SEATTLE, WA – Aptevo Therapeutics (“Aptevo” or “the Company”) (NASDAQ:APVO), a clinical-stage biotechnology company developing novel bispecific and trispecific immuno-oncology therapeutics, today announced a 100% remission rate in Cohort 3 of its Phase 1b/2 RAINIER trial evaluating mipletamig, the Company’s first-in-class CD123 x CD3 bispecific antibody, in combination with venetoclax + azacitidine for newly diagnosed patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy. Aptevo also reported that no dose-limiting toxicities or cytokine release syndrome have been observed in the RAINIER trial, or among any frontline patients treated with mipletamig to date.
Efficacy and Market Opportunity
The 100% remission rate (CR/CRi) achieved at the highest dose level of the RAINIER trial to date demonstrates mipletamig’s potential to redefine the frontline treatment landscape for newly diagnosed AML patients who are unfit for intensive chemotherapy. Additionally, 40% of patients treated to date have achieved minimal residual disease (MRD)-negative status, a critical marker of remission that is strongly associated with improved overall outcomes in AML. Frontline AML represents a multibillion-dollar global market where current standard regimens achieve lower remission rates than those observed in RAINIER, leaving a substantial need for more effective options. By consistently delivering remissions across three increasing dose cohorts, and among frontline patients in prior trials, mipletamig positions Aptevo to compete for-and potentially expand-a high-value segment of the AML market, offering a therapy that could raise the bar for clinical outcomes and capture meaningful share of an underserved population.
Safety
Equally compelling is mipletamig’s clean safety profile. Across Cohort 3 and the two prior RAINIER cohorts, no dose-limiting toxicities have been observed, and tolerability remains strong even at the highest dose tested. This differentiated safety record, reinforced by two earlier trials, supports the drug’s use alongside venetoclax and azacitidine and sets it apart from many emerging AML combinations that struggle with cytokine release syndrome and other immune-related toxicities. The combination of efficacy and consistently favorable safety underscores mipletamig’s potential to integrate smoothly into the standard of care for frontline AML.
“Cohort 3 demonstrates the kind of progress that changes expectations for frontline AML therapy, ” said Marvin White, President and Chief Executive Officer of Aptevo. “ Delivering a 100% remission rate reinforces our conviction that mipletamig is more than an active agent-it’s a differentiated medicine designed to integrate with the venetoclax and azacitidine backbone and elevate outcomes for patients who have had too few options for too long.”
“The Cohort 3 results are exceptional both in depth of response and in consistency ,” said Dirk Huebner, MD, Chief Medical Officer. “ Across the RAINIER trial to date, mipletamig has achieved near-universal remissions while maintaining a safety profile that is very well managed in the clinic. This balance of potency and tolerability is exactly what physicians need to confidently adopt a new frontline regimen.”
Next Steps
Cohort 3 enrollment is complete and Cohort 4 is actively enrolling patients at the next dose level. The Company anticipates that current findings will be presented at a major medical conference in Q4.
About RAINIER
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 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, ADAPTIRTM and ADAPTIR-FLEXTM . The Aptevo mission is to improve treatment outcomes and transform the lives of cancer patients. For more information, please visit www.aptevotherapeutics.com.
Aptevo Therapeutics Contact
Miriam Weber Miller
Aptevo Therapeutics
[email protected] or [email protected]
+1 (206) 859 662