tambiciclib (SLS009) / GenFleet Therap, SELLAS Life Sciences - LARVOL DELTA

Tambiciclib (SLS009), a novel, potent CDK9 inhibitor is effective in killing ASXL1 mutated and TP53 knockout Acute Myeloid Leukemia cell lines (ASH 2025) - "Tambiciclib has steadily advanced in early-phase clinical trials and has already shown promising clinical benefits when combined with azacitidine, a hypomethylating agent, and venetoclax, a BCL-2 inhibitor; however, there is still a need for optimization of the treatment window for maximal benefit. Inhibition of CDK9 with tambiciclib is a promising and effective approach for inducing cell death in AML. Our preliminary data warrants further investigation to optimize the therapeutic window for tambiciclib treatment in repeated doses and combination therapies."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ASXL1 • GLI2 • MCL1 • MEIS1 • MYC • TP53

Phase 2 study of SLS009 in combination with azacitidine and venetoclax for relapsed/refractory AML with MDS-related changes (AML-MR) after prior venetoclax treatment (ASH 2025) - "Addition of SLS009 30 mg IV BIW to AZA/VEN was found to be safe and feasible without DLTs. Clinicalefficacy was seen in pts with AML-MR, with a signal of activity in pts with ASXL1 mutated AML. Pts withonly 1 line of ven-based prior therapy experienced the greatest benefit in terms of response and longterm survival, implying a role in patients progressing after HMA + ven."

Combination therapy • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia • ASXL1 • CDK9 • MCL1 • MECOM • RUNX1 • SRSF2 • TP53

SELLAS Life Sciences Presents Positive Phase 2 Data of SLS009 in Combination with AZA/VEN in Relapsed/Refractory AML-MR at ASH 2025 (GlobeNewswire) - "SLS009 in combination with AZA/VEN demonstrated clinically meaningful activity in patients with R/R AML-MR, and among the 35 evaluable patients, the overall response rate (CR+CRi+MLFS) was 46%, including 29% achieving CR/CRi. Patients harboring ASXL1 or TP53 mutations achieved response rates of 48% (19% CR/CRi) and 57% (29% CR/CRi), respectively. The median overall survival (mOS) was exceedingly higher than the expected 2.6 months in this R/R AML patient population, and in the least pretreated cohort, mOS reached 8.9 months....Study expansion to evaluate SLS009 plus AZA/VEN in newly diagnosed AML with high-risk features is planned for Q1 2026."

P2 data • Trial status • Acute Myelogenous Leukemia

Phase 2a Study of SLS009, a Highly Selective CDK9 Inhibitor, in Combination with Azacitidine and Venetoclax for Relapsed/Refractory Acute Myeloid Leukemia after Prior Venetoclax Treatment (ASH 2024) - "Clinical activity was seen particularly in pts with ASXL1 mutation which may be a subpopulation of patients with preferential sensitivity to SLS009 + AZA/VEN. Further development will be focused on AML-MR patients with and without ASXL1 mutations."

Combination therapy • P2a data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Nephrology • Neutropenia • Oncology • Renal Disease • ASXL1 • FLT3 • IDH1 • IDH2 • MCL1 • RUNX1 • SRSF2 • TET2 • TP53

SELLAS Life Sciences Announces Presentation of Phase 2 Data of SLS009 in Combination with Azacitidine and Venetoclax in Relapsed/Refractory AML with MDS-Related Changes (AML-MR) at the 2025 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "In addition, an abstract highlighting the proposed mechanism of action of SLS009 has been published on the ASH Annual Meeting website and will also be available in Blood. The published preclinical abstract describes studies demonstrating the cytotoxic effects of SLS009 in AML cell lines with leukemia-driving mutations."

P2 data • Preclinical • Acute Myelogenous Leukemia

CDK9 inhibition enhances venetoclax activity and prolongs survival in a T-PLL patient-derived xenograft model (ESMO 2025) - "The model was expanded and used in a pre-clinical trial to evaluate a novel therapeutic combination using SLS009 (GFH009), a specific CDK9 inhibitor and Venetoclax, a BCL2 inhibitor. Our T-PLL PDX model can be used to evaluate the effect of new drugs for T-PLL in a preclinical setting. Legal entity responsible for the study The authors."

Preclinical • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • IL2RG • PRKDC • PTPRC

SELLAS Life Sciences to Present In Vivo Preclinical Data Demonstrating Statistically Significant Survival Benefit of SLS009 in T-Cell Prolymphocytic Leukemia at the European Society for Medical Oncology (ESMO) Congress 2025 (GlobeNewswire) - "The results highlight an in vivo patient-derived xenograft (PDX) model of relapsed/refractory T-PLL that reproduced key human clinicopathological features of the disease....Both SLS009 monotherapy and the combination prolonged overall survival (7.4 weeks and 7.9 weeks, respectively) compared to venetoclax alone (4.4 weeks)..."

Preclinical • T-Cell Prolymphocytic Leukemia

SELLAS Life Sciences Group to Host Virtual R&D Day on October 29, 2025: Advancing Novel Therapies in Acute Myeloid Leukemia (AML): An Overview of the Ongoing Phase 3 REGAL Trial of Galinpepimut-S (GPS) and SLS009 Program Update (GlobeNewswire) - "SELLAS will also present an update of SLS009....plans for a newly diagnosed and frontline AML study anticipated to begin in the first quarter of 2026."

New trial • Trial status • Acute Myelogenous Leukemia

Preclinical Efficacy of SLS009 in T-Cell Prolymphocytic Leukemia (T-PLL) to be Showcased at ESMO 2025 (GlobeNewswire) - "The poster, entitled, CDK9 Inhibition Enhances Venetoclax Activity and Prolongs Survival in a T-PLL Patient-Derived Xenograft Model, will be presented during the ESMO congress to be held in Berlin, 17-21 October 2025."

Preclinical • T-Cell Prolymphocytic Leukemia

GFH009X2101: Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: Sellas Life Sciences Group | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial primary completion date • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Oncology

Front Line Trial Planning Underway Following FDA Guidance (SELLAS Life Sciences Press Release) - "Following a productive end of Phase 2 meeting, the FDA recommended that SELLAS proceeds into a trial to include newly diagnosed, first-line AML patients eligible for venetoclax/azacitidine (aza/ven) therapy, where the agency believes clinical benefit might be greatest; The randomized 80-patient trial is currently in preparation and is expected to begin enrollment by Q1 2026. The trial will include two groups: Predictive biomarker cohort: Newly diagnosed patients unlikely to benefit from standard aza/ven therapy based on molecular profiling; Early resistance cohort: Patients who initiate treatment with aza/ven but demonstrate confirmed lack of any response after two treatment cycles; This precision approach allows SELLAS to target subpopulations with high unmet need and greatest potential for benefit."

FDA event • New trial • Acute Myelogenous Leukemia

SELLAS Meets All Primary Endpoints in Phase 2 Trial of SLS009 in r/r AML... (SELLAS Life Sciences Press Release) - P1/2a | N=160 | NCT04588922 | Sponsor: Sellas Life Sciences Group | "The results exceeded the pre-specified ORR threshold of 20%, demonstrating robust clinical activity and supporting advancement into late-stage development; The ORR in all evaluable patients was 33% across all cohorts and dose levels and 40% for the 30mg BIW dose level; At the 30 mg BIW dose, among AML MR patients, the ORR was 44%; The highest efficacy was observed among patients with ASXL1 mutations, with an ORR of 50% (9/18) at 30 mg BIW dose levels and M4/M5 patients with 50% (6/12) ORR; The mOS surpassed the historical benchmark of best available therapy of 2.4 months1 for patients who received one prior line of therapy and 1.8 months for those who received more than one prior line of therapy....The addition of SLS009 to the venetoclax/azacitidine regimen was well tolerated and did not result in increased toxicities compared to ven/aza alone. No dose-limiting toxicities were observed across all dose levels."

P2 data • Acute Myelogenous Leukemia

In vitro efficacy of CDK9 inhibitor tambiciclib (SLS009) in ASXL1 mutated colorectal cancer cell lines. (ASCO 2025) - "Results indicate that ASXL1 mutations may be oncogenic drivers in some solid tumors, like CRC MSI-H, similar to those in AML and that efficacy of CDK9 inhibition with SLS009 may be similar in some solid tumors to the efficacy observed in AML."

