Geron Corporation (GERN) Q1 2020 Earnings Report, Transcript and Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Q1 2020 Geron Earnings Conference Call. [Operator Instructions]. I would now like to hand the conference over to your speaker today, Head of Investor Relations, Suzanne Messere. Thank you. Please go ahead.

Thank you, Chantal, 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; and Olivia Bloom, the company's Chief Financial Officer. Also joining me today are Aleksandra Rizo, our Chief Medical Officer; and Anil Kapur, our Head of Corporate Strategy and Chief Commercial Officer. After the market closed today, we announced our first quarter 2020 financial results via press release. It is available on our website under www.geron.com/investors, as well as several other press releases announcing recent developments in the month of May. In addition, a live webcast of the 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, time lines, beliefs, statements of potentiality and projections. These include, without limitation, those regarding the time lines for completion of enrollment of and the results from the ongoing Phase III IMerge and planned refractory MF clinical trial, that Geron's existing financial resources will be sufficient to fund operations into the second half of 2022, potential revenues and that Geron's 2020 operating expense burn will be in the range of $70 million to $75 million. 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 company may be able to overcome all the clinical, safety, efficacy, technical, scientific, operational, manufacturing and regulatory challenges to enable the expected time lines for the IMerge and planned refractory MF clinical trials; that regulatory authorities may not permit the further development of imetelstat on a timely basis or at all; that the COVID-19 pandemic may significantly impact the time line for both the enrollment and the results of the clinical trials and/or drug supply; that competition or other factors result in lower than projected revenues; and that there may be unexpected operating expenses or events or changes in Geron's plans that caused the $70 million to $75 million 2020 financial guidance to be revised. 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 March 31, 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. I will now turn the call over to Dr. John Scarlett, Geron's Chairman and CEO. Chip?

Thank you, Suzanne. I would like to welcome everyone to our first quarter 2020 conference call. On today's call, I'll have some introductory remarks. Olivia will cover Q1 results, 2020 guidance and the recent financing. And Aleksandra will discuss recently announced clinical development activities in MF and MDS. To start our call today, I'd like to share with you my conviction that Geron today is a fundamentally different company. It's a company in which all the pieces necessary to become a leader in the treatment of hematologic myeloid malignancies are now in place. We have a novel drug and a unique target; meaningful clinical activity and indications with significant unmet need; 2 Phase III trials, one ongoing and another planned, both based on compelling Phase II data; a highly experienced team to execute all aspects of drug development; and the financial resources to reach significant value inflection points. We've known for many years that imetelstat has a unique mechanism of action. A malignant stem for gender and blood cells, telomerase, is continuously upregulated, resulting in malignant hematopoiesis. Imetelstat selectively targets malignant cells with continuously upregulated telomerase, inducing their apoptosis or cell death and enabling potential recovery of normal hematopoiesis. As we continue to treat and follow patients in our Phase II IMerge trial in lower-risk MDS, data continued to mature and improve. We have an increasingly differentiated profile of imetelstat compared to other agents with a high rate of transfusion independence that is similar in both the RS-positive and RS-negative patients; a remarkable durability of transfusion independents, even in patients with high baseline transfusion burdens; and substantial rises in hemoglobin levels that suggest potential recovery of normal hematopoiesis in patients treated with imetelstat. The Phase III trial in lower-risk MDS continues to enroll patients, and enrollment is currently expected to be completed by the end of the first quarter of 2021, with top line results expected in the second half of 2022. Imetelstat also represents a highly differentiated therapy designed to address the current unmet need in patients with Intermediate-2 or high-risk myelofibrosis unresponsive to JAK inhibitor therapy. Imetelstat-treated MF patients, who were relapsed or refractory to JAK inhibitors in our Phase II IMbark trial, exhibited a median overall survival that compares very favorably to both historical controls into a real-world data analysis of closely matched patients who discontinued JAK inhibitors and were treated with best available therapy. Based on these analyses and our data and the regulatory clarity we have from our recent interactions with the FDA, we've designed a randomized Phase III trial in refractory MF patients with overall survival as a primary end point and a control arm of best available therapy that excludes JAK inhibitors. We expect that trial to be open for screening and enrollment in the first quarter of 2021. Both the lower-risk MDS and refractory MF indications represent very substantial unmet medical need. And if we are successful in bringing imetelstat to the market for both indications, we believe they represent a combined annual revenue potential of approximately $1.25 billion in the United States and approximately $2.5 billion worldwide. To execute successfully on our plans in these indications, we'll be relying on our very experienced, dedicated in-house professional drug developers. This extraordinary group includes individuals who are key team members working with imetelstat at Janssen, including our Chief Medical Officer, Dr. Aleksandra Rizo; and our Chief Commercial Officer, Anil Kapur. These individuals have followed imetelstat to Geron, bringing with them years of experience in clinical science, regulatory affairs, statistics, clinical operations and commercial strategy. We've also recruited other talented professionals with experience from other very successful companies in those areas as well as others in drug safety, manufacturing and quality operations. And finally, due to our successful recent public offering, today, we have the money to achieve our development plans in 2 Phase III indications. It was particularly gratifying to see the response of investors to this transaction, especially leading biotechnology specialist investors such as EcoR1, Great Point, NEA, RA Capital and Sentara. They joined with other investors in making a very significant investment, which we believe provides strong affirmation for both imetelstat and Geron. Perhaps that's a good segue to Olivia's discussion of the financing and our updated financial guidance. Olivia?

