BioWorld Today - April 8, 2013


Published on

Covered in this Issue:

• In Q1 Public Biopharmas Shift Fundraising into Overdrive

• Syk 'Em? Rigel Says RA Data Not Far from Pfizer's Phase III

• Ambrx Lands Another Pharma In Potential $300M Astellas Deal

• IPO Flurry Continues: Receptos Files Proposed $86M Offering

• Other News To Note
- QLT Inc., of Vancouver, British Columbia, completed the sale of its punctal plug drug delivery system to Mati Therapeutics Inc.

• Clinic Roundup
- Emergent BioSolutions Inc., of Rockville, Md., expanded the protocol for its ongoing Phase Ib, single-arm, open-label study (Protocol 16009) that is evaluating the safety and efficacy of TRU-016 in combination with rituximab in previously untreated patients with chronic lymphocytic leukemia (CLL).

• Pharma: Other News To Note
- Pozen Inc., of Chapel Hill, N.C., disclosed results of a company-sponsored study at the Academy of Managed Care Pharmacy's 25th Annual Meeting and Expo on April 4.
Read More »

• Bench Press: BioWorld Looks at Translational Medicine
- Researchers from Stanford University published new evidence to support the surprising notion that amyloid fibrils, best known as the likely culprits in Alzheimer's disease, can be beneficial in multiple sclerosis and other neuroinflammatory diseases.

  • Be the first to comment

  • Be the first to like this

BioWorld Today - April 8, 2013

  1. 1. BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARSMONDAY VOLUME 24 , NO. 66APRIL 8, 2013 PAGE 1 OF 7Market Report Q113 Mixed Results for Xeljanz ChallengerIn Q1 Public Biopharmas Shift Syk ’Em? Rigel Says RA DataFundraising into Overdrive Not Far from Pfizer’s Phase IIIBy Peter Winter By Randy OsborneBioWorld Insight Editor Staff Writer Biotech companies generated $5 billion in the first Analysts took as less serious one of two primaryquarter of 2013, just 3 percent less than the $5. 15 billion endpoints that fostamatinib, the oral spleen tyrosineraised in the first quarter last year. The heavy lifting for the kinase (syk) inhibitor for rheumatoid arthritis (RA), missedperiod was carried out by public companies, which were in Phase III trial, and focused skeptically instead on theresponsible for 65 percent of the total. successfully reached goal in the study, known as OSKIRA-1 . The $3.25 billion raised by these public companies was London-based AstraZeneca plc disclosed that33 percent higher than the $2.5 billion total raised in the fostamatinib missed the X-ray endpoint of modified Totalsame period of 2012. The amount included almost $3 billion Sharp Score (mTSS), but hit statistical significance inin follow-on financings with public companies seizing the ACR20 scoring. Results in the latter still fell short of thoseopportunity in a favorable investor climate to sell shares at achieved by Pfizer Inc.’s approved ’s Janus kinase inhibitoror near their prevailing market value with little to no price Xeljanz (tofacitinib citrate) in RA, causing AstraZenecadiscount. partner Rigel Pharmaceuticals Inc.’s stock (NASDAQ:RIGL) In January, for example, Onyx Pharmaceuticals Inc., of to tumble, closing Friday at $4.50, down $3.03, or 40.3South San Francisco, padded its bank balance with $358.6 percent. See Market Report, Page 3 See Rigel, Page 4Ambrx Lands Another Pharma Financings RoundupIn Potential $300M Astellas Deal IPO Flurry Continues: ReceptosBy Marie Powers Files Proposed $86M OfferingStaff Writer By Jennifer Boggs Privately held Ambrx Inc. gained another partner for Managing Editorone of its signature technologies, attracting Tokyo-based Receptos Inc. became the seventh U.S. biotech toAstellas Pharma Inc. to an oncology-focused discovery and file for an initial public offering (IPO) this year, takingdevelopment collaboration in antibody drug conjugates advantage of the emerging growth company provision in(ADCs). the Jumpstart Our Business Start-ups Act and aiming to The economics are mostly back-loaded, with Ambrx raise as much as $86.3 million to support clinical work inreceiving an up-front payment of $15 million and up to multiple sclerosis, inflammatory bowel disease (IBD) and$285 million in potential near- and long-term research, allergic/immune-mediate disorders.development, regulatory and sales-based milestones for The number of shares and share price have not yetan undisclosed number of ADC targets in oncology. A been determined. But the trend of late has been at least aportion of the milestones and royalties are contingent on modestly positive one for biotech, with most companiessuccessful commercialization of products resulting from the to price IPOs in the last six months coming within or atpartnership, with Astellas gaining global rights to develop least close to their anticipated price ranges. The most See Ambrx, Page 5 See Financings Roundup, Page 6 Don’t miss this week’s Bench Press, attached to this issue.INSIDE: OTHER NEWS TO NOTE: QLT, TRIMEL PHARMACEUTICALS, VERTEX ................2 CLINIC ROUNDUP: ARENA, EMERGENT BIOSOLUTIONS, SAREPTA.......................7 To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at
  2. 2. MONDAY, APRIL 8, 2013 BIOWORLD® TODAY PAGE 2 OF 7 Other News To Note Stock Movers 4/5/1 3 • The Chinese Center for Disease Control andPrevention reported the first three confirmed human Company Stock Changecases of avian influenza H7N9 on March 31 . Since then, anadditional 13 cases have been confirmed, mainly in Shanghai. Nasdaq Biotechnology -$3.37 -0.20%Six people with the virus have died. An additional 520 close BioCryst Pharmaceuticals Inc. +$0.37 +28.09%contacts of confirmed cases are being monitored. H7N9 Rigel Pharmaceuticals Inc. -$3.03 -40.24%had previously only been isolated in birds, with outbreaksdocumented in the Netherlands, Japan and the U.S. The Supernus Pharmaceuticals Inc. +$0.39 +7.71%agency is investigating the outbreak to determine the Zogenix Inc. -$0.22 -12.57%source of infection. The virulence and transmission ability(including human-to-human transmission) of the virus are (Biotechs showing significant stock changes Friday)not yet known, and there are no known epidemiologicallinks