

Nastech Pharmaceutical Co. Inc. (NSTK), Bothell, Wash.Business: Drug deliveryAppointed: Myron Holubiak, former president of Roche LaboratoriesInc.; Leslie Michelson, vice chairman and CEO of the Prostate CancerFoundation; and Gerald Stanewick, former institutional bond salesmanat 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 forpublic affairs at FDA; and Michael Sorell, managing member of MS Capital

Management

Advanced Viral Research Corp. (ADVR), Yonkers, N.Y.

Business: InfectiousDeparted: Alan Gallantar as CFO and treasurer; Martin Bookman,assistant controller, becomes acting CFO

Agencourt Bioscience Corp., Beverly, Mass.Business: GenomicsHired: John Linnan as VP of sales, formerly district sales manager

New England at Applied Biosystems Group

Avecia Ltd., Manchester, U.K.Business: Supply/ServiceHired: Daniel Moore as VP of manufacturing and Avecia’s Ave

Biotechnology Inc. subsidiary

Bioreason Inc., Santa Fe, N.M.Business: BioinformaticsHired: Andrew DePristo as president and CEO, formerly sendirector of research and preclinical development information systeat 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 prdent of Strategic Pharmaceutical Solutions Inc.

Conforma Therapeutics Corp., San Diego, Calif.Business: CancerHired: Christopher LeMasters as VP of corporate development, fmerly a corporate business development executive at Eli Lilly and

Edwards Lifesciences Corp. (EW), Irvine, Calif.Business: CardiovascularHired: John Alexander Martin as president of the North Amer

region, formerly SVP-international at Cordis Corp., a subsidiary Johnson & Johnson

Genencor International Inc. (GCOR), Palo Alto, Calif.Business: Infectious

Hired: Philip Haworth as VP of business development for health caformerly VP of business development at Galileo Pharmaceuticals I

Genitope Corp. (GTOP), Redwood City, Calif.Business: CancerHired: John Vuko as VP of finance and CFO, formerly EVP and CFOIncyte Corp.

MedImmune Inc. (MEDI), Gaithersburg, Md.Business: Infectious

Promoted: Lota Zoth to SVP and CFO from VP and controller; JoBrandt to VP of corporate quality control from senior director; MichCowan to VP of corporate quality assurance from senior direct

Christine Dingivan to VP of clinical development and head of strateoperations from director of medical sciences; Lori Weiman to VP

corporate communications from senior director; and Peter YoungVP of information technology from senior director

Metaphore Pharmaceuticals Inc., Fort Lee, N.J.Business: Neurology, Autoimmune, InflammationHired: Per Lindell as VP of corporate development, formerly VPbusiness development at Avalon Pharmaceuticals Inc.

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Take advantage of BioCentury Extra.

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CLINICAL NEWS

Clinical activities and selected announcements for the week ended April 23.

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CLINICAL RESULTS

Alexion Pharmaceuticals Inc. (ALXN), Cheshire, Conn.

Product: Eculizumab (5G1.1)Business: HematologyMolecular target: Complement 5 (C5)Description: Humanized monoclonal antibody targeting C5Indication: Treat Paroxysmal nocturnal hemoglobinuria (PNH)Endpoint: Need for blood transfusionStatus: Phase Ib dataMilestone: NA

Cumulative 12-month results from a previously reported open-

label, U.K. Phase Ib trial in 11 patients showed eculizumab therapyresulted in 76% fewer packed red blood cell transfusions compared tothe 12 month clinical history (p=0.001). The number of paroxysm

events was reduced 94% from 3.2 days of paroxysms/patient /month to0.2 days (p<0.001). Patients showed significant improvements in sev-

eral quality of life parameters. Data were presented at the BritishSociety of Hemotology meeting in Cardiff.

Bioenvision Inc. (BIV), New York, N.Y.Product: ClofarabineBusiness: CancerMolecular target: DNA polymerase; ribonucleotide reductaseDescription: Second-generation nucleoside analogIndication: Treat older patients with acute myelogenous leukemia(AML) for whom chemotherapy is not suitable

Endpoint: Response rateStatus: Phase II dataMilestone: NA

Interim data from a Phase II trial of clofarabine as a first-line thershowed 9 of 14 (64%) evaluable patients have had a complete respon

To date, the study has enrolled 18 of an expected 25 patients. Reswere presented at the Bristish Society of Hematology meetingCardiff.

