Core Insights - InnoCare Pharma presented three studies on its BCL2 inhibitor, Mesutoclax (ICP-248), at the 67th Annual Meeting of the American Society of Hematology, showcasing its efficacy and safety in treating various hematologic malignancies [1][2]. Group 1: Efficacy in Relapsed/Refractory Mantle Cell Lymphoma (MCL) - Mesutoclax monotherapy demonstrated an overall response rate (ORR) of 87.5% and a complete response rate (CRR) of 46.9% in MCL patients, with an ORR of 84.0% and CRR of 36.0% in BTK inhibitor-refractory patients [3][4]. - The drug was well tolerated across all dose levels (50-150 mg), with no dose-limiting toxicities (DLTs) observed, indicating a promising safety profile [4]. Group 2: Efficacy in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) - In CLL/SLL patients, both treatment-naive and relapsed/refractory, the ORR was 100% for those receiving 125 mg of mesutoclax, with a 65% undetectable minimal residual disease (uMRD) rate at week 36 when combined with orelabrutinib [5][6]. - Mesutoclax exhibited a tolerable safety profile, with no DLTs reported up to 150 mg QD [6]. Group 3: Efficacy in Acute Myeloid Leukemia (AML) - The combination of mesutoclax and azacitidine (AZA) achieved a composite complete response (CR+CRi) rate of 92% in treatment-naive AML patients, with 82.6% achieving undetectable minimal residual disease (uMR) [7][8]. - The combination therapy was well tolerated, with no DLTs or tumor lysis syndrome (TLS) events reported, and a 90-day mortality rate of 0% [8]. Group 4: Ongoing Clinical Trials - InnoCare is conducting two registrational clinical trials: one for the combination of mesutoclax and orelabrutinib for treatment-naive CLL/SLL, and another for MCL patients refractory to BTK inhibitors [9]. - The clinical study of mesutoclax as a first-line treatment for AML has entered the dose expansion phase globally, and a study for myelodysplastic syndrome (MDS) is being launched [9].

Core Insights - Aptose Biosciences Inc. presented clinical data for its lead compound tuspetinib (TUS) in combination with venetoclax (VEN) and azacitidine (AZA) at the 67th American Society of Hematology Annual Meeting, highlighting promising safety and antileukemic activity in treating 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 TUS [5][6] - High-quality clinical responses were observed across various genetic subgroups, including FLT3 wildtype and those with adverse mutations such as TP53 and RAS [6][7] - Minimal residual disease (MRD) negativity was achieved in 78% of responding subjects, indicating effective treatment outcomes [6][7] Group 2: Safety and Tolerability - TUS+VEN+AZA therapy demonstrated a favorable safety profile with no dose-limiting toxicities reported across all evaluated TUS dose levels [6][7] - No drug-related deaths or significant adverse events such as differentiation syndrome or QTc prolongation were reported [6][7] - The therapy was well tolerated, with 8 out of 10 evaluable subjects achieving red cell and platelet transfusion independence for over 8 weeks after their best response [6][7] Group 3: Future Directions - The company has commenced treating patients at the highest dose level of 160 mg TUS, with early responses already observed [3][6] - The ongoing TUSCANY Phase 1/2 study aims to further evaluate the efficacy and safety of TUS in combination with standard therapies for newly diagnosed AML patients ineligible for induction chemotherapy [7][8]

