Geron Corporation (GERN) Q1 2023 Earnings Call Transcript
Good morning. My name is Rob, and I will be your conference operator today. At this time, I would like to welcome everyone to the Geron Corporation’s First Quarter 2023 Earnings Conference Call. [Operator Instructions] Thank you.
Aron Feingold, Vice President, Investor Relations and Corporate Communications, you may begin your conference.
Good morning, everyone. Welcome to the Geron Corporation First Quarter 2023 Earnings Conference Call. I am Aaron 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 and Chief Financial Officer; Dr. Faye Feller, Executive Vice President and Chief Medical Officer; and Anil Kapur, 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 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 March 31, 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.
Please refer to the press release and slide deck for today’s call under Events in the Investors & Media section of our website at www.geron.com/investors for our first quarter 2023 financial results as well as business highlights.
The agenda for today’s conference call will be as follows: Chip will provide introductory remarks; Faye will give a regulatory update, discuss key data accepted for presentation at ASCO and EHA and provide a medical affairs update; Anil will highlight our progress and launch planning and provide an overview of the lower risk MDS commercial opportunity, including physician insights and perception; Olivia will review first quarter 2023 financial results and current capital resources; and Chip will provide concluding remarks before going to the Q&A session.
With that, I will turn the call over to Chip. Chip?
Dr. John Scarlett
Thanks, Aaron. Good morning, everyone. Thanks for joining us today.
At Geron, we aim to transform the treatment of heme malignancies, which we believe will provide a significant compelling commercial value proposition. Imetelstat, our first-in-class telomerase inhibitor is poised to become a highly differentiated standard of care in lower risk MDS and in relapsed/refractory myelofibrosis.
In lower risk MDS, this is based on our IMerge Phase 3 data, which showed an unprecedented durability of transfusion independence as well as the breadth of that TI benefit across major MDS subtypes, including both, RS+ and RS- patients. No other drug we know of today can match this level of durability in this patient population. Imetelstat’s activity in RS- patients is particularly noteworthy because there is no approved agent today specifically for this patient population, which represents about 75% of the patient opportunity in lower risk MDS.
In fact, these RS- patients generally are harder to treat compared to RS+ patients and therefore, critically require new treatment options. Unlike the current treatment options, imetelstat has a novel mechanism of action as a telomerase inhibitor that confers strong clinical and molecular evidence for disease modification as well as a well-defined safety profile of on-target cytopenias seen in some patients that have limited clinical consequences. Faye will further discuss these data, which are featured in two abstracts accepted for oral presentation at EHA.
Faye will also highlight another accepted EHA abstract that is based on patient-reported outcome data from IMerge Phase 3. This abstract illustrates that compared to placebo, imetelstat-treated patients were more likely to have sustained meaningful improvement in fatigue and experience such improvements more quickly.
Based on these compelling Phase 3 data, we’re on track to submit our new drug application to the FDA next month. The submission will include a request for priority review.
Our goal is to be ready for a commercial launch in early 2024. We’re planning for the U.S. commercial launch to ensure broad reimbursement for imetelstat and deliver a seamless customer experience to all stakeholders. Under Anil’s leadership, we’re taking a deeply integrated and cross-functional approach to prepare our product, the market and our organization for commercialization, which Anil will elaborate on later in the call.
After lower risk MDS, Geron also has a significant follow-on indication in JAKi relapsed/refractory MF patients that’s anchored by the first and only Phase 3 study that has a primary endpoint of overall survival. If that study reads out positively, we expect imetelstat to become a transformational standard of care for these MF patients who today have very limited treatment options. We believe imetelstat can address significant unmet needs for lower risk MDS in relapsed/refractory MF patients, leading to a potential total addressable market opportunity or TAM in the U.S. and EU of greater than $7 billion in 2033. About half of that TAM or approximately $3.5 billion is attributable to the lower risk MDS indication.
