BioWorld Today - April 8, 2013

BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARS

MONDAY VOLUME 24 , NO. 66
APRIL 8, 2013 PAGE 1 OF 7

Market Report Q113 Mixed Results for Xeljanz Challenger
In Q1 Public Biopharmas Shift Syk ’Em? Rigel Says RA Data
Fundraising into Overdrive Not Far from Pfizer’s Phase III
By Peter Winter By Randy Osborne
BioWorld Insight Editor Staff Writer
Biotech companies generated $5 billion in the first Analysts took as less serious one of two primary
quarter of 2013, just 3 percent less than the $5. 15 billion endpoints that fostamatinib, the oral spleen tyrosine
raised in the first quarter last year. The heavy lifting for the kinase (syk) inhibitor for rheumatoid arthritis (RA), missed
period was carried out by public companies, which were in Phase III trial, and focused skeptically instead on the
responsible 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 that
33 percent higher than the $2.5 billion total raised in the fostamatinib missed the X-ray endpoint of modified Total
same period of 2012. The amount included almost $3 billion Sharp Score (mTSS), but hit statistical significance in
in follow-on financings with public companies seizing the ACR20 scoring. Results in the latter still fell short of those
opportunity in a favorable investor climate to sell shares at achieved by Pfizer Inc.’s approved ’s Janus kinase inhibitor
or near their prevailing market value with little to no price Xeljanz (tofacitinib citrate) in RA, causing AstraZeneca
discount. 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 40.3
South San Francisco, padded its bank balance with $358.6 percent.
See Market Report, Page 3 See Rigel, Page 4

Ambrx Lands Another Pharma Financings Roundup

In Potential $300M Astellas Deal IPO Flurry Continues: Receptos
By Marie Powers Files Proposed $86M Offering
Staff Writer By Jennifer Boggs
Privately held Ambrx Inc. gained another partner for Managing Editor
one of its signature technologies, attracting Tokyo-based Receptos Inc. became the seventh U.S. biotech to
Astellas Pharma Inc. to an oncology-focused discovery and file for an initial public offering (IPO) this year, taking
development 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 in
receiving 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 yet
an undisclosed number of ADC targets in oncology. A been determined. But the trend of late has been at least a
portion of the milestones and royalties are contingent on modestly positive one for biotech, with most companies
successful commercialization of products resulting from the to price IPOs in the last six months coming within or at
partnership, 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
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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 and
Prevention reported the first three confirmed human Company Stock Change
cases of avian influenza H7N9 on March 31 . Since then, an
additional 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 outbreaks
documented 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 epidemiological
links between the three cases, although there is one lead
in a Jiangsu case where a contact of an earlier confirmed
case developed symptoms. The symptoms include acute
high 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 that
progressing rapidly to acute respiratory distress syndrome. Trimel BioPharma SRL made an agreement with M&P Patent
Virus from the three cases were sequenced and found to AG that a $2 million milestone owed by Trimel on March 31
be almost identical. The virus contained genes from both may be paid in two equal installments on April 25 and May
influenza A(H7N9) and A(H9N2), suggesting a reassortant 7, respectively. Trimel also amended its loan agreement
avian 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 from
the 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, to
agreement between the companies on Dec. 24, 2012, which carry out Phase II studies of hepatitis C virus treatment
granted Mati a 90-day option to acquire assets related to PPDS regimens that contain Vertex’s nucleotide analogue
technology in exchange for $500,000. Under terms of the asset polymerase inhibitor VX-135. Vertex will run two Phase
purchase agreement, QLT received an additional $750,000 II studies including one in treatment-naïve people with
payment at closing, and is eligible for developmental and genotype 1 infection in the second quarter of 2013. The
commercial milestone payments up to $19.5 million, and a company will launch a second study in treatment-naïve
low single-digit royalty on worldwide net sales of all products people with genotype 1 , 2 or 3 virus, including patients with
developed out of it. QLT will also receive a fee on payments cirrhosis, in the second half of 2013.

