CLDN1

First anti-Claudin-1 antibody-drug conjugate (ADC) to enter the clinic Phase 1/2 clinical trial in patients expected to start Q1 2025 BASEL, Switzerland I October 02, 2024 I Alentis Therapeutics (“Alentis”), the clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, announced today that the U.S. Food & Drug Administration (FDA) cleared an IND application for ALE.P02, an anti-CLDN1 ADC with a tubulin inhibitor payload. A Phase 1/2 clinical trial in patients with CLDN1+ squamous tumors is expected to start during the first quarter of 2025. “ ADCs have shown great potential in the treatment of cancer, ” said Luigi Manenti, Chief Medical Officer of Alentis. “ Squamous cancers originating in the head and neck, cervix, esophagus and lung are characterized by high CLDN1 expression, and ALE.P02 provides a first-in-class opportunity for these patients who need new therapies after first-line treatment fails. ” “ Anti-CLDN1 ADCs are exciting because they address the urgent need for novel targets in the ADC space, ” added Tony Mok, Professor of Clinical Oncology at the Chinese University of Hong Kong . “ ALE.P02 is particularly promising for squamous cancers, including HNSCC and NSCLC, where CLDN1 is often overexpressed. The unmet medical need in these indications is significant, and I look forward to the results of the Phase 1/2 study. ” Dr. Roberto Iacone, Chief Executive Officer of Alentis said, “ ALE.P02, entering the clinic, marks a significant advancement in our oncology pipeline. We can maximize our development plan by leveraging insights from human clinical trials of lixudebart (ALE.F02), used as the backbone antibody for Alentis’ ADCs.” Dr. Iacone added,“ For our second ADC program, ALE.P03, with its topoisomerase I inhibitor payload, we plan to initiate a first-in-human clinical trial in 2025. ” About ALE.P02 ALE.P02 is a first-in-class ADC designed by linking a tubulin inhibitor, a potent cancer drug, to our antibody that specifically targets a unique CLDN1 epitope exposed on cancer cells. This combination could be a powerful new tool to fight the many squamous cancers that overexpress CLDN1 with less toxicity than traditional cancer drugs. About Alentis Therapeutics Alentis Therapeutics, the CLDN1 company, is a clinical-stage biotech developing breakthrough treatments for CLDN1+ tumors and organ fibrosis. CLDN1 is a previously unexploited target that plays a key role in the pathology of cancer and fibrotic disease. Alentis is the leading company pioneering anti-CLDN1 antibodies and ADCs to modify and reverse the course of disease. Alentis was founded based on ground-breaking research in the laboratory of Prof. Thomas Baumert, MD at the University of Strasbourg and the French National Institute of Health and Medical Research (Inserm). Alentis is headquartered at the pharma-biotech hub in Basel, Switzerland with an R&D subsidiary in Strasbourg, France and clinical operations in the US. Visit www.alentis.ch SOURCE: Alentis Therapeutics