Thank you, Chip, and good afternoon, everyone. Before discussing the recent public offering, I will briefly summarize our financial results for the first quarter of 2020. Overall, the financial results are in line with our expectations. Operating expenses are generally higher in comparison to the first quarter of 2019 due to increases in headcount across the company as well as increasing activity for the IMerge Phase III clinical trial in lower-risk MDS. As of March 31, 2020, we had approximately $133 million in cash, cash equivalents and current and noncurrent marketable securities. Our spending in the first quarter of 2020 reflected normal business activities into March and then a curtailment of certain costs due to the impact of the COVID-19 pandemic. Although certain external vendor costs related to the IMerge Phase III clinical trial are estimated to be lower in the second quarter of 2020 as a result of a reduction in clinical trial activity, limited by the COVID-19 pandemic, we expect much of our personnel-related expenses will continue in line with the first quarter of 2020 with some decline as a result of travel restrictions. However, we project expenses will increase in the future as we begin to support 2 Phase III clinical trials of imetelstat: the ongoing IMerge Phase III clinical trial and the planned Phase III clinical trial in refractory MF. Regarding financial guidance for 2020, we expect our operating expense burn to range from $70 million to $75 million. The guidance reflects cash conservation measures implemented in April due to the COVID-19 pandemic such as suspending travel and postponing a planned imetelstat proof-of-concept study. It also includes new costs for start-up activities associated with the planned Phase III clinical trial in refractory MF, and additional costs for the expansion of clinical sites for the IMerge Phase III clinical trial. 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. Yesterday, we closed an underwritten public offering of common stock and warrants. Due to the strong demand, not only was the offering upsized but it was also oversubscribed. We expect the estimated net cash proceeds to Geron from the public offering to be approximately $140 million after deducting the underwriting discount and estimated offering expenses payable by the company. Based on current planning assumptions, we estimate that these net proceeds, together with our existing financial resources, will provide sufficient funds for our operations into the second half of 2022 when we expect top line results for the IMerge Phase III clinical trial in low-risk MDS and completion of patient enrollment for our planned Phase III clinical trial in refractory MF. With that, I will now turn the call over to Aleksandra to provide details around our clinical development activities. Aleksandra?

