WEEK OF APRIL 12, 2010 BioCentury THE BERNSTEIN REPORT ON BIOBUSINESS Volume 18 • Number 17 • Page A1 of 19 Regulation Forest runs into tree By Steve Usdin BioCentury This Week Washington Editor The presentation Forest Laborato- ries Inc. made at last week’s Pulmonary- Cover Story was able to identify and in-license what the newco believes to be best-in-class topical Allergy Drugs Advisory Committee about Forest Runs into Tree — An FDA panel Rho kinase inhibitors for glaucoma from Daxas roflumilast to treat COPD would voted against Daxas for COPD because Asahi Kasei./A11 have been perfect — if it had been made Forest did not address the agency’s de facto a decade ago. For better or worse, FDA has moved on, so instead of the endorse- comparative effectiveness hurdles. Approval Emerging Company Profile for life-long use based on modest efficacy ment Forest hoped for, a regulatory strat- vs. was possible a decade ago, but Impossible to Ignore — Selecta is egy and procedural tactics out of synch the agency now wants clear benefit over building nanoparticle that can with the realities of 2010 produced a 10- standard of care. stimulate a strong response in lymph node 5 recommendation against approval. cells against antigens that the immune Forest’s experience hammers home Strategy system otherwise would ignore./A12 some of the changes a decade’s focus on drug safety have wrought. pRED: Making the Transition — Roche Ebb & Flow Simply showing an incremental, statis- has refined the structure of its early R&D tically significant improvement over pla- organization to put decisions into the Crunch Time — Tengion’s down round. De- cebo for a broad, undifferentiated popula- hands of scientists while defining success as risking: Horizon-Nitec. Dinove, Neovacs ready tion with multiple treatment options is no the number of projects that make the to IPO. DRI hits a triple. Orbimed in Israel. longer a safe regulatory strategy. handoff to later-stage development./A7 Revisiting Achaogen. Tongjitang tries again. Submitting an NDA for chronic use of gRED: Small Company Sensibilities — Also: Carlyle Group. Cell Therapeutics; Keryx; a compound with known adverse effects Former Cytokinetics Chairman and CEO Basilea, Crucell et al./A13 without a proposed risk evaluation and James Sabry says he will bring small biotech mitigation strategy (REMS) invites skepti- experience and expertise in as Online this week/A18 cism from advisory committee members. And the need to cram additional time- the new VP of Genentech partnering./A8 Stock charts & tables/A17 consuming safety reviews into drug Stahel Sees Scale in India — Indian Company index/A18 evalutions has squeezed flexibility out of company Connexios is patterning the process, making the agency reluctant itself after Western biotechs. A big research to consider changes to an indication sub- TM team focused on understanding of disease BioCentury 100 Indicators See next page biology has attracted former Shire CEO Week ended 4/9/10 Rolf Stahel as chairman./A10 PRICES VOLUME Mining its Rho-lodex — Based on its 2001.04 1302.3M shrs Global Health Forum founders’ relationships in Japan, Altheos up 0.8% up 76% Registration is open for the Partnering for Global Health Forum 2010 in Chicago. Please see announcement following A19.

This Week in SciBX BIO India The first BIO India International Partnering Managing Microglia in Alzheimer’s — New research indicates microglia play opposing roles Conference includes a special tour of the in AD, and provide a road map for how to clear ß-amyloid plaques without destroying healthy nation’s top biotech sites. Please see announce- . Please see Table of Contents on A9. ment following A19. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A2 OF 19 Regulation, varies based on disease severity and smok- efits are minimal, or if efficacy is restricted from previous page ing status. Smokers with severe COPD to a small portion of the total population have a life expectancy of 8.5 years, ac- (see “Modest Efficacy”). mitted six months after filing of an NDA. cording to a study by Robert Shavelle and Daxas was developed based on the As a result, the Daxas NDA, which has colleagues at the Life Expectancy theory that a selective phosphodiesterase- an undisclosed mid-May PDUFA date, is Project published in the International Jour- 4 (PDE-4) inhibitor would target systemic virtually certain to receive a complete nal of Chronic Obstructive Pulmonary Disease and pulmonary inflammation, and that it response letter. in April 2009. would be free of the off-target adverse The questions going forward are what Moreover, Forest is pursuing a com- effects associated with theophylline, a ge- needs to be done to salvage the NDA — pound that has demonstrated only modest neric non-selective PDE-3 and PDE-4 in- whether FDA will be satisfied with essen- efficacy and that has no discernable ben- hibitor approved for COPD. A range of tially repackaging the application with a efit for at least half the patients who take serious cardiac and other adverse effects revised indication and a REMS, or if it will it. This is bound to raise questions in an prevent widespread use of theophylline. require lengthy clinical trials — and era in which FDA is becoming increasingly However, and Forest have whether Forest will be willing to invest concerned about exposing massive num- not determined Daxas’s precise mecha- sufficient additional resources to meet the bers of patients to adverse effects if ben- See next page agency’s demands. The specialty pharma company, which Modest efficacy faces patent cliffs for its Namenda memantine for Alzheimer’s disease and Forest Laboratories Inc. (NYSE:FRX) submitted four one-year Phase III trials comparing Daxas to Lexapro escitalopram for depression and placebo. Co-primary endpoints were the number of moderate or severe exacerbations and forced anxiety, paid Nycomed $100 million last expiratory volume at one second (FEV1). Studies M2-111 and M2-112 evaluated a broad population summer for U.S. rights to Daxas (see of patients with severe COPD, while the subsequent M2-124 and M2-125 trials included only patients BioCentury, Nov. 23, 2009). with a defined history of exacerbations, signs of chronic bronchitis and a defined cough/sputum The asset was attractive because Daxas symptom score at randomization. Studies 124 and 125 allowed concomitant treatment with long is intended to address a serious and large- acting beta-2 agonists (about 50% of the patients in each study took LABAs) but prohibited the use scale unmet medical need. If approved, it of inhaled corticosteroids and long-acting muscarinic antagonists during the treatment period. would be the first new type of therapy in Conversely, studies 111 and 112 allowed inhaled corticosteroids and prohibited use of LABAs and 30 years, and perhaps the only disease- LAMAs altogether. modifying drug, for the estimated 7.6 million Americans who suffer from COPD Daxas produced a statistically significant reduction in the annual rate of moderate or severe associated with chronic bronchitis. exacerbations in the 124 and 125 trials. However, about half the patients had no exacerbations during That potential emerged unscathed the trials, meaning no treatment benefit could be measured based on the primary endpoints.There from the advisory committee meeting, as was an increase of 3-5% in FEV1 in the Daxas arms of the Phase III trials. FDA concluded the increase patients have few good treatment options. was statistically significant but not clinically meaningful. (A) Intent to treat (ITT) population. (B) The But a number of problems, including exacerbation endpoint for Study 112, but not 111, reached statistical significance when the sponsor some that could be expensive and time- performed an FDA-requested post hoc analysis using the same exacerbation definition and analysis consuming to overcome, also came to method used in Studies 124 and 125. Source: FDA briefing documents light. Annual rates of moderate or severe exacerbations (A) Trial Daxas 500 µg Placebo Rate ratio P-value Pooled rate ratio De facto realities M2-124 1.1 (n=765) 1.3 (n=758) 0.85 0.028 0.83 The Daxas clinical development pro- M2-125 1.2 (n=772) 1.5 (n=796) 0.82 0.004 gram, which started with an IND filing in M2-111 (B) 0.6 (n=567) 0.7 (n=606) 0.86 0.129 0.85 1999, left Forest ill-equipped to deal with FDA’s current de facto comparative effec- M2-112 (B) 0.5 (n=760) 0.5 (n=753) 0.85 0.085 tiveness and safety requirements. Frequency of exacerbations (%) (A) Although more than 15,000 COPD patients have received Daxas in four 52- week and two 24-week Phase III trials, it has never been compared to or combined with standard of care, which is use of a long-acting muscarinic agonist (LAMA) and an inhaled corticosteroid in combina- tion with a long-acting adrenergic recep- tor beta 2 (ADRB2) agonist (LABA). Forest is seeking a maintenance indica- tion, with the expectation that patients might take Daxas for the rest of their lives. But in over a decade of clinical develop- 'D[DV 3ODFHER 'D[DV 3ODFHER ment, no one has taken it for longer than 12 months.           Life expectancy for COPD patients BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A3 OF 19 Regulation, Late revision from previous page “It takes five years to get the At the start of the meeting, Badrul benefit of not having one Chowdhury, director of the Division of nism of action, so they can’t explain why Pulmonary, Allergy, and Rheumatology it causes its own adverse effects, particu- exacerbation.” larly weight loss and neuropsychiatric Products, reported that Forest had sub- mitted a revised indication to FDA in symptoms. Anthony Durmowicz, FDA February. At last week’s meeting, panel member Thomas Alexander Platts-Mills challenged Forest wanted to change the indication from “for the maintenance treatment of Forest for repeatedly calling it an anti- 2009, narrowed the total market size from COPD associated with chronic bronchitis inflammatory drug. “I had the sense [For- up to 24 million Americans to 7.6 million. est thought] if it was said often enough it In all four 52-week Phase III trials, and in patients at risk of exacerbations” to “as maintenance treatment to reduce exacer- would be true,” he said. Platt-Mills is two additional 24-week Phase III trials, bations of COPD associated with chronic director of the Asthma and Allergy Dis- Daxas produced a 3-5% increase in FEV1 ease Center at the University of Vir- that was statistically significant (p<0.001). bronchitis in patients at risk of exacerba- tions.” ginia Medical Center. Even though this bronchodilation ef- The modification could change the Since taking over the Daxas NDA in fect was measureable, FDA said in its August 2009, Forest has taken steps to review that it “would not constitute a way physicians and patients think about Daxas by removing any suggestion that it cope with some of these problems, and if clinically meaningful benefit.” alleviates quotidian symptoms of COPD, things had gone according to plan, those Indeed, the Daxas NDA is based prin- steps clearly would have yielded much cipally on reduction in COPD exacerba- instead highlighting its use to reduce the relatively infrequent, but often debilitating more favorable advisory committee rec- tions. exacerbations. ommendations. In the 124 trial, the rate of moderate or But Forest’s strategy, which hinged on severe exacerbations was reduced from The change also would more accu- rately reflect the benefits achieved in tri- modifying the indication Nycomed had 1.3 in the placebo arm to 1.1 in the Daxas als, and although the company is seeking sought in its NDA, was blunted by FDA’s arm, a 14.9% reduction (p=0.0278). In the refusal to revise its review to evaluate the 125 trial it was reduced by 18.5% from 1.5 approval as monotherapy, clearly would suggest Daxas should be used in combina- new indication. in the placebo arm to 1.3 in the Daxas arm tion with drugs that address COPD symp- FDA also clashed with Forest at the (p=0.0035). panel meeting, refusing to allow the com- FDA was not impressed. toms other than exacerbation, such as lung function. pany to present a draft REMS that had not Anthony Durmowicz, clinical team been submitted to the agency in advance. leader in the Division of Pulmonary, Al- Bruce Burlington, who served as the lergy, and Rheumatology Products, told industry representative to the advisory the advisory committee that for an indi- committee, questioned FDA’s refusal to Exacerbations vidual COPD patient treated with Daxas, accept the modified indication. He is former EVP and worldwide head of regulatory The original roflumilast IND was filed “it takes five years to get the benefit of not affairs at Wyeth and former director of in 1999 by Altana AG, and became having one exacerbation.” FDA’s Center for Devices and Radiologi- Nycomed’s when it acquired Altana’s It would take “30 years to show a cal Health (CDRH). Altana Pharma unit in September 2006 benefit of not having a hospitalization” as “Over my career I have taken many, (see BioCentury, Sept. 25, 2006). a result of an exacerbation, he added. many drugs through approval, [and] FDA Based on feedback from FDA, Altana More than half of the patients in both always interacts on the label,” Burlington launched two Phase III studies, MS-111 arms of the 124 and 125 trials did not told the panel, noting that “changing the and MS-112, with 1,173 and 1,513 pa- experience an exacerbation during the indication happens frequently at many tients, respectively. FEV1 and exacerba- trial. As a result it is impossible to deter- divisions at FDA.” tion rate were the co-primary endpoints. mine if they would benefit from Daxas if it Durmowicz replied that label changes The trials failed to demonstrate statisti- has been administered for a longer period. “generally are an FDA-driven issue.” cally significant reductions in exacerba- FDA’s briefing document also noted He added: “This was specifically a tions. that “in no study was the efficacy of company-derived issue that occurred af- A post hoc analysis of the 111 and 112 roflumilast evaluated compared to what ter we had done a substantial amount of trials led Altana to design two additional has become standard of care treatment for review on the entire NDA. From our Phase III trials with inclusion criteria in- patients with COPD, concomitant use of a standpoint that changed the way we looked tended to enrich for responders. LAMA and an inhaled corticosteroid in at things, and in preparation for the advi- The MS-124 and MS-125 trials enrolled combination with a LABA.” sory committee, and subsequently we de- only COPD patients with chronic bronchi- Durmowicz told the committee it is cided to stick with the initial indication.” tis and a history of cough, sputum produc- difficult to put Daxas’s efficacy into con- Chowdhury told the committee the tion, and recent exacerbations. Concomi- text because “use of standard therapies “change in indication came more than six tant inhaled corticosteroids, which had been for COPD was heavily restricted” in the months into the review cycle, approxi- permitted in the 111 and 112 trials, were development program. mately two to three months before the prohibited in 124 and 125. “The use of roflumilast in addition to [advisory committee] meeting, and the Changing the indication from all COPD standard treatments would allow for bet- review documents are due one month patients to those with bronchitis, which ter characterization of risk/benefit deter- before the meeting. We didn’t have time Nycomed did in the NDA submitted in July mination,” he said. See next page BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A4 OF 19 Regulation, had a history of depression. from previous page “It was a very limited change Forest stressed that two of the suicides in our minds, and we were occurred 20 and 22 days after discontinu- to look at implications” of the change. ation of Daxas. The modified indication is “more pre- surprised the agency wasn’t Durmowicz told the committee that “a cise in terms of really defining the popula- willing to review it.” lot of neuro-psychotropic drugs take awhile tion that would benefit the greatest from the to take effect and awhile to go out of drug,” Lawrence Olanoff, president and effect,” suggesting that Daxas could cause Lawrence Olanoff, COO of Forest, told reporters after the suicidal behavior three weeks after dis- Forest Laboratories meeting. “It was a very limited change in our continuation. minds, and we were surprised the agency Forest CMO Marco Taglietti argued “it wasn’t willing to review it.” is impossible to conclude there is an association between Olanoff suggested that consideration of Forest’s preferred roflumilast and risk of suicidality.” However, he added, “the fact indication may have changed some advisory committee votes. that there is an imbalance remains an area of concern that needs Indeed, one temporary voting member, Jesse Joad, said she to be managed properly when the drug is available.” might have changed her no vote on efficacy to yes if the Durmowicz also noted FDA had initially dismissed reports of committee had considered Forest’s preferred indication. dose-related increases in nasal carcinomas in hamsters exposed Joad, professor emerita at the University of California, to Daxas as irrelevant for humans, but has recently revised its Davis, told the panel it would have been easier to vote for an opinion. indication that matched the criteria and outcome of the clinical When FDA first reviewed Daxas toxicological data, it thought trials. a metabolite of the compound that causes tumors in rodents Explaining her vote against efficacy to the committee, Joad does not occur in humans, but it later determined that the said: “It is effective, especially in preventing exacerbations, [but] metabolite is present in human urine. As a result, FDA’s maintenance to me means everyday symptoms and they have not Executive Carcinogenicity Assessment Committee “changed shown that.” their position and stated that [the hamster data] is not irrelevant Ganesh Raghu, also a temporary voting member, said the for humans and could be relevant for human patients,” Durmowicz wording of the indication was the primary reason for his negative reported. votes. Raghu is director of the Interstitial Lung Disease, Sarcoid Durmowicz also noted a doubling of some common cancers, and Pulmonary Fibrosis Program at the University of Wash- including lung, prostate and urinary tract, in patients exposed to ington. Daxas compared to placebo. Taglietti said that many of the tumors were detected within a month or two of exposure to Daxas, which he argued was far Safety too soon to be drug-induced. He suggested that adverse effects, FDA’s safety presentation focused on weight loss, gastrointes- such as weight loss, might have triggered workups that revealed tinal effects, psychiatric events, and a preclinical cancer signal. tumors that were present before patients enrolled in the trial. GI effects, including diarrhea and nausea, are “known class effects of PDE-4 inhibitors, [and] were the most common adverse events reported from all roflumilast clinical trials and were the No submission, no discussion leading cause for early study termination,” FDA reported in its Near the end of the day, when the committee was starting to briefing memo. focus on safety and the question of a REMS came up, FDA Daxas has been associated with weight loss in trials of COPD, asserted its authority to quash discussion of any material it hasn’t asthma, diabetes and arthritis, suggesting it is a drug-specific vetted. event, according to the agency. Daren Knoell, a standing member of the committee, asked if Pooled results of the 124 and 125 trials indicate that 62% Forest had any plans for post-market surveillance and for patients on Daxas lost weight, compared to 38% in the placebo “making sure the drug gets into the right kind of patient.” Knoell group. FDA noted weight loss was “most prominent in those is professor of pharmacy and medicine at the Ohio State least likely to tolerate it: patients who are underweight and University Davis Heart and Lung Research Institute. patients with severe COPD.” Taglietti offered to share a draft version of risk mitigation There was a 6% incidence of psychiatric adverse events in proposals that had not been submitted to FDA. But Durmowicz Daxas-treated patients, twice that in the placebo arms. There told the committee: “I don’t think you should be discussing a risk were two to three times more reports of insomnia, anxiety and management plan with a drug before determining how safe it is.” depression in the Daxas group. Other committee member asked about risk mitigation plans, FDA expressed particular concern about suicides, noting saying restrictions on marketing and use could influence their there were three completed suicides and two suicide attempts in votes on safety. COPD patients who had received Daxas compared to no “You can’t know how the drug will play out unless you know suicides or suicide attempts in the placebo group. how it is marketed,” Platt-Mills said. And Krishnan asked FDA FDA and Forest presented contradictory information about “why is it not reasonable to hear from the sponsor their the mental health status of the individuals who committed particular approach to mitigate these effects?” suicide, and sharply different interpretations about the possibil- Chowhdury responded that it is inappropriate to discuss a ity that they were linked to Daxas. REMS “on the fly” without thorough FDA vetting to determine its At the panel meeting and in a briefing memo, FDA reported practicality. He also said the “REMS doesn’t necessarily change the that none of the individuals who committed suicide had a prior safety of a drug. It may change the way the drug is used.” history of depression, while Forest told the committee that one See next page BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A5 OF 19 Regulation, reasons for psychiatric effects and I worry that weight loss is from previous page a marker of something systemic happening that is not good,” he said. Curtis Rosebraugh, director of the Office of Drug Evaluation A REMS plan might “make me feel better” about safety, II, became visibly angry at suggestions from Forest and the Krishnan concluded. committee that the company should be allowed to discuss risk Several committee members expressed concerns about inap- mitigation steps that had not been reviewed by FDA. propriate off-label use, noting that many COPD patients find it “It is not unusual for sponsors, if there is a risk issue, to difficult to use inhalers and speculating that the ease of use of an present at a meeting their risk mitigation strategy,” Rosebraugh oral drug would prompt physicians to prescribe Daxas for many said. “However, it is usually one that has been submitted to us, patients. not one where the panel members seem to be upset about “There is a very high potential for misuse and abuse of the something and [the company says] ‘let’s throw something out drug,” said Robert Fink, director of the Regional Cystic Fibrosis that will appease them.’” Center at The Children’s Medical Center of Dayton. He is At the end of the day, Krishnan indicated that a REMS a temporary voting member. presentation might have turned his vote on safety from a no After the meeting, Olanoff said Forest did not file a draft REMS to a yes. “I think there is uncertainty in my mind about the See next page

Loves me, loves me not

FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 10-5 that safety and efficacy data taken together do not provide substantial evidence to support the approval of Daxas roflumilast from Forest Laboratories Inc. (NYSE:FRX) and Nycomed for maintenance treatment of chronic obstructive pulmonary disease (COPD). The negative vote came after two separate votes on safety and efficacy, in which a majority of committee members voted in the affirmative. Although both tallies were 9-6, some committee members voted differently on the safety and efficacy votes, which led to the overall negative vote when FDA asked them to integrate the two issues in a vote on approval. Member Substantial Sufficient Efficacy and safety evidence of safetyprofile? support approval? efficacy?

