Aptevo Therapeutics Announces Substantial Reduction In Infusion-Related Reactions For Mipletamig Following Successive Refinements To Its Priming-Dose Regimen; Improvement Builds On Mipletamig's Already Favorable Safety And Tolerability Profile

The improvement builds on mipletamig's already favorable safety and tolerability profile, including encouraging cytokine release syndrome (CRS) findings observed throughout its clinical development. Mipletamig data will be presented at the American Society of Hematology (ASH) 68th Annual Meeting in New Orleans, Louisiana from December 12-15, 2026.

The ongoing RAINIER dose optimization study has demonstrated encouraging clinical activity and a favorable safety and tolerability profile for mipletamig, including favorable findings related to cytokine release syndrome (CRS). Building on these results, Aptevo has further improved tolerability through refinements to the priming-dose regimen, substantially reducing infusion-related reactions (IRRs) during initial treatment. The Company believes this achievement is a key part of creating an optimized dose that delivers safety, tolerability and efficacy, consistent with the objectives of its discussions with the U.S. Food and Drug Administration (FDA), as it prepares for Phase 2 development.

Mipletamig is being evaluated in combination with standard-of-care venetoclax and azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. The Company expects to complete the current study by year-end 2026.

"We have made substantial progress in improving mipletamig's tolerability for patients with frontline AML," said Dirk Huebner, M.D., Chief Medical Officer of Aptevo Therapeutics. "Mipletamig has demonstrated a differentiated safety and tolerability profile, and successive refinements to the priming-dose regimen have substantially reduced the occurrence of infusion-related reactions. Reducing these reactions matters to patients: it has the potential to make treatment easier to tolerate and limit complications that can disrupt care. These findings are an important part of our preparations for the next stage of clinical development."

A Targeted Improvement with Meaningful Patient Benefits

Infusion-related reactions can occur during or after intravenous treatment and may include fever, chills, rash or nausea. Although often manageable, these reactions can be uncomfortable for patients and, depending on their severity, may require additional medical intervention, treatment interruptions or discontinuation.

This is particularly relevant in frontline AML, where patients who are unfit for intensive chemotherapy are often older or have additional health conditions that make treatment tolerability especially important.

Mipletamig's priming-dose regimen gradually introduces treatment before escalation to higher doses. Aptevo has refined this approach over the course of RAINIER to reduce treatment-related reactions during early dosing, building on the favorable tolerability observations previously reported for mipletamig.

Successive refinements to the initial dosing regimen have been associated with substantial reductions in the occurrence of treatment-related reactions, including IRRs. For patients, fewer treatment-related reactions may mean a more comfortable and predictable treatment experience, less need for additional medical intervention and fewer disruptions during treatment. These considerations are especially important for patients with frontline AML, who may be older or have other health conditions.

Building on an Already Favorable Safety Profile

Mipletamig has demonstrated an encouraging safety and tolerability profile throughout its clinical development, including highly favorable findings related to cytokine release syndrome (CRS), a potentially serious inflammatory reaction associated with certain immune-based cancer therapies.

The latest refinements to mipletamig's priming-dose regimen build on that foundation by substantially reducing infusion-related reactions during initial treatment. Together, these findings underscore Aptevo's continued focus on optimizing treatment tolerability while advancing mipletamig as a potential addition to the frontline AML standard of care.

Together, these observations reinforce Aptevo's focus on improving the patient treatment experience as it optimizes mipletamig for combination therapy. Reducing treatment-related reactions could lessen interruptions that interfere with care and help preserve patients' opportunity to receive treatment and potentially benefit from it.

Making the Case in Frontline AML

The dosing refinement adds to a growing body of clinical evidence supporting mipletamig's potential as an addition to the current frontline AML standard of care.

Aptevo has previously reported encouraging clinical activity in the RAINIER study, including remission responses in patients with TP53-mutated AML, a high-risk population with historically poor outcomes. The Company has also reported that patients initially considered unfit for intensive chemotherapy have advanced to allogeneic stem cell transplantation, a potentially curative treatment option.

These findings support the continued evaluation of mipletamig in combination with venetoclax and azacitidine, with the goal of improving outcomes beyond those achieved with the current standard-of-care doublet.

The refined priming-dose regimen strengthens the tolerability component of mipletamig's development profile. While these findings do not establish improved efficacy or treatment persistence, reducing reactions that can interrupt therapy is clinically meaningful and may lessen a potential obstacle to continued treatment.

Advancing Toward Phase 2 Development

The substantial reductions in IRRs and CRS observed following successive priming-dose refinements represent important progress in Aptevo's preparation for Phase 2 development.

These observations add to the clinical evidence informing dose selection and upcoming regulatory discussions, reflecting Aptevo's continued focus on improving tolerability while evaluating mipletamig's therapeutic potential in frontline AML.

The Company continues to evaluate clinical activity, safety and tolerability in RAINIER and expects to complete the current study by year-end 2026, conduct regulatory interactions and initiate Phase 2 development in 2027.

Aptevo's objective remains to develop mipletamig as an effective, well-tolerated addition to the current frontline AML standard of care, offering patients the potential for better outcomes without unnecessarily increasing the burden of treatment.