Geron Corporation

Good afternoon, everyone. Welcome to the Geron Corporation second quarter 2023 earnings conference call. I am Erin Feingold, Geron's Vice President of Investor Relations and Corporate Communications. I'm joined today by several members of Geron's management team. Dr. John Scarlett, Chairman and Chief Executive Officer. Olivia Bloom, Executive Vice President and Chief Financial Officer. Dr. Faye Feller, Executive Vice President and Chief Medical Officer, Anil Kapoor, Executive Vice President of Corporate Strategy and Chief Commercial Officer, and Dr. Andrew Grethlein, Executive Vice President and Chief Operating Officer. Before we begin, please note that during the course of this presentation and question and answer session, we will be making forward-looking statements regarding future events, performance, plans, expectations, and other projections including those relating to the therapeutic potential and potential regulatory approval of Immateltat, anticipated clinical and commercial events, and related timelines, the sufficiency of Jerron's financial resources, and other statements that are not historical fact. Actual events or results could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Jerron's Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statement. Jaron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Chip.

Chip? Thanks, Erin. Good afternoon, everyone. Thanks for joining us today. Jaron's most recent quarter was punctuated by important achievements which support our evolution from a late-stage clinical development company toward one with future substantial commercial capabilities. Foremost among these achievements was the submission in mid-June of a new drug application for Imatelstat in lower-risk MDS. This was the first NDA ever submitted for a telomerase inhibitor and reflects our team's dedication, commitment, and focus on groundbreaking and innovative drug development over many years. Other important milestones included presentations at both ASCO and EHA of new data and analyses from the eMERGE Phase III lower-risk MDS trial. These data contributed to the evidence for a compelling imitelstat efficacy profile, including durable continuous transfusion independence, as well as substantial increases in serum hemoglobin. Broad responses across MDS subtypes, including in ring sideroblast-positive and negative patients, as well as in high transfusion-burdened patients were also reported. Further, the presentations reflected strong evidence for potential disease-modifying activity, as well as patient-reported outcomes of improved fatigue in imetelstat-treated patients. Faye will comment in more detail on these clinical data updates later on this call. Collectively, these data distinguish Imatelstat from other treatments for patients with lower risk MDS that are available commercially or that are in development today. Based on our market research, including perspectives gained from both academic and community hematologists, we believe the broad hematology community considers Imatelstat an important potential treatment option for patients with lower risk MDS. Our market insights show that Imatelstat is positioned to become a new standard of care in lower risk MDS. particularly for difficult to treat subgroups who have very limited options today. As a result, we believe the total addressable market and lower risk MDS for Imatelstat is approximately $3.5 billion in 2033. In order to execute on that large of an opportunity, we're in a full court press to push forward our launch readiness and expect to be ready for a U.S. commercial launch upon potential approval in early 2024. Anil will re-priorize the latest Imatelstat market research and lower-risk MDS and launch readiness update in more detail later on this call today. Another important element of Geron's value proposition is IMPACT-MF, our pivotal trial evaluating Imatelstat in myelofibrosis patients who are relapsed or refractory to JAK inhibitors. This is the only Phase III clinical trial in myelofibrosis using overall survival as a primary endpoint. We believe a positive outcome could transform the treatment landscape for these MF patients who have limited treatment options and a dismal survival outlook. Faye will be providing further detail on enrollment in the IMPACT-MF trial later on the call. Based on our current planning assumptions for both enrollment and death rates in the trial, today we're updating our guidance for the interim analysis to be expected in the first half of 2025 and for the final analysis to be expected in the first half of 2026. From a financial resource perspective, we have approximately $400 million in the balance sheet as of the second quarter close. This gives us the financial wherewithal to fund potential successful launch in lower risk MDS and also to support operations through the first year of launch. Olivia will comment during the call on the status of warrant exercises and our expectations regarding our cash runway based on these current financial resources. Before I turn this call over to Faye, I'm very pleased to announce today the appointment of Scott Samuels as Geron's new chief legal officer, following Steven Rosenfield's retirement at the beginning of this month. Steven's been the chief legal officer of Geron since shortly after I came to the company more than a decade ago. And both I and the board are deeply grateful for Steven's partnership and contributions to Geron since then. I'm personally very pleased for Steven that he'll now be able to enjoy his much deserved retirement. Prior to joining Jaron as our new Executive Vice President, Chief Legal Officer, and Corporate Secretary, Scott Samuels recently served as the General Counsel of Beijing, where he built a large global legal and compliance team, oversaw launches of three internally developed drug products in the US, Europe, and China, developed a global healthcare compliance program, and led key strategic transactions with Amgen, Novartis, and Celgene, which of course is now BMS. Prior to Beijing, Scott was the Assistant General Counsel and then Acting General Counsel at Ariad, where he managed the company's legal affairs, including SEC compliance and corporate governance, and key licensing and distribution agreements prior to Ariad's acquisition by Takeda. I believe Scott's experience, technical expertise, and history of success in building legal and compliance organizations to meet the needs of a commercial company epitomizes what our current and our many new employees are focused on as we pursue the future evolution and growth of Geron. Both the board and I greatly look forward to working with Scott. With that, I'll turn the call over to Faye for a regulatory and clinical development update. Faye?