William Calhoun, professor of internal medicine, Y Y Y U of Texas Medical Branch (chairman) Paula Carvalho, professor of medicine, U of Washington, and chief N Y N of the intensive care unit, VA Medical Center, Boise Leslie Hendeles, professor of pharmacy and pediatrics, N N N U of Florida Health Science Ctr John Hoidal, professor of medicine and chair, N Y N Dept. of Internal Medicine, U of Utah Richard Honsinger, physician, Los Alamos Medical Ctr Clinic Y Y N Daren Knoell, professor of pharmacy and medicine, N Y N Ohio State U Davis Heart and Lung Research Institute Jerry Krishnan, associate professor of medicine and health studies, Y N N U of Chicago Rodney Mullins, national director, Public Health Consultants Y N N and Advocates (consumer representative) Thomas Alexander Platts-Mills, director of the Asthma and Y Y Y Allergy Disease Ctr, U of Virginia Medical Ctr Robert Fink, director of the Regional Cystic Fibrosis Ctr, Y N N Children’s Medical Ctr of Dayton (temporary voting) Edna Fiore (patient representative, temporary voting) Y Y Y Jesse Joad, professor emerita, UC Davis (temporary voting) N N N Ganesh Raghu, professor of medicine, director of the N N N Interstitial Lung Disease, Sarcoid and Pulmonary Fibrosis Program and medical director of the lung transplant program, U of Washington School of Medicine (temporary voting) David Schoenfeld, professor of medicine, Massachusetts Y Y Y General Hospital Biostatistics Ctr (temporary voting) Erik Swenson, professor of medicine, U of Washington Y Y Y (temporary voting) BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A6 OF 19

Regulation, ably could be dealt with relatively quickly. from previous page But other concerns raised by panel mem- bers would require long-term trials. BioCentury in part because it was waiting to receive For example, explaining his no vote on THE BERNSTEIN R EPORT ON BIOBUSINESS™ FDA’s briefing documents, to learn which safety, Fink said he was “particularly both- safety issues the agency considered most ered by the fact that there were no open- Editorial & Research important. label, add-on studies to provide anything Newsroom: beyond a year of therapy. Maintenance [email protected] implies years of therapy in these patients.” San Carlos, CA: +1 650-595-5333; 9-6 + 9-6 = 5-10 Honsinger said he voted no on efficacy Fax: +1 650-595-5589 At the end of the day, the committee because “I felt the benefit of this drug, Chicago: +1 312-755-0798; concluded in separate votes that Daxas is though there, is meager.” He said a com- Fax: +1 312-755-0658 safe, and that it is effective, but that it parative effectiveness study should be an Washington, DC: +1 202-462-9582; Fax: +1 202-667-2922 should not be approved because it is not approval requirement. “The drug does have side effects,” Oxford, UK: +44 (0)1865-512184; safe AND effective. Fax: +44 (0)1865-311195 The result wasn’t as odd as it seems at Honsinger said. “You need to compare first glance. To vote for approval, a mem- this drug with existing drugs to show it has www.biocentury.com ber would have to conclude both safety as much benefit or less side effects before and efficacy had been demonstrated. it is released.” Three members who voted that Forest Leslie Hendeles, professor of pharmacy Editor-in-Chief: Karen Bernstein, Ph.D. had demonstrated efficacy turned around and pediatrics at the University of Managing Editor: Susan Schaeffer and voted that it had not demonstrated Florida Health Science Center, also Director of Research: Walter Yang Research Managers: Juli Balestrieri, safety, and three who voted that it had not called for pre-market comparative studies. Kevin Lehnbeuter demonstrated efficacy voted that it had Daxas provides a “meager degree of Senior Editors: Jeff Cranmer (BioCentury demonstrated safety (see “Loves Me, Loves benefit, and has side effects and nothing Extra), Steve Edelson (SciBX), Me Not,” A5). unique. If there had been data presented Steve Usdin (Washington), Mike Ward One member, Richard Honsinger, an showing this meager advantage in patients (Europe) immunologist at the Los Alamos Medi- on other standard therapy, I might have Senior Writers: Aaron Bouchie, voted differently. So that’s the study that Michael Flanagan, Tim Fulmer, Ph.D., cal Center Clinic Ltd. who had voted Michael J. Haas, Stacy Lawrence, yes on the safety and efficacy questions, would convince me.” Erin McCallister, Lev Osherovich, Ph.D. changed his mind and voted no on ap- Paula Carvalho, professor of medicine Staff Writers: Jacquelyn Cafasso, proval. He said the benefit is “meager” in the University of Washington Division Matt Crockett, Meredith Durkin, and cited the “need to compare this drug of Pulmonary and Critical Care Medicine, Stephen Hansen, Mabel Lam, with existing drugs to show it has as much said she voted no on efficacy for similar Kai-Jye Lou, Lauren Martz, Brian Moy, Derek Smith benefit or less side effects before it is reasons. A standing member of the com- mittee, Carvalho said: “I would be much released.” BioCentury Summing up the views of the five mem- more comfortable with the data if there bers who voted for approval, committee was a study with corticosterioids, LABA BioCenturyTM; The Bernstein Report on TM chairman William Calhoun said “most of and LAMA against this agent.” BioBusiness ; Because Real Intelligence is Hard the adverse events in my view are toler- to Find; BCIQ; The BioCentury 100; and The Clear Route to ROI are trademarks of BIOCENTURY COMPANIES AND INSTITUTIONS MENTIONED ability issues and not safety issues. The PUBLICATIONS, INC. All contents Copyright © Altana AG (Xetra:ALT), Konstantz, Ger- two safety issues that come to the level of 2010, BIOCENTURY PUBLICATIONS, INC. my concern are suicide, and I think the many ALL RIGHTS RESERVED. SciBX and SciBX: agency should work with the sponsor to The Children’s Medical Center of Dayton, Science-Business eXchange are trademarks of Na- monitor and gather more data, and the Dayton, Ohio ture America, Inc. that are jointly used by BioCentury weight loss issue, which requires some Forest Laboratories Inc. (NYSE:FRX), New Publications, Inc. and Nature America, Inc. No part follow-on.” York, N.Y. of BioCentury’s Publications or Website may be Calhoun, the Sealy and Smith Distin- Life Expectancy Project, San Francisco, copied, reproduced, retransmitted, disseminated, guished Professor of Internal Medicine in Calif. sold, distributed, published, broadcast, circulated, the Department of Internal Medicine at Los Alamos Medical Center Clinic Ltd., commercially exploited or used to create derivative works without the written consent of BioCentury. the University of Texas Medical Los Alamos, N.M. Branch, said he is “unconcerned about Nycomed, Zurich, Information provided by BioCentury’s Pub- lications and Website is gathered from sources that Ohio State University, Columbus, Ohio the carcinogenicity signal. The biological BioCentury believes are reliable; however, University of California, Davis, Davis, Calif. plausibility isn’t there.” BioCentury does not guarantee the accuracy, com- Calhoun said “there is an efficacy sig- University of Florida Health Science pleteness, or timeliness of the information, nor does nal, although as indicated, it is modest. Center, Jacksonville, Fla. BioCentury make any warranties of any kind The safety issues are addressable” by University of Texas Medical Branch, regarding the information. The contents of physicians who care for COPD patients. Galveston, Texas BioCentury’s Publications and Website are not Some of the concerns that led commit- University of Virginia Medical Center, intended as investment, business, tax or legal tee members to vote no, such as the need Charlottesville, Va. advice, and BioCentury is not responsible for any for a REMS to prevent widespread off-label University of Washington, Seattle, Wash. investment, business, tax or legal opinions cited use, and a narrower indication, conceiv- U.S. Food and Drug Administration (FDA), therein. Silver Spring, Md. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A7 OF 19 Strategy pRED: Making the transition

By Susan Schaeffer the transfer of a program to late-stage Managing Editor “No matter how good development. The key is that a pRED With the integration of Genentech program has to be good enough for late- Inc. now complete, Roche has refined the you are, 99.5% of good stage development to be willing to pick it structure of its early R&D organization. research is being done up. The new approach places decision-mak- “In the past, we were looking at more ing about early stage programs into the outside your place.” intermediate milestones, and the tendency hands of scientists, streamlines and con- is to do the minimum amount of work to solidates key functions supporting early Jean-Jacques Garaud, Roche achieve the milestone,” he said. R&D, and defines success as the number According to Garaud, focusing on the of projects that make the hand off into later-stage development. transition to late-stage development should optimize allocation As a result, according to Jean-Jacques Garaud, head of Roche of resources to the programs that are most likely to succeed. As Pharma Research & Early Development, the group most likely a result, he expects pRED to focus on fewer programs, but with will take on fewer projects at a time, but increase its rate of a lower the attrition rate. success. Garaud told BioCentury the new definition of success has pRED, as the group is known internally, was formally already led some of the DTAs to reprioritize their portfolios. launched in January as one of Roche’s autonomous centers, “The incentives are the same, but we have aligned goals between alongside Genentech Early Research & Development (gRED). early stage and late stage development,” he said. Each group is given an annual budget and a target for the number of projects it is expected to pass into Phase III development, and each is supported by its own business Consolidating support development and licensing organization (see “gRED: Small Com- Another important part of the reorganization, Garaud said, pany Sensibilities,” A8). is the creation of five “enabling functions” under pRED’s roof. pRED still focuses on the same diseases Roche organized These include a group responsible for selecting the best thera- around in 2007, when it established five R&D units called DBAs peutic modality for a given program, and groups for translational in oncology, virology, metabolism, inflammation and CNS. But science, clinical development operations, non-clinical safety and the units are now structured and managed differently. informatics. “We wanted to build on what was working well,” Garaud told Some of these functions, such as non-clinical safety, have not BioCentury. “The DBAs were very successful: they delivered six changed. But for the first time, all the therapeutic modalities have molecules into late-stage development. What we have now are been housed together, including small molecules, , discovery and translational areas; we call them DTAs.” peptides, RNAi and stem cells. The main difference is the decision-making structure. Previ- “It’s a one-stop-shop for the biology people. They go to this ously, each DBA had a leadership team, called a DBLT, that group to figure out the best modality,” Garaud said. included four executives representing research, clinical develop- At Roche’s investor day in New York last month, Garaud ment, strategic marketing, and clinical research and exploratory noted that 35 compounds from pRED could enter late-stage development (see BioCentury, Feb. 12, 2007). development between 2010 and 2014; 60% of them are small “One of the four was selected to be the leader — but the molecules, and the remainder are antibodies or proteins. leader did not necessarily have decision-making authority,” The translational science function also represents a consoli- Garaud said. “If there were disagreements, the leader was the tie- dation of capabilities that had been spread throughout the breaker. This could be time-consuming.” company. Now, each DTA has one head from within pRED who is “This includes, for example, the wet labs to do biomarker responsible for deciding how to allocate resources. Thus, similar work, the dry labs with bioinformatics — all the ‘super brain to Genentech’s gRED group, decision-making is now more in the power’ needed to do the research,” Garaud told BioCentury. hands of the scientists. Gaining and managing access to translational science outside “It’s a subtle difference, but it’s important,” Garaud said. of Roche’s walls is one of the tasks assigned to the development Representatives from late-stage development, marketing and operations group, which also houses clinical pharmacology, regulatory affairs still provide input into early R&D, but instead clinical operations and portfolio management. of sitting on a DBLT and sharing decision-making, they now “No matter how good you are, 99.5% of good research is provide advice via portfolio committees: one for each DTA, and being done outside your place. Industry in the past has been another high-level portfolio committee for all of pRED. under the belief you had to build it all yourself. I think that’s a In addition, pRED is represented on the late-stage develop- bit of a folly — and it creates an inflexible cost structure,” said ment group’s portfolio committee. Garaud. This cross-representation, combined with clear expectations On the other hand, he added, “some companies may say for the number of transitions from pRED to late-stage develop- they don’t need anything internally — they can outsource it ment, is intended to ensure alignment across all stages of R&D. all — and that’s also folly. I think there’s a sweet spot in According to Garaud, the company now defines success as See next page BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A8 OF 19 Strategy gRED: Small company sensibilities

By Susan Schaeffer of gRED’s pipeline, while neurology comprises 13%. Managing Editor “I’m a neurologist and neuroscientist by training,” Sabry told Genentech Inc. used to represent everything that was BioCentury. “If you think back to when Genentech got into quintessentially best about biotech: nimbleness, the quick com- oncology, there were very few targeted therapies. Most of munication and decision-making that small size brings, and the pharma was working on chemotherapeutics. Neuroscience is ability to do good experiments on a shoestring. But success has similar in some ways. There is unmet need not only in areas like brought the kind of size that makes all that more difficult. Thus Alzheimer’s disease, but also in autism, schizophrenia, etc.” it may be ironic, but should hardly be surprising, that the Two groups totalling about 40 people report to Sabry. The company’s most recent major hire is a larger group is business development, former CEO who brings small biotech which includes the transaction profes- experience. “I’d argue that often when sionals who identify products and com- James Sabry, the former chairman and plete scientific due diligence. The second CEO of Cytokinetics Inc., has taken trials fail, it’s not because of group is alliance management, whose task over as VP of Genentech partnering, re- the compound itself.” is to ensure that Genentech and its part- porting to Richard Scheller, head of ners are communicating and working well Genentech Research & Early Develop- James Sabry, Genentech together. ment (gRED). As the former head of a small biotech, Sabry told BioCentury he expects to Sabry believes the latter is especially im- draw on his experience inside a small biotech, as well as his portant when it comes to clinical development strategy. expertise in neurology, an area the company is moving into “Strong communication between scientists in a biotech and quickly. scientists in gRED is really important. You wouldn’t believe the “We’re going to have interest not only in targets and number of times in pharma that communication is not as clear technology, which has been Genentech’s historical focus, but as you’d like. I believe that’s an unmeasured cost of alliances,” also on compounds that fall within our remit of discovery and Sabry said. early development,” Sabry said. “Those could be Phase I prod- “I’d argue that often when trials fail, it’s not because of the ucts, Phase II products, or products within a year of entering an compound itself,” he continued. “So the important thing is IND. We’re interested broadly in therapeutics: small molecules, having a meeting of minds in research and early development.” as well as antibodies and proteins.” According to Sabry, “the most important thing is how Sabry declined to give details about the targets and indica- strategy aligns between discovery and development. For the tions gRED is looking to pursue. But at the Roche investor day design of clinical trials in Phase I and II, it is so essential that last month, Scheller said gRED would be shifting its focus more designs line up beautifully with the mechanism of action of the toward neurology, even if oncology remains the “major empha- compound. Many companies — and I’ll go out on a limb and say sis” for the next several years. Oncology now accounts for half See next page pRED: Making the Transition, sity Hospital, Nanyang Technologi- of this nature are being prepared, and from previous page cal University, National Healthcare that up to five could be executed this Group and Singapore Health Services year. between. We need to have a strong Pte Ltd. “Five would be a stretch; I don’t network so we can be close to research The hub initially will employ 30 re- expect to do more than 10 in total,” he that could help us.” searchers. A joint steering committee will said. To this end, Roche has begun to estab- define the strategic direction of the alli- lish “translational hubs” to provide the ance and oversee its research projects. COMPANIES AND INSTITUTIONS MENTIONED pharma with access to new science. “The government in Singapore has Agency for Science, Technology and A recent example is the Hub for invested a lot in basic science over the last Research (A*STAR), Singapore Translational Medicine in Singapore. In 10-15 years and has reached a level of Genentech Inc., South San Francisco, Calif. January, Roche and collaborating insti- excellence in basic science, but is lacking National Healthcare Group, Singapore tutions said they would invest CHF100 in translational science,” Garaud said. Nanyang Technological University, million ($96.2 million) to expand knowl- “They need more translational sci- Singapore edge of disease biology to accelerate de- ence, and they want to collaborate to be National University Hospital, Singapore velopment of personalized treatment ap- more practical about it,” he added. “We National University of Singapore, proaches. have identified programs in oncology, vi- Singapore The collaborators include the Agency rology and imaging. We will have a few Roche (SIX:ROG; OTCQX:RHHBY), , for Science, Technology and Re- Roche employees there and will have col- Switzerland search (A*STAR), National Univer- leagues doing programs for us.” Singapore Health Services Pte Ltd., sity of Singapore, National Univer- Garaud said three more agreements Singapore BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A9 OF 19 gRED: Small Company Sensibilities, from previous page

many pharma companies — don’t make the connection as well as you’d like. And that often is where deals fail.” SciBX This Week Sabry emphasized the importance of understanding a compound’s mechanism of action. ANALYSIS “How far can you take a compound forward if the mechanism is not understood?” he said. “It’s like driving a car with blinders COVER STORY on: at some point, you may hit a tree. It doesn’t mean you can’t Managing microglia in Alzheimer’s continue, but it will slow you down. Medivation is a great German researchers have evidence that microglia play example.” opposing roles in AD: they not only eliminate ß-amyloid Medivation Inc. has been developing Dimebon latrepirdine aggregates via phagocytosis but also kill nearby neurons. The two functions are controlled by different cell-surface for Alzheimer’s disease (AD), although the company has not receptors, thus providing a road map for how to clear ß- been able to pin down the compound’s MOA beyond a belief that amyloid plaques without destroying healthy neurons. the oral small molecule enhances mitochondrial function. Last month, Dimebon missed the primary and secondary TRANSLATIONAL NOTES endpoints in the Phase III CONNECTION trial to treat AD, even Combining against tuberculosis though CONNECTION was designed to replicate a Russian Drawing on lessons learned from the fight against HIV, the Phase II trial that met all its primary and secondary endpoints. Global Alliance for TB Drug Development has partnered The company now says it has to reconsider the entire program, with the Critical Path Institute to map out a strategy for which is partnered with Pfizer Inc. (see BioCentury, March 8). testing combinations of new classes of tuberculosis “If you have a miracle compound, where the magnitude of the therapeutics in industry’s pipeline. clinical effect is very high, maybe you can go forward. But more TARGETS & MECHANISMS often than not, that’s not the case,” said Sabry. miRNA inhibition of metastasis Sabry’s counterpart on the Roche side is Dan Zabrowski, EVP A U.S. team that included researchers from Regulus and global head of pharma partnering. He is responsible for deal Therapeutics has reported the first successful inhibition of making for Roche Pharma Research & Early Development, or a microRNA in tumor cells. The biotech’s anti-miRNA pRED, as well as for late-stage development. oligonucleotide prevented breast cancer metastasis in “Certain deals will be in the sweet spot for gRED, and those mice, thus showing the potential of miR-10b as an will come our way,” said Sabry. “We want to ensure that we antimetastatic target. don’t step on each other’s toes.” TOOLS Zabrowski and Sabry will continue to collaborate via the GEO: world of diagnostic potential partnering model Roche announced last July (see BioCentury, July Researchers from California and Taiwan have transformed 13, 2009). genetic information contained in public repositories into a Genentech and Roche Pharma maintain separate BD organi- searchable database that they anticipate could help zations that mirror each unit’s R&D remit. To make sure the diagnose diseases more efficiently than current gene- groups don’t act at cross-purposes and that opportunities don’t based methods. fall through the cracks, Roche has designated individuals who act as single points of contact, dubbed SPOCs, to determine which THE DISTILLERY organization is best suited to work on a given idea. This week in therapeutics “A side effect of the collaboration model is sharing best Treating cancer with ATX inhibitors; preventing cardiac practices,” Zabrowski told BioCentury. “We’ve assigned learn- hypertrophy with TRPC inhibitors; using IL-18 agonists to ing coordinators in each group to find a way to share best treat colitis; treating CNS injury with triazine-based practices.” compounds; and more… For example, he said, “gRED has had a very strong legacy of This week in techniques working early in research collaborations. On the flip side, the A mouse model of spinocerebellar ataxia type 5; synthetic, Genentech partnering group has wanted to learn more about skin-permeable proteins for topical ; isolation how we approach VCs.” of early cardiovascular progenitor cells for cardiovascular repair; and more… COMPANIES AND INSTITUTIONS MENTIONED Cytokinetics Inc. (NASDAQ:CYTK), South San Francisco, Calif. Genentech Inc., South San Francisco, Calif. Medivation Inc. (NASDAQ:MDVN), San Francisco, Calif. Pfizer Inc. (NYSE:PFE), New York, N.Y. FROM THE MAKERS OF BioCentury AND nature Roche (SIX:ROG; OTCQX:RHHBY), Basel, Switzerland Request a Free Trial [email protected] Stay Alert with BioCentury: A New Custom Publications Alert Service BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A10 OF 19 Strategy Stahel sees scale in India By Stephen Hansen late all the key pathways that are critical Staff Writer “They spend about the in linking the targets to their physiologi- Indian biotech Connexios Life Sci- cal impact and hence their clinical rel- ences Pvt. Ltd. is hoping to pattern itself same amount of money evance,” CEO Suri Venkatachalam told after Western R&D-focused biotechs by that we would in a biotech BioCentury. building a pipeline of compounds against “If you have 30 biologists working novel targets backed by a strong under- company in the West, for three years on nothing else but standing of disease biology. The scale of but they increase the studying the disease in every relevant the company’s research team has attracted organ of the body, then you know their Rolf Stahel as non-executive chairman to number of scientists approach is very serious,” Stahel said. add international business development The company’s lead compound is CNX- and marketing acumen to the science that employed tenfold.” 011-326, an agonist of free fatty acid recep- is already in development. tor 1 (FFAR1; GPR40). It is in preclinical Like other small biotechs, Connexios Rolf Stahel, Connexios Life Sciences development for Type II diabetes. The com- hopes to fill the gap at pharma companies pany also has 11beta-hydroxysteroid dehy- such as AstraZeneca plc that have become more dependent drogenase type 1 (11b HSD1) inhibitors in preclinical development upon in-licensing to offset cuts in their own discovery research (see for the indication. BioCentury, March 15). Connexios has disclosed two other programs in discovery for Developing relationships with pharma and big biotech is where Type II diabetes: AMP-activated protein kinase (AMPK) activa- Stahel will play a role. Stahel became CEO of Shire plc in 1994 tors and retinoid X receptor (RXR) activators. RXR modulators following 27 years at Burroughs Wellcome Co. (now are used to treat cancer, such as Targretin bexarotene from GlaxoSmithKline plc). At the time, Shire had 15 employees and Eisai Co. Ltd., which is approved to treat cutaneous T cell about $1 million in revenue, with a valuation of around $30 million. lymphoma (CTCL). Venkatachalam said he isn’t aware of any When he left in 2003, Shire had annual revenues exceeding $1.2 other programs focused on RXR as a target for diabetes. billion, more than 1,800 employees and a $4.8 billion market cap. Connexios also is validating undisclosed targets for metabolic After leaving Shire, Stahel didn’t want to start over building disorders. “We are reasonably sure that there aren’t any active another company. Instead, he decided to accept a limited number drug discovery programs on these targets. We hope to disclose of offers to serve as non-executive chairman. some of these targets in the coming months,” Venkatachalam said. “As non-executive chairman, I can focus on transferring the Stahel said Connexios hopes to have 5-10 projects under knowledge that I gained at Wellcome in terms of marketing and development within two or three years and will seek to out- the interaction of marketing and R&D, and the knowledge I license them in preclinical or early clinical development. He gained at Shire of it being a tiny company and bringing it to the hopes Connexios will announce its first out-licensing deal within FTSE 100. I thought that knowledge could be valuable to smaller the next 12 months. companies that are perhaps less business-oriented but strong in “Ultimately, maybe even this company will try to keep one or science,” Stahel told BioCentury. two projects in-house so that would then lead toward a company Stahel is non-executive chairman of neurology company that maybe 15 years from now might have its own marketing Newron Pharmaceuticals S.p.A., drug delivery company organization. But that’s a long shot,” Stahel said. Cosmo Pharmaceuticals S.p.A. and cancer and neurology Connexios is developing its compounds for a global market company EUSA Pharma Inc. and will pursue IP protection on a global scale. Connexios was founded in 2003 to develop small molecules The biotech has raised an undisclosed amount of money from for diabetes and related metabolic disorders. Stahel said at first its sole investor, Nadathur Holdings and Investments, an invest- he was skeptical that a small company could be doing innovative ment firm for the N.S. Raghavan family in Bangalore. science in a developing country like India. What changed his Stahel said Nadathur has a long-term vision for building the mind was the company’s approach to R&D spending. company, but “it may not be a bad idea to invite a high quality Connexios takes advantage of the low cost of high quality international VC to join the party, simply because of the network scientists in India, which Stahel put at 10% of Western salaries, and they bring. These are options that over the next two to three “instead of saving the money, they spend about the same amount years the company will regularly review.” of money that we would in a biotech company in the West, but they increase the number of scientists employed tenfold, which allows COMPANIES AND INSTITUTIONS MENTIONED them to take a very detailed approach to a limited field,” he said. AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K. The company hasn’t disclosed how much it spends on R&D, Connexios Life Sciences Pvt. Ltd., Bangalore, India but 130 of the about 170 employees are scientists. This is “a very Cosmo Pharmaceuticals S.p.A. (SIX:COPN), Lainate, Italy rich set of employees” compared to most startup or small cap Eisai Co. Ltd. (Tokyo:4523; Osaka:4523), Tokyo, Japan biotechs, Stahel said. EUSA Pharma Inc., Doylestown, Pa. The biotech has used this headcount to research the detailed GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. pathophysiology underlying disease. Newron Pharmaceuticals S.p.A. (SIX:NWRN), Bresso, Italy “Our network biology approach has allowed us to articu- Shire plc (LSE:SHP; NASDAQ:SHPGY), Basingstoke, U.K. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A11 OF 19 Strategy Altheos mines its Rho-lodex

