Aug 01, 2023

Lift Biosciences Looks to Outlicense Cell Therapy Platform to Partners After Preclinical Findings

NEW YORK – Lift Biosciences said on Thursday that following encouraging preclinical results it will begin discussing licensing deals with biopharma companies for its N-LiFT platform for producing genetically engineered CAR-IMANs.

The platform that London-based Lift is developing — dubbed Neutrophil Only Leukocyte Infusion Therapy, or N-LIfT — involves producing different immunomodulatory alpha neutrophils (IMANs) to kill cancer cells in two ways, both directly and by recruiting the patients' own immune cells. To accomplish the latter, the IMANs are designed to change the tumor microenvironment into "hot" tumors.

On Thursday, Lift said it had successfully added a HER2-targeted chimeric antigen receptor to its IMANs, which it says resulted in a four-fold increase in cancer cell killing compared to unmodified IMANs. In preclinical studies on ex-vivo patient tumoroid models, even the unmodified IMANs demonstrated cell killing in difficult-to-treat solid tumors such as pancreatic, lung, gastric, and rectal cancers, according to Lift.

Based on the enhanced results seen when adding the HER2 CAR, Lift is talking with biopharma companies to license the platform, which it said could be used to produce "a whole new type of cell therapy platform for [those companies'] own CAR assets."

To be eligible for the HER2 CAR-IMAN, patients will ultimately need to be tested for HER2 expression, Lift CEO Alex Blyth said in an email, adding that HER2 is just one example of a CAR Lift the company will use with this approach. "We can use many different CARs to try and cover all patients and will use CARs with partners based on their targets," he said.

Lift's own internal CAR program is focused on the HER2 CARs as well as mesothelin-directed CARs, which are two targets Lift chose to cover a broad patient population, according to Blyth. Around half of non-small cell lung cancer patients express mesothelin and another third express HER2, he said.

Because of the way that the CAR-IMANs work, by directing the immune system to attack the cancers rather than only attacking the cancers themselves, Blyth clarified further that "unlike CAR T-cell therapies, IMANs' success is not completely dependent on these antigens' overexpression," but the antigen overexpression "just helps to accelerate their activation if it is present."

"We anticipate that we will be assessing patients' tumor expression of these antigens to determine which CAR-IMAN is most suitable," Blyth said. The firm is also considering using patient-derived tumoroids to test the IMAN therapies ex vivo to determine patients' likelihood of response. Because neutrophils are known to rapidly attack these types of patient models, Blyth said the tumoroid approach is "well-suited as a patient stratification tool."