SGR-1505 / Schrodinger - LARVOL DELTA

SGR-1505, a potent and selective MALT1 inhibitor with preliminary efficacy in BTKi exposed Waldenström macroglobulinemia (WM) and "double-exposed" CLL/SLL (ASH 2025) - P1 | "In B-cell lymphoma lines with acquired BTKiresistance, SGR-1505 exhibited comparable IC50 values as compared to the parental cell lines, andcombining SGR-1505 with venetoclax or NX-2127 enhanced growth inhibition.As of 13 May 2025, a total of 49 patients had been treated in study SGR-1505-101, including 6 WMrelapsing or refractory to BTKi and 6 CLL/SLL who were double-exposed to prior BTKi and BCL2i.In the 6 WM subjects, median prior lines of therapy was 2 (range: 2-6) and all received prior BTKi as theirlast line of therapy and were refractory or relapsed due to development of BTK resistance mutations orbypass mechanisms...Preclinically, SGR-1505 demonstrated the ability to overcome BTKi resistance in multiple in vitro and invivo models. Clinically, SGR-1505 demonstrated encouraging anti-tumor activity in prior BTKi exposedWM, BTKi/BCL2i double-exposed CLL/SLL and other B-cell malignancies. MALT1 inhibition represents apromising novel therapeutic option with broad..."

Clinical • IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia • CARD11 • MALT1 • MYD88

A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of Sgr-1505 As Monotherapy in Subjects with Mature B-Cell Malignancies (ASH 2023) - P1 | "Furthermore, a MALT1 inhibitor (JNJ-67856633) showed efficacy in mature B cell malignancies from phase 1 studies (ref 1, 2)...SGR-1505 administered as a single agent and in combination with the approved Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, demonstrates tumorostatic and regressive antitumor activity in ABC-DLBCL cell line-derived and patient-derived xenograft models...Subjects with symptomatic or active CNS involvement, and other conditions or laboratory findings placing them at increased risk to the use of an investigational drug are excluded. SGR-1505 is initially dose-escalated using an accelerated titration design in cohorts of 1-6 subjects, and at higher dose levels using a conventional 3+3 design."

Clinical • Monotherapy • P1 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CARD11 • MALT1

Sgr-1505 Is a Potent MALT1 Protease Inhibitor with a Potential Best-in-Class Profile (ASH 2023) - P1 | "When administered as a single agent and in combination with the approved Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, SGR-1505 demonstrated tumorostatic and regressive antitumor activity in ABC-DLBCL cell line-derived xenograft and patient-derived xenograft models... SGR-1505, a MALT1 protease small molecule inhibitor, consistently demonstrated better potency in in vitro and ex vivo assays when compared to the clinical-stage JNJ-6633 compound and greater effects on NF-kB pathway gene expression in in vivo tumor samples based on RNA-seq analysis. Changes in biological pathways mediated by MALT1 were also observed at relevant doses in the ongoing SGR-1505 healthy volunteer study. Currently, a phase 1 clinical trial in patients with mature B cell neoplasms is also ongoing (NCT05544019)."

B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CARD11 • MALT1

Accelerated In Silico Discovery of SGR-1505: A Potent MALT1 Allosteric Inhibitor for the Treatment of Mature B-Cell Malignancies. (PubMed, J Med Chem) - "Multiparameter optimization allowed efficient prioritization of molecules with good potency and drug-like properties during lead optimization, which led to the discovery of a highly potent MALT1 inhibitor, SGR-1505, with a well-balanced property profile. It demonstrated strong antitumor activity alone and in combination with BTK inhibitor in multiple in vivo B-cell lymphoma xenograft models and progressed to a phase 1 clinical trial in patients with mature B-cell neoplasms."

Journal • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CARD11 • MALT1

Schrödinger Reports Second Quarter 2025 Financial Results (Businesswire) - "Key Highlights:...(i) Schrödinger is completing the Phase 1 package and expects to meet with the FDA later this year to discuss the recommended Phase 2 dose. The company is also exploring strategic opportunities to advance the development of SGR-1505...; (ii) Schrödinger is continuing to progress the Phase 1 clinical study of SGR-2921, the company’s CDC7 inhibitor, in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Initial clinical data from this study are expected in the fourth quarter of 2025...; (iii) Schrödinger is continuing to progress the Phase 1 clinical study of SGR-3515, the company’s Wee1/Myt1 co-inhibitor, in patients with advanced solid tumors. Initial clinical data from this study are expected in the fourth quarter of 2025."