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Market Report of health care investment banking at Roth Capital, told
Continued from page 1 BioWorld Today. “With the strong after-market performance
million following a public offering of 4.4 million shares. The for public companies that have completed financings, the
company said the financing will fund clinical development of momentum for the sector should continue into the second
carfilzomib and oprozomib, as well as sales and marketing quarter.”
of new multiple myeloma drug Kyprolis (carfilzomib), Chambers also noted that the first quarter was not
which gained accelerated approval as a third-line treatment dissimilar to a year earlier, which saw investors zeroing in
in patients with relapsed and refractory disease and was on blue chip biotech companies. Given the current positive
launched in the second half of last year. (See BioWorld markets, investors should also begin to take some liquidity
Today, 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 to
of 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 of
Mass., which raised $323 million a month after the earlier- NBI was also mirrored by the BioWorld Stock Report, which
than-expected approval of Iclusig (ponatinib) for the recorded an average share price change for the 231 public
treatment of chronic myelogenous leukemia (CML). (See biotechnology companies tracked by the report at 15.6
BioWorld 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 – Intercept
markets was Pharmacyclics Inc., of Sunnyvale, Calif., who Pharmaceuticals Inc. (NASDAQ:ICPT) and Kythera
in March priced a public offering of 2.2 million shares Biopharmaceuticals Inc. (NASDAQ:KYTH) – which priced
of 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, with
its other pipeline compounds. Ibrutinib, an investigational new issues few and far between since then. In the first
cancer compound, received an FDA new Breakthrough quarter, BioWorld Snapshots shows that four U.S biotechs
Therapy Designation that could allow approval of priced IPOs – the same number completed in the first
particularly 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 shares
trials. at $14 apiece – at the low end of its range of $14 to $16.
Shares of Pharmacyclics (NASDAQ:PCYC) performed Antibiotic drug developer Tetraphase Pharmaceuticals
well in the quarter to close, March 28 at $80.41 , up 39 Inc., of Watertown, Mass., priced its IPO and achieved its
percent. objective of raising $75 million. Initially, the company
planned to offer 6.8 million shares in the price range of $10
Capital 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 many
as the sector continued to remain hot with investors. companies that have gone before it, Tetraphase ended up
According to BioWorld Insight analysis, large biotech reducing its share price target and boosting the number of
companies, 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 upsized
21 .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 Therapeutics
Industrial average, which hit a new historical high and Inc., which also priced an IPO the same week, KaloBios came
closed 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 7
for biotechs,” John Chambers, managing director and head



Rigel PiperJaffray analyst Ian Somaiya wrote in a research
Continued 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 that
vs. placebo in the latest trial, but J.P. Morgan analyst Cory “structural progression is just a difficult [endpoint] in RA
Kasimov, in a research report, called the results with the now, because the placebo groups don’t seem to progress
syk inhibitor “a little underwhelming” – 10 percent to 15 very much – that is, they don’t get much worse in the term
percent (placebo-adjusted) for the AstraZeneca/Rigel drug, of the study,” and ethical concerns prevent continuing
compared 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 “a
for regulators,” but called them “a little lower than what clear win is fostamatinib’s safety profile vs. tofacitinib and
we 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 six
Francisco-based Rigel, pointed out that the ACR20 score weeks, but the compound fell short of a secondary goal
before placebo adjustment was 49 percent, “which isn’t that of noninferiority against Humira (adalimumab, Abbott), in
different 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 not
trials we’ve done, we’ve seen 27, 28 and 32 percent. We’ve show an improvement in structural progression (using
averaged about 30 [percent].” Results from the latest trial mTSS, the other primary endpoint) [in the latest study], we
show 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 www.BioWorld.com
safety profile, which is “the biggest thing that will keep you
or call customer service at 1-800-477-6307
off the market.” ■



