Geron Corporation

Ladies and gentlemen, thank you for standing by. And welcome to the Geron Corporation fourth quarter fiscal 2021 earnings call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, please press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press star one. Thank you. Olivia Bloom, you may begin your conference.

Good afternoon, everyone. Welcome to the Geron Corporation fourth quarter and year-end 2021 conference call. I'm Olivia Bloom, Geron's Chief Financial Officer. I'm joined today by Dr. John Scarlett, Geron's Chairman and Chief Executive Officer, Dr. Alexander Rizzo, Geron's Executive Vice President and Chief Medical Officer, and Anil Kapoor, Geron's 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 relating to the therapeutic potential and potential regulatory approval of IMITEL stats, anticipated clinical and commercial events and related timelines, the sufficiency of Geron's financial resources, and other statements that are not historical facts. actual results and events could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Jerron's annual report on Form 10-K for the year ended December 31, 2021, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Jerron undertakes no duty or obligation to update our forward-looking statements. And now I will turn the call over to Dr. Scarlett. Chip?

Thanks, Olivia. Good afternoon, everyone. Before reviewing our significant accomplishments of 2021, and even before discussing how we plan to build on those accomplishments in 2022 and beyond, I'd like to spend a moment putting into context why we believe in the Telstat can potentially be such a transformative drug, especially in the treatment of hematologic malignancies. Next slide, please. As many of you know, telomerase is an enzyme that adds length to the ends of chromosomes, thus allowing for continued cell proliferation. This enzyme is transiently expressed in normal hematopoietic stem cells during blood cell production. In contrast, telomerase is continuously expressed in malignant hematopoietic stem and progenitor cells, leading to their uncontrolled proliferation. Imitelstat is an oligonucleotide discovered and developed by Geron. that inhibits telomerase and limits the proliferation of malignant cells where telomerase is continuously expressed. It thereby selectively induces apoptosis or killing of those malignant cells. This mechanism of action is unique and first in class, but what makes this drug so exciting and of very substantial potential value is that data from both Phase II trials in low-risk MDS and MF provide strong evidence of disease-modifying activity. Next slide, please. Here we summarize that key evidence. In both Phase II trials, Imatel-STAT's target engagement of telomerase led to reduction of telomerase activity. and depletion of malignant stem and progenitor cells in the bone marrow as evidenced by elimination of the malignant cells marked by molecular and cytogenetic abnormalities. Importantly, in our Phase II trials, the reduction in telomerase activity and depletion of malignant cells in the bone marrow is reinforced as clinically meaningful through the correlations of those biologic effects. With clinical benefits such as anemia responses in MDS, and in MF, reduction in bone marrow fibrosis, as well as, for the first time, correlation with improvement in overall survival. These data, which are of keen interest to the hematologic community, provide strong evidence of the disease modification potential of Imatelstat, which we expect will allow Imatelstat to significantly advance patient care in both lower-risk MDS and refractory MF. Now, let's talk about what happened in 2021. Next slide, please. A critical focus in 2021 involved advancing our two ongoing Phase III trials toward important readouts. These trials are designed to address high-end medical needs in lower-risk MDS and refractory MDS and are intended to be registration-enabling trials in those indications. In our eMERGE Phase III trial in lower-risk MDS, we completed patient enrollment in October of 2021. That milestone achievement enables top line results for the key efficacy and safety parameters, what we call TLR, to be announced in early January of 2023. If those phase three top line results confirm the similar safety as well as the depth, breadth, and durability of transfusion independence that was observed in our phase two trial in the same lower risk MDS patient population, Then we expect to submit an NDA for lower-risk MDS within the first half of 2023. And assuming approval, we expect Imatel stat to be commercialized as early as the first half of 2024. I can't wait to get to TLR and see those data. The next 10 months cannot come fast enough. In 2021, we also made progress in our second phase three trial, ImpactMF, with 50% of the sites being open for enrollment. We also started several new programs with high strategic value and only modest initial costs that are designed to broaden Imatelstat's potential use in additional indications and combination regimens. Alexander will provide more detail on ImpactMF and the rest of the Imatelstat clinical development programs later in the call. Finally, in 2021, we began the process of transforming Geron into a commercial stage company. We're doing this by utilizing a comprehensive milestone-driven stage-gated commercialization. We've already engaged in preparation of long lead time items for our first MBA, such as validation of commercial batches by our contract manufacturers, and are beginning to populate several key modules for the Intel Stat MBA. We also began hiring key executives in areas needed to support a commercial organization, including medical affairs, market access, and a chief business officer. Many of our internal activities are focused on keeping to aggressive timelines for submission of an NDA in the U.S. and ultimately an MAA in Europe, assuming the TLR data supports such submissions. Both the lower-risk MDS program and the refractory MF program are potentially of very significant commercial value. These two indications, assuming regulatory approval and launch in the U.S. and EU five countries, have the potential to generate annual peak revenue of greater than $3 billion in 2030. As a result, and in parallel with our continuing preparations to commercialize Imatel staff, for actively investigating potential relationships with appropriate partners. These include exploration of regional and other deal structures, possible mutual interest, which could potentially further accelerate Intel stat development and commercialization. I'd like to have the call over now to our Chief Medical Officer, Alexander Rizza. Alex will provide you with an update of our clinical efforts. Following that, our Chief Commercial Officer and Head of Corporate Strategy, Anil Kapoor, will share with you his synthesis of the expected differentiated role of Immatel stat in both lower risk MBS and refractory MF. Before I make some final comments at the end of the call about upcoming milestones, Olivia Bloom, our Chief Financial Officer, will review our fourth quarter and year-end 2021 results and provide financial guidance for 2022. Alex? Thanks, Chief.