FDA Grants Fast Track Designation to ALE.P02 for CLDN1+ Squamous Solid Tumors

The FDA has granted fast track designation to the anti–Claudin-1 (CLDN1) antibody-drug conjugate (ADC) ALE.P02 as a potential therapeutic option for patients with CLDN1-positive squamous solid tumors.¹

The first-in-class ADC features a tubulin inhibitor that is linked to an antibody designed to specifically target the CLDN1 epitope expressed on cancer cells. By targeting CLDN1 that is overexpressed in some squamous solid tumors, the agent could represent a less toxic treatment option compared with traditional anticancer therapies.

“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,” Tony S. K. Mok, MD, professor of clinical oncology at the Chinese University of Hong Kong, stated in a news release. “CLDN1 is an exciting new target for ADCs, and Alentis [Therapeutics] has been the frontrunner in developing anti-CLDN1 therapeutics.”

In October 2024, the FDA issued clearance for an investigational new drug (IND) application for ALE.P02, which enabled the initiation of a first-in-human phase 1/2 trial evaluating the ADC in patients with CLDN1-positive squamous solid tumors.² The trial is expected to launch in the first quarter of 2025.

Fast track designation is intended to expedite the development and review of drugs meant for patients with serious or life-threatening conditions that could address an unmet medical need.¹

“We are encouraged by the FDA’s recognition of ALE.P02’s potential as a treatment for CLDN1-positive squamous cancers,” Roberto Iacone, chief executive officer of Alentis Therapeutics, stated in a news release. “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.”

In healthy cells, CLDN1 is hidden in tight junctions, and its normal function is to bind with other healthy cells.³ 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.

Alentis Therapeutics is currently developing 2 CLDN1-directed ADCs: ALE.P02 and ALE.P03. Similar to ALE.P02, ALE.P03 features a CLDN1-targeting antibody; however, the antibody is linked to a topoisomerase I inhibitor in this ADC.

Preclinical data for both agents demonstrated that the ADCs selectively were able to bind to and internalize CLDN1-positive tumor cells, which inhibited tumor growth across tumor models and generated CDLN1-expression levels in vivo. A single dose of ALE.P02 or ALE.P03 led to complete tumor regression in patient-derived xenograft models in vivo compared with a control ADC.

Good laboratory practice toxicology studies are ongoing for ALE.P03.

“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,” Luigi Manenti, chief medical officer of Alentis Therapeutics, added in a new release.¹ “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

1. 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://alentis.ch/alentis-receives-fda-fast-track-designation-for-ale-p02-for-the-treatment-of-cldn1-squamous-solid-tumors/
2. 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://alentis.ch/alentis-therapeutics-receives-fda-ind-clearance-for-ale-p02-a-novel-cldn1-adc-for-the-treatment-of-squamous-cancers/
3. 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/