Ambrx receiving accelerated approval in 2011 in two lymphoma
Continued from page 1 indications. After a lull of 18 months, in February the FDA
and 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 DM1
collaboration in less than two years for San Diego-based maytansinoid cell-killing agent in HER2-positive metastatic
Ambrx. 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, Celldex
front. Last year, Ambrx signed a potential $303 million Therapeutics Inc. raised $90 million plus $12.7 million for
agreement 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 factor
Today, 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 that
oncology indications, with the goal of targeting delivery of is in Phase II development in breast cancer. (See BioWorld
a 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 hot
signaling pathway. Preclinically, the company’s ADCs contestant in the ADC race. In December 2012, the company
have demonstrated high potency and a wider therapeutic inked a potential $500 million deal with Celgene Corp. that
index than ADCs created using conventional nonspecific includes two undisclosed targets against which ADCs and
conjugation. 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 in
acting 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 ABT
multiple 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 million
only its pharma partners but also CEO Lawson Macartney, (US$1 billion) in a portfolio of OBT-discovered ADCs. (See
who 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, Progenics
A trained pathologist, Macartney also spent nearly 20 years Pharmaceuticals Inc., Immune Pharmaceuticals, Mersana
at GlaxoSmithKline plc, moving up to senior vice president of Therapeutics, ADC Therapeutics Sarl and Intellect
global 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-limiting
conjugating have relied on molecules such as lysine, which toxicities, the new generation can be considered “designer
are 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” rather
with none, some with 10. The problem is that, in some than blossoming overnight, Ambrx has snagged partners
circumstances, some of these molecular species, which are by sharing its technology before a deal is signed. “We want
actually 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 to
chemistry 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 scientists
attach a molecule and where we attach a molecule to an at Astellas and at subsidiary Agensys Inc., which specializes
antibody,” Macartney said. in therapeutic antibody R&D in cancer.
The result is a homogenous population of molecules, Internally, Ambrx is using revenue from outside
offering enormous advantages in potency, selectivity, partnerships to expand the breadth and depth of its
stability 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 our
Next-Generation ADCs New ‘Designer’ Drugs platform and continue to validate partners’ targets,”
A number of other biotechs have married their futures Macartney said.
to ADCs, which so far have seen two FDA approvals. Seattle Although the biotech doesn’t plan to expand
Genetics Inc.’s Adcetris (brentuximab vedotin) was the first, See Ambrx, Page 6



Financings Roundup Receptos said it might also in-license additional programs.
Continued from page 1 Besides its internal pipeline, the firm of 35 employees
recent 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. and
the 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 of
another 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 (15.7
scientists Raymond Stevens and Hugh Rosen, San Diego- percent), Flagship Ventures (14.6 percent), Lilly Ventures (15.6
based Receptos boasts a G protein-coupled receptor (GPCR) percent), Polaris Venture Partners (8.3 percent) and Venrock
structure-based drug discovery and design technology it is Associates (14.6 percent). The company’s management and
using 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 outstanding.
best in class. The sphingosine 1-phosphate receptor (S1PC) Credit Suisse, Leerink Swann, Wedbush PacGrow
modulator is expected to go up against marketed S1PC Life Sciences and BMO Capital Markets are serving as
modulator 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, entered
and 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 largest
dubbed RADIANCE, in relapsing MS patients, with top- shareholder, for a financing of up to $4 million in gross
line data from the Phase II portion expected in mid-2014. proceeds. Under the terms, the regenerative medicine firm
Phase II data will look for a significant reduction in the agreed to issue up to 4,012 shares of zero coupon Series
cumulative number of total gadolinium-enhancing lesions A convertible preferred stock, with each share having
as determined by magnetic resonance imaging, while a purchase price and liquidation preference of $1 ,000
the primary endpoint in the Phase III portion, according per share while held as preferred stock, or they may be
to 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’s
will look for a partnership, though it plans to retain some listing exchange, granted an additional quarterly extension
rights and has visions to ultimately build its own specialty of the firm’s listing compliance plan to June 30, in view of
sales 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 offering
Top-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. Gross
monoclonal antibody directed against interleukin-13, a proceeds are expected to total about $15.2 million. Funds
known target for treating allergic/immune-mediated will be used to progress the clinical development program
disorders such as asthma. Receptos is moving the drug into for lead candidate, Pracinostat, its oral histone deacetylase
Phase 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 and
meeting with the FDA this year and an IND filing expected Co. acted as joint bookrunners for the offering, while Roth
in 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 Friday
giving 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 opt
in, the firms would share equally in the Phase III costs, and Ambrx
Continued from page 5
Receptos would retain co-promotion rights in the U.S. But
even 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 licensing
go toward advancing those two compounds, though activity of one or two of our internal assets.” ■



Market Report a 5 percent decline (13.4 meters) from baseline in walking
Continued from page 3 ability. As previously reported, Study 202 met its primary
of 3.8 million shares, including the exercise in full of the endpoint of increased novel dystrophin as assessed by
overallotment 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 significant
support 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 . (See
companies 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 newly
minted public companies has not deterred others from Pharma: Other News To Note
adding themselves to the IPO queue.
In March alone, four companies – Alcobra Ltd., GW • Actavis Inc., of Parsippany, N.J., and Valeant
Pharma 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 exclusive
dosing in a Phase I trial of APD334, an oral drug candidate right to co-promote Actavis Specialty Brands’ Cordran Tape
targeting 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) and
volunteers. Kayexalate (sodium polystyrene sulfate). The products cover
• Emergent BioSolutions Inc., of Rockville, Md., a broad array of treatments and disease states: Nilandron
expanded 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 high
lymphocytic leukemia (CLL). The expanded protocol will levels of potassium in the blood. Altogether, the products
include 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 in
evaluate the combination in relapsed CLL patients. TRU- countries outside the U.S. Terms of the agreement were not
016 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 of
technology platform, for the treatment of CLL. Data from a company-sponsored study at the Academy of Managed
both TRU-016 trials are expected to report in the second half Care Pharmacy’s 25th Annual Meeting and Expo on April
of the year. The compound has received orphan drug status 4. The abstract, “The Burden of Secondary Cardiovascular
from 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 of
reported updated data from Study 202, a Phase IIb open- cardiovascular events with aspirin, plus a proton pump
label extension study of eteplirsen in Duchenne’s muscular inhibitor, compared to aspirin alone is associated with a net
dystrophy (DMD). Results at 74 weeks showed continued per-patient per-year cost decrease of $103 and $145 and a
stabilization of walking ability in eteplirsen-treated patients potential overall cost decrease of $1 .8 million and $11 million
evaluable on the 6-minute walk test (6MWT). Patients in the for a typical 1 million-member commercial and Medicare
30 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 www.twitter.com/bioworld
patients in the mITT population demonstrated less than


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 2

Anti-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-repairing
new evidence to support the surprising notion that amyloid enzyme, and inhibiting that enzyme is one antitumor
fibrils, best known as the likely culprits in Alzheimer’s strategy. The authors found that they were able to get
disease, can be beneficial in multiple sclerosis and other stem cells to differentiate and stop dividing when their
neuroinflammatory diseases. (See BioWorld Today, Aug. telomeres were short. However, the cells tended to revert
2, 2012.) The team had shown in earlier studies that to a stem cell-like phenotype rather easily, given the right
amyloid beta could affect T cells to ultimately improve microenvironmental cues. The authors concluded that “it
the symptoms of mice with the animal equivalent of will be important to test whether critically short telomeres
multiple sclerosis. In their follow-up work, the researchers also influence cell fate in human cancer cells, particularly
identified a group of six amino acid long peptides that are in the case of telomerase-inhibition strategies designed to
capable of binding to dozens of proteins, including pro- instigate telomere instability.” Their findings appeared in
inflammatory cytokines, and improving the symptoms of the April 4, 2013, issue of Cell Stem Cell.
multiple sclerosis in animals. Those peptides are found in
multiple amyloid-forming proteins, including amyloid beta, Anthracycline Chemo Is Immunotherapy, Too
tau and prion protein. The authors said their work “adds Researchers from the French Institute Gustave
further experimental support that fibrils might be active Roussy gained new insights into how one class of
therapeutic agents and could represent a new class of chemotherapy, the anthracyclines, activates the immune
drugs for the treatment of neuroinflammation.” It appeared system. Though chemotherapy’s main goal, and its main
in 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 production
of Hong Kong discovered that Sirtuin-6 has a role in of a specific subtype of myeloid cells in response to ATP
controlling the signaling of the pro-inflammatory cytokine that was released from dead tumor cells. The myeloid cells
TNF-alpha, suggesting a previously unknown mechanism presented antigens to T cells, leading to the production of
by which that molecule may exert its effects. Sirtuins are antitumor T cells. Mice receiving such T cells via transplant
a class of proteins whose activation appears to link caloric were protected against tumor xenografts. Though it is
restriction to life span extension, but how they work at the not clear whether the T cells are newly generated or are
molecular level has been the subject of spirited debate. The reactivated memory T cells, the authors concluded that
going 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 dendritic
only weak effects on histones, which are the chromatin cells and T cells against cancer. Their findings appeared in
structural 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 Symptoms
cytokine’s secretion from cells into the bloodstream. The Scientists from the Spanish Universitat Pompeu
work “reveals a novel physiological activity for SIRT6,” as Fabra have discovered that blocking endocannabinoid
well as identifying a new mechanism for regulating protein signaling can treat many aspects of Fragile X syndrome, the
secretion. 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 type
Commitment Won’t Last with Short Telomeres
Researchers at the Canadian University of Montreal
have discovered that stem cells with short telomeres could Let Us Know What You Think
be induced to differentiate, but such differentiation was
Have comments? Questions? Complaints? We'd like
short-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
yoffee@bioworld.com, or (404) 262-5408.
division counter, as they cannot be fully replicated during

Copyright © 2013 AHC Media. Reproduction is strictly prohibited. Visit our web site at www.bioworld.com.