between the three cases, although there is one leadin a Jiangsu case where a contact of an earlier confirmedcase developed symptoms. The symptoms include acutehigh fever onset, cough and respiratory symptoms. Patients received by Mati other than net sales.developed severe pneumonia after five to seven days, • Trimel Pharmaceuticals Corp., of Toronto, said thatprogressing rapidly to acute respiratory distress syndrome. Trimel BioPharma SRL made an agreement with M&P PatentVirus from the three cases were sequenced and found to AG that a $2 million milestone owed by Trimel on March 31be almost identical. The virus contained genes from both may be paid in two equal installments on April 25 and Mayinfluenza A(H7N9) and A(H9N2), suggesting a reassortant 7, respectively. Trimel also amended its loan agreementavian influenza A virus. with General Electric Capital Corp. to temporarily reduce • QLT Inc., of Vancouver, British Columbia, completed the amount of cash holdings it is required to maintain fromthe sale of its punctal plug drug delivery system to Mati $3.75 million to $1 million until May 1 .Therapeutics Inc. Mati was founded by QLT’s former president • Vertex Pharmaceuticals Inc., of Cambridge, Mass.,and CEO, Robert Butchofsky. The sale is pursuant to an agreed with Bristol-Myers Squibb Co., of New York, toagreement between the companies on Dec. 24, 2012, which carry out Phase II studies of hepatitis C virus treatmentgranted Mati a 90-day option to acquire assets related to PPDS regimens that contain Vertex’s nucleotide analoguetechnology in exchange for $500,000. Under terms of the asset polymerase inhibitor VX-135. Vertex will run two Phasepurchase agreement, QLT received an additional $750,000 II studies including one in treatment-naïve people withpayment at closing, and is eligible for developmental and genotype 1 infection in the second quarter of 2013. Thecommercial milestone payments up to $19.5 million, and a company will launch a second study in treatment-naïvelow single-digit royalty on worldwide net sales of all products people with genotype 1 , 2 or 3 virus, including patients withdeveloped out of it. QLT will also receive a fee on payments cirrhosis, in the second half of 2013. SUBSCRIBER INFORMATION BioWorld® Today (ISSN# 1541-0595) is published every business day by AHC Media, 3525 Piedmont Road, Call (800) 477-6307 to subscribe or if you Building Six, Suite 400, Atlanta, GA 30305 U.S.A. Opinions expressed are not necessarily those have fax transmission problems. Outside U.S. of this publication. Mention of products or services does not constitute endorsement. BioWorld® and Bio- and Canada, call (404) 262-5476. Customer World® Today are trademarks of AHC Media, a Thompson Media Group LLC company. Copyright © 2013 service hours are 8:30 a.m. to 6:00 p.m. EST. AHC Media. All Rights Reserved. No part of this publication may be reproduced without the written con- Jennifer Boggs, (404) 262-5427 sent of AHC Media. (GST Registration Number R128870672). Anette Breindl, (518) 595-4041 ATLANTA NEWSROOM: Executive Editor: Lynn Yoffee, Managing Editor: Jennifer Boggs Donald R. Johnston, (404) 262-5439 Managing Editor: Amanda Lanier, BioWorld Insight Editor: Peter Winter Sharon Kingman, 44 20-8995-3336 Database Editor: Karen Pihl-Carey, Senior Production Editor: Ann Duncan Nuala Moran, 44 127-0812775 Staff Writers: Marie Powers, Randy Osborne Randy Osborne, (415) 328-7323 WASHINGTON BUREAU: Washington Editor: Mari Serebrov Marie Powers, (770) 487-8673 EAST COAST BUREAU: Science Editor: Anette Breindl, Staff Writer: Catherine Shaffer Mari Serebrov, (703) 678-7376 EUROPEAN BUREAU: Staff Writers: Sharon Kingman, Nuala Moran, Cormac Sheridan Catherine Shaffer, (734) 883-7224 BUSINESS OFFICE: Senior Vice President/Group Publisher: Donald R. Johnston Cormac Sheridan, 353-87-6864323 Director of Brand Management: Beth Schilling Peter Winter, (204) 269-0660 Senior Marketing Manager: Sarah Cross, Marketing Coordinator: Tessa Turner Lynn Yoffee, (404) 262-5408 Account Representatives: Matt Hartzog, Paul Marino, Greg Rouse, Chris Wiley Internet: DISPLAY ADVERTISING: For ad rates and information, please call Stephen Vance at (404) 262-5511 or email him at REPRINTS: For photocopy rights or reprints, call our reprints department at (404) 262-5476 PRESS MATERIALS: Send all press releases and related information to
  3. 3. MONDAY, APRIL 8, 2013 BIOWORLD® TODAY PAGE 3 OF 7Market Report of health care investment banking at Roth Capital, toldContinued from page 1 BioWorld Today. “With the strong after-market performancemillion following a public offering of 4.4 million shares. The for public companies that have completed financings, thecompany said the financing will fund clinical development of momentum for the sector should continue into the secondcarfilzomib and oprozomib, as well as sales and marketing quarter.”of new multiple myeloma drug Kyprolis (carfilzomib), Chambers also noted that the first quarter was notwhich gained accelerated approval as a third-line treatment dissimilar to a year earlier, which saw investors zeroing inin patients with relapsed and refractory disease and was on blue chip biotech companies. Given the current positivelaunched in the second half of last year. (See BioWorld markets, investors should also begin to take some liquidityToday, Jan. 17, 2013.) risk and look for investment opportunities in smaller market Onyx rewarded its investors with its stock cap biotech companies.