NXE0039732 / Nxera Pharma, Cancer Research UK - LARVOL DELTA

Cancer Research UK’s Centre for Drug Development is sponsoring and managing the ongoing Phase 1/2a clinical trial of HTL0039732 (GlobeNewswire) - "The Phase 2a trial expands four cohorts of patients from MSS CRC, gastric or gastroesophageal junction (GOJ) adenocarcinoma, clear cell renal cell carcinoma, and metastatic castration-resistant prostate cancer backgrounds. The first patient was dosed in the Phase 2a portion of the trial in September 2025."

Trial status • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Prostate Cancer

Cancer Research UK first-in-human (FIH) phase I/IIa trial of the prostaglandin E2 (PGE2) receptor 4 (EP4) antagonist HTL0039732 (HTL) as monotherapy and in combination with immunotherapy in patients with advanced solid tumours (ESMO 2025) - P1/2 | "Clinical trial identification NCT05944237 EudraCT 2022-000775-39. Conclusions HTL is well tolerated with no DLTs; based on PK and target engagement assay data, HTL 160 mg QD in combination with atezolizumab has been selected as the RP2D. This will be tested in four cohorts in Phase IIa: MSS-CRC, gastro-oesophageal, castration-resistant prostate and renal cancers."

Clinical • Combination therapy • First-in-human • Metastases • Monotherapy • P1/2 data • Castration-Resistant Prostate Cancer • Colorectal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • GPRC6A • PTGER4

Nxera Pharma…announces that its partner, Cancer Research UK, presented data from the successfully completed Phase 1 part of the ongoing Phase 1/2a clinical trial (NCT05944237) of Nxera’s immunotherapy drug HTL0039732 (also known as NXE0039732) at the European Society for Medical Oncology Congress (ESMO) 2025 (GlobeNewswire) - "HTL’732 was well tolerated with no grade 4/5 treatment-related adverse events and no dose limiting toxicities in monotherapy or in combination. Grade 3 treatment-related adverse events occurred in 14% of combination patients (3 of 22), similar to established atezolizumab monotherapy data; Confirmed partial responses to the combination of HTL’732 and atezolizumab – as determined by RECIST criteria and showing >30% tumor reduction – were seen in two patients."

P1 data • Clear Cell Renal Cell Carcinoma • Colorectal Cancer

Nxera Pharma…and Cancer Research UK announce that the first patient has been dosed in a Phase 2a clinical trial (NCT05944237) evaluating Nxera’s investigational immunotherapy drug HTL0039732 (also known as NXE0039732) for advanced solid tumors (GlobeNewswire) - "Study participants had advanced solid tumors that were resistant or refractory to standard therapy, and the Phase 1 trial showed encouraging early efficacy including two confirmed partial responses in two distinct tumor types when administered in combination use with atezolizumab. The Phase 1 trial results to date will be presented at the European Society for Medical Oncology Congress (ESMO) 2025 in October."

P1 data • Trial status • Solid Tumor

HTL0039732 in Participants With Advanced Solid Tumours (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Cancer Research UK | Trial primary completion date: Sep 2026 ➔ Jun 2027 | Trial completion date: Sep 2026 ➔ Jun 2027

Monotherapy • Trial completion date • Trial primary completion date • Bladder Cancer • Castration-Resistant Prostate Cancer • Cervical Cancer • Colorectal Cancer • Endocrine Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Mesothelioma • Oncology • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer

Cancer Research UK phase I/IIa trial of the prostaglandin E2 (PGE2) receptor 4 (EP4) antagonist HTL0039732 as monotherapy and in combination with immunotherapy in patients (pts) with advanced solid tumors (ESMO 2024) - P1/2 | "HTL0039732 has demonstrated antitumor efficacy in preclinically relevant syngeneic tumor models, with evidence of significant synergy between HTL0039732 and blockade of the PD-1/PD-L1 pathway.Trial design: This is a first-in-human trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of HTL0039732 as monotherapy and in combination with atezolizumab, in pts with advanced solid tumors. Correlative studies to determine target engagement will include mandatory paired tumor biopsies in Phase I Part B and Phase IIa to evaluate tumor T cell infiltration and correlation with participant response, together with TME and peripheral blood immunophenotyping. As of May 2024, three dose levels within Phase I Part A have been completed without DLT and recruitment to Phase I Part B has commenced."

Clinical • Combination therapy • Metastases • Monotherapy • P1/2 data • Castration-Resistant Prostate Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Nxera’s Partner Cancer Research UK to Present on Phase 1/2a Clinical Trial with Cancer Immunotherapy Drug HTL0039732 at ESMO (GlobeNewswire) - "Nxera Pharma...and Cancer Research UK announce an upcoming presentation on the ongoing Phase 1/2a clinical trial (NCT05944237) of Nxera’s immunotherapy drug HTL0039732 (also known as NXE0039732) at the European Society for Medical Oncology Congress (ESMO) 2024, taking place on 13–17 September in Barcelona, Spain...'We are excited to present this ‘Trials in Progress’ poster at ESMO, outlining the scientific rationale and design of the clinical trial of HTL0039732, given alone and in combination with immunotherapy for patients with advanced solid cancers.'"

Clinical protocol • Oncology • Solid Tumor

Sosei Heptares Operational Highlights and Consolidated Results for 12 Months ended 31 December 2023 (GlobeNewswire) - "First patient dosed with cancer immunotherapy candidate HTL0039732 in Phase 1/2a trial – HTL’732 is an orally available small molecule EP4 antagonist for advanced solid tumors being evaluated under an agreement with Cancer Research UK."

Trial status • Solid Tumor

Sosei Heptares and Cancer Research UK Announce the Dosing of the First Patient in a Phase I/IIa Trial with Cancer Immunotherapy Drug HTL0039732 (GlobeNewswire) - "Sosei Group Corporation...today announce that the first patient has been dosed in a Phase I/IIa clinical trial evaluating Sosei Heptares’ orally available small molecule cancer immunotherapy drug HTL0039732 for advanced solid tumors....Cancer Research UK’s Centre for Drug Development (CDD) is sponsoring, designing and conducting the Phase I/IIa trial with three main objectives: to define the toxicity, tolerability and pharmacokinetics of HTL0039732, to identify the recommended dose for Phase II studies, and to assess its antitumor activity as a monotherapy and in combination with the PD-L1 inhibitor atezolizumab. Phase IIa of the trial will expand the optimal combination dose in up to four cohorts in specified cancer indications. Sosei Heptares holds a license to the results generated under the trial to continue the clinical development and commercialization of HTL0039732."

Trial status • Colorectal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Prostate Cancer • Solid Tumor

HTL0039732 in Participants With Advanced Solid Tumours (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Cancer Research UK

Combination therapy • Metastases • Monotherapy • New P1/2 trial • Bladder Cancer • Cervical Cancer • Colorectal Cancer • Endocrine Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Mesothelioma • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • Uterine Cancer • CD8

Cancer Research UK and Sosei Heptares sign agreement to advance cancer immunotherapy candidate into clinical trials (GlobeNewswire) - "Sosei Group Corporation...and Cancer Research UK...announce the signing of an agreement to bring Sosei Heptares’ cancer immunotherapy drug candidate into a first-in-human trial. Under the Clinical Trial and Licence Agreement (CTLA), Cancer Research UK’s Centre for Drug Development will sponsor, design and execute a Phase I/IIa clinical trial of HTL00397322, a novel selective EP4 antagonist...HTL0039732 has been proposed for a range of cancers including microsatellite stable3 colorectal, gastroesophageal, head and neck and castrate resistant prostate cancer."

Licensing / partnership • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Prostate Cancer