Aptevo Therapeutics Presents New Preclinical Data for APVO436 and ALG.APV-527 at the American Association for Cancer Research 2019 Annual Meeting
APVO436 Preclinical Data Continue to
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
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
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
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.”
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
Senior Director, Investor Relations and Corporate Communications
Source: Aptevo Therapeutics Inc.