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Celldex
Continued from page 1
positive disease, since it would not hit statistical significance
on the primary endpoint: overall survival (OS) in those with
minimal residual disease. DSMB investigators found that the
Rintega arm and the control arm data worked out about the
same, and nobody knows why. “Obviously, there’s something
we’re missing,” he said.
Shares of Hampton, N.J.-based Celldex (NASDAQ:CLDX)
closed Monday at $3.79, down $4.40, or 53.7 percent.
Davis called the ACT IV experiment “relatively complicated”
with “high stakes. Hence, we chose a very experienced DSMB,
including two senior statisticians who fully understand all
of the calculations and ramifications. They looked at the full
complement of data available to them at all endpoints before
making a decision” to put the kibosh on the study. “Right now,
we’re just poring through the data so we can’t tell you what
additional signs or signals might be in there,” he said. “We’ll
talk about that later. [But] the DSMB did the job they were
supposed to do in looking at the study overall, and determining
there was not a chance it would be positive at the end of
the day.” He called the outcome “unfortunate” with “broad
ramifications for scientists and patients.”
In ACT IV, Rintega worked like it has in phase II studies, but the
control arm results turned up way better than history would
suggest: hazard ratio = 0.99; median OS: RINTEGA 20.4
months vs. control 21.1 months. All patients on the Rintega arm
of the ACT IV study, as well as those from prior phase II studies
and existing compassionate use recipients, will be offered
ongoing access to Rintega. Individual patients may be getting
benefit from the drug, and “we would hate to pull the rug out
from under [those] patients” Davis said, speaking to investors
during a conference call.
Roth Capital Partners analyst Joseph Pantginis called the ACT
IV results “a major shock,” especially the “unprecedented”
showing of the control arm, since survival with standard-of-
care therapy is generally around 15 months. “The question is,
what now?” he wrote in a research report. “We do not believe a
downgrade is warranted, based on the quality of the company’s
pipeline and upcoming news flow.” Celldex has five active
programs and is “financially strong,” he noted.
Company officials said cash on hand is sufficient through
2017, which had been the case earlier, Brean Capital analyst
Jonathan Aschoff pointed out during the call. “I’m curious
as to why the cash runway isn’t something you can say today
is longer than it was two weeks ago,” he said. CEO Marucci
replied that “we’re going to have to go through the budget,
as you would expect. What we can say, 48 hours after the
[DSMB] event, is that we still have cash through 2017. This is
just a preliminary estimate. I’m sure we’ll tighten our belt even
further.” Asked whether Celldex would “look more aggressively
to purchase something or ramp up internal discovery” post-
ACT IV’s blowup, he said the firm “keep[s] our options open and
we’re always looking at different things.”
NEXT UP, VARLILUMAB
Meanwhile, the mystery remains. “This happens constantly,”
Aschoff said, “where people are blown away by the control-arm”
performance in phase III trials after a smaller, encouraging phase
II studies led researchers to hope for better. He wanted to know if
Celldex has any preliminary theories.
CMO Davis said the matter is “something we spent a lot of
time thinking about this weekend. In most other diseases,
there’s a broader range of survival and you can identify
patient populations within your group who will do well.” In
glioblastoma, though, the survival range is narrower and
usually more predictable. “We can’t come up with any reason
for this right now,” he said.
At last year’s meeting of the American Society of Clinical
Oncology (ASCO) in Chicago, Celldex’s phase II data with
Rintega, an immunotherapy vaccine targeting EGFRvIII, created
a major buzz. The trial called React had yielded first results the
previous November, when investigators reported interim data
through October 2014. Numbers presented at ASCO included
outcomes through March, showing that, of patients given
Rintega plus standard-of-care Avastin (bevacizumab, Roche
AG), 45 percent were alive after 12 months, compared with
31 percent absent Rintega. A median OS rate of 11.6 months
turned up in the Rintega cohort, compared with 9.3 months
in the control group. Patients were Avastin-naïve when they
started the trial. While the data were early and continue to
mature, the company said, at 18 months, 30 percent of Rintega
patients lived vs. 15 percent of control subjects. (See BioWorld
Today, Nov. 17, 2014, and June 2, 2015.)
The drug, which gained breakthrough status from the FDA in
February 2015, seemed set up for a win in phase III. “We will be
looking to identify potential biomarkers or subsets,” Davis said.
“We hope to better understand what happened here, and we’ll
use that information to improve our research moving forward.
We said before that, from a regulatory perspective, this [React]
study really was just too small. It didn’t have adequate power to
justify approval. As disappointing as the ACT IV data are, [they
don’t] change that position.”
Oppenheimer analyst Christopher Marai said Celldex investor
focus likely will shift now to CD27-targeting varlilumab, subject
of a 2014 deal with New York-based Bristol-Myers Squibb Co.
(BMS) for testing with the latter’s approved PD-1 checkpoint
inhibitor Opdivo (nivolumab) in non-small-cell lung cancer
(NSCLC). BMS made a one-time payment of $5 million to
Celldex, and the parties agreed to share development costs
of the effort, which could turn up efficacy in NSCLC and more.
“Varlilumab’s advancement into phase II is promising, in our
view, as BMS is funding half the cost,” Marai wrote in a research
report, and phase I results are expected in the first half of this
See Celldex, page 5](https://image.slidesharecdn.com/4fd90db7-c120-46b6-83fc-c1c39847bde1-160308131722/85/BioWorldToday03082016-3-320.jpg)
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EMA
Continued from page 1
committee and more help with plotting a route through to
approval.
The new priority medicines (Prime) designation also will provide
enhanced support at the early stages of development for small
biotechs and academic groups that have limited experience of
the regulatory system.
Small and medium-sized entities (SMEs) will be eligible
to secure Prime designation prior to phase II, while larger
companies can sign up before starting phase III. Anyone
seeking the designation will be required to provide compelling
evidence of a product’s potential public health impact.
Overall, the scheme should lead to better informed
development plans and improve the quality of marketing
submissions. EMA committees will have greater awareness and
knowledge of products coming up the pipeline, enabling the
review process to be abbreviated.
Launching the scheme at EMA’s headquarters in London, Guido
Rasi, executive director of the EMA, said that currently two out
of three development programs are inadequate to produce
the evidence the agency needs to make its assessments. “As
a consequence, many of the very promising medicines fail to
reach patients, resources are wasted, costs increase and more
importantly patients are enrolled in useless trials.” That is
particularly the case for studies sponsored by academic groups
and SMEs, Rasi said.
In addition to honing regulatory strategies, health technology
assessment agencies will provide input on how development
should be shaped to generate information for reimbursement,
pricing and access bodies, a move that the EMA claims will
improve resource planning in Europe’s hard-pressed health
care systems.
“Ultimately, this will promote the possibility of earlier access to
promising new medicines,” the EMA said.
The agency is responding to critics who complain its convoluted
assessment procedures are slowing access to innovative drugs,
both undermining commercial potential and failing patients.
EU Health Commissioner Vytenis Andriukaitis said Prime is a
major step forward in providing earlier access to treatments
for unmet medical needs such as rare cancers, Alzheimer’s
disease and other dementias. “This scheme could also help, for
example, to accelerate the development and authorization of
new classes of antibiotics,” he said.
In addition, Andriukaitis said Prime will optimize the use of
the regulatory framework in order to boost pharmaceutical
innovation and employment in the sector.
Over the past year, the EMA’s Committee for Medicinal
Products for Human Use (CHMP) has worked with other EMA
committees, and in consultation with national drugs regulators,
on re-interpreting the agency’s legislative framework to devise
Prime. The result is a scheme which will take time and cost out
of clinical development and make better use of the broad range
of expertise to which the EMA has access, giving a helping
hand to small biotechs and academics with exciting science but
limited resources. (See BioWorld Today, Nov. 9, 2015.)
The goal is to foster better development strategies to help
companies generate the high quality data the EMA needs, Rasi
said. “Patients with no or insufficient treatments could then
benefit from scientific progress and cutting-edge medicines as
soon as possible.”
Zaide Frias, head of human research and development at
the EMA, told BioWorld Today it is not possible to say to what
extent Prime will cut development timelines. “It is difficult to
predict how much faster Prime will be; we will have to gain
experience,” she said.
Frias noted that to back up the aims of the Prime scheme, the
European Commission has said it will cut the time it takes to
rubber stamp EMA recommendations to approve a drug, from
22 days to 10 days.
“So we are confident there will be earlier access, but at this
time we can’t [quantify] this, Frias said.
Similarly, Hans-Georg Eichler, senior medical officer of the
EMA, told BioWorld Today it is not possible to say if approval
rates will go up. “Prime can’t rescue a molecule that is not
beneficial or causes a nasty adverse event, but it can help avoid
avoidable errors on the part of companies,” Eichler said.
A HIGH LEVEL OF ENGAGEMENT
Only innovative products will make the cut, with the EMA
saying that providing an alternative treatment or incremental
benefit will not qualify for Prime. Rather companies will need
to demonstrate potential to address “to a significant extent” an
unmet medical need.
That could include the duration of effect, as is expected to be
the case for regenerative and gene therapies, where one or a
few treatments may show long-term efficacy.
The review of applications for Prime designation will be
carried out by the Scientific Advice Working Party, with
recommendations forwarded to CHMP for rubber-stamping.
Although the EMA intends to publish details of all applications,
it will withhold the names of products that fail to win Prime
status. The agency said this is because failure to secure the
designation does not signify that a product is no good.
SMEs and academic groups whose products are accepted for
Prime may also get reduced-price scientific advice.
A key feature of the Prime scheme is that products which
qualify will be assigned a rapporteur from CHMP, who will
act as chaperone. There will also be access to other EMA
committees, for example the Committee for Advanced
Therapies, as appropriate.
Chair of CHMP Tomas Salmonson said, “By strengthening
collaboration between the scientific committees, and by
See EMA, page 9](https://image.slidesharecdn.com/4fd90db7-c120-46b6-83fc-c1c39847bde1-160308131722/85/BioWorldToday03082016-6-320.jpg)
![TUESDAY, MARCH 8, 2016 BIOWORLD™ TODAY PAGE 7 OF 14
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Spark
Continued from page 1
rhodopsin-linked autosomal-dominant retinitis pigmentosa, or
RHO-adRP, an inherited retinal disease that, in severe cases,
leads to blindness.
“We certainly have an interest in expanding the remit of AAV-
mediated gene therapy,” Katherine High, Spark’s co-founder,
president and chief scientific officer, said of the deal’s rationale.
“If we can tackle autosomal-dominant diseases as well as the
X-linked and autosomal-recessive diseases that we’re working
on now, that just expands our armamentarium.”
