Core Insights - 100% of patients in Cohorts 1-3 remain free of cytokine release syndrome, indicating a strong safety profile for the CD3 design used in the study [1] - The study evaluates mipletamig, a CD123 x CD3 bispecific molecule, in combination with azacitidine and venetoclax for newly diagnosed acute myeloid leukemia patients unfit for intensive chemotherapy [1] - Preliminary results were presented at the American Society of Hematology Annual Meeting, highlighting the potential of the ADAPTIR™ and ADAPTIR-FLEX™ platform technologies developed by the company [1] Company Summary - Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics [1] - The company utilizes proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies in its research and development efforts [1] Industry Context - The ongoing Phase 1b/2 RAINIER study is significant for the treatment of acute myeloid leukemia, particularly for patients who cannot undergo intensive chemotherapy [1] - The combination of mipletamig with standard treatments like azacitidine and venetoclax represents a potential advancement in the therapeutic options available for AML [1]

Core Insights - The combination of ziftomenib with venetoclax and azacitidine shows promising clinical activity in treating acute myeloid leukemia (AML) with NPM1 mutations and KMT2A rearrangements, with high rates of complete remission and molecular negativity [2][3][8] Group 1: Clinical Efficacy - In newly diagnosed NPM1-m AML, 86% achieved composite complete remission (CRc) and 73% achieved complete remission (CR), with 68% of CRc responders attaining molecular minimal residual disease (MRD) negativity [1][2] - In relapsed/refractory (R/R) NPM1-m AML, the overall response rate (ORR) was 65%, and in venetoclax-naïve patients, the ORR was 83% [1][2] - For R/R KMT2A-r AML, the ORR was 41%, with 70% in venetoclax-naïve patients [1][2] Group 2: Safety Profile - The triplet combination of ziftomenib, venetoclax, and azacitidine was well tolerated, with low rates of ziftomenib-related myelosuppression and no increase in toxicity beyond venetoclax/azacitidine alone [1][4][7] - Adverse reactions included differentiation syndrome and QTc prolongation, but these were managed without treatment discontinuation [4][7] Group 3: Ongoing Development - Kura Oncology is conducting registrational trials for ziftomenib in both intensive chemotherapy-eligible and -ineligible patients [1][2][8] - The ongoing KOMET-007 Phase 1a/1b trial is evaluating ziftomenib's efficacy across multiple AML subtypes, reinforcing its potential as a foundational treatment option [1][8][12] Group 4: Company Information - Kura Oncology is focused on precision medicines for cancer treatment, with KOMZIFTI (ziftomenib) being the first oral menin inhibitor approved for adult patients with R/R AML harboring NPM1 mutations [12][28] - Kyowa Kirin collaborates with Kura Oncology, emphasizing their commitment to innovative treatments for high unmet medical needs [29]

Core Viewpoint - Aptose Biosciences Inc. presented promising clinical data for its lead compound tuspetinib (TUS) in combination with venetoclax (VEN) and azacitidine (AZA) at the 67th American Society of Hematology (ASH) Annual Meeting, indicating its potential as a treatment for acute myeloid leukemia (AML) [1][2][3] Group 1: Clinical Data and Efficacy - The TUSCANY trial showed a 100% clinical response rate (CR/CRh) at the higher doses of 80 mg and 120 mg of TUS [5][6] - The triplet therapy demonstrated high rates of efficacy and minimal residual disease (MRD)-negative remissions across diverse AML mutations, including FLT3 wildtype and adverse genetic subgroups [5][6] - Preliminary findings at the 160 mg dose level indicate early responses and blast clearance in patients [6][7] Group 2: Safety Profile - TUS-based therapies exhibited notable safety, with no dose-limiting toxicities (DLTs) reported across all evaluable TUS dose levels [6][7] - No drug-related deaths, differentiation syndrome, QTc prolongation, or CPK elevation were observed, and febrile neutropenia was reported in only 16.7% of subjects [6][7] - 8 out of 10 evaluable subjects achieved red cell and platelet transfusion independence for over 8 weeks after their best response [6][7] Group 3: Mechanism and Development - Tuspetinib is an oral agent that targets multiple kinases associated with AML, including SYK, FLT3, and JAK1/2, while minimizing typical toxicity concerns [7][8] - The ongoing TUSCANY Phase 1/2 study aims to evaluate various doses and schedules of TUS in combination with standard therapies for newly diagnosed AML patients ineligible for induction chemotherapy [7][8]