Preclinical • Acute Myelogenous Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Microsatellite Instability • Oncology • Solid Tumor • ASXL1 • MSI • TP53

SELLAS Presents Preclinical Efficacy of SLS009 in ASXL1 Mutated Colorectal Cancer at 2025 ASCO Annual Meeting (GlobeNewswire) - "In a panel of cell lines, SLS009 demonstrated potent anti-proliferative activity: In 50% (4/8) of ASXL1 mutant cell lines showed an IC50<100 nM, compared to 0% (0/4) of ASXL1 wild-type lines; Among cell lines harboring ASXL1 frameshift mutations (FSMs), 75% (3/4) responded with IC50 <100 nM versus only 12.5% (1/8) in cell lines without FSMs; All cell lines (3/3) with ASXL1 FSMs in the 637-638 protein region responded to treatment with SLS009; In cell lines with IC50 <100 nM, 75% (3/4) also demonstrated IC99 values below 100 nM, indicating steep dose response curve."

Preclinical • Colorectal Cancer

SELLAS Life Sciences Announces First Pediatric AML Patient Dosed in the Ongoing Phase 2 Trial of SLS009 r/r AML (GlobeNewswire) - "SELLAS Life Sciences Group, Inc...today announced that the first pediatric AML patient has been dosed in the ongoing Phase 2 trial of SLS009 (tambiciclib), a highly selective CDK9 inhibitor, in relapsed/refractory acute myeloid leukemia (r/r AML)....The Phase 2 clinical trial of SLS009 is an open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with venetoclax and azacitidine at two dose levels, 45 and 60 mg."

Trial status • Acute Myelogenous Leukemia

PIVOT - Received Preliminary Data for Pediatric Acute Lymphoblastic Leukemia (ALL) Patients Derived Xenografts (PDX) (GlobeNewswire) - "The experiment conducted and funded by the National Institute of Health (NIH) through the PIVOT program included 27 patient-derived ALL tumors from pediatric patients. Tumors were xenografted in mice in two groups: vehicle control arm and SLS009 arm. Mice were treated with a fractionated dose once per week for 6 consecutive weeks. The treatment was well tolerated. For all models, median survival was approximately tripled in the SLS009 arm compared to the vehicle control arm. SLS009 demonstrated delayed progression in 25/27 (93%) models and more than 2 times longer time to progression in 15/27 (56%) of ALL models. In addition, there were complete responses (CR) in 2 models, and in one of the two models, CR was maintained after the treatment had been completed until the end of the study (4 months)."

Preclinical • Acute Lymphocytic Leukemia

SELLAS Unveils Breakthrough Preclinical Data Highlighting Efficacy of SLS009 in TP53 Mutated AML at the 2025 AACR Conference (GlobeNewswire) - "Preclinical data suggest that SLS009, a highly selective CDK9 inhibitor, can induce apoptosis downstream of p53 by targeting critical proteins such as MCL-1 and survivin, regardless of p53 status. Immunoblot analysis reveals near-complete removal of these proteins in treated cells within 8 hours of exposure to SLS009. Furthermore, the treatment reduced TP53-mutated leukemia cell populations by up to 97% in combination with azacitidine–venetoclax, and by up to 80% as monotherapy."

Preclinical • Acute Myelogenous Leukemia

SELLAS to Present at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "SELLAS Life Sciences Group...announced that preclinical efficacy of SLS009 in ASXL1 mutated colorectal cancer lines will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting..."

Preclinical • Colorectal Cancer

SELLAS Announces Positive Overall Survival in Cohort 3 from the Ongoing Phase 2 Trial of SLS009 in r/r AML (GlobeNewswire) - P1/2 | N=160 | NCT04588922 | Sponsor: Sellas Life Sciences Group | "8.9 Months Median Overall Survival (mOS) in Patients with AML-Myelodysplasia-Related Changes (AML-MRC) and 8.8 mOS in All Relapsed or Refractory to Venetoclax-Based Regimens Patients; Surpassing Historical Benchmark of 2.5 Months; Overall Response Rate (ORR) of 67% Achieved in Patients with AML-MRC (Target Patient Population of SLS009 in r/r AML) – Exceeding Targeted 20% ORR; Trial Continues with Full Data and FDA Regulatory Path Feedback Expected in 1H 2025."

