Kristen Buck
Analyst · WBB Securities
Thank you, James, and good afternoon, everyone. As I've mentioned many times in the past, Lisata's development programs are built upon a strong foundation of published preclinical and early clinical research. Notably, our CendR Platform technology is rooted in pioneering discoveries recognized by the Lasker Prize awarded to Dr. Erkki Ruoslahti. A product of the CendR Platform, Certepetide is designed to address the major impediments to the successful treatment of advanced solid tumors. This is especially relevant in an environment of increasing prevalence of these cancers and growing pharmacoeconomic pressures. Our clinical studies have been rigorously designed with the end in mind, that is eventual product registration and are optimized to generate clinically meaningful unambiguous data. As such, unlike many studies at a similar stage of development, our studies are placebo controlled, appropriately sized and employee primary end points that are preferred by regulatory authorities in support of pivotal trials. Further, our trials evaluate Certepetide in combination with current standard-of-care therapies to allow for clear discernment of treatment effect and to fit with current treatment practices at clinical sites. These strategic design choices are not always the least expensive, but they do afford us the most scientifically rigorous methodology by which to generate clinically meaningful data as efficiently and rapidly as possible. This is in keeping with our development mantra of do the last experiment first to avoid time and capital consumption on work that could become unnecessary. We have also devised and implemented a regulatory strategy that optimizes Certepetide's regulatory review and future commercialization. This strategy includes obtaining special regulatory designations that afford us priority reviews and the possibility of accelerated approvals. However, before I get to the specifics of each of the clinical studies in our development portfolio, please allow me to summarize some important background information, especially for those who are listening for the first-time. Despite advances in cancer therapy, including CAR-T cell therapy and immunotherapy, many solid tumors are still associated with poor outcomes for patients. Cancers, such as pancreatic cancer, gastric cancers, glioblastoma multiform and other solid tumors are surrounded by a dense fibrotic tissue known as the stroma, which limits access of most pharmacotherapies to the tumor. In addition, many subtle tumors also present a hostile tumor microenvironment, or TME, which suppresses the patient's immune system and makes it less effective in fighting cancer. The combination of a dense stroma and a hostile tumor microenvironment prevents many chemotherapy and immunotherapies from being optimally effective in treating 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, our investigational product, Certepetide leverages the naturally occurring CendR active transport system to provide an innovative approach to the selective delivery of anticancer drugs through the tumor stroma and directly into the tumor. Simultaneously, Certepetide has been shown to modify the tumor microenvironment, making it less immunosuppressive, and therefore, increasing the tumor susceptibility to immunotherapy while also inhibiting the metastatic cascade. Certepetide is a 9 amino acid cyclic peptide with high binding affinity and specificity for alpha v beta 3 and beta5 integrin receptors, which are significantly upregulated on tumor vascular endothelial cells and tumor cells themselves, but not on healthy tissue. Once bound to these integrins, Certepetide is subjected to proteolytic cleavage by enzymes naturally occurring in the tumor microenvironment to produce two linear fragments, one of which is a 5 amino acid CendR peptide fragment. Upon association of the CendR fragment from the integrin receptor, it binds to another receptor called neuropilin-1 on the same or a nearby cell. Once neuropilin-1 is activated, it actuates the CendR active transport mechanism, which is manifested by the formation of microvesicles at the surface of the cells. These microvesicles encapsulate any co-administered anticancer drugs, unbound Certepetide and CendR fragments in the circulatory system and ferry them through the stroma and vasculature into the tumor. Certepetide's mechanism of action is agnostic to the modality of the companion anticancer drugs with which it is administered and can be combined with a wide range of existing or even emerging anti-cancer therapies, including chemotherapies, immunotherapies and RNA-based therapies. Additionally, as I previously mentioned, Certepetide has been shown in a range of preclinical models to modify the tumor microenvironment, making it less hostile to immune cells, reducing tumor resistance to anticancer medications, and impeding and/or preventing the metastatic cascade. These results come from Lisata sponsored studies and from collaborators and research groups around the world and have been the subject of more than 350 scientific publications relevant to Certepetide's mechanism of action. Along with our collaborators, we also have amassed significant non-clinical data demonstrating enhanced delivery and augmented efficacy of a range of anticancer therapy modalities, including chemotherapies, immunotherapies, RNA-based therapeutics and even cell therapies. To date, Certepetide has also demonstrated favorable clinical safety, tolerability and activity to enhance delivery of standard-of-care chemotherapy