NDI-101150 / Nimbus Therap, Schrodinger - LARVOL DELTA

Ongoing phase 1/2 trial of the hematopoietic progenitor kinase 1 (HPK1) inhibitor NDI-101150 as monotherapy or in combination with pembrolizumab: Clinical safety and efficacy update in clear cell renal cell carcinoma (ccRCC). (ASCO 2025) - P1/2 | "NDI-101150 continues to demonstrate an acceptable safety profile and encouraging antitumor activity in patients with ccRCC, supporting continued clinical development of NDI-101150 as monotherapy and in combination with other agents as a promising next-generation immunotherapy oral small molecule."

Clinical • Combination therapy • IO biomarker • Monotherapy • P1/2 data • Anemia • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

Yale Cancer Center Experts set to Present Advances in Cancer Research at the World’s Largest Clinical Oncology Conference (Newswise) - "Over 40 Yale Cancer Center (YCC) physicians and scientists will present new research at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago from May 30 to June 3. This is the largest and most attended conference for oncology professionals, who are interested in learning about the latest, practice-changing cancer research....YCC researchers will share advances for new therapies with research areas covering breast, lung, prostate, head and neck, early onset, and metastatic cancers."

Clinical data • Acute Myelogenous Leukemia • Clear Cell Renal Cell Carcinoma • Estrogen Receptor Positive Breast Cancer • Head and Neck Cancer • HER2 Negative Breast Cancer • Non Small Cell Lung Cancer • Prostate Cancer

Tumor immune microenvironment characterization from pre- and post-dose tumors collected from a phase 1/2 study of NDI-101150, a hematopoietic progenitor kinase 1 (HPK1) inhibitor (SITC 2024) - P1/2 | "Background NDI-101150, an oral, selective, small molecule inhibitor of HPK1, is being studied as monotherapy and in combination with pembrolizumab. Ethics Approval This multicenter study was approved by the relevant Ethics Board at each study site. All participants gave informed consent before taking part."

IO biomarker • P1/2 data • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • GZMB • PTPRC

A Study of NDI 1150-101 in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=106 | Active, not recruiting | Sponsor: Nimbus Saturn, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ May 2025 | Trial primary completion date: Sep 2024 ➔ Feb 2025

Combination therapy • Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Ongoing phase 1/2 trial of the HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab: clinical safety update and renal cell carcinoma (RCC) efficacy analysis (SITC 2024) - P1/2 | "Ethics Approval This multicenter study was approved by the relevant Ethics Board at each study site. All participants gave informed consent before taking part.View this table:View inline View popup Download powerpoint Abstract 682 Table 1 Treatment-related adverse events (safety analysis set)*"

Clinical • Combination therapy • IO biomarker • Monotherapy • P1/2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Nimbus Therapeutics Presents Positive Updated Data from Phase 1/2 Clinical Trial of HPK1 Inhibitor for Advanced Solid Tumors at SITC 39th Annual Meeting (Businesswire) - P1/2 | N=106 | NCT05128487 | Sponsor; Nimbus Saturn, Inc. | "NDI-101150 monotherapy achieved 18% objective response rate in heavily pretreated renal cell carcinoma (RCC) patients with prior exposure to checkpoint inhibitors; Clinical benefit rate of 29% and disease control rate of 65% observed in RCC patients treated with NDI-101150 monotherapy; Acceptable safety profile maintained across expanded population of 88 patients; Clinical samples showed broad immune system activation through multiple cell types, supporting HPK1’s proposed mechanism of action."

P1/2 data • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Discovery of NDI-101150, A highly potent and selective HPK1 inhibitor for the treatment of cancer, through structure-based drug design (ACS-Fall 2024) - "The culmination of this approach was the identification of the potent HPK1 inhibitor, NDI-101150, which exhibits excellent selectivity both within the MAP4K family and in the wider kinome, translating to excellent T-cell activation in vitro and robust tumor growth inhibition in diverse in vivo syngeneic models. This presentation will disclose the discovery, preclinical evaluation, and early clinical data of NDI-101150 which is currently in a Phase 1/2 clinical trial."