Thank you, Chip, and good afternoon to everyone on the call. As Chip mentioned, we are thrilled to have submitted our Imatelstat new drug application in June 2023 for the treatment of transfusion-dependent anemia in adult patients with low to intermediate one-risk MDS who have failed to respond or have lost response to or are ineligible for erythropoiesis stimulating agents, or ESAs. As permitted under the Mattel Fast Track designation, we have requested that the FDA grant priority review of the NDA. We expect FDA will communicate potential acceptance of the NDA within 60 days of submission, that is sometime in mid-August, and reveal the PDUFA date for such a review. Under a priority review scenario, we would expect potential MDA approval timing in the first quarter of next year. Under standard review, we would expect potential approval timing in the second quarter of 2024. To expand Immatel-STAS potential reach outside of the US, we remain on track to submit a marketing authorization application in the European Union for lower risk MDS in the fourth quarter of 2023. As we await potential commercialization in the U.S., we initiated an expanded access program, or EAP, in June 2023. This is a program that enables us to make Imatel stat available to clinicians and patients prior to FDA approval. Treatment of low-risk MDS patients in this program is based on a protocol approved by FDA, which requires each treating physician to apply for access for their patients. We have heard physicians in both academic and community settings express the need for new treatment options for their lower-risk MDS patients, and we are pleased to be able to offer this expanded access program to the lower-risk MDS community. Patients treated with Imatelstat in the expanded access program are expected to ultimately be transitioned to commercial supply within three months after a potential future FDA approval of the drug. As Chip described, at ASCO and EHA, we presented new data and analyses from eMERGE. These data further differentiate Imatel Stats from existing treatments and support its role as a potential new standard of care in lower-risk MDS. The content of these presentations were also reported on June 14th during the Geron-hosted investor event. We encourage investors to access the archived webcast, which is available on the investor portion of our website under Events. There you can hear hematologic malignancy key opinion leaders and eMERGE investigators, Drs. Uva Plostbecker and Rami Kamrochi, present these data in detail. For the purposes of our call today, I will provide an overview of the key points of imetelstat differentiation highlighted in our ASCO and EHA presentations. First, the clinically meaningful and durable transfusion independence, or TI, experienced by imetelstat-treated patients in eMERGE is unprecedented for patients with lower risk MDS. We observed a highly statistically significant improvement in TI rates in Imatelstat-treated patients for eight-week, 16-week, and 24-week TIs compared with placebo. Even more exciting, with three months of additional follow-up, nearly 20% of Imatelstat-treated patients experienced a one-year TI, which represents approximately 60% of Imatelstat 24-week responders. Additionally, heme malignancy KOLs at ASTHO and EHA noted the statistically significant improvement of anemia with a median hemoglobin rise of 3.6 grams per deciliter for imital sat treated eight-week TI responders as a very important point of differentiation. Second, a breadth of clinically meaningful responses was observed across key MDS subgroups, including difficult-to-treat populations such as those without ring-sitter blast or RS-negative patients, as well as high transfusion burden patients and those with high serum EPO levels. These patient populations have not been studied with most other agents used to treat the anemia of lower-risk MDS, nor have such results been seen with other treatments. At EHA, we presented important new subgroup analysis showing that the rate and durability of TI for 24-week TI responders is similar across key lower-risk MDS subgroups. regardless of ring sideroblast status, prior transfusion burden, iPSS risk category, or baseline serum EPO levels. Third, we have presented robust evidence of imetelstat's potential to alter the underlying biology of lower-risk MDS by reducing or eliminating malignant clones. In imetelstat-treated patients, we saw a reduction in mutation burden as measured by variant allele frequency, or VAS. Furthermore, new data on cytogenetic responses and reductions in bone marrow RS cells reported Imatelstat's mechanism of action. In totality, these data indicate that Imatelstat may have disease-modifying potential in patients with lower-risk MDS. Fourth, data on patient-reported outcomes presented at EHA were also very encouraging. These data describe a sustained, meaningful improvement in fatigue for Imatelstat-treated patients versus placebo. This specific patient-reported outcome is of particular importance because lower-risk MDS patients experience fatigue that is not fully alleviated by red blood cell transfusions. Additionally, many of the current treatments for lower-risk MDS are associated with an increase in fatigue, and Metelstat is the first treatment we are aware of to show an improvement in patient-reported fatigue in lower-risk MDS patients. In eMERGE Phase III, and consistent with prior clinical experience, grade three, four thrombocytopenias and neutropenias were the most frequently reported adverse events. Unlike several of the treatments in hematologist armamentarium, such as HMAs and lenalidomide, which may cause prolonged myelosuppression, the severe cytopenias associated with the metastat were short-lived, resolving to grade two or lower in less than four weeks in most cases. And most importantly, only rarely resulted in severe clinical consequences, such as bleeding or infection. In total, the eMERGE clinical data support a profile for imetelstat that, if approved, we believe will serve as a very impactful option for the treatment of transfusion-dependent anemia in lower-risk MDS patients. Next, I'd like to discuss IMPACT-MS, our second Phase III trial of imetelstat in patients with JAK inhibitor relapsed refractory myelofibrosis. Today, treatment of myelofibrosis is dominated by JAK inhibitors, or therapies with other mechanisms of action in combination with JAK inhibitors. The currently available therapies have been improved based on their ability to improve symptoms and reduce splenomegaly. Approximately 75% of patients discontinue JAK inhibitor after five years, and once they do so, they face a dismal overall survival of approximately 11 to 16 months. We believe that imetalifat could be transformational for these patients. In the EMBARQ Phase II study and JAK inhibitor relapse refractory and mask patients, the overall survival in IMATELSAT-treated patients was 30 months, or nearly double compared to historical controls. Additionally, a comparison of EMBARQ Phase II data to real-world data from a closely matched cohort of patients confirmed improvement in overall survival and lower risk of death for IMATELSAT-treated patients compared with patients treated with best available therapy. Importantly, in Embark, there was strong evidence of the disease-modifying potential of imital stat in relapsed refractory MS, with improvements in bone marrow fibrosis and reduction in key MS driver mutations, and these reductions correlated to improved survival and other clinical outcomes. These data were the basis for the design and initiation of the IMPACT-MS Phase III study in JAK inhibitor relapsed refractory MS patients. with overall survival as the primary endpoint. The IMPACT-MF protocol calls for a planned interim analysis when approximately 35% of the planned enrolled patients have died, and a final analysis when over 50% of the planned enrolled patients have died. As an OS study, the timeline for the interim and final analysis depends not only on enrollment rate, but also on death rate. Today, based on achieving over 40% enrollment in IMPACT-MF, and our planning assumptions for enrollment and death rates in the trial, we are updating our guidance for the interim analysis to be projected in the first half of 2025 and for the final analysis to be in the first half of 2026. Because these analyses are event-driven and it is uncertain whether actual rates for enrollment and events will reflect current planning assumptions, the results may be available at different times than currently projected. As can be expected for a study and an indication for which there are multiple ongoing trials, constraints on clinical site personnel resources due to the COVID-19 pandemic and other competing trials in MF have led to some challenges in recruitment and enrollment. We are working closely with the MF community and our clinical trial sites on recruitment for the trial and continue to plan to announce when the trial is 50% enrolled. As Chip mentioned, this is the first and only myelofibrosis trial with overall survival as a primary endpoint. Our MS investigators remain very excited about this study and the potential of a new treatment that could improve survival for these patients who currently have few treatment options and dismal survival rates. We are also pleased to report that the first patient was dosed this June in the investigator-led Phase II IMPRESS trial. that is evaluating in Matelstat in patients with relapsed refractory acute myeloid leukemia or high-risk MDS. This trial is based on preclinical publications that describe the role of telomerase in AML disease progression and which have reported that inhibiting telomerase in both mouse and human-derived AML models targets and potentially depletes leukemic stem cells, thus impairing leukemic progression. Relapsed refractory AML and higher-risk MDS or high unmet need areas, and we look forward to understanding more about the potential efficacy of Imatelstat in this patient population. With that, let me turn the call over to Anil to provide a commercial update. Anil.