Aptevo Highlights APVO603: A Novel Bispecific Antibody Targeting 4-1BB and OX40 for Enhanced Solid Tumor Immunotherapy

Rhea-AI Summary

Aptevo Therapeutics (NASDAQ:APVO) has provided an overview of APVO603, a novel bispecific antibody in preclinical development for solid tumor treatment. The drug targets 4-1BB and OX40 receptors to enhance anti-tumor immune responses.

Preclinical studies demonstrate that APVO603:

• Enhances T cell and NK cell proliferation
• Maintains favorable safety profile
• Inhibits immune exhaustion
• Shows robust anti-tumor response

The company also updated on other pipeline developments:

• Mipletamig: Phase 1b/2 RAINIER trial showing 100% remission in Cohort 1 within 30 days
• ALG.APV-527: Phase 1 trial for solid tumors showing 59% stable disease rate in 17 evaluable patients

Positive

• 100% remission rate in Mipletamig's RAINIER trial Cohort 1 within 30 days
• 59% of patients achieved stable disease in ALG.APV-527 Phase 1 trial
• No cytokine release syndrome reported in current Mipletamig trial
• Successful immune activation biomarkers confirmed in tumor microenvironment

Negative

• APVO603 still in preclinical stage, requiring significant development time before potential commercialization
• patient data available from ongoing trials

Continues focus on development of bispecific anti-cancer agents with differentiated mechanisms of action

SEATTLE, WASHINGTON / ACCESS Newswire / March 18, 2025 / Aptevo Therapeutics (NASDAQ:APVO), a leader in the development of novel bispecific antibodies for cancer treatment, based on its proprietary ADAPTIR^® and ADAPTIR-FLEX^® platform technologies provided an overview of solid tumor anti-cancer compound APVO603, currently in preclinical development for the treatment of solid tumors. APVO603 is a novel bispecific antibody designed to enhance anti-tumor immune responses through dual targeting of 4-1BB (CD137) and OX40 (CD134), two key co-stimulatory receptors involved in T cell and NK cell activation.

APVO603 is part of Aptevo's solid tumor anti-cancer pipeline and represents a significant step forward in leveraging the company's proprietary ADAPTIR^® platform to develop safer and more effective immuno-oncology therapies.

Targeted Immune Activation for Solid Tumors
APVO603 is designed to activate the costimulatory 4-1BB and OX40 pathways in the tumor microenvironment, leading to enhanced T cell expansion, survival, and cytotoxic function while avoiding systemic toxicity. This targeted immune activation could overcome immune suppression in solid tumors, a major challenge in cancer immunotherapy.

Preclinical studies have shown that APVO603:

• Enhances T cell and NK cell proliferation and tumor lysis, while maintaining a favorable safety profile and inhibiting immune exhaustion

• Induces a robust anti-tumor response in preclinical tumor models, suggesting strong therapeutic potential

"We are excited about the potential of APVO603 to enhance the potency of T cells and NK cells while addressing the limitations of current therapies for solid tumors," said Michelle Nelson, PhD, Director of Immunobiology at Aptevo. "Our preclinical findings support APVO603's ability to deliver 4-1BB and OX40 synergistically resulting in targeted immune stimulation with reduced toxicity risks, differentiating it from existing immunotherapies."

Aptevo's Advancing Immuno-Oncology Pipeline

APVO603 is one of three promising preclinical candidates in Aptevo's bispecific antibody pipeline, alongside APVO711, a bispecific + checkpoint inhibitor, and APVO442, a T-cell engager targeting prostate cancer. These programs build on Aptevo's expertise in bispecific antibody engineering and reinforce the company's commitment to developing novel immunotherapies that improve outcomes for cancer patients.

Clinical Programs
Lead Candidate Mipletamig for Acute Myeloid Leukemia (AML): Mipletamig, Aptevo's lead bispecific antibody, is currently in a frontline Phase 1b/2 combination trial, RAINIER, following positive results from earlier studies.

RAINIER results reported to date include:

• 100% of patients in Cohort 1 of the trial achieved remission within 30 days

• One patient experienced complete remission with minimal residual disease (MRD)-negative status (100% elimination of cancer cells)

• Favorable safety profile consistent with prior trials, showing no incidences of cytokine release syndrome (CRS) in the current trial to date, a common and often dose limiting side effect seen in similar therapies

ALG.APV-527: ALG.APV-527 is being evaluated in a Phase 1 trial for solid tumors likely to express the tumor antigen 5T4. Tumor types treated to date include breast, colon, pancreatic and non-small cell lung cancer. Positive preliminary data from the study were presented at the European Society of Medical Oncology Congress in September and at the Society for Immunotherapy of Cancer conference in 2024. These results showed that ALG.APV-527 demonstrated positive safety and tolerability across all cohorts, ten of 17 evaluable patients (59%) achieved stable disease (SD), and biomarker analysis confirmed immune activation in the tumor microenvironment.

This drug has the potential to advance treatment in hard-to-treat solid tumors, demonstrating the versatility of Aptevo's technology across a wide range of cancer types.

About Aptevo Therapeutics
Aptevo Therapeutics Inc. (Nasdaq:APVO) is a clinical-stage biotechnology company focused on developing novel bispecific immunotherapies for the treatment of cancer. The company has two clinical candidates. Mipletamig is currently being evaluated in RAINIER, a Phase 1b/2 trial for the treatment of frontline acute myeloid leukemia in combination with standard of care venetoclax + azacitidine. Mipletamig has orphan status for AML according to the Orphan Drug Act. ALG.APV-527, a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4, is being co-developed with Alligator Bioscience and is being evaluated in a Phase 1 clinical trial for the treatment of multiple solid tumor types likely to express 5T4. The Company has three pre-clinical candidates with different mechanisms of action designed to target a range of solid tumors. All pipeline candidates were created from two proprietary platforms, ADAPTIR^® and ADAPTIR-FLEX^®. The Aptevo mission is to improve treatment outcomes and transform the lives of cancer patients. 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. All statements, other than statements of historical fact, including, without limitation, Aptevo's expectations about the activity, efficacy, safety, tolerability and durability of its therapeutic candidates and potential use of any such candidates, including in combination with other drugs, as therapeutics for treatment of disease, its expectations regarding the effectiveness of its ADAPTIR^® and ADAPTIR-FLEX^® platforms, statements related to Aptevo's technology utilizing various mechanisms of action and whether such mechanisms of action will improve patient outcomes, statements related to the progress of Aptevo's clinical programs, including initial results from the Phase 1b/2 dose optimization trial to further evaluate mipletamig in combination with venetoclax and azacitidine , whether further study of mipletamig in Phase 1b/2 trial focusing on a targeted patient population will continue to show clinical benefit, whether Aptevo's strategy will translate into an improved overall survival rate in acute myeloid leukemia, whether the mipletamig data in combination therapy and monotherapy will be indicative of later stage clinical trials, whether further study of ALG.APV-527 across multiple tumor types will continue to show clinical benefit, whether biomarker analyses will continue to confirm biological activity of ALG.APV-527, the possibility and timing of future preliminary or interim data readouts for mipletamig and ALG.APV-527, whether Aptevo's final trial results will vary from its preliminary or interim assessments, statements related to the progress of and enthusiasm for Aptevo's preclinical and clinical programs, statements related to Aptevo's ability to generate stockholder value, whether Aptevo will continue to have momentum in its business in the future, and any other statements containing the words "may," "believes," "expects," "potential," "designed," "engineered," "innovative," "initiate," "allow," "promise," "plans," "will" and similar expressions are intended to identify 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.

There are several 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; further assessment of preliminary or interim data or different results from later clinical trials; adverse events and unanticipated problems, adverse developments in clinical development, including unexpected safety issues observed during a clinical trial; adverse developments in the U.S. or global capital markets, credit markets or economies generally; and changes in regulatory, social, macroeconomic, and political conditions. For instance, actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the uncertainties inherent in the initiation, enrollment and maintenance of patients in clinical trials, uncertainties inherent in the results of preliminary or interim data and preclinical and clinical studies being predictive of the results of later-stage clinical trials, the availability and timing of data from ongoing clinical trials, the trial design includes combination therapies that may make it difficult to accurately ascertain the benefits of mipletamig, expectations for the timing and steps required in the regulatory review process, expectations for regulatory approvals, the impact of competitive products, our ability to enter into agreements with strategic partners or raise funds on acceptable terms or at all and other matters that could affect the availability or commercial potential of the Company's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises such as the novel coronavirus (referred to as COVID-19), geopolitical risks, including the current war between Russia and Ukraine as well as the war between Israel and Hamas, and macroeconomic conditions such as rising inflation and interests rates, increased market volatility and decreased consumer confidence. These risks are not exhaustive, Aptevo faces known and unknown risks. Additional risks and factors that may affect results are set forth in Aptevo's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2024, 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. Any forward-looking statement speaks only as of the date of this press release, and, except as required by law, Aptevo does not assume any obligation to update any forward-looking statement to reflect new information, events, or circumstances.

Aptevo Therapeutics
Miriam Weber Miller |
Email: IR@apvo.com or millerm@apvo.com
Phone: 206-859-6629

SOURCE: Aptevo Therapeutics

View the original press release on ACCESS Newswire

FAQ

What are the key findings from APVO603's preclinical studies for solid tumors?

APVO603 demonstrated enhanced T cell and NK cell proliferation, tumor lysis capabilities, and maintained a favorable safety profile while showing robust anti-tumor response in preclinical models.

What are the latest results from Aptevo's RAINIER trial for Mipletamig in AML?

The RAINIER trial showed 100% remission rate in Cohort 1 within 30 days, with one patient achieving complete remission with MRD-negative status and no cytokine release syndrome reported.

How effective is ALG.APV-527 in treating solid tumors based on Phase 1 data?

ALG.APV-527 showed positive safety and tolerability, with 59% of evaluable patients (10 out of 17) achieving stable disease across various tumor types including breast, colon, pancreatic and lung cancer.

What makes APVO603's mechanism of action unique for cancer treatment?

APVO603 uniquely targets both 4-1BB and OX40 costimulatory receptors simultaneously, enabling targeted immune activation in the tumor microenvironment while avoiding systemic toxicity.