P2 data • Acute Myelogenous Leukemia

SELLAS Life Sciences Reports Full Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Reported Positive Overall Survival and Overall Response Rate Data from the Ongoing Phase 2 Trial of SLS009 (Tambiciclib) in r/r AML – Full Data and FDA Regulatory Path Feedback Expected in 1H 2025"

FDA event • P2 data • Acute Myelogenous Leukemia

SELLAS Announces Positive Data from Phase 2a Trial of SLS009 in Combination with Zanubrutinib in DLBCL (GlobeNewswire) - PIb/II | N=51 | NCT06375733 | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | "SELLAS Life Sciences...announced data from Phase 2a trial of SLS009 (tambiciclib), a highly selective CDK9 inhibitor, in relapsed/refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL)...The results showed an overall response rate of 67%, more than double the expected overall response rate (ORR) of zanubrutinib alone. Among responders, one achieved complete response (CR), while three had partial response (PR) with target lesion shrinkages of 89%, 78%, and 56%, respectively. As of the last follow-up, after the median of 4.6 (range: 1.4 - 7.4) months follow-up, median overall survival (OS) was not reached, and six out of 9 patients were alive....Genetic data of 6 out of 9 enrolled patients showed that none of the patients carried MYD88 or CD79B mutations predictive of better response to BTK inhibitors."

P2a data • Diffuse Large B Cell Lymphoma

Expected Milestones in 2025: SLS009: highly selective CDK9 inhibitor (GlobeNewswire) - "Phase 2 clinical trial in AML: Full topline data from expansion cohorts which include AML-MRC patients with ASXL1 mutation (cohort 4) and mutations and cytogenic changes other than ASXL1 (cohort 5) are expected in 1H 2025; FDA feedback on regulatory path for r/r AML study expected in 1H 2025."

FDA event • P2 data • Acute Myelogenous Leukemia

SELLAS Announces Positive Overall Survival and Overall Response Rate Data from the Phase 2 Trial of SLS009 in r/r AML (GlobeNewswire) - P1/2a | N=160 | NCT04588922 | Sponsor: Sellas Life Sciences Group | "Key Highlights from the updated topline data: As of December 4, 2024, data cutoff, 14 patients were enrolled in Cohort 3 and 14 in Cohort 4 and 5, of which 9 were evaluable at the time of analysis. At latest follow-up, the mOS has not been reached yet but has exceeded 7.7 months in Cohort 3. This is particularly significant as the expected mOS for patients in this setting is typically 2.5 months. In expansion cohorts 4 and 5, in patients with AML-myelodysplasia-related changes (AML-MRC) with ASXL1 mutation (cohort 4) and mutations and cytogenic changes other than ASXL1 (cohort 5) the ORR was 56% in 9 evaluable for efficacy patients. SLS009 was well-tolerated with no new safety signals observed to date as the regimen remains safe in additional patients enrolled to date."

P2a data • Acute Myelogenous Leukemia

SELLAS Announces Positive Data from Preclinical Studies Indicating ASXL1 Mutations as Predictor of Response to SLS009 in Solid Cancers (GlobeNewswire) - "SELLAS Life Sciences Group, Inc...announced data from preclinical studies identifying ASXL1 mutation as key predictor of SLS009, a highly selective CDK9 inhibitor, response in solid cancers....In CRC MSI-H, ASXL1 mutations were observed in 7/12 (58%) of PDCs, aligning with predicted frequency of ~55%; In NSCLC, ASXL1 mutations occurred in 2/6 (33%) studied cell lines, higher than predicted 2.6%; Overall, in 18 studied solid cancer cell lines, ASXL1 mutations were recorded in 9 cell lines and no ASXL1 mutations were recorded in 9 cell lines which were designated as control; In ASXL1 mutated cell lines, high SLS009 efficacy (IC50 <100 nM) was observed in 6/9 (67%) solid cancer cell lines and in non-ASXL1 mutated cancer high SLS009 efficacy was observed in 0/9 (0%) of studied solid cancer cell lines."

Preclinical • Colorectal Cancer • Microsatellite Instability • Non Small Cell Lung Cancer

Preclinical metabolism and disposition of [14C]GFH009, a novel selective CDK9 inhibitor. (PubMed, Xenobiotica) - "Besides, the major clearance pathway for GFH009 was excretion and the minor one was metabolism.5. GFH009 exhibits favourable drug metabolism and pharmacokinetics (DMPK) properties, which provides valuable insights into the disposition of GFH009 and can be used to guide future clinical studies."

Journal • Preclinical • CDK9