Core Insights - Aptose Biosciences is presenting promising data from the TUSCANY trial, which evaluates the safety and efficacy of the tuspetinib-based triplet therapy (TUS+VEN+AZA) for newly diagnosed AML patients ineligible for induction chemotherapy [1][2][3] Group 1: Clinical Trial Data - The TUSCANY trial has shown that the addition of tuspetinib to the standard treatment of venetoclax and azacitidine has resulted in complete remission (CR) or complete remission with incomplete hematologic recovery (CRh) in 100% of patients treated at higher doses of 80 mg and 120 mg [5][6] - Overall, 90% of patients in the trial have achieved CR/CRh responses, with 88% of FLT3 wildtype AML patients responding positively [6][8] - The therapy has demonstrated activity across diverse genetic subtypes, including those with unmutated FLT3, FLT3-ITD, NPM1c, biallelic TP53, RAS, and myelodysplasia-related mutations [3][14] Group 2: Safety Profile - The TUS+VEN+AZA combination has been well tolerated, with no significant safety concerns or dose-limiting toxicities reported, including no prolonged myelosuppression, differentiation syndrome, QTc prolongation, or treatment-related deaths [2][6] - Dosing has commenced at the 160 mg level, indicating ongoing escalation in the trial [5][14] Group 3: Trial Design and Objectives - The TUSCANY trial is a Phase 1/2 study being conducted at 10 leading U.S. clinical sites, aiming to establish a safe and effective frontline therapy for a broad range of newly diagnosed AML patients [9][11] - The trial is designed to test various doses and schedules of tuspetinib in combination with standard dosing of azacitidine and venetoclax, with an anticipated enrollment of 18-24 patients by the end of 2025 [9][10]

Core Insights - The TUSCANY trial is evaluating the safety and efficacy of a triplet therapy combining tuspetinib (TUS) with venetoclax (VEN) and azacitidine (AZA) for newly diagnosed acute myeloid leukemia (AML) patients who are ineligible for induction chemotherapy [1][8] - Initial results from 10 patients show promising clinical safety and antileukemic activity, with a high rate of complete remissions (CR) and minimal safety concerns [2][3] Summary by Sections Trial Overview - The TUSCANY Phase 1/2 trial is designed to test various doses of TUS in combination with standard dosing of AZA and VEN for AML patients [9] - The trial is being conducted at 10 leading U.S. clinical sites, with an expected enrollment of 18-24 patients by the end of 2025 [9] Safety and Efficacy - No significant safety concerns or dose-limiting toxicities (DLTs) have been observed in the TUSCANY trial, including no prolonged myelosuppression or treatment-related deaths [2][6] - The addition of TUS to VEN+AZA achieved CR/CRh responses in 100% of patients treated at higher dose levels of 80 mg and 120 mg, exceeding the expected 66% response rate from VEN+AZA alone [5][6] Patient Responses - Out of 10 patients, 9 achieved complete remissions, with 7 demonstrating minimal residual disease (MRD) negativity [3][14] - The therapy has shown effectiveness across diverse genetic subtypes, including those with unmutated FLT3, FLT3-ITD, and TP53 mutations [3][14] Current Developments - Dosing has progressed to the 160 mg TUS level, with ongoing assessments of safety and efficacy [2][5][14] - The triplet therapy is being developed as a mutation-agnostic frontline treatment for AML, targeting a broad range of patient populations [2][8]

Core Insights - Aptose Biosciences Inc. presented data from its Phase 1/2 TUSCANY trial for newly diagnosed AML patients treated with tuspetinib in combination with venetoclax and azacitidine at the EHA 2025 Congress [1][3] Group 1: Study Overview - The TUS+VEN+AZA triplet is being developed as a mutation-agnostic frontline therapy for newly diagnosed AML patients who cannot receive induction chemotherapy [2][8] - The TUSCANY trial is designed to test various doses of tuspetinib in combination with standard dosing of azacitidine and venetoclax [9] Group 2: Key Findings - The addition of tuspetinib to standard care creates a well-tolerated and mutation-agnostic frontline therapy for newly diagnosed AML [5] - Ten AML patients have been treated with the TUS+VEN+AZA combination, with complete remissions and minimal residual disease negativity observed across diverse mutations [6][7] - At the 40 mg dose level, three out of four patients achieved complete remissions and were MRD-negative, while at the 80 mg dose level, all three patients achieved composite complete remissions [6] Group 3: Safety and Efficacy - No dose-limiting toxicities (DLTs) have been observed to date, and all ten subjects treated remain alive [6][7] - TUS demonstrated activity across diverse genetic populations, including those with adverse TP53 mutations [6][8] - The triplet therapy continues to be well tolerated, with no treatment-related deaths or significant adverse events reported [6][7]