SGR-2921 / Schrodinger - LARVOL DELTA

Sgr-2921, a Potent CDC7 Inhibitor, Demonstrates Significant Anti-Leukemic Responses in Patient-Derived AML Models Representing Difficult-to-Treat Disease (ASH 2023) - P1 | "Our data show remarkable dose-dependent in vivo activity of SGR-2921 in AML PDX models, including in those representing difficult-to-treat disease. Direct inhibition of CDC7 by SGR-2921 in AML blasts was demonstrated by a dose-dependent reduction of phosphorylated MCM2. Together, these data demonstrate that SGR-2921-mediated CDC7 inhibition is an attractive novel treatment opportunity in AML, with potential utility in patients with high risk mutations and relapsed and refractory AML."

Clinical • Acute Myelogenous Leukemia • Oncology • BRCA1 • CDC7 • MCM2 • PTPRC • TP53

A First-in-Human, Phase 1, Dose Escalation Study of Sgr-2921 As Monotherapy in Subjects with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (ASH 2023) - "The study primary objectives are to evaluate the safety and tolerability of SGR-2921 as monotherapy and identify RP2D including MTD. Secondary objectives include evaluating the pharmacokinetics (PK) of SGR-2921 and investigating preliminary antitumor activity (composite complete remission rate, objective response rate, duration of response, etc.)."

Clinical • First-in-human • Monotherapy • P1 data • Acute Myelogenous Leukemia • Central Nervous System Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CDC7 • FLT3 • TP53

SGR-2921-101: Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=66 | Terminated | Sponsor: Schrödinger, Inc. | N=50 ➔ 66 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Aug 2025; Company decision

Enrollment change • First-in-human • Monotherapy • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

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 Announces Discontinuation of SGR-2921 Program (Schrödinger Press Release) - "Despite early evidence of monotherapy activity observed in the Phase 1 study, based on the profile observed to date, including two emergent events where SGR-2921 was considered to have contributed to two deaths in patients with AML, Schrödinger believes the path to development as a combination therapy would be difficult to pursue."

Discontinued • Acute Myelogenous Leukemia

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:...In January, the U.S. Food and Drug administration granted SGR-2921, the company’s CDC7 inhibitor, Orphan Drug Designation for the treatment of acute myeloid leukemia (AML). Schrödinger expects to present initial clinical data from the ongoing Phase 1 study of SGR-2921 in patients with AML and myelodysplastic syndrome (MDS) in the second half of 2025."

Orphan drug • P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

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:...Schrödinger announced today that the FDA has granted SGR-2921, the company’s investigational CDC7 inhibitor, FDA Fast Track Designation for the treatment of relapsed/refractory acute myeloid leukemia. The Phase 1 study of SGR-2921 in patients with acute myeloid leukemia or myelodysplastic syndrome continues to enroll patients in the U.S. and EU. The company expects to report initial clinical data from this study in the second half of 2025."

Enrollment status • Fast track • P1 data • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

A FIRST-IN-HUMAN, PHASE 1, DOSE ESCALATION STUDY OF SGR-2921 AS MONOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA OR MYELODYSPLASTIC SYNDROME (EHA 2024) - "Preclinical studies demonstrate that SGR-2921 haspotent anti-proliferative activity in AML cell lines representative of difficult to treat patient populations and isagnostic of mutational status (including those with p53 mutations), venetoclax resistance, and prior lines oftreatment... SGR-2921 is an oral, small molecule inhibitor of CDC7. It has demonstrated promising anti-proliferative activityin AML cell lines and anti-tumor activity in CDX and PDX AML animal models. The ongoing phase 1 clinical trialwill evaluate the safety and tolerability of SGR-2921 in subjects with r/r AML and HR or VHR-MDS anddetermine RP2D for future expansion studies."

Clinical • Monotherapy • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BRCA1 • CDC7 • HRD • MCM2 • MCM4 • TP53

A first-in-human, phase 1, dose escalation study of SGR-2921 as monotherapy in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome. (ASCO 2024) - P1 | "The primary objectives are to evaluate the safety and tolerability of SGR-2921 as monotherapy and to identify the RP2D. Secondary objectives include evaluating SGR-2921 pharmacokinetics and investigating preliminary antitumor activity."

Clinical • Monotherapy • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CDC7 • TP53

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 Progress of Clinical Programs and Discloses Three New Programs at First Therapeutics Pipeline Investor Event (Businesswire) - "'CDC7 is a promising therapeutic target for the treatment of myelodysplastic syndromes and acute myeloid leukemia, diseases for which there is a significant unmet need in treating both frontline and relapsed/refractory patients,' stated Elie Traer...'Targeting CDC7 with emerging investigational therapeutics, such as SGR-2921, represents an opportunity to expand our armamentarium of treatment options beyond existing targeted therapies.'"

