Nxera's Partner Cancer Research UK Presents Data from Successfully Completed Phase 1 Clinical Trial of Cancer Immunotherapy Drug HTL0039732 at ESMO

Executive Summary

• Nxera Pharma’s oral EP4 antagonist HTL0039732 (NXE0039732) completed the Phase 1 portion of its first‑in‑human trial, meeting primary safety objectives and identifying a recommended Phase 2 dose of 160 mg QD in combination with atezolizumab.
• The drug was well tolerated (no grade 4/5 treatment‑related AEs, no DLTs) and showed encouraging early efficacy, including confirmed partial responses in 1/2 ccRCC patients and 1/11 MSS‑CRC patients.
• Phase 2a expansion into four tumor cohorts (MSS‑CRC, gastric/GOJ adenocarcinoma, clear‑cell RCC, metastatic castration‑resistant prostate cancer) has begun, with the first patient dosed in September 2025.

Key Details

• Trial Design: First‑in‑human Phase 1/2a (NCT05944237); monotherapy arm n=13, combination arm (HTL0039732 + atezolizumab) n=22; advanced solid tumours refractory to standard therapy.
• Safety Findings: No grade 4/5 treatment‑related adverse events; no dose‑limiting toxicities. Grade 3 TRAEs in 14% of combination patients (3/22).
• Efficacy Signals:
• Confirmed partial responses per RECIST (>30% tumour reduction) in two patients:
  • 1/2 clear‑cell renal cell carcinoma (ccRCC) patients (50%).
  • 1/11 microsatellite stable colorectal cancer (MSS‑CRC) patients (~9%).
• Recommended Phase 2 Dose (RP2D): 160 mg once daily in combination with atezolizumab.
• Phase 2a Expansion: Four cohorts – MSS‑CRC, gastric/GOJ adenocarcinoma, clear‑cell RCC, metastatic castration‑resistant prostate cancer; first dose administered September 2025.
• Sponsorship & Management: Sponsored and managed by Cancer Research UK’s Centre for Drug Development; lead investigators Dr. Bristi Basu (University of Cambridge) and Dr. Debashis Sarker (King’s College London); primary site Addenbrooke’s Hospital, Cambridge with additional ECMC network sites.
• License: Nxera Pharma holds a license to the trial results.

Notable Quotes

“We are encouraged by the robust safety profile and promising results from the completed Phase 1 study of our novel EP4 antagonist HTL0039732… Radiological responses in otherwise immunotherapy‑resistant tumors demonstrate a potential to improve on current treatments…” – Dr. Alastair Brown, SVP, Future Therapeutic Strategy, Nxera Pharma.