Two years ago, Jason Loveridge, Genable’s CEO, called the
collaboration with Spark a “coup,” telling BioWorld Today the
original partnership was “really driven by the quality of the
science. Spark is not a contract manufacturer.” (See BioWorld
Today, March 26, 2014.)
In return for a license to its adeno-associated virus (AAV)
manufacturing intellectual property, Spark received revenues
from the manufacture and supply of the product and was
entitled to development milestones and sales royalties.
Genable, in turn, was able to piggyback on the experience
of Spark’s team. The Irish firm’s gene suppression-and-
replacement approach is designed to address all mutations
in the gene encoding rhodopsin. The protein, a photosensitive
G protein-coupled receptor, is expressed in retinal cells and
plays a central role in the transduction of light to electrical
signals.
By delivering AAV vectors developed and manufactured at
Spark, Rhonova is designed at once to suppress the expression
of a faulty gene by encoding an RNAi molecule to suppress
translation of mutated (and wild-type) RHO transcripts and to
deliver normal copies of the gene by encoding a wild-type RHO
protein from which the RNAi recognition sequence has been
eliminated.
“The ability to address autosomal-dominant diseases by using
a suppression-and-replacement therapy strategy is something
we want to be able to do for a wide range of diseases,” High
told BioWorld Today. “In some ways, the ability to address
it first in an ocular target where you can be very sure that
you’re delivering the vector to the target cells of interest is an
attractive way to start.”
Rhonova has orphan drug designation both in the U.S. and EU,
in addition to advanced therapy medicinal product designation
from the EMA. RHO-adRP, which affects an estimated 12,000
patients in the U.S. and the five major European markets,
currently has no approved pharmacologic treatment.
‘THEY’RE A MODEL OF CLARITY’
Ena Prosser, a partner in the Dublin office of Genable investor
Fountain Healthcare Partners and member of Genable’s
board, credited Jane Farrar, the company’s co-founder and
chief scientific officer, and her team at Trinity College Dublin
(TCD) for shepherding the asset through more than 30 years
of research, “and it really is fueled by the patients and their
families,” Prosser said. “Our main priority is to allow the
Genable team and the product’s dedicated creators to integrate
Rhonova into Spark’s pipeline and see if this really can cure
[RHO-adRP].”
High also praised Farrar, a member of Spark’s scientific
advisory board, and the Genable scientific team.
“We had been working with Jane and her colleagues at
Genable for a number of years, and they’ve been a great
group of collaborators,” High said, singling out TCD’s Sophia
Millington-Ward and Naomi Chadderton as well as Paul
Kenna, an ophthalmologist and Genable’s co-founder and
chief medical officer. “Together, they’ve really driven he work
forward.”
As a fellow scientist, High placed a high priority not only on
identifying “first-rate collaborators, and Jane Farrar definitely
meets that bar,” but also on liaising with researchers who were
focused on the endgame of treating patients.
“Jane really is therapeutically oriented,” she said. “She is
always thinking about how what she’s doing can be safely and
effectively translated for patients. If you look at their papers,
they’re a model of clarity. No controls are left out. That’s just a
great collaborator for a company like Spark.”
The companies have been working together through a joint
steering committee since initiating their 2014 collaboration,
with face-to-face meetings every three months that rotate
between Philadelphia and Dublin. That process will continue,
High said.
Genable had raised €5 million (US$6.8 million) in November
2011 and aimed to raise another €8 million to enable it to
advance Rhonova into a phase I study that aimed to enroll 30
to 35 patients. (See BioWorld Today, Nov. 14, 2011.)
The timetable for a first-in-human trial still depends on a few
interim steps, High said. Genable published proof-of-concept
data on Rhonova and designed a number of experiments
in a large animal model to optimize the relative ratios of
suppression and replacement. The next step is to execute those
studies with the material supplied by Spark.
Genable also has designed some natural history and run-in
studies, “and we’ll be working together on those, too,” High
said.
At first blush, J.P. Morgan analyst Cory Kasimov liked the deal.
“This is probably best characterized as a modest deal (in
terms of price and stage), but it appears to be a prudent
strategic decision for Spark,” he wrote in an email. “In
addition to full rights to the lead program, this acquisition
also gives Spark access to Genable’s suppression/
augmentation approach with potential applications outside
the primary indication.”
See Spark, page 8](https://image.slidesharecdn.com/4fd90db7-c120-46b6-83fc-c1c39847bde1-160308131722/85/BioWorldToday03082016-7-320.jpg)
![TUESDAY, MARCH 8, 2016 BIOWORLD™ TODAY PAGE 8 OF 14
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Capella
Continued from page 1
program through to phase IIa development by the end of
2018, and to complete preclinical development of four other
products.
That follows an initial investment of £1.5 million seed funding
in 2014, with which, rather than shaping up an existing body of
academic research, Capella Chief Operating Officer (COO) Steve
Holmes was charged to go out and prospect for five therapeutic
antibody projects around which to form a company.
The seed money came from the founding investors, Advent
Life Sciences and Medicxi Ventures (then Index Ventures). As
Holmes explained, the idea was to draw on his experience, and
that of the VC backers, to select the best monoclonal antibody
projects.
“The key was the targets; they had to be novel, and to have
good biology to go with them,” Holmes said.
Antibody generation has now advanced to the point where a
number of platforms are available and in that sense products
are commoditized.
“We are agnostic about platforms. Making antibodies is
relatively straightforward; it is the targets that make the
difference,” Holmes told BioWorld Today. “[Products] could be
fully human or mouse, it depends what we want to get out of
the antibody,” he said.
From initial prospecting in 2014, London-based Capella has
advanced to the point of having lead panels of antibodies for
its top three programs and has in-licensed target biology for a
further two programs.
The first program, in inflammatory bowel disease, rests on
research from Sanford Burnham Prebys Medical Discovery
Institute in La Jolla, Calif. Although not revealing any details,
Holmes said that is a known target in which Capella is aiming
at a particular aspect of the biology that has not been exploited
previously,
“It happens to be a difficult concept for developing an antibody,
but we’ve got initial [constructs],” Holmes said.
The second program, in fibrosis, is based on intellectual
property from Leeds University.
If target biology is now the key to antibody drug development,
the central requirement in its selection is expertise in
therapeutic targets.
Holmes has some form here, being former COO of murine
antibody company Kymab Ltd. and of Domantis Ltd., and
heading the monoclonal antibody group at Smithkline
Beecham plc and then Glaxosmithkline plc, during the
pioneering decade from 1990 to 2001.
Capella’s clinical and scientific advisory group include antibody
doyen Don Drakeman, founder of two leading U.S. and
European companies, Medarex Inc. (acquired by Bristol-Myers
Squibb Co. for $2.4 billion in 2009) and Genmab A/S.
Meanwhile, Kevin Johnson, partner at Medicxi and board
member at Capella, was head of research at Cambridge
Antibody Technology plc, a corporate foundation stone of the
monoclonal antibody therapeutics sector.
In addition to reflecting the maturity and quality of monoclonal
antibody platforms, Capella exemplifies the asset-based
investment strategies of the founding VCs.
Rather than making an initial investment in forming a
company, the two invest in taking on half-formed assets and
shaping them up to be suitable for pharma pipelines.
The focus then is on conducting a program of research that
will validate – or not - a particular asset, with the aim of
establishing proof of concept in around three years for an
investment of around $20 million.
“The intention with our five therapeutic monoclonal antibodies,
is quick in, quick out. This is a really good model for a start-up;
we have been completely funded by Advent and Medicxi from
nothing,” Holmes said.
“In fact, we started one program and dropped it after five
months and found a substitute - so we are very lethal. But with
the last five targets everything has worked,” said Holmes.
The intention will be to find commercialization partners at an
early stage, and Holmes said he expects to be ready to start the
hunt for partnerships before the end of the year.
The profile and connections of the investors and the board
means Capella “can go straight to the top” when trying to
attract big pharma, he added.
Joining the founding investors Advent and Medicxi in the
series A is Philadelphia-based Osage University Partners, a VC
specializing in the commercialization of academic research.
The series A investment in Capella is Medicxi’s first since
splitting from Index Ventures and launching a new $250 million
fund dedicated to early stage European research in February.
(See BioWorld Today, Feb 3, 2016.) //
This could be a busy year for Spark. Initial efficacy data for
SPK-FIX in hemophilia B, partnered with New York-based Pfizer
Inc., are due midyear along with initial safety and efficacy data
for SPK-CHM in choroideremia due in the second half of 2016.
With a biologics license application filing for lead therapy SPK-
RPE65 (voretigene neparvovec) in RPE65-mediated inherited
retinal dystrophy following positive phase III data last year and
investigational new drug filings for SPK-FVIII in hemophilia A
and SPK-TPP1 in TPP1 deficiency, a form of Batten disease, also
expected in the second half, “we continue to believe that ONCE
is an underappreciated story in SMID biotech,” Kasimov added.
(See BioWorld Today, Oct. 6, 2015.)