MONDAY, APRIL 8, 2013 BWT’S BENCH PRESS PAGE 2 OF 2

of glutamate receptor signaling is overactive, as is mTOR that “HLA effects in disease pathogenesis go beyond peptide
signaling. Fragile X syndrome produces changes in synaptic specificity to include the strength of immune responses
plasticity, cognitive performance, anxiety, pain sensitivity as dictated by levels of HLA expression.” Their findings
and 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 the
effects of blocking endocannabinoid signaling in mice with Amyloids, Antimicrobials Act Together
Fragile X. They found that blocking one endocannabinoid Antimicrobial and amyloid peptides have at least one
receptor, CB1 , in Fragile X mice “through pharmacological thing in common: Both types of peptides can form pores
and genetic approaches normalized cognitive impairment, that make cell membranes permeable to substances that
nociceptive desensitization, susceptibility to audiogenic would otherwise remain locked out. Now, scientists from
seizures, overactivated mTOR signaling and altered Yale University have shown that both types of peptides
spine morphology,” while blocking CB2 reduced anxiety. can cooperate in making membranes leaky. The authors
The authors concluded that blocking endocannabinoid looked at the effects of an amyloid peptide, an antimicrobial
signaling “is a potential therapeutic approach to normalize peptide, and mixtures of the two. They found that despite
specific alterations in [Fragile X syndrome].” Their work the fact that the peptides cannot interact directly due to their
appeared in the March 31 , 2013, issue of Nature Medicine. physical properties, mixtures of the two were synergistic
in inducing membrane leakiness. The authors concluded
Opening 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, they
a new innate immune system pathway that influences the concluded, because they “induce membrane leakage and
release 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 in
suppresses inflammation by marking pro-inflammatory TRAF the April 1 , 2013, advance online edition of the Proceedings
proteins for destruction. In their studies, they discovered that of the National Academy of Sciences.
the protein Fbxo3 degrades the key Fbox protein Fbxl2. In a
study of patients with sepsis, the team found that they had Inhibitor Works, but Not as Suspected
high levels of Fbxo3 and low levels of Fbxl2. Decreasing the A team from Agios Pharmaceuticals Inc., along with
activity 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-1
pneumonia 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 them
to detect subjects with altered immune responses during from continuing to divide. Interestingly, though IDH-1 has
critical illness or provide a basis for therapeutic intervention well-known epigenetic functions, the authors showed that
targeting TRAF protein abundance.” Their work appeared in inhibiting mutant IDH-1 in glioma cells slowed down tumor
the March 31, 2013, issue of Nature Medicine. growth without any appreciable changes in DNA methylation
in treated cells. They concluded “a broader investigation of
Why 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 the
have 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 Healthy
the genes it is near, rather than variants in specific genes. Researchers from the British King’s College London
Previous work had shown that HIV-infected Caucasians with have shown that mice lacking the transcription factor T-bet
a 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 supposedly
antigens, were better able to hold the virus at bay and unhealthy visceral fat. The authors looked at the role of
progressed more slowly toward AIDS. In their current work, T-bet because it is an immune transcription factor and
the authors looked at overall HLA-C expression levels and inflammation is associated with metabolic problems. In
how it correlated with resistance to HIV across different racial their work, they found that T-bet acts through the adaptive
groups. They found that even in groups where the upstream immune system to influence the levels of cytokines in fat
SNP is in linkage disequilibrium with HLA-C, meaning that its tissue. Mice lacking the transcription factor remained
presence does not correlate with HLA-C expression strength, insulin sensitive even on a high-fat diet, so long as they
higher levels of HLA-C gene expression was protective. had a functioning adaptive immune system. Their work
Those 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

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