Opportunity in treating HPV infections

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Anaconda Pharma
www.anacondaphar ma.com
Opportunity in treating HPV infections
Targets for the most common sexually transmitted viral disease, human papilloma virus, have eluded the
pharmaceutical industry. Innovation stemming from cutting-edge research exposed a protein-protein interaction
target, and Anaconda’s phase 2 candidate takes aim.
biopharmadealmakers
W
ith Anaconda Pharma, a phase 2
clinical trial candidate for the treatment
of genital warts or condyloma is the tip
of the iceberg. The company’s lead candidate,
AP611074, is the product of its discovery
approach, which can successfully disclose
targets once considered undruggable by the
pharmaceutical industry.
A spin-out of the Pasteur Institute, Anaconda’s
robust intellectual property position is related
to a cadre of unprecedented research discoveries relevant to replication mechanisms of
certain human papilloma viruses (HPVs). Three
academic experts, together with a proven
biotech management executive, founded the
company in 2003 on the basis of groundbreaking research on HPV expression of genes and
proteins. In the late 1980s and early 1990s,
epidemiological evidence clearly established a
causal relationship between HPV and cervical
cancer. The international academic research
community delved in to uncover the mechanisms of HPV viral infection and their link to cell
immortality. At the time, the company’s three
academic founders, Moshe Yaniv, Françoise
Thierry and Michael Botchan, were undertaking efforts at two leading research institutions
to understand aspects of HPV’s ability to promote infection and disease. Yaniv and Botchan
each ran prestigious labs in viral research
(at the Pasteur Institute and the University of
California, Berkeley, respectively), and Thierry
was investigating the role of HPV E2 proteins
in tumor progression at the Pasteur Institute.
The market opportunity associated with treating
infections related to HPV rests with the diversity
of HPV subtypes and the frequency with which the
virus is transmitted sexually. Of more than 100
subtypes of HPV, roughly 40 can infect the skin
and mucosa of the anogenital area. HPV infection prompts viral replication that can give rise to
anogenital warts, cervical cancer and also common warts, when other mucosal or skin areas
are affected. Approximately 50–80% of sexually
active adults acquire one or more types of HPV
during their lifetimes, making HPV infection the
most common sexually transmitted disease.
Despite the high incidence rates for clinically relevant HPV-related conditions, targeting HPV proved
too challenging for the pharmaceutical industry
beyond the development of prophylactic vaccine
programs that protect from the initial infection
by some HPV types. Anaconda has broken away
from the industry by focusing on protein-protein
interactions. Accordingly, Anaconda’s team is
advancing AP611074, a phase 2 compound
that inhibits the E1-E2 interaction essential for
B12
Anaconda Pharma.indd 12
the pathogenesis of HPV
6 and HPV 11, the two
subtypes that give rise
to anogenital warts or
condyloma.
Anaconda’s antiviral
was discovered through
a combination of in silico
screening with biological
and cellular proprietary
assays designed to identify protein interactions Anaconda Pharma's structural models showing the HPV E1:E2 proteinbroadly relevant to these protein interaction-nucleation (left) and the E2 pocket binding (right).
viral infections.
AP611074 is the first compound in clinical
programs that overlap in covering HPV 6 and
development that directly tackles HPV and pre11, these programs are relatively young, and
vents its replication in infected cells. “Condyloma
coverage of the world’s sexually active population
is one of the world’s most frequent sexually
is limited.
transmitted diseases. Condyloma is mostly perCondyloma still affects about 1% of the global
ceived by affected individuals as a disfiguring and
sexually active population, with several million new cases reported each year. According
shameful condition, causing anxiety and severe
to Marta Blumenfeld, cofounder and CEO of
social and psychological stress. Unfortunately,
Anaconda, AP611074’s favorable efficacy and
there is no satisfactory treatment available so
safety results stand out, as other therapies
far. AP611074 has the potential to meet the
substantial medical need of patients impacted
(immunomodulator drugs) take up to 16 weeks to
by condyloma,” said Silvio Tatti, president of the
clear condyloma lesions or they have compliance
International Federation of Cervical Pathology
issues, owing mostly to the high rate of local reacand Colposcopy and principal investigator of
tions resulting from their mechanism of action.
Anaconda’s phase 2a clinical study.
“The presentation of our phase 2a results at
recent scientific meetings has drawn significant
AP611074 phase 2 success
interest from fellow scientists and clinicians
in our company,” said Blumenfeld. “Scientists
In a double-blind, randomized phase 2a clinical
trial, patients with condyloma applied AP611074
were close to abandoning the idea of developing
gel twice daily for six weeks. Compliance with
antiviral treatments specific for HPV. AP611074
the treatment protocol was high in the trial, and
clinical results are an excellent surprise for the
no patients terminated treatment before the end
medical community.”
of the six-week period. Response to treatment
To build on the success of these clinical results,
was observed in 57% of the participants, with
the company is currently seeking partnerships to
13% showing complete clearance of the lesions
further the clinical development of AP611074.
and 44% showing partial clearance. The lesions
“The company’s greatest challenge lies in
continued to clear during the weeks following
placing the treatment of condyloma back on the
the end of the treatment, suggesting that extenstrategic map of the pharmaceutical industry,”
sion of the AP611074 treatment period could
said Blumenfeld.
potentially clear the lesions in a large proportion
of the patients. In addition, AP611074 was well
References
tolerated; in particular, local tolerance was excel1. Fouéré, S. et al. Abstract no. SS 15-5,
lent, and no adverse events were reported1. “The
EUROGIN conference (2013).
safety profile of AP611074 looks excellent. No
relevant side effects, and a very low incidence of
local skin reactions, occurred during the phase
2a trial or in the two phase 1 studies, which is
a great potential advantage compared to existCONTACT DETAILS
ing therapies,” said Olivier Chosidow, chairman
Marta Blumenfeld, President
Anaconda Pharma,
of the department of dermatology at Henri
Villejuif, France.
Mondor Hospital and investigator coordinator of
Tel: + 33 (0)1 8228 7302
Anaconda’s clinical studies.
Email: [email protected]
Even though there are prophylactic vaccine
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15/05/2014 09:38

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