By Aaron Bouchie compounds wouldn’t be competing for resources within a big Senior Writer pipeline, like they would at a bigger company,” he said. After concluding that all the interesting new projects in the As with other Japanese companies, personal relationships U.S. and Europe had been picked over, the founders of Altheos were key, Kengatharan said. “Henry has known them for about Inc. turned to Asia to find assets for in-licensing. Based on the eight years, and I’ve known them for four or five years.” strength of their relationships with Asahi Kasei Pharmaceu- Asahi Kasei also liked Hsu and Kengatharan’s experience with tical Corp., their experience with ophthalmic products and ophthalmic drug development at CoMentis. That company (for- their willingness to forgo other projects they’d been evaluating, merly Athenagen Inc.) was based on work by Kengatharan and they were able to secure rights to what they believe to be best- fellow Stanford University researcher John Cooke on the in-class topical Rho kinase inhibitors for glaucoma. nicotinic acetylcholine receptor (nAchR) pathway in angiogenesis. Altheos also closed a $20 million series A round on the same In 2006, CoMentis’ ATG3 became the first topical anti- day last week, which helped convince angiogenic therapy to enter Phase I trials Asahi Kasei of the biotech’s ability to for a back-of-the-eye disease, specifically focus on developing the compounds, ac- “There is lots of good stuff for age-related macular degeneration cording to President and CSO M. (Ken) in , Japan and India.” (AMD). The formulation of mecamylamine Kengatharan. is in two Phase II trials for AMD, with data Kengatharan and CEO Henry Hsu, Ken Kengatharan, Altheos Inc. expected this year. Altheos’ co-founders, are serial entrepre- At least four Rho kinase inhibitors are neurs who most recently worked together in clinical testing for glaucoma, but Altheos at neurology and ophthalmic company CoMentis Inc. They left believes the Asahi Kasei compounds will be best in class. CoMentis last year to start a newco. In glaucoma, the eye’s drainage system breaks down, causing “We were ready to move on and liked working with each a build-up of aqueous humor that leads to IOP, vision loss and other, so we basically went through our Rolodexes and con- eventual blindness. Marketed prostaglandin analogs increase tacted BD people whom we had interacted with over the past 10 drainage via the scleral pathway, and generic beta blockers are years,” Kengatharan said. used to reduce IOP by slowing down aqueous humor produc- “It became apparent that all the interesting new projects in tion. the U.S. and Europe had already been mined, so we decided to Rho kinase inhibitors relax the trabecular meshwork, which look outside. There is lots of good stuff in China, Japan and is the primary route of aqueous clearance in the eye. India,” he added. ATS907 was designed to be highly specific for Rho kinase, Kengatharan said he and Hsu were looking at four projects whereas other compounds hit off-target kinases, according to in parallel, and it became clear early on that glaucoma was a good Kengatharan. “This is a testament to Asahi Kasei’s expertise in place to focus because it would be a relatively easy indication for chemistry and biology,” he said. a small company. Kengatharan also said ATS907 has a much wider therapeutic “You can do late-stage trials in glaucoma for a small amount window than Rho kinase inhibitors in the clinic, which are of money, and there have been no new glaucoma treatments associated with vasodilation, resulting in redness (see BioCentury, based on new mechanisms in the past 15 years, so there is an Oct. 26, 2009). unmet need,” he said. “The other great thing about glaucoma is Altheos also obtained rights to backup Rho kinase com- that you can go straight into patients in Phase I trials, plus the pounds, called the AK138 series, some of which Kengatharan endpoint you use in Phase IIa — IOP [intraocular pressure] believes to be even better than ATS907. reduction — is more or less what you use for approval.” The companies are not disclosing many details of the agree- Kengatharan said the company has enough cash to get lead ment, other than it is a staged, exclusive deal for worldwide rights compound ATS907 through Phase IIb testing. He would not outside of Japan and Korea, and Asahi Kasei is taking a stake in disclose when he hopes to start Phase I trials, but said it would Altheos. be “not too far” in the future. The A round financing was led by Bay City Capital. Novo A/ Asahi Kasei’s portfolio is focused on neurology, autoimmune S; Canaan Partners; Life Science Angels; and Atheneos Capital and genitourinary indications, so it was primarily looking for a also participated. company that would be totally committed to developing the ophthalmic compounds, according to Kengatharan. COMPANIES AND INSTITUTIONS MENTIONED Multiple parties were interested in the compounds, so Altheos Inc., South San Francisco, Calif. Kengatharan and Hsu closed their interests in the other three Asahi Kasei Pharmaceutical Corp. (Tokyo:3407), Tokyo, Japan projects to prove that they were serious. “We focused only on CoMentis Inc., South San Francisco, Calif. this deal to show that we were dedicated and that their Stanford University, Stanford, Calif. Email Alerts Click on Set Email Alert from the biocentury.com home page to get started. Now you can get alerted when BioCentury publishes an article on topics you are interested in. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A12 OF 19 Emerging Company Profile Selecta: Impossible to ignore

By Michael Flanagan As a result, Langer believes Selecta’s Senior Writer Selecta Biosciences Inc. targeted delivery of the adjuvant and T Selecta Biosciences Inc. is devel- cell epitope should have fewer off-target oping synthetic nanoparticle vaccines de- Watertown, Mass. effects and better safety. He also expects signed to mimic invading pathogens in Technology: Targeted Synthetic Vac- that presenting all three components to- order to elicit an immune response against cine Particle (tSVP) platform gether will produce immune responses as molecules that would ordinarily be ig- Disease focus: Infectious, metabolic, good as or better than conventional vac- nored. The company believes its vaccines neurology and inflammation cine approaches. could be safer, more efficacious and appli- The T cell stimulatory peptide was an cable to more diseases than conventional Clinical status: Preclinical in-house discovery. It is composed of a vaccines. Founded: 2008 by Robert Langer, Omid universal epitope 9-12 amino acids in Executive Chairman Robert Bratzler Farokhzad and Ulrich von Andrian length, which is recognized by dormant told BioCentury Selecta’s targeted Syn- University collaborators: Massachu- memory T cells, which become activated thetic Particle (tSVP) platform setts Institute of Technology, Brigham and help bring about a faster and more combines a pair of discoveries made by and Women’s Hospital and Harvard robust immune response. the company’s three scientific founders, Medical School In preclinical models, “we have seen Ulrich von Andrian and Omid Farokhzad Corporate partners: None strong immune responses without stimu- at Harvard Medical School, and Rob- Number of employees: 22 lating any systemic cytokine releases,” ert Langer at Massachusetts Institute said Bratzler. Funds raised: $32.6 million of Technology. Langer also developed a single-step, According to Bratzler, while research- Investors: Polaris Venture Partners, self-assembly production process. The ing how viruses are handled immunologi- Flagship Ventures, NanoDimension, nanoparticles are stable in serum and cally, von Andrian identified “a certain OrbiMed Advisors and Leukon Invest- offer high yield, he said. type of cells in the lymph node that were ments Selecta plans to use the tSVP platform not previously thought to be part of the CEO: None to generate a variety of prophylactic and antigen-processing hardware.” Patents: Undisclosed therapeutic vaccine candidates by mixing Bratzler said these cells “are capable of and matching the antigen, adjuvant and T triggering the adaptive arm of the immune cell stimulatory peptide components. response within minutes of an initial viral take a protein and make it the antigen of Selecta plans to focus on CNS, infec- challenge.” interest. But what we have done is to take tious, inflammatory and metabolic dis- von Andrian worked out the ideal peptides, oligonucleotides and small mol- eases. According to Langer, the company specifications for a delivery vehicle to ecule haptens, and make them immuno- has demonstrated proof of concept in reach the lymph node cells, based on the genic when otherwise the immune system various animal models, though the disease size and shape as well as sequence and would ignore them,” Langer told areas and lead program are undisclosed. density of viral surface antigens. While BioCentury. The lead candidate is in preclinical Bratzler declined to provide more details, The nanoparticles do this by packag- development, with Phase I testing slated to he said the goal is to specifically target ing the antigen with an adjuvant and a T begin in 2011. macrophages and make the particle re- cell stimulatory peptide, and delivering all Following a $15 million series C round semble a virus to elicit a strong immune three directly to antigen presenting cells, that closed this month, the company has response. which in turn stimulate both a B cell and sufficient cash to take it well into 2012, Langer and Farokhzad then worked T cell immune response, according to when it expects to have data from human together to develop a lipid-polymer hy- Bratzler. volunteers (see BioCentury, April 5). brid nanoparticle that fit von Andrian’s “When the vaccine and adjuvant are specifications. The particles consist of a delivered independently, you invariably COMPANIES AND INSTITUTIONS MENTIONED hydrophobic polymeric core, which en- find adjuvant going into cells not involved Harvard Medical School, Boston, Mass. capsulates the water-soluble drug compo- in stimulating an immune response, which Massachusetts Institute of Technology, nents, surrounded by a lipid monolayer leads to the unwanted release of Cambridge, Mass. and a hydrophilic polymeric shell. chemokines and cytokines. It also results Selecta Biosciences Inc., Watertown, Mass. “The normal vaccine approach is to in wasted antigen,” he said.

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. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A13 OF 19 Ebb & Flow Crunch time

By Stacy Lawrence For Horizon, these were Essex Woodlands Health Ventures; Senior Writer Scale Venture Partners; Sutter Hill Ventures; and FirstMark Venture investors worried about down rounds will not be Capital (formerly Pequot Ventures). encouraged by the story of newly-public regenerative medicine Nitec investors were TVM Capital; Deutsche Bank; NGN company Tengion Inc. Capital; Global Life Science Ventures; and Atlas Ventures. In three private rounds, Tengion raised net proceeds of Prior to the merger, Horizon Therapeutics had raised at least $143.5 million through the sale of 82 million shares of convert- $51 million, while Nitec had raised at least $58 million. ible preferred stock. The price at the series A round was $1.62 per share, while the share price at the series B and C rounds was $1.82. Pipeline profile A few weeks before the IPO, the investors conducted a 1-for- The newco will include Nitec’s Lodotra modified-release oral 14.5 reverse stock split, effectively putting the series A price at tablet of low-dose prednisone, which is marketed in Europe to $23.44 per share and the series B and C at $26.39. reduce morning stiffness associated with rheumatoid arthritis The existing investors also committed to purchasing about (RA). The newco expects to submit an NDA in the U.S. next half. $17.2 million of Tengion shares in the IPO, according to the Merck KGaA (Xetra:MRK) has marketing rights in company’s latest S-1 filing, which means the VCs may have and Austria and Mundipharma International Ltd. has rights accounted for more than half of the $30 million raised in last in the rest of Europe. week’s offering, which sold 6 million shares at $5 per share. From its side, Horizon recently submitted an NDA to FDA for The IPO price valued Tengion at $61.8 million, leaving the Duexa (HZT-501) to treat mild to moderate , and expects to post-money value of the private rounds at only $31.8 million. submit an MAA in the EU next half. The compound is a fixed- Three of the seven Tengion board members are VCs. Existing dose combination of 800 mg ibuprofen and 26.6 mg famotidine, investors include Oak Investment (19.6% pre-IPO); HealthCap a histamine H2 receptor (HRH2; H2R) antagonist. (14.3%); Johnson & Johnson Development Corp. (12.5%); Brookside Walbert said he’s hoping for approvals in the U.S. and Europe Capital (8.6%); Bain Capital (8.5%); Quaker BioVentures (8.3%); next year, but declined to say when Horizon Pharma plans to file and L Capital (6.4%). for an IPO, Tengion has just reached the clinic with its Neo-Urinary “With two late-stage products in the U.S. and an approved Conduit, which is in Phase I testing for bladder cancer patients product in Europe, we are well positioned to access the public requiring a urinary diversion following bladder removal. markets,” he said. “Some of the other companies that have gone Like the other biotech IPOs this year, Tengion priced below out or are in the queue still have significant clinical risk. We’re its anticipated range of $8-$10. It had aimed to sell 4.4 million past our clinical risk and see ourselves as having relatively low shares, which would have raised $40 million at the mid-point and regulatory risk.” valued the company at $97.2 million. The pipeline also contains Nitec’s One bit of good news — Tengion TruNoc tarenflurbil, an inhibitor of NF- managed to keep from breaking its issue “We’re past our clinical kappa B and activator protein (AP-1) in price, closing its first day of trading up Phase II testing to treat pain. Horizon’s $0.02 to $5.02. risk and see ourselves as HZN-602 is an orally available combina- having relatively low tion of immediate release naproxen and high-dose famotidine in Phase I testing to Merging for an IPO regulatory risk.” reduce the risk of upper gastrointestinal By combining one marketed drug and (GI) ulcers in patients with pain and ar- regulatory filings in the queue in both the Timothy Walbert, Horizon Pharma thritis. U.S. and Europe, Illinois-based Horizon Horizon Pharma will be headquartered Therapeutics Inc. and Swiss biotech Nitec Pharma AG believe in Northbrook, Ill., with offices in Reinach, Switzerland. their merger has created the de-risked profile that investors want Bank of America Merrill Lynch advised Horizon. JMP Securi- to see in an IPO. ties LLC advised Nitec. The newco, Horizon Pharma Inc., will focus on pain and inflammation. Chairman, President and CEO Timothy Walbert told Ebb & IPO watch Flow the “whole strategy was to better position the company for Two French companies updated their IPO terms last week, as the U.S. public markets, to strengthen the company with addi- bioprocessing play Deinove and autoimmune and inflammation tional late stage products.” company Neovacs S.A. aim to complete their deals over the Details of the all-stock deal and a subsequent financing earlier next two weeks. this month weren’t undisclosed. Walbert, who was president and Deinove is using deinococci bacteria to develop technologies CEO of Horizon Therapeutics, noted that all nine institutional to make biofuels and antibiotics, which are in discovery. It is investors from both companies participated in the financing, seeking to raise about €12 million ($16.2 million) through the which he said gives the newco runway into 2Q11. sale of 1.4 million shares at €7.50-€9.16 in an IPO on Euronext See next page BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A14 OF 19

Ebb & Flow, Money Raised in 2010 of the previous fund, the strategy, and the from previous page fact that this is an “asset class that is Last week, the biotech industry raised $652 uncorrelated to the general market.” Paris. million, bringing to $6.2 billion the total raised He said investors in the first fund have If sold in full at the midpoint of €8.33, seen a gross return on investment of close € year-to-date. In 2009, a total of $24.8 billion was the company would be valued at 40.3 raised, including $0.9 billion in IPOs, $6 billion to 40%. million ($54.4 million) and have 4.8 mil- in follow-ons, $5.2 billion in venture capital, and The new fund already has made three lion shares outstanding. $12.6 billion in other fundraising. Totals include investments. Two are undisclosed, and The offer, which is underwritten by overallotments and warrants, and are rounded to the third was with NPS Pharmaceuti- Invest Securities and Dexia Securities, is the nearest millions. cals Inc. (NASDAQ:NPSP). NPS sold its expected to close on April 20, with the royalty rights for Regpara cinacalcet in first day of trading slated for April 27. Japan and other Asian countries to DRI for Existing investor Truffle Capital has com- $38.4 million (see BioCentury, March 8). mitted to subscribe for €2 million ($2.7 The deal covers royalties from Kyowa million) of the offering. Hakko Kirin Co. Ltd. (Tokyo:4151), Deinove said the number of shares which markets the second-generation also may be increased by up to 216,000 calcimimetic in Japan to treat secondary shares in addition to a 254,000-share hyperparathyroidism during maintenance overallotment. dialysis. Kyowa also has rights to Regpara Neovacs now hopes to raise about from NPS in China, North and South €11 million ($14.8 million) through the Korea, and Taiwan. sale of up to 2.3 million shares at €4.80- If DRI receives cumulative royalties € 5.60 on Euronext. Source: BCIQ: BioCentury Online Intelligence from Kyowa of $96 million, 2.5 times the If sold at the midpoint of €5.20, the upfront purchase price, the agreement company would be valued at €66.1 mil- will terminate and future royalties will lion ($89.1 million) based on 12.7 million revert to NPS. shares outstanding. In March, Neovacs filed to sell up to 4.4 million shares at €5.20-€6. Israeli LP incentives The offer is expected to close on April In anticipation of the completion of a 14, with the first day of trading slated for life sciences fund raised in partnership April 21. Existing investors Truffle Capi- with the Israeli government, OrbiMed tal; Venture Funds; and OTC Advisors disclosed four new venture hires have committed to subscribe for €2.5 last week. million ($3.4 million) of the shares. Although the firm would not comment, Neovacs said the number of new shares rumors are the new fund will be in the in the offering may be increased by up to $100-$150 million range, with the Israeli 344,000 shares via an extension clause, government contributing about one-quar- not including the overallotment of 395,000 Source: BCIQ: BioCentury Online Intelligence ter of the final amount. shares. OrbiMed was one of four life sciences The company is in Phase II testing of its TNF-alpha Kinoid for venture firms selected for similar funds by the Israeli government. rheumatoid arthritis (RA). The immunotherapy against tumor The other three funds are outside the biopharmaceutical space. necrosis factor alpha is expected to enter Phase II testing in The fund is said to contain both downside protection and Crohn’s disease mid-year. upside bonuses for participating LPs. On the upside, the govern- ment will be taking a smaller cut of the upside and would subordinate its interests in any losses. Hitting a triple OrbiMed brought on four new team members for its Israeli DRI Capital closed its Drug Royalty II at $701 million last office: Senior Managing Director Nissim Darvish; Managing week, almost triple the $240 million raised in its 2006 fund, Drug Directors Anat Naschitz and Erez Chimovits; and Venture Royalty I. Partner Aya Jakobovits. The firm’s strategy will remain the same: purchasing royalties Darvish was a general partner at Pitango, where he managed on approved biopharmaceutical products with demonstrated life sciences investments. Naschitz was a managing partner at sales histories, according to Alex Leykikh of Atlantic-Pacific Axiom One, while Chimovits was CEO of vaccine and immuno- Capital. Atlantic-Pacific was the global placement agent and therapy company NasVax Ltd. (Tel Aviv:NSVX). advisor. Jakobovits will be with OrbiMed part-time and remain EVP Leykikh told Ebb & Flow the fundraising took about 18 and head of R&D at Agensys Inc., which Inc. months and was oversubscribed, having had an original target of (Tokyo:4503) acquired in 2007 for $387 million in cash and $500 million. $150 million in milestones. Agensys was an OrbiMed portfolio Investors include state pension plans, family offices and company. sovereign wealth funds from the U.S., Canada, Europe, Australia OrbiMed has more than $5 billion in assets under manage- and Asia. ment. Leykikh said the biggest selling points were the track record See next page BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A15 OF 19 Ebb & Flow, Wyeth, which was acquired last year for $68 billion in cash and from previous page stock by Pfizer Inc. (NYSE:PFE) (see BioCentury, Oct. 19, 2009).

