Geron - Earnings Call - Q3 2020

Transcript

Operator (participant)

Good afternoon. My name is Lisa, and I will be your conference operator today. At this time, I would like to welcome everyone to the Q3 2020 Geron Earnings 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. If you would like to ask a question during this time, simply press star, then the number one on your telephone keypad. If you would like to withdraw your question, press the pound key. Thank you. I would now like to turn the call over to Ms. Suzanne Messere. Please go ahead, ma'am.

Suzanne Messere (Head of Investor Relations)

Thank you, Lisa, and good afternoon, everyone. Thank you for joining us for today's conference call. I am joined today by Dr. John Scarlett, Geron's Chairman and Chief Executive Officer; Olivia Bloom, the company's Chief Financial Officer; and Aleksandra Rizo, our Chief Medical Officer. After the market closed today, we announced our third quarter 2020 financial results and recent events by a press release. It is available on our website under www.geron.com/investors. In addition, a live webcast of this call is available on our website and will be archived for 30 days. Before we begin, please note that this presentation and question-and-answer session will contain forward-looking statements relating to Geron's plans, expectations, timelines, beliefs, statements of potentiality, and projections.

These include, without limitation, those regarding the timelines for completion of enrollment of and the results from the Emerge and IMpact clinical trials, that Geron's existing financial resources will be sufficient to fund the operations into the second half of 2022, and that Imetelstat has the potential to be disease-modifying. These and other forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements.

These risks and uncertainties include, without limitation, those regarding that the COVID-19 pandemic may significantly impact the timelines for enrollment and results of the clinical trials and/or drug supply. That the company may be unable to overcome all the clinical, safety, efficacy, technical, scientific, operational, manufacturing, and regulatory challenges to meet the expected timelines for IMerge and IMpactMF. That in clinical trials, Imetelstat may be unsafe or fail to demonstrate that it is disease-modifying or efficacious. That regulatory authorities may not permit the further development of Imetelstat on a timely basis or at all. That Geron may need additional financial resources before the end of 2022 for the development and commercialization of Imetelstat.

Detailed information on the above risks and uncertainties, and additional risks, uncertainties, and factors that could cause actual results to differ materially from those in the forward-looking statements, are explained under the heading Risk Factors in Geron's quarterly report on Form 10-Q for the quarter ended September 30, 2020, filed with the SEC. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. On today's call, Dr. Scarlett plans to make a few introductory comments, after which Ms. Bloom will cover the recent debt financing, third quarter financial results, and 2020 guidance. Dr.

Rizo will provide clinical development updates regarding the ongoing Emerge phase III clinical trial in lower-risk myelodysplastic syndrome, or MDS, and the upcoming IMpactMF phase III trial in refractory myelofibrosis, or MF, and recent data announcements, including publication of the Emerge phase II data in the Journal of Clinical Oncology, also JCO, and the 10 abstracts accepted for presentation at this year's American Society of Hematology, or ASH, annual meeting. Dr. Scarlett will then finish the call with closing remarks. I will now turn the call over to Dr. John Scarlett, Geron's Chairman and CEO. Chip.

John Scarlett (Chairman and CEO)

Thanks, Suzanne. I'd like to welcome everyone to our third quarter 2020 conference call. Before we begin, I'd like to make a few comments on the COVID-19 pandemic and how we're managing it. In compliance with state and local rules and for the health and safety of our employees, access to our offices remained closed, and our employees are working from home. We also continue to limit business travel to essential business needs only. Although all of us would like to return to our normal pre-COVID schedules and routines, employee productivity and efficiency continues to be very high. Later in the call, Aleksandra will comment on the effect of COVID on our clinical activities. In the third quarter, we actively pursued our clinical, regulatory, and publication plans for the Imetelstat program.

Enrollment in the ongoing IMerge phase III clinical trial in lower-risk MDS and startup activities for the upcoming phase III clinical trial in refractory MF, which we have named IMpactMF, continued to progress. We also secured orphan drug designation in lower-risk MDS in Europe, received acceptance for presentation of all 10 abstracts submitted to the ASH annual meeting, published IMerge phase II data in the Journal of Clinical Oncology, and strengthened our balance sheet with a loan facility that provides additional financial flexibility to further support our plans for Imetelstat development going forward. We continue to work toward completing enrollment in IMerge in the first quarter of 2021. However, given the recent resurgence of the COVID-19 pandemic, it is causing an uncertain and unpredictable impact on clinical trial activities.

