ALE.P02 Gains FDA Fast Track Status in CLDN1+ Solid Tumors
The FDA granted fast track designation to ALE.P02, an antibody-drug conjugate targeting Claudin-1 (CLDN1), for use in patients with advanced/metastatic CLDN1-positive squamous solid tumors.
- The FDA has granted fast track designation to ALE.P02 for treating patients with Claudin-1 (CLDN1)-positive squamous solid tumors.
- ALE.P02 is an anti-CLDN1 antibody-drug conjugate (ADC) and the first of its kind to enter the clinic.
- A phase 1/2 trial is planned to assess the agent in patients with advanced or metastatic CLDN1-positve squamous solid tumors.
ALE.P02, an anti-CLDN1 ADC, has been granted FDA fast track designation for the potential treatment of patients with CLDN1-positive squamous solid tumors.1
“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, in a press release. “CLDN1 is an exciting new target for ADCs, and Alentis [Therapeutics] has been the frontrunner in developing anti-CLDN1 therapeutics.”
The agent is a first-in-class ADC that works by linking a tubulin inhibitor with an antibody that is designed to target the CLDN1 epitope, which is expressed on cancer cells. By targeting CLDN1 which is overexpressed in certain squamous solid tumors, ALE.P02 may offer a less toxic alternative to traditional anticancer therapies.1
In healthy cells, CLDN1 is hidden in tight junctions, and its normal function is to bind with other healthy cells.2 However, solid tumors can overexpress CLDN1, where it is exposed outside of the normal junctions. This makes CLDN1 a potential tumor target since it can be recognized by the anti-CLDN1 antibody on tumor cells without affecting healthy tissue.
Cancer detection and screening as a treatment for malignant cells with a biopsy or testing caused by carcinogens and genetics with a cancerous cell as an immunotherapy symbol: © freshidea - stock.adobe.com
In October 2024, an investigational new drug (IND) application for ALE.P02 was cleared by the FDA, allowing for the start of a first-in-human phase 1/2 trial. This study, which is planned to begin in the first quarter of 2025, is evaluating ALE.P02 in patients with CLDN1-positive squamous solid tumors.3
Aside from ALE.P02, Alentis Therapeutics is developing ALE.P03, a similar ADC that utilizes a CLDN1-targeting antibody to selectively bind and internalize into CLDN1-positive tumor cells. While ALE.P02 is linked to a potent cytotoxic payload, ALE.P03 is conjugated to a topoisomerase I inhibitor.2
In preclinical studies, promising results have been observed for both ADCs. In vivo models demonstrated significant tumor growth inhibition and complete tumor regression with single-dose administration of either ALE.P02 or ALE.P03. Currently, good laboratory practice toxicology studies are underway for ALE.P03 to assess its safety profile.2
“We are encouraged by the FDA’s recognition of ALE.P02’s potential as a treatment for CLDN1-positive squamous cancers,” said Roberto Iacone, chief executive officer of Alentis Therapeutics, in the press release.1 “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.”
“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,” added Luigi Manenti, chief medical officer of Alentis Therapeutics, in the press release. “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.”
REFERENCES
Alentis receives FDA fast track designation for ALE.P02 for the treatment of CLDN1+ squamous solid tumors. News release. Alentis Therapeutics. November 18, 2024. Accessed November 19, 2024. https://tinyurl.com/bdpyr2zh
ALE.P02 & ALE.P03 ADCs for Claudin-1 positive tumors. Alentis Therapeutics. Accessed November 19, 2024. https://alentis.ch/ale-p02-ale-p03-adcs-for-claudin-1-positive-tumors/
Alentis Therapeutics receives FDA IND clearance for ALE.P02, a novel CLDN1-ADC for the treatment of squamous cancers. News release. October 2, 2024. Accessed November 19, 2024. https://tinyurl.com/2542u7uj
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