Back for More Regulatory milestones Like a good book, some investment stories hold their appeal Cell Therapeutics Inc. (NASDAQ:CTIC; Milan:CTIC) on a second reading. That’s why Robert More at Frazier Healthcare gained $0.09 (18%) to $0.63 last week after FDA issued a Ventures led last week’s $56 million series C round for Achaogen complete response letter for an NDA for Pixuvri pixantrone to Inc., after having raised a $26.5 million B round for the antibiotic treat relapsed or refractory aggressive non-Hodgkin’s lymphoma play when he was at Domain Associates in 2006. (NHL). The agency requested an additional to With the latest infusion, Achaogen hopes to get lead candi- demonstrate safety and efficacy (see B7). date ACHN-490 through Phase II trials. The biotech plans to Forest Laboratories Inc. (NYSE:FRX) was off $3.18 (10%) start Phase II testing this quarter for the next-generation to $28.25 last week after FDA’s Pulmonary-Allergy Drugs aminoglycoside antibiotic to treat complicated urinary tract Advisory Committee voted 10-5 that safety and efficacy data do . not provide enough evidence to support the approval of Daxas More, who re-joined Achaogen’s board, told Ebb & Flow that roflumilast for chronic obstructive pulmonary disease (COPD). the company is working in a space “that’s been downplayed by Forest has U.S. rights from Nycomed (see Cover Story). big pharma for a long time,” despite the fact that “the bugs don’t Keryx Biopharmaceuticals Inc. (NASDAQ:KERX) gained stop evolving.” $0.61 (22%) to $3.35 on Monday after FDA granted Fast Track The biotech has several preclinical programs developing designation to perifosine (KRX-0401) to treat advanced, refrac- neoglycosides, next-generation aminoglycoside antibiotics. tory colorectal cancer. Keryx, which gained $0.73 (27%) to All told, the biotech has brought in $96 million in venture $3.47 on the week, has North American rights from Aeterna capital and $65 million from grants and contracts, including one Zentaris Inc. (TSX:AEZ; NASDAQ:AEZS). from the Defense Threat Reduction Agency (DTRA), to work on Aeterna gained C$0.16 (20%) to C$0.96 in Toronto and pathogens for biodefense and biowarfare. $0.15 (19%) to $0.95 on NASDAQ on Monday. For the week, the New investor Alta Partners and existing investors 5AM stock was up C$0.06 to C$0.86 in Toronto and gained $0.08 Ventures; Arch Venture Partners; Domain Associates; Venrock (10%) to $0.88 on NASDAQ. Associates; Versant Ventures; and the Wellcome Trust also participated in the new round. Ebb & Flow Ardea Biosciences Inc. (NASDAQ:RDEA) was up $1.62 Take private, take two to $22.12 last week after the infectious disease, cancer and Xiaochun Wang, chairman and CEO of Tongjitang Chi- inflammation company raised $70 million through the sale of 3.5 nese Medicines Co. (NYSE:TCM), is taking a second shot at million shares at $20 in a follow-on underwritten by Jefferies and taking the company private — this time at less than half the share Oppenheimer (see B14). price previously offered to investors. Shares of Basilea Pharmaceutica AG (SIX:BSLN) could Hanmax Investment Ltd., controlled by Wang and Fosun move on Monday this week, after the company announced late Industrial Co. Ltd., is proposing to pay $1.125 per share or Friday that former partner Johnson & Johnson (NYSE:JNJ) is $4.50 per ADS. In 2008, Wang tried to take the company private discontinuing sales of Zeftera ceftobiprole to treat compli- at $2.55 per share, or $10.20 per ADS. He had to withdraw the cated skin and skin structure infections (cSSSIs) in Canada as proposal due to the deterioration of the credit markets (see of April 16. Basilea said the decision came after discussions BioCentury, June 30, 2008). with Health Canada in response to recent negative regulatory The current offer values the company at $125 million based actions by FDA and the European Medicines Agency (EMA) (see on shares outstanding at Dec. 31. Tongjitang was valued at $334 B4). million when it went public in 2007. The company raised $85 Crucell N.V. (Euronext:CRXL; NASDAQ:CRXL) was off million by selling 8.4 million ADSs at $10. €0.10 to €15.19 on Euronext last week and lost $0.31 to $20.38 Tongjitang’s shares drifted downward after the IPO and then on NASDAQ after the company partnered with GlaxoSmith- nose-dived last June when the plan to take the company private Kline plc (LSE:GSK; NYSE:GSK) to develop a second-genera- was withdrawn. tion . The project will be based on Crucell’s Phase Last week’s proposal is a 19% premium to Tongjitang’s close I AdVac Ad35-CS recombinant malaria vaccine, and GSK’s of $3.78 on April 7, the day before the deal was proposed. Each Phase III Mosquirix malaria vaccine. Terms weren’t disclosed. ADS is equal to 4 shares. Mosquirix uses the QS-21 Stimulon adjuvant from Antigenics Tongjitang markets 37 modernized traditional Chinese medi- Inc. (NASDAQ:AGEN), which was up $0.05 to $0.75 last week. cines and 37 Western medicines. Its lead product is Xianling Dara BioSciences Inc. (NASDAQ:DARA) was off $0.01 to Gubao, an osteoporosis treatment approved in 2002 in China. $0.43 last week after the endocrine, metabolic and neurology Investors bought into the proposal, sending the ADSs up company announced plans to sell up to $10 million in units in a $0.66 (18%) to $4.40 on the week. follow-on underwritten by C.K. Cooper (see B14). Valeant Pharmaceuticals International (NYSE:VRX) lost $0.17 to $43.09 last week after the neurology and dermatol- Buyside tracks ogy company raised $400 million in a bumped-up private place- Robert Essner joined The Carlyle Group as senior advisor ment of 7.625% senior unsecured notes due 2020 (see B14). to its global healthcare group. He was the Chairman and CEO of — Staff Writer Mabel Lam contributed to this week’s Ebb & Flow. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A16 OF 19

Analyst picks & changes

Company Bank Analyst Coverage Opinion Wk chg 4/9 cls Actelion Ltd. (SIX:ATLN) UBS Martin Wales Upgrade Buy (from neutral) 3% CHF49.85 Wales said he thinks the shares have been oversold since Tracleer bosentan failed in the Phase III BUILD-3 trial to treat idiopathic pulmonary fibrosis (IPF) (see BioCentury, March 8). However, Wales lowered his target to CHF55 from CHF58 to reflect a bearish view on the company’s pipeline and weaker sales for Ventavis iloprost, an inhaled prostacyclin analog for pulmonary arterial hypertension (PAH), partnered with Bayer AG (Xetra:BAY). Celgene Corp. Baird Christopher Raymond Price target Market outperform 0% $61.89 (NASDAQ:CELG) Jefferies Thomas Wei Downgrade Hold (from buy) Raymond raised his target to $70 from $65 after Celgene held its R&D day. He was “impressed” by the company’s “increasingly diverse and robust pipeline.” Raymond believes there is upside with Phase III data of Revlimid lenalidomide as maintenance therapy for multiple myeloma (MM) following autologous stem cell transplantation to be presented at the American Society of Clinical Oncology (ASCO) meeting in June. The thalido- mide analog is approved for MM in the U.S. and Europe and for myelodysplastic syndromes (MDS) with 5q chromosomal deletion in the U.S. Wei said the upside has already been priced into the company’s valuation. Forest Laboratories Inc. Baird Thomas Russo Price target Neutral -10% $28.25 (NYSE:FRX) Jefferies Corey Davis Price target Buy Lazard William Tanner Downgrade Hold (from buy) Summer Street Jon Stephenson Price target Buy Wedbush Patricia Bank Price target Neutral Russo lowered his target to $33 from $34 after FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 10-5 that safety and efficacy data do not provide substantial evidence to support the approval of Daxas roflumilast for chronic obstructive pulmonary disease (COPD). The PDUFA date for the oral phosphodiesterase-4 (PDE-4) inhibitor, which is partnered with Nycomed, is in May (see Cover Story). Davis lowered his target to $34 from $42 on the Daxas news. He thinks the compound still will be approved and launched in 2011, however, he believes its commercial potential to be “dramatically lower” because of the psychiatric adverse events, which were not previously disclosed. Tanner also lowered his target to $32 from $34 on the Daxas news. Stephenson lowered his target to $40 from $43 on the Daxas panel vote. He now believes the product won’t be launched until FY12. Bank lowered her target to $33 from $35 on the Daxas news. Pharmasset Inc. JMP Securities Liisa Bayko Price target Market outperform 0% $27.33 (NASDAQ:VRUS) Lazard Terence Flynn Price target Buy Bayko raised her target to $35 from $27 after meeting with management. She thinks lack of news from a Phase IIb trial of RG7128 (formerly R7128) to treat HCV indicates that there are no safety issues and derisks the company. Bayko increased the probability of RG7128 reaching the market to 50% from 35%. She expects final data for RG7128 in 3Q11. The compound is a prodrug of PSI-6130, a cytidine nucleoside analog non-structural protein 5B (NS5B) polymerase inhibitor partnered with Roche (SIX:ROG; OTCQX:RHHBY). Flynn raised his target to $35 from $28. He thinks PSI-7977 and RG7128 are highly attractive HCV assets that could become central components of all oral combination regimens given their potential. PSI-7977 is the single isomer form of PSI-7851, a nucleotide analog polymerase inhibitor, and is in Phase IIa testing. Preliminary data for PSI-7977 are expected next quarter. Sequenom Inc. Wedbush Zarak Khurshid New Underperform -4% $6.10 (NASDAQ:SQNM) Khurshid set a $0.50 target, saying he has “significant reservations” about the stock due its “inconsistent track record, lack of visibility into R&D missteps, dearth of publications, financing risk, and competitive threats.” In February, the company launched its SensiGene Fetal RHD Genotyping test to diagnose fetal Rhesus D (RhD) incompatibility in RhD-negative pregnant women and SensiGene Fetal (XY) test determine the sex of the fetus during the first trimester of pregnancy, but Khurshid noted competitors have had tests on the market for about two years and the “opportunities remain small.” United Therapeutics Corp. Summer Street Jon Stephenson Upgrade Buy (from neutral) 5% $57.75 (NASDAQ:UTHR) Stephenson also set a $68 target after a survey of 30 physicians showed they favor United Therapeutics’ Tyvaso treprostinil over Ventavis iloprost from Actelion Ltd. (SIX:ATLN) and Bayer AG (Xetra:BAY) to treat pulmonary arterial hypertension (PAH) on multiple metrics. The survey also suggested the inhaled market is expected to grow by 30-65% over the next year, with Tyvaso gaining the leading share over Ventavis within the next six months. Ventavis and Tyvaso are inhaled prostacyclin analogs. Valeant Pharmaceuticals Jefferies Corey Davis Price target Buy 0% $43.09 International (NYSE:VRX) Davis raised his target to $54 from $49. He thinks management has executed a two-year turnaround and expects Street estimates will continue to rise. Davis raised his FY10 and 1Q10 EPS estimates to $2.74 and $0.60 from $2.70 and $0.57, respectively. The company’s is under FDA review as an adjunctive therapy for partial-onset seizures in adults with epilepsy. The potassium channel opener and potentiator of GABA is partnered with GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) and has an Aug. 30 PDUFA date. BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A17 OF 19 BioCentury 100 Price & Volume Trend Price Gains Cumulative weekly performance of 100 bioscience stocks. 12-week period. Stocks with greatest % price increase in the week ended April 9. Line shows Price Level change (Left scale. Index base=1000 on May 10, (Priced above $2; 5,000 minimum share volume) 1996). Bars show cumulative volume in millions (right scale). Company Ticker $Close $Chg %Chg Vol(00) Rexahn RNN 2.650 1.020 63% 143201 Gentium1 GENT 5.100 1.530 43% 41397 Geneart G6A €13.20 €2.99 29% 715 Keryx KERX 3.470 0.730 27% 432458 Response Genetics RGDX 2.350 0.491 26% 1728 Symyx SMMX 5.610 1.140 26% 18987 Avanir AVNR 3.270 0.610 23% 141932 SciClone SCLN 4.250 0.720 20% 34826 BioCryst BCRX 8.190 1.360 20% 59041 Idenix IDIX 3.380 0.530 19% 9827 pSivida2 PSDV 4.700 0.710 18% 7736 Tongjitang3 TCM 4.400 0.660 18% 31208 Price Declines Stocks with greatest % price decline (criteria as above). BioCentury London Index Company Ticker $Close $Chg %Chg Vol(00) 4 Weekly change in the combined market capitalization for 14 bioscience MediciNova MNOV 6.430 -1.080 -14% 1589 stocks listed on the LSE or AIM, 12-week period. Index base =1000 on Vermillion VRML 24.750 -3.650 -13% 5700 May 10, 1996. 3SBio5 SSRX 10.800 -1.200 -10% 23466 CPEX CPEX 15.590 -1.610 -9% 1285 Paion PA8 €2.278 -€0.222 -9% 3608 EpiStem EHP 405p -30p -7% 314 CombiMatrix CBMX 4.680 -0.310 -6% 826 Orexigen OREX 5.630 -0.360 -6% 30016 Apr 9 Synta SNTA 4.420 -0.270 -6% 5635 Gen-Probe GPRO 48.030 -2.870 -6% 21453 Volume Gains Greatest changes in volume above 5,000 shares. Company Ticker Vol(00) %Chg $Close $Chg EpiStem EHP 314 5361% 405p -30p Tongjitang3 TCM 31208 1779% 4.400 0.660 Keryx KERX 432458 1427% 3.470 0.730 MediBIC 2369 65 1038% ¥8950 ¥2060 Thomson Reuters Life Sciences Indexes Pronova PRON 10414 741% NOK19 -NOK0.1 Algeta ALGETA 7413 585%NOK66.75NOK5.25 Weekly change in combined market capitalization. 12-week period. Tier Rexahn RNN 143201 523% 2.650 1.020 I = market caps>$1B; Tier II <$1B. Base =100 on Dec. 31, 1998. Photocure PHO 1046 481%NOK44.8 -NOK0.2 DUSA DUSA 10801 480% 2.080 0.260 Tier II (180 companies) Acura ACUR 8610 436% 6.000 0.450 Talecris TLCR 32090 387% 21.890 2.020 1 Volume figure is of ADS (ADS = 1 share) 2 Includes volume from ASX 3 Volume figure is of ADSs (ADS = 4 shares) Apr 9 4 Includes volume from Osaka Stock Exchange 5 Volume figure is of ADSs (ADS = 7 shares) BioCentury 100 Advance-Decline Trend BC100 BC100 BC100 Week Price Stocks Gaining Stocks Declining Tier I (20 companies) ended level gaining vol. (00) declining vol. (00) Source: Thomson Reuters Mar 12 1971.05 71 8249679 29 3074144 BioCentury tracks 562 issues that report prices and volume daily. The Mar 19 1980.93 47 4103555 53 6937333 BioCentury 100 is a subset used to monitor price and volume trends. Thomson Mar 26 1982.38 47 3567831 49 9776458 Reuters Life Sciences Indexes are compiled by Thomson Reuters, provider of Apr. 02 1984.38 53 3397192 46 3974496 market intelligence services to publicly held companies. Apr 09 2001.04 63 11225551 37 1797378 BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A18 OF 19 Online links this week

™ Links to the following documents reside online on the BioCentury Extra BioCentury page within the Publications section of www.biocentury.com. BioCentury’s mission is to provide value-added business information & Biosimilars analysis for life science companies, investors, academia and government on the strategic issues essential to the formation, development and European Medicines Agency (EMA) concept papers on similar sustainability of life science ventures. biological products containing recombinant follicle stimulation hormone (FSH) and recombinant Interferon (IFN) beta. BioCentury Publications, Inc. Healthcare professionals’ BioCentury International Inc. Revised 2010 work plan for the CHMP’s Working Group with Main Offices Healthcare Professionals’ Organizations. PO Box 1246 PDUFA San Carlos CA 94070-1246 +1 650-595-5333; Fax: +1 650-595-5589 FDA webinar to inform stakeholders about the PDUFA program. Chicago: +1 312-755-0798; Fax: +1 312-755-0658 Pharmacovigilance Washington, DC: +1 202-462-9582; Fax: +1 202-667-2922 European Medicines Agency (EMA) 15th pandemic pharmaco- Oxford, UK: +44 (0)1865-512184; Fax: +44 (0)1865-311195 vigilance weekly update. Transparency www.biocentury.com HHS Open Government Plan, which details the agency’s steps to Corporate make itself more transparent (see BioCentury Extra, Wednesday, Karen Bernstein, Ph.D., Chairman & Editor-in-Chief April 7). David Flores, President & CEO Product documentation Thomas C. Carey, Vice President/Commercial Operations Bennet Weintraub, Vice President/Administration & CFO — Altargo: CHMP revised EPAR updating the SPC to reflect data Kris Hall, Executive Administrator from a pediatric pharmacokinetics study for Altargo retapamulin to treat impetigo, infected small lacerations, abrasions or sutured Eric Pierce, Publisher wounds, from GlaxoSmithKline plc (LSE:GSK; NYSE:GSK). Tim Tulloch, Associate Publisher — Daxas: Briefing documents for the April 7 meeting of FDA’s Julia Kulikova, Director/Production & Information Services Pulmonary-Allergy Drugs Advisory Committee, which voted 10- Susan Morgan, Director/Administration & Human Resources 5 that safety and efficacy data do not provide substantial Jennifer Policky, Director/Data Solutions evidence to support the approval of Daxas roflumilast to treat Jenny Nichols, Production chronic obstructive pulmonary disease (COPD), from Forest Laboratories Inc. (NYSE:FRX) and Nycomed (see Cover Story). Subscriber Services — Rotarix: FDA notice of a May 7 public advisory committee Subscriber Services: [email protected] meeting of the agency’s Vaccines and Related Biological Products Strategic Account Director: Diana Cabral Advisory Committee on the presence of DNA from porcine Account Managers: Orlando Abello, Michelle Ortega, Graham Pairman, Ron Rabinowitz circovirus type 1 in batches of Rotarix oral vaccine to prevent gastroenteritis due to rotavirus , from GlaxoSmithKline plc (LSE:GSK;NYSE:GSK). Business Services Accounting & Billing: [email protected] Conferences: [email protected] BioCentury Anthera (NASDAQ:ANTH) B14, Data Solutions Support: [email protected] Company Index B15 Privacy Policy: [email protected] Antigenics (NASDAQ:AGEN) Reprints/Permissions: [email protected] April 12, 2010 A15, B2 AcelRx B6 Apieron B5 Privacy & Advertising Achaogen B6, B14 Applied Pharma Res B4 In accordance with its Privacy Policy, BioCentury does NOT sell or Actelion (SIX:ATLN) A16, B4 Ardea (NASDAQ:RDEA) A15, rent its customer information or usage data to third parties. Aerocrine B5 B14 BioCentury does NOT sell advertising in any of its publications. Aeterna Zentaris (TSX:AEZ; Asahi (Tokyo:3407) A11, B2 BioCentury is pleased to acknowledge its conference partners and NASDAQ:AEZS) A14, B7, B11 Astellas (Tokyo:4503) A14, B11 sponsors through promotional announcements in its publications and on Agency for Sci, Tech & Res( A8 AstraZeneca (LSE:AZN; NYSE: its website, but such announcements do not constitute paid advertising. Alimera B15 AZN) A10, B5 Allon (TSX:NPC) B7 Aushon Bio B4 Altana (Xetra:ALT) A3 Axerion B14 Altheos A11, B2, B6, B14 See next page BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS APRIL 12, 2010 PAGE A19 OF 19

Company Index, Pervasis Therap B12 from previous page Pfizer (NYSE:PFE) A9, A15, B2, The search for intelligent life B3, B9 Basilea (SIX:BSLN) A15, B4 PharmaJet B3 Baxter (NYSE:BAX) B6 We know you have many choices for PharmAthene (NYSE-A:PIP) B6 Bayer (Xetra:BAY) A16 headlines. But finding real intelligence is a lot PhytoMedical (OTCBB:PYTO) BioAlliance (Euronext:BIO) B4 B15 Biocartis B2, B6, B14 harder. That’s why top managers and P&G (NYSE:PG) B5 Biogen Idec (NASDAQ:BIIB) B8, investors in the life sciences community Prometheus B5 B11 depend on BioCentury, the Bernstein Report Protein Bio B4 BioServe B4 on BioBusinessTM for its leading perspective on pSivida (NASDAQ:PSDV; ASX: Biota ASX:BTA) B6 the strategic issues essential to the formation, PVA) B11 Calistoga Pharma B11 Purdue Pharma B8 Carlyle Group A15 development and sustainability of life science Quest (TSX-V:QPT) B12 Celgene (NASDAQ:CELG) A16, ventures in 2010 and beyond. RegeneRx (NYSE-A:RGN) B15 B8, B11 ‘It’s the BioCentury’TM Repros (NASDAQ:RPRX) B13 Cell Therap (NASDAQ:CTIC; Roche (SIX:ROG; OTCQX: Milan:CTIC) B7 RHHBY) A7, A8, A16, B10, Celldex (NASDAQ:CLDX) B7 B11, B13 Cellestis (ASX:CST) B8, B10 Rosetta (NASDAQ:ROSG) B5 Cell Therap A15 Epix (Pink:EPIX) B5 Map (NASDAQ:MAPP) B12 sanofi-aventis (Euronext:SAN; Celltrion B4 EUSA A10 MIT A12 NYSE:SNY) B2, B5, B10 Celprogen B10 Fate Therap B3 MDRNA (NASDAQ:MRNA) B3 Seattle Genetics (NASDAQ: Celtic Pharma B5 Fed Ministry of Educ and Res B3 Medivation (NASDAQ:MDVN) A9 SGEN) B13 Cempra B6 FDA A2 Merck KGaA (Xetra:MRK) A13, Sequenom (NASDAQ:SQNM) A16 Ctre of Excellence B3 Forest (NYSE:FRX) A1, A15, A16, B3, B5, B9, B13 Selecta A12 Cephalon (NASDAQ:CEPH) B2, A18, B7 MGB Bio B14 Shire (LSE:SHP; NASDAQ: B11 Fosun Indust B3 MicuRx B2 SHPGY) A10 Cepheid (NASDAQ:CPHD) B4 Fraunhofer USA Center for Mo- Miraculins (TSX-V:MOM) B14 Simcere (NYSE:SCR) B8 Ception Therap B2 lecular Bio B3 Mitsubishi (Tokyo:4508; Osaka: Singapore Health Svcs A8 Ceregene B11 Genentech A7, A8 4508) B7, B10 Source Bio (LSE:SBS) B5 Cerus (NASDAQ:CERS) B14 Genta (OTCBB:GETA) B7 Mologen (Xetra:MGN) B3 Stanford U A11 Children’s Med Ctr of Dayton A5 GlaxoSmithKline (LSE:GSK; MonoSol B4 Sunesis (NASDAQ:SNSS) B15 Chronix Biomedical B9 NYSE:GSK) A10, A15, A16, A18, Mundipharma A13, B3, B11 Swedish Orphan Bio (SSE:BVT) B5 CoMentis A11 B2, B3, B6, B7 Nabi (NASDAQ:NABI) B5 SymBio Pharma B11 Connexios Life Sci A10 Graceway Pharma B6 Nanyang Tech U A8 Synvolux B3 Cosmo (SIX:COPN) A10 H. Lundbeck (CSE:LUN) B12 NasVax (Tel Aviv:NSVX) A14 Takeda (Tokyo:4502) B13 Critical Outcome Tech (TSX- Hanmax B3 Natl Healthcare Group A8 Tengion (NASDAQ:TNGN) A13, V:COT) B10 Harvard Med Schl A12 Natl U Hospital A8 B14 Crucell (Euronext:CRXL; Hikma (LSE:HIK) B4 Natl U of Singapore A8 tesa B4 NASDAQ:CRXL) A!5, B2 Horizon A13, B3 Nektar (NASDAQ:NKTR) B12 Therabel B4 Cryo-Cell Intl (OTCBB:CCEL) iBio (OTCBB:IBPM) B3 Neovacs A13, B12, B15 Tioga Pharma B13 B10 Illumina (NASDAQ:ILMN) B4 Netherlands Vaccine Inst B3 Tongjitang (NYSE:TCM) A15, B3 Cumencor B2 Immunovaccine (TSX-V:IMV) B10 NeurogesX (NASDAQ:NGSX) B4 TopoTarget (CSE:TOPO) B6 CureDM B2 Independent Pharmaceutica B5 Newron (SIX:NWRN) A10 Tragara Pharma B13 Cytokinetics (NASDAQ:CYTK) InnoPharmax B11 Nile (NASDAQ:NLTX) B15 U.K. Dept of Health B6 A8 Inovio (NYSE-A:INO) B12 Nitec Pharma B3 U.S. Dept of Defense B3 Cytos (SIX:CYTN) B5 Invida Group B4 Novartis (NYSE:NVS; SIX:NOVN) United Therap (NASDAQ:UTHR) Daiichi (Tokyo:4568; Osaka: J&J (NYSE:JNJ) A15, B4, B10 B2, B5, B7 A16 4568) B7 Juventas B12 NPS (NASDAQ:NPSP) A14 U of California A4 Dara (NASDAQ:DARA) A15, B14 Keryx (NASDAQ:KERX) A14, Nycomed A2, A15, A16, A18, U of Florida A6 Debiopharm B2 B7, B11 B6, B7, B8 U of Texas Med Branch A6 Deinove A13, B15 King (NYSE:KG) B11 Odyssey Thera B4 U of Virginia Med Ctr A3 Dendreon (NASDAQ:DNDN) B6 Koronis B9 Ohio State U A4 U of Washington A4 DRI Capital B15 Kyoma (Tokyo:4151) A14 Ondine (TSX:OBP) B14 Valeant (NYSE:VRX) A15, A16, Durect (NASDAQ:DRRX) B11 Labtec B4 Oraya Therap B8 B14 Dyax (NASDAQ:DYAX) B9, B15 Life Expectancy Project A6 Ore (Pink:ORXE) B15 Verio Therap B3 Eisai (Tokyo:4523; Osaka:4523) Living Cell (ASX:LCT; OTCQX: OSI (NASDAQ:OSIP) B13, B15 Vertex (NASDAQ:VRTX) B10 A10, B5, B11 LVCL) B9 Osta (TSX-V:OBI) B14 ViraCor-IBT B8 Elan (NYSE:ELN) B8 Lonza (SIX:LONN) B4 Oxford Immunotec B9, B10 Vivalis (Euronext:VLS) B3 EMA A18 Lorus (TSX:LOR) B14 OxiGene (NASDAQ:OXGN; SSE: Warner Chilcott (NASDAQ: Emory U B9 Los Alamos Med Ctr Clinic A6 OXGN) B15 WCRX) B5 Entest (OTCBB:ENTB) B6 Luminex (NASDAQ:LMNX) B3 Patheon (TSX:PTI) B14 Ziopharm (NASDAQ:ZIOP) B6 ON MAY 3 CONNECT WITH PEOPLE AND IDEAS THAT CAN SAVE LIVES IN THE DEVELOPING WORLD

