Aptevo Debuts First Trispecific Antibody Candidate, APVO451, with Preclinical Data Demonstrating Immune Activation in Hard-to-Treat Solid Tumors

Rhea-AI Summary

Aptevo (NASDAQ:APVO) presented first preclinical data for its trispecific antibody candidate APVO451 at the Society for Immunotherapy of Cancer Annual Meeting on November 8, 2025. APVO451 targets nectin-4 to localize activity, uses a CRIS-7-derived CD3 binding domain to activate T cells without observed cytokine release syndrome in related programs, and engages CD40 to restore antigen-presenting cell function.

Key preclinical findings showed tumor-localized T‑cell and APC activation, superior elimination of nectin-4+ tumor cells versus a standard CD3 engager in suppressive tumor models, and ongoing IND‑enabling preclinical studies.

Positive

• Tumor-localized T-cell and APC activation reported
• Superior elimination of nectin-4+ tumor cells versus standard CD3 engager
• Design aims to limit systemic activation and potential CRS

Negative

• APVO451 remains in preclinical stage; no human data yet
• IND-enabling studies are ongoing; clinical timing uncertain

Insights

Translational Immunotherapy Analyst

Preclinical data show tumor‑directed dual immune activation by APVO451 and a path toward IND‑enabling studies.

Aptevo presented preclinical evidence at the Society for Immunotherapy of Cancer on November 8, 2025 and announced the news on November 10, 2025 showing that APVO451 binds nectin‑4, engages T cells via the CRIS‑7‑derived CD3 domain, and engages CD40 on antigen‑presenting cells to restore intratumoral immunity. The data reported include tumor‑restricted T‑cell and APC activation, activity in suppressive cultured tumor models, and superior elimination of nectin‑4‑positive cells versus a standard CD3 T‑cell engager in those models. The company also frames the CRIS‑7 CD3 domain as having shown clinical activity with limited safety challenges and no cytokine release syndrome in mipletamig frontline AML patients to date.

Mechanistically, the molecule combines targeting (nectin‑4) and two immune signals (CD3 activation plus CD40 agonism) to localize and amplify anti‑tumor responses where intratumoral suppression exists. Key dependencies and risks include confirmation of tumor‑restricted activation in relevant in vivo models, reproducible safety signals across dose ranges, and successful translation from cultured models to complex human tumors. Concrete near‑term items to watch are completion of IND‑enabling studies, specific in vivo safety/toxicity readouts, and timing for an IND filing or first‑in‑human study; those milestones are expected as APVO451 advances through ongoing preclinical work toward IND‑enabling work within the stated development plan.

First data on Aptevo's new molecule presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting

SEATTLE, WASHINGTON / ACCESS Newswire / November 10, 2025 / Aptevo Therapeutics ("Aptevo" or the "Company") (Nasdaq:APVO), a clinical-stage biotechnology company advancing differentiated immunotherapies, announced the first presentation of preclinical data for its new trispecific antibody, APVO451, at the Society for Immunotherapy of Cancer (SITC) Annual Meeting on Saturday, November 8, 2025. The poster was presented by Michelle H. Nelson, PhD, Director of Immunobiology and Hieu Nguyen, BS, Senior Scientist, both of Aptevo.

APVO451 is designed to solve a central challenge in the treatment of certain solid tumor types {such as urothelial, breast and pancreatic cancers}: The tumor microenvironment often shuts down the immune system's ability to fight cancer. The new molecule leverages Aptevo's proprietary use of the CRIS-7-derived CD3 binding domain-the same binding domain used in the Company's lead clinical drug, mipletamig, which has shown strong clinical activity with limited safety challenges and, no cytokine release syndrome (CRS) in frontline AML patients to date.

"Solid tumors are often difficult to treat because the immune system within the tumor gets switched off," said Michelle H. Nelson, PhD, Director of Immunobiology at Aptevo. "APVO451 is designed to wake up the intratumoral immune system so it can more effectively target and kill tumor cells."

APVO451 brings two coordinated immune signals together in a single, targeted molecule. First, it binds to nectin-4, a protein commonly found on numerous solid tumors, which guides the drug directly to the tumor site and helps ensure that immune activation happens locally rather than throughout the body. Once there, the molecule uses the Company's proprietary CRIS-7-derived CD3 binding domain to activate T cells, triggering tumor-killing activity without inducing CRS that can occur with many T-cell engagers. Finally, APVO451 binds to CD40 and restores the inflammatory function of antigen-presenting cells (APCs), helping to ramp up the immune response. Working together, these signals are intended to re-activate anti-tumor immunity where it has been suppressed -a key shortcoming for many existing immunotherapies.

Key Findings from the Presentation

• Local Activation in the Tumor: APVO451 triggered T-cell and APC activation only when bound to the target nectin-4, suggesting the potential for strong immune activity without systemic over-activation resulting in a potentially favorable safety profile.

• Dual Immune Re-Activation: The molecule stimulated the effector functions of T-cells and restored APC function - two arms of the immune system that cause treatments to often fail in solid tumors due to the tumors' ability to suppress the immune system.

• Activity Under Suppressive Conditions: In cultured tumor models designed to mimic tumor suppression, APVO451 eliminated nectin-4-positive tumor cells more effectively than a standard CD3 T-cell engager potentially demonstrating the ability of APVO451 to overcome a suppressive tumor microenvironment.

"These findings reinforce a key principle we believe in at Aptevo," said Dr. Nelson. "Redirecting T cells is important and has been effective in liquid tumors-but sometimes it is not enough for solid tumors. In these cases, the drug must also address the intratumoral immune suppression. APVO451 is engineered to simultaneously do both in a tumor-directed way."

Next Steps
APVO451 is advancing through ongoing preclinical studies with the goal of supporting IND-enabling work and future clinical development in nectin-4-expressing solid tumors.

About APVO451
APVO451 is a trispecific ADAPTIR-FLEX^™ therapeutic candidate designed to target nectin-4 while engaging CD3 and CD40 to orchestrate coordinated T-cell activation and APC costimulation in the tumor microenvironment. The molecule is designed to restore productive immune engagement in suppressive solid tumors while minimizing off-tumor immune activation.

About Aptevo Therapeutics
Aptevo Therapeutics Inc. (Nasdaq: APVO) is a clinical-stage biotechnology company focused on developing novel bispecific and trispecific 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 AML 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 that is 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. Aptevo has six 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 the progress of Aptevo's clinical programs, including statements related to anticipated clinical and regulatory milestones, whether further study of mipletamig in a Phase 1b/2 dose optimization trial focusing on multiple doses of mipletamig in combination with venetoclax + azacitidine on a targeted patient population will continue to show remissions, whether Aptevo's final remission data or trial results will vary from its earlier assessment, whether Aptevo's strategy will translate into an improved overall survival in AML, especially among patient subgroups with poor prognosis, whether further study of ALG.APV-527 across multiple tumor types will continue to show clinical benefit, the possibility and timing of future preliminary or interim data readouts for ALG.APV-527, development and continued development of Aptevo's current and potential future molecules, APVO451's future development and efficacy with respect to addressing multiple solid tumor types, whether pre-clinical studies of Aptevo's trispecific candidate APVO451 will show the desired anti-tumor efficacy, mechanism of action and safety profile and whether APVO451 will function with new mechanisms of action compared to our previous candidates and synergistically induce a biological response, statements related to the progress of and enthusiasm for Aptevo's 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," "continue to," "believes," "knows," "expects," "optimism," "potential," "designed," "promising," "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; 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 results of preliminary or interim data and preclinical studies being predictive of the results of later-stage clinical trials, initiation, enrollment and maintenance of patients, and the completion of 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 Aptevo's product candidates, business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises, geopolitical risks, including the current wars between Russia and Ukraine and any other military event that could evolve out of any of the current conflicts and macroeconomic conditions such as economic uncertainty, imposition of tariffs, rising inflation and interest rates, continued 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
Aptevo Therapeutics
IR@apvo.com or millerm@apvo.com
+1 (206) 859 6629

SOURCE: Aptevo Therapeutics

View the original press release on ACCESS Newswire

FAQ

What is APVO451 and which company develops it (APVO)?

APVO451 is a trispecific antibody developed by Aptevo (APVO) targeting nectin-4, CD3 and CD40.

When and where were APVO451 preclinical data presented for APVO?

Data were presented at the SITC Annual Meeting on November 8, 2025.

What were the main preclinical results reported for APVO451?

APVO451 triggered tumor-localized T-cell and APC activation and outperformed a standard CD3 engager in suppressive models.

Does APVO451 cause cytokine release syndrome (CRS) in these studies?

Preclinical findings indicate localized activation; no clinical CRS data exist yet.

What cancer indications is APVO451 aimed at for APVO?

APVO451 is being developed for nectin-4‑expressing solid tumors such as urothelial, breast, and pancreatic cancers.

What are the next development steps for APVO451 (APVO)?

APVO451 is in ongoing preclinical and IND-enabling studies to support future clinical development.