(NASDAQ:ONXX) closing the first quarter at $88.86, a gain There is already some evidence that this is starting toof 17.6 percent. happen with the Nasdaq Biotechnology Index (NBI), which The second largest follow-on offering in the quarter includes a broad range of large and smaller companies,was conducted by Ariad Pharmaceuticals Inc., of Cambridge, jumping 16 percent in the first quarter. The performance ofMass., which raised $323 million a month after the earlier- NBI was also mirrored by the BioWorld Stock Report, whichthan-expected approval of Iclusig (ponatinib) for the recorded an average share price change for the 231 publictreatment of chronic myelogenous leukemia (CML). (See biotechnology companies tracked by the report at 15.6BioWorld Today, Jan. 25, 2013.) percent. Shares of Ariad (NASDAQ:ARIA) closed the quarter at$18.08, down almost 6 percent. IPOs Slow Out of the Gate Another company that was able to tap into the capital There was hope that the two biotech IPOs – Interceptmarkets was Pharmacyclics Inc., of Sunnyvale, Calif., who Pharmaceuticals Inc. (NASDAQ:ICPT) and Kytherain March priced a public offering of 2.2 million shares Biopharmaceuticals Inc. (NASDAQ:KYTH) – which pricedof common stock at $94.20 per share, for a total raise of their offerings at the top end of their ranges on the same$207.2 million. (See BioWorld Today, March 11 , 2013.) day in October was a good indication that better times were The funds will help the company prepare for the ahead for companies thinking about testing the market.commercial launch of ibrutinib, as well as expand (See BioWorld Today, Oct. 12, 2012.)development of the drug in other indications and advance Unfortunately, it hasn’t turned out that way so far, withits other pipeline compounds. Ibrutinib, an investigational new issues few and far between since then. In the firstcancer compound, received an FDA new Breakthrough quarter, BioWorld Snapshots shows that four U.S biotechsTherapy Designation that could allow approval of priced IPOs – the same number completed in the firstparticularly promising drug candidates to be attained based quarter of last year.on a single Phase I trial. All four debuts this year had to adjust their pricing Pharmacyclics is studying ibrutinib, an inhibitor of expectations to get the deals done. Hepatitis C virus (HCV)Bruton’s tyrosine kinase (BTK), in several Phase III trials in player Watertown, Mass.-based Enanta Pharmaceuticals Inc.,hematologic malignancies, as well as some Phase I and II for example, raised $56 million by offering 4 million sharestrials. at $14 apiece – at the low end of its range of $14 to $16. Shares of Pharmacyclics (NASDAQ:PCYC) performed Antibiotic drug developer Tetraphase Pharmaceuticalswell in the quarter to close, March 28 at $80.41 , up 39 Inc., of Watertown, Mass., priced its IPO and achieved itspercent. objective of raising $75 million. Initially, the company planned to offer 6.8 million shares in the price range of $10Capital Market Performance to $12 before filing an amendment with plans to sell 8.3 It has been a great quarter for public biotech companies million shares at a range of $8 to $10. However, like manyas the sector continued to remain hot with investors. companies that have gone before it, Tetraphase ended upAccording to BioWorld Insight analysis, large biotech reducing its share price target and boosting the number ofcompanies, with market caps greater than $1 billion, shares offered.collectively saw their share prices jump by an average of KaloBios Pharmaceuticals Inc. priced a slightly upsized21 .5 percent in the first quarter. offering of 8.75 million shares at $8 apiece for gross That performance almost doubled the Dow Jones proceeds of $70 million, and like Stemline TherapeuticsIndustrial average, which hit a new historical high and Inc., which also priced an IPO the same week, KaloBios cameclosed the quarter up 11 .25 percent. (See BioWorld Insight, in at the low end of its expected pricing range.April 1 , 2013.) Stemline Therapeutics Inc., of New York, closed its IPO “The first quarter scenario continued to be positive See Market Report, Page 7for biotechs,” John Chambers, managing director and head To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at
  4. 4. MONDAY, APRIL 8, 2013 BIOWORLD® TODAY PAGE 4 OF 7Rigel PiperJaffray analyst Ian Somaiya wrote in a researchContinued from page 1 report that “lack of radiographic benefit represents the new Fostamatinib hit the ACR20 endpoint at 24 weeks reality in RA trials.” Rodriguez echoed the point, saying thatvs. placebo in the latest trial, but J.P. Morgan analyst Cory “structural progression is just a difficult [endpoint] in RAKasimov, in a research report, called the results with the now, because the placebo groups don’t seem to progresssyk inhibitor “a little underwhelming” – 10 percent to 15 very much – that is, they don’t get much worse in the termpercent (placebo-adjusted) for the AstraZeneca/Rigel drug, of the study,” and ethical concerns prevent continuingcompared to a range of 18 percent to 26 percent for Xeljanz. beyond six months. “Pfizer had exactly the same problem Kasimov said the numbers are “likely good enough with their results,” Rodriguez said. Somaiya wrote that “afor regulators,” but called them “a little lower than what clear win is fostamatinib’s safety profile vs. tofacitinib andwe had hoped for,” in order to put the compound ahead of marketed biologics.”competitors. In December, top-line results from a Phase IIb study Raul Rodriguez, chief operating officer of South San of fostamatinib in RA showed it superior to placebo at sixFrancisco-based Rigel, pointed out that the ACR20 score weeks, but the compound fell short of a secondary goalbefore placebo adjustment was 49 percent, “which isn’t that of noninferiority against Humira (adalimumab, Abbott), indifferent from [Pfizer’s] 50 percent.” The 15 percent placebo- a market valued around $20 billion. (See BioWorld Today,adjusted score is “lower than we’ve seen historically with Dec. 14, 2012.)this product,” he told BioWorld Today. “In the other three “While it is disappointing that fostamatinib did nottrials we’ve done, we’ve seen 27, 28 and 32 percent. We’ve show an improvement in structural progression (usingaveraged about 30 [percent].” Results from the latest trial mTSS, the other primary endpoint) [in the latest study], weshow a placebo-adjusted number that is “lower, but not view this as more of a missed opportunity [for fostamatinib]crazy lower,” Rodriguez added. to differentiate itself vs. the competition than a surprising finding,” Somaiya added. No new safety signals turned up in the latest study to report, though hypertension remained Clarifying the Regulatory Road a concern. “After speaking with management, we were encouraged to learn that there was a low drop-out rate in for Combination Products the trial,” because of blood pressure or diarrhea problems. A FREE Webinar from Medical Device Daily Major adverse cardiovascular events were below the normal and BioWorld Today range, about 0.5 events per 100 patient years for the drug Tuesday, April 9, 2013 vs. about 0.9 for placebo. 1:00 p.m. to 2:30 p.m. Eastern AstraZeneca licensed worldwide rights to fostamatinib in Through Sponsorship by Novella Clinical 2010 for $100 million up front, an early $25 million milestone payment, $345 million in development, regulatory and initial Novel combination products offer new innovative sales milestones, and $800 million in commercial milestones. diagnostic and treatment options for patients and are Rigel could also get stepped, double-digit royalties on net becoming more prevalent. Register for this FREE webinar sales. (See BioWorld Today, Feb. 17, 2010.) as experts from Novella Clinical and TARIS Biomedical The continuing OSKIRA – a rough acronym that stands explain the regulatory challenges surrounding for “Oral SYK Inhibition in RA” – program is designed to test combination products and provide you with strategies fostamatinib as an oral alternative for RA patients with less and recommendations for avoiding costly mistakes. than optimal response to conventional disease-modifying Key Learning Points: anti-rheumatics, including methotrexate (OSKIRA-1 and • Learn how combination products are defined by FDA OSKIRA-2) and those with an inadequate response to tumor • Explore strategies to obtain the preferred Request for necrosis alpha antagonists (OSKIRA-3). Designation (RFD) response and the process steps Jefferies analyst Thomas Wei noted that two more Phase • Identify clinical requirements, timing and implications III trials are yet to report in the second quarter of this year, for sponsors including OSKIRA-3 in biologic failures, “which is considered • Learn when to engage a CRO partner to be a high-risk study,” he wrote in a research report, choosing to “await the data from the next two studies prior Our experts are Kristin Neff, Sr. Dir. of Clinical Operations to re-evaluating our stance on Rigel.” Jefferies maintains a at TARIS Biomedical; David Novotny, VP of Medical Device “buy” rating on the stock. & Diagnostics at Novella Clinical; and Cynthia Pritchard, “It’s a major amount of data that we just got, literally, PhD, Sr. Regulatory Specialist at Novella Clinical. yesterday,” Rodriguez said Friday. “We’re still plowing through it.” The company officials are encouraged by the Learn more and register today at safety profile, which is “the biggest thing that will keep you or call customer service at 1-800-477-6307 off the market.” ■ To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at
  5. 5. MONDAY, APRIL 8, 2013 BIOWORLD® TODAY PAGE 5 OF 7Ambrx receiving accelerated approval in 2011 in two lymphomaContinued from page 1 indications. After a lull of 18 months, in February the FDAand commercialize the ADCs in oncology. green-lighted T-DM1 , branded Kadcyla, which pairs Roche Still, the partnership represents the third big pharma AG’s Herceptin (trastuzumab) with ImmunoGen Inc.’s DM1collaboration in less than two years for San Diego-based maytansinoid cell-killing agent in HER2-positive metastaticAmbrx. In 2011 , the company inked a deal with Bristol-Myers breast cancer. (See BioWorld Today, Aug. 22, 2011 , and Feb.Squibb Co. for pegylated versions of fibroblast growth 25, 2013.)factor 21 protein and relaxin hormone, for $24 million up Others are nearing the finish line. Last month, Celldexfront. Last year, Ambrx signed a potential $303 million Therapeutics Inc. raised $90 million plus $12.7 million foragreement with Merck & Co. Inc. to design and develop overallotments in a public offering to advance rindopepimut,rationally optimized biologic drug conjugates. (See BioWorld its immunotherapy targeting epidermal growth factorToday, Sept. 23, 2011 , and June 19, 2012.) variant III, in a registration study in front-line glioblastoma The company also has several undisclosed partnerships. multiforme, and CDX-011 (glembatamumab vedotin), a fully Ambrx is developing ADCs for oncology as well as non- human monoclonal ADC targeting glycoprotein NMB thatoncology indications, with the goal of targeting delivery of is in Phase II development in breast cancer. (See BioWorlda cytotoxic payload to a tumor cell or an agonist/antagonist Today, Feb. 7, 2013.)payload to modulate a specific biological receptor or Sutro Biopharma Inc., of San Francisco, is another hotsignaling pathway. Preclinically, the company’s ADCs contestant in the ADC race. In December 2012, the companyhave demonstrated high potency and a wider therapeutic inked a potential $500 million deal with Celgene Corp. thatindex than ADCs created using conventional nonspecific includes two undisclosed targets against which ADCs andconjugation. bispecific antibodies will be deployed, plus the manufacturing Internally, the company is developing ARX201 , a long- of a Celgene-owned antibody to explore Sutro’s platform inacting growth hormone that successfully completed Phase multiple areas. (See BioWorld Today, Dec. 19, 2012.)IIb trials. The company also has earlier stage candidates in Oxford BioTherapeutics Ltd. (OBT) also has several ABTmultiple sclerosis, oncology, hepatitis C virus and diabetes. collaborations, including a deal with Menarini in which the The “elegance of the chemistry” at Ambrx reeled in not Italian pharma company is poised to invest €800 milliononly its pharma partners but also CEO Lawson Macartney, (US$1 billion) in a portfolio of OBT-discovered ADCs. (Seewho joined the company in January from Shire plc, where he BioWorld Today, Oct. 30, 2012.)served as senior vice president of the emerging business unit. Earlier stage, Synthon Biopharmaceuticals, ProgenicsA trained pathologist, Macartney also spent nearly 20 years Pharmaceuticals Inc., Immune Pharmaceuticals, Mersanaat GlaxoSmithKline plc, moving up to senior vice president of Therapeutics, ADC Therapeutics Sarl and Intellectglobal product strategy and project/portfolio management. Neurosciences Inc. are among the biotechs working in the “I am a huge believer in molecular specificity,” Macartney ADC space.told BioWorld Today, noting that past approaches to While the first approved ADCs have dose-limitingconjugating have relied on molecules such as lysine, which toxicities, the new generation can be considered “designerare widely present on the antibody or protein of interest. ADCs,” Macartney said. “This is what is attractive to our“You end up with a really heterogeneous population of strategic collaborators, as well.”molecules – some with two or three payloads added, some Although large collaborations tend to be “organic” ratherwith none, some with 10. The problem is that, in some than blossoming overnight, Ambrx has snagged partnerscircumstances, some of these molecular species, which are by sharing its technology before a deal is signed. “We wantactually in the medicine, are completely inactive.” to make sure that everybody’s clear about the technology The Ambrx ADC technology follows the same medicinal and how it performs,” Macartney said. “We allow them tochemistry approach that’s been used for generations in play around with the technology and get their hands dirty.”small molecules. “It allows us to design exactly how we Going forward, Ambrx will work closely with scientistsattach a molecule and where we attach a molecule to an at Astellas and at subsidiary Agensys Inc., which specializesantibody,” Macartney said. in therapeutic antibody R&D in cancer. The result is a homogenous population of molecules, Internally, Ambrx is using revenue from outsideoffering enormous advantages in potency, selectivity, partnerships to expand the breadth and depth of itsstability and pharmacokinetics – all factoring into the platform science, both in mammalian and non-mammalian“efficacy/safety ratio,” he explained. expression, and to its in-house development activities. “We’re in the position of being able to validate ourNext-Generation ADCs New ‘Designer’ Drugs platform and continue to validate partners’ targets,” A number of other biotechs have married their futures Macartney ADCs, which so far have seen two FDA approvals. Seattle Although the biotech doesn’t plan to expandGenetics Inc.’s Adcetris (brentuximab vedotin) was the first, See Ambrx, Page 6 To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at
  6. 6. MONDAY, APRIL 8, 2013 BIOWORLD® TODAY PAGE 6 OF 7Financings Roundup Receptos said it might also in-license additional programs.Continued from page 1 Besides its internal pipeline, the firm of 35 employeesrecent pricing, Enanta Pharmaceuticals Inc.’s $56 million has leveraged its GPCR technology in deals with Johnson &IPO, fell at the low end of the estimated price range, though Johnson unit Janssen Pharmaceuticals, Eli Lilly and Co. andthe shares of the hepatitis C developer jumped a whopping Japanese firm Ono Pharmaceutical Co. Ltd.23 percent on the first day of trading and have since gained Since its founding, Receptos has accumulated a deficit ofanother 11 percent. (See BioWorld Today, March 22, 2013.) $47.6 million. It closed a $25 million Series A round in 2009, Founded in 2008 by Scripps Research Institute and principal stockholders include ARCH Ventures (15.7scientists Raymond Stevens and Hugh Rosen, San Diego- percent), Flagship Ventures (14.6 percent), Lilly Ventures (15.6based Receptos boasts a G protein-coupled receptor (GPCR) percent), Polaris Venture Partners (8.3 percent) and Venrockstructure-based drug discovery and design technology it is Associates (14.6 percent). The company’s management andusing to build a pipeline of internal and partnered programs, board members hold a total stake of 36.9 percent.aiming either for best-in-class or first-in-class distinctions. As of March 27, Receptos had about 93 million shares The company’s lead program, RPC1063, is targeting in class. The sphingosine 1-phosphate receptor (S1PC) Credit Suisse, Leerink Swann, Wedbush PacGrowmodulator is expected to go up against marketed S1PC Life Sciences and BMO Capital Markets are serving asmodulator Gilenya (fingolimod), the oral multiple sclerosis underwriters for the proposed IPO. Upon pricing, Receptos’(MS) drug sold by Novartis AG, but Receptos is hoping data shares would trade on Nasdaq under the ticker “RCPT.”will confirm a better safety profile for its drug, including In other financings news:reduced cardiovascular side effects, reduced liver toxicity • Cardium Therapeutics Inc., of San Diego, enteredand fewer off-target side effects. a definitive agreement with a single institutional health RPC1063 is in an accelerated design Phase II/III study, care fund managed by Sabby Management LLC, its largestdubbed RADIANCE, in relapsing MS patients, with top- shareholder, for a financing of up to $4 million in grossline data from the Phase II portion expected in mid-2014. proceeds. Under the terms, the regenerative medicine firmPhase II data will look for a significant reduction in the agreed to issue up to 4,012 shares of zero coupon Seriescumulative number of total gadolinium-enhancing lesions A convertible preferred stock, with each share havingas determined by magnetic resonance imaging, while a purchase price and liquidation preference of $1 ,000the primary endpoint in the Phase III portion, according per share while held as preferred stock, or they may beto a special protocol assessment with the FDA, will be converted into 10,989 shares of voting common stock.annualized relapse rate. Net proceeds will be used for general corporate purposes. Pending positive Phase II data, Receptos said it likely Cardium also reported that the NYSE MKT, the company’swill look for a partnership, though it plans to retain some listing exchange, granted an additional quarterly extensionrights and has visions to ultimately build its own specialty of the firm’s listing compliance plan to June 30, in view ofsales force. the proposed financing. Ladenburg Thalmann & Co. served The company also is testing RPC1063 in IBD, with a as exclusive placement agent.Phase II study ongoing in