Alentis Therapeutics' investigational antibody-drug conjugate (ADC) ALE.P02, which targets anti-claudin-1 (CLDN1), has received Fast Track designation from the FDA for the treatment of advanced or metastatic CLDN1+ squamous cancers, regardless of the organ of origin. This designation aims to expedite the development and review of ALE.P02, potentially offering a new treatment option for lung, head and neck, cervical, and esophageal CLDN1+ squamous cancers, among others.
Tony Mok, a professor of Clinical Oncology at the Chinese University of Hong Kong, noted, "Squamous cancers of various origin have been shown to overexpress CLDN1, making ALE.P02 a promising ADC to address the unmet medical needs of these patients. CLDN1 is an exciting new target for ADCs and Alentis has been the frontrunner in developing anti-CLDN1 therapeutics."
Mechanism of Action
ALE.P02 is a first-in-class ADC comprising a tubulin inhibitor linked to an antibody designed to target a unique CLDN1 epitope exposed on cancer cells. This combination aims to selectively attack squamous cancers that overexpress CLDN1, potentially reducing toxicity compared to standard cancer drugs. ADCs like ALE.P02 can selectively target and kill tumor cells, differing from chemotherapy and other cancer drugs that often exhibit low specificity and cause substantial toxicity to healthy tissues.
In healthy cells, CLDN1 is typically hidden within tight junctions, where it functions to bind with other healthy cells. However, solid tumors can overexpress CLDN1, exposing it outside of these normal junctions. This allows the anti-CLDN1 antibody in ALE.P02 to recognize and bind to tumor cells without impacting healthy tissue, making CLDN1 a promising tumor target.
Clinical Development
The FDA cleared an investigational new drug (IND) application for ALE.P02 in October 2024, enabling the initiation of a first-in-human phase 1/2 trial. This trial, expected to begin in the first quarter of 2025, will assess the safety and efficacy of ALE.P02 in individuals with CLDN1-positive squamous solid tumors.
Luigi Manenti, chief medical officer of Alentis, stated, "We are optimistic about the potential of ALE.P02 and look forward to the start of our first-in-human clinical trial in Q1 2025."
Additional Pipeline ADC: ALE.P03
Alentis Therapeutics is also developing ALE.P03, another ADC similar to ALE.P02, which utilizes a CLDN1-targeting antibody to selectively bind and internalize into CLDN1-positive tumor cells. However, ALE.P03 is engineered with a topoisomerase I inhibitor ADC, whereas ALE.P02 uses a tubulin inhibitor ADC. Preclinical trials have demonstrated selective binding and internalization in CLDN1+ tumor cells, leading to strong tumor growth inhibition across different tumor models with CLDN1 expression levels in vivo for both ALE.P02 and ALE.P03. Toxicology studies for ALE.P03 are currently ongoing.
Roberto Iacone, chief executive officer of Alentis Therapeutics, commented, "We are encouraged by the FDA’s recognition of ALE.P02’s potential as a treatment for CLDN1+ squamous cancers. It reflects the importance of advancing ALE.P02 through clinical development, and it brings us one step closer to providing a new treatment option for patients."
