Dr. Kristen Buck
Analyst · WBB Securities
Thank you, James, and good morning, everyone. As those that follow us know, Lisata's pipeline is built on a portfolio of proprietary and patented technology that is grounded in strong scientific rationale and a body of published preclinical and early clinical data. Our platform technology is designed to address major impediments to the successful treatment of advanced solid tumors in the context of increasing pharmacoeconomic pressures on the health care system. We appreciate the critical importance of generating meaningful clinical data to advance our platform technology, and I can assure you that our entire organization has this goal top of mind in everything we do. With that, I will now provide an overview of our lead product candidate, LSTA1, LSTA1, for the treatment of advanced solid tumors in combination with other anticancer agents. Despite advances in cancer therapy today, many solid tumors remain difficult to effectively treat. Cancers, such as pancreatic cancer, gastric cancers and other solid tumor cancers are surrounded by a dense fibrotic tissue known as the Stroma, which limit the access of most pharmacotherapies to the tumor. Many tumors also exhibit a hostile tumor microenvironment, or TME, which suppresses the patient's immune system and makes it less effective in fighting cancer. The combination of dense stroma on a hostile tumor microenvironment negatively impacts the ability of many cytotoxic agents and immunotherapies to effectively treat these cancers. This coupled with the fact that most anticancer therapies are not efficient in targeting only cancer tissue defines the major challenge of maximizing effectiveness and safety in the treatment of solid tumors. To combat this, Lisata's approach is to activate the C-end rule, or CendR system, a naturally occurring active transport system to selectively deliver anticancer drugs through the stroma and into the tumor. Lisata's lead product candidate, LSTA1 is an investigational drug that actuates the CendR active transport mechanism while also having the potential to modify the tumor microenvironment and make it less immunosuppressive. LSTA1 targets tumor vascular endothelial cells as well as tumor cells themselves based on its affinity for alpha v beta three and beta five integrins that are upregulated on these cells but not on healthy tissue. LSTA1 is a 9-amino acid cyclic internalizing RGD peptides that once found in these integrins, is cleaved by protease. Protease is expressed in the tumor microenvironment to release a peptide fragment called the CendR Fragment. The CendR fragment then has high affinity for and binds to an adjacent receptor called neuropilin-1 also upregulated on tumor endothelial and tumor cells to activate the Cend C-end rule active transport pathway and bury anticancer drugs more efficiently into solid tumors. Additionally, LSTA1 one has been shown in a range of preclinical models to modify the tumor microenvironment, making it less hostile to immune cells and adding to the efficacy of anticancer drugs used against solid tumors. These results come internally from Lisata and from collaborators and research groups around the world and have been the subject of over 300 scientific publications. Along with our collaborators, we have amassed significant nonclinical data, demonstrating enhanced delivery of a range of emerging anticancer therapy, including immunotherapy and RNA-based therapeutics. Clinically, LSTA1 has demonstrated favorable safety, tolerability and activity to enhance delivery of standard of care chemotherapy for patients with metastatic pancreatic cancer. Our development programs are designed to exploit the potential of LSTA1 to enhance a variety of anticancer treatment modality in a range of solid tumors. Currently, LSTA1 is the subject of about a dozen plans for active clinical trials globally for the treatment of various solid tumors. Let me touch on a few of these individually. The ASCEND trial is a 155 patients, double-blind, randomized, placebo-controlled clinical trial evaluating LSTA1 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma. The trial is being conducted at up to 40 sites in Australia and New Zealand led by the Australasian Gastro-Intestinal Cancer Trials Group or AGITG, in collaboration with the NHMRC clinical trial center at the University of Sydney. We originally projected enrollment completion by the second quarter of 2024. However, with the study nearly 75% enrolled, we could achieve last patient in sooner than that. Just recently, we, along with our clinical research partner, Warpnine treated our first five patients in the iLSTA1 trial in Australia, evaluating LSTA1 in combination with standard of care chemotherapy that is gemcitabine and nab-paclitaxel chemotherapy and immunotherapy using durvalumab as a first-line treatment in locally advanced non-resectable pancreatic ductal adenocarcinoma. This is the first of several planned trials in which we are expanding the study of LSTA1's impact on existing therapies to include immunotherapies. We also expect enrollment completion in this trial by the second quarter of 2024. The Company's BOLSTER trial of LSTA1 is a Phase IIa placebo-controlled basket trial in the United States, Europe, Canada and Asia, evaluating LSTA1 in combination with standards of care in solid tumors, including head and neck, esophageal and cholangiocarcinoma. This trial includes both cytotoxins and immunotherapy standards of care. Enrollment is now open. However, we, like many others, are being impacted by the global cisplatin shortage, which is part of the standard of care regimen for cholangiocarcinoma patients. This has led to severe shortages of the drug, long delays in obtaining any available material and unfortunately price gouging by some suppliers resulting in prices reaching hundreds of times of what cisplatin would normally cost. Despite these challenges, our team has identified and secured a supply of cisplatin, sufficient to the needs of the BOLSTER trial, and we expect this material in our hands and available to patients in our studies within about one month. Once this requirement -- this required component of Bolsters protocol is at the investigational sites, we look much forward to announcing the first patient treated in the cholangiocarcinoma arm. Next is the CENDIFOX trial, a Phase Ib/IIa open-label trial of LSTA1 in combination with neoadjuvant folfirinox based therapies in pancreatic, colon and appendiceal cancers. It continues to make steady progress with approximately 80% of the study enrolled. We expect enrollment completion by the fourth quarter of this year with data readout in 2024. This trial will provide us with post treatment biopsy immuno-profiling data as well as long-term outcome data. LSTA1 is also currently being evaluated in combination with gemcitabine and nab-paclitaxel in a Phase Ib/IIa open trial -- open-label trial in China, led by our licensee in that territory, Qilu Pharmaceutical. During the 2023 ASCO Annual Meeting, Qilu Pharmaceutical presented an abstract during preliminary data from the study, which corroborated previously reported findings from the Phase Ib/IIa trial of LSTA1 plus gemcitabine and nab-paclitaxel conducted in Australia in patients with metastatic pancreatic ductal adenocarcinoma. Final data are expected by the end of the second quarter of 2024. iGoLSTA, a Phase Ib/IIa proof-of-concept, safety and early efficacy studies, evaluating LSTA1 in combination with nivolumab and FOLFIRINOX as a first-line treatment in locally advanced non-resectable gastroesophageal adenocarcinoma, is still pending initiation as a function of availability of funding by our partner, WARPNINE. We hope to have further update on timing related to the execution of the study by the end of the third quarter of this year. In addition to the ongoing clinical trials I just mentioned, we also plan to have other studies up and running in the next few months, including LSTA1 in combination with temozolomide in Glioblastoma Multiforme, commonly known as GBM. This study is designed as a Phase IIa double-blind, placebo-controlled randomized proof-of-concept study evaluating LSTA1 when added to standard of care Temozolomide versus temozolomide and matching LSTA1 placebo in patients with newly diagnosed Glioblastoma Multiform. It will be conducted across multiple sites in Estonia and Latvia, and it is targeted to enroll 30 patients with the randomization of 2:1, LSTA1 plus standard of care versus placebo plus standard of care. Target for first patient treated is in the fourth quarter of 2023. Importantly, and as recently announced, LSTA1 has been granted orphan designation by the U.S. Food and Drug Administration for malignant glioma. This action by FDA not only highlights the unmet medical need but also recognizes the potential of LSTA1 to benefit patients in this indication. Lastly, we are planning to study LSTA1 in combination with hyperthermic intraperitoneal chemotherapy or commonly referred to as HIPEC, delivered via intraoperative intraperitoneal lavage in peritoneal carcinomatosis, a cancer that develops as a result of the contiguous spread of primary cancers such as ovarian, colorectal and appendiceal along the peritoneal layer. The study will be a Phase I single-center unblinded randomized controlled trial to determine the safety and tolerability of LSTA1, administer intraperitoneal in patients with currently on metastasis for colorectal, appendiceal or ovarian cancer undergoing cytoreductive surgery and HIPEC. 21 total patients will be randomized 2:1 to receive LSTA1 with HIPEC versus HIPEC alone after cytoreduction surgery. We anticipate that this study will also be up and running in the fourth quarter of 2023 and the first patient being treated shortly thereafter. For those who are interested, a more complete description of our trials is available in the Appendix section on the corporate presentation on our website. Additionally, in the body of the presentation, there are two milestone slides that displays the anticipated timing of key execution milestones and data readouts for the clients. With that, I will now turn the call back to Dave.