for patients with metastatic pancreatic cancer. In addition, our strategic focus on regulatory optimization has yielded significant results as evidenced by multiple special designation awarded to Certepetide. To-date, Certepetide is the recipient of a fast track designation by the FDA, which affords us more frequent interactions with the FDA and the ability to submit NDA components early for a rolling review. Certepetide will also be eligible for accelerated approval and priority review if relevant criteria are met. Further, Certepetide has received multiple orphan drug designations, including one for pancreatic cancer, in both the United States and Europe, as well as for malignant glioma in the U.S. orphan drug designation. Orphan Drug designation affords Lisata exemption from FDA user fees and provides extended market exclusivity as well as other potential sponsor benefits. In just the first half of 2024, Certepetide has not only been granted a pediatric investigation plan waiver by the EMA for the treatment of pancreatic cancer, but has also received an orphan designation and a rare pediatric disease designation for osteosarcoma in the United States. For background, the FDA defines rare pediatric diseases, as diseases with fewer than 200,000 cases in the United States that are serious or life threatening and primarily affect individuals under 18 years of age. This program is set to expire on September 30, 2024. However, our expectation and the expectation of many in the industry is that the program will be reauthorized. We will, of course, be monitoring those developments closely. A substantial benefit under the current Rare Pediatric Disease Designation program is receipt of a priority Review Voucher, often referred to as a golden ticket once the FDA approves the new drug application, or NDA for the product and indication having received the designation. Vouchers are especially valuable as they can be used to compel a priority review of an additional NDA or biologic license application for another product or indication reducing the standard review time of approximately 10 months to six months. The voucher may be used by the sponsor or sold to another sponsor for their use. Priority Review Vouchers have sold for as much as $350 million historically and more recently have sold for $75 million to $100 million. Overall, our development strategy includes the pursuit of a rapid Certepetide registration for the treatment of pancreatic cancer. Alongside studies, which further exploit Certepetide's ability to enhance a variety of anticancer treatments in a range of advanced solid tumors. To this end, Certepetide is currently the subject of nearly a dozen planned or active clinical trials globally for the treatment of various solid tumors. For example, the ASCEND trial is a 158 patient, double-blind, randomized, placebo-controlled clinical trial evaluating Certepetide in combination with standard of care gemcitabine and nab-paclitaxel chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma or mPDAC. The trial is being conducted at 25 sites in Australia and New Zealand, led by the Australasian Gastro-Intestinal Trial Group or AGITG, in collaboration with the NHMRC clinical trial center at the University of Sydney. The study consists of two cohorts. Cohort A of the study received a single dose of 3.2 milligram per kilogram Certepetide, essentially simultaneously with standard-of-care. While Cohort B is identical to Cohort A, but with a second dose of 3.2 milligram per kilogram Certepetide given 4 hours after the first. As previously reported, a positive outcome from the planned interim futility analysis in 2023 was announced by the study's independent Data Safety Monitoring Committee, which recommended continuation of the study without modification. With trial enrollment completed in the fourth quarter of 2023, we expect top line data from the 95 patients assigned to Cohort A of the study to be reported in the fourth quarter of 2024 and the complete data set of all 158 patients from the study to be available by mid-2025. The prospect of positive data is encouraging, and we have begun planning the subsequent development steps. For example, we have already received an opinion from the Therapeutic Goods Administration, or TGA, which is the Medicine and Therapeutic Goods Regulatory Agency of the Australian Government that they believe positive data from the ASCEND Cohort A in conjunction with our Phase 1b/2a data could warrant submission of an application for provisional determination, the Australian version of a conditional approval. We expect similar discussions with the FDA and EMA once the data are in hand. We have already anticipated and designed the required Phase 3 study that will be necessary to maintain a conditional approval and support a full registration once completed. The ASCEND data anticipated this year will further inform and optimize our proposed Phase 3 clinical program in metastatic pancreatic cancer. The BOLSTER trial is our Phase 2a double-blind placebo-controlled multicenter randomized trial in the United States evaluating Certepetide in combination with standard of care in first-line cholangiocarcinoma. As we have reported recently, Lisata achieved complete enrollment in this study nearly six months ahead of plan, accelerating top line data readout to mid-2025. Based on this rapid enrollment rate and the pressing need to improve treatment outcomes in patients that have progressed after first-line treatment, a second cohort of patients has been added to the BOLSTER trial, evaluating subjects in second-line cholangiocarcinoma, and we expect to enroll the first patient by the fourth quarter of 2024. CENDIFOX is a Phase 1b/2a open-label trial in the United States evaluating Certepetide in combination with neoadjuvant FOLFIRINOX based therapies in pancreatic, colon and appendiceal cancers. The trial has completed enrollment in the pancreatic cohort and remains on track to complete enrollment in the remaining two cohorts by the end of 2024. Qilu Pharmaceutical, the licensee of Certepetide in the Greater China territory is also currently evaluating Certepetide in combination with gemcitabine and nab-paclitaxel as a treatment for metastatic pancreatic cancer. During the 2023 ASCO Annual Meeting, Qilu Pharmaceutical presented an abstract sharing preliminary data from the study, which corroborated previously reported findings from the Phase 1b/2a trial of Certepetide plus gemcitabine and nab-paclitaxel conducted in Australia in patients with pancreatic cancer. Additionally, Qilu has begun treating patients in their Phase 2 placebo-controlled trial in metastatic pancreatic cancer. The study is planned to take approximately 18 months to complete enrollment accrual and another 13 months for patient follow-up and data analysis and reporting. In collaboration with our funding partner, WARPNINE, the iLSTA trial is a Phase 1b/2a randomized, placebo-controlled single-blind, single-center safety, early efficacy and pharmacodynamic trial in Australia. This three cohort study is evaluating Certepetide in combination with the checkpoint inhibitor, durvalumab plus standard of care gemcitabine and nab-paclitaxel chemotherapy versus Certepetide in combination with standard of care alone versus standard of care alone in patients with locally advanced nonresectable pancreatic cancer. Enrollment completion is expected in the second half of 2024. iGoLSTA, a Phase 1b/2a proof-of-concept safety and early efficacy study evaluating Certepetide in combination with nivolumab and FOLFIRINOX as a first-line treatment in locally advanced nonresectable gastroesophageal adenocarcinoma is pending initiation as a function of availability of funding by our partner, WARPNINE. The inspiration for this study actually comes from the findings recently published in the oncology and cancer case reports Journal, which details a patient with metastatic gastroesophageal adenocarcinoma, who achieved a complete response when given Certepetide in combination with standard of care, FOLFIRINOX and pembrolizumab. The subject initially underwent months of standard of care treatment and only achieved a partial response. Upon the subsequent addition of Certepetide to the existing standard of care therapeutic regimen, the subject achieved a complete response, confirmed both radiographically and surgically. Remarkably and thankfully, the subject remains healthy since achieving complete response in February of 2023. We hope to provide an update on timing related to the execution of the iGoLSTA study in coming quarters. A study of Certepetide in combination with temozolomide in Glioblastoma multiform or GBM, has been initiated with several patients already enrolled and treated. This study is designed as a Phase 2a double-blind placebo-controlled randomized proof-of-concept study evaluating Certepetide when added to standard of care temozolomide versus temozolomide alone and matching Certepetide placebo in subjects with newly diagnosed GBM. This actively enrolling study is being conducted across multiple sites in Estonia and Latvia, and is targeted to enroll 30 patients with a randomization of 2:1 Certepetide plus standard of care versus placebo plus standard of care. FORTIFIDE is a Phase 1b/2a double-blind, placebo-controlled three arm randomized study in the United States, evaluating the safety, tolerability and efficacy of a 4 hour continuous infusion of Certepetide in combination with standard of care in patients with second-line metastatic pancreatic cancer who have progressed on first-line FOLFIRINOX. As part of this study, we have engaged Haystack Oncology to use their MRD technology to measure circulating tumor DNA levels at multiple time points in patients throughout the study as an exploratory endpoint for analyzing the early therapeutic effect of Certepetide. We expect to enroll the first patient in this study by the first half of 2025. On top of the previously described studies, we are exploring additional trials supporting our general development strategy. However, we remain steadfast in only starting trials that can be funded through data and trials that can be executed within a reasonable period of time. Finally, I would be remiss if I didn't remind you that several of the studies I mentioned are investigator-initiated trials. And although, we have great confidence in the investigators running these studies, Lisata has limited control and thus, time lines and expectations may be subject to change. That said, we are extremely grateful to the investigators and especially to the patients participating in Certepetide clinical trials around the world. For those of you who are interested in more comprehensive description of each trial is available in the appendix section of the corporate presentation on our website. Additionally, in the body of the presentation, there are two slides that depict the anticipated timing and execution of key milestones and data readouts from our trials. As you will see, there are numerous execution and data milestones projected from our portfolio of clinical trials over the next year and beyond. With that, I will now turn the call back to Dave.