Oncology

Phase 1/2 trial of the HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab: Clinical update. (ASCO 2024) - P1/2 | "The observed clinical benefit and safety profile support continued evaluation of NDI-101150 as a viable next-generation immunotherapeutic."

Clinical • Combination therapy • Monotherapy • P1/2 data • Endometrial Cancer • Esophageal Cancer • Fatigue • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • CD8

Nimbus Therapeutics Presents New Positive Monotherapy Phase 1/2 Clinical Data of HPK1 Inhibitor in Treatment of Advanced Solid Tumors at 2024 ASCO Annual Meeting (Businesswire) - P1/2 | N=106 | NCT05128487 | Sponsor: Nimbus Saturn, Inc. | "The results being presented at the ASCO Annual Meeting include updated data from 44 patients in the dose escalation cohorts (n=38 on monotherapy, n=6 on combination therapy) and additional data from 15 patients in the dose expansion cohorts. Results, as of March 18, 2024, showed: Treatment with NDI-101150 monotherapy was associated with clinical benefit in five out of 30 (16.7%) response-evaluable patients. One patient with renal cell carcinoma (RCC) in the dose escalation cohort exhibited a complete response, and one patient with RCC in the dose expansion cohort exhibited a partial response. Both patients were pre-treated with multiple lines of therapies including checkpoint inhibitors. Three patients with RCC, pancreatic cancer and endometrial cancer, respectively, maintained durable stable disease (SD) for more than six months while on treatment (21 months for the patient with RCC)."

P1/2 data • Endometrial Cancer • Pancreatic Cancer • Renal Cell Carcinoma

NDI-101150 is a potent and highly selective HPK1 inhibitor that both synergizes with and differentiates from anti-PD1 immune checkpoint blockade (AACR 2024) - P1/2 | "Furthermore, NDI-101150 seemed to induce a durable immune memory response as evidenced by the combination-treated animals showing complete rejection of tumor growth upon subsequent re-challenge, without any further dosing of NDI-101150.Conclusions Pharmacological inhibition of HPK1 with NDI-101150 represents a powerful system-wide immunomodulatory approach with the potential to enhance anti-tumor immunity in patients failing to respond to currently approved immune checkpoint therapies or in combination with immune checkpoint blockade therapies. NDI-101150 is currently being tested in a Phase 1/2 trial (NCT05128487) in patients with advanced solid tumors."

Checkpoint block • Checkpoint inhibition • Oncology • Solid Tumor • TGFB1

Nimbus Therapeutics Announces Expansion of Its Immunology Drug Discovery Pipeline (Businesswire) - "Nimbus Therapeutics, LLC...announced the advancement and expansion of its pipeline with the addition of discovery programs targeting innate immunity pathways...'SIK and cGAS are critical targets in highly prevalent diseases that are well suited to Nimbus’ structure-based drug design approach. We look forward to advancing our discovery and development programs across oncology, immunology, and metabolism to deliver transformative medicines to patients.'...Nimbus is advancing its Phase 1/2 trial (NCT05128487) of NDI-101150...and has reported positive dose escalation data showing potential monotherapy clinical benefit for patients with solid tumors. Furthermore, the company expects to initiate IND-enabling activities this year for its oncology program targeting Werner syndrome helicase (WRN)....Jeb Keiper...will provide an overview of the company’s progress and pipeline and anticipated milestones for 2024 and beyond at the 42nd Annual J.P. Morgan Healthcare..."