CV Therapeutics Inc. (CVTX), Palo Alto, Calif.Product: RanexaBusiness: CardiovascularMolecular target: Enoyl-CoA-hydrataseDescription: Partial inhibitor of enoyl-CoA-hydrataseIndication: Treat chronic stable angina

Endpoint: Exercise durationStatus: Phase III dataMilestone: NA

Previously reported result from the Phase III MARISA trial in angina patients showed Ranexa increased symptom-limited exerc

duration (p<0.005). Ranexa also increased the secondary endpointime to onset of angina pain during exercise testing and time

electrocardiographic evidence of ischemia (p<0.005). Mean QTc diffences for Ranexa vs. placebo were <1.0 msec at 500 mg & 1000 mg doData were published in the Journal of the American College of Cardiolo

InKine Pharmaceutical Co. Inc. (INKP), Blue Bell, Penn.Product: Visicol (INKP-100)Business: GastrointestinalMolecular target: NADescription: Sodium phosphate gastrointestinal cleansing/purging agIndication: Treat chronic functional constipation or constipatipredominant irritable bowel syndrome (IBS)

Endpoint: Safety; laxative effects

Management,from previous page

Scientific Advisory Boards

Benitec Ltd. (ASX:BLT), Queensland, AustraliaBusiness: Functional genomicsAppointed: Cy Stein, professor of medicine, urology and molecu

pharmacology at the Albert Einstein College of Medicine; and DaEngelke, professor of biological chemistry at The University of Michi

RegeneRx Biopharmaceuticals Inc. (RGRX), Bethesda, Md.Business: Dermatology

Appointed: Jo-David Fine, professor of dermatology at the Univerof Kentucky School of Medicine; and Claudio De Simone, associprofessor of experimental medicine at the University of L’Aquila

Semafore Pharmaceuticals Inc., Indianapolis, Ind.Business: CancerAppointed: Donald Durden, professor of pediatric oncology and hetology at Emory University School of Medicine

Tissera Inc. (TSSR), Tel Aviv, Israel

Business: TransplantAppointed: Giuseppe Remuzzi, director of the Mario Negri InstitutePharmacological Research; Sir Roy Caln, professor of surgery at

National University of Singapore

Protherics plc (LSE:PTI), Macclesfield, U.K.Business: Inflammation, CancerHired: Sally Waterman as director of R&D, formerly director of

development operations at Xenova Group plc

Scancell Ltd., Nottingham, U.K.Business: CancerHired: Michael Capaldi as CEO, formerly CEO of Synaptica Ltd.

Structural GenomiX Inc., San Diego, Calif.

Business: ChemistryHired: Neill Giese as SVP of drug development, formerly seniordirector of cancer and cardiovascular biology at Millennium Pharmaceu-

ticals Inc.

Tercica Inc. (TRCA), South San Francisco, Calif.

Business: EndocrineHired: Thomas Silberg as COO, formerly EVP and COO of Ligand

Pharmaceuticals Inc.

Vical Inc. (VICL), San Diego, Calif.Business: CancerResigning: Martha Demski as VP, CFO, treasurer and secretary

Try the searchable BioCentury Archives.

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Clinical Results,from previous page

BioCentury Part IIBioCentury Part II is published by B IOCENTURY 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®; TheBioCentury 100™ ; and The Clear Route to ROI™ are trademarks of BIOCENTURY PUBLICATIONS INC.All contents ©Copyright 2004, BIOCENTURY PUBLICATIONS INC.ALL R IGHTS R ESERVED. No part of this publication may be photocopied or reproduced in any form, retransmitted, or stored in a retrievalsystem without prior written consent of the publisher.

Status: Phase IV dataMilestone: NA

In a dose-ranging, U.S. Phase IV trial in 40 evaluable patients,88% responded to Visicol treatment during the first week. Pati entsreceived 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 and92% of those in the 8 tablet group responded. Both groups showedsignificant improvements in constipation-associated symptoms suchas straining, cramping, bloating, and stool consistency when com-pared to baseline. In the 8 tablet group, 4 patients withdrew fromthe study due to non-serious adverse events. No patients in the 4

tablet group withdrew due to adverse events . INKP intends to usedoses of 2-4 tablets in the future.