patients with ulcerative colitis. • MEI Pharma Inc., of San Diego, priced a public offeringTop-line results from that trial are due in mid-2014. of about 2 million shares of common stock at $7.50 apiece, Earlier in development, the firm has RPC4046, a a 9.5 percent discount to Thursday’s closing price. Grossmonoclonal antibody directed against interleukin-13, a proceeds are expected to total about $15.2 million. Fundsknown target for treating allergic/immune-mediated will be used to progress the clinical development programdisorders such as asthma. Receptos is moving the drug into for lead candidate, Pracinostat, its oral histone deacetylasePhase II testing for orphan disease eosinophilic esophagitis inhibitor for advanced hematologic malignancies, and for(EoE), with a pre-investigational new drug application (IND) other general corporate purposes. Stifel and Cowen andmeeting with the FDA this year and an IND filing expected Co. acted as joint bookrunners for the offering, while Rothin the first half of 2014. Capital Partners acted as co-manager. The offering is set to Last month, it inked a deal with AbbVie, of Chicago, close on April 10. Shares of MEI (NASDAQ:MEIP) closed Fridaygiving the big pharma firm an option to RPC4046 following at $8.35, up 6 cents. ■the Phase II proof-of-concept trial in EoE. Should AbbVie optin, the firms would share equally in the Phase III costs, and Ambrx Continued from page 5Receptos would retain co-promotion rights in the U.S. Buteven if AbbVie declines, Receptos said it potentially has significantly beyond 65 employees in the near term,the resources to drive development of the drug all the way Macartney hinted more deals are in the works.through approval on its own. “We have some very interesting collaborations under Most of the net proceeds from the proposed IPO would discussion,” he said. “And we may see some licensinggo toward advancing those two compounds, though activity of one or two of our internal assets.” ■ To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at
  7. 7. MONDAY, APRIL 8, 2013 BIOWORLD® TODAY PAGE 7 OF 7Market Report a 5 percent decline (13.4 meters) from baseline in walkingContinued from page 3 ability. As previously reported, Study 202 met its primaryof 3.8 million shares, including the exercise in full of the endpoint of increased novel dystrophin as assessed byoverallotment option covering 497,647 shares, at a price of muscle biopsy at week 48. Through 74 weeks, eteplirsen$10 per share. Gross proceeds totaled $38.2 million and will was well tolerated and there were no clinically significantsupport the firm’s work on therapies targeting cancer stem treatment-related adverse events, serious adverse events,cells. hospitalizations or discontinuations. On Friday, Sarepta’s The collective post-IPO performance of those four shares (NASDAQ:SRPT), gained $1 .78, closing at $36.21 . (Seecompanies at the end of the first quarter was down 5 BioWorld Today, Oct. 4, 2012.)percent, and only Enanta posted a gain (30 percent). The mixed after-market performance of the newlyminted public companies has not deterred others from Pharma: Other News To Noteadding themselves to the IPO queue. In March alone, four companies – Alcobra Ltd., GW • Actavis Inc., of Parsippany, N.J., and ValeantPharma plc, Chimerix Inc. and Omthera Pharmaceuticals Inc. Pharmaceuticals International Inc., of Aliso Viejo, Calif.,– joined six other biotechs with IPOs filed and pending.  entered into an agreement for Actavis to be the exclusive marketer and distributor of an authorized generic of Valeant’s Zovirax ointment (acyclovir 5 percent) product. Clinic Roundup Valeant has granted Actavis the exclusive right to co- promote Zovirax cream to obstetricians and gynecologists • Arena Pharmaceuticals Inc., of San Diego, initiated in the U.S., and Actavis has granted Valeant the exclusivedosing in a Phase I trial of APD334, an oral drug candidate right to co-promote Actavis Specialty Brands’ Cordran Tapetargeting the sphingosine 1-phosphate subtype 1 receptor, (flurandrenolide) product in the U.S.for the potential treatment of autoimmune diseases. The • Covis Pharmaceuticals Inc., of Cary, N.C.,randomized, double-blind, placebo-controlled study will disclosed an agreement today to distribute in the U.S.evaluate the safety, tolerability and pharmacokinetics of Nilandron (nilutamide), Plaquenil (hydroxychloroquine),single-ascending doses of APD334 in up to 64 healthy adult Rilutek (riluzole), Uroxatral (alfuzosin hydrochloride) andvolunteers. Kayexalate (sodium polystyrene sulfate). The products cover • Emergent BioSolutions Inc., of Rockville, Md., a broad array of treatments and disease states: Nilandronexpanded the protocol for its ongoing Phase Ib, single- is used to treat prostate cancer; Plaquenil is an anti-arm, open-label study (Protocol 16009) that is evaluating malarial drug; Rilutek treats amyotrophic lateral sclerosis;the safety and efficacy of TRU-016 in combination with Uroxatral is used to treat benign prostatic hyperplasia;rituximab in previously untreated patients with chronic and, Kayexalate is prescribed to remove dangerously highlymphocytic leukemia (CLL). The expanded protocol will levels of potassium in the blood. Altogether, the productsinclude two additional study cohorts to examine a lower sold $114.6 million in the U.S. last year. Sanofi-Aventis SA,dose of TRU-016 with rituximab in front-line CLL and to of Paris, will retain the existing rights for the products inevaluate the combination in relapsed CLL patients. TRU- countries outside the U.S. Terms of the agreement were not016 is the company’s humanized anti-CD37 monospecific disclosed.protein therapeutic, built on its ADAPTIR modular protein • Pozen Inc., of Chapel Hill, N.C., disclosed results oftechnology platform, for the treatment of CLL. Data from a company-sponsored study at the Academy of Managedboth TRU-016 trials are expected to report in the second half Care Pharmacy’s 25th Annual Meeting and Expo on Aprilof the year. The compound has received orphan drug status 4. The abstract, “The Burden of Secondary Cardiovascularfrom the FDA and