Geron Corporation

Everyone, welcome to the Geron Corporation third quarter 2022 conference call. I am Erin Feingold, Geron's Vice President of Investor Relations and Corporate Communications. I'm joined today by the following members of Geron's management team. Dr. John Scarlett, Chairman and Chief Executive Officer. Olivia Bloom, Executive Vice President of Finance and Chief Financial Officer and Treasurer. Dr. Fay Feller, Executive Vice President and Chief Medical Officer, and Anil Kapoor, Executive Vice President of Corporate Strategy and Chief Commercial 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 related to the therapeutic potential and potential regulatory approval of Immatelstat, 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 10Q, for the quarter ended June 30, 2022, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Jaron undertakes no duty or obligation to update our forward-looking statements. And now, I will turn the call over to CEO, Dr. Scarlett. Chip?

Thanks, Erin. Good morning, everyone. Thanks for joining us today. Throughout the year, we've highlighted our vision for Geron, which is to become a leader in the treatment of hematologic malignancies. The strategic pathway to achieving this goal is defined by our expected journey to develop and commercialize Imatelstat. Based on the Imatelstat Phase II data in lower-risk MDS and in relapsed and refractory myelofibrosis, we believe Imatelstat has a highly differentiated, compelling clinical profile. First, as a telomerase inhibitor, imitelstat has a unique mechanism of action that strikes at the very heart of these malignancies by targeting the malignant stem and progenitor cells that drive both lower-risk MDS and JAKI relapsed and refractory MF. Second, the Phase II data also provided strong evidence for disease modification. At a molecular level, In both Phase II studies, we reported depletion of mutated and cytogenetically abnormal mortality cells that have been correlated with the direct clinical benefits of Imatelstat, providing additional evidence of disease modification. Imatelstat's potential for disease modification not only differentiates it from other currently available therapies, but also directly addresses critical unmet needs in lower-risk MDS and relapsed refractory MF which we expect will provide a needed treatment option for patients with these diseases. Third, in both lower-risk MDS and relapsed refractory MF patients treated with Dimetilstat, we saw unprecedented durability of clinical effects. For instance, Fay will describe an ASH abstract published today in which we reported the approximately one-third of the 38 patients in our Phase II lower-risk MDS study. who despite a median pretreatment transfusion burden of six RBC units per eight weeks, experienced one year or more of transfusion independence. Similarly, in our Phase II relapsed refractory MS study, median overall survival for patients improved to almost twice as long as has been reported in medical literature. Based on these attributes of Imatelstat and compelling Phase II data, We expect potentially highly differentiated clinical profiles from the results of our ongoing in the Telstat phase three trials and these indications. We are therefore very excited by the lineup of expected milestones coming soon and over the next two years. We expect disclosure of top line results or TLR from our emerge phase three trial in lower risk MDS in only two months from now in early January of 2023. If TLR is positive, we expect great value will be unlocked for both patients and for shareholders. Assuming positive TLR, the next expected key GERON milestones are regulatory submissions for Imatelstead and lower-risk MDS. As of today, we expect submission of the MDA during the first half of 2023 and of the EU MAA during the second half of 2023. As Faye will discuss in a few minutes, We've been actively preparing for many months for both disclosure of TLR in early January 2023, as well as for these key regulatory submissions later in the year. Similarly, we've also been preparing for potential commercialization of Imatelstat and have recently made key hires across the team in order to begin building the foundation for a successful commercial launch for lower risk MDS. Finally, becoming a leader in the treatment of hematologic malignancies requires breadth of effect. Thus, the next significant step is to bring IMITEL staff to patients who suffer from JAKI relapsed refractory myelofibrosis. To achieve this, we're working towards having an interim analysis from our IMPACT-MF Phase III trial in patients with this indication in 2024, and then the final analysis in 2025. This study is the first and only phase three myelofibrosis trial with overall survival as the primary endpoint, and thus represents great potential value for patients as well as for our shareholders. Achieving these milestones requires the motivation and expertise of each Geron team member. Their continued dedication and commitment inspire me every day. With that, I'll turn the call over to our Chief Medical Officer, Dr. Faye Feller, for a clinical update, okay?

Thank you, Chip, and good morning to everyone on the call. We at Geron are incredibly excited that the top-line results of the eMERGE Phase III study in lower-risk MDS are just two months away. The clinical team has been actively preparing for the readout in accordance with industry best practices. The clinical cutoff for the top-line results occurred last month, which per protocol is one year following the first dosing of the last patient randomized in the study. We have been continuing database cleaning activities and monitoring visits with our clinical sites in preparation for database lock, which is expected to occur before the end of the year. In early January 2023, we expect to deliver the Phase 3 eMERGE top-line results, which will comprise a robust package of data that we believe will highlight the differentiating qualities of Imatel's stats. We anticipate sharing data on the primary endpoint of eight-week transfusion independence, or TI, as well as key secondary endpoints of 24-week TI and hematologic improvement erythroid, or HIE, which is a composite measure of the percentage of patients who experience an increase in hemoglobin and or a reduction in their transfusion burden. We also plan to provide safety data in order to give a balanced benefit-risk profile of imetelstat in lower-risk MDS. As is typical for a Phase III trial, top-line results represent only a portion of the full clinical study readout, and we anticipate to present more comprehensive results at a future medical meeting. We expect the later additional data will include information on molecular indicators of disease modification, such as mutational burden reductions, and an effect on cytogenetic abnormalities. The Phase III eMERGE trial design matches many of the elements of the Phase II, including clinical site locations and investigators, patient population and enrollment eligibility criteria, Immatel-STAT dose and schedule, primary and secondary endpoints, and other protocol-specified guidelines. Given such similarities, we believe the Phase II results will help inform us on the phase three. As Chip alluded to in his comments this morning, on Sunday, December 11th, longer-term follow-up data from the eMERGE phase two study will be presented in an oral presentation at ASH this year. The abstract for this upcoming presentation, published this morning, is summarized on slide nine of our Q3 earnings call deck. and is currently displayed on the webcast for those watching. The abstract describes the 29% of patients in the eMERGE Phase II study who achieved sustained transfusion independence for greater than one year in the setting of a median pretreatment transfusion burden of six units of red blood cells over eight weeks. We believe this to be an unprecedented durability effect in patients with lower-risk MDS post-ESA treatment. These 11 transfusion-dependent patients were treated with Imatelstaf for a median of approximately 2.4 years, and their median duration of TI was 1.8 years. After a median follow-up of 4.3 years, median progression-free survival was 2.9 years, and median overall survival was 4.8 years. none of these patients progressed to AML. Mutation data was available for the majority of the patients who achieved greater than one year sustained TI, and 89% had any reduction in SF3B1 variant allele frequency, or VAF, while 56% achieved greater than or equal to 50% VAF reduction. Reduction in VAF correlated with longer TI duration and shorter time to onset of TI. We believe these data, along with the long-term sustained TI, indicate strong evidence of disease modification. Safety findings for these patients were consistent with the overall population, and the most frequent adverse events were reversible thermocytopenia and neutropenia. The abstract concludes that the greater than one year periods of transfusion independence observed in these patients represents relief from iron overload and other transfusion-associated complications, and a decreased demand on healthcare resources. Furthermore, durable TI, meaningful reduction in mutation burden, and good survival post-ESA suggested in Telstat may have disease-modifying activity. These recent data, as well as the prior publications, of eMERGE Phase II data reinforce what we believe are key attributes of imetelstat in lower-risk MDS. First, we observed durability of continuous transfusion independence, which we consider differentiating from any treatment currently on the market or being investigated today. Second, broad efficacy was observed across patient subtypes, including RS positive, RS negative, high, and very high. transfusion burden patients. Third, there was strong evidence of disease modification. As described previously by Chip, that due to Imatelstat's unique mechanism of action aims at the very nature of the disease mechanistically and that has not been previously observed with other treatments for this patient population. Moving on to myelofibrosis. There are two posters being presented at ASH this year, for our current MS trials in progress. As many of you know, abstracts for this category describe innovative ongoing clinical trials that have not yet reached their primary endpoint. The first trial in progress abstract describes our pivotal phase three IMPACT-MS study, which is designed to enroll approximately 320 patients with relapsed refractory and myelofibrosis. IMPACT-MS is the first and only phase three MF trials with overall survival as primary endpoint. Approximately 85% of clinical trial sites are open to date, and we remain on track to open all selected clinical sites by the end of this year. Under current planning assumptions, we continue to project the interim analysis for impact MF will occur in late 2024. Of course, because these analysis are event driven, and it is uncertain whether actual rates for enrollment and rates for events will reflect current planning assumptions, the results of the interim analysis may be available at a different time than currently expected. The second trial-in-progress abstract accepted at ASH describes IMPROVE-MF, which is our Phase I study designed to evaluate the safety and clinical activity of imetelstat in combination with rexalitinib. in patients with frontline MF. This study design was informed by preclinical data that showed that sequential treatment with Ruxolitinib followed by Imatelstat had a selective inhibitory effect on malignant MF stem cells while sparing normal hematopoietic stem cells. In this clinical study, we expect to determine the safety profile of combination therapy and explore any potential for disease-modifying activity in a frontline MF disease setting, similar to what was observed with Imatelstat treatment in the Phase II EMBARQ trial in a relapsed refractory MF patient population. Two of the three trial sites for this study are open for patient enrollment. We expect to present preliminary data from this study by the end of 2023. As part of our Imatelstat pipeline expansion, we are also exploring use of the drug in other indications and combination regimens. At ASH this year, additional non-clinical data related to acute myeloid leukemia, or AML, will be presented. The abstract for the upcoming oral presentation describes results from non-clinical in vitro and in vivo experiments with Imatelstat using AML cell lines and AML patient samples. Conducted by our collaborators in Australia, Germany, and the U.S., the experiments found that imetelzad promotes the formation of polyunsaturated fatty acid-containing phospholipids, which cause excessive levels of lipid peroxidation and oxidative stress in AML cells, potentially leading to programmed cell death. The abstract concludes that this mechanistic insight could be leveraged to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patients to imetelstat and potentially cause significant delay of relapse in AML. Based on these and other non-clinical data in AML, as well as the clinical data we have in lower-risk MDS, We are supporting an investigator-led study called IMPRESS in relapsed refractory AML and higher-risk MDS. In that study, Imatelstat is being evaluated as a single agent. We continue to expect the first site to be open for the study by the end of this year. Meanwhile, we have another investigator-led study in relapsed refractory AML named Telomere. In this study, we plan to evaluate imetelstat in combination with a hypomethylating agent and in combination with venetoclax. This study has been deferred until we have data from the IMPRESS single agent study in relapsed refractory AML. We expect data from IMPRESS to help inform the dose and schedule to be used in the two combination dosing regimens that will be evaluated in telomere. The principal investigators for both studies continue to be highly enthusiastic as relapsed refractory AML remains an extraordinarily difficult malignancy to treat. They believe a new mechanism of action from a drug like Imatelstat that directly affects the malignant stem and progenitor cells that drive disease progression could provide an effective treatment option for patients suffering from relapsed refractory AML. Also, in keeping with our pipeline expansion activities, new non-clinical data with imitelstat and lymphoid malignancies will be published online in blood. The abstract describes the characterization of telomerase activity and telomere length and results from in vitro experiments of imitelstat on a panel of diffuse large B-cell lymphoma, or DLBCL, and peripheral T-cell lymphoma, or PTCL cell lines. Conducted by our collaborators at MD Anderson Cancer Center, these in vitro experiments demonstrated that Imatelstat reduced cell viability and increased apoptosis in DLBCL cell lines. In contrast, Imatelstat's single agent activity on cell viability was limited in PTCL cell lines. even though a time- and dose-dependent reduction of telomerase activity was noted. The greater inhibitory effect of imetalstat in DLBCL compared to PTCL may be attributed to the observation of higher telomerase activity in DLBCL compared to PTCL cell lines. Furthermore, the PTCL cell lines had an approximately 7.3-fold longer telomere length than the DLBCL cell lines, which potentially also influenced the lower response to imetelstat. We expect further experiments to be conducted to explore these insights and to assess the potential therapeutic effect of imetelstat in lymphoid malignancies. Finally, I am pleased to report that we are making progress in our next generation telomerase inhibitor program. from which we anticipate generating lead compounds for further characterization and evaluation. We anticipate completion of the current discovery effort in 2023, upon which we plan to potentially advance any lead compounds into the next step of discovery research. If successful, these efforts would permit initiation of IND-enabling nonclinical studies. Overall, I am delighted with the progress of the research and development team, both with regards to advancing critical activities for our lead indications in lower-risk MDS and relapsed refractory myelofibrosis, as well as our pipeline expansion programs, which aim to understand the broader potential of imithelstat. With that, I will turn the call over to Olivia for a financial update. Olivia?