Prana Biotechnology Ltd. (ASX:PBT; PRNAY), Melbourne, AustraliaProduct: PBT-1

Business: NeurologyMolecular target: Cu ion; Zn ion

Description: Small molecule that binds copper and zinc to preventaggregation of amyloid betaIndication: Treat Alzheimer’s disease (AD)Endpoint: ADAS-Cog; safety, serum amyloid levelsStatus: Phase II updated dataMilestone: NA

Results from a 48-week extension of a previously reported 36-week Phase II trial showed that PBT-1 slowed decline in cognitivefunction. The longer-term treatment was well tolerated. Data werepresented at the International Springfield/Montreal Symposium onAdvances in Alzheimer’s Disease.

Valeant Pharmaceuticals International (VRX), Costa Mesa, Calif.Product: Viramidine

Business: InfectiousMolecular target: NA

Description: Ribavirin prodrugIndication: Treat hepatitis C virus (HCV)Endpoint: HCV RNA levelsStatus: Phase II dataMilestone: NA

Interim results from an open-label, U.S. Phase II trial in 180treatment-naïve patients showed 83% of those given Viramidine pluspeginterferon alfa-2a had ≥2 log10 reduction or had non-detectableHCV RNA at 24 weeks, the same proportion as those receiving ribavirinand peginterferon alfa-2a. The Viramidine group had a significantly

lower incidence of anemia (2% versus 24%, p<0.001). All 3 tested doses

of Viramidine (400 mg, 600 mg and 800 mg, twice daily) were comparato ribavirin 1000 or 1200 mg/day. Data were presented at the EuropAssociation for the Study of the Liver conference in Berlin. T

compound is in Phase III testing in combination with pegylated intferon alpha 2b. Roche (SWX:ROCZ; Basel, Switzerland) mark

Pegasys peginterferon alfa-2a, while Schering-Plough (SGP, NBrunswick, N.J.) markets Peg-Intron peginterferon alfa-2b.

ZymoGenetics Inc. (ZGEN), Seattle, Wash.Product: rhThrombinBusiness: HematologyMolecular target: NADescription: Recombinant human thrombinIndication: Control blood loss during surgeryEndpoint: Safety

Status: Phase I dataMilestone: Phase I data 2H04

In an ongoing, open-label, U.S. Phase I study in 9 lumbar sp

surgery patients, ZGEN said instances of hemostatic response wrhThrombin were observed. The trial has completed enrollment.

PRECLINICAL RESULTS

DynPort Vaccine Co. LLC, Frederick, Md.Product: rF1VIndication: Prevent Yersinia infection

DynPort said that in mice, rF1V protected against both bubonic apneumonic forms of plague.

Myriad Genetics Inc. (MYGN), Salt Lake City, UtahProduct: MPC-4505Indication: Treat chemotherapy-induced nausea and vomiting

MYGN said that in a monkey model, MPC-4505 achieved signific

blood levels and had peak blood levels about 4 hours after oral dos

CLINICAL STATUS

Advanced Biotherapy Inc. (ADVB), Woodland Hills, Calif.

Product: TNF alpha inhibitorBusiness: InfectiousMolecular target: NA

Description: Tumor necrosis factor (TNF) alpha inhibitorIndication: Treat HIV infectionEndpoint: Safety; viral load, increase in CD4 countStatus: Phase I startedMilestone: Phase I data 2004

ADVB started an open-label, U.S. Phase I trial in about 10 patiewho are in virologic failure.

Alkermes Inc. (ALKS), Cambridge, Mass.Product: Vivitrex

Business: NeurologyMolecular target: Opioid receptors

Description: Injectable sustained-release formulation of naltrexonpolylactide co-glycolide polymer microspheresIndication: Treat alcohol- and opiate-dependence

Endpoint: SafetyStatus: Phase III completed enrollmentMilestone: Complete Phase III 1H05; submit NDA 1H05

ALKS completed enrollment in an open-label, Phase III safety stcomparing once-monthly injections of Vivitrex (380 mg) to once-doral naltrexone (50 mg) in more than 400 alcohol- and opiate-dep

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Clinical Status,from previous page

dent patients. ALKS said an interim safety analysis will be complete inabout 6 months.

