- Preclinical data demonstrate enhanced anti-tumor efficacy by
combining PD-1/PD-L1 pathway blockade and NKG2A checkpoint
inhibitor;
- Resistance to PD-1 pathway blockers is associated with
upregulation of NKG2A;
- Provides in vivo preclinical validation of the rationale for
the ongoing clinical trial investigating this combination.
Innate Pharma SA (the "Company" - Euronext Paris: FR0010331421 -
IPH) today presented data demonstrating enhanced anti-tumor
efficacy and survival by combining anti-NKG2A with PD-1/PD-L1
pathway inhibitors in murine models at the American Association for
Cancer Research (AACR) Annual Meeting 2016 in New Orleans,
Louisiana, USA.
The NKG2A checkpoint receptor is expressed on a
subset of NK cells. Similar to the PD-1 receptors, NKG2A can also
be induced on tumor-infiltrating CD8 T cells. Therefore, PD-1 and
NKG2A may both inhibit anti-tumor immune responses in situations
where cancers express the ligands of both these checkpoint
receptors. Conversely, anti-tumor immune responses might be
enhanced by combined NKG2A and PD-1 pathway blockade.
Poster #2342 reports preclinical data based on
an in vivo model of PD-L1 expressing solid tumors. In this model,
treatment with either an antibody blocking PD-1 or NKG2A as single
agents resulted in modest anti-tumor efficacy. The frequency of
tumor-infiltrating NKG2A+ CD8 T cells was increased in anti-PD-1
resistant mice, suggesting that NKG2A is a pathway involved in
adaptive PD-1 resistance. Treatment with combination of NKG2A and
PD-1 checkpoint inhibitors resulted in significantly enhanced
anti-tumor responses. Nearly twice as many mice achieved complete
tumor cell regression compared to treatment with anti PD-1
alone.
Nicolai Wagtmann, CSO of Innate Pharma, said:
"We are very excited by these data showing that the NKG2A pathway
acts as a major mechanism of tumor escape in this model.
Considering the high frequency of patients who respond inadequately
to PD-1 pathway blockade, we are intrigued by the observations that
NKG2A expression on CD8 T cells was increased in PD-1 resistant
mice". He added: "These data and the striking efficacy of the
combination treatment in this model provide strong support for the
clinical trial that was just initiated, testing the combination of
monalizumab, Innate's first-in-class NKG2A checkpoint inhibitor,
and durvalumab, AstraZeneca/Medimmune's investigational PD-L1
checkpoint inhibitor".
***** Reminder:
Nicolai Wagtmann, Chief Scientific Officer of
Innate Pharma, will hold a conference call to the attention
of analysts and portfolio managers to discuss the data published
and Company's innovative pipeline.
Time and dial in: Tuesday, April 19th 10:30am
Eastern Time USA: 888 504
7963
International: +1 719 325 2452 Access code: 1890466
Webcast: http://urlz.fr/3pxC
*****
About monalizumab (IPH2201):
Monalizumab is a first-in-class immune
checkpoint inhibitor targeting NKG2A receptors expressed on tumor
infiltrating cytotoxic CD8 T lymphocytes and NK cells.
NKG2A is an inhibitory receptor binding HLA-E.
By expressing HLA-E, cancer cells can protect themselves from
killing by NKG2A+ immune cells. HLA-E is frequently up-regulated
and widely expressed on cancer cells of many solid tumors or
hematological malignancies. In some cancers, HLA-E expression is
associated with poor prognosis.
Monalizumab, a humanized IgG4, blocks the
binding of NKG2A to HLA-E allowing activation of NK and cytotoxic T
cell responses. By blocking the inhibitory NKG2A receptors,
monalizumab may re-establish a broad anti-tumor response mediated
by NK and T cells. Monalizumab may also enhance the cytotoxic
potential of other therapeutic antibodies.
