The FDA has granted Fast Track designation to Alentis Therapeutics' ALE.P02, an anti-Claudin-1 (CLDN1) antibody-drug conjugate (ADC), for the potential treatment of patients with CLDN1-positive squamous solid tumors. This designation aims to expedite the development and review of ALE.P02, addressing an unmet medical need in patients with serious or life-threatening conditions.
ALE.P02 is a first-in-class ADC that features a tubulin inhibitor linked to an antibody specifically targeting the CLDN1 epitope expressed on cancer cells. CLDN1 is often overexpressed in squamous solid tumors, making it a promising target for ADCs. By targeting CLDN1, ALE.P02 could offer a less toxic treatment option compared to traditional anticancer therapies.
Rationale for CLDN1 Targeting
In healthy cells, CLDN1 is typically hidden within tight junctions, where it functions to bind with other healthy cells. However, in solid tumors, CLDN1 can be overexpressed and exposed outside of these normal junctions. This aberrant expression makes CLDN1 a potential tumor target, as it can be recognized by the anti-CLDN1 antibody on tumor cells without affecting healthy tissue.
Clinical Development and Preclinical Data
The FDA cleared the 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 launch in the first quarter of 2025, will evaluate the ADC in patients with CLDN1-positive squamous solid tumors.
Preclinical data for ALE.P02 has demonstrated selective binding to and internalization by CLDN1-positive tumor cells, leading to inhibited tumor growth across various tumor models. In patient-derived xenograft models, a single dose of ALE.P02 resulted in complete tumor regression compared to a control ADC. Alentis Therapeutics is also developing another CLDN1-directed ADC, ALE.P03, which uses a topoisomerase I inhibitor as its payload.
Expert Commentary
"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," said Tony S. K. Mok, MD, professor of clinical oncology at the Chinese University of Hong Kong. "CLDN1 is an exciting new target for ADCs, and Alentis has been the frontrunner in developing anti-CLDN1 therapeutics."
Roberto Iacone, chief executive officer of Alentis Therapeutics, stated, "We are encouraged by the FDA’s recognition of ALE.P02’s potential as a treatment for CLDN1-positive 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."
Luigi Manenti, chief medical officer of Alentis Therapeutics, added, "We have set out to develop ALE.P02 in the most rational way, following CLDN1 science and the clinical understanding of squamous cancers. The FDA’s support in this endeavor is certainly motivating. We are optimistic about the potential of ALE.P02 and look forward to the start of our first-in-human clinical trial in the first quarter of 2025."