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)RU%,2FXVWRPHUVHUYLFHSOHDVHFDOO 86 RU ,QWHUQDWLRQDO RUHPDLOELRSDUWQHULQJ#ELRRUJ WEEK OF APRIL 12, 2010 BioCenturyPartII ESSENTIAL SURVEILLANCE FOR BIOTECH & PHARMA Volume 18 • Number 17 • Page B1 of 15 BioBusiness for the week ended April 9

Ziopharm (NASDAQ:ZIOP) COMPANY NEWS Using BioCentury Part II CLINICAL NEWS Deals (Page B2) BioCentury Part II is a comprehensive compendium of business news for man- Altheos/Asahi Kasei (Tokyo:3407) agement and investors in bioscience com- Regulatory (Page B7) Biocartis/Debiopharm panies. It is organized into three depart- Aeterna (TSX:AEZ; NASDAQ:AEZS)/Keryx Cephalon (NASDAQ:CEPH)/Ception ments: Company News, Clinical News and (NASDAQ:KERX) Crucell (Euronext:CRXL; NASDAQ:CRXL)/ Financial News. Allon (TSX:NPC) GlaxoSmithKline (LSE:GSK; NYSE:GSK) The index on this page lists all the Cell Therap (NASDAQ:CTIC; Milan:CTIC) Cumencor/MicuRx/Pfizer (NYSE:PFE) companies covered this week. The news Celldex (NASDAQ:CLDX)/GlaxoSmithKline CureDM/sanofi-aventis (Euronext:SAN; items in each department are organized (LSE:GSK; NYSE:GSK) NYSE:SNY) alphabetically by company. When more Daiichi (Tokyo:4568; Osaka:4568) Fate Therap/Verio Therap than one company is listed, the biotech Forest (NYSE:FRX)/Mitsubishi (Tokyo:4508; Horizon Therap/Nitec Pharma company is shown first. Each brief is la- Osaka:4508)/Nycomed iBio (OTCBB:IBPM)/Fraunhofer USA Ctr/U.S. beled with one or more applicable busi- Genta (OTCBB:GETA)/Daiichi (Tokyo:4568; Dept of Defense ness categories from the following list: Osaka:4568) Luminex (NASDAQ:LMNX)/Ctre of Excellence ADMET; Agbio/Environmental; Anti- Mitsubishi (Tokyo:4508; Osaka:4508)/Novartis MDRNA (NASDAQ:MRNA)/Pfizer (NYSE:PFE) bodies; Autoimmune; Bioinformatics; (NYSE:NVS; SIX:NOVN) Mologen (Xetra:MGN)/Synvolux Therap Biomanufacturing; Biopharmaceuticals; Nycomed PharmaJet/Netherlands Vaccine Inst Biosimilars; Cancer; Cardiovascular; Oraya Therap Tongjitang (NYSE:TCM)/Fosun/Hanmax Chemistry; Combinatorial biology; Com- Purdue Pharma Vivalis (Euronext:VLS)/GlaxoSmithKline putational chemistry/biology; Dental; Der- Simcere (NYSE:SCR) (LSE:GSK; NYSE:GSK) matology; Diagnostic; Drug delivery; En- Clinical Results (Page B8) Sales & Marketing (Page B4) docrine; Finance; Functional genomics; Gastrointestinal; Gene/Cell therapy; Ge- Biogen Idec (NASDAQ:BIIB)/Elan (NYSE:ELN) Actelion (SIX:ATLN)/Invida Group nerics; Genitourinary; Genomics; Hema- Celgene (NASDAQ:CELG) Aushon tology; Hepatic; High throughput screen- Cellestis (ASX:CST) Basilea (SIX:BSLN)/J&J (JNJ) ing; Infectious; Inflammation; Metabolic; Chronix Bio BioAlliance (Euronext:BIO)/Therabel Microarrays; Microfluidics; Musculoskel- Dyax (NASDAQ:DYAX) BioServe/Protein Bio etal; Neurology; Nutraceuticals; Oph- Emory U Celltrion/Hikma (LSE:HIK) thalmic; Other; Pharmaceuticals; Pharma- Koronis Pharma Cepheid (NASDAQ:CPHD) cogenetics; Proteomics; Pulmonary; Re- Living Cell (ASX:LCT; OTCQX:LVCLY) Illumina (NASDAQ:ILMN) nal; Supply/Service; Transplant; Veterinary Merck KGaA (Xetra:MRK)/Pfizer (NYSE:PFE) Lonza (SIX:LONN)/Odyssey Thera Oxford Immunotec NeurogesX (NASDAQ:NGSX) sanofi-aventis (Euronext:SAN; NYSE:SNY) Prometheus Labs/Rosetta (NASDAQ:ROSG) GlaxoSMithKline (LSE:GSK; NYSE:GSK)/U.K. Vertex (NASDAQ:VRTX)/Mitsubishi (Tokyo: Source BioSci (LSE:SBS)/AstraZeneca (LSE: Dept of Health 4508; Osaka:4508)/J&J (NYSE:JNJ) AZN; NYSE:AZN) Graceway Pharma Swedish Orphan Biovitrum (SSE:BVT)/Merck TopoTarget (CSE:TOPO) Preclinical Results (Page B10) KGaA (Xetra:MRK) Celprogen Warner Chilcott (NASDAQ:WCRX)/sanofi- Management Tracks (Page B6) Critical Outcome Tech (TSX-V:COT) aventis (Euronext:SAN; NYSE:SNY) AcelRx Cryo-Cell Intl (OTCBB:CCEL) Achaogen Other News (Page B5) Immunovaccine (TSX-V:IMV) Altheos pSivida (NASDAQ:PSDV; ASX:PVA) Apieron Biocartis Cytos (SIX:CYTN)/Independent Pharma/Nabi Cempra Clinical Status (Page B11) (NASDAQ:NABI)/Novartis (NYSE:NVS; Dendreon (NASDAQ:DNDN) Aeterna Zentaris (TSX:AEZ; NASDAQ:AEZS)/ SIX:NOVN)/Celtic Pharma Entest (OTCBB:ENTB) Keryx (NASDAQ:KERX) Epix (Pink:EPIX) PharmAthene (NYSE-A:PIP) See next page BioCentury Part II APRIL 12, 2010 PAGE B2 OF 15

COMPANY NEWS/Deals, Sales & Marketing, Other News, Management Tracks

Crucell N.V. (Euronext:CRXL; NASDAQ:CRXL), Leiden, the Nether- DEALS lands GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. Altheos Inc., South San Francisco, Calif. Business: Infectious Asahi Kasei Pharma Corp. (Tokyo:3407), Tokyo, Japan Crucell and GSK partnered to develop a second-generation malaria Business: Ophthalmic vaccine. Crucell will contribute its AdVac Ad35-CS recombinant malaria Asahi Kasei granted Altheos exclusive, worldwide rights, excluding vaccine, and GSK will contribute its Mosquirix malaria vaccine. Ad35- Japan and Korea, to develop and commercialize ATS907 for all indica- CS, which is based on Crucell’s AdVac adenovirus technology and tions. ATS907, a Rho kinase inhibitor, is in preclinical development to PER.C6 manufacturing platform, is in Phase I trials in the U.S. Mosquirix, treat glaucoma. The license also includes Asahi’s AK138 series of small which utilizes RTS,S peptide and TRAP sporozoite antigen together molecule Rho kinase inhibitors to treat glaucoma and other ophthalmic with the QS-21 Stimulon adjuvant from Antigenics Inc. (NASDAQ:AGEN, indications. Financial terms were not disclosed. New York, N.Y.), is in Phase III testing. The partners plan to begin a U.S. Phase I/IIa trial of the vaccine combination when they secure third-party Biocartis S.A., Lausanne, Switzerland funding. Financial terms were undisclosed. Debiopharm S.A., Lausanne, Switzerland Business: Diagnostic Cumencor Pharmaceuticals Inc., Shanghai, China The companies partnered to develop companion diagnostics for MicuRx Pharmaceuticals Inc., Union City, Calif. cancer and infectious disease therapies developed by Debiopharm. Pfizer Inc. (NYSE:PFE), New York, N.Y. Debiopharm said the initial focus would be HCV and include alisporivir Business: Infectious (Debio 025). Debiopharm will be responsible for identifying and MicuRx and Cumencor partnered with Pfizer to discover and providing biomarkers, while Biocartis will develop the test using its develop antibiotics to treat multi-drug resistant tuberculosis (MDR- molecular diagnostic platform. IP ownership will be determined by TB) using MicuRx’s combinatorial and medicinal chemistry technology. inventorship. Financial terms were not disclosed. Debiopharm also MicuRx and Cumencor will be responsible for discovery and develop- participated in Biocartis’ €30 million ($40.5 million) series B round as ment, with all research taking place at ZhangJiang High-Tech Park in a new investor (see BioCentury, Feb. 15). Shanghai. Pfizer will receive an exclusive, worldwide license to develop In February, Debiopharm granted Novartis AG (NYSE:NVS; and commercialize resulting antibiotics, and will provide an upfront SIX:NOVN, Basel, Switzerland) exclusive, ex-Japanese rights to payment and funding for discovery and preclinical development. The alisporivir, a cyclophilin inhibitor that is in Phase IIb testing for HCV. pharma also will make development and commercialization payments, and pay any resulting royalties. Further terms were not disclosed. Cephalon Inc. (NASDAQ:CEPH), Frazer, Pa. Ception Therapeutics Inc., Malvern, Pa. CureDM Inc., Wilmington, Del. Business: Inflammation sanofi-aventis Group (Euronext:SAN; NYSE:SNY), Paris, Cephalon completed its previously announced acquisition of Business: Endocrine Ception for $250 million in cash. Former Ception shareholders are CureDM granted sanofi-aventis an exclusive, worldwide license to eligible for undisclosed clinical and regulatory milestones (see BioCentury, develop and commercialize Pancreate proisletide, which is in develop- March 1). See next page

Clinical Status, Tioga Pharma Proposed Offerings (Page B14) from previous page Tragara Pharma Dara (NASDAQ:DARA) Lorus (TSX:LOR) Calistoga Pharma FINANCIAL NEWS Nile (NASDAQ:NLTX) Cephalon (NASDAQ:CEPH)/InnoPharmax/ PhytoMedical (OTCBB:PYTO) SymBio/Astellas (Tokyo:4503)/Eisai (To- Completed Offerings (Page B14) kyo:4523; Osaka:4523)/Mundipharma Amended Offerings (Page B15) Achaogen Ceregene Alimera Altheos Durect (NASDAQ:DRRX)/King (NYSE:KG) Deinove Anthera (NASDAQ:ANTH) H. Lundbeck (CSE:LUN) Neovacs Inovio (NYSE-A:INO) Ardea (NASDAQ:RDEA) Juventas Therap Axerion Other Financial News (Page B15) Biocartis Map (NASDAQ:MAPP)/Nektar (NASDAQ: Anthera (NASDAQ:ANTH) Cerus (NASDAQ:CERS) NKTR) DRI Capital MGB Biopharma Neovacs Dyax (NASDAQ:DYAX) Miraculins (TSX-V:MOM) Pervasis Therap Ore (Pink:ORXE) Ondine (TSX:OBP) Quest (TSX-V:QPT) OSI (NASDAQ:OSIP) Osta (TSX-V:OBI) Repros (NASDAQ:RPRX) OxiGene (NASDAQ:OXGN; SSE:OXGN) Patheon (TSX:PTI) Seattle Genetics (NASDAQ:SGEN)/Takeda RegeneRx (NYSE-A:RGN) Tengion (NASDAQ:TNGN) (Tokyo:4502) Sunesis (NASDAQ:SNSS) Valeant (NYSE:VRX) BioCentury Extra: Online every business day. BioCentury Part II APRIL 12, 2010 PAGE B3 OF 15

Deals, discovered and internally validated blood-based proteomic and ge- from previous page nomic biomarker tests to diagnose and predict allograft immune rejection. It hopes to seek regulatory approval for the tests next year. ment for Type I and Type II diabetes. This year, sanofi-aventis plans to Further terms were not disclosed. begin Phase I trials of the human proislet peptide that stimulates formation of insulin producing islet cells from pancreatic progenitor MDRNA Inc. (NASDAQ:MRNA), Bothell, Wash. cells. CureDM could receive as much as $335 million, plus tiered Pfizer Inc. (NYSE:PFE), New York, N.Y. royalties. Further terms were not disclosed. Business: Drug delivery MDRNA will formulate Pfizer oligonucleotides using its di-alky- Fate Therapeutics Inc., San Diego, Calif. lated amino acid (DiLA2) delivery technology for preclinical evaluation Verio Therapeutics Inc., Ottawa, Ontario to be performed by Pfizer. MDRNA also will design and synthesize Business: Gene/Cell therapy, Cardiovascular, Endocrine UsiRNAs against targets selected by Pfizer. UsiRNAs are duplex small Fate acquired Verio for an undisclosed amount. Fate said Verio’s interfering RNAs (siRNAs) modified with non-nucleotide acyclic mono- biologics capabilities and preclinical programs complement its pipeline mers. Further terms were undisclosed. of stem cell modulators. Verio’s pipeline includes candidates for promoting the growth of new insulin-producing beta cells to treat Mologen AG (Xetra:MGN), Berlin, Germany diabetes and for regenerating cardiomyocytes following heart attack to Synvolux Therapeutics B.V., Groningen, the Netherlands treat severe cardiac dysfunction. Federal Ministry of Education and Research, Bonn, Germany Fate’s FT1050, a small molecule prostaglandin E2 analog, is in Phase Business: Infectious Ib testing for hematopoietic stem cell (HSC) support in patients with The companies partnered to develop a DNA vaccine to treat and hematologic malignancies undergoing non-myeloablative therapy. prevent HBV infection using Mologen’s MIDGE DNA vectors against HBV and Synvolux’s SAINT transfection reagent as an adjuvant. Mologen Horizon Therapeutics Inc., Skokie, Ill. said it expects to complete preclinical testing by the end of 2012. The Nitec Pharma AG, Reinach, Switzerland German Federal Ministry of Education and Research will fund 50% of Business: Autoimmune, Neurology, Inflammation Mologen’s portion of the project, or about €280,000 ($377,748), with The companies merged in a stock deal to form Horizon Pharma Inc. Mologen funding the remaining portion. IP ownership resulting from Horizon Therapeutics President and CEO Timothy Walbert will be the deal was not disclosed. chairman, president and CEO of the newco, which will be headquar- tered in Northbrook, Ill. Financial terms of the merger were not PharmaJet Inc., Golden, Colo. disclosed. Netherlands Vaccine Institute, Bilthoven, the Netherlands The combined company’s pipeline includes Nitec’s Lodotra and Business: Drug delivery, Infectious Horizon’s Duexa (formerly HZT-501). The newco expects to submit PharmaJet and the institute partnered to evaluate PharmaJet’s intra- an NDA in the U.S. for Lodotra next half. The modified-release oral dermal needle-free delivery technology with the institute’s marketed tablet of low-dose prednisone is already marketed in Europe to reduce Salk inactivated (IPV). The partners will share expenses morning stiffness associated with rheumatoid arthritis. Merck KGaA and conduct the trials, which would include non-inferiority studies, (Xetra:MRK, Darmstadt, Germany) has marketing rights to Lodotra in with testing expected this year. Further financial terms were not Germany and Austria and Mundipharma International Ltd. (Cambridge, disclosed. U.K.) has rights in the rest of Europe. Horizon submitted an NDA to FDA for Duexa, a fixed-dose Tongjitang Chinese Medicines Co. (NYSE:TCM), Shenzhen, China combination of 800 mg ibuprofen and 26.6 mg famotidine and expects Fosun Industrial Co. Ltd., Hong Kong, China to submit an MAA in the EU next half. Bank of America Merill Lynch Hanmax Investment Ltd., British Virgin Islands advised Horizon. JMP Securities LLC advised Nitec. Business: Musculoskeletal, Neurology, Dermatology Hanmax, a company controlled by Tongjitang Chairman and CEO iBio Inc. (OTCBB:IBPM), Newark, Del. Xiaochun Wang, and Fosun proposed to acquire all outstanding shares Fraunhofer USA Center for Molecular Biotechnology, Newark, of Tongjitang for $1.125 per share or $4.50 per ADS. The proposal Del. values the musculoskeletal, neurology and dermatology company at U.S. Department of Defense, Washington, D.C. $125 million based on 111.1 million shares outstanding at Dec. 31, 2009. Business: Infectious The price is a 19% premium to Tongjitang’s close of $3.78 on April 7, iBio granted the not-for-profit center a research license to use its the day before the deal was proposed. Each ADS is equal to 4 shares. iBioLaunch plant-based biomanufacturing technology for a combination In 2008, Wang and Yongcun Chen, a Tongjitang director, withdrew vaccine to protect against anthrax and plague. The center is developing a proposal to acquire all outstanding shares of the company for $2.55 the vaccine, which is in preclinical testing, as part of a $5.3 million per share, or $10.20 per ADS, citing the deterioration of the credit program funded by the DoD’s Defense Threat Reduction Agency. In markets. Tongjitang markets nearly 80 modernized traditional Chinese 2004, iBio acquired the technology from the center. iBio will own the medicines and Western medicines. Its lead product is Xianling Gubao, vaccine-related IP. Financial terms were not disclosed. an osteoporosis treatment approved in 2002 in China (see BioCentury, June 30, 2008). Luminex Corp. (NASDAQ:LMNX), Austin, Texas The Centre of Excellence for the Prevention of Organ Failure, Vivalis (Euronext:VLS), Nantes, France Vancouver, B.C. GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. Business: Pharmacogenetics Business: Infectious Luminex and the not-for-profit PROOF Centre partnered to de- Vivalis received an undisclosed milestone payment from velop biomarker tests for heart and kidney transplant patients. The GlaxoSmithKline under a 2007 deal to use Vivalis’ avian embryonic stem tests will be run on Luminex’s xMAP technology. PROOF said it has See next page BioCentury Part II APRIL 12, 2010 PAGE B4 OF 15

