mipletamig (APVO436) / Ligand, Aptevo Therap - LARVOL DELTA

Aptevo Reports 93% Clinical Benefit Rate with Mipletamig Triplet in Difficult-to-Treat TP53-Mutated Frontline AML (Yahoo Finance) - "Of 14 evaluable TP53-mutated patients treated with mipletamig in combination with venetoclax and azacitidine, including two patients from the previously completed dose expansion trial, 13 (93%) experienced clinical benefit. Eleven patients achieved CR or CRi (79%), including nine complete remissions....These results are encouraging because patients with TP53-mutated AML have historically had limited treatment success. The 79% CR/CRi rate observed with the mipletamig triplet compares favorably with a published 41% composite remission rate for venetoclax plus azacitidine in treatment-naïve patients with poor-risk cytogenetics and TP53-mutated AML....This phase of the trial is expected to be completed by year-end, and regulatory interaction is planned for 1H27 to determine next steps."

P1/2 data • Regulatory • Trial status • Acute Myelogenous Leukemia

Mipletamig Drives Clinical Momentum with Strong Frontline AML Data and a Path Toward Phase 2 (Yahoo Finance) - "RAINIER has entered the final stage of dose optimization, positioning Aptevo to complete the Phase 1b RAINIER trial and select the recommended Phase 2 dose this year in anticipation of a Phase 2 regulatory interaction in 1Q27."

Trial status • Acute Myelogenous Leukemia

Aptevo Therapeutics Provides a 1Q26 Business Update; RAINIER on Track for 2026 Completion and Phase 2 Dose Selection (ACCESS Newswire)

Trial status • Acute Myelogenous Leukemia

Aptevo Reports 87% Clinical Benefit and 81% Remission in 31 Evaluable Frontline AML Patients Through Cohort 5, Substantially Outperforming Benchmark; RAINIER on Track for 2026 Completion and Phase 2 Dose Selection (ACCESS Newswire) - "Program Enters Final Stage of Dose Optimization...65% achieved CR (complete remission), comparing favorably to the historical benchmark; 55% of patients who achieved CR/CRi had blast reductions that reached the important measurable residual disease-negative level, a result that is typically associated with stronger, more durable responses; 36% of patients with remissions had the TP53 genetic mutation, a high-risk biomarker typically associated with poor prognosis in AML and for which most treatment options frequently fail; 6 patients treated to date have proceeded to allogeneic stem cell transplant, which represents the best possible outcome in AML treatment and is rarely achieved in the older or unfit frontline patient population."

P1/2 data • Trial completion date • Acute Myelogenous Leukemia

2025 Summary Financial Results (ACCESS Newswire) - "Research and Development Expenses: Research and development expenses was $14.5 million and $14.4 million for the years ended December 31, 2025, and 2024, respectively. The increase was primarily due to increased mipletamig and employee costs and was offset by lower costs on ALG.APV- 527 as we concluded the dose escalation trial."

Commercial • Acute Myelogenous Leukemia • Solid Tumor

Mipletamig Delivers Compelling 86% Clinical Benefit Rate and No CRS as Evaluable AML Patient Data increases by Nearly 50% (ACCESS Newswire) - "Among the evaluable frontline patient population treated to date (N=28), including 24 patients from the RAINIER trial and 4 patients from the completed dose expansion trial, mipletamig in combination with venetoclax and azacitidine has demonstrated: 100% of frontline patients have remained free of cytokine release syndrome (CRS)...79% achieved CR or CRi; 61% achieved CR; 55% of patients who achieved CR/CRi had blast reductions that reached the important measurable residual disease-negative level, a result that is typically associated with stronger, more durable responses...'As enrollment continues, we remain focused on advancing our RAINIER trial and generating the data needed to support mipletamig's long-term role in AML treatment.'"

Cytokine release syndrome • Retrospective data • Acute Myelogenous Leukemia

A dose optimization phase 1b/2 study evaluating mipletamig (formerly APVO436), a novel bispecific CD123 x CD3 ADAPTIRÒ molecule in combination therapy for the treatment of frontline acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy (ASH 2025) - "Introduction Despite azacitidine and venetoclax (AZA/VEN) being a new standard treatment for newly diagnosedolder/unfit AML, overall outcomes remain poor. CRS has not been detectedwith the addition of the new priming dose schedule, while manageable IRRs were observed during thatphase. The study is actively enrolling, and higher dose level results will be presented at the congress."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Constipation • Cough • Gastroenterology • Gastrointestinal Disorder • Hypotension • Inflammation • Neutropenia • Respiratory Diseases • CD123 • IL3RA • TP53

Aptevo Therapeutics Highlights Compelling Safety and Strong Remission Rates for Mipletamig in Frontline AML at ASH 2025 (ACCESS Newswire) - "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....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."