Thanks, Olivia, and good afternoon, everyone. Due to its novel mechanism of action, imetelstat remains unique in comparison to the currently available treatment in myelofibrosis as well as other investigational agents in Phase III clinical trials today. The overall survival data from our IMbark Phase II clinical trial in the Intermediate-2 or high-risk MF patients, relapsed or refractory to JAK inhibitor, highlights the potential clinical benefit achievable with imetelstat treatment and indicate the potential disease-modifying activity of the drug. Today, there are limited treatment options available for patients who become relapsed or refractory to JAK inhibitors and discontinue ruxolitinib. Approximately 75% of patients discontinued treatment with ruxolitinib, as you might know, within 5 years. And median survival after discontinuation is dismal and has been reported to be 14 to 16 months. Meanwhile, as we have previously reported, the median overall survival in IMbark was 28.1 months, And it was similar for both refractory and relapsed patients. This potential improvement in overall survival associated with imetelstat treatment, was further corroborated by rigorous real-world data analysis from patients treated with best available therapy at the multi-cancer center, who are closely matched for demographic and disease characteristics with imetelstat-treated patients from IMbark. In those analysis, the patients treated with BAT had a median overall survival of approximately 12 months compared to the imetelstat-treated IMbark patients who had an overall survival of approximately 30 months. A few weeks ago, we announced the 3 abstracts were accepted for poster presentations at the upcoming European Hematology Association or EHA Annual Congress. These abstracts report the recent IMbark data analysis and provide further support to the OS results from IMbark. In one of the abstracts, the new data analysis suggested that the improvement in overall survival and IMbark correlate with other clinical benefits observed in its trial, most notably with fibrosis improvement as well as symptom and spleen response. The second abstract reports improvement in OS in triple-negative MF patients treated with imetelstat in IMbark. Triple-negative patients represent a patient subpopulation that affects the 3 driver mutations in myelofibrosis and that have a poor prognosis. The third abstract reports biomarker data, indicating on-target, dose-dependent distribution of telomerase after treatment with imetelstat, and this correlated with the improvement in overall survival in IMbark. Taken together, we believe that the 3 MF abstracts substantiate the OS data observed in IMbark and support the plans with 3 clinical trials in refractory myelofibrosis. Let me now discuss the planned Phase III trial in a bit more detail. Since we disclosed, we discussed this trial design with the FDA, and they agree that we could move forward, which will be an open-label, one randomized Phase III trial of imetelstat compared with best available therapy in approximately 320 patients with Intermediate-2 or high-risk MF for refractory to JAK inhibitor treatment. Patients eligible for the trial will be required to be refractory to a JAK inhibitor, defined as patients who have had an adequate -- inadequate spleen response or symptom response after treatment with a JAK inhibitor for at least 6 months and who had received an optimal dose of a JAK inhibitor for at least 2 months during the treatment period with a JAK inhibitor. Given this definition, we believe that refractory MF patients meeting these criteria will not benefit from further JAK inhibitor treatment, which is why the control arm of best available therapy will exclude JAK inhibitors. In the imetelstat treatment arm, 9.4 milligrams per kilogram of imetelstat will be administered intravenously every 3 weeks. As Chip mentioned, the primary end point for the trial is planned to be overall survival. And we believe this is the first trial in refractory myelofibrosis to use overall survival as a primary end point. Planned key secondary end points include symptom response, spleen response, progression-free survival, complete and partial response, clinical improvements, duration of response, safety, pharmacokinetics and patient-reported outcomes. The trial has been designed to have more than 80 -- 85% power to detect a 40% reduction in the risk of death for imetelstat-treated patients. In making these power calculations and starting the trial size, we assumed a hazard ratio of 0.6 and a one-sided alpha of 0.025. For example, we made the assumption that the best available therapy arm will have a median overall survival of 14 months and the imetelstat arm will have a median overall survival of 23 months. The final analysis for OS is planned to be conducted after more than 50% of the total enrolled patients have died. An interim analysis of OS, in which the alpha spend is expected to be approximately, 0.01, is planned to be conducted after approximately 70% of the total projected number of deaths for the final analysis have occurred. At the interim analysis, if the prespecified statistical OS criterion is met, then we expect such data may support registration of imetelstat in refractory MF. If the prespecified OS criterion is not met at an interim analysis, the trial will continue to a final analysis. Currently, we expect to engage over 150 sites across North America, South America, Europe and Asia. Start-up activities have already begun and we plan to open the trial for screening and enrollment in the first quarter of 2021. Under current assumptions, we expect to complete patient enrollment in the second half of 2022, to conduct an interim analysis in the first half of 2023 and to conduct a final analysis in the first half of 2024. However, both the interim and the final analysis are event-driven and could occur on a different time line than currently expected. We believe that in this planned Phase III trial in refractory MF, if successful, imetelstat will be the first drug to demonstrate a survival benefit in this poor prognosis patient population. Moving on to the ongoing IMerge Phase II/III clinical trial in lower-risk MDS. As of the end of April 2020, approximately 68% of the originally planned clinical sites for the IMerge Phase III clinical trial in lower-risk MDS were opened for enrollment. As we previously announced, COVID-19 has had a significant impact on site initiation and enrollment in this trial. We're doing everything we can to ensure we meet our enrollment goals in IMerge. This has included consistent contacts with our clinical investigators and working with our CRO on enrollment-boosting activities. Now on top of those activities, we are currently evaluating the addition of potentially 6 new countries and approximately 40 new clinical sites for participation in the trial, which could result in a total of up to approximately 130 sites. As for top line results, the protocol-defined final analysis will be conducted 16 months after the last patient is enrolled, and that's based on our updated enrollment exceptions. We expect top line results to be available in the second half of 2022. Compelling data from the Phase II portion of IMerge continue to highlight the differentiating effect of imetelstat in lower-risk MDS patients. First, our data indicates meaningful transfusion independence, or TI, achievable with imetelstat treatment at 42% of patients achieved the primary end point of 8-week TI and 68% achieved hematologic improvement-erythroid. Second, similar rates of clinical benefit, including TI, have been observed in both RS-positive and RS-negative patient subgroups. RS-positive patients represent approximately 10% to 25% of lower-risk MDS patients, while RS-negative patients represent approximately 75% to 90% of the lower-risk MDS patients. Being able to show transfusion independence across these patient subgroups allows imetelstat to potentially address a broad patient relation. Third and the most significant differentiator of imetelstat in lower-risk MDS, which is observed to date, is the durability of transfusion independence. Namely, this year's EHA abstract, which was accepted for an oral presentation, reported a 24-week TI rate of 32%. For the first time, we are now reporting a 1-year TI rate of 29%, representing patients being transfusion free for at least 1 year with the longest transfusion-free period being 2.7 years. In addition, the new median duration of transfusion independence is 88 weeks, which is, to our knowledge, the longest reported to date in the non-del(5q) lower-risk MDS [indiscernible]. Finally, 75% of the 8-week RBC-TI responders showed a hemoglobin rise greater than 3 grams per deciliter during the transfusion-free interval when compared to their pretreatment level. A hemoglobin rise of this magnitude is not achievable with a blood transfusion or growth factor treatment. We believe that the increase of hemoglobin, together with the durability of TI, is indicative of the disease-modifying activity with imetelstat treatment, which aligns with imetelstat's mechanism of action. As a telomerase inhibitor, imetelstat has potential to inhibit the uncontrolled proliferation of malignant stem and progenitor cells and potentially enable recovery of normal hematopoiesis. Now I'd like to hand the call back to Chip. Chip? Chip, are you maybe on mute?

