SGR-3515 / Schrodinger - LARVOL DELTA

ACR-2316 is a novel, differentiated, clinical-stage WEE1/PKMYT1 inhibitor designed by Acrivon's Generative Phosphoproteomics AP3 Platform for optimal pro-apoptotic pathway effects in tumor cells resulting in superior preclinical activity (AACR-NCI-EORTC 2025) - "In cellular TE assays, ACR-2316 displayed more potent WEE1 TE than all benchmark WEE1 inhibitors (azenosertib, adavosertib, Debio0123), while simultaneously targeting MYT1... WEE1 inhibitor-induced MYT1 activation constitutes a resistance mechanism that may limit the clinical efficacy of WEE1 inhibition. ACR-2316 is a potent, selective WEE1/MYT1 inhibitor that displays superior preclinical efficacy via its differentiated profile optimized by AP3 pathway-based structure-activity relationships in the intact cell. Acrivon's ongoing Phase 1 ACR-2316 monotherapy trial in solid tumors has already demonstrated clinical activity during dose escalation prior to reaching Recommended Phase 2 Dose."

Preclinical • Tumor cell • Oncology • Solid Tumor • BRAF • CDK1 • CDK2 • PKMYT1 • PLK1

SGR-3515: Initial data from P1 trial (NCT06463340) for solid tumors in Q4 2025 (Schrödinger) - Q2 2025 Results

P1 data • Oncology • Solid Tumor

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 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

INK4A/B as predictive biomarkers for enhanced efficacy of dual WEE1 and PKMYT1 inhibition in CDK4/6 inhibitor-resistant breast cancer (AACR 2025) - "This study aimed to identify predictive biomarkers of response to WEE1/PKMYT1 dual inhibition while maintaining manageable toxicity. Evaluating WEE1 inhibitors (adavosertib or azenosertib) in combination with the PKMYT1 inhibitor (lunresertib) across CDK4/6i-R and TNBC models, including patient-derived xenografts (PDXs) and organoids, demonstrated significant tumor suppression, with the novel dual WEE1/PKMYT1 inhibitor SGR-3515 showing comparable efficacy... Dual inhibition of WEE1 and PKMYT1 presents a compelling therapeutic strategy for CDK4/6i-R breast cancer and TNBC. Elevated baseline levels of INK4A and INK4B are strongly associated with enhanced treatment responses, highlighting their potential as predictive biomarkers for selecting patients likely to benefit from WEE1/PKMYT1 dual inhibition therapy."

Biomarker • Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • CDKN2A • CDKN2B • ER • HER-2 • PKMYT1

Schrödinger Presents New Preclinical Data at AACR Annual Meeting (Businesswire) - "SGR-3515 Data at AACR: The poster (Abstract #3025)...includes preclinical data demonstrating that SGR-3515 monotherapy has superior anti-tumor activity compared to the Wee1 inhibitor ZN-c3 and the Myt1 inhibitor RP-6306 in multiple tumor models as well as synergistic efficacy when used in combination with chemotherapy. The poster also shares for the first time preclinical data demonstrating that the potential efficacy and tolerability of SGR-3515 can be optimized with three to five days of dosing, depending on the tumor type, in a two-week dosing cycle across multiple tumor settings."

Preclinical • Oncology

Optimization of therapeutic index of SGR-3515, a first-in-class Wee1/Myt1 inhibitor through intermittent dosing for monotherapy and combination with chemotherapy in xenograft tumor models (AACR 2025) - P1 | "Furthermore it suppresses the acquired resistance associated with a Wee1 inhibitor (ZNc3). The robust anti-tumor activity of SGR-3515, a first-in-class Wee1/Myt1 inhibitor confirms the synergy of Wee1 and Myt1 co-inhibition. SGR-3515 dosing schedule optimization improves therapeutic index as a monotherapy and in combination with Carboplatin. The preclinical data supported the progression of SGR-3515 to clinical study (NCT06463340)."

Monotherapy • Preclinical • Oncology • Solid Tumor • CDK1 • PKMYT1

Machine learning-based combination prediction for Wee1 inhibitor (AACR 2025) - "Motivation: Wee1 is the gatekeeper gene that allows proper DNA damage repair (DDR) during the G2/M cell cycle transition. We integrated drug combination response data from two publications and trained LTR models based on the data. In 5-fold cross-validations for the different prediction scenarios, new entry, new matrix, new drug combo, the model achieved a Pearson correlation of above 0.8 between predicted and measured response data. The final model was trained to predict responses of drug combinations between Wee1i and 130 other drugs in 53 cell lines."

Machine learning • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • WEE1

Schrödinger to Present Preclinical Data at AACR Annual Meeting (Businesswire) - "The SGR-3515 presentation will include data demonstrating that an optimized, intermittent dosing schedule of SGR-3515 resulted in an improved therapeutic index in preclinical oncology models. Preclinical data also showed that SGR-3515 has a differentiated profile supporting continued development as a potential therapy for patients with advanced solid tumors. A Phase 1 clinical trial in this patient population is ongoing, and Schrödinger expects to report initial clinical data from the trial in the second half of 2025."