On Monday, Spark’s shares closed at $35.69 for a gain of
$1.16. //
Spark
Continued from page 7](https://image.slidesharecdn.com/4fd90db7-c120-46b6-83fc-c1c39847bde1-160308131722/85/BioWorldToday03082016-8-320.jpg)
BioWorldToday03082016
- 1. For Sales Inquiries:http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. MARCH 8 , 2016 VOLUME 27, NO. 45BIOTECH’S MOST RESPECTED NEWS SOURCE FOR MORE THAN 20 YEARS BIOWORLD TODAYTM THE DAILY BIOPHARMACEUTICAL NEWS SOURCE See Celldex, page 3 See Abbvie, page 4 See EMA, page 6 See Spark, page 7 See DBV, page 5 RINDO AT INTERMISSION AS CONTROL ARM OVERPERFORMS IN THE CLINIC IN THIS ISSUE REGULATORY NEWCO NEWS DEALS AND M&A See Capella, page 8 Regulatory front, p. 2 Other news to note, p. 2, 4, 5, 9, 11, 12 In the clinic, p. 9-11, 13 Financings, p. 14 Phase II data keep DBV’s Viaskin peanut allergy therapy on track By Cormac Sheridan, Staff Writer DUBLIN – DBV Technologies SA reported further progress from its patch-based peanut allergy therapy, Viaskin Peanut, at the American Academy of Allergy, Asthma and Immunology (AAAAI) Abbvie strikes $595M deal for Boehringer anti-IL-23 MAb By Michael Fitzhugh, Staff Writer Abbvie Inc. agreed to pay Boehringer Ingelheim GmbH $595 million up front for the opportunity to co-develop and later sell BI 655066, a phase III anti-IL-23 monoclonal antibody for psoriasis that could eventually help the North Chicago- based company replace revenue losses that it will face as its largest product, Celldex lowers curtain on ACT IV phase III in glioblastoma; subset data under study By Randy Osborne, Staff Writer Regarding the stopped phase III glioblastoma trial with Rintega (rindopepimut), Celldex Therapeutics Inc. CEO Anthony Marucci said the firm is “well positioned to weather this temporary setback,” and during the weeks ahead will ransack data from ACT IV for clues to why control arm patients did just as well as those on the drug. Thomas Davis, chief medical officer (CMO), said the firm learned only late Friday that the data safety monitoring board (DSMB) recommended Celldex pull the plug on the study in patients with newly diagnosed, epidermal growth factor variant III (EGFRvIII)- Antibody firm Capella raises $15.5M for novel targets, good biology By Nuala Moran, Staff Writer LONDON – The U.K.’s latest antibody company, Capella Biosciences Ltd., announced the closing of an £11 million (US$15.5 million) series A round, providing the funding to take the lead EMA launches Prime to accelerate, improve regulatory process By Nuala Moran, Staff Writer LONDON – The EMA has launched its latest scheme for accelerating the assessment of drugs, promising support tailored to the stage of development, ongoing access to its approvals ‘Spark’ plug: Genable’s Rhonova adds inherited retinal disease asset By Marie Powers, News Editor Two years after inking an agreement to provide manufacturing services and clinical development assistance for GT038, the lead program at Genable Technologies Ltd., Spark Therapeutics Inc. is acquiring the Dublin-based company and its technology, now known as Rhonova. Terms call for Spark to pay Genable shareholders $6 million in cash and 265,000 shares of Spark’s common stock (NASDAQ:ONCE), valued at $9.15 million, based on Friday’s closing price of $34.53. Additional details were not disclosed, but Genable said its board’s endorsement of the deal was unanimous. Although Genable will operate as a wholly owned subsidiary and remain in Ireland, the deal gives Philadelphia- based Spark control over the future of Rhonova, which targets the treatment of BIOWORLD™ IS ON TWITTER Stay connected — follow us on Twitter! www.twitter.com/bioworld
- 2. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 2 OF 14 BIOWORLD TODAY BioWorld™ Today (ISSN# 1541-0595) is published every business day by Thomson Reuters, 115 Perimeter Center Place, Suite 1100, Atlanta, GA 30346 U.S.A. Opinions expressed are not necessarily those of this publication. Mention of products or services does not constitute endorsement. All Rights Reserved. No part of this publication may be reproduced without the written consent of Thomson Reuters (GST Registration Number R128870672). OUR NEWSROOM Atlanta - Lynn Yoffee (News Director), Jennifer Boggs & Amanda Lanier (Managing Editors), Peter Winter (BioWorld Insight Editor), Karen Pihl-Carey (Database Editor), Ann Duncan (Senior Production Editor), Marie Powers (News Editor), Randy Osborne (Staff Writer) // East Coast - Anette Breindl (Senior Science Editor), Mari Serebrov (Regulatory Editor) // West Coast - Michael Fitzhugh (Staff Writer) // Europe - Nuala Moran & Cormac Sheridan (Staff Writers) // Asia: John Fox, Shannon Ellis, Alfred Romann, Dave Silver, Cornelia Zou (Staff Writers) PRACTICAL INFORMATION For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_ Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336- 4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. For ad rates & information, contact Tyler Beatty toll free at (855) 260-5607 or, outside the U.S. and Canada, at (646) 223-7585, email tyler.beatty@thomsonreuters.com. For photocopy rights or reprints, please contact Tyler Beatty toll free at (855) 260-5607 or, outside the U.S. and Canada, at (646) 223-7585, or by email at tyler.beatty@ thomsonreuters.com. Send all press releases and related information to newsdesk@bioworld.com. BUSINESS OFFICE Donald R. Johnston (Senior Director, Current Awareness), Sarah Cross (Marketing Director), Penney Holland (Web Production Manager) CONTACT US Jennifer Boggs, (770) 810-3120 // Anette Breindl, (770) 810-3134 // Sarah Cross, (770) 810-3138 // Michael Fitzhugh, (770) 810-3064 // Penney Holland, (770) 810-3047 // Donald R. Johnston, (770) 810-3118 // Nuala Moran, 44-7778-868-579 // Randy Osborne, (770) 810-3139 // Marie Powers, (770) 810-3136 // Mari Serebrov, (770) 810-3141 // Cormac Sheridan, 353-87- 6864323 // Peter Winter, (770) 810-3142 // Lynn Yoffee, (770) 810-3123 REGULATORY FRONT OTHER NEWS TO NOTE The FDA is launching a lean management mapping approach to build a better system to review combination products that include a device and a drug or biologic. With an eye on encouraging innovation and supporting the development of the products, the agency aims to create a review process that’s efficient, consistent and predictable, according to an FDAvoice blog posted Monday. As a first step, the agency will look at how combination products are currently being reviewed, highlighting areas of delay or redundancy. Creating a baseline map will allow the FDA to identify metrics for success and assess the impact of improvements as they’re implemented. The second step will be to develop a “future state” map showing a streamlined, efficient process that will eliminate delays and redundancies. The National Cancer Institute (NCI) is considering the development of a specimen bank for tube and ovary tissues from women undergoing surgery for benign conditions, risk reduction and early stage cancer. Collecting tube and ovary tissues containing clinically unsuspected precursors or early stage cancer has been challenging, especially from women who are not at increased genetic risk, according to an NCI notice to be published in Tuesday’s Federal Register. However, many pathology laboratories have enhanced their processing protocols for gynecologic surgical specimens removed for benign indications, which might make a specimen bank possible. The NCI is proposing a survey to determine the volume of samples at different pathology labs and the methods the labs use to process the samples. The survey results would enable the NCI to determine the feasibility of establishing a tissue bank for research and provide insights into the design of a pilot study. Comments on the survey are due by May 7. The FDA finalized a draft guidance released nearly a year ago about when sponsors of drugs with potential estrogenic, androgenic or thyroid (E, A or T) activity should submit an environmental assessment (EA) or a claim of categorical exclusion. The guidance also clarifies what information should be included in an exclusion claim, according to a notice published in Monday’s Federal Register. Since late cycle requests for additional environmental information could delay approval, sponsors should consult with the FDA early on about the information that may be needed to determine whether an EA or an exclusion claim would be required. Failure to submit an EA or exclusion claim for a drug with E, A or T activity could lead to the FDA refusing to file an application or denying approval. Adma Biologics Inc., of Ramsey, N.J., presented findings from preclinical experiments conducted in collaboration with Baylor University College of Medicine at the American Academy of Allergy Asthma and Immunology meeting in Los Angeles. The studies compared the effects of RI-002, an intravenously administered human immunoglobulin preparation containing a high titer anti-respiratory syncytial virus (RSV) polyclonal antibody, to monoclonal anti-RSV antibody Synagis (palivizumab, Medimmune) in cotton rats infected with a palivizumab-resistant strain of RSV. The data suggested that RI-002 and palivizumab were comparable in diminishing the viral load in the lungs of RSV-infected cotton rats but only RI- 002 prevented RSV infection when a palivizumab-resistant strain of RSV was administered. Serum neutralization titers achieved by palivizumab at the approved dose level of 15 mg/ kg were about fourfold lower than those achieved by a dose of 1,500 mg/kg of RI-002. (See BioWorld Today, Feb. 26, 2015.) Arrowhead Research Corp., of Pasadena, Calif., presented preclinical data at the American Academy of Allergy, Asthma and Immunology meeting in Los Angeles, suggesting that ARC-F12, an RNAi therapeutic that inhibits the production of factor XII, has the potential to treat hereditary angioedema and to prevent thrombosis. Data showed that ARC-F12 had the desired effects of significantly reduced swelling in a rat model of edema and inhibition of blood clot formation in a mouse model of thrombosis, without the undesired effect of increased bleeding risk. The company is conducting studies in order to advance ARC-F12 into clinical trials.
- 3. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 3 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. Celldex Continued from page 1 positive disease, since it would not hit statistical significance on the primary endpoint: overall survival (OS) in those with minimal residual disease. DSMB investigators found that the Rintega arm and the control arm data worked out about the same, and nobody knows why. “Obviously, there’s something we’re missing,” he said. Shares of Hampton, N.J.-based Celldex (NASDAQ:CLDX) closed Monday at $3.79, down $4.40, or 53.7 percent. Davis called the ACT IV experiment “relatively complicated” with “high stakes. Hence, we chose a very experienced DSMB, including two senior statisticians who fully understand all of the calculations and ramifications. They looked at the full complement of data available to them at all endpoints before making a decision” to put the kibosh on the study. “Right now, we’re just poring through the data so we can’t tell you what additional signs or signals might be in there,” he said. “We’ll talk about that later. [But] the DSMB did the job they were supposed to do in looking at the study overall, and determining there was not a chance it would be positive at the end of the day.” He called the outcome “unfortunate” with “broad ramifications for scientists and patients.” In ACT IV, Rintega worked like it has in phase II studies, but the control arm results turned up way better than history would suggest: hazard ratio = 0.99; median OS: RINTEGA 20.4 months vs. control 21.1 months. All patients on the Rintega arm of the ACT IV study, as well as those from prior phase II studies and existing compassionate use recipients, will be offered ongoing access to Rintega. Individual patients may be getting benefit from the drug, and “we would hate to pull the rug out from under [those] patients” Davis said, speaking to investors during a conference call. Roth Capital Partners analyst Joseph Pantginis called the ACT IV results “a major shock,” especially the “unprecedented” showing of the control arm, since survival with standard-of- care therapy is generally around 15 months. “The question is, what now?” he wrote in a research report. “We do not believe a downgrade is warranted, based on the quality of the company’s pipeline and upcoming news flow.” Celldex has five active programs and is “financially strong,” he noted. Company officials said cash on hand is sufficient through 2017, which had been the case earlier, Brean Capital analyst Jonathan Aschoff pointed out during the call. “I’m curious as to why the cash runway isn’t something you can say today is longer than it was two weeks ago,” he said. CEO Marucci replied that “we’re going to have to go through the budget, as you would expect. What we can say, 48 hours after the [DSMB] event, is that we still have cash through 2017. This is just a preliminary estimate. I’m sure we’ll tighten our belt even further.” Asked whether Celldex would “look more aggressively to purchase something or ramp up internal discovery” post- ACT IV’s blowup, he said the firm “keep[s] our options open and we’re always looking at different things.” NEXT UP, VARLILUMAB Meanwhile, the mystery remains. “This happens constantly,” Aschoff said, “where people are blown away by the control-arm” performance in phase III trials after a smaller, encouraging phase II studies led researchers to hope for better. He wanted to know if Celldex has any preliminary theories. CMO Davis said the matter is “something we spent a lot of time thinking about this weekend. In most other diseases, there’s a broader range of survival and you can identify patient populations within your group who will do well.” In glioblastoma, though, the survival range is narrower and usually more predictable. “We can’t come up with any reason for this right now,” he said. At last year’s meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Celldex’s phase II data with Rintega, an immunotherapy vaccine targeting EGFRvIII, created a major buzz. The trial called React had yielded first results the previous November, when investigators reported interim data through October 2014. Numbers presented at ASCO included outcomes through March, showing that, of patients given Rintega plus standard-of-care Avastin (bevacizumab, Roche AG), 45 percent were alive after 12 months, compared with 31 percent absent Rintega. A median OS rate of 11.6 months turned up in the Rintega cohort, compared with 9.3 months in the control group. Patients were Avastin-naïve when they started the trial. While the data were early and continue to mature, the company said, at 18 months, 30 percent of Rintega patients lived vs. 15 percent of control subjects. (See BioWorld Today, Nov. 17, 2014, and June 2, 2015.) The drug, which gained breakthrough status from the FDA in February 2015, seemed set up for a win in phase III. “We will be looking to identify potential biomarkers or subsets,” Davis said. “We hope to better understand what happened here, and we’ll use that information to improve our research moving forward. We said before that, from a regulatory perspective, this [React] study really was just too small. It didn’t have adequate power to justify approval. As disappointing as the ACT IV data are, [they don’t] change that position.” Oppenheimer analyst Christopher Marai said Celldex investor focus likely will shift now to CD27-targeting varlilumab, subject of a 2014 deal with New York-based Bristol-Myers Squibb Co. (BMS) for testing with the latter’s approved PD-1 checkpoint inhibitor Opdivo (nivolumab) in non-small-cell lung cancer (NSCLC). BMS made a one-time payment of $5 million to Celldex, and the parties agreed to share development costs of the effort, which could turn up efficacy in NSCLC and more. “Varlilumab’s advancement into phase II is promising, in our view, as BMS is funding half the cost,” Marai wrote in a research report, and phase I results are expected in the first half of this See Celldex, page 5
- 4. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 4 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. Abbvie Continued from page 1 Humira (adalimumab), begins to lose patent protection and incur competition from biosimilars. Ingelheim, Germany-based Boehringer will be eligible to receive additional development and regulatory milestone payments as part of the deal as well as royalties on net sales, the terms of which are not disclosed. In the initial period, the companies will share the responsibility for development of BI 655066. Abbvie will be solely responsible for commercialization, while Boehringer will retain an option to co-promote the compound in asthma, another indication the partners are exploring, alongside Crohn’s disease and psoriatic arthritis. The candidate has entered phase II studies for both asthma and Crohn’s and is about to enter phase II development for psoriatic arthritis. As it advances, BI 655066 could also create competition for Janssen Biotech Inc.’s anti-IL-12/IL-23 psoriasis drug, Stelara (ustekinumab), a therapy that generated $2.47 billion in 2015 sales. More than 100 million people suffer from psoriasis, a chronic, systemic, immune-mediated disease. Boehringer reported phase II data in October showing that BI 655066 demonstrated superior efficacy over Stelara. After nine months, 69 percent of patients with moderate to severe plaque psoriasis maintained clear or almost clear skin in the higher dose group, compared to 30 percent of patients on Stelara. Patients also achieved skin clearance significantly faster – in about eight weeks vs. about 16 weeks – and for two months longer. Completely clear skin was maintained after nine months in 43 percent of BI 655066 patients compared with 15 percent of Stelara patients. The data were presented at the 24th European Academy of Dermatology and Venereology congress in Copenhagen. The candidate is administered as a subcutaneous injection and was generally well tolerated in the 12-week treatment portion of the phase II study. Serious adverse events were reported for patients in the BI 655066 18-mg treatment group (7 percent) and Stelara group (2.5 percent), while there were no serious adverse events in the 90-mg and 180-mg treatment groups. One patient discontinued treatment in the BI 655066 18-mg dose group. The most common adverse events across the BI 655066 treatment groups were common cold and headache, at 7.3 percent – 11.6 percent across the dose groups and 2.4 percent – 7 percent, respectively. The most common adverse events in the Stelara group were common cold, injection site pain and redness, sore throat and myalgia; each of which occurred in 5 percent of patients. Abbvie also gained rights to another Boehringer candidate, the anti-CD-40 antibody, BI 655064, which is currently in phase I development. Boehringer is retaining responsibility for further development of that drug, but Abbvie now has the option to advance the program after it hits certain undisclosed clinical milestones. // OTHER NEWS TO NOTE Antabio SAS, of Labege, France, said it achieved two milestones in its antibacterial drug discovery collaborations with the Wellcome Trust, resulting in the release of a further €3.1 million (US$3.4 million) from the seeding drug discovery awards. The first collaboration began in February 2013 when the Wellcome Trust awarded Antabio €4.7 million to fund the discovery of a safe and efficacious inhibitor of bacterial metallo beta-lactamases (MBLs). Antabio has identified a highly active in vivo lead series with drug-like features and MBL coverage against clinical isolates, including NDM variants. The Wellcome Trust aims to nominate a preclinical development candidate by the first quarter of 2017. The second collaboration began in May last year when the Trust awarded Antabio €4 million to fund the development of small-molecule drugs for the treatment of chronic Pseudomonas aeruginosa infections in cystic fibrosis patients. Antabio said it has identified a selective in vitro lead series with all the physicochemical properties required for the achievement of the first milestone within that program. Astrazeneca plc, of London, said its biologics research and development arm, Medimmune, has received fast track designation from the FDA for its human monoclonal antibody, MEDI8852, for the treatment of patients hospitalized with type A strain influenza. MEDI8852 is being evaluated in a phase Ib/IIa trial to investigate the safety and efficacy of a single intravenous dose in combination with Tamiflu (oseltamivir, Gilead Sciences Inc. and Roche AG) , and as a monotherapy in adult patients with confirmed acute, uncomplicated influenza caused by type A strains. Biocryst Pharmaceuticals Inc., of Research Triangle Park, N.C., said a preclinical study of its broad-spectrum antiviral, BCX4430, in immune-deficient mice infected with Zika virus showed that overall survival for the standard dose level of BCX4430 was superior to both placebo and ribavirin treatment control groups (p < 0.0001). Median survival exceeded 28 days for animals treated with the standard dose of BCX4430 and was 23 days for the low dose, compared to 14 to 17 days for controls. In the standard-dose group, seven of eight mice survived through day 28. No animals survived to day 28 in the low-dose, ribavirin or placebo groups. Cellectar Biosciences Inc., of Madison, Wis., completed a 1-for- 10 reverse stock split of its common stock, reducing the number of outstanding common shares to about 860,000. Citius Pharmaceuticals Inc., of Maynard, Mass., said it entered a nonbinding letter of intent to acquire all of the outstanding shares of Leonard Meron Biosciences Inc., (LMB) of Cranford, N.J., and its lead drug candidate, Mino-Lok, an antibiotic lock solution used to treat patients with catheter-related bloodstream infections. Mino-Lok is entering phase III trials. Citius is expected to issue shares of its stock in exchange for shares of LMB in which, after the completion of the transaction, all prior common shareholders of LMB will retain about 49 percent of the common stock in Citius.
- 5. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 5 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. DBV Continued from page 1 congress in Los Angeles over the weekend, including 52-week data from a phase II trial conducted by the Consortium of Food Allergy Research (Cofar) and sponsored by the National Institute of Allergy and Infectious Disease. The trial, called Cofar6, met its primary endpoint of desensitization to peanut protein, defined as an ability to tolerate 5,044 mg of protein, or a 10-fold increase from baseline in the maximum tolerated dose. Shares of DBV (NASDAQ:DBVT) gained $3.96, or 15.1 percent, Monday to close at $30.11. The study assigned 75 patients (54 children, ages 4 to 11; and 21 adolescents and young adults, ages 12 to 25) to one of two dose arms (100 mcg or 250 mcg) or placebo, on a 1-to-1-to-1 basis. Each dose arm attained the primary endpoint. In the high-dose group, the overall response rate was 48 percent vs. 12 percent in the placebo group, a difference that was statistically significant (p=0.03). One-third of those on the high dose could tolerate a dose of peanut protein of at least 1,000 mg, equivalent to four peanuts. The response rate increased when children, ages 4 to 11, only were considered – to 61.1 percent vs. 5.6 percent. “It is a very strong response,” David Schilansky, chief operating officer of Paris-based DBV, told BioWorld Today. Treatment adherence was 97.1 percent, while the study had a dropout rate of 8 percent. No withdrawals occurred in the high-dose arm, and no emergency use of epinephrine was recorded. DBV has dubbed its patch-based delivery system as epicutaneous immunotherapy. Unlike most other patches, it delivers antigen directly to intact skin, trapping it within the stratum corneum. Systemic delivery does not occur. The study confirms data from the company’s own phase IIb Vipes trial, in which 50 percent of patients (ages 6 to 55) in the 250-mcg dose arm responded to the therapy – defined as an ability to tolerate at least 1,000 mg of peanut protein, or a 10- fold increase over baseline in the amount they could tolerate – vs. 25 percent in the placebo group. Significantly, the Cofar data also provided the first evidence in patients that the Viaskin therapy dampened the Th2 humoral response in recipients without prompting a shift to a Th1 cellular immune response. A marked decline in levels of IgE was detected, whereas, CEO and Chairman Pierre-Henri Benhamou said, a halt in the increase of IgE is more common in clinical trials. “Here it’s 40 percent below baseline,” he told BioWorld Today. At the same meeting, the company also reported two-year follow-up data from the Vipes study. The fraction of patients able to consume 1,000 mg or more of peanut protein almost doubled from 33 percent to 60 percent. “It shows that by adding another year of therapy, you continue to increase the therapeutic benefit,” Schilansky said. The overall response rate at two years was 69.7 percent, up from 50 percent at one year. In children ages 6 to 11, the two-year response rate was 80 percent, up from 53.6 percent at one year. The study outcomes augur well for DBV’s ongoing phase III trial, which is recruiting patients from the 4 to 11 age range only. Enrollment is due to be completed in the third quarter of this year, and data are expected before the end of next year. A regulatory decision could follow in 2018 – the program has fast track status from the FDA. Also at AAAAI, the company demonstrated preclinical proof of concept for the Viaskin technology in desensitizing the hemophiliac mice to factor VIII during replacement therapy. “For the moment it’s research data. We need to have further confirmation to move into the clinic with this program,” Benhamou said. DBV is currently valued at €1.1 billion (US$1.2 billion) and exited 2015 with €324 million on its balance sheet. It plans to use that cash to complete the clinical development and commercialization of the product – it aims to market the therapy itself in U.S. and Europe but will enter deals in other regions. “We have enough cash to carry out our mission and bring the product to market,” Schilansky said. // year. The companies have completed dose-escalation work and chose 3 mg/kg for varlilumab, with no maximum tolerated dose reached. Phase II experiments are expected to start enrolling in the second quarter of this year and include patients with solid tumors. (See BioWorld Today, May 15, 2014.) // Celldex Continued from page 3 OTHER NEWS TO NOTE CSL Behring, of King of Prussia, Pa., said the FDA approved Idelvion (coagulation factor IX), its long-acting albumin fusion protein linking recombinant coagulation factor IX with recombinant albumin for the treatment of hemophilia B. The company said the product is the first and only factor IX therapy that delivers high-level protection with up to 14-day dosing in appropriate patients. That dosing interval has been achieved while maintaining high levels of factor activity, above 5 percent over 14 days at 75 IU/kg, which the company said reduces the monthly number of units needed for prophylaxis therapy. ADVERTISE HERE Reach high-level biotechnology professionals every week! For advertising opportunities in BioWorld Today, please contact Tyler Beatty toll free at (855) 260-5607 or, outside the U.S. and Canada, at (646) 822-4549, or by email at tyler.beatty@thomsonreuters.com.