Thank you. The trials and tribulations of the era. So thank you, Aleksandra. So with all the pieces now in place to capture the value from 2 significant indications, we believe we have strategically positioned Geron to become a leader in the treatment of hematologic myeloid malignancies. And perhaps with that, we'd like to answer your questions. So I'll turn the call back to our operator. Operator?

[Operator Instructions]. Your first question comes from Charles Duncan with Cantor Fitzgerald.

Chip and team, congratulations on the recent equity raise as well as the planned route forward in myelofibrosis in addition to MDS. I had a couple of questions on the pipeline and just one operational. So first question is regarding the pipeline in MDS. I'm not sure if I'm reading this right. But in the corporate debt, it looks like there is 29% of patients or so achieved a 24-week red blood cell transfusion independence. But in the EHA abstract, it seemed longer. And I think Aleksandra just addressed this, but I'm assuming these are the same patients. Please correct me if I'm wrong. And in addition, I'm wondering if you could compare the patient sample characteristics and durability of treatment or of transfusion independence to that of the emerging HM luspatercept.

Thanks, Charles. Well, Aleksandra perhaps compared some of those numbers, which I'm confident are correct. I'll take the luspatercept comments. I think that the things that really distinguish the imetelstat in lower-risk MDS are -- and first of all, that we are treating both RS-positive and RS-negative patients. The RS-positive, as you recall, are somewhere around 20-ish, 25% quoted as anywhere from 10% to 25% of patients with lower-risk MDS. And that will be -- that is both the limitation within the accepted labeling for the U.S. for luspatercept to RS-positive patients, and the CHMP positive opinion also mentions that. We include both RS-positive and RS-negative patients in our studies and would anticipate heading in that direction from a submission perspective. The second is that we had significantly higher baseline transfusion burden in our Phase II study compared to the MEDALIST Phase III study. The median baseline translation burden was 8 units per 8 weeks compared to 5 for MEDALIST. And the interesting feature about MEDALIST was that they did include patients in MEDALIST who had less than 4 units per 8 weeks of RBC transfusion burden. About 29% of their patients had less than 4 units. When you sort of just look at the patients who had greater than or equal to 4 units per 8 weeks as the baseline transfusion burden, which was the case for both studies for our study, and if you take only those patients in MEDALIST, you end up with transfusion 8-week RBC-TI rates of 42% for IMerge and 32% for MEDALIST. And as we commented earlier, the 24-week RBC TI rate of 32% and 29% for the 1-year RBC-TI rate have not -- for imetelstat, those rates, the 24-week and the 1-week, have not been reported for the MEDALIST study anywhere we've been able to find. Finally, the last point is that in -- if you look at the median duration of RBC-TI, it's 88 weeks for the IMerge data in the Phase II, and it was 31 weeks for the median duration of the TI in MEDALIST. Now I would hasten to add that the IMerge study was a Phase II study and MEDALIST study was, of course, Phase III. And second, I would make the point that MEDALIST has a very, I would say, benign side effect profile. So the drugs are -- the drugs are not entirely comparable. But I think that when you look across the opportunity, I think we feel very good about where imetelstat stacks up, particularly in the higher transfusion burden and the RS-negative as well as RS-positive patients. Aleksandra, did you have any other further comments about numbers?

No, Chip. I think you covered everything, Charles, please let us know if there's anything we didn't answer.

Yes. No, I think that was very clear, and I appreciate the added color. My second question was regarding the myelofibrosis protocol, and which I think is pretty interesting because I believe it's quite well suited to show mechanistically driven differentiation of clinical profile for imetelstat relative to standard of care. However, for the planned control arm, which is best available therapy, since it does not include a JAK inhibitor, how would you characterize what BAT is, if -- in any way? And then given that it's an open-label study, I know overall survival probably, pretty hard to say. But in terms of some of the secondary end points, like some of the patient-reported outcomes, how do you plan to maintain some level of control regarding patient communication?

So why don't you start off and I'll supplement, if needed.

I can take. Yes, Chip, for sure. So let me start with the question around the best available therapy. So we have defined the patient population in our study very carefully. And the patient population, as such, right, has exhausted or has -- had put the chance to respond to a JAK inhibitor treatment. They would have had, as I mentioned, 6 months of treatment with the JAK inhibitor, and 2 months of those would have been a stable dose for the JAK inhibitor. Therefore, with this definition, patients would not need a treatment, a further treatment with a JAK inhibitor. Therefore, the BAT arm can exclude the JAK inhibitor. Now in this setting, the BAT arm will include most likely agents like hydroxyurea, steroids, danazol, IMiDs, potentially HMAs, right? So we believe that with this, we've addressed the need for the defined patient population. I believe that...