Due to these challenges, we now believe the trial will most likely be fully enrolled in the second quarter of 2021. As long as enrollment is completed by the end of the first half of 2021, we continue to expect top-line results from Emerge to be available in the second half of 2022, as previously guided. Switching studies, based on current feedback from the clinical sites that are planned to participate in IMpactMF, we continue to expect that trial to be open for screening and enrollment in the first quarter of 2021. I would like to hand over the call now to Olivia to discuss what the debt financing means for our cash position, our third quarter financial results, and our guidance. Olivia?

Olivia Bloom (CFO)

Thank you, Chip. Good afternoon, everyone. As of September 30, 2020, we had approximately $274 million in cash, cash equivalents, and current and non-current marketable securities. Our cash position reflects net proceeds of approximately $140 million from a public offering in May 2020 and approximately $24 million in initial net proceeds from a non-dilutive $75 million loan facility that closed at the end of the third quarter. The loan facility will be available to Geron through year-end 2022 in three tranches, subject to certain terms and conditions, including the achievement of certain clinical, financial, and regulatory milestones. The loan facility provides us with access to non-dilutive financial resources to support the Imetelstat development program, as well as working capital and general corporate purposes.

Based on current planning assumptions, we estimate our current financial resources to be sufficient for our operations until the end of 2022, during which time we plan to reach two significant inflection points: top-line results for the IMerge phase III clinical trial in lower-risk MDS and completion of patient enrollment for the upcoming IMpactMF phase III clinical trial in refractory MF. Overall, the financial results for the third quarter and year-to-date period were in line with our expectations. Operating expenses for the three and nine months ended September 30, 2020, were generally higher in comparison to the same period in 2019 due to headcount increases in 2019 across the company, increased activity for the IMerge phase III clinical trial in lower-risk MDS, startup activities for the upcoming IMpactMF phase III clinical trial in refractory MF, and costs associated with validating Imetelstat manufacturing processes.

Importantly, our manufacturing and quality teams recently accomplished an operational milestone in establishing our Imetelstat supply chain. Our clinical sites are now starting to receive Geron-manufactured Imetelstat and placebo in the IMerge phase III. This achievement helps ensure uninterrupted drug supply for both current and future clinical trials, as well as enables Geron-manufactured materials to be included in the current phase III registration enabling trials. We plan to use the same manufacturers that produce these clinical materials for potential future commercial manufacture of the drug. We expect operating expenses to be higher in the second half of 2020 in comparison to the first half as we begin to support two phase III clinical trials with Imetelstat, the ongoing IMerge phase III, and the upcoming IMpactMF phase III.

Regarding financial guidance for 2020, we are reiterating our expectation of operating expense burn to range from $70-$75 million. Financial guidance is based on a set of assumptions at a point in time, and if the company's plans change, causing assumptions to be revised, then we expect to update guidance at that time. With that, I will now turn the call over to Aleksandra to provide an update on our phase III clinical development activities and to discuss the data published recently in the Journal of Clinical Oncology and the multiple presentations upcoming at the ASH conference in December. Aleksandra?

Aleksandra Rizo (CMO)

Thanks, Olivia. Good afternoon, everyone. Before I discuss recently published Imetelstat data, I'd like to give a brief update on our phase III clinical trials in refractory MF and lower-risk MDS. The clinical protocol for our upcoming phase III clinical trial in refractory MF, called IMpactMF, has been finalized, and the trial is now listed on clinicaltrials.gov. We continue to expect the trial to be open for screening and enrollment in the first quarter of 2021. Startup activities are ongoing and include site selection, engagement of vendors, building of the clinical database, among others. In the IMpactMF trial, the final analysis for the primary endpoint of overall survival, or OS, is event-driven and is planned to be conducted after more than 50% of the patients involved in the trial have died.