Pipeline update • Trial status • Immunology • Metabolic Disorders • Oncology • Solid Tumor

NDI-101150 is a potent and highly selective hematopoietic progenitor kinase 1 (HPK1) inhibitor that promotes a robust and broad anti-tumor immune response (SITC 2023) - "Conclusions Pharmacological inhibition of HPK1 with NDI-101150 represents a powerful system-wide immunomodulatory approach for enhancing anti-tumor immunity in patients failing to respond to currently approved immune checkpoint therapies. NDI-101150 is currently being tested in a Phase 1 trial in patients with advanced recurrent or metastatic solid tumors."

Oncology • Solid Tumor • CD8 • ITGAX • PTPRC

Monotherapy results from an ongoing phase 1a dose escalation study of NDI-101150, a highly selective oral hematopoietic progenitor kinase 1 (HPK1) inhibitor (SITC 2023) - P1/2 | "1 Methods NDI-101150 is being studied in a dose escalation and expansion study as monotherapy and in combination with pembrolizumab. Conclusions Preliminary results from the NDI-101150 monotherapy dose escalation demonstrate an acceptable safety profile, proximal target engagement and evidence of single agent activity with this novel class of oral immunotherapy in patients with relapsed and metastatic solid tumors. Updated clinical, PK and PD data will be presented."

Monotherapy • P1 data • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • LCP2

Nimbus Therapeutics Presents Positive Preliminary Data from Clinical Trial of HPK1 Inhibitor in Solid Tumors at SITC Annual Meeting (Businesswire) - P1/2 | N=106 | NCT05128487 | Sponsor: Nimbus Saturn, Inc. | "Nimbus Therapeutics, LLC...today announced initial data from the company’s ongoing Phase 1/2 study of NDI-101150...The data presented at SITC include initial safety and efficacy results from single agent therapy (n=13) in the dose escalation portion of the trial. Monotherapy treatment with NDI-101150 resulted in clinical benefit in 3 patients: One patient with renal cell carcinoma exhibited a complete response (CR)—the absence of all detectable cancer following treatment—while two patients with pancreatic cancer and renal cell carcinoma, respectively, exhibited prolonged (> 6 months) stable disease....In a second poster at SITC, Nimbus is presenting new preclinical data which support the potential for both broad immunotherapeutic potential and best-in-class selectivity of NDI-101150 among publicly disclosed HPK1 inhibitor programs to date."

P1/2 data • Preclinical • Oncology • Solid Tumor

Nimbus Secures $210M in Private Funding on Heels of $4B Takeda Deal (BioSpace) - "Nimbus Therapeutics announced Wednesday that it raised $210 million to advance its next wave of small-molecule medicines, making it one of 2023’s larger rounds of private financing. The Boston biotech company will be putting the cash towards a variety of initiatives including its ongoing clinical development of NDI-101150, a hematopoietic progenitor kinase 1 inhibitor in patients with solid tumors."

Financing • Oncology • Solid Tumor

Nimbus Therapeutics Closes $125M Private Financing to Advance Clinical Programs in Autoimmune Diseases and Oncology (Businesswire) - "The financing also will support the ongoing Phase 1/2 clinical trials of NDI-101150, Nimbus’ hematopoietic progenitor kinase 1 (HPK1) inhibitor, in patients with solid tumors, as well as preclinical development of programs targeting Casitas B-lineage lymphoma b (Cbl-b) and Werner syndrome helicase (WRN), along with ongoing discovery efforts across a range of targets."

Financing • Oncology • Solid Tumor

A Study of NDI 1150-101 in Patients With Solid Tumors (clinicaltrials.gov) - P1/2; N=106; Recruiting; Sponsor: Nimbus Saturn, Inc.

Clinical • Combination therapy • Monotherapy • New P1/2 trial • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Nimbus Therapeutics Announces First Patient Dosed in Phase 1/2 Study of a Highly Selective HPK1 Inhibitor in Patients with Solid Tumors (Businesswire) - "Nimbus Therapeutics...announced the first patient dosed in the first-in-human Phase 1/2 study of their small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, NDI-101150...It is planned to enroll approximately 106 subjects."

Trial status • Oncology