Deals, investment in BioAlliance at €5.89. The price is a 15% premium to the from previous page stock’s 20-day trading average. Therabel plans to make a second €3 million investment at a 15% premium in 2011. cell-derived EBx cell lines and related technology to produce seasonal Loramyc, a mucoadhesive buccal tablet formulation of imidazole and pandemic human flu vaccines. The payment was triggered by the antifungal agent, is approved in 26 EU countries to treat oropharyngeal characterization of the EB66 cell line. Vivalis is eligible for a total of candidiasis. Setofilm is a dissolving oral film strip formulation of the €10-€20 million ($13.5-$27 million) in milestones (see BioCentury, June serotonin (5-HT3) receptor antagonist ondansetron that is approved 4, 2007 & Feb. 16, 2009). in 16 European countries to treat and prevent chemotherapy- and radiation-induced nausea and vomiting and post-operative nausea and SALES & MARKETING vomiting (PONV). BioAlliance has European commercialization rights to Setofilm, which was developed by Applied Pharma Research S.A. Actelion Ltd. (SIX:ATLN), Allschwil, Switzerland (Balerna, Switzerland); Labtec GmbH, a subsidiary of tesa AG (Ham- Invida Group Pte. Ltd., Singapore burg, Germany); and MonoSol Rx LLC (Warren, N.J.). Business: Cardiovascular The companies added Vietnam and extended to 2015 a 2005 deal BioServe Biotechnologies Ltd., Beltsville, Md. granting Invida exclusive rights to commercialize pulmonary arterial Protein Biotechnologies Inc., Ramona, Calif. hypertension (PAH) drug Tracleer bosentan in Hong Kong, Malaysia, Business: Microarrays the Philippines and Thailand. Financial terms were not disclosed. The The companies launched the SomaPlex Reverse Phase Protein dual endothelin receptor antagonist is already approved all five terri- Microarray to profile protein expression in breast serum for research tories. use. The microarrays were developed using serum samples from BioServe’s Global BioRepository library and custom microarray tech- Aushon BioSystems Inc., Billerica, Mass. nology from Protein Biotechnologies. The companies will co-market Business: Proteomics the array and plan to launch additional cancer arrays this year. Aushon launched its Human Vascular Injury Panels to quantify seven biomarkers related to drug-induced vascular injury, including E selectin Celltrion Inc., Incheon, South Korea (SELE; CD62E); P selectin (SELP; CD62P); intercellular adhesion mol- Hikma Pharmaceuticals plc (LSE:HIK), London, U.K. ecule-3 (ICAM-3; CD50); thrombomodulin (THBD; CD141); intercel- Business: Biosimilars, Antibodies, Biomanufacturing lular adhesion molecule-1 (ICAM-1; CD54); vascular cell adhesion Celltrion granted Hikma exclusive rights to distribute and market molecule-1 (VCAM-1); and serum amyloid A (SAA). The panels were nine biosimilar products in the Middle East and North Africa (MENA) developed using the company’s Aushon SearchLight protein array region. The portfolio consists mainly of mAbs. Under the deal, Hikma technology, which is a multiplex, sandwich ELISA system based on also may collaborate on development and manufacture of the products chemiluminescent or infrared detection of analytes. for supply in the MENA region. An IND for the first biosimilar product has been filed in the EU. Further terms were undisclosed. Basilea Pharmaceutica AG (SIX:BSLN), Basel, Switzerland Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J. Cepheid Inc. (NASDAQ:CPHD), Sunnyvale, Calif. Business: Infectious Business: Diagnostic Basilea said former partner J&J’s Janssen-Ortho Inc. unit will Cepheid launched its GenXpert Infinity-48 system for molecular discontinue sales of Zeftera ceftobiprole to treat complicated skin and diagnostic testing. The system can hold up to 48 testing modules. The skin structure infections (cSSSIs) in Canada as of April 16. Basilea said company’s original GenXpert system holds up to 16. the decision came after discussions with Health Canada in response to recent regulatory actions by FDA and the European Medicines Agency Illumina Inc. (NASDAQ:ILMN), San Diego, Calif. (EMA). In February, the EMA’s CHMP issued a negative opinion on an Business: ADMET, Pharmacogenetics MAA for the compound after EMA inspections showed clinical studies Illumina launched its VeraCode ADME Core Panel containing 184 had not been conducted in compliance with good clinical practice. FDA biomarkers in 34 genes to assess pharmacogenetic profiles for drug issued a complete response letter for an NDA for ceftobiprole in metabolism studies. December, citing similar concerns (see BioCentury, Jan. 4 & Feb. 22). Basilea, which is in arbitration with J&J over the pharma’s handling Lonza Group (SIX:LONN), Basel, Switzerland of the trials, said no safety observations have been made that would be Odyssey Thera Inc., San Ramon, Calif. in conflict with the label of Zeftera, which was approved in Canada in Business: High throughput screening, Supply/Service June 2008. The broad spectrum anti-MRSA cephalosporin antibiotic is Lonza will offer Odyssey’s protein-fragment complementation assay marketed in Switzerland as Zevtera. (PCA) technology as part of compound profiling services to life science and drug discovery researchers. Lonza also received an option to an exclusive, BioAlliance Pharma S.A. (Euronext:BIO), Paris, France worldwide license to undisclosed technologies. The partners also are Therabel Group, Brussels, Belgium collaborating to develop and commercialize other undisclosed technol- Business: Infectious, Gastrointestinal ogies and products. Odyssey received an undisclosed equity investment Therabel received exclusive rights to market BioAlliance’s Loramyc and will receive technology development funding. Odyssey is eligible for miconazole and Setofilm ondansetron in Europe. BioAlliance will additional option exercise payments, plus milestones and royalties. Lonza receive €4.5 million ($6.1 million) at signing and two annual payments will become a minority shareholder in Odyssey. of €1 million ($1.4 million) at the end of 2011 and 2012. BioAlliance also is eligible to receive €3 million ($4.1 million) when reimbursement is NeurogesX Inc. (NASDAQ:NGSX), San Mateo, Calif. obtained for Loramyc in three undisclosed EU countries, and €33 Business: Neurology million ($44.5 million) in sales-based milestones, plus royalties. NeurogesX launched its Qutenza patch in the U.S. to Therabel also plans to make a €3 million ($4.1 million) equity See next page BioCentury Part II APRIL 12, 2010 PAGE B5 OF 15

Sales & Marketing, which include co-promotion as Actonel in Canada, eight European from previous page countries and Australia; co-marketing with Warner Chilcott under separate brands in Italy and ; and independent marketing in all manage due to postherpetic (PHN). The other countries except Germany, the Netherlands and Belgium, where wholesale acquisition cost (WAC) is $675 for a one-patch kit or $1,350 Warner Chilcott markets the product independently, and Japan, where for a two-patch kit. The company said the recommended dose is a single, Eisai Co. Ltd. (Tokyo:4523; Osaka:4523, Tokyo, Japan) has rights. In one-hour application of up to four patches. December, sanofi-aventis declined to exercise an option to put its interest in the osteoporosis drug to Warner Chicott at fair market Prometheus Laboratories Inc., San Diego, Calif. value. The option was triggered when Warner Chilcott acquired the Rosetta Genomics Ltd. (NASDAQ:ROSG), Rehovot, Israel pharmaceutical business of Procter & Gamble Co. (NYSE:PG, Cincin- Business: Pharmacogenetics nati, Ohio) (see BioCentury, Dec. 21, 2009). Rosetta’s miRview squamous test can now be run using fine-needle aspirate cell blocks. The test differentiates between squamous and non- OTHER NEWS squamous non-small cell lung cancer (NSCLC) to help guide treatment decisions. Previously, the test used formalin-fixed paraffin-embedded Apieron Inc., Menlo Park, Calif. tumor samples obtained after tumor resection. Prometheus markets Business: Diagnostic miRview squamous in the U.S. as ProOnc squamous under a 2009 deal Apieron filed for Chapter 7 bankruptcy. As a result of the bankruptcy (see BioCentury, April 20, 2009). filing, patent infringement suits filed against Apieron by Aerocrine AB (SSE:AERO, Stockholm, Sweden) will be stayed. The suits alleged that Source BioScience plc (LSE:SBS), Nottingham, U.K. Apieron’s Insight eNO system infringed Aerocrine’s patents covering its AstraZeneca plc (LSE:AZN; NYSE:AZN), London, U.K. Niox Mino and Niox Flex tests. All three products measure exhaled nitric Business: Pharmacogenetics oxide in asthma patients’ breath as a measure of airway inflammation. Under a deal with AstraZeneca, Source BioScience will provide an EGFR testing service in the U.K. to help identify lung cancer patients with Cytos Biotechnology AG (SIX:CYTN), Zurich, Switzerland mutations or deletions that confer sensitivity or resistance to tyrosine Independent Pharmaceutica AB, Stockholm, Sweden kinase inhibitors. Source BioScience said AstraZeneca will fund the Nabi Biopharmaceuticals (NASDAQ:NABI), Rockville, Md. service. The pharma markets Iressa gefitinib, an EGFR tyrosine kinase Novartis AG (NYSE:NVS; SIX:NOVN), Basel, Switzerland inhibitor, outside the U.S. to treat non-small cell lung cancer (NSCLC) in Celtic Pharmaceutical Holdings L.P., Hamilton, Bermuda patients with activating mutations. Further terms were not disclosed. Business: Neurology In an opposition brought by Nabi, Cytos, Novartis and Independent Swedish Orphan Biovitrum (SSE:BVT), Stockholm, Sweden Pharmaceutica, the European Patent Office (EPO) revoked Xenova Merck KGaA (Xetra:MRK), Darmstadt, Germany Group plc’s European Patent No. EP1329226 covering the use of a Business: Other therapeutic hapten-carrier conjugate comprising a hapten derived from The companies added Ireland, the U.K. and the Netherlands to the nicotine and a protein carrier. EP1329226 is a divisional patent that territories in which Swedish Orphan Biovitrum distributes Merck’s amended claims from parent application EP0814843, which describes Cyanokit hydroxocobalamin. The precursor of vitamin B12 is approved therapeutic hapten-carrier conjugates to treat drug abuse and claims to treat cyanide poisoning. Swedish Orphan Biovitrum already distrib- such therapeutics to treat cocaine abuse. The Opposition Division utes Cyanokit in Nordic and Baltic countries. found that EP1329226 went beyond the scope of the parent application, because nicotine was not singled out in the parent application. Celtic Warner Chilcott plc (NASDAQ:WCRX), Ardee, Ireland Pharma, which acquired Xenova in 2005, has the option to appeal but sanofi-aventis Group (Euronext:SAN; NYSE:SNY), Paris, France declined to comment on its plans. Business: Musculoskeletal Nabi’s NicVax nicotine is in Phase III testing to Under an amendment to a 1997 deal, sanofi-aventis returned to prevent nicotine dependence. Independent Pharmaceutica’s Niccine, a Warner Chilcott rights to co-develop and market Actonel risedronate in vaccine that generates antibodies against nicotine, is in Phase II trials the U.S. and Puerto Rico. sanofi-aventis will receive payments based on a to prevent smoking relapse. Novartis has rights to Cytos’ Nicotine- percentage of net sales until the expiration of the agreement on December Qbeta, a vaccine consisting of nicotine plus a carrier particle in Phase 31, 2014. Also, sales reps currently promoting Actonel for sanofi-aventis II testing to treat nicotine addiction. Celtic Pharma’s TA-NIC, a vaccine in the U.S. are expected to join Warner Chilcott’s sales force. with nicotine butyric acid attached to cholera toxin B subunit, is in Phase sanofi-aventis retains the remainder of its rights to risedronate, II testing to treat nicotine addiction (see BioCentury, June 27, 2005).

Epix Pharmaceuticals Inc. (Pink:EPIX), Lexington, Mass. BioCentury Part II Business: Diagnostic, Neurology, Pulmonary BioCentury Part II is published by BIOCENTURY PUBLICATIONS INC., On May 28, Epix’s IP covering MRI imaging programs will be PO Box 1246 San Carlos CA 94070-1246. Phone 650-595-5333. auctioned. The programs include MS-325 (gadofosveset trisodium), EP- Fax 650-595-5589. David Flores, President & CEO; 2104R and EP-3600. MS-325, an injectable gadolinium MRI contrast Karen Bernstein, Ph.D., Chairman & Editor-in-Chief agent, is marketed by Lantheus Medical Imaging Inc. (North Billerica, BioCentury™ ; The Bernstein Report on BioBusiness™ ; The Mass.) in the U.S. as Ablavar. EP-2104R, a fibrin-binding thrombus BioCentury 100™ ; and The Clear Route to ROI™ are trademarks imaging agent used to identify clots using MRI is in Phase II testing. EP- of BIOCENTURY PUBLICATIONS INC. 3600, a collagen-binding MRI imaging agent, is in preclinical develop- All contents © Copyright 2010, BIOCENTURY PUBLICATIONS INC. ment to detect myocardial perfusion. Lantheus acquired U.S., Canadian ALL RIGHTS RESERVED. No part of this publication may be and Australian rights to MS-325 from Epix in 2009. Epix said it will be photocopied or reproduced in any form, retransmitted, or stored in a retrieval system without prior written consent of the publisher. dissolved, but did not provide a timeline (see BioCentury, July 27, 2009). See next page BioCentury Part II APRIL 12, 2010 PAGE B6 OF 15

Other News, company’s research and preclinical development organization. The from previous page company expects the reductions to generate annual savings of about DKK6-DKK7 million ($1.1-$1.3 million) starting next year. At Dec. 31, GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. 2009, the company reported DKK130.1 million ($25.2 million) in cash U.K. Department of Health, London, U.K. and a 12-month operating loss of DKK132.5 million ($25.7 million). Business: Infectious TopoTarget also announced that it hired Anders Fink Vadsholt as GlaxoSmithKline and the U.K. Department of Health reached an CFO and head of investor relations. Vadsholt, a TopoTarget director, agreement that allows the government to reduce its order for was previously a partner at BankInvest Biomedical Venture. adjuvanted swine influenza A (H1N1) vaccine and instead purchase GSK’s avian influenza (H5N1) vaccine and the neuraminidase inhibitor MANAGEMENT TRACKS Relenza zanamivir. Orders of Pandemrix will be capped at 34.8 million doses, including doses already received. There will be no cancellation Boards of Directors fee. Health Secretary Andy Burnham said the agreement saves the government about one-third of the original value of the order from Achaogen Inc., South San Francisco, Calif. GSK. Business: Infectious The original order was for 90 million doses, of which 29.6 million Appointed: Robert More, general partner at Frazier Healthcare Ven- have been received. Last May, the government said it ordered up to 90 tures million doses of pandemic H1N1 vaccines from GSK and Baxter International Inc. (NYSE:BAX, Deerfield, Ill.) The Department of Health Altheos Inc., South San Francisco, Calif. also disclosed last week that, in February, it cancelled the Baxter Business: Ophthalmic contract. Appointed: Lester Kaplan, a member of Bay City Capital’s scientific The government will continue to immunize priority groups, such as advisory board, as chairman; Peter Bisgaard of Novo A/S; Rob Hopfner pregnant women and plans to donate 3.8 million doses to the World of Bay City Capital; and Wende Hutton of Canaan Partners Health Organization (WHO) for use in Africa. Unused vaccine will be stored as a strategic reserve. GSK has rights to Relenza from Biota Biocartis S.A., Lausanne, Switzerland Holdings Ltd. (ASX:BTA, Notting Hill, Australia). Business: Diagnostic Appointed: Dinko Valerio, a director, as chairman; and Pietro Scalfaro, Graceway Pharmaceuticals LLC, Bristol, Tenn. director of the diagnostics business unit at Debiopharm Group Business: Pharmaceuticals Graceway reduced headcount by about 40%. The decision followed Ziopharm Oncology Inc. (NASDAQ:ZIOP), New York, N.Y. a March 8 ruling by the U.S. District Court for the District of New Jersey Business: Cancer that denied Graceway’s request for a temporary restraining order Appointed: Murray Brennan, a director, as chairman; and George preventing Nycomed (Zurich, Switzerland) from selling its generic Abercrombie, former president and CEO of Roche’s Hoffmann-La version of Graceway’s Aldara imiquimod cream 5%. Graceway markets Roche Inc. unit Aldara in the U.S. to treat actinic keratosis (AK), external genital and perianal and superficial basal cell carcinoma (BCC). Management TopoTarget A/S (CSE:TOPO), Copenhagen, AcelRx Pharmaceuticals Inc., Redwood City, Calif. Business: Cancer Business: Neurology, Drug delivery TopoTarget reduced headcount by eight (17%) to 40, with the cuts Hired: Richard King as president and CEO, formerly president and including CFO Tim Corcoran, COO Steven Butcher and members of the general manager of Tercica Inc. (now part of Ipsen Group)

Cempra Pharmaceuticals Inc., Chapel Hill, N.C. Business: Infectious Hired: Jennifer Schranz as VP of clinical affairs; and Susan Moriarty as VP BioCentury makes people think of clinical research Resigned: J. Gordon Still as CMO We know you have many choices for headlines. But if you need to know what the Dendreon Corp. (NASDAQ:DNDN), Seattle, Wash. Business: Cancer news means, there is only one journal — Hired: Varun Nanda as SVP of global commercial operations, formerly BioCentury, the Bernstein Report on SVP and global head of oncology at Genentech Inc. (now part of Roche) BioBusiness® — that is recognized by key decision makers as the best source of Entest BioMedical Inc. (OTCBB:ENTB), San Diego, Calif. perspective, interpretation and analysis for top Business: Neurology, Endocrine Hired: Tammy Reynolds as CFO, formerly with Science Applications managers and investors in the biotech International Corp. community. PharmAthene Inc. (NYSE-A:PIP), Annapolis, Md. Business: Infectious Hired: Thomas Fuerst as SVP and CSO, formerly senior science and technology advisor for the U.S. Department of Health and Human Services BioCentury Part II APRIL 12, 2010 PAGE B7 OF 15

CLINICAL NEWS

Clinical activities and selected announcements for the week ended April 9. Daiichi submitted an NDA to Japan’s Ministry of Health, Labor and Welfare for edoxaban to prevent venous thromboembolism (VTE) REGULATORY after major orthopedic surgery. Edoxaban is an oral Factor Xa inhibitor.

Aeterna Zentaris Inc. (TSX:AEZ; NASDAQ:AEZS), Quebec City, Forest Laboratories Inc. (NYSE:FRX), New York, N.Y. Quebec Mitsubishi Tanabe Pharma Corp. (Tokyo:4508; Osaka:4508), Osaka, Keryx Biopharmaceuticals Inc. (NASDAQ:KERX), New York, N.Y. Japan Product: Perifosine (KRX-0401) Nycomed, Zurich, Switzerland Business: Cancer Product: Daxas roflumilast (APTA-2217) FDA granted Fast Track designation to perifosine to treat advanced Business: Pulmonary refractory colorectal cancer. Keryx began a Phase III trial of perifosine FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 10-5 for the indication last week. Keryx has North American rights to the against recommending approval of an NDA from Forest for Daxas compound from Aeterna Zentaris. Perifosine, an alkylphosphocholine roflumilast for the maintenance treatment of chronic obstructive modulator of the phosphoinositide 3-kinase (PI3K)/protein kinase B pulmonary disease (COPD) associated with chronic bronchitis. The (PKB; Akt) and other signal transduction pathways, also has Fast Track committee said safety and efficacy data do not provide substantial and Orphan designations in the U.S. for multiple myeloma (MM), for evidence to support the approval of Daxas. The negative vote came after which it is in Phase III testing. two separate 9-6 votes in which a majority of committee members said there was substantial evidence of efficacy and a safety profile that Allon Therapeutics Inc. (TSX:NPC), Vancouver, B.C. supported approval. Although those tallies were the same, some Product: Davunetide (AL-108) committee members voted differently on the safety and efficacy votes, Business: Neurology which led to the overall negative vote when FDA asked them to FDA granted Fast Track designation for Allon’s davunetide to treat integrate the two issues in the vote on approval. There was consensus progressive supranuclear palsy (PSP), a fatal degenerative brain disease. among advisory committee members that Daxas has “modest” efficacy The compound, an eight amino acid activity-dependent neuroprotective compared to approved COPD treatments. Forest and FDA clashed on protein (ADNP), also has Orphan designation in the U.S. and is in Phase several regulatory and procedural issues related to the Daxas review, I testing for PSP. Davunetide also is in Phase IIa testing to treat amnestic including the agency’s refusal to accept the company’s proposal to mild cognitive impairment (aMCI), a precursor to Alzheimer’s disease, narrow the indication from maintenance therapy for a broad COPD and cognitive impairment in schizophrenia. population with chronic bronchitis to maintenance treatment to re- duce exacerbations of COPD in that population. FDA also blocked the Cell Therapeutics Inc. (NASDAQ:CTIC; Milan:CTIC), Seattle, Wash. company’s attempt to brief the advisory committee on a draft risk Product: Pixantrone management plan that had not been submitted to the agency. The PDUFA Business: Cancer date for the oral phosphodiesterase-4 (PDE-4) inhibitor is in May. FDA issued a complete response letter for an NDA from Cell Forest has exclusive, U.S. rights to the oral phosphodiesterase-4 (PDE- Therapeutics for Pixuvri pixantrone to treat relapsed or refractory 4) inhibitor from Nycomed, which also granted Mitsubishi co-develop- aggressive non-Hodgkin’s lymphoma (NHL). The agency requested an ment and commercialization rights in Japan (see BioCentury, Aug. 17, additional clinical trial to demonstrate the safety and efficacy of the aza- 2009). anthracenedione DNA intercalating agent that inhibits topoisomerase II (TOP2). Cell Therapeutics said it hopes to start this study in Genta Inc. (OTCBB:GETA), Berkeley Heights, N.J. September, and in the meantime plans to work with FDA to establish Daiichi Sankyo Co. Ltd. (Tokyo:4568; Osaka:4568), Tokyo, Japan an expanded access program for Pixuvri. Last month, FDA’s Oncologic Product: Tesetaxel (DJ-927) Drugs Advisory Committee voted 9-0 against recommending approval Business: Cancer of the compound (see BioCentury, March 29). Cell Therapeutics said it FDA granted Fast Track designation to tesetaxel to treat advanced plans to submit an MAA to the European Medicines Agency (EMA) next gastric cancer in patients who failed a platinum and fluoropyrimidine- quarter. containing first-line regimen. The oral, semi-synthetic taxane deriva- tive is in a Phase IIb trial for the indication. Genta licensed tesetaxel, Celldex Therapeutics Inc. (NASDAQ:CLDX), Needam, Mass. which has Orphan designation for advanced gastric cancer and mela- GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K. noma, from Daiichi Sankyo (see BioCentury, March 10, 2008). Product: Rotarix (RIX4414) Business: Infectious Mitsubishi Tanabe Pharma Corp. (Tokyo:4508; Osaka:4508), Osaka, FDA’s Vaccines and Related Biological Products Advisory Commit- Japan tee will meet on May 7 to discuss the use of Rotarix from GlaxoSmithKline Novartis AG (NYSE:NVS; SIX:NOVN), Basel, Switzerland after an independent academic research team found DNA from porcine Product: Gilenia fingolimod (FTY720) circovirus 1 (PCV1) in the oral attenuated . FDA Business: Autoimmune recommended temporary suspension of Rotarix in March. GSK has FDA’s Peripheral and Central Nervous System Drugs Advisory rights to the vaccine from Celldex (see BioCentury, March 29). Committee will meet on June 10 to discuss an NDA from Novartis for Gilenia fingolimod to treat relapsing forms of multiple sclerosis (MS). Daiichi Sankyo Co. Ltd. (Tokyo:4568; Osaka:4568), Tokyo, Japan The NDA is under Priority Review, with a PDUFA date of June 21. Product: Edoxaban (DU-176b) Novartis licensed the sphingosine 1-phosphate (S1P) receptor agonist Business: Cardiovascular from Mitsubishi Tanabe. See next page BioCentury Part II APRIL 12, 2010 PAGE B8 OF 15

Regulatory, Endpoint: NA from previous page Status: Extension study data Milestone: NA Nycomed, Zurich, Switzerland Additional data from the open-label, international STRATA safety Product: TachoSil extension study showed that JC virus (JCV) DNA was detected in 4 of Business: Hematology 1,397 patients using the quantitative PCR assay from ViraCor-IBT FDA approved Nycomed’s TachoSil surgical patch for use in cardio- Laboratories (Kansas City, Kan.). In a subset of 205 plasma samples, JCV vascular surgery to prevent mild and moderate bleeding from small DNA was detected in an additional 2 patients using a more sensitive blood vessels. The hemostatic surgical patch contains human fibrinogen assay from the NIH. Of the 6 patients with JCV DNA, 3 were Tysabri- and thrombin. naïve.In 1,094 patients from the STRATA study monitored with the ViraCor assay, there was no difference between JCV presence in plasma Oraya Therapeutics Inc., Newark, Calif. before Tysabri treatment and 48 weeks after treatment, with the Product: IRay system overall incidence <1%. Data were presented at the American Academy Business: Ophthalmic of Neurology meeting in Toronto. Biogen Idec and Elan market Tysabri Oraya received CE Mark approval in the EU for its IRay stereotactic in more than 45 countries. radiotherapy system to treat wet age-related macular degeneration (AMD). The device is designed to deliver low-energy X-rays to the eye. Indication: Treat multiple sclerosis Endpoint: Clinical relapse rate at 1 year and cumulative probability of Purdue Pharma L.P., Stamford, Conn. progression of disability sustained for 12 weeks at 2 years; number of Product: OxyContin new or enlarging T2-hyperintense lesions, number of gadolinium- Business: Neurology enhancing lesions, proportion of relapse-free patients at 1 year and FDA approved an NDA from Purdue for a reformulated version of clinical relapse rate and volume of T2-hyperintense lesions and disabil- controlled-release OxyContin oxycodone to manage moderate to ity at 2 years severe pain. Purdue said the reformulation is intended to be more Status: Additional Phase III data difficult to manipulate; however, the company added that “there is no Milestone: NA evidence that the reformulation of OxyContin is less subject to misuse, A post-hoc analysis of the Phase III AFFIRM trial in relapsing- abuse, diversion, overdose or addiction.” The approval comes with a recurring MS (RRMS) patients showed that improvements in disability REMS that includes a requirement for prescriber education regarding significantly correlated with improvements in patient-reported Quality the proper use of analgesics for pain. FDA is planning a class- of Life measurements. Data were presented at the American Academy wide REMS for extended-release . Purdue expects to launch the of Neurology meeting in Toronto. Biogen Idec and Elan market Tysabri product, which is intended to replace the marketed original formula- in more than 45 countries. tion, in 3Q10. Celgene Corp. (NASDAQ:CELG), Summit, N.J. Simcere Pharmaceutical Group (NYSE:SCR), Nanjing, China Product: PDA-001 Product: Human use Business: Autoimmune Business: Infectious Molecular target: NA Simcere said that China’s State Food and Drug Administration Description: Immunomodulatory human placenta-derived stem cells (SFDA) found that 4 batches of the human use rabies vaccine manufac- Indication: Treat moderate to severe Crohn’s disease (CD) tured by its Jiangsu Yanshen Biological Technology Stock Co. Ltd. Endpoint: Safety; clinical disease severity (as assessed by Crohn’s subsidiary and marketed between July and October 2008 had an Disease Activity Index) and quality of life (as assessed by Inflammatory insufficient amount of active compound. SFDA determined that produc- Bowel Disease Questionnaire) tion of substandard vaccine product was a result of illegal activities, Status: Phase I data including inadequate quality control processes as well as misrepresen- Milestone: NA tation and avoidance of regulatory inspection. Simcere acquired a Top-line data from a Phase I trial in 12 patients who were unrespon- controlling interest in Jiangsu Yanshen in October 2009. Simcere said sive to at least 1 prior therapy showed that both doses of PDA-001 met it subsequently discovered the quality control problems that led to a the primary safety endpoint. There were 4 clinical remissions, all in the voluntary suspension of operations, which led to SFDA’s investigation low-dose arm. Remission was defined by a CDAI score <150. Patients (see BioCentury, Dec. 7, 2009). received 2 infusions of 2x108 or 8x108 cells one week apart. The The rabies vaccine is produced in Vero cells. Simcere said there have company plans to start multiple Phase II studies in undisclosed indica- been no adverse events reported as a result of the quality control tions. issues, while certain employees are facing criminal investigations. Operations at Jiangsu Yanshen remain suspended pending further Cellestis Ltd. (ASX:CST), Carnegie, Australia investigation. Product: QuantiFeron-TB Gold Business: Diagnostic CLINICAL RESULTS Molecular target: Interferon (IFN) gamma Description: Tuberculosis diagnostic system Biogen Idec Inc. (NASDAQ:BIIB), Cambridge, Mass. Indication: Diagnose tuberculosis (TB) Elan Corp. plc (NYSE:ELN), Dublin, Ireland Endpoint: Specificity and sensitivity Product: Tysabri natalizumab Status: Post-marketing study data Business: Autoimmune Milestone: NA Molecular target: Integrin alpha(4) (VLA-4 ) (CD49D) A meta-analysis of 42,745 patients enrolled in 124 trials showed Description: Humanized mAb against integrin alpha(4) that QuantiFeron-TB Gold (QFT) and T-Spot.TB tuberculosis assays Indication: Treat multiple sclerosis See next page BioCentury Part II APRIL 12, 2010 PAGE B9 OF 15

Clinical Results, the researchers, standardized diagnostic testing is needed to deter- from previous page mine whether XMRV is an oncogenic virus or is simply associated with prostate cancer. Data were published in Urology. had higher specificity and sensitivity vs. the standard TB skin test (TST). Sensitivities were 84.5% for QFT and 88.5% for T-Spot vs. 71.5% for Koronis Pharmaceuticals Inc., Redmond, Wash. TST. Specificities were 99.2% for QFT and 86.3% for T-Spot vs. 59% for Product: KP-1461 TST in vaccinated patients. QFT is marketed by Cellestis. Oxford Business: Infectious Immunotec Ltd. (Oxford, U.K.) markets T-Spot. Data were published Molecular target: NA in Chest. Description: Oral prodrug of KP-1212, a small molecule nucleoside analog that works through Viral Decay Acceleration (VDA) Chronix Biomedical, San Jose, Calif. Indication: Treat HIV-1 infection Product: Multiple sclerosis serum DNA assay Endpoint: Safety; antiretroviral activity Business: Diagnostic Status: Additional Phase IIa data Molecular target: NA Milestone: Start Phase II (year end 2010) Description: Serum assay detecting circulating DNA associated with In the open-label, U.S. Phase IIa 201 trial in 24 evaluable patients, multiple sclerosis KP-1461 showed a non-significant viral load decrease of 0.22 log10; Indication: Diagnose relapsing-remitting multiple sclerosis (RRMS) CD4 decrease of 16 cells/µL; and reverse transcriptase activity increase Endpoint: NA of 0.27 log10 compared with baseline. In the 13 patients who completed Status: NA all 124 days of treatment, KP-1461 resulted in a non-significant viral load Milestone: NA decrease of 0.32 log10; CD4 increase of 60 cells/µL; and reverse Chronix’s MS serum DNA assay differentiated 28 RRMS patients transcriptase activity increase of 0.36 log10. KP-1461 significantly from 50 healthy volunteers. Of the RRMS patients, the test discerned increased the rate of accumulation of mutations in HIV genomes vs. the 13 who were undergoing clinical relapse from the 15 who had been untreated controls.Drug-related adverse events occurred in 12 pa- in remission for 6 months. Data were published in the Journal of tients and included gastrointestinal and nervous system disorders. Two Molecular Diagnostics. The company initially plans to offer the diagnostic patients withdrew from the study due to adverse events. as a research tool and later hopes to commercialize the test to monitor patient response to MS treatment. Living Cell Technologies Ltd. (ASX:LCT; OTCQX:LVCLY), Sydney, Australia Dyax Corp. (NASDAQ:DYAX), Cambridge, Mass. Product: DiabeCell Product: Kalbitor ecallantide (DX-88, CB-500,929) Business: Endocrine Business: Cardiovascular Molecular target: Not available Molecular target: Kallikrein Description: Encapsulated porcine pancreatic islet cells Description: Yeast-derived recombinant plasma kallikrein inhibitor Indication: Treat Type I diabetes Indication: Treat hereditary angioedema (HAE) Endpoint: Safety and insulin production Endpoint: NA Status: Additional Phase I/IIa data Status: Post-marketing study data Milestone: Phase I/IIa data (06/2010) Milestone: NA Additional data from a Russian Phase I/IIa trial in 8 patients showed Researchers at Massachusetts General Hospital and colleagues that DiabeCell implant reduced HbA1c in 6 patients by 0.2-2.8% and published an analysis of the economics of managing acute HAE. In 457 reduced daily insulin by 13-100% at 6 months. In 5 patients receiving a HAE patients from November 2007 to January 2008, the total annual second implant, DiabeCell reduced HbA1c by 0.5-2.1% and reduced cost per patient was about $42,000. The cost was $14,000 for mild daily insulin by 10-25% at 12 months. In 4 patients receiving a third attacks, $27,000 for moderate attacks and $96,000 for severe attacks. implant, DiabeCell reduced HbA1c by 0.2-1.3% and daily insulin by 10- The total annual direct medical cost per patient was $25,884, of which 100% at 15 months. The company previously reported interim data from 67% was due to hospital costs. Indirect costs averaged $16,108 annually, the trial (see BioCentury, Feb. 16, 2009 & April 13, 2009). and included costs from missed work, travel, childcare, reduced productivity and reduced income. Data were published in Annals of Merck KGaA (Xetra:MRK), Darmstadt, Germany Allergy, Asthma and Immunology. Dyax, which supported the study, Pfizer Inc. (NYSE:PFE), New York, N.Y. markets Kalbitor to treat acute attacks of HAE in the U.S. Product: Rebif interferon beta-1a Business: Autoimmune Emory University, Atlanta, Ga. Molecular target: Type I interferon (IFN) receptor Product: XMRV serum assay Description: Recombinant interferon beta-1a Business: Diagnostic Indication: Treat multiple sclerosis (MS) Molecular Target: NA Endpoint: Tumor incidence Description: Serum assay to detect xenotropic murine leukemia virus- Status: Post-marketing study data related virus (XMRV) retrovirus neutralizing antibodies Milestone: NA Indication: Diagnose XMRV infection in prostate cancer patients Data from the Merck Serono Global Drug Safety (GDS) database, Endpoint: Ability to detect XMRV neutralizing antibodies which includes about 660,000 patient-years of data collected over the Status: Data past 11 years, showed that Rebif did not increase the risk of malignan- Milestone: NA cies. Additionally, pooled data from 4,570 subjects in 12 clinical trials In serum samples from 40 patients with prostate cancer, Emory’s showed no increased incidence of tumors per 1,000 patient-years for XMRV serum assay detected neutralizing antibodies against XMRV in 11 Rebif vs. placebo (4 vs. 6.4). Data will be presented at the American (27.5%) patients. The results were in concordance with independent Academy of Neurology meeting in Toronto on Tuesday. PCR and FISH assays designed to detect XMRV infection. According to See next page BioCentury Part II APRIL 12, 2010 PAGE B10 OF 15

Clinical Results, Final data from the double-blind, placebo-controlled, international from previous page Phase IIb PROVE 3 trial in 453 patients showed that 750 mg thrice-daily telaprevir plus Pegasys peginterferon alfa-2a and ribavirin resulted in Oxford Immunotec Ltd., Abingdon, U.K. a significantly higher sustained viral response (SVR) vs. Pegasys plus Product: T-Spot.TB ribavirin alone for 48 weeks. Triple therapy for 12 weeks followed by Business: Diagnostic Pegasys and ribavirin for 12 weeks resulted in a 51% SVR rate, as Molecular target: Not applicable measured by undetectable HCV RNA (<10 IU/mL) (p<0.001). Triple Description: Enzyme-linked immunospot assay (ELISPOT) assay to therapy for 24 weeks followed by Pegasys and ribavirin for 24 weeks diagnose tuberculosis resulted in a 53% SVR rate (p<0.001). Telaprevir plus Pegasys for 24 Indication: Diagnose tuberculosis (TB) weeks resulted in a 24% SVR rate vs. a 14% SVR rate for the control Endpoint: Specificity and sensitivity group (p=0.02). All patients had failed prior treatment with Pegasys and Status: Post-marketing study data ribavirin. Discontinuation due to adverse events was more frequent in Milestone: NA the telaprevir arms than the control group (15% vs. 4%). Severe rash A meta-analysis of 42,745 patients enrolled in 124 trials showed occurred in 5% of telaprevir patients, and a decrease in hemoglobin that QuantiFeron-TB Gold (QFT) and T-Spot.TB tuberculosis assays levels was more common in telaprevir-based regimens than in controls. had higher specificity and sensitivity vs. the standard TB skin test (TST). Data were published in the New England Journal of Medicine.The Sensitivities were 84.5% for QFT and 88.5% for T-Spot vs. 71.5% for company previously reported top-line data last May (see BioCentury, May TST. Specificities were 99.2% for QFT and 86.3% for T-Spot vs. 59% for 4, 2009). Roche (SIX:ROG; OTCQX:RHHBY, Basel, Switzerland) mar- TST in vaccinated patients. QFT is marketed by Cellestis Ltd. (ASX:CST, kets Pegasys. Vertex, which owns North American rights to telaprevir, Carnegie, Australia). Oxford Immunotec markets T-Spot. Data were granted J&J rights to telaprevir in Europe, South America, the Middle published in Chest. East, Africa and Australia, while Mitsubishi has rights in certain Asian countries sanofi-aventis Group (Euronext:SAN; NYSE:SNY), Paris, France Product: Multaq dronedarone PRECLINICAL RESULTS Business: Cardiovascular Molecular target: Sodium channel; Potassium channel Celprogen Inc., San Pedro, Calif. Description: Multichannel blocker with properties of antiarrhythmics Product: Stem Cell Differentiation system in Vaughan-Williams classes I-IV Indication: Treat infertility Indication: Treat atrial fibrillation (AF) Celprogen’s stem cell differentiation system de-differentiated hu- Endpoint: NA man somatic fibroblasts into induced pluripotent stem (iPS) cells that Status: Data then differentiated into germ progenitor cells. Celprogen sells kits that Milestone: NA differentiate adult stem cells from cord blood into ooginia and sperm. Researchers from Cedars-Sinai Medical Center and colleagues analyzed 7 clinical trials of Multaq and recommended that the drug Critical Outcome Technologies Inc. (TSX-V:COT), London, Ontario should be used only as second- or third-line therapy for atrial fibrilla- Product: COTI-2 tion (AF) in cases where amiodarone is effective but not tolerated. The Indication: Treat triple receptor-negative breast cancer researchers said the trials showed that Multaq was about half as In an animal model of breast cancer, 200 mg/kg oral COTI-2 daily for effective as amiodarone and had only a slightly better safety profile. 5 days prior to tumor implantation and 5 days/week thereafter inhibited Current joint guidelines from the American College of Cardiology, the tumor growth by 78% at day 38 vs. vehicle control (p<0.001). The American Heart Association and the European Society of Cardiology compound also significantly inhibited the growth of established tumors Committee (ACC/AHA/ESC) recommend use of Multaq or amiodarone versus placebo, although the inhibition was significantly better in as first- or second-line therapy in the indication. Data were published animals pretreated with the compound. The small molecule inhibitor in a commentary in the Journal of the American College of Cardiology. sanofi- of protein kinase B (PKB; Akt) phosphorylation was well tolerated. aventis markets Multaq in the U.S. to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or atrial Cryo-Cell International Inc. (OTCBB:CCEL), Oldsmar, Fla. flutter. Product: MenSCs, Menstrual blood stem cells Indication: Treat stroke Vertex Pharmaceuticals Inc. (NASDAQ:VRTX), Cambridge, Mass. In a rat model of ischemic stroke, menstrual blood-derived stem Mitsubishi Tanabe Pharma Corp. (Tokyo:4508; Osaka:4508), Osaka, cells (MenSCs) significantly reduced behavioral and histological impair- Japan ments vs. vehicle control at day 14 (p<0.0001). In an in vitro stroke Johnson & Johnson (NYSE:JNJ), New Brunswick, N.J. model, MenSCs significantly reduced cell death (p<0.0001). Data were Product: Telaprevir (VX-950, MP-424) published in Stem Cells and Development. Business: Infectious Molecular target: HCV protease Immunovaccine Inc. (TSX-V:IMV), Halifax, Nova Scotia Description: Small molecule HCV NS3 protease inhibitor Product: DPX-0907 Indication: Treat hepatitis C virus (HCV) infection Indication: Treat breast, ovarian and prostate cancer Endpoint: Undetectable HCV RNA 24 weeks after treatment comple- In a transgenic mouse model of breast, ovarian and prostate cancers, tion; undetectable HCV RNA at 48 weeks after treatment completion, DPX-0907 produced more than twice as many peptide-specific inter- adverse events and clinical laboratory assessments including ALT and feron (IFN) gamma secreting CD8 T-cells compared to a control other liver function tests emulsion-based vaccine (p=0.03). A single injection of DPX-0907 Status: Final Phase IIb data produced a significantly stronger immune response compared to 3 Milestone: Phase III data (2Q10); submit NDA (2H10); Phase III data injections of the control vaccine (p=0.02). Mice vaccinated with emul- (3Q10) See next page BioCentury Part II APRIL 12, 2010 PAGE B11 OF 15

Preclinical Results, Frazer, Pa.) markets bendamustine as Treanda in the U.S. and from previous page Mundipharma International Ltd. (Cambridge, U.K.) markets it as Ribomustin in Germany. sion vaccine had significantly higher percentages of regulatory T cells compared to mice vaccinated with DPX-0907 (p=0.008) and naïve mice Cephalon Inc. (NASDAQ:CEPH), Frazer, Pa. (p=0.003). DPX-0907 did not produce significant tissue reactions at the InnoPharmax Inc., Taipei, Taiwan injection site compared to emulsion vaccine. Data were published in the SymBio Pharmaceuticals Ltd., Tokyo, Japan Journal of Immunotherapy. DPX-0907 is a vaccine against seven cancer Astellas Pharma Inc. (Tokyo:4503), Tokyo, Japan specific antigens using DepoVax delivery technology. Eisai Co. Ltd. (Tokyo:4523; Osaka:4523), Tokyo, Japan Mundipharma International Ltd., Cambridge, U.K. pSivida Corp. (NASDAQ:PSDV; ASX:PVA), Watertown, Mass. Product: Treanda bendamustine (SDX-105) Product: Fluocinolone acetonide Business: Cancer Indication: Treat retinitis pigmentosa (RP) Molecular target: DNA In a rat model of RP, low-dose, sustained-release fluocinolone Description: Alkylating agent acetonide delivered intravitreously by pSivida’s Durasert device re- Indication: Treat multiple myeloma (MM) duced retinal neuroinflammation vs. controls. Fluocinolone acetonide Endpoint: Maximum tolerated dose (MTD); response rate is a synthetic corticosteroid. Data were published in Investigative Status: Phase Ib/II started Ophthalmology & Visual Science. Milestone: Phase Ib data (mid-2011); Phase II data (year end 2011) The Multiple Myeloma Research Consortium (MMRC) began an CLINICAL STATUS open-label, U.S. Phase Ib/II trial to evaluate Treanda plus Revlimid lenalidomide and dexamethasone in about 80 patients with relapsed Aeterna Zentaris Inc. (TSX:AEZ; NASDAQ:AEZS), Quebec City, MM. Astellas granted rights for bendamustine to Cephalon in the U.S., Quebec to Mundipharma in Europe and to SymBio in Japan and certain Asian Keryx Biopharmaceuticals Inc. (NASDAQ:KERX), New York, N.Y. countries. Symbio then partnered the compound with Eisai in Japan, Product: Perifosine (KRX-0401) South Korea and Singapore. Cephalon markets bendamustine as Treanda Business: Cancer in the U.S. to treat CLL and indolent B cell NHL. Mundipharma markets Molecular target: Protein kinase B (PKB) (Akt); Phosphoinositide 3- it as Ribomustin in Germany to treat CLL, NHL and MM. Celgene Corp. kinase (PI3K) (NASDAQ:CELG, Summit, N.J.) markets Revlimid in the U.S. to treat Description: Alkylphosphocholine modulator of the phosphoinositide relapsed or refractory MM and myelodysplastic syndromes (MDS). 3-kinase (PI3K)/protein kinase B (PKB; Akt) and other signal transduc- tion pathways Ceregene Inc., San Diego, Calif. Indication: Treat refractory metastatic colorectal cancer (mCRC) Product: CERE-110 Endpoint: Overall survival (OS); overall response rate (ORR), progres- Business: Neurology sion-free survival (PFS) and safety Molecular target: Not applicable Status: Phase III started Description: Adeno-associated viral (AAV) vector encoding nerve Milestone: Complete Phase III enrollment (2Q11); complete Phase III growth factor (NGF) (2H11); Market launch (mid-2012) Indication: Treat mild to moderate Alzheimer’s disease Keryx began the double-blind, placebo-controlled, U.S. Phase III X- Endpoint: Alzheimer’s Disease Assessment Scale - Cognitive subscale PECT trial to evaluate Xeloda capecitabine with or without perifosine (ADAS-Cog); Neuropsychological Test Battery, Mini-Mental State Ex- in about 430 patients. Keryx, which has an SPA from FDA for the study, amination (MMSE), Neuropsychiatric Inventory (NPI) and ADAS - has North American rights to perifosine from Aeterna Zentaris. Activities of Daily Living (ADCS-ADL) Perifosine has Fast Track designation in the U.S. to treat advanced Status: Phase II started refractory colorectal cancer. Roche (SIX:ROG; OTCQX:RHHBY, Basel, Milestone: NA Switzerland) markets Xeloda. Researchers began a double-blind, placebo-controlled, U.S. Phase II trial to evaluate Ceregene’s CERE-110 delivered into the brain of 50 Calistoga Pharmaceuticals Inc., Seattle, Wash. patients. The trial is being conducted by the Alzheimer’s Disease Product: CAL-101 Cooperative Study (ADCS), a nationwide consortium supported by Business: Cancer NIH’s National Institute on Aging. Molecular target: Phosphoinositide 3-kinase (PI3K) delta Description: Small molecule inhibitor of phosphoinositide 3-kinase Durect Corp. (NASDAQ:DRRX), Cupertino, Calif. (PI3K) delta King Pharmaceuticals Inc. (NYSE:KG), Bristol, Tenn. Indication: Treat relapsed or refractory hematological malignancies Product: Eladur transdur-bupivacaine (DUR-843) Endpoint: Safety; clinical activity as measured by clinical response rate Business: Neurology assessed by CT scan, clinical laboratory tests and bone marrow biopsy Molecular target: Undisclosed if indicated, pharmacokinetics and pharmacodynamics Description: Transdermal pain patch Status: Phase I started Indication: Treat chronic low back pain Milestone: NA Endpoint: Mean change from baseline to 12 weeks in pain in the last 24 Calistoga began an open-label, U.S. Phase I trial to evaluate oral hours; proportion of patients determined to be “much” or “very much” CAL-101 plus Rituxan rituximab and/or Treanda bendamustine in 36 improved at 12 weeks patients. Biogen Idec Inc. (NASDAQ:BIIB, Cambridge, Mass.) and Status: Phase IIb started Genentech Inc, a unit of Roche (SIX:ROG; OTCQX:RHHBY, Basel, Milestone: NA Switzerland) co-market rituximab as Rituxan in the U.S., while Roche King began a double-blind, placebo-controlled Phase IIb trial to markets it as MabThera elsewhere. Cephalon Inc. (NASDAQ:CEPH, See next page BioCentury Part II APRIL 12, 2010 PAGE B12 OF 15