An interim analysis of OS is planned to be conducted after approximately 70% of the total projected number of death events for the final analysis have occurred. If the pre-specified statistically significant difference in OS between the two treatment arms is met at the interim analysis, it is possible that data from the interim analysis could support registration filing. Moving on to the ongoing Emerge phase III clinical trial in lower-risk MDS. Enrollment for this trial continued to progress in the third quarter. In August, all 92 of the originally planned clinical sites were open for enrollment. To address enrollment delays related to the COVID-19 pandemic experienced earlier this year, we implemented several enrollment-boosting activities. These include engaging clinical science liaisons to interface directly with the clinical sites, establishing a digital presence for the trial, and expanding the number of clinical sites in existing and new countries.

We currently expect to open approximately 30 new clinical sites, although at this time only a handful are open. As a result, we believe the full benefits of the additional sites have not yet been realized. We expect almost all of these sites to be open for screening and enrollment by the end of 2020. Our team internally is continuing to target completion of enrollment in Emerge by the end of the first quarter. Despite our efforts, given the recent resurgence of the COVID-19 pandemic, particularly in many of the countries where Emerge is being conducted, and the uncertainty and unpredictability regarding its impact on clinical trials activities this coming fall and winter, we now believe it is most likely the trial will be fully enrolled sometime in the second quarter of 2021.

However, it is important to note that as long as enrollment is completed by the end of the first half of 2021, we continue to expect top-line results to be available in the second half of 2022, which is consistent with our previous guidance. As announced in a press release last week, the data from IMerge phase II trial in lower-risk MDS was published in the well-respected Journal of Clinical Oncology, or JCO. We believe this publication further indicates the recognition of the importance of the IMerge data by experts in the MDS field. As you may recall, meaningful and durable transfusion independence with Imetelstat treatment has been highlighted consistently in previous medical conference presentations, as it is in the JCO article. The median duration of transfusion independence of 21 months is a critical clinical outcome for these transfusion-dependent patients.

Moreover, as reported, approximately 30% of the patients were transfusion-free for over a year. To our knowledge, this is the longest duration of transfusion independence reported in lower-risk MDS patients. In addition to the durable transfusion independence, a decrease in SF3B1, one of the key mutations correlated with ineffective erythropoiesis in lower-risk MDS, was observed in the trial, although only a small number of patient samples were available for testing. Of critical importance, the duration of the transfusion-free period was correlated with the decrease of the SF3B1 mutation, and patients that had the highest decrease of SF3B1 also had the longest transfusion-free period. To put these data in context, we hope that telomerase is continuously upregulated in malignant stem and progenitor cells, resulting in malignant hematopoiesis.

As a telomerase inhibitor, Imetelstat selectively targets malignant cells with continuously upregulated telomerase to induce their death and enable potential recovery of normal hematopoiesis. Decrease in disease mutations, such as the SF3B1 mutation, is an indicator of potential impact on the malignant cells of the underlying disease, which suggests disease-modifying activity. In addition, observations of clinical outcomes, such as the durable transfusion-free period experienced by the patients in the IMerge phase II, indicate potential recovery of normal hematopoiesis suggesting disease-modifying activity. Therefore, we believe both the durable transfusion independence and the reduction in the SF3B1 mutation observed in the IMerge phase II suggest disease-modifying activity for Imetelstat treatment in these patients. Regarding ASH, yesterday we announced that a total of 10 abstracts have been accepted, of which four will be oral presentations.

In summary, the data and analysis reported in all of the abstracts support our phase III clinical trials and highlight the clinical benefits observed in both phase III IMerge and IMbark trials. There are several abstracts covering the IMbark phase II, including new data on patient-reported outcomes, data on improved OS in triple-negative MF patients, as well as biomarker data and analysis supporting the on-target activity of the drug. Also, there are two abstracts called Trials in Progress that provide further detail of the trial design for the ongoing IMerge phase III and the upcoming IMpactMF phase III. This afternoon, I would like to focus on the data suggesting potential disease-modifying activity of Imetelstat from the IMbark phase II trial in relapsed refractory MF that were reported in two of the ASH abstracts.

One of the ASH abstracts, number 346, which is scheduled for an oral presentation, reports new analysis from the IMbark phase II trial that shows significant dose-dependent reduction of the mutation burden of key driver mutations for MF, as measured by reduction in the variant allele frequency, or VAF, of the mutations. The data showed that the patients who had reduction in VAF had prolonged median OS of 31 months versus 21 months for those patients that did not have reduction in VAF. The abstract concludes that depletion of cytogenetically abnormal clones and reduction in mutation burden, together with the improvement in median OS, further demonstrate that Imetelstat has disease-modifying activity by targeting malignant cells.

The second abstract in MF, number 658, which is scheduled for an oral presentation, describes a set of data from the IMbark phase II showing that there was a correlation between the improvement in fibrosis and improved median OS. In other words, the patients that had at least one degree of fibrosis improvement had significantly longer survival than those who had worsening of fibrosis. In conclusion, we believe that the data from the JCO publication and these two abstracts highlight Imetelstat's impact on the malignant cells responsible for the underlying disease, as well as the clinical outcomes of durable transfusion independence for lower-risk MDS patients and improved overall survival for relapsed and refractory MF patients. Taken together, these data continue to build the clinical and biomarker evidence suggesting disease-modifying activity, which we believe differentiates Imetelstat from other treatments for low-risk MDS and refractory MF.

Now I'd like to hand the call back to Chip. Chip?

John Scarlett (Chairman and CEO)

Thanks, Aleksandra. In closing, I'd like to reiterate that we continue to advance both the IMerge and IMpactMF phase III clinical trials. Through medical conferences like ASH and in scientific and clinical journals, we continue to raise awareness of Imetelstat's disease-modifying data. We are also pleased to report that we have established our own Imetelstat supply chain, which will allow Geron-manufactured materials to be included in the current phase III registration enabling trials, which is an important step in NDA readiness. Finally, we have also strengthened our balance sheet to further support our plans for Imetelstat development going forward. We believe that these efforts will help establish Geron as a leader in hematologic myeloid malignancies, thus creating long-term shareholder value. With that, we'd like to answer your questions. I'll turn the call back over to our operator, Lisa.

Operator (participant)

At this time, I would like to remind everyone, if you would like to ask a question, please press star and the number one on your telephone keypad. Your first question comes from the line of Gil Blum, the Needham & Company.

Gil Blum (Analyst)

Hi, good afternoon, everyone, and thank you for taking our questions. I'm on here for a chat. Maybe a bit of a strange question. Is there any overlap between the IMerge and IMpactMF study sites?

John Scarlett (Chairman and CEO)

Aleksandra, can you take that? Overlap between the two studies and sites in terms of sites?

Aleksandra Rizo (CMO)

Yeah, there are sites that are overlapping for sure between the two studies.

Gil Blum (Analyst)

Gotcha. It looks like you have a very big ASH ahead of you, lots of presentations. What can you share about some plans for KOL outreach and those kinds of activities, considering this is a virtual format? Go ahead.

Aleksandra Rizo (CMO)

Yeah, I mean, it's a good question. He just gave the answer, I guess. Because it's a virtual meeting at the moment, we have not planned a KOL activities, but that's at the moment. However, we will be sponsoring a few of the educational sessions that will be at ASH.

Gil Blum (Analyst)

Kind of last, we know that getting your own supply of Imetelstat gives you flexibility and control over your own supply chain. Is there any situation in which that supply chain would be affected by the ongoing pandemic?

John Scarlett (Chairman and CEO)

Gil, we don't see that as a major risk. Much of our supply chain is in South Korea, which is probably one of the best-controlled countries so far, and so I would comment on that. Second of all, we managed all of this, all of these activities, which were very substantial during the height of the pandemic. While it's impossible to never say never, or I guess we shouldn't say never say never, I think it's pretty low risk right now.

Gil Blum (Analyst)

Excellent. Thank you for taking our questions, and congratulations on all the progress.

John Scarlett (Chairman and CEO)

Thanks.

Aleksandra Rizo (CMO)

Thanks.

Operator (participant)

Your next question comes from the line of Bonnie Quach with Stifel.

Bonnie Quach (Analyst)

Hi, this is Bonnie. I'm from Stifel. Thanks for taking my question. I wanted to ask more about the enrollment of the Emerge study. Is the patient population that you're enrolling so far somewhat similar to the patient population enrolled in the phase II trial in terms of RS positive and RS negative, as well as transfusion burden? Because I remember the phase II patients had a pretty high transfusion burden.

John Scarlett (Chairman and CEO)

Correct. I'll let Aleksandra answer that first. If you have it more on, I may take them. Go ahead.

Aleksandra Rizo (CMO)

Right. The inclusion and the exclusion criteria for the phase III part of the study have not changed to those of the phase II part of the study that were defined for the target patient population, which means that we are still enrolling patients irrespective of the presence or absence of ring sideroblasts, and we are still enrolling patients that had at least four units prior to the enrollment on the study, prior to the randomization on the study. Again, we are enrolling the same patient population from the target population.

Bonnie Quach (Analyst)

Thank you. For the MDS patients who achieve transfusion independence but then end up requiring transfusions again, is there any evidence of the potential of achieving a durable transfusion or achieving that transfusion independence again with continued treatment? Is this something you looked into?

Aleksandra Rizo (CMO)

Absolutely. That has been already reported in a few of the patients at last ASH. We do have patients that achieved transfusion independence, for some reason had to stop or had to, sorry, had to receive transfusion and then again became transfusion independent.

Bonnie Quach (Analyst)

Just a small follow-up to that. How do you see this playing out in a real-world setting in terms of keeping patients on drugs once they've gone back to receiving transfusions again?

Aleksandra Rizo (CMO)

How we can see.

John Scarlett (Chairman and CEO)

If I understand the question, it was, so what happens in the real world if a patient has achieved transfusion independence and then they require a transfusion? Are they going to just stop the drug or are they going to potentially continue on? Is that your question?

Bonnie Quach (Analyst)

Yes.

John Scarlett (Chairman and CEO)

Okay. I'll let Aleksandra know.

Aleksandra Rizo (CMO)

Right. I mean, at the moment, I really don't see a reason why they wouldn't continue, right? If you are transfusion independent and you are benefiting from the drug, you're feeling better, you don't need transfusions, I believe you would like to continue receiving treatment. I don't see a problem in keeping the patients on treatment once they have potentially—yeah, sorry, Chip.

John Scarlett (Chairman and CEO)

Yeah. I think just to answer the question very directly, I think if a patient for whatever reason requires a transfusion, these patients are used to requiring different levels of transfusion, etc. If they require a transfusion, I think our experience suggests that they would likely continue to give Imetelstat an opportunity to keep them transfusion-free again. It goes back to the question that you asked before. What happens to patients who quit having transfusion independence? Do they then reestablish transfusion independence after getting a transfusion? Can the drug continue to work? The answer is unequivocally yes. I think because of that, the likelihood is that investigator, or sorry, in this case, treating physicians and patients would have a very high incentive to continue on the drug even if there was an interruption of their transfusion-free period of time.

Aleksandra Rizo (CMO)

Yeah.

Bonnie Quach (Analyst)

Yeah.

Aleksandra Rizo (CMO)

Chip, I just wanted to add, oh, I'm sorry. Go ahead, Bonnie.

Bonnie Quach (Analyst)

Oh, no. I have nothing. Please go ahead.

Aleksandra Rizo (CMO)

I just wanted to add one more item. I know we are discussing transfusion independence, but recall in our study we have 68, about 70% of the patients who have hematologic improvement, and those are the patients that actually have decreasing the need of transfusion. It is a large proportion of patients that benefit from our drug, irrespective whether they would achieve eventually transfusion independence, which still happens in a large in 42% of the patients. Again, 68 have hematologic improvement and decrease in transfusion need. I believe that is really a good reason to stay on drugs.

Bonnie Quach (Analyst)

Very true. Thank you so much for answering all my questions.

Aleksandra Rizo (CMO)

Okay. Thank you.

Operator (participant)

Your next question comes from the line of Charles Duncan with Cantor Fitzgerald.

Charles Duncan (Analyst)

Hi, John and team. Congrats on continued enrollment in IMerge and the manufacturing milestone as well as the ASH abstracts. Thanks for taking my questions. I had a couple, so I'm going to try to be quick. First of all, with regard to IMerge and the enrollment discussion around 1Q or 2Q next year, is it the result of an observed kind of change in enrollment patterns or getting new sites up and running in terms of executing on that, or just prudence?

John Scarlett (Chairman and CEO)

I'll take that, Chaz. Thanks for the question. First of all, let me make a couple of comments. Look, we debate a long time about how to characterize the uncertainty that was caused by COVID and also the comment that many experts believe that the worst is yet to come, right? At the same time, we have not yet begun to see the kind of the broad-based self-imposed holds similar to what we saw early in spring and summer of the year when sites were initially feeling the first effects of COVID. What we are seeing is that sites are beginning to adapt in order to enable patient treatment to continue. These are kind of the unknowns at the point. What? How severe is the increase going to be this fall and winter? How effective are the measures employed by these sites to stay open?

How effective are they going to be despite increasing numbers of COVID cases? How effective are our enrollment-boosting activities going to be at the existing sites? How effective will we have, how many of these new sites will come online by the end of the year? As we said, we hope that most will come on. COVID makes this all pretty tough. Our best assessment was that we believe it's most likely that we'll be fully enrolled in the second quarter. I really want to make the point that, and we did, by the way, feel like that was the best and most responsible way to weigh and communicate these various scenarios.

I do want to be really clear that also if we achieve that by the end of the second quarter, we will still be on track and on time for our top-line results as previously communicated.

Charles Duncan (Analyst)

Okay. Yeah. I understand that's an event-driven study, so there may be a little bit of conservatism in that as well. It sounds like it's a prudence thing in terms of enrollment on IMerge. Are you detecting the same kind of level of enthusiasm around the profile of Imetelstat for investigators in terms of enrolling patients as you did when you launched this study?

John Scarlett (Chairman and CEO)

Yeah. I'll let Aleksandra comment on that.

Aleksandra Rizo (CMO)

Yeah. Yeah. I can just reaffirm and reconfirm that that's the case. The data that had been published in JCO has really even further raised enthusiasm. We work very closely. I mean, even though I answered we're not maybe having an event at ASH, we're working very, very closely with all of the key opinion leaders in the field. We feel confident about the outreach to the KOLs and the interest from the KOLs in our study and the sites, just the PIs that are participating on our study.

Charles Duncan (Analyst)

Oh, okay. That's helpful. With regard to the IMpactMF trial, which I got to tell you I really like because it says something more to me than the previous study names. Can you just remind me, or maybe I should go to clinical trials, but can you remind me the event rate that you were assuming in IMpactMF or kind of time to event that you're looking at going in on that?

Aleksandra Rizo (CMO)

In terms of, I don't think that information will be on ClincalTrials.gov. We have not published that. As I was saying, the study is eventually, as you said, we do plan to have an interim analysis when 70% of the events that were planned for the final analysis to occur will happen. At that point, if there is statistically significant difference between the two arms, it is possible that data is used to support a filing. It is 70% of the 50% that are required at the end of the study.

Charles Duncan (Analyst)

Okay. The kind of time to that, you really haven't published, and I can understand why. Is that clear? Is that the answer?

Aleksandra Rizo (CMO)

Oh, Chaz, just a little bit just to remind you. As of now, we're projecting that it's in the first half of 2023 potentially for the interim and the final potentially first half of 2024.

Charles Duncan (Analyst)

Okay. Last question is regarding manufacturing. It's cool to see that you folks have been able to get that up and running despite the challenges of COVID. I guess I'm wondering if any patients have been dosed with older drug or the drug from Janssen, and is there any bridging or anything, or can you handle kind of the comparisons through analytical methods?

John Scarlett (Chairman and CEO)

Let me comment on that. Fundamentally, we're using the same manufacturing process. The sponsorship changed. The vast majority of the processes and even the companies involved and the contract manufacturing groups involved are the same. This is now made completely under our aegis, under our sponsorship. All of the patients treated so far in the MDS study have been using material made by Janssen and under Janssen sponsorship. What's changing is it will be feeding the new material made under our sponsorship into this study as it progresses. As you may know, although it's not a high-risk situation because it's all the same process, it is kind of a regulatory box to tick that what is expected to be the final commercial process and group is being used in the phase III study.

I think we've avoided a footfall here, certainly, and likely have ticked off an important but key-ish regulatory box to check.

Charles Duncan (Analyst)

Got it. Okay. Congrats on the progress. Excuse me. Thanks for taking my question.

John Scarlett (Chairman and CEO)

Sure.

Operator (participant)

Your next question comes from the line of Tom Shrader with BTIG.

Tom Shrader (Analyst)

Hi, good afternoon. Thanks for the update, as always. A quick question on IMpact. The interim look, is that a tiny alpha spend? The bar is very high. Is that reasonable for us to, or is that a real, would the drug have to just perform spectacularly?

Aleksandra Rizo (CMO)

I would say that it's a reasonable alpha that we've allocated for the interim analysis.

Tom Shrader (Analyst)

Okay. Then.

Aleksandra Rizo (CMO)

If there is a statistically significant difference, Tom, right? It is reasonable, but there has to be a statistically significant difference, and thereby it is possible still to have the data from the interim to support the registration.

Tom Shrader (Analyst)

Okay. Got it. I was a little surprised by first half interim in 2023 and first half full for 2024. A lot of these trials enroll sort of very slowly, and once they get rolling, they enroll like mad. Do you expect this to enroll more linearly because all the centers are well established and the patients are pretty well known? Just kind of an unusually linear forecast you see enrollment?

Aleksandra Rizo (CMO)

Yeah. I don't think we can predict the pattern for this study specifically. However, again, based on clinical oncology experience in general, as you say, most of the enrollment happens towards the end of the study. I mean, I just don't think I can comment or I can predict how that will be for this study.

Tom Shrader (Analyst)

All right. One more. You started to talk about mutant clones and treatment rates. Do telomerase lengths correlate with any of the mutant clones? At this point, it's not so relevant, but is it validating the mechanism of the drug as originally proposed?

Aleksandra Rizo (CMO)

If I would have to choose between telomerase, sorry, telomere length, telomerase activity, and age tert, I would rank telomere length last, to be honest, just because of the assay and of the difficulty to really measure telomere length. We have good assays and good correlations with TA and age tert as the PD markers with the response or, I would say, clinical outcomes in our studies. That's not always the case with telomere length.

Tom Shrader (Analyst)

All right. Great. Okay. Great. Thanks, guys. Look forward to ASH.

Aleksandra Rizo (CMO)

Thank you.

John Scarlett (Chairman and CEO)

Thanks, Tom.

Operator (participant)

Your next question comes from the line of Justin Dillon with B Riley Securities.

Justin Dillon (Analyst)

Hi, team. Congrats on all the progress and also on a couple of the abstracts at ASH. I found one of the abstracts on the PRO data to be interesting that you have here. I'm curious on whether you'll be capturing similar PRO-type data in the IMpactMF study, whether it be fatigue measures or priorities in the trial?

Aleksandra Rizo (CMO)

Thank you for that question. Yes, as you noticed already in the phase II study, we used a lot of the measures that are typically used for registration studies. Yes, we will be using, again, the ERTC, QLQ230, the BPI. All of the right scales, if you will, to prove the significance of the patient-reported outcomes and benefits.

Justin Dillon (Analyst)

Got it. That's great. Maybe just turning over to manufacturing. I understand the process that you've outlined there, Chip, and congrats again on that milestone. I just wanted to confirm that you don't expect the FDA will ask you for any type of analytical comparability study or bridging study that needs to be done between the different material batches that you've had in your studies. Thanks.

John Scarlett (Chairman and CEO)

I'm not the expert in the company by any means on the manufacturing. I think that we don't think there will necessarily be a defined requirement for a separate, certainly not a separate clinical study because we haven't really changed the process that much. There will, of course, be many comparisons of the materials made, right? As long as they're staying within certain bounds. That wouldn't be a clinical study. Those would be analytic comparisons, etc., which, by the way, occurs at some level in any of these various manufacturing batches. I'm sure those comparisons will be made. I am unaware personally of any requirement for any kind of clinical study to make that change or to confirm that it's the same material. Yeah. Sorry.

Justin Dillon (Analyst)

Got it. Got it. No, that's great. It's very helpful to hear. Congrats on all the progress. I'm looking forward to seeing all the ASH presentations. Thanks.

John Scarlett (Chairman and CEO)

Okay. Thanks.

Operator (participant)

That concludes our Q&A session for today. I would now like to turn the call back over to Dr. John Scarlett.

John Scarlett (Chairman and CEO)

Thanks, everybody, for joining us today. We really look forward to sharing the achievement of several milestones in the remainder of this year, including the presentations to be made at ASH. Everyone, please stay healthy and safe, and we'll look forward to the next time we get a chance to at least talk, if not meet in person. I think that concludes our call today, Operator. Thank you.

Operator (participant)

This concludes today's conference. You may now disconnect.