the European Commission in CLL. Disease in Commercial and Medicare Patients: A Managed • Sarepta Therapeutics Inc., of Cambridge, Mass., Care Perspective,” demonstrated that the prevention ofreported updated data from Study 202, a Phase IIb open- cardiovascular events with aspirin, plus a proton pumplabel extension study of eteplirsen in Duchenne’s muscular inhibitor, compared to aspirin alone is associated with a netdystrophy (DMD). Results at 74 weeks showed continued per-patient per-year cost decrease of $103 and $145 and astabilization of walking ability in eteplirsen-treated patients potential overall cost decrease of $1 .8 million and $11 millionevaluable on the 6-minute walk test (6MWT). Patients in the for a typical 1 million-member commercial and Medicare30 mg/kg and 50 mg/kg dose cohorts who were able to plan, respectively.perform the 6MWT (modified Intent-to-Treat population,n = 6) showed a statistically significant treatment benefit BioWorld is on Twitter!of 65.2 meters (p </= 0.004) compared to the placebo/ Stay Connected, Follow Us on Twitter!delayed-treatment cohort (n = 4). The eteplirsen-treated in the mITT population demonstrated less than To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at
  8. 8. Bench Press BIOWORLD LOOKS AT T R A N S L AT I O N A L M E D I C I N E MONDAY, APRIL 8, 201 3 PAGE 1 OF 2Anti-Inflammatory Amyloids… DNA replication and so shorten a bit with each cell division. Researchers from Stanford University published Some cancer cells have high levels of a telomerase-repairingnew evidence to support the surprising notion that amyloid enzyme, and inhibiting that enzyme is one antitumorfibrils, best known as the likely culprits in Alzheimer’s strategy. The authors found that they were able to getdisease, can be beneficial in multiple sclerosis and other stem cells to differentiate and stop dividing when theirneuroinflammatory diseases. (See BioWorld Today, Aug. telomeres were short. However, the cells tended to revert2, 2012.) The team had shown in earlier studies that to a stem cell-like phenotype rather easily, given the rightamyloid beta could affect T cells to ultimately improve microenvironmental cues. The authors concluded that “itthe symptoms of mice with the animal equivalent of will be important to test whether critically short telomeresmultiple sclerosis. In their follow-up work, the researchers also influence cell fate in human cancer cells, particularlyidentified a group of six amino acid long peptides that are in the case of telomerase-inhibition strategies designed tocapable of binding to dozens of proteins, including pro- instigate telomere instability.” Their findings appeared ininflammatory cytokines, and improving the symptoms of the April 4, 2013, issue of Cell Stem Cell.multiple sclerosis in animals. Those peptides are found inmultiple amyloid-forming proteins, including amyloid beta, Anthracycline Chemo Is Immunotherapy, Tootau and prion protein. The authors said their work “adds Researchers from the French Institute Gustavefurther experimental support that fibrils might be active Roussy gained new insights into how one class oftherapeutic agents and could represent a new class of chemotherapy, the anthracyclines, activates the immunedrugs for the treatment of neuroinflammation.” It appeared system. Though chemotherapy’s main goal, and its mainin the April 4, 2013, issue of Science Translational Medicine. mechanism of action, is to kill rapidly dividing cells, it has been clear for some time that anthracyclines also work via. . . And Sirtuins effects on the human immune system. In their studies, the A team from Cornell University and the University authors showed that anthracyclines induced the productionof Hong Kong discovered that Sirtuin-6 has a role in of a specific subtype of myeloid cells in response to ATPcontrolling the signaling of the pro-inflammatory cytokine that was released from dead tumor cells. The myeloid cellsTNF-alpha, suggesting a previously unknown mechanism presented antigens to T cells, leading to the production ofby which that molecule may exert its effects. Sirtuins are antitumor T cells. Mice receiving such T cells via transplanta class of proteins whose activation appears to link caloric were protected against tumor xenografts. Though it isrestriction to life span extension, but how they work at the not clear whether the T cells are newly generated or aremolecular level has been the subject of spirited debate. The reactivated memory T cells, the authors concluded thatgoing theory has been that they affect gene expression “anthracyclines promote a crucial ATP-dependent pathway”via their effects on chromatin, but several sirtuins have that ultimately facilitates the activation of both dendriticonly weak effects on histones, which are the chromatin cells and T cells against cancer. Their findings appeared instructural proteins they supposedly work on. In their the April 4, 2013, advance online edition of Immunity.paper, the authors showed SIRT6 works directly on TNF-alpha by cutting a long-chain fatty acid that regulates the Endocannabinoids Mellow Fragile X Symptomscytokine’s secretion from cells into the bloodstream. The Scientists from the Spanish Universitat Pompeuwork “reveals a novel physiological activity for SIRT6,” as Fabra have discovered that blocking endocannabinoidwell as identifying a new mechanism for regulating protein signaling can treat many aspects of Fragile X syndrome, thesecretion. It appeared in the April 4, 2013, issue of Nature. most common inherited cause of intellectual disability and an autism spectrum disorder. In Fragile X syndrome, a typeCommitment Won’t Last with Short Telomeres Researchers at the Canadian University of Montrealhave discovered that stem cells with short telomeres could Let Us Know What You Thinkbe induced to differentiate, but such differentiation was Have comments? Questions? Complaints? Wed likeshort-lived unless their telomeres were also lengthened. to hear it all. Contact Executive Editor Lynn Yoffee at lynn.Telomeres are the tips of chromosomes and a molecular, or (404) 262-5408.division counter, as they cannot be fully replicated during To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at