Monalizumab is partnered with AstraZeneca and
MedImmune, AstraZeneca's global biologics research and development
arm, through a co-development and commercialization agreement. The
initial development plan includes a combination trial with
durvalumab (MEDI4736) in solid tumors conducted by AstraZeneca as
well as multiple Phase II trials conducted by Innate Pharma, to
study monalizumab efficacy as a monotherapy and in combinations
with currently approved treatments in several cancer indications.
As previously announced, under the terms of this agreement, Innate
Pharma is eligible to cash payments of up to $1.275 billion as well
as double digit royalties on sales. In addition to the initial
payment of $250 million, AstraZeneca will pay Innate Pharma a
further $100 million at the decision to go into Phase III
development, as well as additional regulatory and sales-related
milestones of up to $925 million. AstraZeneca will book all sales
and will pay Innate Pharma double-digit royalties on net sales. The
arrangement includes the right for Innate Pharma to co-promote in
Europe for a 50% profit share in the territory.
About durvalumab:
Durvalumab is an investigational human
monoclonal antibody directed against programmed death ligand-1
(PD-L1). PD-L1 expression enables tumours to evade detection from
the immune system through binding to PD-1 on cytotoxic T
lymphocytes. Durvalumab blocks PD-L1 interaction with both PD-1 and
CD80 on T cells, countering the tumour's immune- evading tactics.
Durvalumab is being developed alongside other immunotherapies to
activate the patient's immune system to attack the cancer.
Durvalumab is being investigated in an extensive clinical trial
programme, as monotherapy or in combination with tremelimumab, in
NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood
cancers. In 2015, durvalumab received Fast Track Designation for
the treatment of patients with PD-L1-positive metastatic SCCHN, and
in 2016, durvalumab was granted Breakthrough Therapy Designation by
the U.S. Food and Drug Administration as a potential treatment for
metastatic urothelial bladder cancer.
About Innate Pharma:
Innate Pharma S.A. is a biopharmaceutical
company discovering and developing first-in-class therapeutic
antibodies for the treatment of cancer and inflammatory
diseases.
Innate Pharma specializes in immuno-oncology, a
new therapeutic field that is changing cancer treatment by
enhancing the capability of the body's own immune cells to
recognize and kill cancer cells.
The Company has pioneered the development of
antibodies that block inhibitory checkpoint receptors on NK cells.
Today, Innate Pharma has three first-in-class antibodies in
clinical development in immuno-oncology and a pipeline of
preclinical candidates to novel targets and mechanisms.
Its innovative approach has translated into
alliances with leaders in the biopharmaceutical industry such as
Bristol-Myers Squibb and AstraZeneca, Sanofi and Novo Nordisk
A/S.
Based in Marseille, France, Innate Pharma had
118 employees as at December 31, 2015. The company is listed on
Euronext-Paris.
Learn more about Innate Pharma at
www.innate-pharma.com.
Practical Information about Innate Pharma
shares:
ISIN
code Ticker code |
FR0010331421 IPH |
Disclaimer:
This press release contains certain
forward-looking statements. Although the company believes its
expectations are based on reasonable assumptions, these
forward-looking statements are subject to numerous risks and
uncertainties, which could cause actual results to differ
materially from those anticipated. For a discussion of risks and
uncertainties which could cause the company's actual results,
financial condition, performance or achievements to differ from
those contained in the forward-looking statements, please refer to
the Risk Factors ("Facteurs de Risque") section of the Document de
Reference prospectus filed with the AMF, which is available on the
AMF website or on Innate Pharma's website.
This press release and the information contained
herein do not constitute an offer to sell or a solicitation of an
offer to buy or subscribe to shares in Innate Pharma in any
country.
For additional information, please
contact:
Innate Pharma |
ATCG
Press |
Laure-Hélène Mercier Director,
Investor Relations |
Marie
Puvieux (France) Mob: +33 (0)6 10 54 36 72 Jean-Medhi Grangeon
(ROW) |
Tel.: +33 (0)4 30 30 30 87 |
Mob: +33
(0)6 62 22 00 24 |
investors@innate-pharma.com |
presse@atcg-partners.com |
IPH AACR 2016 monalizumab
http://hugin.info/155662/R/2004568/740206.pdf
HUG#2004568
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