- 6. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 6 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. EMA Continued from page 1 committee and more help with plotting a route through to approval. The new priority medicines (Prime) designation also will provide enhanced support at the early stages of development for small biotechs and academic groups that have limited experience of the regulatory system. Small and medium-sized entities (SMEs) will be eligible to secure Prime designation prior to phase II, while larger companies can sign up before starting phase III. Anyone seeking the designation will be required to provide compelling evidence of a product’s potential public health impact. Overall, the scheme should lead to better informed development plans and improve the quality of marketing submissions. EMA committees will have greater awareness and knowledge of products coming up the pipeline, enabling the review process to be abbreviated. Launching the scheme at EMA’s headquarters in London, Guido Rasi, executive director of the EMA, said that currently two out of three development programs are inadequate to produce the evidence the agency needs to make its assessments. “As a consequence, many of the very promising medicines fail to reach patients, resources are wasted, costs increase and more importantly patients are enrolled in useless trials.” That is particularly the case for studies sponsored by academic groups and SMEs, Rasi said. In addition to honing regulatory strategies, health technology assessment agencies will provide input on how development should be shaped to generate information for reimbursement, pricing and access bodies, a move that the EMA claims will improve resource planning in Europe’s hard-pressed health care systems. “Ultimately, this will promote the possibility of earlier access to promising new medicines,” the EMA said. The agency is responding to critics who complain its convoluted assessment procedures are slowing access to innovative drugs, both undermining commercial potential and failing patients. EU Health Commissioner Vytenis Andriukaitis said Prime is a major step forward in providing earlier access to treatments for unmet medical needs such as rare cancers, Alzheimer’s disease and other dementias. “This scheme could also help, for example, to accelerate the development and authorization of new classes of antibiotics,” he said. In addition, Andriukaitis said Prime will optimize the use of the regulatory framework in order to boost pharmaceutical innovation and employment in the sector. Over the past year, the EMA’s Committee for Medicinal Products for Human Use (CHMP) has worked with other EMA committees, and in consultation with national drugs regulators, on re-interpreting the agency’s legislative framework to devise Prime. The result is a scheme which will take time and cost out of clinical development and make better use of the broad range of expertise to which the EMA has access, giving a helping hand to small biotechs and academics with exciting science but limited resources. (See BioWorld Today, Nov. 9, 2015.) The goal is to foster better development strategies to help companies generate the high quality data the EMA needs, Rasi said. “Patients with no or insufficient treatments could then benefit from scientific progress and cutting-edge medicines as soon as possible.” Zaide Frias, head of human research and development at the EMA, told BioWorld Today it is not possible to say to what extent Prime will cut development timelines. “It is difficult to predict how much faster Prime will be; we will have to gain experience,” she said. Frias noted that to back up the aims of the Prime scheme, the European Commission has said it will cut the time it takes to rubber stamp EMA recommendations to approve a drug, from 22 days to 10 days. “So we are confident there will be earlier access, but at this time we can’t [quantify] this, Frias said. Similarly, Hans-Georg Eichler, senior medical officer of the EMA, told BioWorld Today it is not possible to say if approval rates will go up. “Prime can’t rescue a molecule that is not beneficial or causes a nasty adverse event, but it can help avoid avoidable errors on the part of companies,” Eichler said. A HIGH LEVEL OF ENGAGEMENT Only innovative products will make the cut, with the EMA saying that providing an alternative treatment or incremental benefit will not qualify for Prime. Rather companies will need to demonstrate potential to address “to a significant extent” an unmet medical need. That could include the duration of effect, as is expected to be the case for regenerative and gene therapies, where one or a few treatments may show long-term efficacy. The review of applications for Prime designation will be carried out by the Scientific Advice Working Party, with recommendations forwarded to CHMP for rubber-stamping. Although the EMA intends to publish details of all applications, it will withhold the names of products that fail to win Prime status. The agency said this is because failure to secure the designation does not signify that a product is no good. SMEs and academic groups whose products are accepted for Prime may also get reduced-price scientific advice. A key feature of the Prime scheme is that products which qualify will be assigned a rapporteur from CHMP, who will act as chaperone. There will also be access to other EMA committees, for example the Committee for Advanced Therapies, as appropriate. Chair of CHMP Tomas Salmonson said, “By strengthening collaboration between the scientific committees, and by See EMA, page 9
- 7. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 7 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. Spark Continued from page 1 rhodopsin-linked autosomal-dominant retinitis pigmentosa, or RHO-adRP, an inherited retinal disease that, in severe cases, leads to blindness. “We certainly have an interest in expanding the remit of AAV- mediated gene therapy,” Katherine High, Spark’s co-founder, president and chief scientific officer, said of the deal’s rationale. “If we can tackle autosomal-dominant diseases as well as the X-linked and autosomal-recessive diseases that we’re working on now, that just expands our armamentarium.” Two years ago, Jason Loveridge, Genable’s CEO, called the collaboration with Spark a “coup,” telling BioWorld Today the original partnership was “really driven by the quality of the science. Spark is not a contract manufacturer.” (See BioWorld Today, March 26, 2014.) In return for a license to its adeno-associated virus (AAV) manufacturing intellectual property, Spark received revenues from the manufacture and supply of the product and was entitled to development milestones and sales royalties. Genable, in turn, was able to piggyback on the experience of Spark’s team. The Irish firm’s gene suppression-and- replacement approach is designed to address all mutations in the gene encoding rhodopsin. The protein, a photosensitive G protein-coupled receptor, is expressed in retinal cells and plays a central role in the transduction of light to electrical signals. By delivering AAV vectors developed and manufactured at Spark, Rhonova is designed at once to suppress the expression of a faulty gene by encoding an RNAi molecule to suppress translation of mutated (and wild-type) RHO transcripts and to deliver normal copies of the gene by encoding a wild-type RHO protein from which the RNAi recognition sequence has been eliminated. “The ability to address autosomal-dominant diseases by using a suppression-and-replacement therapy strategy is something we want to be able to do for a wide range of diseases,” High told BioWorld Today. “In some ways, the ability to address it first in an ocular target where you can be very sure that you’re delivering the vector to the target cells of interest is an attractive way to start.” Rhonova has orphan drug designation both in the U.S. and EU, in addition to advanced therapy medicinal product designation from the EMA. RHO-adRP, which affects an estimated 12,000 patients in the U.S. and the five major European markets, currently has no approved pharmacologic treatment. ‘THEY’RE A MODEL OF CLARITY’ Ena Prosser, a partner in the Dublin office of Genable investor Fountain Healthcare Partners and member of Genable’s board, credited Jane Farrar, the company’s co-founder and chief scientific officer, and her team at Trinity College Dublin (TCD) for shepherding the asset through more than 30 years of research, “and it really is fueled by the patients and their families,” Prosser said. “Our main priority is to allow the Genable team and the product’s dedicated creators to integrate Rhonova into Spark’s pipeline and see if this really can cure [RHO-adRP].” High also praised Farrar, a member of Spark’s scientific advisory board, and the Genable scientific team. “We had been working with Jane and her colleagues at Genable for a number of years, and they’ve been a great group of collaborators,” High said, singling out TCD’s Sophia Millington-Ward and Naomi Chadderton as well as Paul Kenna, an ophthalmologist and Genable’s co-founder and chief medical officer. “Together, they’ve really driven he work forward.” As a fellow scientist, High placed a high priority not only on identifying “first-rate collaborators, and Jane Farrar definitely meets that bar,” but also on liaising with researchers who were focused on the endgame of treating patients. “Jane really is therapeutically oriented,” she said. “She is always thinking about how what she’s doing can be safely and effectively translated for patients. If you look at their papers, they’re a model of clarity. No controls are left out. That’s just a great collaborator for a company like Spark.” The companies have been working together through a joint steering committee since initiating their 2014 collaboration, with face-to-face meetings every three months that rotate between Philadelphia and Dublin. That process will continue, High said. Genable had raised €5 million (US$6.8 million) in November 2011 and aimed to raise another €8 million to enable it to advance Rhonova into a phase I study that aimed to enroll 30 to 35 patients. (See BioWorld Today, Nov. 14, 2011.) The timetable for a first-in-human trial still depends on a few interim steps, High said. Genable published proof-of-concept data on Rhonova and designed a number of experiments in a large animal model to optimize the relative ratios of suppression and replacement. The next step is to execute those studies with the material supplied by Spark. Genable also has designed some natural history and run-in studies, “and we’ll be working together on those, too,” High said. At first blush, J.P. Morgan analyst Cory Kasimov liked the deal. “This is probably best characterized as a modest deal (in terms of price and stage), but it appears to be a prudent strategic decision for Spark,” he wrote in an email. “In addition to full rights to the lead program, this acquisition also gives Spark access to Genable’s suppression/ augmentation approach with potential applications outside the primary indication.” See Spark, page 8