P1/2 data • Acute Myelogenous Leukemia

4th Annual ROTH Healthcare Opportunities Conference (ACCESS Newswire) - "Aptevo will participate in a panel on Acute Myeloid Leukemia titled 'Novel AML Therapies Showing Clear Clinical Progress,' discussing progress and recent trial outcomes of its lead asset, mipletamig, and sharing emerging evidence of its differentiated clinical profile in frontline AML-where strong safety, tolerability, and early efficacy continue to demonstrate meaningful potential for improved patient outcomes."

Clinical data • Acute Myelogenous Leukemia

American Society of Hematology (ASH) 2025 - 67th American Society of Hematology Annual Meeting & Exposition (ACCESS Newswire) - "Interim results from the ongoing Phase 1b/2 RAINIER trial evaluating mipletamig in frontline combination therapy for the treatment of AML, will be presented in a poster session by the clinical team."

P1/2 data • Acute Myelogenous Leukemia

Mipletamig Delivers 100% Remission Rate in Cohort 3 of RAINIER Trial for AML (ACCESS Newswire) - "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...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....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."

P1/2 data • Trial status • Acute Myelogenous Leukemia

Mipletamig Demonstrates Compelling Clinical Activity in Frontline AML (ACCESSWIRE) - P1b/2 | N=39 | RAINIER (NCT06634394) | Sponsor: Aptevo Therapeutics | "85% remission rate observed in evaluable frontline AML patients; Mipletamig combination enables rare pathway to transplant in a previously ineligible unfit patient; No dose-limiting toxicities observed among evaluable patients; safety profile remains strong; Evidence mounts for mipletamig as a potentially transformational addition to standard of care in frontline AML as targeted CD123 x CD3 approach showing power and precision, limited added toxicity; mipletamig trial momentum builds as cohort 3 nears full enrollment at highest dose level evaluated to date in combination therapy; No CRS has been reported in either cohorts 1 or 2"

P1/2 data • Acute Myelogenous Leukemia

RAINIER: APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML (clinicaltrials.gov) - P1 | N=39 | Recruiting | Sponsor: Aptevo Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Aptevo Therapeutics Reports 1Q25 Financial Results And Provides an Update on Mipletamig (ACCESSWIRE) - P1b/2 | N=39 | RAINIER (NCT06634394) | Sponsor: Aptevo Therapeutics | "Data from Six frontline AML patients has been reported in the ongoing RAINIER Phase 1b/2 trial evaluating mipletamig in combination with venetoclax and azacitidine. Of these, five of six (5/6) patients have achieved remission within 30 days of being dosed; One patient progressed after the first cycle and passed away due to reasons unrelated to the study drug; These results build on data from a prior expansion study, in which four additional frontline patients treated with the same triplet combination also achieved remission."

P1/2 data • Acute Myelogenous Leukemia

Aptevo Therapeutics Provides Program Update for Bispecific APVO711, a PD-L1 X CD40 that Combines a Checkpoint Inhibitor and Immune Activation (ACCESSWIRE) - "As lead candidate mipletamig continues to outperform efficacy and safety benchmarks in AML trials, APVO711 exemplifies emerging innovation from Aptevo's proprietary ADAPTIR platform; In preclinical studies, APVO711 demonstrates dual anti-cancer functionality with broad solid tumor potential and developability."

Clinical data • Preclinical • Acute Myelogenous Leukemia • Solid Tumor

Across two trials, 9 of 10 frontline AML patients achieved remission when treated with mipletamig in combination with the standard of care (ACCESSWIRE) - P1b/2 | N=39 | RAINIER (NCT06634394) | Sponsor: Aptevo Therapeutics | "Aptevo Therapeutics...today announced two additional frontline AML patients have achieved remission within 30 days of treatment in the Company's RAINIER dose optimization trial...Notably, no CRS has been reported in the RAINIER trial to date...Together with the addition of these interim Cohort 2 results, mipletamig has achieved a compelling overall remission rate of 90% among frontline patients. This outperforms the doublet remission rate from a venetoclax + azacitidine only study, of 66%. Additionally, the frontline patient triplet therapy CR rate of 70% outperforms the CR rate from a venetoclax + azacitidine only study of 36% (Viale-A Pivotal trial)...Three patients evaluable for efficacy achieved the following outcomes: Two patients achieved remission withing 30 days of being dosed; One patient progressed after the first cycle and passed away for reasons unrelated to study drugs."

P1 data • Acute Myelogenous Leukemia

100% of Patients Achieve Remission Within 30 Days in Cohort 1 of Bispecific Mipletamig Frontline AML Trial (ACCESSWIRE) - P1b/2 | N=39 | RAINIER (NCT06634394) | Sponsor: Aptevo Therapeutics | "Aptevo Therapeutics...announced 100% of patients achieved remission within 30 days, in Cohort 1 of the RAINIER frontline acute myeloid leukemia (AML) Phase 1b trial, including two patients who experienced complete remission with minimal residual disease (MRD)-negative status (100% elimination of cancer cells)....Cohort 2 enrollment is commencing, marking the next step in the study."

P1 data • Trial status • Acute Myelogenous Leukemia

First Patient Dosed in Aptevo’s Ongoing RAINIER Trial Achieves 90% Reduction in Leukemic Blasts Within the First 30 Days of Treatment, Continues Overall Efficacy Trend Seen in Prior Mipletamig AML Studies (ACCESSWIRE) - P1b/2 | N=39 | RAINIER (NCT06634394) | Sponsor: Aptevo Therapeutics | "Aptevo Therapeutics...expanded on the potential of mipletamig, currently being evaluated as frontline therapy for the treatment of Acute Myeloid Leukemia (AML), in combination with standard of care venetoclax and azacitidine, noting the first patient dosed in the ongoing RAINIER trial achieved a 90% reduction in leukemic blasts within the first 30 days of treatment, continuing the overall efficacy trend seen in prior studies."

P1/2 data • Acute Myelogenous Leukemia

Phase 1b/2 “RAINIER“ Frontline Acute Myeloid Leukemia (AML) Trial Initiated (ACCESSWIRE) - "Aptevo Therapeutics...announced initiation of the Company's Phase 1b/2 dose optimization trial, 'RAINIER,' as part of its ongoing program to evaluate APVO436 in combination with venetoclax + azacitidine for frontline patients with acute myeloid leukemia (AML). RAINIER will be conducted in two parts. First, a Phase 1b frontline AML study followed by a Phase 2 study. The Company also announced that APVO436 has received its generic name, mipletamig (mih-ple'-tah-mig) and will refer to its lead candidate by this name moving forward."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML (clinicaltrials.gov) - P1 | N=39 | Not yet recruiting | Sponsor: Aptevo Therapeutics

Combination therapy • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Aptevo Therapeutics Reports 2Q 2024 Financial Results and Provides a Business Update (Aptevo Therapeutics Press Release) - "APVO436: The Company is planning to initiate the first part of the Phase 1b/2 dose optimization program in this quarter."

Trial status • Acute Myelogenous Leukemia • Oncology

OUTCOMES WITH IMMUNE-BASED THERAPIES FOR TP53 MUTATED ACUTE MYELOID LEUKEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2024) - "Immune therapies were Magrolimab 4 (40%), Durvalumab 1 10%),Nivolumab 1 (10%), Flotetuzumab 1 (10%), Pembrolizumab 1 (10%), CLL1-CD33 CAR-T 1 (10%), and APVO436 1(10%). Non-allogeneic transplant immune-based therapies show encouraging response rates, offering a potential treatmentoption for patients with TP53 mutated AML for whom options are limited. Prospective randomized studies withreasonable long follow up are needed to establish the efficacy of immune-based therapies in this difficult to treat population."

IO biomarker • Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • TP53

Aptevo Therapeutics Reports 1Q 2024 Financial Results and Provides a Business Update (ACCESSWIRE) - "The Company is on track to initiate its upcoming dose optimization trial in 2Q 2024 to further evaluate APVO436 for the treatment of frontline acute myeloid leukemia (AML). Aptevo has partnered with premier CRO, Prometrika, for the upcoming study. The first part of the Phase 1b/2 study is a dose optimization trial evaluating standard of care venetoclax + azacitidine along with APVO436 as a frontline treatment for AML patients. It is planned as an open-label, multi-center, multi-cohort study. The trial will evaluate safety/tolerability and efficacy of the triplet combination at multiple dose levels....Research and development expenses decreased by $0.4 million...The decrease was primarily due to lower spending on APVO436 clinical trial as we concluded the Phase 1b study and are preparing to initiate the frontline AML dose optimization study and lower spending on preclinical projects and employee costs. The decrease was partially offset by higher spending on ALG.APV-527..."

Commercial • Licensing / partnership • New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Aptevo Therapeutics Reports 2023 Financial Results and Provides a Business Update (Aptevo Therapeutics Press Release) - "Upon review of this data and in consultation with the FDA, Aptevo intends to initiate an open- label Phase 1b/2 trial in 1H24 to further evaluate APVO436 in combination with the current standard of care, venetoclax + azacitidine, in frontline, venetoclax naïve AML patients....The Company plans to report interim data in late 2H24."

New P1/2 trial • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Aptevo Therapeutics Reports 3Q23 Financial Results and Provides a Business Update (Aptevo Therapeutics Press Release) - "Planning for initiation of the Company's Phase 2 program evaluating APVO436 in two clinical trials (relapsed/refractory and frontline AML) is ongoing."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology