New Autoimmune Candidate APVO210
Demonstrates Targeted Cytokine Delivery for Application in Various
Autoimmune and Inflammatory Diseases
Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology
company focused on developing novel immuno-oncology and hematology
therapeutics, today announced that it presented information on a
new ADAPTIR™ candidate, APVO210, at the Inflammation Research
Association meeting in Seattle, WA, October 13, 2017.
In a presentation entitled, “APVO210 an ADAPTIR
Targeted Cytokine Delivery Molecule for Autoimmune and Inflammatory
Diseases,” Dr. Gabriela Hoyos, presented an overview of Aptevo’s
novel ADAPTIR candidate, APVO210, designed to deliver an
immunosuppressive cytokine to modulate the body’s inflammatory
response in various autoimmune and inflammatory conditions like
irritable bowel disease (IBD), rheumatoid arthritis (RA) and
transplant related disorders such as graft versus host disease.
Cytokines function by promoting or suppressing a
variety of cellular functions, including inflammatory
responses. Unregulated inflammation can result in disease and
chronic inflammatory conditions like IBD. IL-10 is a cytokine
that is known to suppress inflammation. However, IL-10 also
has stimulatory functions on lymphocytes, enhancing B cell
proliferation and cytotoxic T cell function, reducing its potential
anti-inflammatory therapeutic properties.
APVO210 is a novel targeted cytokine therapeutic
based on Aptevo’s ADAPTIR modular protein therapeutic platform.
It targets a modified version of IL-10 to CD86+ cells,
increasing its immunosuppressive properties without stimulating T
and B lymphocytes, as demonstrated in preclinical studies.
APVO210 improves the anti-inflammatory properties of IL-10 in two
ways. First by specifically targeting cells expressing CD86, such
as monocyte, macrophage, and dendritic cells, and secondly by
delivering a modified form of IL-10 that does not stimulate
lymphocytes. This lack of lymphocyte stimulation may reduce the
toxicities previously observed following repeat administration of
IL-10 in humans, and potentially allow for increased dosing. In
addition, APVO210 has demonstrated a longer half-life in non-human
primates and may improve dosing regimens.
Preclinical data confirm the mechanism of action
of APVO210 and show the effective targeting of APVO210 to antigen
presenting cells with limited effects on lymphocytes.
Pharmacokinetic studies also demonstrate that APVO210 is potent and
well tolerated in preclinical models at doses up to 10 mg/kg in
single dose studies in non-human primates, and 30-fold more potent
than CTLA4-Ig in in vitro and in vivo animal systems.
Additionally, preclinical data show proof of
concept for APVO210 in a humanized transplant model. In a
prophylactic model of graft versus host disease (GvHD), APVO210
showed strong inhibition of T cell expansion at very low doses (~70
ug/kg) and reduced the accumulation of cytokines in
circulation. In this model, APVO210 was 100-fold more potent
than abatacept at maximum inhibition of T cell expansion.
“Targeted cytokine delivery represents an
evolving approach for the treatment of autoimmune and inflammatory
diseases and we are excited to expand the application of our
ADAPTIR technology platform to include additional candidates like
APVO210, featuring a novel mechanism of action distinct from
redirected T cell cytotoxicity (RTCC), which is the basis of many
of our ADAPTIR oncology candidates,” remarked Dr. Jane Gross, Chief
Scientific Officer for Aptevo. “Modulating the immune system
using a bispecific antibody opens up new frontiers in the treatment
of many debilitating and serious autoimmune disorders with high
unmet medical need and the preclinical data for APVO210 suggest it
may be effective in the treatment of such disorders. We are
very encouraged by the preclinical data and look forward to
advancing APVO210 towards clinical development.”
ADAPTIR Bispecific Antibody Platform:
Differentiating Characteristics
- Unique Homodimer Structure - simplifies candidate generation;
facilitates rapid substitution of target binding domains to
evaluate numerous candidates simultaneously
- Bivalent for Both Binding Domains - increases the avidity and
potency of ADAPTIR candidates
- Unique IgG Fc ‘Backbone’ - extends the half-life of ADAPTIR
molecules (up to ~12.5 days in rodents)
- Antibody-like Production Processes – demonstrated capability to
produce up to 2.0g/L comparable to traditional antibody
manufacturing processes
- Improved Yield and Cost of Goods - use of a single gene and
ease of CHO cell line production enhances ADAPTIR bispecific
manufacturing productivity
- Flexible Platform Technology – ability to produce protein
therapeutics with different structural elements fused to an
antibody backbone for different mechanisms of action.
ADAPTIR Clinical and Preclinical
Portfolio:
- APVO414 – a bispecific ADAPTIR candidate,
currently in Phase 1 development, targeting prostate specific
membrane antigen (PSMA), an enzyme that is expressed on the surface
of prostate cancer cells, and, CD3, a component of the T cell
receptor complex expressed on all T cells. APVO414 redirects
T cells to specifically kill PSMA expressing tumors and is being
developed for metastatic castration-resistant prostate cancer,
which is advanced prostate cancer that has spread to other organs
and no longer responds to hormone blocking therapies.
- Otlertuzumab – a monospecific ADAPTIR
candidate currently in Phase 2 development for the treatment of
chronic lymphocytic leukemia (CLL). Data from a Phase 2
clinical trial evaluating otlertuzumab in combination with
bendamustine, compared to bendamustine alone, demonstrated a
significant increase in median progression free survival for the
combination, from approximately 10 to 16 months.
- APVO436 – a bispecific ADAPTIR candidate
currently in preclinical development targeting CD123, a cell
surface receptor highly expressed on several hematological
malignancies and CD3, a component of the T-cell receptor. APVO436
engages T cells to kill tumor cells.
- ALG.APV-527 – a bispecific antibody candidate,
partnered with Alligator Bioscience, featuring a novel mechanism of
action designed to simultaneously target 4-1BB (CD137) and an
undisclosed tumor antigen. 4-1BB, a costimulatory receptor on
T cells, is known to enhance the immune response to cancer through
activation of tumor-specific T cells and is believed to be a
promising target for new immunotherapeutic approaches. ALG.APV-527
could potentially have utility in the treatment of a broad spectrum
of cancers over-expressing the tumor antigen, in multiple solid
tumors including breast, cervical, non-small-cell-lung, prostate,
renal, gastric, colorectal and bladder cancers.
- APVO210 – a bispecific ADAPTIR preclinical
candidate with a novel mechanism of action based on targeted
cytokine delivery. APVO210 is composed of a humanized
anti-CD86 antibody fused with a modified form of IL-10 that
specifically induces IL-10 signaling on antigen presenting cells,
but not on lymphoid populations. APVO210 functions by suppressing
immune responses and inducing certain tolerogenic responses and
therefore may have potential benefit for the treatment of
autoimmune and inflammatory diseases.
- ROR1 Bispecific – a proof-of-concept
bispecific candidate targeting ROR1, an antigen found on several
solid tumors and hematologic, or blood-related malignancies.
Initial preclinical data demonstrate redirected T cell killing of
tumors expressing ROR1 in vitro and in vivo in animal models.
About Aptevo Therapeutics
Inc.
Aptevo Therapeutics Inc. is a clinical-stage
biotechnology company focused on novel oncology and hematology
therapeutics to meaningfully improve patients’ lives. Aptevo
has a commercial product, IXINITY®, approved and marketed in the
United States for the treatment of Hemophilia B, and a versatile
core technology – the ADAPTIR™ modular protein technology platform
capable of generating highly-differentiated bispecific antibodies
with unique mechanisms of action to treat cancer or autoimmune
diseases. Aptevo has two ADAPTIR antibody candidates
currently in clinical development and a broad pipeline of novel
investigational-stage bispecific antibody candidates focused in
immuno-oncology and autoimmune disease and inflammation. For more
information, please visit www.aptevotherapeutics.com
Safe Harbor Statement
This press release includes forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. Any statements, other than statements of
historical fact, including, without limitation, statements
regarding potential milestone payments, Aptevo’s outlook, financial
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realize that if underlying assumptions prove inaccurate or unknown
risks or uncertainties materialize, actual results could differ
materially from Aptevo’s expectations. Investors are, therefore,
cautioned not to place undue reliance on any forward-looking
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There are a number of important factors that
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negative effects on our business operations, assets or financial
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affect results are set forth in Aptevo’s filings with the
Securities and Exchange Commission, including its most recent
Annual Report on Form 10-K, as filed on March 31, 2017, and its
subsequent reports on Form 10-Q and current reports on Form 8-K.
The foregoing sets forth many, but not all, of the factors that
could cause actual results to differ from Aptevo’s expectations in
any forward-looking statement.
For Further Information:
Aptevo Therapeutics Stacey JurchisonSenior Director, Investor
Relations and Corporate Communications206-859-6628
JurchisonS@apvo.com
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