Download Idiotype builder - Bullet Biotechnology

BioCentury,
THE
BERNSTEIN R EPORT
ON
B IOB USINESS
MARCH 24, 2014
P AGE A17 OF 26
Emerging Company Profile
Bullet: Idiotype builder
By Michael Flanagan
Senior Writer
Bullet Biotechnology Inc. is using
new sequencing and manufacturing methods to develop an idiotype cancer vaccine
that it anticipates will be more effective
than first-generation products.
President and CEO Willie Quinn said
the first wave of idiotype vaccines established proof of principle by showing that
an epitope lifted from the clonal immunoglobulin region of a patient’s malignant B
cells can be reintroduced along with an
immune stimulator and engender an immune response against the cancerous cells.
He thinks products like Genitope Corp.’s
MyVax lymphoma vaccine never made it
across the finish line for two main reasons
— they were tested in the wrong patients
and did not always generate an immune
response due to poor conjugation.
MyVax was an autologous idiotype
protein coupled to keyhole limpet
hemocyanin carrier protein (KLH) given
with GM-CSF. It failed a Phase III trial to
treat follicular non-Hodgkin’s lymphoma
(NHL) in 2007, and Genitope went out of
business the following year.
“The first vaccines were treating patients who had received chemotherapy or
Rituxan, which do a lot of damage to the
immune system,” making them poor candidates for products designed to work by
stimulating an immune response, said
Quinn.
He noted the first-generation vaccines
took six to nine months to prepare, which
likely played a role in the decision to test
them after patients had undergone treatment with chemotherapy or Rituxan.
He also believes the 33-40% response
rates reported in the literature for the
first-generation products were likely a result of inadvertent changes to the epitope
structure during the conjugation process,
which resulted in diminished immune
stimulation.
Quinn thinks Bullet can overcome the
problems of laborious production cycles
and poor epitope expression through use
of new manufacturing and sequencing technologies.
Bullet Biotechnology Inc.
Menlo Park, Calif.
Technology: Active immunotherapies
consisting of virus-like particles combined with antigens and immune stimulants
Disease focus: Cancer
Clinical status: Preclinical
Founded: 2011 by Willie Quinn and
Thomas Theriault; James Swartz and
Diego Fonstad
University collaborators: Stanford University
Corporate partners: Aragen Bioscience
Inc. and Applied Immunology Inc.
Number of employees: 2
Funds raised: $2.5 million
Investors: Individual investors
CEO: Willie Quinn
Patents: None issued
The company uses next-generation
sequencing to identify the idiotype epitope
from hundreds of thousands of B cells. The
epitope then is conjugated without modification to a synthetic virus-like particle
plasmid that triggers an adaptive immune
response.
Bullet is not disclosing many details
about the design of its vaccine, though
Quinn said toll-like receptor (TLR) ligands
on the outside of the product help engage
the innate immune system.
Lead vaccine BB-001 is being tested in
in vitro and in vivo models of lymphoma.
Quinn said unpublished data show the
compound significantly improved eventfree survival vs. first-generation KLH-based
vaccines in a mouse model of lymphoma.
Importantly, Quinn said the company
will be able to manufacture an entire sixmonth course of monthly therapy of BB001 from a fraction of a single blood draw.
“Our manufacturing process takes less
than a month,” he said.
Quinn also said Bullet’s product should
not be significantly more expensive than a
small molecule. “We will not struggle with
issues on cost of goods or cumbersome
manufacturing and distribution processes,”
he said, adding that the company’s vaccines will be stable at room temperature.
Bullet’s plan is to move BB-001 into the
clinic for chronic lymphocytic leukemia
(CLL) and NHL in 2015.
“The key will be showing it is safe
enough to test in front-line patients or, if
not there, then just behind it with kinase
inhibitors as part of a cytoreductive
therapy,” Quinn said.
Indeed, Quinn thinks BB-001 will be
complementary to kinase inhibitors like
Imbruvica ibrutinib as well other immune
stimulating agents, such as agents that
target checkpoint targets like programmed
cell death 1 (PDCD1; PD-1; CD279) or
CTLA-4 (CD152).
Pharmacyclics Inc. and Johnson &
Johnson market Imbruvica, a Bruton’s
tyrosine kinase (Btk) inhibitor, for CLL and
mantle cell lymphoma (MCL).
Bullet raised $2.5 million in two tranches
of a series A round that closed last summer.
The company is using a virtual model
with minimal infrastructure and has enlisted Aragen Bioscience Inc. to conduct the preclinical mouse studies and
Applied Immunology Inc. to handle
the peripheral blood processing.
Quinn expects Bullet to raise $5-$15
million in a series B round this year.
Rituxan rituximab is marketed by Biogen Idec Inc. and Roche’s Genentech
Inc. unit.
COMPANIES AND INSTITUTIONS MENTIONED
Applied Immunology Inc., Menlo Park, Calif.
Aragen Bioscience Inc., Morgan Hill, Calif.
Biogen Idec Inc. (NASDAQ:BIIB), Weston,
Mass.
Bullet Biotechnology Inc., Menlo Park, Calif.
Genentech Inc., South San Francisco, Calif.
Johnson & Johnson (NYSE:JNJ), New
Brunswick, N.J.
Pharmacyclics Inc. (NASDAQ:PCYC),
Sunnyvale, Calif.
Roche (SIX:ROG; OTCQX:RHHBY), Basel,
Switzerland
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