- 8. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 8 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. Capella Continued from page 1 program through to phase IIa development by the end of 2018, and to complete preclinical development of four other products. That follows an initial investment of £1.5 million seed funding in 2014, with which, rather than shaping up an existing body of academic research, Capella Chief Operating Officer (COO) Steve Holmes was charged to go out and prospect for five therapeutic antibody projects around which to form a company. The seed money came from the founding investors, Advent Life Sciences and Medicxi Ventures (then Index Ventures). As Holmes explained, the idea was to draw on his experience, and that of the VC backers, to select the best monoclonal antibody projects. “The key was the targets; they had to be novel, and to have good biology to go with them,” Holmes said. Antibody generation has now advanced to the point where a number of platforms are available and in that sense products are commoditized. “We are agnostic about platforms. Making antibodies is relatively straightforward; it is the targets that make the difference,” Holmes told BioWorld Today. “[Products] could be fully human or mouse, it depends what we want to get out of the antibody,” he said. From initial prospecting in 2014, London-based Capella has advanced to the point of having lead panels of antibodies for its top three programs and has in-licensed target biology for a further two programs. The first program, in inflammatory bowel disease, rests on research from Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Calif. Although not revealing any details, Holmes said that is a known target in which Capella is aiming at a particular aspect of the biology that has not been exploited previously, “It happens to be a difficult concept for developing an antibody, but we’ve got initial [constructs],” Holmes said. The second program, in fibrosis, is based on intellectual property from Leeds University. If target biology is now the key to antibody drug development, the central requirement in its selection is expertise in therapeutic targets. Holmes has some form here, being former COO of murine antibody company Kymab Ltd. and of Domantis Ltd., and heading the monoclonal antibody group at Smithkline Beecham plc and then Glaxosmithkline plc, during the pioneering decade from 1990 to 2001. Capella’s clinical and scientific advisory group include antibody doyen Don Drakeman, founder of two leading U.S. and European companies, Medarex Inc. (acquired by Bristol-Myers Squibb Co. for $2.4 billion in 2009) and Genmab A/S. Meanwhile, Kevin Johnson, partner at Medicxi and board member at Capella, was head of research at Cambridge Antibody Technology plc, a corporate foundation stone of the monoclonal antibody therapeutics sector. In addition to reflecting the maturity and quality of monoclonal antibody platforms, Capella exemplifies the asset-based investment strategies of the founding VCs. Rather than making an initial investment in forming a company, the two invest in taking on half-formed assets and shaping them up to be suitable for pharma pipelines. The focus then is on conducting a program of research that will validate – or not - a particular asset, with the aim of establishing proof of concept in around three years for an investment of around $20 million. “The intention with our five therapeutic monoclonal antibodies, is quick in, quick out. This is a really good model for a start-up; we have been completely funded by Advent and Medicxi from nothing,” Holmes said. “In fact, we started one program and dropped it after five months and found a substitute - so we are very lethal. But with the last five targets everything has worked,” said Holmes. The intention will be to find commercialization partners at an early stage, and Holmes said he expects to be ready to start the hunt for partnerships before the end of the year. The profile and connections of the investors and the board means Capella “can go straight to the top” when trying to attract big pharma, he added. Joining the founding investors Advent and Medicxi in the series A is Philadelphia-based Osage University Partners, a VC specializing in the commercialization of academic research. The series A investment in Capella is Medicxi’s first since splitting from Index Ventures and launching a new $250 million fund dedicated to early stage European research in February. (See BioWorld Today, Feb 3, 2016.) // This could be a busy year for Spark. Initial efficacy data for SPK-FIX in hemophilia B, partnered with New York-based Pfizer Inc., are due midyear along with initial safety and efficacy data for SPK-CHM in choroideremia due in the second half of 2016. With a biologics license application filing for lead therapy SPK- RPE65 (voretigene neparvovec) in RPE65-mediated inherited retinal dystrophy following positive phase III data last year and investigational new drug filings for SPK-FVIII in hemophilia A and SPK-TPP1 in TPP1 deficiency, a form of Batten disease, also expected in the second half, “we continue to believe that ONCE is an underappreciated story in SMID biotech,” Kasimov added. (See BioWorld Today, Oct. 6, 2015.) On Monday, Spark’s shares closed at $35.69 for a gain of $1.16. // Spark Continued from page 7
- 9. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 9 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. EMA Continued from page 6 gaining and sharing knowledge on the medicine throughout the development, we will not only accelerate patients’ access, but also ensure an efficient use of available resources.” That high level of engagement will underpin the generation of a robust data package that meets marketing authorization application requirements and supports a thorough risk/benefit evaluation of a new medicine, the EMA said. It is expected that if products granted Prime status reach the point of being submitted for approval, they will then qualify for the EMA’s accelerated assessment pathway. Currently, accelerated assessment status is not conferred until just before an application is submitted. The EMA was keen to draw the distinctions between Prime and its Adaptive Pathways pilot, under which the agency is trying to factor real-world evidence into regulatory development. While Prime aims to provide early and enhanced scientific and regulatory support to promising new medicines that fulfill the criteria for accelerated assessment, Adaptive Pathways is for treatments in areas of high medical need, where collection of data via traditional routes is difficult and large clinical trials would unnecessarily expose patients who are unlikely to benefit from the medicine. Instead, products in the Adaptive Pathways pilot will be developed in a restricted patient population as an initial step, following by the gathering of real-life data, with a view to expanding the patient population in which the medicine can be used. // OTHER NEWS TO NOTE Geovax Labs. Inc., of Atlanta, said the simian analogue of its HIV vaccine, GOVX-B11, provided a 76 percent reduction in per- exposure risk of simian immunodeficiency virus (SIV) infection in young adult rhesus macaques. Per-exposure risk was assessed over 12 weekly rectal exposures. The study, supported by the National Institute of Allergy and Infectious Diseases, also showed the vaccine provided much better protection for young adult than middle-aged and older macaques. The test vaccine used a DNA vaccine expressing non-infectious virus-like particles (VLPs) to prime the immune response and a modified vaccinia Ankara (MVA) vaccine, also expressing non-infectious VLPs, to boost the primed response. The vaccine regimen included two DNA primes at weeks zero and eight followed by two MVA boosts at weeks 16 and 32. The efficacy of the vaccine was tested at six months after the final MVA boost by 12 weekly rectal exposures to a pathogenic SIV given at a dose that infected about 30 percent of the unvaccinated animals at each challenge. Animals that were less than 10 years old (estimated human age of about 40) had much better protection than those over 10 years old. The age-dependence for protection was stronger than typically seen for vaccines and likely reflects the HIV target for protective antibody being particularly well- camouflaged. IN THE CLINIC 3SBio Inc., of Shenyang, China, said the CFDA approved its investigational new drug application for peg-irinotecan, a long- acting polymer-drug conjugate that inhibits topoisomerase I. Peg-irinotecan was developed by Jenkem Technology Co. Ltd., of Beijing, which inked an exclusive license agreement with 3SBio in 2014 to develop, manufacture and market the candidate in mainland China. 3SBio plans to develop peg- irinotecan as a National Class I drug for relapsed or refractory cancers, including colorectal, metastatic breast and platinum- resistant ovarian cancer. (See BioWorld Today, Sept. 19, 2014.) Acelrx Pharmaceuticals Inc., of Redwood City, Calif., said it initiated patient enrollment and dosing in an open-label phase III study (SAP303) of ARX-04 (sufentanil sublingual tablet, 30 mcg) in patients 40 years and older with moderate to severe acute pain following a surgical procedure. Patients will be administered one dose of ARX-04 every 60 minutes, as needed for pain management, for up to 12 hours. The study is expected to enroll up to about 100 patients who underwent a surgical procedure with general or spinal anesthesia. The primary efficacy endpoint is the summed pain intensity difference over the 12-hour study period. Safety endpoints include adverse events and vital signs. The study is expected to be completed by the third quarter. (See BioWorld Today, Nov. 2, 2015.) Advaxis Inc., of Princeton, N.J., said it dosed the first patient in the expansion phase of an ongoing phase II trial of its lead Listeria monocytogenes (Lm) immunotherapy candidate, axalimogene filolisbac (AXAL), in patients with persistent or recurrent metastatic (squamous or nonsquamous cell) cervical cancer. The open-label, nonrandomized, dose-escalation study is designed to evaluate the safety, efficacy and immunological effect of AXAL at doses of up to 1 x 1010 colony forming units in repeat treatment cycles in about 25 women with cervical cancer whose disease recurred after one prior cytotoxic treatment regimen. The high-dose expansion phase will include 15 patients. (See BioWorld Today, Dec. 17, 2015.) Aimmune Therapeutics Inc., of Brisbane, Calif., reported data from its phase II study of AR101 for the treatment of peanut allergy, showing that all patients who completed 12 weeks of low-dose maintenance therapy were desensitized to levels of peanut protein beyond the 250 mg to 300 mg typically found in one peanut kernel. Data were presented at the American Academy of Allergy, Asthma and Immunology meeting in Los Angeles. The firm is now enrolling patients in the phase III PALISADE trial testing the drug, a formulation of peanut flour and pharmaceutical ingredients, in peanut allergy. Antibe Therapeutics Inc., of Toronto, said it received approval from Health Canada to start a phase II trial testing lead drug ATB-346, a hydrogen sulfide-releasing derivative of naproxen, in osteoarthritis of the knee. The study is set to start this month.
- 10. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 10 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. IN THE CLINIC Beigene Ltd., of Beijing, said the CFDA cleared the firm to start clinical testing with BGB-3111, a selective small-molecule Bruton’s tyrosine kinase inhibitor, for the treatment of B-cell malignancies. Trials already are ongoing in Australia. (See BioWorld Today, Dec. 10, 2015.) Brickell Biotech Inc., of Miami, reported phase IIb data at the American Academy of Dermatology meeting in Washington, showing that BBI-4000 (sofpironium bromide) for the topical treatment of primary axillary hyperhidrosis, or excessive underarm sweating, met its primary endpoint in the intent- to-treat analysis by achieving a statistically significant two- grade improvement in the Hyperhidrosis Disease Severity Score (HDSS), in a dose-related fashion. At the maximum dose (15 percent), 38.3 percent of participants receiving the anticholinergic improved more than two points on HDSS at day 29 vs. 12.2 percent with vehicle (p<0.01). Celgene Corp., of Summit, N.J., said long-term safety findings from ongoing studies of Otezla (apremilast), presented at the American Academy of Dermatology meeting in Washington, showed no increase in exposure-adjusted incidence rates of adverse events, serious adverse events or drug discontinuations for the 182-week data compared with the first 52 weeks of treatment. The rates of major cardiac events, malignancies, depression and attempted suicide, respectively, were comparable across the Otezla-exposure periods. No serious opportunistic infections, reactivation of tuberculosis infection, completed suicide or clinically meaningful effects on laboratory measurements were reported. Weight loss above 5 percent of body weight was experienced by 21.9 percent of participants, compared with 18.8 percent during the first 52 weeks. Data were from pooled analyses from the ESTEEM 1 and 2 trials and the PALACE 1-3 trials testing the phosphodiesterase 4 inhibitor in patients with plaque psoriasis and psoriatic arthritis. Cempra Inc., of Chapel Hill, said it received authorization under its existing contract with the Biomedical Advanced Research and Development Authority to receive funding of $25 million through mid-2018 for a phase II/III trial of solithromycin. Cempra is responsible for an additional designated portion of the cost of the planned study, which will enroll pediatric patients, ages 2 months to 17 years, with community-acquired bacterial pneumonia to receive either intravenous, oral suspension or oral capsule formulations of solithromycin, a fourth-generation macrolide antibiotic, or a comparator treatment. The study, set to start in the first half of this year, will enroll about 400 patients, with full enrollment expected during the first half of 2018. Chugai Pharmaceutical Co. Ltd., of Tokyo, reported results from a phase II study of anti-IL-31 receptor A, humanized monoclonal antibody nemolizumab (CIM331), currently in development for atopic dermatitis, at the American Academy of Dermatology meeting in Washington. Data showed the percent change in pruritus visual analogue scale at week 12, which was the primary endpoint, was significantly higher in the CIM331 treatment groups than in the placebo group (p<0.01 in all). The study enrolled 264 patients randomized to one of four CIM331 groups or placebo. Corbus Pharmaceuticals Holdings Inc., of Norwood, Mass., said Resunab, its oral endocannabinoid-mimetic, will be tested in a phase II trial in systemic lupus erythematosus (SLE) that was selected for funding by the NIH Autoimmunity Centers of Excellence program. The study will test the efficacy, safety, tolerability and biologic effects of Resunab as a non- immunosuppressive oral treatment to improve signs and symptoms of SLE. About 100 adult SLE patients with active musculoskeletal disease will be randomized to receive either placebo or three different doses of Resunab daily for 84 days, with 28 days follow-up. Derma Sciences Inc., of Princeton, N.J., said results from a peer-reviewed comparative study of Amnioexcel Amniotic Allograft Membrane plus standard of care vs. standard of care alone for the closure of hard-to-treat diabetic foot ulcers, published in Wounds, were both statistically significant and clinically meaningful, with the closure rate at six weeks in the Amnioexcel arm far exceeding the standard of care alone treatment arm. Eli Lilly and Co., of Indianapolis, said treatment for moderate to severe plaque psoriasis with ixekizumab, its IgG4 monoclonal antibody, resulted in clinically meaningful improvements as early as one week, compared to patients treated with Enbrel (etanercept, Amgen Inc.) or placebo, according to detailed results of the combined analysis of UNCOVER-2 and UNCOVER-3 phase III studies presented at the American Academy of Dermatology meeting in Washington. Data showed significant differences in mean percentage improvement of psoriasis plaques among patients treated with ixekizumab compared to etanercept and placebo, including one-week data showing a mean percentage improvement of 32.7 percent in the ixekizumab group, 10.3 percent in the etanercept group and 5.31 percent in the placebo group (p < 0.001 for all comparisons.) At two weeks, the mean percentage improvement was 53.6 percent for ixekizumab, 23.3 percent for etanercept and 9.25 percent for placebo (p<0.001 for all comparisons). Green Cross Biotherapeutics Corp., of Montreal, a member of the Green Cross family, said Health Canada approved its application for a phase III trial of immune globulin intravenous (human) 10 percent GC5107, intended for the treatment of primary humoral immunodeficiency. An investigational new drug application to the FDA is expected to follow. Index Pharmaceuticals AB, of Stockholm, said the FDA cleared the firm to start a phase IIb study of lead candidate cobitolimod (Kappaproct), a Toll-like receptor 9 agonist, in patients with moderate to severe ulcerative colitis. The trial will evaluate the safety and efficacy of cobitolimod in inducing clinical remission in patients with chronic active moderate to severe ulcerative colitis as compared to placebo and will evaluate higher doses and more frequent dosing than those used in previous studies.
- 11. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 11 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. OTHER NEWS TO NOTE Leo Pharma A/S, of Ballerup, Denmark, said data presented at the American Academy of Dermatology meeting in Washington demonstrated that calcipotriol/betamethasone dipropionate 50 mcg/0.5 mg/g) foam formulation is a stable supersaturated solution of the active ingredients, compared to calcipotriol/ betamethasone dipropionate 50 mcg/g/0.5 mg/g ointment in which the active ingredients are suspended. The data presented showed that no calcipotriol or betamethasone dipropionate crystals were identified in the foam spray following application and for up to 18 hours. However, crystals were present immediately upon application of the ointment formulation. Those data may provide a potential explanation for the improved clinical efficacy observed in clinical trials. IN THE CLINIC International Stem Cell Corp., of Carlsbad, Calif., said it is enrolling patients in the phase I trial if ISC-hpNSC, human parthenogenetic stem cell-derived neural stem cells, for the treatment of moderate to severe Parkinson’s disease. The 12-patient, dose-escalation and preliminary efficacy study will test ISC-hpNSC, intracranially transplanted into patients at three different dose regimens of 30 million to 70 million neural cells. Following transplantation, the patients will be monitored for 12 months at specified intervals, to evaluate safety and biologic activity. PET scan will be performed at baseline, as part of the screening assessment, and at six and 12 months after surgical intervention, and clinical responses compared to baseline after the administration of ISC-hpNSC will be evaluated using various neurological assessments such as Unified Parkinson Disease Rating Scale, Hoehn and Yahr and other rating scales. Ix Biopharma Ltd., of Singapore, said its multidose, placebo- controlled study, called KET0090, testing Wafermine, an oral, sublingual analgesic employing ketamine as its active compound, confirmed that Wafermine was well tolerated with no serious adverse effects at the maximum accumulated dosage of 315 mg over a 14-hour period. The most frequent adverse events reported were nausea, vomiting and dizziness, which are common in postoperative populations. It was noted that the same adverse events occurred with similar frequency in all treatment groups. The trial’s objective was to test Wafermine, administered alone or in combination with opioids, in subjects undergoing bunionectomy. Kempharm Inc., of Coralville, Iowa, said it filed an investigational new drug application with the FDA to start studies of KP511, its prodrug of hydromorphone that is intended for development as abuse-deterrent ER medication for treating moderate to severe pain. Kempharm plans to conduct a clinical program for KP511 that will assess the product’s tamper and extraction resistance, intranasal and intravenous abuse potential, as well as the potential to limit oral abuse and/or overdose. Additionally, the firm intends to investigate KP511’s potential for improving or reducing opioid-induced constipation. Medicinova Inc., of La Jolla, Calif., presented phase II results at the Behavior, Biology and Chemistry: Translational Research in Addiction meeting in San Antonio from a study of MN- 166 (ibudilast) in opioid dependence, showing that ibudilast significant decreased the reinforcing effects of oxycodone (p < 0.05); significantly decreased the craving for heroin (p < 0.01), cocaine (p < 0.01) and tobacco (p < 0.05); and significantly decreased participants’ rating for “liking” oxycodone (p < 0.05). Ibudilast, an oral, small-molecule phosphodiesterase 4 and 10 inhibitor and macrophage migration inhibitory factor inhibitor, also was safe and well tolerated. Novartis AG, of Basel, Switzerland, said data from the head- to-head CLEAR study, presented at the American Academy of Dermatology meeting in Washington, demonstrated that its fully human interleukin 17A inhibitor, Cosentyx (secukinumab), remains superior to Stelara (ustekinumab, Johnson & Johnson) in achieving sustained skin clearance (PASI 90 response) at 52 weeks for adults living with moderate to severe psoriasis. At weeks four, 16 and 52, Cosentyx achieved and sustained PASI 90 responses vs. Stelara (76.2 percent vs. 60.6 percent, p < 0.0001) and achieved greater PASI 100 responses (45.9 percent vs. 35.8 percent, p = 0.0103) at 52 weeks. The study also demonstrated Cosentyx had a superior rapid onset of action compared to Stelara, with half of Cosentyx patients achieving PASI 75 as early as week four (50 percent vs. 20.6 percent, p < 0.0001). Nuvo Pharmaceuticals Inc., of Mississauga, Ontario, reported top-line results from its randomized, placebo-controlled, double-blind, parallel-group study in patients with grade I or II ankle sprains, showing that, on average, patients treated with Pennsaid 2 percent had a larger reduction in pain on movement scores over the course of the study, though the full analysis set missed the primary endpoint, as measured on day five (p=0.2430), while showing a statistically significant difference on the secondary time point on day three (p=0.0119). In the per-protocol group, which excluded those patients with a lower usage of medication, the Pennsaid 2 percent group showed a statistically significant improvement at both the primary time point (day five; p=0.0416), as well as the secondary time points (day three; p=0.0018; and day eight; p=0.0490). Prexton Therapeutics SA, of Geneva, said it launched a phase I trial testing its mGluR4 positive allosteric modulator in 72 healthy volunteers. Results are expected in August. Prexton previously reported preclinical data showing the molecule’s potential in alleviating motor complications by modulating glutamate over activity in the central nervous system of Parkinson’s disease patients. The phase I study will be financed by a $10 million series A round that closed in February 2015. (See BioWorld Today, Feb. 25, 2015.)
- 12. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 12 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. OTHER NEWS TO NOTE Matinas BioPharma Holdings Inc., of Bedminster, N.J., said its investigational drug, MAT2501 (encochleated amikacin), was granted orphan designation by the FDA for the treatment of nontuberculous mycobacteria (NTM) infections, its lead chronic indication. MAT2501, an orally administered, encochleated formulation of the broad-spectrum intravenous- only aminoglycoside antibiotic agent amikacin, utilizes the company’s lipid-crystal, nanoparticle delivery technology. The company recently received FDA clearance to initiate a phase I study of MAT2501 for the treatment of NTM infections. Merck & Co. Inc., of Kenilworth, N.J., said the FDA accepted for review a new supplemental biologics license application for Keytruda (pembrolizumab), the company’s anti-PD-1 therapy, to include data from Keynote-010. The trial was a pivotal phase II/III study designed to evaluate Keytruda compared to chemotherapy based on prospective measurement of PD-L1 expression in previously treated patients with advanced non- small-cell lung cancer. (NSCLC) The drug is currently indicated in the U.S. for the treatment of patients with metastatic NSCLC, whose tumors express PD-L1 as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for those aberrations prior to receiving Keytruda. The NSCLC indication, approved under accelerated approval, was based on tumor response rate and durability of response in patients with PD-L1 expression on 50 percent or more of the cancer cells. In accordance with the accelerated approval process, the data from Keynote-010 was intended to serve as the confirmatory trial for receiving full approval, establishing the clinical benefit by demonstrating improved survival over standard chemotherapy. Molecular Partners AG, of Zurich-Schlieren, Switzerland, disclosed details about its immuno-oncology pipeline, including two early stage multi-Darpin programs. The first program targets the validated immune checkpoint PD-1 as well as VEGF-A, aiming to enhance PD-1 efficacy. The second program is designed to potently activate T cells in the tumor without activating circulating T cells, thus circumventing systemic toxicities. Darpins are described as potent, specific and versatile small-protein therapies that could offer benefits over conventional monoclonal antibodies or other currently available protein therapeutics. Opiant Pharmaceuticals Inc., of Santa Monica, Calif., received a $2.5 million milestone payment from Adapt Pharma Ltd., of Dublin, following its first commercial sale of Narcan (naloxone hydrochloride) for the emergency treatment of known or suspected opioid overdose. Oxford Biomedica plc, of Oxford, U.K., disclosed a new and expanded collaboration with Immune Design Corp., of Seattle, as well as a nonexclusive, royalty-bearing, intellectual property license to Immune Design. The license involves the use of lentiviral vector-based products for the in vivo treatment or prevention of cancer. The collaboration builds on Immune Design’s earlier process development collaboration with Oxford, signed in 2012, which covered the development of analytic assays. Financial terms were not disclosed. Peptidream Inc., of Tokyo, said it entered a technology license agreement with Indianapolis-based Eli Lilly and Co. for nonexclusive access to Peptidream’s peptide discovery platform system. Under the terms, Peptidream will receive up-front and annual technology access payments, and will be eligible to receive development milestones and royalties on future sales of products (both peptide and small-molecule therapeutics) that arise from use of the technology. Similar to previous technology licenses, this one will exclude work on peptide-drug conjugate programs, as Peptidream has internal development efforts ongoing there. Specific financial terms were not disclosed. Pharmaengine Inc., of Taipei, Taiwan, said the Taiwan FDA approved the product license of Onivyde (irinotecan liposome injection, nal-IRI). Onivyde is indicated, in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. The company expects that the product will be available during the second quarter of this year. Specialized Therapeutics Pty Ltd., of Melbourne, Australia, and Mundipharma Pty Ltd., of Cambridge, U.K., disclosed a sublicense agreement enabling Mundipharma to assume all commercialization responsibilities for the anti-emetic products Aloxi (palonosetron hydrochloride) and Akynzeo (netupitant/ palonosetron) in Australia and New Zealand. Financial terms were not disclosed. VBI Vaccines Inc., of Cambridge, Mass., reported that manufacturing characterization data confirmed the purity and quality of its therapeutic vaccine candidate against glioblastoma multiforme (GBM). The company said the purity measurements are expected to meet regulatory requirements for clinical evaluation, and VBI plans to hold a pre-investigational new drug meeting with the FDA in the first half of the year. The data were presented in a poster at the Keystone Symposia Cancer Vaccines Conference in Whistler, British Columbia. Ex vivo studies have shown the vaccine candidate’s ability to induce desired antitumor immunity in peripheral blood mononuclear cells obtained from healthy subjects and patients with GBM. The candidate stimulated strong T-cell immunity, including both CD4+ and CD8+ T-cell responses, as well as secretion of IFN-γ and CCL3, biomarkers associated with positive clinical outcomes. Vericel Corp. (formerly Aastrom Biosciences Inc.), of Cambridge, Mass., said the FDA accepted its biologics license application for MACI (matrix applied characterized autologous cultured chondrocytes), its autologous cellular candidate to treat symptomatic cartilage defects of the knee in adults. Vericel said the FDA set a PDUFA date of Jan. 3, 2017, and said it does not plan to hold an advisory committee meeting to discuss the application.
- 13. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 13 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. IN THE CLINIC Revance Therapeutics Inc., of Newark, Calif., reported results from its phase II BELMONT trial testing DaxibotulinumtoxinA for injection (RT002) at the American Academy of Dermatology meeting in Washington, showing that all three dose levels of RT002 achieved the primary endpoint by demonstrating at least a one-point improvement in frown lines based on the Investigator Global Assessment-Facial Wrinkle Severity (IGA-FWS) scale at four weeks. That measurement showed a statistically significantly greater response as compared to placebo for each dose level. The study demonstrated a six- month median duration of effect for RT002 based upon at least a one-point improvement in glabellar lines at maximum frown on the IGA-FWS scale. Samumed LLC, of San Diego, presented results from its phase II androgenetic alopecia trial at the American Academy of Dermatology meeting in Washington, showing that topically applied small molecule SM04554 appeared to be safe and well tolerated, with no adverse events observed in the treatment groups. Over the 135-day study, both treatment arms showed an increase in hair count and hair density, objectively measured by macrophotography. By contrast, the vehicle group showed a decline in both measures. Under the a priori statistical analysis plan, between day 90 and day 135, the 0.15 percent treatment group had a statistically significantly higher increase in both hair count and hair density, as compared to vehicle. Spectrum Pharmaceuticals Inc., of Henderson, Nev., said it started the planned phase II trial of poziotinib, its pan-HER2 inhibitor. The study is expected to enroll about 70 patients with HER2-positive metastatic breast cancer who have failed at least two prior HER2-directed therapies. Summit Therapeutics plc, of Oxford, U.K., reported data from the phase II CoDIFy trial showing that narrow-spectrum antibiotic ridinilazole preserves the gut microbiome in patients with Clostridium difficile infection (CDI). Ridinilazole- treated patients in CoDIFy exhibited no further damage to their microbiome during therapy, with a proportion of patients showing initial evidence of recovery of key bacterial groups with roles in protecting from CDI. In stark contrast, vancomycin-treated patients in the study suffered substantial damage to their gut microbiome during treatment and that persisted in many patients during the 30-day post-treatment period. Tigenix NV, of Leuven, Belgium, reported that a single injection of Cx601, its allogeneic expanded stem cell product, was statistically superior to placebo in achieving combined remission at week 52 in the phase III ADMIRE-CD trial in Crohn’s disease patients with complex perianal fistulas with inadequate response to previous therapies, including anti- TNFs. Data showed that 54.2 percent of patients treated with Cx601 achieved combined remission vs. 37.1 percent in the placebo arm, while 75 percent of Cx601-treated patients who achieved combined remission at week 24 remained in combined remission at week 52, compared to 55.9 percent in the placebo arm. The one-year data also confirm the favorable safety and tolerability profile of Cx601 reported at week 24. Vical Inc., of San Diego, said it started a phase I randomized, double-blind trial testing the safety, tolerability and pharmacokinetics of antifungal candidate VL-2397 at single and multiple ascending doses in healthy volunteers. VL-2397 is in development for treating invasive aspergillosis, for which it has orphan drug and qualified infectious disease designations from the FDA. Fast answers for unobstructed paths to market. Ensure your drug approval processes run smoothly and accelerate your regulatory decisions with Cortellis™ Regulatory Intelligence. CLEARLY CORTELLIS
- 14. TUESDAY, MARCH 8,2016 BIOWORLD™ TODAY PAGE 14 OF 14 For Sales Inquiries: http://ip-science.interest.thomsonreuters.com/Bioworld_Sales_Inquiry. NORTH AMERICA, Tel: +1-855-260-5607. Outside of the U.S. and Canada, Tel. +44-203-684-1797. For Customer Service Inquiries, NORTH AMERICA, Tel: +1-800-336-4474. Outside of the U.S. and Canada, Tel. +44-203-684-1796. Or email bioworld.support@thomsonreuters.com. Copyright ©Thomson Reuters. Reproduction is strictly prohibited. Visit our website at www.bioworld.com. FINANCINGS Argos Therapeutics Inc., of Durham, N.C., said it is selling up to $60 million of its common stock and warrants in a private placement financing. Under a securities purchase agreement the financing will take place in up to three tranches; at the initial closing, the investors will purchase a total of 3.65 million shares of common stock and warrants to purchase a total of about 2.74 million shares of common stock for a total purchase price of $19.88 million. At the second closing, investors will purchase a total of 5.47 million shares of common stock and warrants to purchase a total of 4.1 million shares of common stock at the same price and on the same terms as the first tranche for an additional purchase price of $29.8 million. The second closing is conditioned on the independent data monitoring committee (IDMC) for the ADAPT study at, or following the IDMC’s next regular meeting following the initial closing, recommending that Argos continue the study or discontinue it based on favorable efficacy data. Participants in the financing include Pharmstandard International SA, Forargos BV, Tianyi Lummy International Holdings Group Ltd., China BioPharma Capital I LP, TVM V Life Science Ventures GmbH & Co. KG and Wasatch Funds Trust. Pharmstandard has also agreed that, at Argos’s option and the status of the ADAPT trial and the company’s cash position at such time, it shall purchase at the third closing up to $10.29 million of shares of common stock (without warrants) at a price per share to be determined pursuant to an agreed upon formulation. Argos expects that proceeds from the initial closing will enable it to fund the company’s ongoing expenses into the third quarter of 2016, and that the proceeds from all three closings, if such closings occur, will enable it to fund the company’s ongoing expenses into the second quarter of 2017 when it expects final data from its pivotal phase III ADAPT trial of AGS-003 for the treatment of metastatic renal cell carcinoma. Hutchison China Meditech, of Hong Kong, set terms for a proposed U.S. IPO, aiming to raise $100 million by offering 6.1 million American depositary shares priced at $16.33 apiece. The company plans to list on Nasdaq under the ticker HCM. (See BioWorld Today, Feb. 17, 2016.) ITM Isotopen Technologien Muenchen AG, of Garching, Germany, said it raised €20 million (US$22 million) in equity from Medtech Focused Family Office. ITM plans to use the funds to further develop its pipeline of targeted radionuclide therapies for therapeutic and diagnostic purposes. Plx Pharma Inc., of Houston, withdrew its proposed IPO, previously filed to raise up to $68 million. Founded in 2002, Plx has a delayed-release aspirin based on its lipid coating technology. ExplorE thE IncIdence & Prevalence database: thE most EfficiEnt way to look at thE world’s EpidEmiology data • Coverage of over 4,500 diseases, procedures, and major health topics • Information from 1000s of sources, including medical journals and health associations • All data contained in the IPD is fully cited and linked to its primary source • Gain insight through comprehensive epidemiology databases designed to provide a “first-look” at any disease, procedure, symptom, or health issue. To learn more, please visit thomsonreuters.com/incidence-and-prevalence-database ©2016 thomson reuters. all rights reserved. thomson reuters and the kinesis logo are trademarks of thomson reuters.
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