Investors

APVO436 Preclinical Data Continue to Show Promising Results Supporting Clinical Development for the Treatment of Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS) and Differentiation from a Competitor Candidate

Phase 1/1b Clinical Study of APVO436 Continuing Dose Escalation in Patients with AML and MDS

Dose-Ranging Preclinical Study of ALG.APV-527, an ADAPTIR™ Bispecific Targeting 4-1BB and 5T4, Shows Encouraging Safety Profile in Relevant Non-Clinical Studies

CTA Submission for ALG.APV-527 Planned in Q4 2019

SEATTLE, April 02, 2019 (GLOBE NEWSWIRE) -- Aptevo Therapeutics Inc. (Nasdaq: APVO), a biotechnology company focused on developing novel oncology, autoimmune and hematology therapeutics, announced today that new preclinical data for two ADAPTIR bispecific candidates, APVO436, a bispecific antibody candidate targeting CD123 and CD3, and ALG.APV-527, a bispecific antibody candidate targeting 4-1BB and 5T4, were presented at the American Association for Cancer Research (AACR) 2019 Annual Meeting.

APVO436 AACR Data

In a poster presentation entitled “APVO436, a Bispecific anti-CD123 x anti-CD3 ADAPTIR Molecule for Redirected T-cell Cytotoxicity with Limited Cytokine Release, is Well Tolerated in Repeat Dose Toxicology Studies,” Aptevo scientists presented new preclinical data demonstrating that APVO436:

• Induces the generation of functional memory T cells with cytolytic function from naïve T cells
• Has good tolerability, antibody-like clearance and volume of distribution parameters
• Has an extended serum half-life of 4.5 days in a relevant non-clinical species

The preclinical data presented at this year’s AACR annual meeting expand on previous findings for APVO436 showing its ability to demonstrate potent T-cell cytotoxicity of tumors expressing CD123 with reduced cytokine release, suggesting the potential for increased clinical benefit and an improved safety profile.  Other T-cell engaging immunotherapies have demonstrated good efficacy in clinical studies but can be associated with severe and sometimes life-threatening complications.    

Due to its structure and unique observation of reduced cytokine release in preclinical studies, Aptevo believes that APVO436 could offer therapeutic efficacy with the potential to moderate the release of inflammatory cytokines that are associated with the deleterious side effects seen in some clinical studies conducted by other companies.

Preclinical data for APVO436 presented at AACR support this hypothesis, showing that APVO436 induces the activation and proliferation of naïve CD4 and CD8 T cells in the presence of CD123-positive tumor target cells, but with reduced levels of cytokine activation compared to an Aptevo-generated version of a competitor anti-CD123 x anti-CD3 bispecific molecule.

“The reduction in cytokine release we’ve observed in preclinical studies with APVO436, vis-à-vis a competitor molecule, is a particularly interesting finding,” said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo.  “The possibility that APVO436 could stimulate an effective immune response against CD123-positive tumors, but with a more controlled cytokine release profile is especially intriguing, offering the potential for reduced toxicities compared to other CD123 x CD3 T-cell engagers at comparable or higher doses. We also show new data demonstrating the differentiation of a memory T cell population by APVO436 in preclinical studies which can potentially contribute to a more sustained clinical response. We are excited to have commenced our Phase 1/1b clinical trial of APVO436 in patients with AML and MDS and are hopeful that the emerging clinical data will validate our preclinical safety hypothesis.  We look forward to reporting a preliminary ADA read-out for APVO436 in the third quarter of 2019 and reporting preliminary Phase 1 safety data in the fourth quarter of 2019.”

APVO436 is currently being evaluated in a Phase 1/1b clinical trial in patients with AML and MDS. The study is being conducted in two parts. The first part is expected to enroll up to 60 patients and is an open-label, dose-escalation study evaluating the safety and pharmacokinetic profile of APVO436 to determine a recommended dose for part 2.  The second part of the study is a Phase 1b open-label expansion study to assess the clinical activity and safety profile of APVO436 at the recommended dose in a larger group of patients.

ALG.APV-527 AACR Data

ALG.APV-527 is a novel tumor-directed anti-4-1BB x anti-5T4 bispecific antibody candidate that is being co-developed with Alligator Bioscience for the treatment of a variety of 5T4-positive solid tumors.  It is designed to induce signaling through the co-stimulatory receptor 4-1BB (CD137), which is present on activated cytotoxic T cells and natural killer (NK) cells.  In preclinical studies, ALG.APV-527 has been shown to promote potent and selective immune activation in the presence of 5T4 antigen-expressing tumor cells, which are present on many different types of solid tumors, including non-small cell lung cancer, head and neck cancer, mesothelioma, and pancreatic cancer, among others.  Recent toxicology studies with ALG.APV-527 also support a favorable safety profile for this molecule.

In a poster presentation entitled “Preclinical Safety and Efficacy of a Tumor-directed T Cell Activating 4-1BB x 5T4 ADAPTIR Bispecific Antibody” Aptevo and Alligator present new preclinical safety data showing that ALG.APV-527:

• Was well tolerated in a dose-range finding pilot toxicology study with no major changes in liver enzyme levels, cytokine levels or immune cell populations observed
• Had an extended serum half-life of 5-7 days when administered by intravenous infusion in a preclinical toxicology study

Previously reported preclinical data also support the tumor-targeting effects of ALG.APV-527, and show that it:

• Augments CD8 T cell proliferation and activation in a 5T4-dependent fashion
• Induces NK cell proliferation and enhances the NK cell cytotoxic profile, but only in the presence of 5T4
• Inhibits tumor growth in a human xenograft colon carcinoma model expressing the tumor antigen 5T4

“Interest in 4-1BB as a promising target for cancer immunotherapy has increased significantly and we are pleased to be at the forefront of research in this exciting field with our novel bispecific antibody candidate, ALG.APV-527,” said Dr. Gross.  “While other 4-1BB antibody therapeutics have been tested in the clinic and shown promising anti-tumor effects, certain of these therapies have also been associated with dose-limiting hepatic toxicities, limiting their therapeutic potential. We believe that a bispecific strategy focused on achieving localized, target-driven T-cell activation could potentially minimize systemic toxicity by avoiding widespread T-cell activation and the accompanying side effects. We are excited to evaluate this approach and look forward to submitting a clinical trial application (CTA) for ALG.APV-527 in the fourth quarter of 2019.”

About Aptevo Therapeutics Inc.

Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel oncology, autoimmune 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 and autoimmune diseases.  Aptevo has 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, milestones, 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 18, 2019 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

Source: Aptevo Therapeutics Inc.