Core Insights - Aptose Biosciences Inc. is developing a triple drug frontline therapy using tuspetinib (TUS) for newly diagnosed acute myeloid leukemia (AML) patients [1][4] - The TUSCANY study's abstract has been selected for poster presentation at the 67th American Society of Hematology (ASH) Annual Meeting scheduled for December 6-9, 2025 [1][2] Presentation Details - The poster presentation will focus on the safety and efficacy of tuspetinib combined with standard care venetoclax and azacitidine for AML patients ineligible for induction chemotherapy [2] - The session will take place on December 6, 2025, from 5:30 PM to 7:30 PM at the OCCC - West Halls B3-B4 [2] Company Overview - Aptose is a clinical-stage biotechnology company focused on precision medicines for oncology, particularly in hematology [4] - Tuspetinib has shown activity as both a monotherapy and in combination therapy for relapsed or refractory AML and is being developed as a frontline triplet therapy for newly diagnosed AML [4]

Core Insights - Aptevo Therapeutics announced a 100% remission rate in Cohort 3 of its Phase 1b/2 RAINIER trial for mipletamig, a bispecific antibody targeting CD123 and CD3, in combination with venetoclax and azacitidine for newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy [1] - The trial has shown no dose-limiting toxicities or cytokine release syndrome to date, indicating favorable safety and tolerability for mipletamig [1] - The RAINIER trial is progressing efficiently, with Cohort 4 now open for enrollment [1]

Core Viewpoint - Aptevo Therapeutics Inc's stock is experiencing a significant surge due to promising clinical data from its RAINIER trial for mipletamig, a bispecific antibody for treating acute myeloid leukemia (AML) [1][2][6]. Group 1: Clinical Trial Results - The RAINIER trial showed that the mipletamig triplet therapy achieved remissions in 85% of evaluable frontline AML patients, outperforming competitor studies [3]. - Updated results indicate a strong efficacy advantage and a favorable safety profile, with no cases of cytokine release syndrome (CRS) reported in the trial cohorts [4][5]. - The trial is nearing full enrollment for Cohort 3 at the highest dose level evaluated to date [5]. Group 2: Market Impact and Financials - Following the positive trial results, Aptevo's stock price increased by 137.2%, reaching $6.69 [7]. - The company announced a registered direct offering of $8 million, involving 2.465 million shares and pre-funded warrants at an exercise price of $3.25 per share [6].

Core Insights - AbbVie announced that the global Phase 3 VERONA trial evaluating venetoclax in combination with azacitidine for newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) did not meet its primary endpoint of overall survival (OS) with a hazard ratio (HR) of 0.908 and a p-value of 0.3772 [1][3] - No new safety signals were observed in the trial, and results will be presented at a future medical congress or publication [1][2] Company Overview - AbbVie is committed to discovering and delivering innovative medicines that address serious health issues, focusing on therapeutic areas such as immunology, oncology, neuroscience, and eye care [21] - The company is advancing a dynamic pipeline of investigational therapies across various cancer types, including blood cancers and solid tumors, with a focus on targeted medicines [22][23] Product Information - VENCLEXTA (venetoclax) is a first-in-class medicine that selectively inhibits the B-cell lymphoma-2 (BCL-2) protein, which is involved in preventing cancer cells from undergoing apoptosis [5][6] - Venetoclax is approved in over 80 countries, including the U.S., and is developed by AbbVie and Roche, with joint commercialization in the U.S. by AbbVie and Genentech [6]