From a financial perspective, we have over $400 million on the balance sheet as of the first quarter close, which gives us the financial wherewithal to operate the company through the end of the third quarter of 2025. As such, we believe we’re positioned to launch imetelstat in lower risk MDS, uncompromised by financial restraints while also supporting the rest of our malignant hematology program, including the expected readout of our Phase 3 overall survival study in relapsed/refractory MF.
I believe our unprecedented clinical data to date driven by our differentiated mechanism of action and potential for disease modification, together with a clear regulatory pathway, solid financial resources and a highly experienced team represent a winning combination to bring imetelstat to the market as a potentially transformational treatment for patients.
With that, let me hand the call over to Faye Feller, our Chief Medical Officer. Faye?
Dr. Faye Feller
Thank you, Chip, and good morning to everyone on the call.
First, as Chip mentioned, we expect to submit the new drug application in lower risk MDS to the FDA next month. I’m deeply impressed by and appreciative of the tremendous teamwork of the preclinical, regulatory, clinical and CMC teams to prepare the NDA. Next, we are very pleased that all of our submitted abstracts have been accepted at the upcoming ASCO and EHA annual meeting. The abstract for IMerge Phase 3 top line results was accepted for oral presentation at ASCO on June 2nd, and will be available on the ASCO website on May 25. The abstract for EHA described longer follow-up data on durability of transfusion independence, further evidence of potential disease modification and favorable patient reported outcomes in imetelstat-treated low-risk MDS patients and IMerge Phase 3. The abstracts are posted online this morning on the EHA website, and I will be covering their contents in my remarks.
The first abstract, which was accepted for oral presentation at EHA, described not only the top line results from IMerge Phase 3 that were released in January of this year, but also new data, including an update to the rate of one-year transfusion independence. Specifically, with three months of additional follow-up, 21 of the 118 imetelstat-treated patients versus 1 of 60 placebo-treated patients achieved one-year TI, representing 63.6% of 24-week TI imetelstat responders. As stated in the abstract, the continuous TI for one year and longer represents substantial relief from transfusion-associated complications for this lower risk MDS patient population. In addition, this abstract describes new data on the correlations of reductions in variant allele frequency, or VAF, to longer TI duration in imetelstat-treated patients. I’ll discuss these data with the next abstract.
The second abstract also was accepted for an oral presentation at EHA and provides further evidence of the disease-modifying activity observed in IMerge Phase 3 with imetelstat. Of the 178 patients enrolled in IMerge Phase 3, 22% of imetelstat-treated patients and 21.7% of placebo-treated patients had baseline cytogenetic abnormalities, a cytogenetic response, which is defined by either a reduction or complete disappearance of abnormal cytogenetic clone characteristic for MDS was observed in 34.6% of imetelstat-treated patients versus 15.4% of placebo-treated patients.
Imetelstat-treated patients achieving 8-week TI, 24-week TI and 1-year TI had VAF reductions of at least 50% that were statistically significantly greater compared to placebo for SF3B1, TET2 and DNMT3A mutations. Importantly, greater VAF reductions in SF3B1 mutation for imetelstat-treated patients were correlated at a highly statistically significant level with increases in hemoglobin and longer TI duration.
The abstract concludes that these data taken together with the robust rates of TI that are continuously durable for imetelstat-tread patients may indicate improvement of the ineffective erythropoiesis characteristic of lower risk MDS and suggest imetelstat may alter the underlying biology of disease in these patients.
Moving along to the third abstract, which will be a poster presentation at EHA. Patients with lower MDS and anemia typically experience severe fatigue that negatively impacts overall functioning in daily life. Further, fatigue can also be commonly reported as a side effect of currently available treatments.
In IMerge Phase 3, an exploratory analysis of patient reported fatigue was conducted using the FACIT fatigue score, a validated 13 item patient questionnaire, to measure the rate of deterioration or improvement of fatigue during treatment with imetelstat or placebo. Based on this analysis, imetelstat did not worsen the rate of deterioration in fatigue. And impressively, patients treated with imetelstat had greater clinically meaningful, sustained improvement in fatigue compared to placebo. An improvement in patient-reported fatigue has not been previously reported with any other treatment for lower risk MDS. Also, the median time to achievement of sustained meaningful improvement in fatigue was shorter for imetelstat versus placebo.
Finally, in imetelstat-treated patients, a significantly higher proportion of responders had sustained meaningful improvement in fatigue scores versus non-responders, consistent across 8- and 24-week TI and HI-E. This association was not observed in placebo-treated patients. These data provide additional evidence for the multifactorial clinical benefit of imetelstat treatment.
Lastly, two imetelstat abstracts submitted by Geron collaborators have been accepted for presentation at EHA. The first, which will be presented in an oral presentation, covers the translational analysis from a subset of lower risk MDS patients from IMerge Phase 2. The abstract concludes that low inflammatory features at baseline and an induction o an adaptive immune profile by imetelstat are associated with TI response, suggesting that immune cell remodeling could contribute to hematopoietic activity of imetelstat treatment. The second, which will be a poster presentation, features imetelstat preclinical data in MS in which the authors demonstrate that imetelstat reduces hTERT expression and telomere length and targets JAK/STAT signaling, particularly in CALR-mutated cells. According to the abstract conclusion, the data proposed that CALR-mutated clones are highly vulnerable to imetelstat treatment.
Next, I will discuss our pivotal Phase 3 IMpactMF study, which is designed to enroll approximately 320 patients with myelofibrosis that is relapsed/refractory to JAK inhibitor. Our Geron clinical operations team has been conducting on-site visits to clinical trial sites around the globe, and we consistently hear significant enthusiasm from investigators around IMpactMF, specifically as the first and only Phase 3 MF trial with overall survival as the primary endpoint. Additionally, we’ve been increasing our engagement with patient advocacy groups in the myelofibrosis space, who have also expressed excitement around the potential to extend survival in this JAK inhibitor relapsed/refractory population.
Lastly, the IMerge Phase 3 readout in lower risk MDS has also spurred an additional way of support about the potential of imetelstat in myelofibrosis. Under our current planning assumptions, we continue to project the interim analysis for IMpactMF to occur in 2024. Of course, because these analyses are event-driven and it is uncertain whether actual rates for enrollment and events will reflect current planning assumptions, the interim analysis may occur at a different time than currently expected.
In addition to engaging in a strong scientific exchange related to imetelstat at ASCO and EHA, our teams are planning to have significant on-site presence to interact directly with the medical community. We have exhibit space at ASCO, offering MDS disease state information and medical resources, for our clinical trials to oncologists and other attendees. Our medical affairs team is also participating in conferences, such as those organized by the Oncology Nursing Society, Society of Hematologic Oncology, Association of Managed Care Pharmacy, and the American Society of Hematology, to support and connect with a broad array of professionals who touch the lives of patients with lower risk MDS and myelofibrosis.
I am very pleased that we have completed the initial hiring of the medical affairs field team, which includes senior field medical liaisons and oncology clinical educators. Experienced scientists and dedicated clinicians will be interacting with the medical community as ambassadors to champion the unmet needs of patients with lower risk MDS and MF. Their efforts are an important piece of our broad launch preparedness planning, which Anil will cover in his remarks as well as providing an overview of the imetelstat market opportunity. Anil?
Thank you, Faye, and good morning, everyone. As Chip mentioned, we believe Geron has a highly compelling commercial value proposition with the potential for imetelstat to become part of the standard of care in lower risk MDS and MF. My comments today will focus on lower risk MDS, our first indication, given the proximity of potential commercial launch. At a future meeting, I’ll discuss the market dynamics and significant potential for imetelstat in MF.
First, I would like to commend the tremendous effort across Geron as we prepare for a successful U.S. commercial launch of imetelstat. As Chip mentioned, our goal is to prepare imetelstat, the lower risk MDS market, and Geron is an organization so that we can deliver a seamless customer experience to all stakeholders while ensuring broad reimbursement for the drug.
This slide 18, for those who are not on the webcast, provides a high-level overview of our launch preparedness progress across many teams and functions within Geron. I’d like to highlight the progress being made across each of the preparation pillars as we continue to target commercial launch readiness in early 2024.
First, with regards to preparing imetelstat for launch, in addition to our regulatory submissions and trademark activities, we continue to build out a comprehensive and integrated clinical and economic value proposition, messaging that conclusively outlines imetelstat’s benefits across key stakeholders. We also continue to make progress in our manufacturing and distribution readiness including on our long lead time supply chain activities, state licensing and third-party logistic efforts in order to facilitate efficient distribution of imetelstat and smooth flow through the U.S. health care system.
Second, with regards to preparing the market, we have extensive efforts ongoing to generate market insights from providers, patient and payer perspectives that are informing our U.S. market access and commercial channel strategy as detailed in this slide’s middle pillar.
Third, we have built out the majority of the commercial organization and are continuing to build out the infrastructure and enterprise-wide functional capabilities. We plan to hire our sales force in a stage-gated manner aligned to our PDUFA date. As I mentioned, to inform our launch strategy and execution, we have a significant effort ongoing to deeply understand the U.S. lower risk MDS market. Over the next few slides, I’ll share some recent insights from this research which we believe support Geron’s strong commercial value proposition.
First, I would like to address the lower risk MDS patient experience. Lower risk MDS, as many of you know, is predominantly a disease of the elderly patients typically present with anemia, and many experience no symptoms in the early stage of the disease. Over time, the disease continues to progress and the majority of patients develop symptomatic anemia. Supportive care, primarily red blood cell transfusions, remains an important component of patients’ treatment but exposes patients to insufficient correction of anemia and other risks, including alloimmunization and organ-iron overload. Erythropoiesis-stimulating agents remain the first-line treatment of choice in lower risk MDS with lenalidomide and hypomethylating agents or HMAs, being used in some patients as well.
There is a significant unmet need for new therapeutics in this setting as patients typically fail frontline treatments, become dependent on frequent red blood cell transfusions, have poor quality of life, heightened risk of transformation to acute myeloid leukemia and shortened survival. Most patients with lower risk MDS and symptomatic anemia receive ESA treatment. However, not all patients respond to or are eligible for ESAs. Even among responders, responses typically last between 18 to 24 months. There also remains very high unmet need in frontline patients who are ESA ineligible given their high baseline serum EPO levels. Treatment options are limited for patients who have failed or are ineligible for ESAs and may include HMAs and luspatercept, which is approved for ring sideroblast positive patients.
RS- patients represent approximately 75% of all lower risk MDS patients, and treatment options in this setting do not offer evidence of durable and continuous transfusion independence. Therefore, we believe this market in ESA relapse/refractory and ESA-ineligible lower risk MDS patients is undersaturated and ripe for innovation with the new innovative and durable treatments that will be able to be broadly used across MDS subtypes. We see a substantial and compelling commercial opportunity for imetelstat as depicted across the key segments in the red boxes on this slide.
This next slide highlights the key attributes of imetelstat Phase 3 IMerge trial that resonated more strongly with community and academic hematologists. Specifically, with regards to efficacy, physicians perceived a strong totality of clinical benefit and meaningful durability of response. This was attributable to compelling TI rates across RS subtypes, sustained reduction of RBC units and continuous rise in hemoglobin levels. Further, 16- and 24-week TI data was regarded as more robust than current standards of care. With regards to safety, physicians perceive the AE profile is predictable with manageable cytopenias.
Given the familiarity of the adverse event profile with transient cytopenias, physicians expect to use imetelstat in their lower risk MDS patients across both, community and academic settings. Our market research also indicates that hematologists perceive imetelstat’s benefit risk profile provides a compelling treatment option across RS subtypes and in high-transfusion burden patients. In additional interviews with over 30 hematologists from U.S. and key European markets, physicians communicated that imetelstat would be strongly preferred treatment of choice for RS-, ESA relapsed/refractory lower risk MDS patients regardless of the level of transfusion burden with enthusiasm for efficacy improvements observed from clinical studies as well as dissatisfaction with current treatments.
In the ESA relapse/refractory RS+ segment, hematologists considered the reported durability of imetelstat’s transfusion independence to be compelling and would provide significant improvement in long-term response over other options. Furthermore, physicians noted that gaining more clinical experience with the drug may increase conviction to prescribe imetelstat ahead of currently available options. Lastly, clinicians stated that imetelstat’s efficacy profile was significantly differentiated in high-transfusion-burden patients which further bolsters their opinion that imetelstat may be a compelling option over currently approved therapies.
We also conducted market research with 50 practicing hematologists in the U.S. recently. Our goal was to understand how they would use imetelstat if available as compared to other potential future therapies. We asked them about future treatment paradigm across key patient segments, second-line patients who may receive ESAs in the frontline setting, second-line patients who may receive luspatercept in the frontline setting and frontline patients who are ESA-ineligible due to serum EPO levels being greater than 500. Their responses indicate strong enthusiasm for imetelstat to be integrated in the low-risk treatment upon potential approval. Imetelstat is expected to become a new standard of care in second-line lower risk MDS, and an important new treatment option.
I look forward to continuing to provide updates on the commercial activities and market insights throughout the year.
Now, I’ll turn the call over to Olivia for a financial update. Olivia?
Thanks, Anil, and thanks to everyone on the call for joining us today. Please refer to the press release we issued this morning, which is available on our website for detailed financial results.
As expected and in line with our financial guidance, there was an increase in operating expenses for the first quarter of 2023 compared to the same period in 2022. The increase in R&D expenses for the first quarter of 2023 compared to the same period in 2022 primarily reflects higher clinical trial costs for increased activity for both Phase 3 trials and the Phase 1 trial in frontline MF, increased personnel-related costs for additional headcount and higher consulting costs to support regulatory submissions. These higher costs were partially offset by lower imetelstat manufacturing expenses due to the timing of batches. The increase in general and administrative expenses for the first quarter of 2023 compared to the same period in 2022 primarily reflects higher personnel-related expenses for additional headcount and increased costs for new commercial preparatory activities.
Turning to our financial resources. As of March 31, 2023, we had approximately $409.2 million in cash and marketable securities. This balance reflects the receipt of $213.3 million in net cash proceeds from an underwritten public offering completed in January 2023, and approximately $59.8 million in proceeds from warrant exercises in the first quarter of 2023.
Based on our current operating plans and our expectations regarding the timing of the submission and potential acceptance and approval of our planned NDA by the FDA for imetelstat in lower risk MDS and the subsequent potential U.S. commercial launch in the first half of 2024, we believe that our existing financial resources will be sufficient to fund our projected operating requirements through the end of the third quarter of 2025.
We continue to expect non-GAAP total operating expenses up to $210 million for the full year of 2023. The fiscal year 2023 financial guidance reflects regulatory submissions in 2023, ongoing clinical trials, IMerge Phase 3, IMpactMF, IMproveMF and IMpress as well as preclinical studies in lymphoid malignancies and discovery research for a next-generation telomerase inhibitor, manufacturing commercial inventory of imetelstat, preparations for potential U.S. commercial launch of imetelstat in lower risk MDS, projected increases in headcount and interest payments on outstanding debt.
The fiscal year 2023 financial guidance is based on a set of assumptions. If those assumptions are updated later in the year due to changes in our plans, including in response to potential revised timing of FDA approval, and U.S. commercial launch of imetelstat in low risk MDS, then we plan to update guidance at that time.
With that, I will now hand the call back to Chip for closing remarks. Chip?
Dr. John Scarlett
I hope everyone can see the remarkable opportunities associated with imetelstat and its profile for patients and shareholders. To finally bring imetelstat to this precipice of potential commercialization after many years of an incredibly dedicated effort from one of the most experienced and committed teams I’ve had the pleasure to work with over a long career in this industry, is a source of great honor and deep satisfaction. I appreciate all of our employees’ continued dedication and collaboration as well as the strong support of our shareholders, many of whom have believed in this drug and the Company for literally decades. Thank you.
So operator, with that, let’s open the call to Q&A.
[Operator Instructions] And your first question comes from the line of Stephen Willey from Stifel.
Just curious how much incremental follow-up will be ASCO and EHA presentations include relative to the 3 additional months that are included in the EHA abstract today? And then, I guess, second to that, does the updated one-year TI data in today’s abstract now include a mature numerator in terms of the valuable number of patients out to 12 months, or should we expect that number to kind of trend up a little bit more as TI achieving patients across that 12-month threshold? And then, I just have a quick follow-up.
Dr. John Scarlett
Okay. Steve, it’s Chip. Thanks. Steve, just a clarification on the first question. You were looking — I think that — the way I interpreted the question about what will be presented at ASCO and EHA was how much incremental follow-up would be represented by those ultimate presentations? And would they be any different from what are in the abstracts? Was that that the question?
Yes. Correct. Right. So presumably, you have an additional three months follow-up relative to the top line cut per today’s EHA abstract. I’m just curious if the actual presentations themselves will have a later cutoff date with more follow-up.
Dr. John Scarlett
Yes. Faye will answer both of these. And the second question was just the — what would be the updated one-year TI…
TI, just whether or not — mature numerator.
Dr. John Scarlett
Is that relatively mature? Yes. Faye, go ahead.
Dr. Faye Feller
Sure. Thanks for the question, Steve. The three-month follow-up that we cite in the abstract will be consistent with what we present during the presentation at EHA. So we don’t anticipate any additional follow-up. And that’s because at this time — or at that time, the one-year TI data is mature, and we don’t anticipate any additional one-year TI patients. Additionally, just to say that the earlier 8- and 24-week TI responders will — are mature as well.
Okay. And then just on the VAF reductions that you guys are describing in the abstract data today, do you see a differential effect at all as a function of baseline risk status, whether a patient is lower intermediate and — I guess I’m just trying to think about how this data could potentially impact the much higher risk of leukemic transformation that it’s typically associated with an intermediate risk patient.
Dr. Faye Feller
Thanks for the question. We will present additional characteristics about baseline statuses with relation to mutation reduction during the presentation.
Okay. And if I could squeeze in just quick more for Anil, actually. Just on the market research slide, I guess, I’m curious about your thoughts regarding — it looks to be about 1/3 of prescribers that are suggesting frontline use of luspatercept in ESA ineligible patients, and then another 30% of prescribers suggesting they’d either resequence luspatercept or using ESA in second-line luspatercept-experienced patients. Just curious about how you’re thinking about that data just given that there’s to my knowledge, no clinical data to support any of this utilization?
We could not agree more, Steve. I think this is all about future anticipated evolution within the market. I think what’s very clear to us, to your point is that there is a very high unmet need, and it is showing clear dissatisfaction with current therapies. In the ESA ineligible patients, obviously, the COMMANDS trial did not recruit patients with the baseline EPO level greater than 500. The data from IMerge is very supportive, and we would expect imetelstat to be well positioned within that marketplace. And I think the entire frontline space is going to be likely a mix of ESAs, potentially some of luspatercept use. And in terms of sequencing, after the first line, I think that’s also dependent pretty heavily on how imetelstat would position itself within the market upon being available. I think right now, these are still fluid, and we would expect over the next year, year and a half to fully understand the evolved low-risk MDS market space.
And your next question comes from the line of Kalpit Patel from B. Riley.
Maybe one more on that market survey. The data in the second column, were these results under the assumption that Reblozyl secures frontline utilization in both RS+ and RS- patients, or was this just assuming usage for Reblozyl in front-line is only in RS+ patients?
We assume the broadest possible label for luspatercept, again, based on publicly available information. And that is how we are even seeing the space for ourselves at this point of time. Obviously, we do not know the full COMMANDS data, the subgroups and their regulatory interactions. But our expectation is — and this research specifically, compared to your question, was based on full approval of Reblozyl across both the indications as a stimuli to the physicians.
Okay. And was this survey conducted before the COMMAND abstract data were out last month, or was it after that data?
We conducted this very, very recently. We conducted this survey with all publicly available information. And we obviously are aware of the data sets from EHA that are available in the public domain. So I’ll just leave it at that, Kalpit.
Okay. And then I had 1 last question on the cytopenias for imetelstat. Do we have a sense of what proportion of lower risk MDS patients have underlying severe cytopenias before they start therapy? And did you exclude those types of patients in the IMerge study?
Dr. Faye Feller
Thanks for the question, Kalpit. It’s Faye. I’ll answer. With respect to lower risk MDS patients, by the nature of the fact that they’re lower risk, it means that they don’t have severe cytopenias in general. I can’t provide you with an exact number, but I know that it’s very few. We did have neutrophil and platelet requirements for entry into the study.
And Kalpit, just to add on all the real-world rate that we have essentially corroborates what Faye pointed out in terms of the baseline characteristics of these patients do not typically indicate severe cytopenias.
And your next question comes from the line of Joel Beatty from Baird.
The first one is on the cash guidance through the end of Q3 2025. Does this include revenue from imetelstat sales in MDS? And also, does it include potential cash received from the exercise of additional warrants?
Joel, it’s Olivia. So, the guidance includes sales from — our revenues from product sales for imetelstat in lower risk MDS. It does not include of future cash proceeds that could be from more exercises.
A question on — could you just discuss launch preparation and kind of the timing that you see the next steps of getting ready for that launch and where you’re currently at?
So, Joel, I’ll take the question first and others can add on as well. So, our anticipation is with regulator filing in June of 2024 as we stated, we would expect to launch imetelstat in first half of 2024, depending upon the PDUFA that gets assigned to our application. We, obviously, are preparing for a successful launch with all the various aspects that are indicated across those buckets. And the most important things for us to highlight continue to be integrated, comprehensive clinical and economic summary, which is really important and very extensive interactions with all set of stakeholders as we bring this drug to the market. And from an organizational perspective, we are preparing ourselves and our — all our enterprise entity functions to be able to successfully commercialize imetelstat. And really grateful for the team that’s been assembled with very, very high talent and high operational experience. So, continue to provide updates over the next 6 months and the year as we go through on our launch prep activities. Is there any question that I didn’t answer, Joel, that we can take away?
No. It’s helpful. Thank you.
And your next question comes from the line of Gil Blum from Needham & Company.
So first one for Anil. Just to put the cash position and perspective, do you think it enables sales expansion on increased demand, if needed?
So, our — and I’ll ask Olivier to comment as well. We, obviously, have our internal projections on the forecast. And we believe that we are in a very strong position as we speak through 2025, and with two years for uptake in this market. This data, Gil, is pretty unprecedented in low-risk MDS. The unmet need remains very high. It has been validated again and gain by physicians. So we expect fast adoption within this marketplace, which should obviously help us. Olivia, anything else from your side?
Gil, just curious, you’re asking the question to ensure that we have enough inventory on hand in case the demand spikes and that that we have the cash to be able to manufacture that inventory? Is that the basis of the question?
No. The question is more of whether you have flexibility to increase your sales exposure, i.e., more reps or centers if there is demand?
Yes. So we — so Joel, even on that — sorry, Gil, on that question as well, we are planning for our national coverage at launch. In the U.S., across all of our key centers, we expect to be share of voice competitors from day one. And we are also planning, obviously, for our second indication in myelofibrosis, which is expected to produce results in either ’24 or ’25, depending upon the data as for events.
And our expectation is, we fully scale for the first indication and we would be appropriately present for the indication as well. And those are all part of our long-term planning assumption. So, hopefully that answers that aspect of the question s well.
And Anil, since I still have you. So I know you touched on this, but how does — in your survey, how does luspatercept — luspatercept makes sense?
I think I did my best to answer that question before. I take all these surveys as directional. I think what is very clear is it’s likely to be an unnatural choice. I think as we all know, when new effective treatments, which are highly differentiated with newer mechanisms, become available. I think physicians start to do what’s best for patients and tailor regimens appropriately. We would expect a similar dynamic. When I look at that research, I come back heavily encouraged as to the clear preference for imetelstat across the second-line settings, irrespective of what happens in the front line, and a very clear indication that the frontline ESA ineligible patients remain high, high unmet need and a preference for new agents in that setting as well. And our data set, our value proposition that we would communicate would highlight each and every one of these activities, and we would expect it to be extremely well adopted at a fast pace within the marketplace. So, we are encouraged but there is a lot more to come. And I think this space will evolve and expand.
Dr. John Scarlett
Hey Gil, it’s Chip. So, I’ll add the obvious since I’m a physician. There’s no accounting for taste sometimes, especially early in the evolution of a market undergoing change. But I would really echo what Anil said. And this actually — I would make the comments from some of the other questioners on the call. I think we see this very much as the glass, very — more than half full here. This is — we’re focused, of course, on our own drug, and we were very encouraged by these findings. The nuances of how all of these different preferences get expressed today. I think Anil put it beautifully. It will evolve as both more data as guidelines — as other elements in the commercial space really evolve. It will all evolve. But we were very encouraged by these perceptions of value that really were exhibited by the surveying physicians.
Dr. Faye Feller
It’s Faye. I’ll add just one more quick comment that I think these maybe unexpected treatment patterns that result from the survey, really what they’re speaking to is the unmet need in this patient population and the lack of therapeutic options so that providers are just like, I’ll give them what I have even if I tried it before, I’ll try it again.
Dr. John Scarlett
Yes. It happens. Thanks for the question.
Maybe a last one on cytogenetics here. First of all, a lot of this data is very consistent with what you saw in the Phase 2 IMerge. I remember you put up pretty significant data analysis on that. And I have a question that I had back then I still have, which is, is there any diagnostic potential here for patients for MDS patients then even early on when they’re just diagnosed. Not that you need to do this because your study is already working in the general population, but if you could predict to who has a higher chance of being a responder?
Dr. Faye Feller
Thanks for the question. I think one of the distinguishing characteristics of imetelstat is that obviously, as a telomerase inhibitor, it can benefit a broad range of subtype cytogenetic types, mutation types. So, I don’t anticipate that we will ever see a selectivity toward any cytogenetic signal or a mutational signal. And I think that’s one of our — and that’s a characteristic of the inherent nature of telomerase inhibition in the target that imetelstat focuses on.
And your next question comes from the line of Corinne Jenkins from Goldman Sachs.
A couple of questions from us. It looks the addressable market you laid out, which is about $3.5 billion in lower risk MDS assumes a price point of about $25,000 per month. Is that roughly the price you’re planning to launch with? And I’m curious what underpins that particular expectation? And if you’ve had any conversations with payers to date on how they think about that?
So, Corinne, I’ll take that question. So first, we have extensive interaction with payers, both in the U.S. and Europe over the last few years and continue to strengthen those interactions. In low-risk MDS, the best analog for us to consider are the currently approved drugs. I’ll specifically point out to luspatercept. And for low-risk MDS, I think it’s publicly known that the average dose is at the — now pretty much at the highest end of their approved labels. And when we look at price points, obviously, that is one anchor. But importantly for us, we continue to focus on our value proposition, both clinical, economic and even through the PRO data, which is highly, highly differentiating. And we would expect favorable pricing for our drug at launch. And within oncology, these price points, as you mentioned, are pretty much the norm. And our expectation is favorable pricing as we bring out our data and our evidence within this space.
Thanks. And then, maybe another one from us. Just how are you thinking as you approach the U.S. launch about ex U.S. commercialization plans? And when should we expect to get more color on filing time lines and whether you plan to go it alone or through a partnership?
So, our guidance for European filing still remains the same, which is in the second half of this year. We are taking appropriate steps to engage with payers, which is pretty mandatory, especially in the key markets today. Our expectation is to make a final decision around European commercialization strategy in the second half of the year. And obviously, we’ll provide guidance at that point in time.
And that is all the time we have for questions. I will now turn the call back over to Ms. Aron Feingold, for some final closing remarks.
Thanks everyone so much for joining us today during this very, very exciting time for Geron. We look forward to continuing to keep you up to date. Have a great day.
This concludes today’s conference call. Thank you for your participation. You may now disconnect.