Good morning. My name is Audrey, and I will be your conference operator today. At this time, I would like to welcome everyone to the Geron Corporation Third Quarter 2023 Earnings Conference Call. Today's conference is being recorded. All lines have been placed on mute to prevent any background noise. After the speakers remarks' there will be a question-and-answer session. [Operator Instructions]. At this time, I would like to turn the conference over to Aron Feingold, VP of Investor Relations and Corporate Communications. Please go ahead.

Good morning, everyone. Welcome to the Geron Corporation third quarter 2023 earnings conference call. I'm Aron 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; Michelle Robertson, Executive Vice President and Chief Financial Officer; Dr. Faye Feller, Executive Vice President and Chief Medical Officer; Anil Kapur, 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 imetelstat, anticipated clinical and commercial events and related time lines, the sufficiency of Geron'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 Geron's quarterly report on Form 10-Q for the quarter ended September 30, 2023, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Geron undertakes no duty or obligation to update our forward-looking statements. With that, I will turn the call over to Chip. Chip?

Thanks, Aron. Good morning, everyone. Thanks for joining us today. This quarter, we continue to make important progress and build momentum along our planned path to develop and commercialize imetelstat, our first in class telomerase inhibitor. This path, we believe, represents a great opportunity for both near and longer-term value creation. 2023 has been a signal year for us, the imetelstat NDA for the treatment of transfusion dependent anemia, and patients with lower risk MDS was submitted and subsequently accepted for FDA review in August, the FDA assigned a PDUFA action date of June 16, 2024. This was followed by validation of the MAA for the same indication in September of this year. Now that our MAA is under review, we expect the earliest potential approval could occur in late 2024 with a European launch potentially in 2025. We're continuing to evaluate our strategic options, including self-commercialization or partnering, and expect to be able to provide an update later in 2024. If approved, we believe the imetelstat commercial opportunity in this indication is both differentiated and compelling for three reasons. First, imetelstat's been shown to be highly effective in several key patient subgroups, where today's available treatments did not satisfactorily address the needs of patients with this disease. These include RS negative patients, patients with high transfusion burdens, and patients with high serum equal levels. These key clinical attributes of imetelstat have been further reinforced by the ASH abstracts published this morning. New analyses using data from the Phase 3 IMerge trial in transfusion dependent lower risk MDS continue to show a significant durability and breadth of transfusion independence across subgroups, including patients whose needs are not being met by current treatments. Second, there's a very large market opportunity for imetelstat and lower risk MDS patients with transfusion dependent anemia,…

Thanks, Chip, and good morning to everyone on the call. As Chip mentioned, we accomplished critical regulatory milestones this quarter, with the acceptance of our regulatory filings in the U.S. and EU for review of imetelstat for the treatment of transfusion dependent anemia in patients with low risk MDS, who have failed to respond or have lost response to or are ineligible for ESAs. The FDA assigned a PDUFA action date of June 16, 2024. The FDA also informed us that they are planning to hold an advisory committee meeting. We have no further details at this time about a potential date or agenda for this meeting. As in best practice in our industry, we are working with a consultancy group who has expertise and advisory committees to complement our deep in-house regulatory experience, and we expect to be highly prepared. We believe we have an important medicine in imetelstat and we look forward to the opportunity to discuss it with experts. As Chip also mentioned, we are pleased that the ASH abstracts published this morning continue to demonstrate what we believe are the unique and differentiated qualities of the imetelstat in lower risk MDS seen in the IMerge Phase 3 study, including the breadth of effect across MDS subgroups and the unprecedented durability of transfusion independence. I will now provide a brief overview of the abstracts. Please note that we issued a press release this morning at 9 am Eastern Time, which describes the abstracts in more detail and that all abstracts are available on the ASH website. The first abstract was accepted for an oral presentation and characterizes TI responses in the imetelstat and placebo treated patients using various risk classification systems. This subgroup analysis demonstrated that imetelstat consistently had higher TI response rates than placebo, across different…

Thank you, Faye, and good morning, everyone. We have made significant progress regarding our commercial efforts in this quarter. We remain on track for launch readiness in the U.S. in early 2024 and are looking forward to the opportunity to bring this important new option to patients as they fight their disease. I'll start by highlighting the recent updates to the NCCN treatment guidelines for MDS. This follows the recent FDA label expansion from this dataset in the frontline space. As you may be aware, the NCCN guidelines, along with publication of the results from randomized trials remain among the most important factors that influence clinical and fair pathways and significantly informed prescribing behavior. This next slide with a simplified schematic reflecting the revised NCCN guidelines shows that for the largest segment of the frontline RS negative patients, PSAs remain the preferred treatment for patients. There also continues to be limited treatment options for patients with serum equal levels greater than 500 and participation in clinical trials is encouraged for those patients. Given these revised guidelines, we expect that the frontline lower risk MDS phase will evolve towards the use of both ESAs and this dataset. It is important to remember that the majority of the patients with symptomatic anemia are treated today with ESAs in the frontline setting and most will fail treatment in approximately two years. From our perspective, these updated guidelines reflect a lack of effective new treatment options. In particular, for the RS negative lower risk MDS patients who constitute 75% of the market, and for those whose serum equal levels are greater than 500. This is a need we believe imetelstat can powerfully address and given the lack of effective treatment options, we expect imetelstat to be adopted for these patients for the treatment of…

Thanks, Anil, and good morning everyone. As this is my first earnings call at Geron, I wanted to start by saying how very excited I am to be part of this amazing team and how privileged I feel to lead the finance function through this pivotal time for the company. With regards to Q3 financial, for detail results, please refer to the press release we issued this morning, which is available on our website. I will now review some highlights from the quarter. At the end of Q3, our cash, cash equivalents and marketable securities were $381.9 million. This balance includes approximately $28.3 million in proceeds from warrant exercises in the third quarter. There are approximately 2.5 million warrants outstanding and the potential proceeds from these warrants is $3.2 million. R&D expenses for the three and nine months ended September 30 were 29.4 million and 92.1 million respectively, compared to 24.6 million and 67.3 million for the same period in 2022. Expenses have increased year-over-year primarily related to supporting our clinical trials IMerge Phase 3, and IMpactMF. Both personnel and consulting costs increased and support regulatory submissions, and increased investment in manufacturing as we prepare for the potential commercialization and transfusion dependent lower risk MDS. G&A expenses were 18.4 million and 47.7 million for the three and nine months ended 9/30/2023 compared to 15.6 million and 29.8 million for the same period in 2022. The increase in G&A expense is primarily attributed to headcount and external expenses to support the commercial readiness activities. At the end of September 30, the company had headcount of 137 employees, which we projected to grow to approximately 160 by the end of 2023. Our projected full year 2023 GAAP operating expenses are expected to be between $200 million and $210 million. Moving forward, we plan to provide only GAAP guidance for consistency with our SEC financial. Based on our current operating plans and expectations regarding the timing of potential approval of our imetelstat NDA that is currently under FDA review and subsequent potential U.S. commercial launch. We believe that our current cash runway together with projected revenues from U.S. sales of imetelstat proceeds from the exercise of outstanding warrants and funding under our loan facility will be sufficient to support our operations through the end of the third quarter of 2025. I will now turn the call back over to Chip.

Thanks very much, Michelle. With our strong IMerge Phase 3 data and with our regulatory submissions based on these data currently under review by both the FDA and EMA, we believe there's a robust market opportunity in front of us in transfusion dependent lower risk MDS. In addition, we remain excited by our second Phase 3 readout and JAK I relapsed and refractory MF for which we expect an interim analysis in the first half of 2025 and the final analysis in the first half of 2026. These programs represent important opportunities for the patients we serve and for our shareholders whose interests we represent. We look forward to keeping you updated on our progress and will now open the line to questions. Operator?

[Operator Instructions] We will go first to Stephen Willey at Stifel.

Yes, this is Tuuli on for Steve. Thank you for taking my questions. We have three questions on our end. Firstly, can you guys give us an additional color on the dose level; one, basically what those dose levels was in ImproveMF study and maybe more color on the dose escalation scheme whether this dosing was higher or about the same dose level as low risk MDS dose. And whether maybe like dosing schedules. That would be helpful. And second, can you guys talk a little bit about whether FDA is granting of broad label to luspatercept in the first line patients impact your perception of risk benefit of imetelstat. And lastly, are you guys planning on actually disclosing or announcing when the enrollment hits 50% target in IMpactMF study? That would be it. Thank you.

Great. Thank you very much. I'm going to invite Faye to make any comments that she can about the ImproveMF dosing, and how that might relate to some of our other dosing in, for example, low risk MDS or MF, a single agent use. Faye?

Thanks, Chip. The dosing for the ImproveMF study is mostly based on -- this is a safety study. So it starts at a lower dose, and then dose escalates to our highest dose that we used in MF. The dosing scheme is publicly available on pt.gov. And I think within the corporate deck, Appendix, that first dose level was 4.7 milligrams per kilogram of imetelstat and the next is six milligrams per kilogram. Importantly, again, this study is really to assess the safety of the combination therapy in a frontline MF setting.

Second question, related, is that did you have any follow up questions or shall we move on to the FDA or sorry, the broad label commentary. Okay, let's move on. So the second question, I'm going to invite Anil to address I believe the question was, did the assignment of a broad label to the luspatercept frontline use? Does that read in any way on from our perception on the risk benefit from imetelstat? I believe I got that right. Anil?

Thank you for the question. The frontline indication in the frontline population is very different from the population that's been studied. For imetelstat and IMerge, our focus was ESA relapsed refractory patients who are transfusion dependent. And so that's a very different population from the frontline commands, which looked at the front -- ESA naive patient population that got treated. So as a non-clinician, my feeling would be that it does not have a risk benefit impact to our trial, but I would invite Faye to provide her clinical judgment as well.

Agree, Anil. The patient population studied in the command has minimal as any overlap with any patient population within IMerge. So impact on risk benefit is negligible or non-existent in my opinion.

And then the third question was, do we plan on disclosing when 50% enrollment is hit in IMpactMF? The answer is, yes, we do. That's historically been our practice with all of the clinical studies we've run for the last many years. I'm not sure exactly the form that will take kind of depends on timing around other activities, et cetera. But we do plan to make that publicly available. Okay, maybe we could go to the next question.

We'll move next to Corinne Jenkins at Goldman Sachs.

Good morning. This is Craig on for Corinne. So one question from us. You previously announced the initiation of your EAP. And I guess now having some time under your belt? Can you give us some color on the types of patients that have enrolled in that and maybe some of the feedback that you've received so far, on the use of imetelstat through it?

That's a great question. I think the question was what kind of feedback or what are we seeing with the types of patients who are being proposed for the EAP? Maybe Faye, you could talk a little bit about that.

Sure. Thanks for this question. Just a reminder that the EAP is similar to a clinical trial in that enrollment criteria and site initiation criteria is similar to that we use on the IMerge Phase 3 study. However, it's different from a clinical trial and that we cannot recruit for it. It is based on investigator request. So as the trial is still in progress and ongoing, we're really assessing enrollment and the types of patients and we're not providing further details at this time.

Got it. That's helpful. And one more from us. So, how are you guys all preparing for the advisory committee meeting with the FDA? And what sorts of topics do you anticipate will be in focus at the event? Thank you.

I'll let Faye take that and I will supplement as needed. But Faye, why don't you take first crack at that.

Sure. Thanks, Chip. So regarding the ODAC we've contracted, we've been, as you know, is common in industry prepare for an ODAC ahead of time. So we even before the announcement, or the communication from the FDA, we have been working with accredited -- like a very well known vendor, who specializes in ODAC preparation in order to anticipate or you gameplan any types of questions or issues that may be of relevance. Overall as with most ODAC, it will be come down to a clinical question of risk versus benefit. And other than that we don't have any further details.

Yes. Thanks, Faye. I think I'd like to make a couple of other points about the ODAC. Just to remind people we were told that the FDA is planning an ODAC, but we don't know if that will actually occur. There's historical. There's historical information about other products in which ODAC had been planned. They've actually been scheduled and they've been cancelled last minute. So I think we'll just have to wait and see on that. We often get a question, Craig, about when did the most ODACs occur? I think in general, our research shows that they occur four to six weeks before the PDUFA date something like that. And I think the other comment is that we have a variety of consultants. So as well as the consultant that Faye was describing who is a very specialized ODAC and advisory committee, consultant. We have other broad, regulatory consultants. So I think we feel like we will be very prepared through this process for whatever may come and as we've commented in the past, and she commented today in her prepared remarks, I think we look forward to discussing the opportunities for treatment with imetelstat in the space.

We'll go next to Kalpit Patel at B. Riley.

Maybe first, related to an earlier question. I know we have the updated guidelines here. But I'm curious if we have a sense of how reblozyl is being utilized in the real world based on your engagement with KOLs. Is a preference to use reblozyl only for RS positive patients in that frontline, ESA naive group, or and does that utilization, at least what you're seeing so far? Does it look consistent to the survey data that you highlighted?

Anil, that's definitely for you reblozyl in the real world and is it consistent with what we've seen from survey data?

Thank you for the question, Kalpit. I think, our survey data which focused on the second line space, you clearly saw where things are, but when we talk to physicians and start to dig into frontline use, what we see clearly is both PSAs and luspatercept to be part of the treatment paradigm when we are speaking to physicians, both academics and community. I think you will see a preference for RS positive patients heading towards luspatercept. But there are also important nuances that need to be kept into effect, especially serum equal levels greater than 200 typically favor luspatercept, less than 200 PSAs are also very much in play. And then for ESA, ineligible patients, commands, as you know, Kalpit, did not study those patients in particular with that study, but they do have a broad level, but physicians continue to side unmet need for that patient population. From our perspective, I think we see both. I think the degree of adoption depends upon dissatisfaction or satisfaction DSAs, in particular prescribers experiences, and we will see both these drugs be used. But it will not be a replacement or a displacement issue for ESAs to the best of our judgment today, as we go forward. And these patients need a lot of new treatments, and imetelstat does get referred as well, as part of the future treatment paradigm when we show them all the data. So hopefully, this will answer your question, Kalpit.

Yes. That's helpful. Thank you. And then, Chip, you mentioned partnering earlier, I guess any more color on, how you're thinking about partnering could be useful to investors, maybe is it just for ex U.S. territories, or both U.S. and ex U.S.?

Sure, Kalpit. Thanks. Yes, look, partnering is part and parcel of our business. It's an arrow that every company would hopefully have in their quiver. And it's a conversation that needs to continue to develop and mature as you move closer and closer to potential approvals and subsequent commercialization. So I think that we have always been open to partnering. What we commented on today was specifically around European commercialization. And I think that, of course, we have the goal to bring imetelstat to patients in that marketplace as efficiently and as effectively as possible. And given that the MAA is now under review, and we have a better feel for timing, I think that we tried to point out that the earliest potential approval would be in quite late 2024. And that means a European launch would be potentially in 2025. So we're going to continue to evaluate our strategic options, which include not only partnering but also self-commercialization, as we go into and progress through 2024. And I would hope we would be able to give an update we expect to give an update later in 2024, in that specific part of the world.

Perfect. And one last question. Do you have this abstract that shows the differences in overall survival between the responders and non-responders for transfusion independence? I guess, have you done any sort of early analysis for your own patients in IMerge study? And whether that data is consistent with what you're showing in that claims data from the [indiscernible]?

Well, I think that claims data first and foremost, I think that claims data is what I would call very mature data. And it was a large number, I don't remember the exact ends, but it is very large number. I think the purpose of that study was to provide additional insights across various platforms and across various drugs as to the supporting the value of transfusion independence. And I think that that's been a staple of belief amongst most practitioners and also, for that matter, academics. But I do think that since we interact with claims databases all the time, in doing our own assessments, we thought this was really valuable and interesting, and collaborated with [indiscernible] and the Moffitt to produce -- to help them analyze these data and make this presentation. So I think it stands on its own, honestly as a overview of the value in this marketplace of transfusion independence -- achieving transfusion independence. Thanks.

Next, we'll move to Gil Blum at Needham & Company.

Hi. This is Ethan Markowski on for Gil. Thank you for taking our questions. So just two quick ones from our side. First one, maybe a little bit of a follow up from one of the previous questions. And I did try to look quickly, but I was unable to find it. Could you give any color on the rux dosing that was used in improving that? I know you've mentioned imetelstat those things. And then the other question, I'm looking at Slide 10 of the presentation. So the ASH abstract regarding mutations, and you can definitely see a pretty clear efficacy across the various mutations. I was just wondering if there's any biologic rationale why, in particular, ASXL-1 appeared to have a little bit lower effect than the others or if you think it's just small numbers. Thank you for taking the question.

Yes. Ethan, thanks very much. Both really interesting and good questions. I will invite Faye to comment on the rux dosing first and then riff a bit on the efficacy across the different mutations and how our old friend ASXL-1 appears to be a difficult patients with that mutation appear to be particularly difficult to treat. Faye?

Thanks. Sure, Chip. And thanks for the question, Ethan. Regarding the start with ASXL-1 first. Regarding ASXL-1, yes, I do believe that, it appears to be a smaller magnitude of benefits, and that's mostly due to a low number of patients with the ASXL-1 mutation. That mutation in particular portents a very poor prognosis and a quick transformation to higher risk disease or AML. So it was even a bit surprising that we had patients with these mutations in the lower risk population that speaks further to the relevance of the IPSS-M classification. And the results that we are showing it ASH regarding that abstract as well. So it all fits together that because of the mechanism of imetelstat that's directed at telomerase and telomerase is overexpressed in malignant cells and drives the malignant phenotype by targeting the disease itself, we have activity across the broad mutations, regardless of what prognosis they portend for patients. To address your second question, or if it was actually your first. To address your first question about ruxolitinib dosing, the aim of the study is to assess safety and make a sense of safety in the context of real-world use. So patients enter the study on ruxolitinib at whatever dose was most beneficial and tolerable for that. And so the ruxolitinib dose varies per patient.

We'll call next to Joel Beatty at Baird.

In considering the market research data that shows a larger market share for imetelstat than luspatercept. Do you expect that upon launch there could be some moving from luspatercept to imetelstat some switching or what would use upon launch mainly being patients who are either like newly diagnosed or failing their previous therapy?

Thanks. Again, I think this is Anil's area to comment on whether there's possibility for at least switching et cetera at launch. Anil?

Sure. Joel, thank you for the question. I think, Joel, just one fact to keep in mind as I answer the question is, there are very few treatment options and low risk MDS. As Chip spoke to earlier, I think the words he used was competitively less intense. In practice physicians only have a handful of choices. So what we feel is, while we may expect or want a patient, I think the key need here is for patient to really be best treated with whatever option the physician thinks for them till they no longer see benefit. So if it's the case of a patient not seeing benefit, and there is a more effective option, I think physicians will consider switching the patient over but if the patient is responding, our belief and typically clinical practices to allow that patient to benefit fully through that disease through that treatment choice. And then, consider other choices for that patient for where they are. But so hopefully that answers that part of the question. The last remark I'll make here is to have a completely new novel mechanism of action with the level of durability and all the clinical effectiveness that we have shown, I think will become a really important tool in armamentarium for physicians to consider and continue to optimize a patient therapy. So I'll stop here, and Faye, is there are any clinical remarks from your side, that might be good.

Okay. Thank you. Any further questions, Joel or did that?

Great. Thank you.

And there are no further questions at this time. I would like to turn the conference back over to Aron Feingold for closing remarks.

Thanks so much, operator. Thank you, everyone so much for your participation today. We look forward to keeping you updated on our progress. Thanks so much.

And this concludes today's conference call. Thank you for your participation. You may now disconnect.