Clinical Status, pharmacodynamic trial to compare Levadex vs. an intravenous DHE in from previous page 24 healthy volunteers. In January, FDA said a second pivotal efficacy trial for Levadex is not required for an NDA submission (see BioCentury, Jan. evaluate 3 Eladur patches administered every 72 hours for 12 weeks in 18). Map has rights to formulations of DHE delivered via inhalation 260 patients. King gained Eladur through its acquisition of Alpharma devices under a license from Nektar. Inc., which licensed exclusive, worldwide rights to the product from Durect under a 2008 deal (see BioCentury, Sept. 22, 2008). Neovacs S.A., Paris, France Product: IFN-alpha kinoid, Antiferon (IFN-K) H. Lundbeck A/S (CSE:LUN), Copenhagen, Denmark Business: Autoimmune Product: Lu AE04621 Molecular target: Interferon (IFN) alpha Business: Neurology Description: Immunotherapy against interferon (IFN) alpha Molecular target: NA Indication: Treat lupus Description: Dopaminergic agent Endpoint: Safety; immune response, measures of disease, including Indication: Treat Parkinson’s disease disease activity indices and markers for IFN-alpha activity Endpoint: Safety and pharmacokinetics Status: Phase I/II started Status: Phase I started Milestone: Phase I/II data (early 2011) Milestone: NA Neovacs began a double-blind, placebo-controlled, dose-escala- H. Lundbeck began a placebo-controlled Phase I trial to evaluate Lu tion, European Phase I/II trial to evaluate IFN-alpha kinoid in 28 patients. AE04621 in about 100 healthy volunteers. Pervasis Therapeutics Inc., Cambridge, Mass. Inovio Biomedical Corp. (NYSE-A:INO), San Diego, Calif. Product: PVS-10200 Product: VGX-3100 Business: Cardiovascular Business: Infectious Molecular target: Not applicable Molecular target: HPV antigens Description: Tissue engineered allogeneic endothelial cells Description: DNA-based therapeutic vaccine targeting the E6 and E7 Indication: Prevent restinosis in peripheral arterial disease (PAD) proteins of HPV 16 and 18 patients undergoing angioplasty or a stent procedure Indication: Treat human papillomavirus (HPV) infection and cervical Endpoint: Safety; rate of primary patency and restenosis and time to re- cancer intervention Endpoint: Safety; humoral and cellular immune responses Status: Phase I/II started Status: Completed Phase I enrollment Milestone: Preliminary Phase I/II data (2H10) Milestone: Final Phase I data (1Q11) Pervasis began an open-label, dose-escalation, French Phase I/II trial Inovio completed enrollment of 18 females with a history of cervical of PVS-10200 to prevent restenosis in about 30 patients undergoing an intraepithelial neoplasia (CIN) 2/3 in an open-label, dose-escalation, intervention for PAD. U.S. Phase I trial to evaluate 0.6, 2 and 6 mg VGX-3100 delivered via in vivo electroporation. Quest PharmaTech Inc. (TSX-V:QPT), Edmonton, Alberta Product: Oregovomab (OvaRex, OvaRex Mab) Juventas Therapeutics Inc., Cleveland, Ohio Business: Cancer Product: JVS-100 Molecular target: CA 125 Business: Cardiovascular Description: Murine monoclonal targeting CA 125 Molecular target: NA Indication: Adjuvant treatment of advanced ovarian cancer Description: Non-viral DNA plasmid encoding stromal cell-derived Endpoint: CA125 specific T cells as measured by ELISPOT assay; time factor-1 to disease progression and progression-free survival Indication: Treat chronic heart failure Status: Phase II start Endpoint: Safety Milestone: Start Phase II (3Q10) Status: Phase I started Next quarter, Quest PharmaTech will begin a double-blind, Italian Milestone: NA Phase II trial to evaluate IV oregovomab plus carboplatin and paclitaxel Juventas began an open-label, dose-escalation Phase I trial to in 80 patients. evaluate JVS-100 in 16 patients with class III heart failure. Indication: Adjuvant treatment of advanced ovarian cancer Map Pharmaceuticals Inc. (NASDAQ:MAPP), Mountain View, Calif. Endpoint: CA125 specific T cells as measured by ELISPOT assay; time Nektar Therapeutics (NASDAQ:NKTR), San Carlos, Calif. to disease progression and progression-free survival Product: Levadex (formerly MAP0004) Status: Phase II start Business: Neurology Milestone: Start Phase II (3Q10) Molecular target: Serotonin (5-HT) receptor Next quarter, Quest PharmaTech will begin a Canadian Phase II trial Description: Dihydroergotamine mesylate (DHE), a serotonin (5-HT) to evaluate IV oregovomab plus a toll-like receptor 3 (TLR3) as a receptor agonist, delivered via Map’s Tempo Inhaler maintenance therapy following front-line chemotherapy in 30 patients. Indication: Treat acute Endpoint: Compare the acute effect of Levadex to intravenous DHE and Indication: Treat resectable pancreatic cancer placebo on pulmonary artery pressure as measured by echocardiography; Endpoint: CA125 specific T cells as measured by ELISPOT assay; time pharmacokinetics to disease progression and progression-free survival Status: PD trial started Status: Phase II start Milestone: Complete enrollment (2010) Milestone: Start Phase II (3Q10) MAP began a double-blind, placebo-controlled, crossover, U.S. See next page BioCentury Part II APRIL 12, 2010 PAGE B13 OF 15

Clinical Status, 3 weeks for up to 1 year following autologous stem cell transplantation from previous page in 325 patients. A pivotal Phase II trial of brentuximab in relapsed/ refractory Hodgkin’s lymphoma is ongoing, with data expected Next quarter, Quest PharmaTech will begin a U.S. Phase II trial to next half. The companies hope the Phase II data will form the basis evaluate IV oregovomab plus gemcitabine in CA 125 associated resec- for accelerated approval of the agent, while AETHERA will fulfill table pancreatic cancer. requirements needed for full approval. Brentuximab has Orphan Drug designation in the U.S. and EU and Fast Track designation in Repros Therapeutics Inc. (NASDAQ:RPRX), The Woodlands, Texas the U.S. Millennium has rights to brentuximab outside the U.S. and Product: Proellex (CDB-4124) Canada, where Seattle Genetics retains rights (see BioCentury, Dec. Business: Genitourinary 21, 2009). Molecular target: Progesterone receptor Description: Oral selective progesterone receptor modulator (SPRM) Tioga Pharmaceuticals Inc., San Diego, Calif. Indication: Treat anemia associated with uterine fibroids Product: Asimadoline Endpoint: NA Business: Gastrointestinal Status: Phase III action Molecular target: Kappa opioid receptor (OPRK1) (KOR) Milestone: NA Description: Small molecule kappa opioid receptor (OPRK1; KOR) Repros requested that FDA lift a clinical hold on Proellex so that agonist it can conduct a study to evaluate a lower dose of the compound. The Indication: Treat diarrhea predominant irritable bowel syndrome (IBS- company said it submitted additional information from a 6-month D) follow up of 400-500 patients who had received Proellex in Phase III Endpoint: Responder analysis with pain and motility components; trials last year after clinically significant increases in liver enzymes were abdominal pain, stool frequency, urgency and stool consistency observed at doses of 25 and 50 mg. The company said all patients now Status: SPA received have liver enzymes within the normal range and that there was a “clear Milestone: Start Phase III (04/2010) dose response” between the Proellex dose and the incidence of liver Tioga received an SPA from FDA for a pair of planned Phase III trials enzyme-related serious adverse events. Repros proposed that a 12.5 of asimadoline, the first of which is slated to begin this month. The mg or lower dose would avoid the safety problems related to the higher double-blind, placebo-controlled, single-dose, U.S. Phase III studies doses. The agency requested follow-up data for patients treated with will enroll 600 patients each. Tioga has rights to the product from Merck Proellex, as well as pharmacokinetics and a mechanism for Proellex- KGaA (Xetra:MRK, Darmstadt, Germany). induced liver toxicity. Proellex is in Phase III testing for uterine fibroids and anemia associated with uterine fibroids, and Phase II testing for Tragara Pharmaceuticals Inc., San Diego, Calif. endometriosis (see BioCentury, Oct. 5, 2009). Product: Capoxigem apricoxib (, CS-706)) (TG01) Business: Cancer Seattle Genetics Inc. (NASDAQ:SGEN), Bothell, Wash. Molecular target: Cyclooxygenase-2 (COX-2) Takeda Pharmaceutical Co. Ltd. (Tokyo:4502), Osaka, Japan Description: Oral cyclooxygenase-2 (COX-2) inhibitor Product: Brentuximab vedotin (SGN-35) Indication: Treat non-small cell lung cancer (NSCLC) Business: Cancer Endpoint: Time to progression; progression-free survival (PFS), re- Molecular target: CD30 sponse rate, duration of response, overall survival and measures of Description: Antibody-drug conjugate (ADC) composed of an anti- symptom relief CD30 mAb and monomethyl auristatin E (MMAE) Status: Completed Phase II enrollment Indication: Treat second-line Hodgkin’s lymphoma Milestone: Phase II data (3Q10) Endpoint: Progression-free survival (PFS); overall survival and safety Tragara completed enrollment of 128 patients in the double-blind, Status: Phase III started placebo-controlled Phase II APRiCOT-L trial evaluating 400 mg/day oral Milestone: Submit NDA (1H11) Capoigem apricoxib plus Tarceva erlotinib. Tarceva is marketed in the Seattle Genetics and Takeda’s Millennium Pharmaceuticals Inc. U.S. by OSI Pharmaceuticals Inc. (NASDAQ:OSIP, Melville, N.Y.) and subsidiary began the double-blind, placebo-controlled, international Genentech Inc., a unit of Roche (SIX:ROG; OTCQX:RHHBY, Basel, Phase III AETHERA trial to evaluate brentuximab vedotin given every Switzerland), and by Roche elsewhere.

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 2010 and beyond. ‘It’s the BioCentury’TM BioCentury Part II APRIL 12, 2010 PAGE B14 OF 15

OFFERINGS & SECURITIES TRANSACTIONS

Week ended 4/9/10. Shares after Shares after offering: 22.6 million Type: Private placement of units million revolving credit facility to offering refers to shares outstanding. Underwriters: Jefferies; Oppen- Raised: C$510,000 (US$506,634) 2014 from 2012. At Oct. 31, 2009 Proceeds are gross, not net. Shares heimer Units: 10.2 million the company had drawn down $40 offered don’t include overallotments. Overallotment: 525,000 Price: C$0.05 (unit) million on its credit facility. Currency rates used in the week: Note: The amount raised and Shares after offering: 43.8 million C$=US$0.9934; €=US$1.3491; share figures include the sale of a Note: In February, the company Tengion Inc. (NASDAQ: £=US$1.5242 525,000 share overallotment on proposed to sell 7.2 million units TNGN), East Norriton, Pa. April 9. at C$0.07. Each unit comprises a Business: Genitourinary, Gene/ share and a one-year warrant to Cell therapy, Transplant Completed Offerings Axerion Therapeutics Inc., purchase a share at C$0.10. Date completed: 4/9/10 New Haven, Conn. Type: IPO Achaogen Inc., South San Fran- Business: Neurology Ondine Biopharma Corp. (TSX: Raised: $30 million cisco, Calif. Date completed: 4/5/10 OBP), Vancouver, B.C. Shares: 6 million Business: Infectious Type: Venture financing Business: Infectious Price: $5 Date completed: 4/7/10 Raised: $750,000 Date completed: 4/6/10 Shares after offering: 12.4 million Type: Venture financing Investors: Connecticut Innova- Type: Private placement of units Underwriters: Piper Jaffray; Leerink Raised: $56 million tions Raised: C$751,800 (US$746,838) Overallotment: 900,000 Investors: Frazier Healthcare Ven- Units: 12.5 million Note: Last month, the company tures; Alta Partners; 5AM Ven- Biocartis S.A., Lausanne, Swit- Price: C$0.06 (unit) amended the offering to sell 4.4 tures; Arch Venture Partners; zerland Shares after offering: 123.1 mil- million shares at $8-$10. Domain Associates; Venrock; Business: Diagnostic lion Versant Ventures; Wellcome Date completed: 4/8/10 Investors: Company management; Valeant Pharmaceuticals In- Trust Type: Venture financing company directors ternational (NYSE:VRX), Aliso Raised: €30 million ($40.5 mil- Note: Each unit comprises a share Viejo, Calif. Altheos Inc., South San Francisco, lion) and a one-year warrant to pur- Business: Neurology, Dermatol- Calif. Investors: Debiopharm Group; chase a share at C$0.075. The ogy Business: Ophthalmic Johnson & Johnson Development company has until April 23 to raise Date completed: 4/7/10 Date completed: 4/5/10 Corp.; Aescap Venture Manage- a second tranche of C$76,200 Type: Private placement of senior Type: Venture financing ment; Biovest CVA; Advent Ven- (US$75,697) through the sale of notes Raised: $20 million ture Partners; company employ- 1.3 million units. Raised: $400 million Investors: Bay City Capital; Novo ees; Benaruca Note: The unsecured notes bear A/S; Canaan Partners; Life Science Osta Biotechnologies Inc. 7.625% interest and mature in Angels Inc.; Atheneos Capital Cerus Corp. (NASDAQ:CERS), (TSX-V:OBI), Dollard-des- 2020. Valeant, which originally Concord, Calif. Ormeaux, Quebec proposed to raise $350 million, Anthera Pharmaceuticals Inc. Business: Cancer, Infectious, He- Business: Cancer, Neurology, plans to use a portion of the pro- (NASDAQ:ANTH), Hayward, Ca- matology Musculoskeletal ceeds to repurchase its $49 mil- lif. Date completed: 4/6/10 Date completed: 4/6/10 lion of outstanding 3% convert- Business: Autoimmune, Cardio- Type: Debt financing Type: Private placement of units ible subordinated notes due 2010. vascular, Pulmonary Raised: $5 million Raised: C$504,000 (US$500,674) Date completed: 3/2/10 Investors: Oxford Finance Corp. Units: 8.4 million Proposed Offerings Type: Private placement Note: The loan bears 12.04% in- Price: C$0.06 (unit) Raised: $18.2 million terest. Cerus may draw down an Shares after offering: 43.8 million Shares: 2.6 million additional $5 million between Underwriter: Sherbrooke Street Dara BioSciences Inc. Price: $7 Sept. 30 and Dec. 31 under the Capital (NASDAQ:DARA), Raleigh, N.C. Shares after offering: 24.8 million credit facility. Note: Each unit comprises a share Business: Endocrine, Metabolic, Investors: Existing investors and a two-year warrant to pur- Neurology Note: The private placement was MGB Biopharma Ltd., Scotland, chase 0.5 shares, with each whole Date announced: 4/2/10 concurrent with the company’s U.K. warrant exercisable at C$0.10. Type: Follow-on March IPO. Business: Infectious To be raised: Up to $10 million Date completed: 4/6/10 Patheon Inc. (TSX:PTI), Missi- Price prior: $0.44 Ardea Biosciences Inc. Type: Venture financing ssauga, Ontario Note: The company plans to sell (NASDAQ:RDEA), San Diego, Raised: £2 million ($3 million) Business: Supply/Service units that consist of a share and Calif. Investors: Archangel Informal In- Date completed: 4/9/10 warrants to purchase additional Business: Infectious, Cancer, In- vestment; Tri Capital Ltd.; Barwell Type: Private placement of senior shares. flammation plc; Scottish Co-investment Fund notes Date completed: 4/6/10 Raised: $280 million Lorus Therapeutics Inc. (TSX: Type: Follow-on Miraculins Inc. (TSX-V:MOM), Note: The secured notes bear LOR), Toronto, Ontario Raised: $80.5 million Winnipeg, Manitoba 8.625% interest and mature in Business: Cancer, Gene/Cell Shares: 4 million Business: Diagnostic, Proteomics 2017. Patheon also plans to ex- therapy Price: $20 Date completed: 4/1/10 tend the maturity date of its $75 See next page BioCentury Part II APRIL 12, 2010 PAGE B15 OF 15

Proposed Offerings, Shares: 6 million ing slated for April 21. Neovacs Ore Pharmaceuticals Inc. (Pink: from previous page Price: $15-$17 said the number of shares in the ORXE), Gaithersburg, Md. Underwriter: Credit Suisse; Citi- offering may be increased by up to Business: Autoimmune, Genomics Date announced: 4/6/10 group; Cowen; Oppenheimer an additional 343,750 shares via an Date announced: 4/1/10 Type: Private placement of units Overallotment: 900,000 extension clause, not including the Ore Pharmaceutical was de- To be raised: Up to US$17.5 million Note: The company amended its overallotment. listed from NASDAQ for failure Placement agent: Global Hunter IPO and hopes to sell 6 million to comply with the exchange’s list- Securities shares at $15-$17. Alimera refiled ing requirements. Other Financial News Shares outstanding prior: 298 mil- last October to raise up to $80 lion million. It had originally filed in OSI Pharmaceuticals Inc. Price prior: C$0.08 July 2008 to raise up to $75 mil- Anthera Pharmaceuticals Inc. (NASDAQ:OSIP), Melville, N.Y. Note: Each unit comprises a share lion, but withdrew the proposed (NASDAQ:ANTH), Hayward, Ca- Business: Cancer, Endocrine and a five-year warrant to pur- IPO last April, citing market con- lif. Date announced: 4/1/10 chase 0.5 shares. ditions. Business: Autoimmune, Cardio- Holders of OSI’s $115 million vascular, Pulmonary in outstanding 2% convertible se- Nile Therapeutics Inc. Deinove S.A., Paris, France Date announced: 4/6/10 nior notes now have the option to (NASDAQ:NLTX), Berkeley, Business: Agbio/Environmental, Anthera raised $4.2 million convert the debt into shares at Calif. Infectious through the sale of 604,492 shares $29.43 though June 30. Business: Cardiovascular Date announced: 4/7/10 at $7 to cover overallotments Date announced: 4/6/10 Type: IPO from its March 1 IPO, bringing the OxiGene Inc. (NASDAQ: Type: Follow-on To be raised: About €12 million total raised to $46.2 million. OXGN; SSE:OXGN), Waltham, To be raised: TBD ($16.2 million) Anthera, which closed Friday at Mass. Price prior: $0.88 Shares: 1.4 million $6.99, has 24.8 million shares Business: Cancer, Ophthalmic Note: Each unit comprises shares Price: €7.50-€9.16 outstanding. Date announced: 4/7/10 and five-year warrants to purchase Underwriters: Dexia Securities; OxiGene received notice shares. Invest Securities DRI Capital Inc., Toronto, from NASDAQ that it regained Overallotment: 248,499 Ontario compliance with a rule related to PhytoMedical Technologies Note: The offer is expected to Date announced: 4/7/10 audit committee composition re- Inc. (OTCBB:PYTO), Princeton, close on April 20, with the first DRI Capital closed its Drug quirements. N.J. day of trading on Euronext Paris Royalty II fund at $701 million, above Business: Endocrine, Nutraceuti- slated for April 27. Deinove said the initial target of $500 million. RegeneRx Biopharmaceuticals cals the number of new shares in the DRI Capital, which has more than Inc. (NYSE-A:RGN), Rockville, Md. Date announced: 4/2/10 offering may be increased by up to $2 billion under management, ac- Business: Dermatology, Oph- Type: Follow-on an additional 216,086 shares via an quires royalties from pharmaceuti- thalmic, Cardiovascular To be raised: Up to $2 million extension clause, and not includ- cal and biotech companies, research Date announced: 4/1/10 Price prior: $0.03 ing the overallotment. institutes, universities and inven- RegeneRx’s 10-K filing con- Note: The offering is not under- tors. Atlantic-Pacific Capital was tained a going concern qualifica- written. Each unit comprises a Neovacs S.A., Paris, France placement agent and advisor. tion from its independent account- share and a two-year warrant to Business: Autoimmune, Inflamma- ing firm. purchase 0.5 shares, with each tion, Cancer Dyax Corp. (NASDAQ:DYAX), whole warrant exercisable at Date announced: 4/9/10 Cambridge, Mass. Sunesis Pharmaceuticals Inc. $0.03. Type: IPO Business: Cardiovascular, Cancer, (NASDAQ:SNSS), South San Fran- To be raised: About €11 million Antibodies cisco, Calif. ($14.8 million) Date announced: 4/5/10 Business: Cancer Amended Offerings Shares: 2.3 million Dyax raised $8.3 million Date announced: 4/1/10 Price: €4.80-€5.60 through the sale of 2.6 million Sunesis received a letter from Alimera Sciences Inc., Alpha- Overallotment: 395,312 shares at $3.25 to cover overal- NASDAQ indicating the company retta, Ga. Note: In March, Neovacs filed to lotments from its March 25 fol- is not in compliance with the $1 Business: Ophthalmic sell up to 4.4 million shares at low-on, bringing the total raised minimum bid price requirement Date announced: 4/6/10 €5.20-€6 in an IPO on Euronext. to $63.5 million. Dyax, which for continued listing. The com- Type: IPO The offer is expected to close on closed Friday at $3.66, has 97.7 pany has until Sept. 27 to regain To be raised: Up to $102 million April 14, with the first day of trad- million shares outstanding. compliance.

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