FDA event • P1 data • Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Solid Tumor

Schrödinger’s MALT1 inhibitor receives FDA fast track designation (Investing.com) - "Schrödinger, In...announced that the U.S. Food and Drug Administration has granted Fast Track designation to its clinical stage MALT1 inhibitor, SGR-1505, for treating adult patients with Waldenström macroglobulinemia who have failed at least two lines of therapy, including a Bruton’s tyrosine kinase inhibitor...The company plans to discuss its Phase 1 study results and recommended Phase 2 dose with the FDA later this year."

Fast track • P1 data • Waldenstrom Macroglobulinemia

Schrödinger Receives Fast Track Designation for SGR-1505 for the Treatment of Relapsed/Refractory Waldenström Macroglobulinemia (Businesswire) - "Schrödinger, Inc...announced that SGR-1505, its clinical stage MALT1 inhibitor, was designated as a Fast Track product by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with Waldenström macroglobulinemia that have failed at least two lines of therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor."

Fast track • Waldenstrom Macroglobulinemia

A PHASE 1 STUDY OF SGR-1505, AN ORAL, POTENT MALT1 INHIBITOR FOR R/R B-CELL MALIGNANCIES, INCLUDING CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL) (ICML 2025) - P1 | "SGR-1505 is well-tolerated with encouraging monotherapy activity in multiple B-cell malignancies. Responses in double-exposed CLL and in WM highlight the potential of SGR-1505 as a novel treatment for relapsed or refractory patients."

IO biomarker • P1 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia • IL2 • MALT1 • UGT1A1

A PHASE 1 STUDY OF SGR-1505, AN ORAL, POTENT MALT1 INHIBITOR FOR RELAPSED/REFRACTORY (R/R) B-CELL MALIGNANCIES, INCLUDING CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL) (EHA 2025) - P1 | "SGR-1505 is well-tolerated with encouraging monotherapy activity in multiple B-cell malignancies. Responses in double-exposed CLL and in WM highlight the potential of SGR-1505 as a novel treatment for relapsed or refractory patients."

IO biomarker • P1 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Fatigue • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia • IL2 • MALT1 • UGT1A1

Schrödinger Reports Encouraging Initial Phase 1 Clinical Data for SGR-1505 at EHA Annual Congress (Businesswire) - P1 | N=52 | NCT05544019 | Sponsor: Schrödinger, Inc. | "As of the data cut-off date, May 13, 2025, 49 patients were enrolled and evaluable for safety, including 18 patients with CLL/SLL, nine with diffuse large B-cell lymphoma (DLBCL), six with Waldenström macroglobulinemia (WM), and five with marginal zone lymphoma (MZL). Patients had a median of four (range two-nine) prior lines of therapy, with the most common being Bruton’s tyrosine kinase (BTK) inhibitors (55.1%), BCL-2 inhibitors (18.4%) and BTK+BCL-2 inhibitors (18.4%). SGR-1505 was well-tolerated with no dose-limiting toxicities or deaths due to treatment-emergent adverse events (TEAEs). Forty three percent of patients (n=21) experienced ≥ 1 treatment-related adverse event (TRAE), with the most common (≥ 10%) being rash (12%) and fatigue (12%)."

P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Marginal Zone Lymphoma • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

Schrödinger to Present Phase 1 Clinical Data on MALT1 Inhibitor SGR-1505 at EHA Annual Congress and International Conference on Malignant Lymphoma (Businesswire) - "Schrödinger...announced that initial Phase 1 clinical data for SGR-1505, its investigational MALT1 inhibitor, will be presented at the European Hematology Association Annual Congress....Additional data from this trial will be presented at the International Conference on Malignant Lymphoma....The Phase 1 study is designed to evaluate the safety, tolerability and anti-tumor activity of SGR-1505 in patients with relapsed/refractory B-cell malignancies. The poster presentations will include initial safety, pharmacokinetic and pharmacodynamic data, as well as preliminary efficacy data across a range of dosing levels, schedules and B cell malignancies. The data support the continued development of SGR-1505 in this patient population."

P1 data • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma

Schrödinger Reports Strong First Quarter 2025 Financial Results (Businesswire) - "Key Highlights:...(i) Schrödinger continues to progress the Phase 1 clinical study of SGR-1505, the company’s MALT1 inhibitor, in patients with relapsed/refractory B-cell malignancies and expects to report initial clinical data from the trial in June; (ii) Schrödinger is continuing to progress the Phase 1 clinical study of SGR-2921, its CDC7 inhibitor, in patients with AML and myelodysplastic syndrome (MDS). The company expects to report initial data from this trial at a medical meeting in the second half of 2025; (iii) Schrödinger is continuing to progress the Phase 1 clinical study of SGR-3515, the company’s Wee1/Myt1 co-inhibitor, in patients with advanced solid tumors. Initial clinical data from this study are expected in the second half of 2025."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Solid Tumor

Schrödinger Reports Strong Fourth Quarter and Full-Year 2024 Financial Results (Businesswire) - "Key Highlights:...(i) Schrödinger continues to progress the Phase 1 clinical study of SGR-1505, the company’s MALT1 inhibitor, in patients with relapsed/refractory B-cell malignancies and expects to report initial clinical data from the trial in the second quarter of 2025; (ii) The Phase 1 study of SGR-3515, Schrödinger’s Wee1/Myt1 inhibitor, continues to enroll patients with advanced solid tumors at sites in the U.S. and Canada. Initial clinical data from this study is expected in the second half of 2025."

P1 data • Trial status • Non-Hodgkin’s Lymphoma • Solid Tumor

Schrödinger Provides Update on Progress Across the Business and Outlines 2025 Strategic Priorities (Businesswire) - "Today Schrödinger outlined the following strategic priorities for 2025: (i) Present initial data from the Phase 1 study of SGR-1505 in patients with relapsed/refractory B-cell lymphomas in the first half of 2025; (ii) Present initial data from the Phase 1 study of SGR-2921 in patients with relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndrome in the second half of 2025; (iii) Present initial data from the Phase 1 study of SGR-3515 in patients with advanced solid tumors in the second half of 2025"

P1 data • Acute Myelogenous Leukemia • Non-Hodgkin’s Lymphoma • Solid Tumor

Schrödinger Reports Third Quarter 2024 Financial Results (Businesswire) - "Proprietary Pipeline:...(i) Schrödinger continues to advance SGR-1505, its MALT1 inhibitor, through the Phase 1 dose-escalation study in patients with relapsed/refractory B-cell malignancies. The company expects to report initial clinical data from this study in the first half of 2025; (ii) SGR-2921, the company’s CDC7 inhibitor, is progressing through a Phase 1 dose-escalation study in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome. Schrödinger expects to report initial clinical data from this study in the second half of 2025."

P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma

Schrödinger Reports Strong Second Quarter 2024 Financial Results (Businesswire) - "Proprietary Pipeline: The company is advancing the Phase 1 dose-escalation study of SGR-1505, its MALT1 inhibitor, in patients with relapsed/refractory B-cell malignancies, and enrollment is ongoing in the U.S. and Europe. The company expects to report initial clinical data from this study in the first half of 2025."

Enrollment status • P2 data • Non-Hodgkin’s Lymphoma

SGR-1505-101: Study of SGR-1505 in Mature B-Cell Neoplasms (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Schrödinger, Inc. | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Monotherapy • Trial completion date • Trial primary completion date • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • BCL2

Schrödinger Reports First Quarter 2024 Financial Results (Businesswire) - "The company is advancing the Phase 1 dose-escalation study of SGR-1505, its MALT1 inhibitor, in patients with relapsed/refractory B-cell malignancies, and enrollment is ongoing in the U.S. and EU. The company expects to report initial data from this study in late 2024 or 2025. Schrödinger also continues to advance its Phase 1 study of SGR-2921, its CDC7 inhibitor, in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome. Patient enrollment is ongoing in the U.S., and the company expects to report initial data from the study in late 2024 or 2025."

P1 data • Trial status • Acute Myelogenous Leukemia • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Mantle Cell Lymphoma • Myelodysplastic Syndrome • Waldenstrom Macroglobulinemia

Schrödinger Highlights Discovery of SGR-1505, Clinical-Stage MALT1 Inhibitor, at American Chemical Society National Meeting (Businesswire) - "Schrödinger...presented the discovery of SGR-1505, its MALT1 inhibitor, during the First Time Disclosure Session at the American Chemical Society (ACS) Spring 2024 Meeting....The oral presentation provided an overview of how Schrödinger leveraged its computational approaches at scale to discover SGR-1505."

Preclinical • Hematological Malignancies • Oncology

Accelerated in silico discovery of SGR-1505: A Potent MALT1 allosteric inhibitor for the treatment of mature B-cell malignancies (ACS-Sp 2024) - "It demonstrated strong anti-tumor activity alone and in combination with BTK inhibitors in multiple in vivo B-cell lymphoma xenograft models. Currently, a Phase 1 clinical trial with SGR-1505 in patients with mature B-cell neoplasms is ongoing."

Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CARD11 • MALT1

Schrödinger Highlights Progress of Clinical Programs and Discloses Three New Programs at First Therapeutics Pipeline Investor Event (Businesswire) - "Today, Schrödinger outlined the anticipated milestones for its proprietary pipeline: Report initial data from the Phase 1 study of SGR-1505 in late 2024 or 2025; Report initial data from the Phase 1 study of SGR-2921 in late 2024 or 2025; Submit IND for SGR-3515 in the first half of 2024 and initiate a Phase 1 study in 2024; Submit an IND from its discovery portfolio in 2025..."

IND • P1 data • Acute Myelogenous Leukemia • CNS Tumor • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor

Schrödinger Highlights Progress of Clinical Programs and Discloses Three New Programs at First Therapeutics Pipeline Investor Event (Businesswire) - P1 | N=52 | NCT05544019 | Sponsor: BicycleTx Limited | "During Pipeline Day, Schrödinger is presenting new data showing that its novel MALT1 inhibitor, SGR-1505, was well tolerated in a Phase 1 study of 73 healthy volunteers. No drug-related serious adverse events or dose limiting toxicities were observed in the study. In the study, SGR-1505 achieved greater than 90 percent inhibition of IL-2 secretion in activated T cells, confirming target engagement and meeting the pharmacodynamic goals for the study. The data support continued evaluation of SGR-1505 in the ongoing Phase 1 study in patients with relapsed or refractory B-cell malignancies....Schrödinger is also presenting preclinical data for SGR-1505 demonstrating that SGR-1505 has favorable attributes and the potential for combination activity with standard-of-care agents in B cell malignancies."

P1 data • Preclinical • Hematological Malignancies • Oncology

Schrödinger Presents Data Supporting Advancement of SGR-1505 and SGR-2921 at American Society of Hematology 2023 Annual Meeting (Businesswire) - P1 | N=52 | NCT05544019 | Sponsor: Schrödinger, Inc. | "Preliminary clinical biomarker data from the Phase 1 study in healthy subjects showed that SGR-1505 inhibited cytokine release in ex vivo stimulation of human whole blood. The inhibition of certain cytokines in whole blood from human subjects dosed with SGR-1505 provides pharmacodynamic evidence of MALT1 inhibition. These data are consistent with prior preclinical observations in an in vitro whole blood assay from healthy human subjects, where approximately a 50-fold lower concentration of SGR-1505 was needed to achieve 90 percent inhibition of cytokine release compared to JNJ-6633."

Biomarker • P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Schrödinger Presents Data Supporting Advancement of SGR-1505 and SGR-2921 at American Society of Hematology 2023 Annual Meeting (Businesswire) - "Preclinical data showed that SGR-1505 is more potent than JNJ-6633, which has previously provided clinical validation for MALT1 inhibition as a potential therapeutic strategy for treating both chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphomas (NHL). In a preclinical model of diffuse large B-cell lymphoma, SGR-1505, in combination with venetoclax, demonstrated a stronger combination impact on cell viability compared to JNJ-633 plus venetoclax. Gene expression analysis showed that SGR-1505 provides greater modulation of NF-ΚΒ and related pathway genes compared to JNJ-6633."

Preclinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Part A, B and D: A Study of SGR-1505 in Healthy Volunteer Participants (ANZCTR) - P1 | N=66 | Completed | Sponsor: Schrödinger, Inc | Not yet recruiting ➔ Completed | Initiation date: Apr 2023

Trial completion • Trial initiation date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology