Geron Corporation

several members of Geron's management team. Dr. John Scarlett, Chairman and Chief Executive Officer. Michelle Robertson, Executive Vice President and Chief Financial Officer. Jim Ziegler, Executive Vice President and Chief Commercial Officer. Dr. Joseph Ede, Executive Vice President, Research and Development. And Dr. Faye Fowler, Executive Vice President and Chief Medical 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 launch, commercial opportunity, and therapeutic potential of Ritello, anticipated clinical and commercial events, and related timelines, the sufficiency of Jerob's financial resources, and other statements that are not historical facts. actual events or results could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Jerron's most recent periodic report filed with the SEC, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements and our future updates to those risk factors. Jerron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Chip.

Chip? Thanks, Erin, and good morning to everyone on the call. Thanks for joining us today. 2024 was a terrific year for Jeron and for Ritello, our first-in-class phelomerase inhibitor. Ritello has a unique mechanism of action that represents a highly differentiated treatment with blockbuster potential in this high, unmet need, lower-risk MBS population. The FDA approved Ritello in June of 2024 for the treatment of certain lower-risk MBS patients including patients in the frontline who are ESA-uneligible, second-line ESA relapsed and refractory patients, and third-line plus patients, regardless of RS status across lines of therapy. In addition, in August of 2024, Ritello received favorable placement in the MDS-MCCN guidelines, including a Category 1 treatment recommendation in second-line RS-positive and RS-negative patients, regardless of prior treatment. We've also been pleased with further validation for Ritello in low-risk MDS in Europe, where the CHMP adopted a positive opinion in December, recommending the approval of Ritello for the treatment of ESA-ineligible and ESA-relapsed refractory non-Delphi-Q adult patients with transfusion-dependent anemia due to low-risk MDS. The European Commission is expected to make a final decision on a Ritello marketing authorization application in the first half of 2025. Beyond lower-risk MDS, our development efforts in myelofibrosis also continued to progress in 2024. We have now achieved 80% enrollment in our pivotal Imatel-STAT Phase III IMPACT-MF trial in JAKI relapsed refractory myelofibrosis. Many of you will recall this is the first myelofibrosis Phase III trial with overall survival as the primary endpoint. This study assesses the potential to alter the course of myelofibrosis with Imatel-STAT. Based on our current enrollment rate and number of death rates, we expect the interim analysis may occur in the second half of 2026, while we expect the final analysis may occur in the second half of 2028. We believe that if this trial is positive, Imatelstat could transform the treatment landscape for this high-end metamine relapsed refractory myelofibrosis patient population that has such additional survival today and in doing so, to potentially double the Rytello commercial opportunity. We're proud of these robust 2024 accomplishments. Since launching in the US lower risk MDS market beginning at the end of June of 2024, we've seen positive uptake of Rytello. In the fourth quarter of 2024, our second full quarter on the market in the US, we achieved $47.5 million in Rytello net product revenue. Since product availability at the end of June 2024 and through year end, we achieved 76.5 million in net product revenue, which exceeded our internal expectations. From a financial perspective, we ended the year with a strong cash position of approximately $503 million, which we expect will enable us to reach profitability without additional financing if our internal sales and operating expense expectations are met. However, despite achieving this revenue in the first two quarters of launch, we have observed flat revenue trends over the last few months. As many of you will recall, beginning a few months into launch, we changed our commercial and medical affairs leadership. Jim Ziegler, our Chief Commercial Officer, and Joe Eade, our EVP of R&D, will discuss their assessments and actions in more detail later in this call. Before I hand the call over to Jim, however, I want to reinforce our confidence in the potential commercial opportunity of Ritello, which is supported by robust clinical and scientific evidence that Ritello is a highly differentiated product. We believe that the compelling Phase III data, along with the favorable FDA label and NCCN guidelines, support Ritello's establishment as a standard of care for high-end net needs eligible lower-risk MDS patients, particularly in the second line. Most importantly, many hematologists that we speak with have the same assessment. So with that, I'll turn the call over to Jim for our commercial update. Jim?

Thank you, Chip, and good morning, everyone. Today, I will address Q4 commercial performance and recent revenue trends, highlight our assessments and actions to focus on our key value drivers, and thus help us realize the significant commercial opportunities we have with Ritello in this high unmet need patient population. As described previously by Chip, we achieved $47.5 million in Ritello net product revenues in the fourth quarter 2024. This demand for Ritello is supported by strong payer access. Payers responsible for approximately 80% of U.S. covered lives have implemented medical coverage policies for Ritello that are consistent with the FDA label, clinical trials, and or NCCN guidelines. New patient starts and duration of treatment are the key primary drivers of revenue. For duration of treatment, it is important to note that even the longest treated patients in the commercial setting are just sitting the median of approximately eight months observed in the Phase III iMERGE trial, and our market research suggests the duration of treatment in commercial Ritello patients treated to date appears consistent with that observed in iMERGE. However, with respect to new patient starts, we have observed flatness over the past few months. Specifically, even though we see Ritello being utilized across RS-negative, an RS positive first line, ESA ineligible, second line ESA relapsed refractory, and third line plus patients. The majority of new patient starts have come from the third line plus patient segment, with the second line new patient starts lower than our expectations. Our priority is to drive new patient starts across the breadth of population in our FDA label. so that we are not niched to a third line treatment. We are particularly focusing on ESA relapsed refractory RS negative patients where we believe Rytella's benefits are notably differentiated and where there is substantially unsatisfied patient population. There are other factors we are also addressing which we believe will help accelerate uptake in earlier line patients. Below the national level trends, we see variability in regional territory and account level performance. Some territories and accounts are performing very well and competing and winning at the local level. Other territories and accounts have opportunities for improvement where we are refocusing our support and sales training efforts. Second, we believe the lower risk MDS market is promotionally sensitive with time in front of the healthcare providers, or HCPs, being a key factor to changing their prescribing behaviors. We are taking steps to optimize our engagement with target HCPs. Jill will also highlight educational efforts by our medical affairs team to increase HCP awareness and education. We expect that as HCPs gain successful clinical experience with Ritello, in later lines and often difficult to treat patients. And as we work to raise awareness and increase engagement, they will choose Vitello in earlier lines of treatment. Third, as Chip mentioned earlier, our organization changed commercial and medical affairs leadership a few months into launch. We have a balanced sense of urgency and a thoughtful approach in implementing changes to quickly drive operational excellence and minimize launch disruption. We have augmented the team with experienced senior leadership to support these efforts. Don Nguyen joined in October 2024 as Senior Vice President, Commercial Strategy and Operations. Prior to joining Geron, Don was at Gilead Sciences for almost 20 years and most recently served as Vice President, Commercial Operations where she led a team of approximately 150 people responsible for supporting the U.S. business. Dawn brings a deep background in commercial analytics to Geron. Jim Hassard joined in November 2024 as Senior Vice President Sales and Marketing. He is another strong commercial leader with a 30-plus year successful track record. His prior experiences include roles as Chief Commercial Officer at two publicly traded biotech companies after spending most of his career at Amgen in senior sales and marketing leadership roles, including a country manager role. Together, Don and Jim and their teams are working to improve insights, strategies, and execution. We are also assessing other possible root causes for the flat revenue trends and have implemented or are in the process of implementing several changes such as scaling up our analytics capabilities, refining our segmentation and targeting, and improving our promotional and sales force effectiveness, which we believe will help us more fully capture the significant commercial opportunity for Ricello in lower risk MDS, which I will speak to on the next slide. As shown on slide eight in our earnings deck, we estimate that in 2025, The U.S. Ritello total addressable lower risk MDS patient population is approximately 15,400 patients and includes patients recommended in the NCCN guidelines. This includes approximately 3,400 first line ESA ineligible patients, approximately 7,600 second line and 4,400 third line plus patients, with approximately 75% of patients with RS negative and 25% of patients with RS positive status. As I mentioned, our efforts are particularly focused on the eligible RS negative population where Ritello is the only drug approved for ESA relapsed refractory patients. Assuming the duration of treatment observed in iMERGE and based on the current net price, there is potential to achieve blockbuster status by treating approximately one-third of the U.S. Ritello total addressable patients. I want to thank our dedicated commercial team and the cross-functional teams at Geron for their hard work to ensure that treatment-eligible patients have broad and timely access to Ritello. I will now turn the call over to Joe for a medical update. Joe?