Alteon Inc. (ALT), Ramsey, N.J.Product: Alagebrium (ALT-711)

Business: CardiovascularMolecular target: Advanced glycosylation endproduct (AGE)Description: AGE crosslink breakerIndication: Treat diastolic dysfunction in patients with grade II-IV heartfailureEndpoint: Quantification of left ventricular mass and diastolic functionas measured by Doppler evaluation; quality of life as measured by

Minnesota Living with Heart Failure questionnaireStatus: Phase II startedMilestone: NA

ALT began a U.S., open-label Phase II trial in 20 patients. The trialwill 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-SBusiness: MusculoskeletalMolecular target: NADescription: Bioabsorbable, chemically modified hylauronic acidIndication: Prevent internal adhesions and scarring following spinalsurgeryEndpoint: NAStatus: Pilot trial startedMilestone: NA

ANIK began a U.K. pilot trial in about 45 patients.

Cell Therapeutics Inc. (CTIC; NMerc:CTIC), Seattle, Wash.Product: CT-2106

Business: CancerMolecular target: Topoisomerase I

Description: Camptothecin topoisomerase I inhibitor attached topolyglutamate polymerIndication: Treat colorectal cancerEndpoint: Maximum tolerated dose; safety, antitumor activityStatus: Phase I/II startedMilestone: NA

CTI started an international, open-label Phase I/II trial of CT-2106plus 5-fluorouracil/folinic acid in about 45 patients with metastaticcolorectal cancer who have failed front-line therapy with oxaliplatin.

CuraGen Corp. (CRGN), New Haven, Conn.Product: CG53135Business: Other

Molecular target: NADescription: Human fibroblast growth factor 20 (FGF-20)

Indication: Treat oral mucositis in patients undergoing bone marrowtransplantationEndpoint: Safety; response

Status: Phase I startedMilestone: Start Phase II 2004

CRGN started an open-label, U.S. Phase I study in 15 cancer patients.

Ilex Oncology Inc. (ILXO), San Antonio, TexasProduct: Campath alemtuzumabBusiness: Autoimmune

Molecular target: CD52Description: Humanized monoclonal antibody against CD52Indication: Treat previously untreated relapsing/remitting mult

sclerosis (MS)Endpoint: Time to sustained accumulative disability (SAD)

Status: Phase II completed enrollmentMilestone: NA

ILXO completed enrollment of 240 patients in an internatio

open-label Phase II trial comparing Campath to Rebif interferon be1a from from Serono SA (SWX:SEO; SRA, Geneva, Switzerland). ILis being acquired by Genzyme Corp. (GENZ, Cambridge, Mass.).

Inspire Pharmaceuticals Inc. (ISPH), Durham, N.C.Product: INS37217Business: Ophthalmic

Molecular target: P2Y(2) receptorDescription: Second-generation P2Y(2) agonistIndication: Treat rhegmatogenous retinal detachment

Endpoint: Surgery-free retinal attachmentStatus: Phase II started

Milestone: Phase II data 2005ISPH began a U.S., double-blind, placebo-controlled Phase II tria

INS37217 as first-line therapy in about 160 patients. The protoallows for up to 2 more injections of INS37217 in patients showing siof improvement after the first intravitreal injection.

Introgen Therapeutics Inc. (INGN), Austin, TexasProduct: Advexin (INGN 201)Business: CancerMolecular target: NADescription: Adenovirus p53 tumor suppressor gene therapy (Ad5CMp53)Indication: Treat stage III or IV squamous cell carcinoma of the oral ca

Endpoint: Progression-free survival; overall survival, overall resporateStatus: Phase II started

Milestone: NAThe Southwest Oncology Group began a U.S. Phase II trial of ING

Advexin to treat about 60 patients who will receive Advexin at the tof surgery. Patients will then receive chemotherapy and radiation

Neurobiological Technologies Inc. (NTII), Richmond, Calif.Product: XereceptBusiness: CancerMolecular target: Corticotropin-releasing factor (CRF1) receptcorticotropin-releasing factor (CRF2) receptorDescription: Synthetic human CRFIndication: Treat peritumoral cerebral edema associated with br

tumorsEndpoint: 50% reduction in steroid use at 3 weeksStatus: Phase III started

Milestone: NANTII began a U.S. and Canadian Phase III trial in about 200 patie

who are taking high doses of dexamethasone. NTII said it will stasecond Phase III trial this summer in 120 steroid-naïve patients who be given either Xerecept or dexamethasone. Both pivotal trials h

been given a Special Protocol Assessment by FDA.