Lixudebart (ALE.F02) is a first-in-class monoclonal antibody in clinical development for multi-organ fibrosis BASEL, Switzerland--(BUSINESS WIRE)-- Alentis Therapeutics (“Alentis”), the clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, announced today that the U.S. Food and Drug Administration (FDA) has granted lixudebart (ALE.F02) Orphan Drug designation for the treatment of Idiopathic Pulmonary Fibrosis (IPF). Dr. Luigi Manenti, Chief Medical Officer of Alentis said, “The Orphan Drug designation for lixudebart underscores the urgent medical need for an effective IPF treatment. We have completed IND-enabling studies for our IPF program, and we strongly believe that targeting CLDN1 in fibrotic lungs with our highly specific antibody has the potential to reverse the course of the disease.” “IPF patients do not have transformative treatment options and often experience tolerability challenges with the current standard of care drugs. Alentis is doing important work on developing lixudebart as a treatment targeting the root causes of disease,” added Prof. Steven Nathan, Medical Director of the Advanced Lung Disease and Transplant Program at Inova Fairfax Hospital. “This molecule has shown a very favorable safety pro Phase 1, and I would be thrilled to see lixudebart tested in IPF patients in the future.” The FDA provides orphan status to drugs or biologics to prevent, diagnose or treat a rare disease or condition. Orphan Drug designation qualifies sponsors for certain incentives, including tax credits for qualified clinical trials, user-fee exemptions and a potential seven years of market exclusivity after approval. About lixudebart (ALE.F02) Lixudebart is a first-in-class monoclonal antibody developed for liver, lung and kidney fibrosis. The investigational antibody is designed to reverse organ fibrosis by specifically targeting a unique CLDN1 epitope exposed in fibrotic tissue. In Phase 1 single- and multiple-ascending dose studies in healthy volunteers lixudebart was observed to be well tolerated, with no serious safety concerns. Lixudebart is currently tested in clinical trials for advanced liver fibrosis (NCT05939947) and ANCA-associated vasculitis (NCT06047171). About IPF Idiopathic pulmonary fibrosis, or IPF, is a rare and serious chronic disease affecting tissue surrounding the air sacs or alveoli in the lungs, resulting in the thickening of lung tissue. Over time, this thickening causes permanent scarring of the lungs, called fibrosis, which makes breathing increasingly difficult. There is currently no cure for this condition with treatments only slowing the progression of IPF. About Alentis Therapeutics Alentis Therapeutics, the CLDN1 company, is a clinical-stage biotech developing breakthrough treatments for CLDN1+ tumors and organ fibrosis. CLDN1 is a previously unexploited target that plays a key role in the pathology of cancer and fibrotic disease. Alentis is the leading company pioneering anti-CLDN1 antibodies and ADCs to modify and reverse the course of disease. Alentis was founded based on ground-breaking research in the laboratory of Prof. Thomas Baumert, MD at the University of Strasbourg and the French National Institute of Health and Medical Research (Inserm). Alentis is headquartered at the pharma-biotech hub in Basel, Switzerland with an R&D subsidiary in Strasbourg, France and clinical operations in the US. Visit

Astellas Pharma’s path to winning the first drug approval for a particular promising gastrointestinal cancer target has hit a detour. The FDA turned down the drugmaker’s application, citing manufacturing issues for the therapy, zolbetuximab. Astellas announced the FDA action earlier this week. The company did not go into detail about the problems spotted by the regulator, but described them as “unresolved deficiencies following its pre-license inspection of a third-party manufacturing facility for zolbetuximab.” Astellas added that the agency did not raise any concerns about the safety or efficacy of the drug, nor is it asking for additional clinical data. Zolbetuximab was developed as a treatment for patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma that is negative for the cancer protein HER2. Cancers that express HER2 already have treatments, such as Herceptin from Genentech and Enhertu from partners AstraZeneca and Daiichi Sankyo. HER2-negative cancers have fewer treatment options. Astellas aims to offer one with zolbetuximab, which targets claudin 18.2, or CLDN18.2. This protein is found only in stomach cells and not in any other healthy tissues. That’s what makes it a promising target for drugs that treat gut cancers. The Astellas drug is a monoclonal antibody designed to target and bind to CLDN18.2 on the surface of cancerous gastric epithelial cells. Doing so is intended to kill the cancer cells by activating two different immune system pathways: antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Astellas added zolbetuximab to its pipeline through the 2016 acquisition of Germany-based Ganymede Pharmaceuticals for €422 million (about $462 million) up front. Zolbetuximab is a key piece of Astellas’s growth strategy. It’s important because it could help make up for coming revenue declines facing Xtandi, the drugmaker’s top-selling product that is facing patent expirations. Zolbetuximab is under regulatory review in other markets including Japan, Europe, and China. “We remain confident in zolbetuximab’s clinical profile and potential to fill a significant therapeutic gap for those diagnosed with advanced gastric or GEJ cancer whose tumors are CLDN18.2 positive,” Moitreyee Chatterjee-Kishore, Astellas senior vice president and head of immuno-oncology, said in a prepared statement. “Astellas is committed to working with the FDA and the third-party manufacturer to address the agency’s feedback, and to bringing zolbetuximab to U.S. patients in need, as soon as possible.” Several other companies are also developing CLDN18.2-targeting drugs. AstraZeneca’s early-stage program, licensed from KYM Biosciences last year, is part of the class of cancer therapies called antibody drug conjugates, or ADCs. Bristol Myers Squibb and Elevation Oncology are also in Phase 1 testing with their respective CLDN18.2-targeting ADCs. Merck KGaA holds an option to license a Jiangsu Hengrui Pharmaceuticals ADC for that target under a deal it struck with the China-based biotech last fall. Meanwhile, Alentis Therapeutics has two programs, an antibody and an ADC, each of them targeting the related claudin 1 protein.