P1 data • Preclinical • 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

Discovery of SGR-3515, a first-in-class Wee1/Myt1 inhibitor with differentiated pharmacological properties in xenograft tumor models (EORTC-NCI-AACR 2024) - "SGR-3515 demonstrates an unique and well differentiated pharmacological profile compared to the Wee1 inhibitor ZN-c3 or the Myt1 inhibitor RP-6306 in preclinical studies. It mediates durable pharmacological effects that enable long dosing holidays to reduce potential on-target myelosuppression and GI toxicity. In addition, the dual inhibition of Wee1 and Myt1 has synergistic effect and drives deeper anti-tumor responses than inhibiting either target alone."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • CDK1 • PKMYT1

Schrödinger Presents SGR-3515 Preclinical Data at 2024 EORTC-NCI-AACR Symposium (Businesswire) - "Schrödinger...announced new preclinical data on SGR-3515, its investigational Wee1/Myt1 inhibitor, during a poster session at the 36th EORTC-NCI-AACR Symposium (ENA 2024). The data demonstrate that in preclinical models, treatment with SGR-3515 results in synergistic anti-tumor activity that leads to deeper and more durable responses compared to inhibitors that target only Wee1 or Myt1. The preclinical data also show that SGR-3515 has a favorable pharmacological profile and dosing schedule that supports evaluating intermittent dosing in patients....A Phase 1 dose-escalation study of SGR-3515 in patients with advanced solid tumors is ongoing in the U.S. and Canada, and initial data from the clinical study is expected in the second half of 2025."

P1 data • Preclinical • Oncology • Solid Tumor

Schrödinger to Present New Preclinical SGR-3515 and PRMT5-MTA Data at 2024 EORTC-NCI-AACR Symposium (Businesswire) - "Schrödinger...announced that new preclinical data on SGR-3515, its investigational Wee1/Myt1 inhibitor, and the company’s PRMT5-MTA inhibitor program, will be presented during poster sessions at the 36th EORTC-NCI-AACR Symposium (ENA 2024) taking place October 23-25, 2024 in Barcelona, Spain. The SGR-3515 presentation will include data further characterizing SGR-3515 in preclinical oncology models....Additionally, preclinical data will be presented on the discovery of highly selective PRMT5-MTA inhibitors."

Preclinical • Oncology • Solid Tumor

AutoDesigner - Core Design, a De Novo Design Algorithm for Chemical Scaffolds: Application to the Design and Synthesis of Novel Selective Wee1 Inhibitors. (PubMed, J Chem Inf Model) - "Several compounds were synthesized and assayed from the scaffold, displaying good potency against Wee1 and excellent PLK1 selectivity. Our results suggest that CoreDesign can significantly speed up the hit-identification process and increase the probability of success of drug discovery campaigns by allowing teams to bring forward high-quality chemical scaffolds derisked by the availability of preliminary SAR."

Journal • PLK1

Schrödinger Reports Strong Second Quarter 2024 Financial Results (Businesswire) - "Proprietary Pipeline:...Today, Schrödinger announced the initiation of dosing in a Phase 1 clinical study of SGR-3515, an investigational Wee1/Myt1 inhibitor in patients with advanced solid tumors. The dose-escalation study is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, preliminary anti-tumor activity, and a recommended Phase 2 dose of SGR-3515. The company expects to report initial clinical data from this study in the second half of 2025."

P1 data • Trial status • Solid Tumor

Study of SGR-3515 In Participants With Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Schrödinger, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

Study of SGR-3515 In Participants With Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Schrödinger, Inc.

Metastases • New P1 trial • Oncology • Solid Tumor

Schrödinger Reports First Quarter 2024 Financial Results (Businesswire) - "Today, Schrödinger also announced that the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for SGR-3515, its Wee1/Myt1 inhibitor. Schrödinger expects to initiate a Phase 1 dose-escalation trial of SGR-3515 in patients with solid tumors in the third quarter of 2024....Schrödinger is progressing its discovery pipeline, including programs targeting EGFRC797S, PRMT5-MTA and NLRP3. The company continues to anticipate submitting at least one IND in 2025."

IND • New P1 trial • Solid Tumor

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 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 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 Reports Strong Fourth Quarter and Full-Year 2022 Financial Results (Businesswire) - "Schrödinger announced today that it has selected SGR-3515 as its development candidate for its Wee1 program. SGR-3515 demonstrated strong anti-tumor activity with limited off-target effects in preclinical studies. Activities to support IND-enabling studies are underway."

Pipeline update • Oncology

Discovery of potent, selective, and orally available WEE1 inhibitors that demonstrate increased DNA damage and mitosis in tumor cells leading to tumor regression in vivo (AACR 2022) - "Small molecule WEE1 inhibitors, such as AZD1775 and Zn-C3, are currently being evaluated in the clinic and have demonstrated promising efficacy in solid tumors including ovarian, colon, and uterine carcinoma.By applying Schrödinger’s computational platform including Free Energy Perturbation (FEP) and Protein FEP, we have identified novel, potent, and highly selective WEE1 inhibitors with IC50 values in the low nanomolar range in a biochemical kinase activity assay and cellular target engagement (CDK1 pTyr15) IC50s of 100 - 300 nM in A427 and OVCAR3 cell lines. In summary, we have identified novel, potent and exquisitely selective WEE1 kinase inhibitors that demonstrate robust anti-tumor activity and sustained target engagement in tumor models. The compound’s anti-tumor effects are maintained with dosing holidays while allowing full recovery of mechanism-based hematological effects."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Uterine Cancer • CDK1 • CDK2 • CYP3A4

Schrödinger Reports New Preclinical Data Supporting Advancement of Its Wee1 Inhibitor Program at American Association of Cancer Research 2022 Annual Meeting (Businesswire) - "Schrödinger...presented new preclinical data from its Wee1 inhibitor program in a poster session at the American Association of Cancer Research (AACR) Annual Meeting taking place in New Orleans. Schrödinger has identified multiple, highly selective and structurally distinct Wee1 inhibitors with optimized physicochemical properties that show strong pharmacodynamic responses and anti-tumor activity in preclinical models....Schrödinger is on track to select a Wee1 development candidate later this year....Schrödinger anticipates submitting an Investigation New Drug (IND) Application to the U.S. Food and Drug Administration (FDA) in 2023."

IND • Pipeline update • Preclinical • Oncology