Media quote

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 Presents Data Supporting Advancement of SGR-1505 and SGR-2921 at American Society of Hematology 2023 Annual Meeting (Businesswire) - "In vitro, SGR-2921 exhibited greater potency compared to other clinical-stage CDC7 inhibitors and showed anti-proliferative activity in AML patient-derived samples regardless of driver mutations. In vivo, SGR-2921 showed dose-dependent reduction of AML blasts in multiple AML models representing difficult-to-treat disease. SGR-2921 also showed synergistic activity in combination with decitabine in p53-mutated AML models in vivo."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

SGR-2921-101: Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Schrödinger, Inc.

Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

Schrödinger Reports Third Quarter 2023 Financial Results (Businesswire) - "Today Schrödinger announced the initiation of the Phase 1 clinical study of SGR-2921, an investigational CDC7 inhibitor, in patients with acute myeloid leukemia or myelodysplastic syndrome. The study is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and determine the recommended dose....Schrödinger continues to advance SGR-3515, an inhibitor of Wee1 and Myt1....IND-enabling activities are ongoing to support an IND submission for SGR-3515 in the first half of 2024....Today Schrödinger announced that one of its previously undisclosed discovery programs is PRMT5-MTA (protein arginine methyltransferase 5/methylthioadenosine)....The company expects to provide more details about its PRMT5-MTA program and other early-stage programs at its Pipeline Day on December 14, 2023."

IND • Pipeline update • Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Schrödinger to Present New Data for SGR-1505 and SGR-2921 at American Society of Hematology 2023 Annual Meeting (Businesswire) - "Presentation of SGR-1505 data will include further characterization in preclinical oncology models as well as preliminary clinical biomarker information from the Phase 1 study in healthy subjects, which is nearing completion. The data support continued development of SGR-1505 as a potential therapy for patients with advanced B-cell malignancies, and a Phase 1 dose-escalation study in this patient population is ongoing....Additionally, data will be presented for SGR-2921 demonstrating strong anti-leukemic activity in preclinical models of acute myeloid leukemia (AML) representing difficult-to-treat disease. CDC7 is a cell cycle kinase in the DNA damage-response pathway and has emerged as a promising therapeutic target in oncology, including for the treatment of AML."

P1 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology

Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Schrödinger, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

Schrödinger Reports Second Quarter 2023 Financial Results (Businesswire) - "The company expects to initiate a Phase 1 clinical trial this year. The study is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and determine the recommended dose of SGR-2921 in patients with acute myeloid leukemia or myelodysplastic syndrome."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study of SGR-2921 in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1 | N=50 | Not yet recruiting | Sponsor: Schrödinger, Inc.

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • BCL2

Schrödinger Reports Strong First Quarter 2023 Financial Results (Businesswire) - "Today Schrödinger announced that it has also initiated a Phase 1 study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SGR-1505. Schrödinger is continuing to progress its CDC7 inhibitor, SGR-2921, through IND-enabling studies to support a planned IND submission in the first half of 2023....Schrödinger continues to advance its Wee1 inhibitor, SGR-3515, through IND-enabling studies to support a potential IND submission in 2024."

IND • New P1 trial • Oncology

Schrödinger Provides Update on Progress Across the Business and Outlines 2023 Company Strategic Priorities (Businesswire) - "Today Schrödinger outlined the following strategic priorities for 2023: Complete dose-escalation portion of the Phase 1 clinical trial of SGR-1505; Submit IND for SGR-2921 and initiate Phase 1 dose-escalation trial; Select Wee1 inhibitor development candidate and initiate IND-enabling studies; Advance LRRK2 program toward development candidate status."

IND • Pipeline update • Trial status • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

Schrödinger Presents New Preclinical Data Supporting Advancement of CDC7 Inhibitor Development Candidate, SGR-2921, at American Society of Hematology 2022 Annual Meeting (Businesswire) - "Schrödinger, Inc...announced new preclinical data on its potent and selective CDC7 inhibitor, SGR-2921, in a poster session at the American Society of Hematology (ASH) 64th Annual Meeting taking place virtually and in New Orleans, Louisiana. The data presented demonstrate that SGR-2921 exhibits strong anti-tumor activity in vivo across multiple acute myeloid leukemia (AML) models, including cell-derived xenograft models, as a monotherapy and in combination with standard of care agents. Moreover, SGR-2921 demonstrates anti-tumor activity in AML patient-derived samples resistant to standard of care agents....Schrödinger is advancing SGR-2921 through investigational new drug (IND)-enabling studies with plans to submit an IND application to the U.S. Food and Drug Administration in the first half of 2023 and to initiate a Phase 1 clinical trial in patients with relapsed/refractory AML in the second half of 2023."

IND • New P1 trial • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology