Geron (NASDAQ:GERN) Corporation (NASDAQ: GERN) has reported a positive outlook in its Q1 2024 earnings call, focusing on the upcoming U.S. launch of its novel drug, Imetelstat, for transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (MDS). The FDA's advisory committee has largely backed the drug, and Geron is in the final stages of preparing for its commercial debut.
The company holds a strong financial position, with $465 million in resources and plans for sustained operations through projected sales until Q2 2026. Geron is also progressing in a Phase 3 trial for Imetelstat in myelofibrosis, with key analyses due in the coming years.
Key Takeaways
- FDA advisory committee votes 12 to 2 in favor of Imetelstat for MDS treatment.
- Geron is finalizing its commercial strategy, including hiring a sales force.
- The company has $465 million to fund the U.S. launch and operations until Q2 2026.
- Market research supports significant use of Imetelstat, especially in RS negative patients.
- Geron expects to grow its workforce to support the commercial launch.
- A Phase 3 trial for Imetelstat in myelofibrosis is underway, with interim and final analyses expected in early 2026 and 2027, respectively.
- Geron aims for Imetelstat patent exclusivity extension until 2037.
Company Outlook
- Geron's financial resources are expected to support the planned U.S. launch of Imetelstat.
- The company projects operating expenses for 2024 between $270 million and $280 million.
- Employee count is expected to reach 50 by end of 2024, with further growth to 250-300 by year-end.
- Imetelstat's U.S. sales, along with other financial strategies, are anticipated to fund operations until Q2 2026.
Bearish Highlights
- Slower than expected enrollment rates in the myelofibrosis trial.
Bullish Highlights
- Strong financial position with significant cash reserves.
- Positive voting outcome from the FDA's advisory committee.
- Broad market access and significant unmet need in the MDS patient population.
- Plans for NCCN guidelines inclusion and patent exclusivity extension.
Misses
- No specific details were provided about manufacturing inspections.
Q&A Highlights
- Geron is confident in the ongoing progress of manufacturing and regulatory inspections.
- The company emphasized the unmet needs in the low-risk MDS market and potential patient segments that could benefit from Imetelstat.
- Expectations for broad physician adoption of Imetelstat based on market research and surveys.
In conclusion, Geron Corporation is poised for the potential U.S. launch of Imetelstat, with strong financial backing and a clear strategy to address a significant unmet medical need. The company's confidence in the drug's market potential and its commitment to clinical development underscore its optimistic outlook for the future.
InvestingPro Insights
Geron Corporation (NASDAQ: GERN) is navigating an exciting phase with the anticipated launch of Imetelstat and a robust financial strategy. Here are some InvestingPro Insights to further inform investors about Geron's market position and outlook:
InvestingPro Data shows Geron's market capitalization stands at $2.32 billion, reflecting investor confidence in the company's growth potential. The company's Price / Book ratio for the last twelve months as of Q4 2023 is 9.35, which is high and suggests a premium valuation by the market. Additionally, Geron has experienced a significant return over the last week, with a 14.61% price total return, indicating strong recent market performance.
Two key InvestingPro Tips for Geron are worth noting. Firstly, the company holds more cash than debt on its balance sheet, which is reassuring for investors concerned about financial stability as Geron transitions to the commercial phase of Imetelstat. Secondly, analysts have revised their earnings upwards for the upcoming period, signaling optimism about the company's revenue prospects following the anticipated product launch.
For those looking to delve deeper into Geron's financial metrics and strategic positioning, InvestingPro offers additional insights and tips. There are 15 more InvestingPro Tips available that can provide a comprehensive understanding of the company's outlook. To access these valuable insights, use the coupon code PRONEWS24 to get an additional 10% off a yearly or biyearly Pro and Pro+ subscription at InvestingPro.
With a strong financial foundation and favorable analyst revisions, Geron Corporation is well-positioned to make a significant impact in the MDS treatment landscape. The InvestingPro insights underscore the company's potential and the market's anticipation of its next steps.
Full transcript - Geron Corp (GERN) Q1 2024:
Operator: Thank you for standing by. My name is Jael and I will be your conference operator today. At this time I would like to welcome everyone to the Geron Q1 2024 Conference 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. [Operator Instructions] I would now like to turn the conference over to Aron Feingold. You may begin.
Aron Feingold: Good morning, everyone. Welcome to the Geron Corporation first quarter 2024 earnings conference call. I am 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. Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer. Dr. Faye Seller, Executive Vice President and Chief Medical Officer. Michelle Robertson, Executive Vice President and Chief Financial 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 timelines, the sufficiency of Geron'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 Geron'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 statement. Geron undertakes no duty or obligation to update our forward-looking statement. With that I'll turn the call over to Chip. Chip?
John Scarlett: Thanks Aron. Good morning everyone. Thanks for joining us. We're poised for a successful U.S. launch of Imetelstat for the treatment of transfusion-dependent anemia in patients with lower risk MDS. If approved we're deeply excited for the opportunity to bring patients what we believe is an important and differentiated medicine. With our PDUFA date on June 16th, we continue to work closely with the FDA as they complete the review of our new drug application. As part of the MDA review process on March 14, the FDA's Oncology Drugs Advisory Committee or ODAC voted 12 to 2 in favor of the clinical benefit risk profile with Imetelstat for its intended indication in lower risk MDS. The resounding support for Imetelstatreflected in the ODAC vote was also echoed in comments from the lower risk MDS community during the public forum. Hematologists and patients alike spoke out about the burden of transfusion-dependent anemia in this disease and the need for new treatments particularly for patients with difficult to treat subtypes such as high transfusion burden and RS negative patients. Imetelstat is uniquely positioned to address these underserved transfusion-dependent MDS patient populations. We're in the final stages of commercial readiness execution which is included bringing on a sales force in April 2024. We're also engaging in marketing, commercial access payer and reimbursement preparatory efforts just as we are completing the build out of our enterprise capabilities and systems to support our transition to commercial stage company. In short, we're building on our momentum acting with urgency and fully confident in our readiness for U.S. launch on potential approval. We're also financially well-resourced to support the planned U.S. commercial launch with approximately $465 million on the balance sheet as of March 31 of this year. On the heels of the highly positive ODAC outcome, we raised approximately $141 million in net proceeds from an underwritten public offering of common stock and a pre-funded warranty. This offering included participation from RA Capital, Fairmont, ObriMed, Farallon, Adage, Boxer, Vivo, Deep Track and multiple large investment management firms in addition to other new and existing investors. From an EU perspective we also have an MAA or Marketing Authorization Application under review in this indication. If Imetelstat is approved by the European Commission, we expect a commercial launch in Europe would occur in 2025. We're continuing to evaluate our strategic options for European commercialization including self-commercialization or partnering and expect to provide an update later this year. I'd like to turn briefly to our ongoing clinical development efforts in JACI relapsed and refractory MF patients. As many of you recall Impact MF is the only Phase 3 MF study with overall survival as the primary endpoint. Last month, the Data Monitoring Committee evaluated unblinded data and recommended the clinical trial continue. In addition the company reviewed enrollment rates and blinded death rates which are lower than anticipated based on the initial planning assumptions. Accordingly, we're updating our guidance to extend the timelines by half a year with the interim analysis now expected in early 2026 and the final analysis expected in early 2027. Even the trial investigators remain excited about this study and the potential of a treatment that could improve survival for these patients who currently have very few treatment options and dismal survival rates. Faye will provide more color on this trial later in this call. Before I turn the call over to the team, I'd like to take a moment to reflect on how inspired I've been by all of our Geron people. Their passion for bringing our medicine to patients is palpable and drives our culture. From our longest tenured colleagues who worked on the Imetelstat IMD to our sales force that joined us just a few weeks ago there is a deeply shared sense of purpose that each one of us can uniquely contribute to improving the lives of patients with hematologic malignancies. I believe that this unity around our mission drives our urgency and collaboration and it's a critical factor in transforming our fast-growing organization into a successful commercial company. With that I'm going to turn the call over to Anil for commercial updates. Anil?
Anil Kapur: Thanks, Chip, and good morning to everyone on the call. We believe that we are positioned very well for commercial value creation and are well-prepared to execute a successful U.S. launch upon potential approval. As Chip mentioned in April, we completed the build-out of our full commercial organization with the hiring of our sales force, which is being now integrated and trained so that they will be prepared to be deployed in the field upon potential approval. I've had the privilege of getting to know this team really well and I'm deeply impressed by their caliber, experience, and commitment. We also have commercial supply arrangements in place and have finalized our specialty distribution network and third-party logistics. From a market perspective, we have worked to identify the concentrated low-risk MDS prescriber base and our patient access and affordability solutions are on target for implementation at launch. To support our launch preparation and commercial strategy, we have collected extensive market insights which suggest that Imetelstat is highly differentiated in this transfusion-dependent low-risk MDS market. Our research has shown that medical and payer stakeholders are dissatisfied with available options in the low-risk MDS space which we believe creates an opportunity for Imetelstat. Additionally they express enthusiasm for the totality of clinical benefits deemed with Imetelstat including durable red blood cell transfusion independence, hemoglobin increases, and reduction in transfusion burden balanced with a generally well-characterized and manageable safety profile. Lastly from a patent and regulatory exclusivity perspective in the U.S. as shown at the end of the slide deck we are using today, we have orphan drug exclusivity through first half 2031 for MDS. Our method of use patent for MDS and MF expires in March 2033, but if the patent term extension is applied to this used patent, we expect exclusivity would be extended to 2037 and would apply to all users covered by the patent including both MDS and MF. We believe Imetelstat is uniquely positioned to address unmet needs in transfusion-dependent low-risk MDS as captured on this slide which depicts the treatment landscape as well as a simplified schematic reflecting the current NCCN guidelines for MDS. As you may be aware, the NCCN guidelines along with published results from the randomized trials remain among the most important factors that influence clinical and pair pathways and significantly inform prescribing behavior. The NCCN guidelines recommend ESAs as the preferred treatment option for the larger segment of frontline RS negative patients. It's important to remember that many of these patients will show a loss of response to ASA treatment in the frontline setting in approximately 18 to 24 months. There also continues to be limited treatment options for patients with serum eco levels greater than 500 ml per mu, and participation in clinical trials for ESA ineligible RS negative patients is encouraged by NCCN guidelines. From our perspective these guidelines reflect a lack of effective treatment options in particular for those patients who are ESA ineligible, high transfusion burden patients and for RS negative lower risk MDS patients who constitute approximately 75% of the market. This is a need, we believe Imetelstat can powerfully address as a potentially durable treatment that can be used broadly across MDS subtypes. This next slide summarizes our latest market research from 2024 of 50 community and academic U.S. hematologists when surveyed about the product profile of hematologist. When surveyed about the product profile of Imetelstat and what factors may drive treatment decisions. It additionally reflects fair priorities in the low-risk MDS space. Our findings show that these physicians note that achievement of RBCTI and rise in hemoglobin are two key factors that drive their decision-making. Further they point to the greater than 24-week TI and patient reported outcome data from IMerge as essential considerations. These physicians view Imetelstat as a likely standard of care across the relapsed refractory RS negative patient population expressing enthusiasm for the significant efficacy improvement in a population with limited current treatments. These physicians also note transfusion burden has strong impact on treatment decisions and believe Imetelstat is a compelling option for patients with high transfusion burden due to differentiated data in this patient population. The Imetelstat profile also resonates with fair priorities and they recognize the unmet need in the transfusion dependent low-risk MDS space. They express that NCCN guidelines inclusion and peer-reviewed publications are seen as important evidence for their consideration. Inclusion in the NCCN guidelines requires an FDA label as well as the publication of the pivotal data which is already available in the line set. Once potential FDA approval is secured, our teams stand ready to engage with NCCN to begin the process of updating the guidelines. It's important to note that given the elderly patient population with transfusion dependent low-risk MDS, the majority of U.S. patients are expected to be treated under the Medicare Part B setting. We are confident patients will have broad access to Imetelstat. We expect to see Imetelstat uptake across ESA ineligible, ESA failed, RS negative, and RS positive high transfusion burden patients. Based on our latest 2024 market research of 50 U.S.-based practicing hematologists across both community and academic settings, on the left-hand side of the slide, you can see that our market research suggests meaningful Imetelstat use in frontline ESA ineligible patients, especially those who are RS negative. The right-hand side of the slide shows the estimated second-line population, approximately 90% of which are expected to be ESA or luspatercept experienced. Our market research suggests a broad use of Imetelstat across the second line, regardless of frontline therapy, particularly for RS negative patients. As you can see on the figures on the right, which are further segmented for RS positive and RS negative patients within these subgroups. Our findings confirm the significant unmet need across the low-risk MDS patient population, and we strongly believe that Imetelstat, if approved, can play a meaningful role in the treatment paradigm of transfusion-dependent low-risk MDS moving forward. We believe we are well-positioned to capitalize on Imetelstat opportunity in transfusion-dependent low-risk MDS by building on the unique product profile and executing on the launch critical success factors that are driving our commercial plan. From a prescriber's perspective, we have a few important goals that prescribers embrace the totality of clinical benefit achievable with Imetelstat and understand the efficacy profiles across MDS subgroups, including RS negative and high-transfusion burden patients. It's also critical that we provide education and support for physicians on the Imetelstat safety profile and help them to contextualize and manage cytopenias so they can offer an optimized patient experience and duration of therapy. This support will also help prescribers have a good first experience with Imetelstat, which is another important goal. From a patient access perspective, as reflected by our research, the need for new treatment options and the high unmet need populations that Imetelstat can address are expected to be important considerations to drive access and reimbursement. We are honored and privileged to have the opportunity to launch a medicine that could have such significant meaning for transfusion-dependent low-risk MDS patients and their families. And we are deeply energized to embark on this journey. With that, I will turn the call over to Faye for a medical and clinical update. Faye?
Faye Feller: Thanks, Anil, and thanks to everyone for joining our call today. As Chip mentioned, on March 14, the FDA Oncologic Drugs Advisory Committee voted 12 to 2 in favor of the clinical benefit-risk profile of the Imetelstat in transfusion-dependent lower-risk MDS indication proposed in our NDA. The ODAC considers the results from our Phase 3 IMerge trial as well as the unmet needs of and limited available treatment options for patients with this cancer. Needless to say, we are very pleased with the committee's decision to recognize the positive clinical benefit-risk profile of Imetelstat for the treatment of transfusion-dependent anemia in adult patients with lower-risk MDS. As Chip mentioned, the public forum provided a critical opportunity for the ODAC to hear from members of the lower-risk MDS community, including hematologists, patient advocates, and patients. Throughout these testimonies, there were several central themes that deeply resonated with me as a hematologist experienced in treating lower-risk MDS patients. These sentiments also echo what we hear in our market research and at medical conferences. The profoundly negative impact of anemia and transfusion-dependence on the quality of life for both patients and their families was strikingly evident. These patients are chronically fatigued and struggle to keep up with their daily activities, commonly resulting in psychosocial and emotional burden. Lower-risk MDS is a progressive disease, and by the time the patients progress to transfusion-dependence, they do not have many treatment options. In fact, hematologists at the ODAC pointed out that they usually end up cycling through most or all of their options, making an additional treatment in their armamentarium potentially practice-changing. There was also significant discussion around the deep meaningfulness of RBC transfusion-independence for these patients, one of whom testified at the ODAC that she believed transfusion-independence would give us more time to have a better quality of life. A nurse commented in a public hearing that time not spent in an infusion chair is time spent living, really living. From a clinical perspective, while transfusions can provide short-term relief, they can also cause long-term consequences. Frequent red blood cell transfusions can lead to [alkalinization] [ ph] and difficulty in identifying a matched donor to support the continuous transfusion need. Over time, patients can develop end-organ dysfunction due to iron overload. This is in addition to the psychosocial and emotional toll that transfusion-dependence can take on patients. The hematology and patient communities expressed that beyond durable RBCTI, the hemoglobin increases and reduction in transfusion burden observed with the Imetelstat are important indicators of clinical benefit. Lastly, several hematologists spoke out about their comfort level managing cytopenias, given their familiarity with these hematologic toxicities as a side effect of many medicines regularly used in clinical practice. This reinforces our belief that, with the proper context and education, these cytopenias should be able to be well-managed by hematologists in a real-world setting. Overall, hematologists, patient advocates, and patients express support for new treatment options in transfusion-dependent, lower-risk MDS, especially for treatment with the durability of RBCTI seen with Imetelstat. Turning next to our medical affairs readiness to support our expected launch. We have a highly-skilled medical affairs team in place. This team has been instrumental in conducting peer-to-peer scientific exchange of medical information, particularly via medical congresses and publications. Awareness about Imetelstat in the hematology community has been heightened by Geron's presence at congresses like EHA and ASH, and particularly by the publication of Phase 3 IMerge data in the Lancet last year. Our medical affairs team will partner with our commercial colleagues on the important effort to have Imetelstat included in the NCCN guidelines once it is approved. Lastly, our field medical colleagues are in place and are prepared to be a critical resource in helping support physicians in managing their lower-risk MDS patients. Turning now to our Phase 3 impact MS trial of a Imetelstat injecting inhibitor-relapsed refractory MS. We are proud to sponsor this first and only Phase 3 trial in MS that has overall survival as its primary end point. A total of 320 patients are planned to be enrolled using the two-to-one randomization for the hematopoietic arm versus the best available treatment arm. A protocol interim analysis has been planned when about 35% of the planned enrolled patients have died, and a final analysis when approximately 50% of the planned enrolled patients have died. As an overall survival study, the timeline for the interim and final analysis is dependent not only on the rate of enrollment, but also on the event rate or patient death rate in the trial. The data monitoring committee evaluated unblinded data last month and recommended the study continue. In addition, we reviewed enrollment rates and blinded death rates, which are lower than anticipated in our initial planning assumptions. Accordingly, we are updating our guidance to extend the timeline by half a year and now expect the interim analysis in early 2026 and the final analysis in early 2027. Because the factors affecting these estimates are highly variable and difficult to predict, the actual interim and final analysis could occur sooner or later than we currently expect. As the trial continues, we'll continue to monitor enrollment and death rates and update guidance, if appropriate. Of note, we have multiple ongoing work streams to increase trial enrollment. Our clinical operations team has been conducting onsite visits to clinical trial sites around the globe. Additionally, we've been increasing our engagement with patient advocacy groups in the myelofibrosis disease space. I think it's important to note that we at Geron, as well as the IMPACT-MS trial investigators and also patient advocates, continue to express excitement around the potential to extend survival in this JAK inhibitor relapse refractory population. Today, treatment of myelofibrosis is dominated by JAK inhibitors or therapies with other mechanisms of action in combination with JAK inhibitors. Once patients become unresponsive to JAK inhibitors, which leads to treatment discontinuation for approximately 75% of patients after five years, they face a dismal overall survival of approximately 11 to 16 months. We believe that if our trial is successful and Imetelstat is approved in this indication, it could transform treatment for these patients. With that, I'll turn the call over to Michelle for a financial update. Michelle?
Michelle Robertson: Thanks, Faye, and good morning, everyone. For detailed Q1 2024 financials, please refer to the press release we issued this morning, which is available on our website. Now, let me bring your attention to a few highlights from the quarter. As of March 31, 2024, the company had approximately $465 million in cash and marketable securities, including proceeds from an underwritten public offering of common stock and a pre-funded warrant in March 2024 for net proceeds of approximately $141 million. Total operating expenses for the first quarter of 2024 were $56.4 million, compared to $40.1 million for the same period in 2023. Research and development expenses for the first quarter of 2024 were $29.4 million, compared to $27.2 million for the same period in 2023. The increase year-over-year primarily reflects higher CMC costs due to the timing of Imetelstat commercial manufacturing batches and increased personnel-related expenses for additional headcount. G&A expenses for the first quarter of 2024 were $27.1 million, compared to $12.9 million for the same period in 2023. The increase primarily reflects our investment in commercial preparatory activities and higher personnel-related expenses for additional headcount, as we have been preparing to transition from a clinical to commercial stage company. As of March 31, 2024, and prior to adding our sales force in April, we had 162 full-time employees. Subject to approval of Imetelstat in the U.S., we plan to grow to a total of approximately 250 to 300 employees by year-end 2024. Our projected full-year 2024 operating expenses are expected to be between $270 million and $280 million. Based on our current operating plans and our assumptions regarding the timing of potential approval and commercial launch of Imetelstat and TDLR-MDS in the U.S., we believe that our existing cash, cash equivalents, and current and non-current marketable securities, together with our projected revenues from U.S. sales of Imetelstat, if approved, potential proceeds from the exercise of our expanded warrants, and future drawdowns under our loan facility, will be sufficient to support our operations into the second quarter of 2026. I will now turn the call back over to Chip.
John Scarlett: Thanks, Michelle. We believe Imetelstat has the potential to offer a life-changing treatment option for patients with transfusion-dependent lower-risk MDS. Building on the momentum from the resoundingly positive ODAC, we're deeply energized and well prepared to launch Imetelstat in the U.S., if approved. Driven by our experienced leaders and expected excellent execution, we feel confident in our ability to capitalize on this robust opportunity and to transform Geron into a successful commercial company. We believe this transformation will create significant value for patients and shareholders alike. Let's now open the line to questions. Operator?
Operator: Thank you. [Operator Instructions] Your first question comes from the line of Tara Bancroft of TD Cowen. Your line is open.
Tara Bancroft: So, mine is regarding the myelofibrosis trial timeline. Can you comment on if it was more so due to slower enrollment or if there was a heavier impact from having fewer events than anticipated? And if it's the latter, can you remind us of the bar here and maybe if your expectations have changed for where OS could land for the control? Like, how should we think about expectations here? Thanks.
John Scarlett: Thanks. Faye, go ahead and take that, please. Faye, are you off mute?
Faye Feller: Oh, apologies. Mute issues. Part of my comments, the enrollment and death rates are both lower than anticipated, and we are not able to provide additional detail into which one is the driving force. And as we noted, this pushes the timelines out about six months. So, we see continued enthusiasm for the study, and we'll continue to monitor and update as appropriate.
Operator: Your next question comes from the line of Corinne Johnson of Goldman Sachs (NYSE:GS). Your line is open.
Unidentified Analyst: This is Craig on for Corinne. So, first one from us. Have you all initiated labeling discussions with the FDA of Imetelstat and low-risk myelodysplastic syndrome?
John Scarlett: Yes. So, we've received, Craig, we've received comments from the FDA on our draft label. However, as you would imagine, the FDA hasn't yet completed its review. So, we certainly look forward to continuing our conversations with the agency as we approach PDUFA, but we do not expect to publicly disclose or discuss any ongoing regulatory interactions with the division prior to PDUFA.
Unidentified Analyst: Got it. That makes a lot of sense. And it seems from like the commercial standpoint and clinical standpoint that getting NCCN guidelines updated is a top priority. So, how quickly do you think that could occur following the potential approval of the Imetelstat?
John Scarlett: Yes. Anil, why don't you take that one?
Anil Kapur: Sure. So, Craig, we are able to provide an official submission to NCCN upon approval, which we are ready to do so. This obviously includes the approved prescribing information or the label. It includes the peer-reviewed publication, Lancet, which exists, and it includes our cover letter highlighting the patient populations. Typically, NCCN updates the guidelines within two to three months for new drugs that are received for low-risk MDS within the NCCN Low-Risk MDS Committee. So, our expectation is, if we submit in June upon approval, about two to three months later, we would expect to see the guidelines reflect Imetelstat.
Operator: Your next question comes from the line of Gil Blum of Needham & Company. Your line is open.
Gil Blum: Maybe a slightly different take on myelofibrosis. So, were there changes to the standard of care over the last couple of years that may explain some of this slower accumulation? And secondly, can you comment on what the challenges are for enrollment? Is it competition from commercial treatments, other studies, whatever information you can provide? Thank you.
John Scarlett: I'll let Faye take it first, and I'll add if necessary. Go ahead, Faye.
Faye Feller: Thanks for the question, Gil. It's pretty observant indeed. We've had the approval of a few more JAK inhibitors over the last couple of years, and I do believe that has impacted the enrollment rate. But it's multifactorial, including the new approvals of JAK inhibitors, the lack of JAK inhibitor treatment option in the BAT (LON:BATS) arm, and even still, challenges of resourcing issues at site and staffing. So, all of these contribute to the lower enrollment rates than we predicted, but this is not unanticipated and can be seen in many surveys.
Operator: [Operator Instructions] Your next question comes from the line of Stephen Willey of Stifel. Your line is open.
Unidentified Analyst: This is Julianne for Steve. Thank you for taking my questions, and congrats on the progress. We have just two questions on our end. The first one is regarding the launch preparation process for that coming approval. So, I mean, like, you've definitely provided a list of things that you guys have accomplished so far. So, in terms of preparation, what are the major steps that need to be done, and maybe, like, additional color on that? And the second question is related to just a follow-up on the prior questions regarding MF trial. So, would it be possible to provide any, like, number or percentage wise in terms of, like, enrollment rate? And also, like, what are the steps that you guys are actually taking in order to expedite enrollment? And what is your confidence level that you guys will not need to actually extend like timelines for interim and final analysis? Thank you.
John Scarlett: Let's take the first question on the launch preparations, and Anil, we'll take that one, and then we'll pivot over after that to your follow-up question on the MF trial. Go ahead, Anil.
Anil Kapur: Sure, sure. So, thanks for the question. A really important step for us is the completion of our onboarding of our full commercial team. As we stated on our call, our key account managers in the field are also now fully onboarded, and we are working very hard towards our potential approval in June, given our PDUFA date. Our concentration is both on ensuring that we have full commercial supply. Our distribution network is fully finalized. We are preparing all materials to inform stakeholders, including payers, our prescribers, and the populations that we interact with. We have identified the prescriber base. We are working towards our access and affordability solutions, everything remains on track, and our expectation is a well-executed launch for Imetelstat in the U.S. market upon approval.
John Scarlett: Thanks a lot, Anil. And Faye, why don't you take on the follow-up question on the MF?
Faye Feller: Thanks for the question. I'm going to try to remember all of the components. Regarding the enrollment rate, we announced last year in November that the study was 50% enrolled, and we plan to provide updates when this material and enrollment is continuing at a study pace. As I mentioned before, enthusiasm has not really diminished for this study. We continue to see movement forward. Remind me the other question.
John Scarlett: I can take it. I think what she was getting at was sort of the issue of how we would follow all of this going forward, and might it be necessary to refine further. Look, I think Faye said in her prepared comments that these estimates are really variable, and pretty difficult, because you have two variables, right? You have an enrollment rate, which really cannot be seen as the only contributor to the timelines here. And as you heard, we're doing everything we can to keep that enrollment rate up, and Faye commented in an answer to a previous question whether there was -- that Gil would ask about commercial launches of other competing JAK products. She mentioned the fact that we don't have a JAK inhibitor in the BAT arm, and so forth. But I think the other side is the pace at which we accrue events, right, death events. And that's a lot harder to predict. And I'll just simply say, because we do not and have not unblinded the study, of course, it's important to note, all we can look at is sort of the pace of those events, and I will remind everybody that the study is a two-for-one randomization. So, I think we made the comment in the prepared remarks that we will have to follow along, and if things require further updates, either we go slower towards the interim and final analysis, or we go faster. We'll certainly need to update, but we don't make a specific commitment on exactly when we would do that. So, I hope we'll continue to monitor both enrollment and event rates and update guidance as required. So, I hope that answers your question. I'm happy to take a follow-on if needed.
Faye Feller: I also believe there was a component to the question about what we're doing to enhance enrollment, and I'll just speak quickly about that, that we are putting a lot of effort to meeting with investigators and country and thought leaders, especially on a one-to-one level with Geron operations and clinical development staff, as well as, frequent virtual meetings and virtual, I guess you can call them, like, investigator-type meetings to remind investigators about the study and to hear any feedback on enrollment. We also, with our medical affairs teams, have been engaging more aggressively with myelofibrosis advocacy groups, both in the U.S. and internationally.
Operator: Your next question comes from the line of Joel Beatty of Baird. Your line is open.
Joel Beatty: The first one is, what percent of luspatercept use is currently in RS positive compared to RS negative, and would you expect a similar split for Imetelstat?
John Scarlett: Anil?
Anil Kapur: Sure. So, we don't have syndicated data to answer this question. What we do have is public statements from the companies stating that in RS positive, they are very well penetrated, and the numbers quoted are in excess of 65% from public statements from Bristol-Myers Squibb (NYSE:BMY), for RS positive. Does that answer your question?
Joel Beatty: Yes. That's helpful. Thank you. And then, the last question is, is there a kind of specific definition of ESA failure that might prompt starting Imetelstat, or is there some clinical judgment involved? I wonder if patients go through a period of time in which they're like partially responding to ESAs.
Faye Feller: I guess I'll take that. For the clinical trial, we have a specific definition, and what will be on the label remains to be seen, but will be according to investigator, oh, I'm sorry, physician assessment.
Joel Beatty: Great. Thank you.
John Scarlett: Anil, any further comments. Sorry. Go ahead. All right. Thanks, Joel.
Anil Kapur: Yes. And Joel, I also will point you to our deck that we are using for the call, because we have recently completed a survey of U.S. physicians, 50 of them, both academic and community, and if you look at their expectations for Imetelstat, we see ourselves being extremely well-positioned across all the patient segments that we serve. In particular, what is highlighted from physicians, and very favorably received by them, are, for Imetelstat, is the population which is ESA-ineligible in the frontline setting, and patients who are RS-negative patients, irrespective of either prior treatment with luspatercept or ESAs. And I think these are the places where we are extremely differentiated and are serving a very high level of unmet need.
Operator: Your next question comes from the line of Kalpit Patel of B. Riley Securities. Your line is open.
Kalpit Patel: I think, Chip, you previously said that you'd make the patent lifecycle decision for applying the PPE to the method of use patent around the time of FDA approval. So the question is, is that guidance unchanged today, or does the delay in the MF trial readout sort of impact the thinking behind the patent strategy?
John Scarlett: Great question. Thanks, Kalpit. I think the specifics of how application for PPE works is a little bit above my pay grade, but I'll give you my understanding of it today as best I can. After you have your first approval, you can consider whether you have a clear, strategic idea of where you would like to apply PPE. And right now, all of that is pointing towards the method of use patent. The reason for that is fairly straightforward. As many people in the investment community have pointed out, many, and you have pointed out in your coverage of us, we're covered quite well with the orphan drug exclusivity, and applying PPE to the [COM] [ph] patent wouldn't really trump that, and so there's every reason to imagine putting the PPE onto the MOU. We've done a lot of consideration in working on this, and at the end of the day, we have to indicate to FDA when, at some point after approval, what we want to do, and they will go and provide us with estimates of the exact timeframes and so forth. There's kind of a process there. Assuming all goes well there, I think it's important to say that we believe, from our analysis of this and our outside firm's analysis of this, that exclusivity would be extended to 2037. And, it would, very importantly for a method of use patent, the PPE would apply to all uses covered by the patent, including both MPS and MF, so a lot of incentives to apply it to the methods of use claim, and we'll take that up. Obviously, the implications come much later, but I don't know of any reason that we should not indicate that that's our current expectations.
Kalpit Patel: Okay. Thank you. And we've been getting questions on the manufacturing in [indiscernible] front, given what's happening in the industry. I guess, if you can comment, did the inspections and everything on that front go okay? And then I have a follow-up.
John Scarlett: Yes. I think we're not going to provide specific follow-up there, but I think that we are comfortable as things have proceeded to date. We're still looking forward to a PDUFA date with an approval, and that's the best I can really say. We all know there's always some degree of uncertainty, but other than that, I don't think we're making specific comments about the piece-by-piece march towards PDUFA on any of the different fronts, including manufacturing and inspections.
Kalpit Patel: Okay. And then, last one, we've been getting questions on how we should be modeling the U.S. launch, the initial ramp. I guess, maybe one for Anil, are there any good examples or analogs that the investor community could use to kind of project this, at least for the initial ramp for the first year or two? [Indiscernible] was obviously approved a few years ago, but that market wasn't built at that time, so people are curious how they should model this now.
Anil Kapur: Yes. So I think, Kalpit, the best guidance I'll give is to focus on unmet need of the patient population. What we have heard very clearly in the low-risk MDS market, there is dissatisfaction with the low-risk MDS market. There is dissatisfaction predominantly along three segments. One is the need for better, more effective products for patients who are high transfusion burden, which remain 40%, 50% of this marketplace, or options for RS-negative patients who today do not have effective therapies, and patients, obviously, who are ineligible for ESAs because their outcomes are pretty dismal. So, our expectation is that those are three patient populations where physicians will use drugs such as ours. We also know that, as you yourself said, luspatercept has been in this marketplace for the last two to three years, so we would expect to see patients who have been treated with luspatercept, and physicians are looking for more options. Both our Phase 2 study and our Phase 3 part of the study covered the luspatercept pre-treated patients, and given uniqueness of our mechanism, we would expect to be effective in that population as well. So, I think it's a mix of these patients. It's hard to point to one effective analog because there are many characteristics, which make each and every one of these launches unique, but I do think the unmet need is very high. Our data remains highly differentiated, and the dissatisfaction and the need for new treatments, we should see Imetelstat well-positioned and we adopted within the armamentarium of physicians as they treat their low-risk MDS patients.
Operator: That concludes our Q&A session. I will now turn the conference back over to Aron Feingold for closing remarks.
Aron Feingold: Thanks so much to everyone for joining us today. We appreciate your interest in Geron and look forward to keeping you updated during this very exciting time for our company. Have a good one, everyone.
Operator: This concludes today's conference call. You may now disconnect.
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