B I O T E C H ’ S M O S T R E S P E C T E D N E W S S O U R C E F O R M O R E T H A N 2 0 Y E A R S Tygacil by the Tail? Tetraphase Partnering Your Way to M&A? IPO: $86M for New Antibiotics Keep Cash Balance, Options
Looking to bolster its planned Phase III trial with TP-434
NEW YORK – How does a biotech company look to set
(eravacycline) for complicated intra-abdominal infections,
itself up as a potential acquisition target down the road?
Tetraphase Pharmaceuticals Inc. fi led for an initial public
The answer, according to a panel at this year’s BIO CEO &
offering (IPO) that would raise up to $86.2 million, though
Investor Conference, is that it depends.
neither the targeted number of shares nor the price of each
On fi nancing, on the indications, the market size
In February 2012, the company landed a $67 million
Heard it at
federal contract for the broad-spectrum antibiotic from the
#BIOCEO13, p. 9
Biomedical Advanced Research and Development Authority,
which came six months after a $36 million National Institutes
One, the number of M&A deals has dropped in the past
of Health (NIH) contract for a separate, respiratory antibiotic,
Only one new compound in the tetracycline class,
StemCells: Spinal Injury Gains
Tygacil (tigecycline, Pfi zer), has been approved in more than 30 years, mainly because semi-synthetic production
Are Sustained After One Year
methods hinder chemical diversity. Tetraphase’s approach
TP-434 is a fully synthetic tetracycline antibiotic, created
StemCells Inc. reported positive results from the fi rst
using Watertown, Mass.-based Tetraphase’s tetracycline
patient cohort of a Phase I/II trial of its human neural
chemistry platform, licensed from Harvard University.
stem cell product for spinal cord injury, and investors
Positive Phase II data were unveiled in September 2012.
responded enthusiastically, driving the Newark, Calif.-
Intended for Gram-negative and Gram-positive
pathogens, TP-434 targets bugs such as Escherichia coli
Out of three patients with complete, chest-level spinal
and Klebsiella pneumonia, in the former category, as well
injury, two had regained sensitivity to heat, touch and
N e w C o N e w s Lycera Expands Partnership With Merck for Potential $600M Swiss Start-up Piqur Developing Dual PI3K-mTOR Inhibitors
Lycera Corp. doubled its sweet 2011 deal with
Merck and Co. Inc., of Whitehouse Station, N.J., in a new
agreement designed to expand on the companies’ prior
Matthias Wymann, the Swiss scientist who discovered
relationship, which has centered on retinoic acid-related
the fi rst phosphoinositide 3-kinase (PI3K) inhibitor, is co-
orphan receptor (ROR[gamma]t). Lycera will receive an
founder of a new cancer drug discovery start-up, Piqur
undisclosed up-front payment and research funding,
OTHER NEWS TO NOTE: ONCOCEUTICS, ORAGENICS, OXYGEN .7
INSIDE: PHARMA OTHER NEWS TO NOTE: NOVO NORDISK, DR. REDDY’S .9
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unwanted activation of PI3K signaling. Yet some level of
mTOR inhibition has a synergistic effect on shutting down
Therapeutics AG, which recently completed a seed fi nancing
round that will enable it take forward a pipeline of next-
Piqur has identifi ed what it believes will be fi nely tuned
dual inhibitors that do not reactivate the PI3K signal.
The company, a spinout from the University of Basel,
“We call it balanced inhibition. We think effi cacy can be
where Wymann is based, is developing dual inhibitors of
improved if you have a balanced way of inhibiting the two
PI3K and mammalian target of rapamycin (mTOR). It has
assembled a veritable who’s who of scientifi c staff and
The company has also opted to focus on dual inhibitors
advisers, who have played leading roles in the development
with pan-PI3K selectivity in order to maximize their
The other co-founders include company chairman
Drugs that target only one of the four Class I PI3K
Bernd Giese, a high-profi le organic chemist best known for
isoforms that are important in cancer, such as GS-1101 (CA-
his work on electron charge transfer in DNA and peptides;
101), the Phase III PI3K delta inhibitor Foster City, Calif.-
CEO Vladimir Cmiljanovic, who spent his scientifi c research
based Gilead Sciences Inc. acquired in its takeover of
career with Giese and Wymann; and Andreas Emmenegger,
Calistoga Pharmaceuticals, have more limited application.
