New Preclinical Data Show APVO436 Demonstrates Rapid and Significant Reduction in Skeletal Tumor Burden in
Mice with Well-Established and Disseminated Tumors
SEATTLE, Oct. 30, 2017 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company
focused on developing novel oncology and hematology therapeutics, today announced that new preclinical data on the Company’s next
generation bispecific antibody candidate, APVO436, were presented at the AACR-NCI-EORTC Molecular Targets and Cancer
Therapeutics 2017 annual meeting.
Aptevo is developing APVO436 for the treatment of acute myeloid leukemia (AML), a form of blood and bone marrow
cancer that is characterized by rapid disease progression. While treatments for AML are available, there remains a high unmet
medical need for targeted immunotherapies like APVO436, that can potentially treat patients with relapsed or refractory disease, or
patients who cannot tolerate traditional chemotherapy.
Aptevo has previously shown APVO436’s ability to induce tumor-specific immune responses and T-cell mediated
cytotoxicity in vitro and in vivo through the simultaneous targeting of CD123 (a cell surface receptor highly
expressed in several hematological malignancies) and CD3 (a T-cell co-receptor that promotes cytotoxicity.)
Preclinical data presented at the AACR-NCI-EORTC meeting further demonstrate the highly-desirable attributes of
APVO436 as a potent and selective immunotherapeutic candidate in the treatment of AML. These data show that APVO436:
- Possesses low (nM) binding affinity; binds with high affinity to human and cynomolgus CD123-expressing cells with
EC50 values in the low nanomolar range
- Demonstrates potent, concentration-dependent, T-cell engagement against multiple CD123 expressing tumor cell lines at low
effector to target ratios, accompanied by target-dependent primary T-cell activation and proliferation
- Dose-dependently inhibits tumor growth and significantly prolongs survival compared to vehicle-treated animals in a
preclinical in vivo xenograft model of human AML (data previously presented at AACR in April 2017)
- Demonstrates a rapid and significant reduction in skeletal tumor burden in mice with well-established and disseminated
tumors
- Is well-tolerated by single intravenous injection in non-human primates at doses up to 1.0 mg/kg with no observable changes
in body weight, food consumption or clinical chemistry
- Has an antibody-like serum half-life of up to 3.5 days in non-human primates (NHP), and 12.5 days in mice, significantly
longer than other bispecific candidates in development
“The accumulating preclinical data suggest a desirable target product profile for APVO436, which support its
role as a targeted immunotherapeutic for the treatment of AML or other hematological malignancies,” said Jane Gross, Chief
Scientific Officer for Aptevo. “Unlike other bispecific candidates targeting CD123, APVO436 has traditional antibody-like
manufacturing characteristics, including a longer half-life that could potentially support a weekly dosing regimen. We look
forward to completing ongoing IND-enabling and CMC activities to advance APVO436 into the clinic next year.”
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, 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 APVO436 and Aptevo’s ADAPTIR Platform
APVO436 is a bispecific antibody candidate designed to simultaneously target CD123 and CD3 and redirect T-cell
cytotoxicity. It was developed based on Aptevo’s proprietary next generation ADAPTIR platform. Focused on generating
novel, targeted bispecific antibody-based immunotherapies for cancer and autoimmune diseases, the ADAPTIR platform offers key
advantages over other bispecific formats, derived in part from the flexible and modular nature of the ADAPTIR structure. These
advantages include: (i) potent biological activity and extended half-life in preclinical studies; (ii) traditional antibody-like
manufacturing processes with the potential for extended dosing regimens; (iii) unique properties for redirecting T-cell
cytotoxicity (RTCC), including a favorable cytokine release profile and the ability to achieve target-dependent induction of RTCC
at low drug concentrations. If these data are confirmed in clinical studies, it could suggest the potential for enhanced
safety and tolerability compared to other immuno-oncology approaches.
Two ADAPTIR molecules are currently undergoing clinical trials, with several more bispecific immunotherapies in
preclinical development. The advantages of the ADAPTIR platform provides an opportunity for diverse therapeutic applications in the
future.
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® coagulation factor
IX (recombinant), 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 performance or financial condition, Aptevo’s technology and related
pipeline, collaboration and partnership opportunities, commercial portfolio, and any other statements containing the words
“believes,” “expects,” “anticipates,” “intends,” “plans,” “forecasts,” “estimates,” “will” and similar expressions are
forward-looking statements. These forward-looking statements are based on Aptevo’s current intentions, beliefs and expectations
regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should 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 statement. Any
forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not
undertake to update any forward-looking statement to reflect new information, events or circumstances.
There are a number of important factors that could cause Aptevo’s actual results to differ materially from those
indicated by such forward-looking statements, including a deterioration in Aptevo’s business or prospects; adverse developments in
research and development; adverse developments in the U.S. or global capital markets, credit markets or economies generally; and
changes in regulatory, social and political conditions. Additional risks and factors that may 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.
Source:
Aptevo Therapeutics
Stacey Jurchison
Senior Director, Investor Relations and Corporate Communications
206-859-6628
JurchisonS@apvo.com