Rigel Pharmaceuticals Inc. (RIGL), South San Francisco, Calif.Product: R112Business: InflammationMolecular target: Syk

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Clinical Status,from previous page

Description: Nasal spray Syk kinase inhibitor that inhibits mast cellactivation

Indication: Treat allergic rhinitisEndpoint: Change from baseline in global symptom score; time to onsetof effect, safety

Status: Phase II startedMilestone: Phase II data 2H04

RIGL began an outdoor, U.S. placebo-controlled Phase II trial in 300patients who have had seasonal allergic rhinitis during the spring pollenseason for at least 2 years.

Vivus Inc. (VVUS), Mountain View, Calif.

Product: Avanafil (TA-1790)Business: GenitourinaryMolecular target: Phosphodiesterase-5 (PDE-5)

Description: Fast-acting oral PDE-5 inhibitorIndication: Treat erectile dysfunction (ED)

Endpoint: Optimal dose rangeStatus: Phase II started

Milestone: Complete enrollment Phase II 2004; Phase II data 1H05VVUS began a U.S., at-home, double-blind, crossover Phase II trial

in about 250 patients.

Xenome Ltd., Brisbane, AustraliaProduct: Xen2174Business: NeurologyMolecular target: Norepinephrine transporterDescription: Synthetic peptide modeled on a peptide isolated from thevenom of the marine coneshellIndication: Treat severe cancer pain

Endpoint: SafetyStatus: IND filedMilestone: Start Phase I 06/04

Xenome filed an IND to begin a placebo-controlled Phase I trial in4 groups of 5 healthy volunteers.

ZymoGenetics Inc. (ZGEN), Seattle, Wash.Product: rhThrombinBusiness: HematologyMolecular target: NADescription: Recombinant human thrombinIndication: Control blood loss during surgeryEndpoint: Safety as measured by immunogenicity; time-to-hemostasis,rhThrombin antibodies at 28 days

Status: Phase II startedMilestone: Complete Phase II 2004

ZGEN started a double-blind, placebo-controlled, U.S. Phasstudy in 40 patients undergoing liver resection. ZGEN said it plansstart this quarter 3 other identical studies in patients undergolumbar spine surgery, lower extremity peripheral artery bypass sgery, and for the formation of vascular access grafts for dialysis. Tendpoints in all 4 studies includes safety , time-to-hemostasis, and a

day follow-up test for antibodies against rhThrombin. ZGEN expeto complete all 4 Phase II studies this year.

OTHER RESEARCH NEWS

Agrobiogen GmbH, Hilgertshausen, Germany, et al.

Product: r38M bispecific single-chain antibodyUse: Treat cancer

Researchers published in the Proceedings of the National AcademSciences the production of a bispecific single-chain antibody in the serof transgenic rabbits and cattle. The antibody, designated r28M, showantitumor activity in culture.

Icon Genetics AG, Munich, Germany

Product: Bacterial expression systemUse: Biomanufacturing

Researchers published in the Proceedings of the National AcademSciences the development of a system that uses bacteria to deliprotein expression vectors to plants.

Novartis AG (NVS; SWX:NOVN), Basel, Switzerland, et al.Product: CGP76030 Src kinase inhibitor

Use: Treat leukemiaResearchers published in Nature Genetics that CGP76030 increa

survival compared to control in a mouse model of B cell acute lympblastic leukemia (B-ALL), but did not significantly increase survival mouse model of chronic myelogenous leukemia (CML). In the mode

B-ALL, animals given CGP76030 plus imatinib survived longer tanimals receiving monotherapy with either agent. NOVN markGleevec imatinib to treat CML.

Yale University, New Haven, Conn., et al.Product: CurcuminUse: Treat cystic fibrosis (CF)

Researchers published in Science that in a mouse model of curcumin restored the nasal membrane potential. Also, the compoupromoted the accumulation of the mature CFTR protein in cel ls gro

in culture. Yale has licensed the technology to Seer PharmaceuticLLC (Southport, Conn.).

The search for intelligent life

We know you have many choices for headlines. But finding real intelligence is a lot harder. That’s 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.


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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 adjustedEPS 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 $2.2billion, up 35% from $1.6 billion in the first quarter of 2003. AMGNclosed 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, thecompany said that FDA is still seeking additional product characteriza-tion for its Oncophage cancer vaccine to treat renal cell carcinoma

(RCC). The agency had a partial hold on the compound, but lifted it lastNovember. AGEN closed Friday at $9.99.