  9. 9. MONDAY, APRIL 8, 2013 BWT’S BENCH PRESS PAGE 2 OF 2of glutamate receptor signaling is overactive, as is mTOR that “HLA effects in disease pathogenesis go beyond peptidesignaling. Fragile X syndrome produces changes in synaptic specificity to include the strength of immune responsesplasticity, cognitive performance, anxiety, pain sensitivity as dictated by levels of HLA expression.” Their findingsand seizure susceptibility, and because the endocannabinoid appeared in the April 5, 2013, issue of Science.system regulates all of those traits, the authors looked at theeffects of blocking endocannabinoid signaling in mice with Amyloids, Antimicrobials Act TogetherFragile X. They found that blocking one endocannabinoid Antimicrobial and amyloid peptides have at least onereceptor, CB1 , in Fragile X mice “through pharmacological thing in common: Both types of peptides can form poresand genetic approaches normalized cognitive impairment, that make cell membranes permeable to substances thatnociceptive desensitization, susceptibility to audiogenic would otherwise remain locked out. Now, scientists fromseizures, overactivated mTOR signaling and altered Yale University have shown that both types of peptidesspine morphology,” while blocking CB2 reduced anxiety. can cooperate in making membranes leaky. The authorsThe authors concluded that blocking endocannabinoid looked at the effects of an amyloid peptide, an antimicrobialsignaling “is a potential therapeutic approach to normalize peptide, and mixtures of the two. They found that despitespecific alterations in [Fragile X syndrome].” Their work the fact that the peptides cannot interact directly due to theirappeared in the March 31 , 2013, issue of Nature Medicine. physical properties, mixtures of the two were synergistic in inducing membrane leakiness. The authors concludedOpening the F Box that the synergy was due to biophysical properties of cell A team from the University of Pittsburgh discovered membranes. The two types of peptides are synergistic, theya new innate immune system pathway that influences the concluded, because they “induce membrane leakage andrelease of pro-inflammatory cytokines. The authors were cytotoxicity through a shared, cross-cooperative, tension-looking at so-called F box proteins, a class of proteins that induced poration mechanism.” Their findings appeared insuppresses inflammation by marking pro-inflammatory TRAF the April 1 , 2013, advance online edition of the Proceedingsproteins for destruction. In their studies, they discovered that of the National Academy of Sciences.the protein Fbxo3 degrades the key Fbox protein Fbxl2. In astudy of patients with sepsis, the team found that they had Inhibitor Works, but Not as Suspectedhigh levels of Fbxo3 and low levels of Fbxl2. Decreasing the A team from Agios Pharmaceuticals Inc., along withactivity of Fbxo3 decreased the severity of inflammation’s academic and industrial collaborators, published proof-of-consequences in several disease models, including concept data that inhibiting the metabolic enzymes IDH-1pneumonia and sepsis. The authors concluded they have and IDH-2 can lead stem-like leukemia and brain tumor cells“identified a pathway of innate immunity that may be useful to differentiate into mature cells, which in turn stops themto detect subjects with altered immune responses during from continuing to divide. Interestingly, though IDH-1 hascritical illness or provide a basis for therapeutic intervention well-known epigenetic functions, the authors showed thattargeting TRAF protein abundance.” Their work appeared in inhibiting mutant IDH-1 in glioma cells slowed down tumorthe March 31, 2013, issue of Nature Medicine. growth without any appreciable changes in DNA methylation in treated cells. They concluded “a broader investigation ofWhy HLA-C Protects Against HIV Infection the role of . . . enzymes” that are affected by IDH-1 “may be Researchers from the National Institutes of Health warranted.” Their findings were published back to back in thehave confirmed that the protective effect of a previously April 4, 2013, advance online edition of Science.identified single nucleotide polymorphism, or SNP, in HIV-infected individuals is due to overall expression levels of All Fat and Healthythe genes it is near, rather than variants in specific genes. Researchers from the British King’s College LondonPrevious work had shown that HIV-infected Caucasians with have shown that mice lacking the transcription factor T-beta specific variant upstream of HLA-C, a group of immune have better insulin sensitivity than their normal peers,molecules that are important for the presentation of viral despite the fact that they also pack more supposedlyantigens, were better able to hold the virus at bay and unhealthy visceral fat. The authors looked at the role ofprogressed more slowly toward AIDS. In their current work, T-bet because it is an immune transcription factor andthe authors looked at overall HLA-C expression levels and inflammation is associated with metabolic problems. Inhow it correlated with resistance to HIV across different racial their work, they found that T-bet acts through the adaptivegroups. They found that even in groups where the upstream immune system to influence the levels of cytokines in fatSNP is in linkage disequilibrium with HLA-C, meaning that its tissue. Mice lacking the transcription factor remainedpresence does not correlate with HLA-C expression strength, insulin sensitive even on a high-fat diet, so long as theyhigher levels of HLA-C gene expression was protective. had a functioning adaptive immune system. Their workThose higher levels, however, also correlated with higher appeared in the April 2, 2013, issue of Cell Metabolism.risk of developing Crohn’s disease. The authors concluded – By Anette Breindl, Science Editor To subscribe, please call BIOWORLD® Customer Service at (800) 477-6307; outside the U.S. and Canada, call (404) 262-5476. Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at