ALE.C04 / Alentis Therap - LARVOL DELTA

Evaluation of a novel target Claudin1 in preclinical models of nasopharyngeal carcinoma (AACR 2025) - P1/2 | "The results generated to date provide a proof-of-concept of targeting NJ-CLDN1 signaling in NPC using ALE.C04, especially in combination with chemotherapy or anti-vascular agent. ALE.C04 is now being evaluated in patients with NPC and other head and neck cancers in a phase 1 clinical trial (NCT06054477)."

Preclinical • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • CLDN1

Study of ALE.C04 in Patients With Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=21 | Terminated | Sponsor: Alentis Therapeutics AG | N=160 ➔ 21 | Trial completion date: Feb 2028 ➔ Feb 2025 | Recruiting ➔ Terminated | Trial primary completion date: Feb 2028 ➔ Feb 2025; Reprioritization of Trial

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review). (PubMed, Int J Mol Med) - "The human/humanized anti‑CLDN18.2 mAb osemitamab, and ADCs AZD0901, IBI343 and LM‑302, with single‑agent ORRs of 28‑60%, have been tested in phase III clinical trials. In addition, bsAbs, CAR T cells and their derivatives targeting CLDN4, 6 or 18.2 are in phase I and/or II clinical trials. AZD0901, IBI343, zolbetuximab and the anti‑CLDN1 mAb ALE.C04 have been granted fast track designation or priority review designation by the US Food and Drug Administration."

Journal • Review • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • CLDN1 • CLDN18 • CLDN4 • CLDN6

Study of ALE.C04 in Patients With Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=220 | Recruiting | Sponsor: Alentis Therapeutics AG

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Study of ALE.C04 in Patients With Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=220 | Recruiting | Sponsor: Alentis Therapeutics AG | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Alentis Therapeutics Doses First Patient in Phase 1/2 Clinical Trial of ALE.C04 in Head and Neck Squamous Cell Carcinoma (HNSCC) (Businesswire) - "Alentis Therapeutics...announced today that the first patient has been dosed in a Phase 1/2 clinical trial of ALE.C04, a Claudin-1 (CLDN1) targeting investigational antibody for the treatment of CLDN1+ tumors. The patient is enrolled under the Phase I program, led by Anthony El-Khoueiry, MD, Associate Director of Clinical Research, at University of Southern California (USC) Norris Comprehensive Cancer Center, part of Keck Medicine of USC. The open-label, multi-center, Phase 1/2 clinical trial (NCT06054477) will investigate ALE.C04 as a single agent and in combination with pembrolizumab (anti-PD-1 antibody) in 220 adults with recurrent or metastatic (R/M) head and neck squamous cell carcinoma. Endpoints include safety, tolerability, pharmacokinetics and anti-tumor efficacy."

Trial status • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Study of ALE.C04 in Patients With Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=220 | Not yet recruiting | Sponsor: Alentis Therapeutics AG

Combination therapy • Metastases • New P1/2 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Alentis Therapeutics Receives FDA Fast Track Designation for ALE.C04 for the Treatment of Claudin-1 Positive HNSCC (Businesswire) - "Alentis Therapeutics...announced today that the US Food and Drug Administration (FDA) has granted Fast Track development program for ALE.C04 for the treatment of patients with recurrent or metastatic, CLDN1-positive HNSCC."

Fast track designation • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Alentis Therapeutics Receives IND Clearance from FDA for ALE.C04 for the Treatment of CLDN1+ Tumors (Businesswire) - "Alentis Therapeutics...announced today the FDA cleared an IND application for ALE.C04 as a monotherapy and in combination with pembrolizumab, in a first-in-human clinical trial in recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) that is expected to start during the second half of 2023....'The planned Phase 1/2 study will tell us a lot about the anti-tumor efficacy of our antibody to treat CLDN1+ tumors'."

IND • New P1/2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

CLAUDIN-1 targeting antibody ALE.C04 drives single activity and restores anti-PD1 efficacy in solid tumors (AACR 2023) - "ALE.C04 perturbs the interface between CLDN1+ tumor cells and the stroma, thus restoring immune cell infiltration. Our pre-clinical data showed that: i) NJ-CLDN1 is a novel and druggable target in solid tumors ii) ALE.C04 is a selective anti-CLDN1 antibody capable of driving anti-tumor activity as both single agent and in combination with anti-PD1."

Clinical • IO biomarker • Late-breaking abstract • Oncology • Solid Tumor • CLDN1

Alentis Therapeutics Closes $105 Million Series C Funding to Advance Transformational Medicines for Claudin-1 (Businesswire) - "Alentis Therapeutics...announced $105 million in Series C financing. The funding round was led by Jeito Capital together with Novo Holdings A/S and RA Capital Management with participation from existing investors including BB Pureos Bioventures, Bpifrance through its InnoBio 2 fund and Schroders Capital....The financing will support Phase II and Phase I programs of Alentis’ lead investigational products ALE.F02 and ALE.C04 respectively as well as the CLDN1 platform development."

Financing • Fibrosis • Immunology • Oncology • Solid Tumor

Novo Holdings invests in US$105 million Series C Funding of Alentis Therapeutics (PRNewswire) - "Novo Holdings A/S...announced it has participated in a new investment in the US$105 million Series C financing of Alentis Therapeutics, a clinical-stage biotech developing breakthrough treatments for organ fibrosis and Claudin-1 (CLDN1) positive tumors. The financing will support clinical development of Alentis' lead investigational products ALE.F02 and ALE.C04 as well as the CLDN1 platform development."

Financing • Immunology • Oncology • Solid Tumor

Positive Results from Single Ascending Dose Phase 1 Study of ALE.F02 Targeting Claudin-1 (Businesswire) - P1 | N=40 | “Alentis Therapeutics…announces positive results from a single ascending dose Phase 1 study of of its lead program ALE.F02...The study found ALE.F02 to be well tolerated in healthy volunteers at all doses with a good safety profile and demonstrated initial evidence of on-target biological activity….Pharmacokinetic results predict an optimal dose for full receptor occupancy in humans within the range. No serious or severe adverse events were recorded. A multiple ascending dose Phase 1 study is ongoing, the results of which will be reported in Q1 2023….‘As we continue to develop breakthrough treatments for solid cancers and fibrosis targeting CLDN1, we look forward to reporting the full Phase 1 results for ALE.F02 in Q1 2023. In addition, we expect to initiate a first-in-human clinical study of our lead oncology asset ALE.C04 in H2 2023.’”

New trial • P1 data • Fibrosis • Immunology • Oncology • Solid Tumor

CLAUDIN-1 Targeting Antibodies in Solid Tumors: from ALE.C04 to CLAUDIN-1 Oncology Platform (ESMO-IO 2022) - "Importantly, ALE.C04 restored T cell infiltration and CPI efficacy in a mouse model for liver tumor . Based on our pre-clinical data, rationale and safety profile, we plan a phase 1b study with ALE.C04 in combination with CPIs in solid tumors."

IO biomarker • Gastrointestinal Cancer • Liver Cancer • Oncology • Solid Tumor • CLDN1