CeNeS Pharmaceuticals plc (LSE:CEN), Cambridge, U.K.

Business: NeurologyNomura analyst Sam Fazeli began coverage with a “buy” rating. CEN

has two products in development: M6G morphine-6-glucuronide is inPhase III testing to treat post-operative pain, and CNS 5161, a glutamatereceptor NMDA ion channel blocker, is in Phase II studies to treatneuropathic pain. Fazeli expects positive news f low from these twocompounds to drive the stock in the next 6-12 months. CEN closedFriday at 11.9p.

Gilead Sciences Inc. (GILD), Foster City, Calif.Business: Infectious

Leerink Swann analyst William Tanner raised his 2004 and 2005revenue estimates to $1.27 billion and $1.68 billion from $1.24 billionand $1.66 billion, respectively. Last week, GILD reported first quarter

non-GAAP EPS of $0.45, beating the Street’s $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 GILD’s increased guid-

ance is conservative. He expects 2004 Viread sales of $809 millionversus the company’s 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 haveto increase R&D and SG&A expenses in order to improve its top linevia new drugs.

Deutsche Bank analyst Dennis Harp raised his 2004 and 2005 EPSestimates 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: CancerWR Hambrecht analyst Jason Kantor began coverage with a “buy”

rating and an $83 price target. He expects the company to turn

profitable next year on strong sales of colorectal cancer antiboErtibux cetuximab.

SG Cowen analyst Eric Schmidt began coverage and expects company to turn profitable this year. His 2004 and 2005 EPS estimaare $0.50 and $1.65. Schmidt said potential upside to sales estima

of Erbitux, plus a strong presence at ASCO, are likely to propel stock. IMCL closed Friday at $70.30.

Invitrogen Corp. (IVGN), Carlsbad, Calif.Business: Supply/Service

Pacific Growth analyst Adam Chazan raised his 2004 EPS revenue estimates to $2.88 and $1.03 billion from $2.84 and $1

billion. Last week, the reagent and tool supplier reported fquarter pro forma EPS of $0.63, which was $0.03 better than consensus estimate of $0.60. For the full year, IVGN raised its reve

and EPS guidance to $1.04 billion and $2.88. IVGN closed Friday$74.74.

Isotechnika Inc. (TSE:ISA), Edmonton, Alberta

Business: Transplant, AutoimmuneDundee Securities analyst David Martin lowered his price targe

C$2. On Tuesday, ISA and Roche (SWX:ROCZ, Basel, Switzerlarenegotiated a 2002 co-development deal for ISA247, restoring devopment rights to ISA and giving ROCZ an option to assume developmafter the start of Phase II transplantation trials. The trans isomversion of ISA247 is in Phase I dose-ranging trials for renal transpand psoriasis. ISA closed Friday at C$2.22.

Lexicon Genetics Inc. (LEXG), The Woodlands, TexasBusiness: Functional genomics, Genomics

WR Hambrecht analyst Jason Kantor began coverage with a “brating and a $10 price target. Kantor expects new partnerships tothe primary driver for the stock over the next 12 months. LEXG clo

Friday $7.06.

MedImmune Inc. (MEDI), Gaithersburg, Md.Business: Infectious, Cancer

Deutsche Bank analyst Dennis Harp raised his EPS estimates$0.52 from $0.50 in 2004 and to $0.53 from $0.52 in 2005 based on fquarter 2004 results and company guidance. On Wednesday, MEreported first quarter EPS of $0.44, beating Street expectations$0.02. The company reiterated 2004 EPS guidance of $0.50-$0.60. Mclosed Friday at $23.95.

Rigel Pharmaceuticals Inc. (RIGL), South San Francisco, Calif.

Business: AutoimmuneNeedham analyst Mark Monane began coverage with a “buy” rat

and a $33 price target. He said a value driver for the company wil

partnerships for its clinical compounds, including R112, an intranamast cell activation inhibitor that is in Phase II testing for aller

rhinitis. RIGL closed Friday at $21.50.

Other Financial News,from previous page

ties; and Fortis. MEMY has 20.2

million shares outstanding.

Business: Cardiovascular

Date announced: 4/21/04

MIVT raised an additional

overallotments from a March

vate placement, bringing to C

million the total raised in the

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