chief fi nancial offi cer of Molecular Partners AG, of Zurich,
“All isoforms are involving in cancer signaling pathways,”
Switzerland. Its chief scientifi c offi cer is Doriano Fabbro,
formerly head of kinase biology at Novartis AG, of Basel,
Although Piqur’s kinase inhibitors can act on all four
Switzerland. Its scientifi c advisory board includes Michael
PI3Ks, as well as the two kinase activities present in the two
Hall, of the University of Basel, who discovered TOR.
mTOR complexes, they do not appear to affect the hundreds
About 20 years ago, Wymann identifi ed PI3K as the
of other kinases that are involved in myriad signaling roles.
target of wortmannin, a fungal metabolite known for
“We know that our front-runner compound doesn’t have
inhibiting respiratory burst (or oxidative burst) activity in
specifi c off-target activities according to the preclinical
neutrophils. (Seattle-based Oncothyreon Inc. is conducting
compound characterization,” Cmiljanovic said.
Phase II trials in multiple cancer indications of a semi-
Piqur – the name is a play on PI3K, the concept that one
in three people have a lifetime risk of developing cancer and
Over the past decade, Wymann and his team have
the notion of a cure for cancer – has not disclosed the size
assisted several large pharma fi rms in the discovery and
of its initial funding round. Its investors are high-net worth
development of PI3K-Akt-mTOR pathway inhibitors. The
individuals with signifi cant experience in the life sciences
pathway plays an important role in down-regulating
industry. The funding will enable the company to advance
apoptosis and prolonging cell survival. Aberrant signaling
its operational set-up, complete preclinical development of
or amplifi cation of the pathway is a signifi cant feature of
its lead compound, PQR-309, and prepare for its fi rst clinical
trial, which could commence later this year. ■
BEZ235 was the fi rst dual inhibitor of PI3K and mTOR
to reach the clinic. Novartis is now conducting Phase II
Other News To Note
trials of the compound in multiple cancer indications. Paris-based Sanofi SA is also in the clinic with a dual inhibitor, SAR245409 (XL765), which it in-licensed from Exelexis Inc.,
• MiReven, of Perth, Western Australia, reported the
publication of an in vitro study where the microRNA miR-
Piqur has identifi ed a series of compounds with attractive
7-5p signifi cantly inhibited the migration and invasion of
profi les using high-throughput screening, combined with in
metastatic melanoma cells in the journal Biochemical and
silico modeling and X-ray crystallographic analysis.
Biophysical Research Communications. In the study, miR-
“What Piqur has today are molecules, which have
7-5p expression was shown to be reduced in metastatic
signifi cantly improved physico-chemical properties, leading
melanoma-derived cell lines compared with primary
to the improved pharmacological properties,” Cmiljanovic
melanoma cells. When the microRNA was reintroduced
and expressed ectopically, migration and invasion of the
The compounds exhibit strong PI3K inhibition and
melanoma cells was signifi cantly inhibited in vitro. The
weaker mTor inhibition, in contrast to BEZ235, a compound
study authors also investigated the mechanism of miR-
which some of the Piqur team worked on during its
7-5p and found that insulin receptor substrate-2 (IRS-2)
preclinical characterization. “BEZ235 is a stronger mTor
is a functional target of miR-7-5p, which then decreases
inhibitor than it is a PI3 kinase inhibitor,” Cmiljanovic said.
activity in the protein kinase B (Akt) signaling pathway, a
However, excessive mTOR inhibition leads to the loss
key regulator of many oncogenic processes including cell
of negative feedback loop, which, ultimately, leads to an
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