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

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

Aptevo Therapeutics Reports 2Q23 Financial Results and Provides a Business Update (Issuer Direct) - "Royalty revenue for the period covered by this report reflects revenue recorded only in the first quarter of 2022 due to our Amendment to Royalty Purchase Agreement with HCR. As a result of the amendment, we ceased reporting as royalty revenue, royalties paid by Pfizer to HCR related to Pfizer's sales of RUXIENCE®....Research and development expenses increased by $1.6 million, from $3.9 million for three months ended June 30, 2022 to $5.5 million for the three months ended June 30, 2023. The increase was primarily due to higher spending on the ALG.APV-527 Phase 1 clinical trial and APVO436 Phase 1b clinical trial. "

Commercial • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

Aptevo Announces Positive Duration of Remission Data from Phase 1b Expansion Trial Evaluating the Bispecific APVO436 for AML (Issuer Direct) - "Phase 2 Program Update: The Company's APVO436 Phase 2 program will further evaluate the triplet combination of APVO436 + venetoclax + azacitidine among frontline and relapsed/refractory AML patients who are venetoclax treatment naïve. The Company intends to conduct two trials. The first, among relapsed/refractory patients, will initiate in 2H23. The second, among frontline patients, will initiate in 1H24. Aptevo anticipates that approximately 100 patients will participate between the two trials and that interim results will be available in late 2H24."

New P2 trial • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Aptevo Announces Positive Duration of Remission Data from Phase 1b Expansion Trial Evaluating the Bispecific APVO436 for AML (Issuer Direct) - P1b | N=136 | NCT03647800 | Sponsor: Aptevo Research and Development LLC | "Aptevo Therapeutics...announced that its bispecific AML drug candidate APVO436, in combination with emerging standard of care venetoclax and azacitidine, achieved positive duration of remission results in its Phase 1b dose escalation trial....Positive and clinically meaningful DOR results was observed from the company's bispecific AML drug candidate APVO436 in combination with the emerging standard of care (venetoclax + azacitidine) in venetoclax treatment naïve patients, as follows: High response rate observed - 82% (9/11) of patients had a favorable response and were eligible for inclusion in the DOR analysis....Sustained complete response -Of the patients with responses, one patient remained on study with sustained complete response for 8 cycles (the maximum allowed per protocol) which translated into at least 8 months of response duration."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Aptevo Therapeutics Reports 2022 Financial Results and Provides Business Update (Yahoo Finance) - "APVO436 (Acute Myeloid Leukemia): Based on Phase 1b outcomes, we plan to initiate a Phase 2 trial in the second half of 2023 to further evaluate APVO436 in combination with venetoclax and azacitidine in venetoclax treatment naïve patients."

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Updated Results from a Phase 1 Study of APVO436, a Novel Bispecific Anti-CD123 x Anti-CD3 Adaptir™ Molecule, in Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome (ASH 2022) - P1b | "The expansion phase is evaluating the safety and tolerability of APVO436 at the RP2D level when it is used as an adjunct to the standard of care to obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy (Cohorts 3 and 5) and combination therapy modalities (Cohort 1 with MEC chemotherapy, Cohort 2 with venetoclax and azacitidine, and Cohort 4 with oral azacitidine). Conclusions Preliminary results from the dose-expansion phase indicate that APVO436 is well tolerated and safe as single agent and in combination across cohorts with different underlying leukemic conditions. Furthermore, anti-leukemic activity has been observed."

P1 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Septic Shock • Thrombocytopenia • Transplantation • CD123

100% Clinical Benefit Rate Achieved in Phase 1b Trial Evaluating APVO436 in Combination with Venetoclax and Azacitidine for Venetoclax Treatment Naïve Patients with Acute Myeloid Leukemia (AML) (Issuer Direct) - P1b | N=136 | NCT03647800 | Sponsor: Aptevo Research and Development LLC | "Aptevo Therapeutics...announced that APVO436, in combination with venetoclax and azacitidine, achieved a 100% clinical benefit rate (CBR) in venetoclax treatment naïve AML patients. The data, which was presented in a poster session at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans, also showed that APVO436, when given in combination with this standard-of-care regimen, was observed to be generally safe and well tolerated....In the Phase 1b trial cohort 2, a total of 16 response-evaluable patients received the combination therapy of venetoclax and azacitidine with APVO436 and 75% experienced clinical benefit. 100% of patients in this cohort who had not received venetoclax previously, experienced clinical benefit; a favorable outcome with respect to a variety of response categories including CR, CRi and MLFS."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology