SEATTLE, WA – Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies, presented preliminary results from its ongoing Phase 1b/2 RAINIER study evaluating mipletamig, a CD123 x CD3 bispecific molecule, in combination with azacitidine and venetoclax (AZA/VEN) for newly diagnosed acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. The data were presented on December 8, 2025, in a poster session at the American Society of Hematology (ASH) Annual Meeting.
Across dose-optimization Cohorts 1-3, mipletamig combined with AZA/VEN demonstrated high remission rates and a compelling safety/tolerability profile, reinforcing the potential of T-cell engagement in frontline AML when safety can be effectively managed. Aptevo’s proprietary use of the CRIS-7-derived CD3 binding domain differentiates mipletamig in the category.
Key Findings
- 100% of treated patients remained free of cytokine release syndrome (CRS) across cohorts to date
- 93% overall response rate (ORR) among evaluable patients
- 87% achieved CR/CRi*
- 73% achieved CR
- 60% of MRD evaluable CR/CRi patients achieved minimum residual disease negative status, a result that is typically associated with stronger, more durable responses
- 43% of ORR patients had a TP53 genetic mutation, a marker that is typically associated with poor prognosis in AML patients
*Remission = complete remission (CR) and, complete remission with blood markers that have not yet recovered (CRi).
Median patient age was 75, reflecting a population that is underserved by intensive therapies. In the RAINIER trial to date, the triplet regimen was generally well tolerated. Infusion-related reactions and hematologic events were the most common adverse events, consistent with expectations for this patient population. Importantly, no CRS was seen, supporting the molecule’s differentiated safety profile in combination therapy.
“These data, particularly the remission rates and absence of CRS, underscore the promise of mipletamig as part of a frontline AML regimen,” said Dirk Huebner, MD, Chief Medical Officer. “We are encouraged by the safety and efficacy profile we are seeing across cohorts, and we look forward to advancing the program into later-stage evaluation.”
The RAINIER study continues to enroll patients across additional dose levels. Mipletamig’s design leverages Aptevo’s ADAPTIR™ platform to deliver targeted T-cell engagement with the goal of minimizing systemic immune activation-an important factor in realizing the full therapeutic potential of T-cell engagers in AML.
About the RAINIER Trial
RAINIER, a frontline AML study, is a Phase 1b/2 dose optimization, multi-center, multi-cohort, open label study. Subjects are adults aged 18 or older, newly diagnosed with AML who are not eligible for intensive induction chemotherapy. RAINIER will be conducted in two parts. First, a Phase 1b dose optimization study in frontline AML patients followed by a Phase 2 study. The Phase 1b trial consists of 28-day cycles of treatment across multiple, sequential cohorts.
About Mipletamig
Aptevo’s wholly owned lead proprietary drug candidate, mipletamig, being evaluated for the treatment of AML, is differentiated by design to redirect the immune system of the patient to destroy leukemic cells and leukemic stem cells expressing the target antigen CD123, which is a compelling target for AML due to its overexpression on leukemic stem cells and AML blasts. This antibody-like recombinant protein therapeutic is designed to engage both leukemic cells and T cells of the immune system and bring them closely together to trigger the destruction of leukemic cells. Mipletamig is purposefully designed to reduce the likelihood and severity of CRS by use of the CRIS-7-derived CD3 binding pathway an approach that differentiates Aptevo from competitors. Mipletamig has received orphan drug designation (“orphan status”) for AML according to the Orphan Drug Act. Orphan drug designation provides key advantages-including the opportunity to seek U.S. market exclusivity for a specific period of time upon approval, FDA fee reductions, and access to development and tax credits. Mipletamig has been evaluated in more than 100 patients over three trials to date.
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 two-part Phase 1b/2 trial for the treatment of frontline acute myeloid leukemia in combination with standard-of-care venetoclax + azacitidine. Mipletamig has received orphan drug designation (“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 was most recently evaluated in a Phase 1 clinical trial for the treatment of multiple solid tumor types likely to express 5T4. The Company has six preclinical candidates with different mechanisms of action designed to target a range of solid tumors. All pipeline candidates were created from two proprietary platforms, ADAPTIRand 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.
CONTACT
Miriam Weber Miller
Head, Investor Relations & Corporate Communications
Aptevo Therapeutics
Email: [email protected] or [email protected]
Phone: 206-859-6628