Lisata Therapeutics, Inc. announced LSTA1 is an investigational drug designed to activate a novel uptake pathway that allows co-administered or tethered (i.e., molecularly bound) anti-cancer drugs to target and penetrate solid tumors more effectively. LSTA1 actuates this active transport system in a tumor-specific manner, resulting in systemically co-administered anti-cancer drugs more efficiently penetrating and accumulating in the tumor, while normal tissues are not expected to be affected. In preclinical models, LSTA1 has also shown the ability to modify the tumor microenvironment, thereby making tumors more susceptible to immunotherapies and inhibiting the metastatic cascade (i.e., the spread of cancer to other parts of the body).

Lisata and its development collaborators have amassed significant non-clinical data demonstrating enhanced delivery of a range of existing and emerging anti-cancer therapies, including chemotherapeutics, immunotherapies, and RNA-based therapeutics. To date, LSTA1 has also demonstrated favorable safety, tolerability and activity in completed and ongoing clinical trials designed to test its ability to enhance delivery of standard-of-care chemotherapy for pancreatic cancer. Currently, LSTA1 is the subject of multiple ongoing or planned Phase 1b/2a and 2b clinical studies being conducted globally in a variety of solid tumor types in combination with a variety of anti-cancer regimens.

These studies include: ASCEND: Phase 2b double-blind, randomized, placebo-controlled clinical trial evaluating LSTA1 in patients with metastatic Pancreatic Ductal Adenocarcinoma (?mPDAC?). The trial is being conducted at up to 40 sites in Australia and New Zealand led by the Australasian Gastro-Intestinal Trials Group in collaboration with the University of Sydney and with the National Health and Medical Research Council Clinical Trial Centre at the University of Sydney as the Coordinating Centre. Planned interim futility analysis by the IDMC received a positive outcome.

Cohort A has been fully enrolled. Total enrollment completion is projected for the second quarter of 2024; however, current total enrollment is at approximately 95% of target, so earlier total enrollment completion may be achieved. BOLSTER: Phase 2a double-blind, placebo-controlled, multi-center, randomized basket trial in the U.S., Europe, Canada, and Asia evaluating LSTA1 in combination with standards of care in advanced solid tumors including head and neck, esophageal and cholangiocarcinoma.

Enrollment is open and proceeding as planned. First patients have been treated in head and neck cancer as well as cholangiocarcinoma cohorts. CENDIFOX: Phase 1b/2a open-label trial in the U.S. of LSTA1 in combination with neoadjuvant FOLFIRINOX based therapies in pancreatic, colon and appendiceal cancers.

The trial continues to make steady progress with enrollment completion expected by the fourth quarter of 2023 and data readouts expected in 2024. LSTA1 is currently being evaluated in combination with gemcitabine and nab-paclitaxel in a Phase 1b/2a open-label trial in China led by Qilu Pharmaceutical. During the 2023 ASCO Annual Meeting, Qilu Pharmaceutical presented an abstract sharing preliminary data from the study which, thus far, has corroborated previously reported findings from the phase 1b/2a trial of LSTA1 plus gemcitabine and nab-paclitaxel conducted in Australia in patients with mPDAC.

Final data is expected by the end of the second quarter of 2024. iLSTA: Phase 1b/2a randomized, single-blind, single-center, safety and pharmacodynamic trial in Australia evaluating LSTA1 in combination with the checkpoint inhibitor, durvalumab, plus standard-of-care chemotherapy, nab-paclitaxel, and gemcitabine, versus standard-of-care alone in patients with locally advanced non-resectable PDAC. Enrollment completion is expected by the end of the second quarter of 2024.

The Company will soon initiate the study of LSTA1 in combination with temozolomide in Glioblastoma Multiforme (?GBM?). This study is designed as a Phase 2a double-blind, placebo-controlled, randomized, proof-of-concept study evaluating LSTA1 when added to standard of care (?SoC?) temozolomide versus temozolomide and matching LSTA1 placebo in subjects with newly diagnosed GBM. It will be conducted across multiple sites in Estonia and Latvia and is targeted to enroll 30 patients with a randomization of 2:1 LSTA1 + SoC versus Placebo + SoC.

Target for the first patient treated is in the fourth quarter of 2023. Importantly and as the Company recently announced, LSTA1 has been granted orphan drug designation by the U.S. FDA for malignant glioma. This action by the FDA not only highlights the unmet medical need but also recognizes the potential of LSTA1 to benefit patients in this indication.

Lisata will also soon initiate a study of LSTA1 in combination with HIPEC interoperative intraperitoneal lavage in peritoneal carcinomatosis, a condition which develops as a result of the contiguous spread of primary cancers such as ovarian, colorectal and appendiceal along the peritoneum. The study is a Phase I single-center, unblinded, randomized controlled trial to determine the safety and tolerability of LSTA1 administered intraperitoneally in patients with peritoneal metastases from colorectal, appendiceal, or ovarian cancer undergoing Cytoreductive Surgery (?CRS?) and HIPEC. Twenty-one total participants will be randomized 2:1 to receive LSTA1 with HIPEC versus HIPEC alone after CRS.

We anticipate the first patient treated to be in the fourth quarter of 2023.