— 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 – —

BOSTON, Mass. — November 7, 2024 — Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, today announced the presentation of new clinical and translational data from its ongoing Phase 1/2 trial of NDI-101150, a novel, oral, potent and selective small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, for the treatment of advanced solid tumors. Results will be highlighted in two poster presentations at the Society for Immunotherapy of Cancer (SITC) 39^th Annual Meeting, taking place November 6-10, 2024 in Houston, Texas.

The Phase 1/2 multicenter, open-label trial (NCT05128487) is designed to assess NDI-101150 as a monotherapy (50-200 mg QD dose) and in combination with pembrolizumab (200 mg Q3W) in the treatment of adults with advanced solid tumors. The clinical results being presented at the SITC Annual Meeting include updated safety data from 53 patients in the dose escalation cohorts (n=41 on monotherapy, n=12 on combination therapy) and additional data from 35 patients in the dose expansion cohorts as well as updated efficacy data from 17 response-evaluable patients with renal cell carcinoma (RCC) who received NDI-101150 monotherapy. Results, as of August 12, 2024, showed:

Safety Profile

• NDI-101150 was generally well-tolerated with immune-related adverse events supporting the proposed mechanism of action of HPK1 inhibition, which results in immune activation.
• Grade ≥3 treatment-related adverse events (TRAEs) occurred in 14% of all patients exposed to NDI-101150 (n=88). The most common TRAEs were nausea, diarrhea, vomiting and fatigue.

Efficacy and Target Engagement

• Treatment with NDI-101150 monotherapy resulted in objective responses in 18% (3/17) of response-evaluable RCC patients, including one complete response (CR) and two partial responses (PRs).

• A clinical benefit rate (CR + PR + stable disease [SD] ≥6 months) of 29% (5/17) and a disease control rate of 65% (11/17) were observed in response-evaluable RCC patients treated with NDI-101150 monotherapy.

• NDI-101150 effectively inhibited its target across multiple dose levels, providing strong pharmacodynamic evidence of the molecule’s activity in patients.

Supporting Mechanistic Evidence

• Analysis of tumor biopsies showed a more robust presence of immune cells post-treatment, with increased numbers of tumor-infiltrating lymphocytes and dendritic cells in the tumor microenvironment.
• Comprehensive gene expression profiling demonstrated broad activation of immune-related pathways, including enhanced interferon response and T cell activation signals.

“These clinical results of NDI-101150 are highly encouraging, particularly in the context of renal cell carcinoma patients who have experienced disease progression on prior checkpoint inhibitors,” said Nathalie Franchimont, M.D., Ph.D., Chief Medical Officer of Nimbus. “The objective responses and disease control rates seen thus far with NDI-101150 in heavily pretreated patients as well as the current safety profile support further evaluation of NDI-101150 in the clinic.”

“The clinical and translational data package being presented at SITC demonstrates both the therapeutic potential of NDI-101150 and the power of our computational drug discovery engine to design highly selective molecules against challenging targets like HPK1,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “The monotherapy activity we observed is particularly noteworthy, as many second-generation immunotherapy compounds have struggled to show clinical benefit on their own. Together with its safety profile and the immune activation signals we’ve observed, these data support NDI-101150’s potential as a novel oral non-checkpoint immunotherapy option for patients who need new treatment approaches beyond current checkpoint inhibitors.”

The abstracts are available in the Journal for ImmunoTherapy of Cancer (JITC), the official journal of SITC, here and the details of the poster presentations are as follows:

 

Title: 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

Lead Author: David Sommerhalder, M.D., Director of Clinical Research, NEXT Oncology

Date: Saturday, November 9, 2024

Time: 9:00 a.m. – 8:30 p.m. CST

Category: Clinical Trials in Progress

Abstract Number: 682

Link to poster here.

 

Title: 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

Lead Author: Scott Daigle, Senior Director, Translational Medicine, Nimbus Therapeutics

Date: Friday, November 8, 2024

Time: 9:00 a.m. – 7:00 p.m. CST

Category: Biomarkers, Immune Monitoring and Novel Technologies

Abstract Number: 83

Link to poster here.

 

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a clinical-stage HPK1 inhibitor for the treatment of cancer (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, including a WRN program for MSI-H cancers, autoimmune conditions, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

Media Contact

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Nimbus Therapeutics

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