PRESS RELEASE AB SCIENCE REPORTS FOURTH CONSECUTIVE CASE OF RESPONSE FROM PHASE 1 DATA FOR THE COMBINATION OF AB8939 WITH VENETOCLAX FOR THE TREATMENT OF REFRACTORY OR RELAPSED ACUTE MYELOID LEUKEMIA The combination treatment was well-tolerated, with no hematological toxicity and no dose limiting toxicity The fourth patient had a complex karyotype including a monosomy of chromosome 5 and TP53 mutation, and was in the third-line of treatment. He had a near complete response after 14 days of treatment with AB ...

BeOne Medicines (ONC/688235.SS): Quick China approval for sonro; eyes on market feedback for differentiation; Buy Sonro approved in China for late-line CLL/MCL: On Jan 5th, China NMPA approved sonrotoclax (BCL2 inhibitor) in R/R CLL/SLL and R/R MCL (post CD20/BTKi treatment), marking the first approval of sonrotoclax across markets (the FDA accepted NDA in R/R MCL in Nov. 2025 with priority review). The China approval took only eight months to complete the NDA review, which we view as quick compared to typi ...

5 1 ®®Resistance to venetoclax (Venclexta and Venclyxto, Abbvie / Genentech), the $2.5 billion blockbuster Chronic Lymphocytic Leukemia (CLL) therapy, is emerging as a therapeutic challenge, with leukemic cells persisting over time, even with combination therapy 2,3Studies show that sphingosine kinase 2 (SPHK2) is overexpressed in venetoclax-resistant cancer cells and that SPHK2 inhibition may reduce T-cell-induced activation and proliferation of venetoclax-resistant CLL cancer cells and resensitize previou ...

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]

Summary of Nurix Therapeutics Conference Call Company Overview - **Company**: Nurix Therapeutics (NasdaqGM:NRIX) - **Event**: Jefferies London Healthcare Conference 2025 - **Date**: November 19, 2025 Key Points Industry and Product Focus - Nurix Therapeutics is focused on developing therapies for Chronic Lymphocytic Leukemia (CLL) and other indications using their BTK degrader platform, specifically Bexobrutideg and NX-5948 [3][4][5] Upcoming Events and Data Releases - The company will present data at the upcoming ASH conference, including follow-up data from Phase 1A and Phase 1B trials for Bexobrutideg and NX-5948 [3][4] - Key metrics to be reported include duration of therapy and duration of response, with patients having been on therapy for over two years [3][4] Pivotal Trial Design - The pivotal trial for Bexobrutideg will focus on a triple-exposed patient population in CLL, with a selected dose of 600 mg once daily based on Phase 1B data [4][6] - The trial aims for accelerated approval, allowing early market access, while full approval will follow a randomized control study [10][11] Competitive Landscape - The company anticipates competition from pirtobrutinib, a non-covalent BTK inhibitor from Eli Lilly, which is expected to gain full approval [8][10] - Nurix is positioning Bexobrutideg as a potential standard of care in the U.S. market for CLL [10] Combination Therapies - Nurix is planning combination studies with Bexobrutideg and other therapies, including venetoclax and anti-CD20 antibodies [22][23] - The company is also exploring the potential of combining with T-cell engagers [23] Autoimmune Indications - The company is developing Bexobrutideg for autoimmune diseases, leveraging its ability to degrade BTK, which may provide advantages over traditional inhibitors [26][27] - A new formulation for Bexobrutideg is in development, with plans for IND submission in 2026 [27] Partnerships and Pipeline - Nurix has partnerships with Gilead for an IRAK4 degrader and with Sanofi for a STAT6 degrader, both of which are in various stages of development [35][36] - The IRAK4 program is in Phase 1, while the STAT6 program is in IND enabling studies [35][36] Financial Position - Nurix recently raised $250 million, bringing total cash reserves to over $650 million, providing a strong financial runway through early 2028 [41][42] Future Considerations - The company is preparing for multiple decisions regarding its partnerships and potential opt-ins based on upcoming clinical data [38][41] Conclusion - Nurix Therapeutics is strategically positioned in the biotech space with a focus on innovative therapies for CLL and autoimmune diseases, backed by a strong financial position and promising clinical data on the horizon [41][42]

Summary of BeOne Medicines FY Conference Call Company Overview - **Company**: BeOne Medicines (NasdaqGS:BGNE) - **Industry**: Biotechnology - **Key Achievement**: First year of profitability and recognized as one of the fastest-growing large biotech companies [3][4] Competitive Advantages - **Integrated Development**: Fully integrated CRO-free clinical development organization with over 3,600 professionals [4] - **Product Pipeline**: Deep product pipeline with 10 internally developed New Molecular Entities (NMEs) entering the clinic in 2024 and 16 to date [3] - **Cost Efficiency**: 70% of the cost to develop medicines is in clinical development; BeOne aims to reduce this through its integrated approach [4] Product Performance - **Brukinsa**: - Leading market share in the BTK inhibitor market with 47% year-over-year growth in the U.S. and 71% growth in Europe [6][8] - Demonstrated durable progression-free survival (PFS) with 74% landmark PFS at 72 months [6][7] - Significant real-world impact and prescription growth globally [8][9] Market Dynamics - **Fixed Duration Treatments**: - BeOne supports finite treatments that meet four criteria: deep response, sustained PFS, acceptable safety profile, and convenience [10][11] - Current market dynamics show continuous use BTK inhibitors capturing about 50% of the market, with opportunities for growth through fixed-duration offerings [11][12] Pipeline Developments - **Sonrotoclax**: - Designed to be more potent and selective than venetoclax, with a half-life of five hours [14][15] - Breakthrough designation in relapsed refractory MCL, with plans for global filing based on upcoming data [30] - Phase 3 study planned for multiple myeloma, targeting the translocation 11;14 population [32][33] - **BDK CDAC**: - A degrader molecule with a different mechanism, potentially effective against mutations that standard inhibitors cannot target [24][25] - Phase 2 cohort fully enrolled, with data expected in the first half of next year [26] Competitive Landscape - **Comparison with Competitors**: - BeOne's zanubrutinib shows superior response rates compared to pirtobrutinib and acalabrutinib in specific patient populations [20][21] - Ongoing head-to-head studies to validate BeOne's offerings against competitors [16][17] Future Outlook - **Clinical Trials**: - Upcoming data presentations at ASH for various products, including BDK CDAC and sonrotoclax [28][29] - Commitment to advancing solid tumor pipeline, particularly CDK4/6 inhibitors, with a focus on first-line breast cancer [34][36] Conclusion - BeOne Medicines is positioned strongly within the biotechnology sector with a robust product pipeline, innovative clinical development strategies, and a commitment to addressing patient needs through differentiated therapies. The company is actively pursuing growth opportunities in both hematology and solid tumors while maintaining a competitive edge against established players in the market.

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]