And then relative to the secondary end points, just kind of, I guess, exercising some control around patient communication and how those read out, given it's an open-label study.

So that's a fair question. It's a question that has an overall survival as an end point -- twice to any study with an overall survival end point. And as you mentioned, right, I mean, overall, the primary end point, you cannot break. It is what it is and for the symptom assessment or some of the PROs. And we will just ensure that they're taken with a high compliance and report the data as such. It's difficult. It's a problem of every survival study.

Got it. And last question, operational. Do you have sufficient quantities of imetelstat for both studies? And if not -- I assume you've contemplated that with regard to the balance sheet and if you need to do additional manufacturing?

Yes. We have sufficient to complete the MDS study and to go at least very far into the MF study. Aleksandra, I don't know if you have any update on that or not?

No, that's accurate, Chip. That's well said, yes.

Yes. So we have multiple years' worth of drug supply at this point and a very well-established manufacturing process.

This is Olivia. What I would add to that, Charles, because you asked about the spend, is that in the guidance that I gave, it does include costs for CMC. As you know, imetelstat is contract manufactured out. And so we have been validating all those vendors as part of the process in readiness for potential not only for Phase III trial supply, but also for potential commercialization down the road. And so those activities are ongoing right now.

Your next question comes from Chad Messer with Needham & Company.

Let me add my congratulations on all the progress, particularly with getting this MF protocol worked out and things moving forward there. It's just -- wondering if there's one thing you can maybe share your thoughts on with me with regards to MF. And that's -- all other drugs approved or late-stage development are kind of getting away with a sort of hybrid off their end point, and you guys are kind of being held to the sort of high bar of OS. But just wondering if you have any follow-ups on why that may be? And whether or not your really strong OS data from the Phase II, though smallish though it may be, is somehow ironically working against you.

Well, let me take that, first of all, and then I'll invite Alex to make additional comments. I would actually look at it differently. I think that we view the ability -- the confidence we have in a potential OS benefit, which, as you commented on, came from both the real-world data analyses that we did and reported previously and also just the comparison in the IMbark study to the historical controls. We always saw that as not a burden to bear, but actually an incredibly valuable finding and a deeply differentiating element to our drug, to imetelstat. So far from viewing it as something that we were going to be held to a higher standard than anyone else, it may be true that it's a higher standard. It takes a little bit longer and it takes substantial resources to do. But on the other hand, coming out at the other end of this, I think we expect to have the only drug that will have been through -- the only drug in JAK refractory patients who make up a very substantial part of the market, the only drug that will have actually demonstrated a survival benefit in such patients and a survival benefit. In fact, JAK is a primary outcome measure. So this is actually new ground. But with new ground also comes high barriers to entry potentially and also a great differentiation. I can tell you the investigators that we engaged in working through the details of this type of approach, we're just simply extremely excited about the possibility of getting a drug that would have this type of benefit demonstrated. So that was our real approach to it. And I think we feel pretty terrific about the opportunity to go there. Did I leave anything out, Alex?

Yes. Maybe I can just reinforce, Chip. I mean, we love the fact that we have a drug that can improve overall survival in this relapsed/refractory setting as there's no other drug, as you mentioned, that has shown that. And as you know, right, other drugs are having primary end points that are addressing the symptom of the disease, whether that's a spleen or a symptom response or an anemia improvement or a combination of the above, right? So what we have here is an overall survival. And I think that we have the possibility or the chance to have a paradigm shift in the thinking of how you approach treatment with myelofibrosis.

All right. Yes, I appreciate that perspective and certainly don't disagree with anything you're saying. It's the go big or go home approach.

Exactly.

Maybe just with regards to the upcoming EHA. Congrats on the strong sort of top line 1-year data that came out in the abstract. What other analyses -- are there any other analyses that you would sort of highlight you should be looking out for in the full oral presentation?

In the model fibrosis presentation, there is one key, I guess, data that I would definitely or -- one bring to the attention. And that would be the correlation that we are now showing of fibrosis improvement with the significantly longer overall survival in these patients, right? So it is the first time ever that in myelofibrosis, there's been the fact that if you have an improvement of fibrosis, you have a better chance to live longer. So I guess that would be the data that I would really highlight from the myelofibrosis abstract. In terms of the MDS, we'll certainly be the [indiscernible] of durability, right, the 1-year transfusion-free period.

[Operator Instructions]. Our next question comes from Andrew D'Silva with B. Riley FBR.

Congrats on the progress. So lots to unpack here. I'll just start. As far as IMbark, the MF Phase III and connecting the recent abstracts and the benefits seen in overall survival in patients that experienced other clinical benefits. And then tying that into the stronger results that we're seeing in the triple-negative patient group that further align with the other clinical benefit statement. Are you looking to have protocols designed in the Phase III in a manner where we should expect triple-negative patients to be a focal point of the enrollment criteria?

Alex?

Yes. The answer to that is yes. However, our focus and priority of the moment is the Phase III study in refractory myelofibrosis patients.

I think Andy might have been asking within the Phase III study, within the refractory Phase III study, will there be a particular focus on triple-negative patients within that broader patient population. And in other words, is there either a major stratification for triple-negative or do we have a particular focus on that? Go ahead, Alex.

Well, triple-negative patients will be also allowed to enter the current -- the refractory study. At the moment, if that was the question, we have not planned for stratification for triple-negative patients.

Right. There's no particular focus on them, Andy.

Okay. And then you noticed the enrollment -- or you noted the enrollment from that standpoint would exclude JAK inhibitors. Did the real-world data Moffitt ran with their -- that population also exclude JAKs?

Yes, yes. The BAT in the Moffitt patients did not include also -- excluded JAK inhibitors.

So it's a fairly clean comparison then, as far as...

Right.

Okay. Okay. Good. And then just...

As far as the outcomes expected, yes.

Okay. Okay. Perfect. And then just last question for me, as far as guidance goes, no change really from a number standpoint. But can you help me crosswalk how it's different today than it was in March? Obviously, you're increasing spend with MF and then reducing enrollment -- or this enrollment is going to be slower, MDS, due to COVID-19, and you're pushing out proof-of-concept studies a little bit. Could you help me get to the same number as far as where the gives and takes are there?

Yes. Andy, this is Olivia. Sure, I can. So you're right. Overall, the range is the same as what we guided earlier this year. But you're right, there's kind of pluses and minuses in many areas. And then they ended up in the same range. So I would say that the composition of the guidance is relatively same. It's just that -- again, there were some pushing from one category to another as the different expenditures were going along. So just to let you know, for the current guidance of -- and the composition, the clinical trial costs, which include the start-up activities that I mentioned for the refractory MF trial, as well as the ongoing support for the IMerge Phase III, that is probably -- represents a little less than 1/5 of the total guidance. FTE costs are a little over 1/3. The manufacturing cost that I mentioned earlier, when we were talking with Charles, that's a little over 1/4. And then overall G&A, kind of supporting the public company, that kind of thing, is a little less than 1/5.

Your next question comes from Tom Shrader with BTIG.

I'd just like to echo the sentiment. Just kind an amazingly long full congratulations on getting this to this stage. I know it's not been easy. So my first question is the MF control arm. Does fedratinib -- is that a complexity for you? They have retreatment data. I know it's highly contentious. But is it a worry for you that as you talk to clinicians that they would want to try fedratinib in rux failures?

Alex, did you get the question? Yes. Go ahead.

Right. I mean I don't -- no, it is not a worry, right? Again, taking the definition of the patient population in our study, we do believe that patients would -- or PIs, investigators would not want to treat patients with a JAK inhibitor. So I don't think we see that as a worry.

Okay. And then kind of a -- so I'm intrigued by your EHA abstract with the telomere length. My memory is that's been very difficult to measure historically and in fact, I think, didn't correlate with early data because you couldn't measure it. Is it now a robust assay and you could actually look at all MF patients as a function of telomere length irrespective of treatment and you might have a subgroup? Just your thoughts on, is that a new assay and how robust is it. I guess my memory is -- telomere length was historically nearly impossible to measure.

You are correct. Telomere length is very difficult to measure, especially due to the fact that you're mixing potentially malignant as well as normal cells. However, as alpha indicated, we've improved on the assay. And now, again, in a limited number of patients, I guess, that's pure caveat. But in a limited number of patients that had a paired analysis, it is the first time that we are able introduce some correlation between the TL, the telomere length and the outcome.

And do you think it will be a biomarker? Is that something that kind of has you excited? Or is it still very exploratory?

I think we look at all the three PD parameters, if you will, right, the telomere length, the telomerase activity and the hTERT expression, right? We look equally at them. I don't think we're thinking of any biomarker at the moment. But it is really good to have them as a PD, pharmacodynamic markers, in order to confirm the on-target mechanism of action of imetelstat.

All right. And then one quick, maybe slightly annoying question because the horse is out of the barn. But in the IMerge trial, you have such a different drug profile where 3/4 of the patients that get an 8-week transfusion gets a year. Do you -- are you sorry you chose such a short end point? Which level would be much noisier? Or do you think you're confident that 8 weeks is long enough so that the placebo rate is going to be very little?

Maybe I can just comment that the 8 week -- Aleksandra, I'm sure will have a few other comments. But Tom, the 8-week RBC-TI is kind of the accepted or approved regulatory outcome or regulatory end point. And so you're -- it's really common in virtually all of these studies in lower-risk MDS to use that as the primary outcome measure. I think we have a very robust -- in the Phase II, we saw a very robust outcome measure. And even in the MEDALIST, when you got into the higher transfusion-burdened patients such as we will have in our study in our Phase III as we had in our Phase II, the noise really goes down low -- much lower. You're bringing up a really interesting point. So for example, with the MEDALIST study, which I just used MEDALIST in this case not to harp on anything with regard to luspatercept, but because it is a study with a wide variety of patients in the baseline transfusion burden. So when you looked at the patients -- just at the placebo rates because that's what you're actually kind of getting at, right? So when you looked at the patient's placebo outcomes, in their study as a whole, which included, remember, from 2 units transfusion burden up to actually 20, their placebo response rate was 16%. And I have to say, when we looked at that, we went, "Oh, holy cow, what was that?" But the reality is that when you knock out the patients who have the less than 4 units per 8-week transfusion burden, so the 2 and 3 patients, okay, that placebo rate comes down to 7%. In the MDS 005 study, which Celgene did couple of years ago and was reported, well, yes, a couple of years ago at ASH, that was Revlimid versus placebo. The placebo rate, as I recall, was 4% or 5%. So I think we don't see a signal-to-noise ratio here as long as you have a sufficiently high transfusion burden. And if memory serves me correct, if you then flip the analysis and you look at the patients in the luspatercept study that had only 2 units or 3 units per 8 weeks in just that subgroup alone, their placebo response rate was extremely high. So it -- I think they're -- it's really defined by the baseline transfusion burden. And that signal-to-noise ratio in the patients that we'll be studying, I think, is more than adequately high. The additional durability is the icing on the cake, right? And I think everyone will pay a great deal of attention to the durability because we would expect an exceptionally low -- I expect a very low placebo response rate there. And I think that will not be an issue at all in signal-to-noise ratio. I hope that didn't [indiscernible] too much and confuse it.

There are no further questions at this time. I'll now turn the call back over to John Scarlett for closing remarks.

Well, I'd just like to thank everybody for participating in this conference call. We're exceptionally pleased by the progress that we've been able to make. I think that we have a really great opportunity to now drive forward with 2 Phase III studies. Not most companies get this far. We thank all of our investors, our long-time investors who have been with the company and supported us, our new investors who we're excited to have and also just simply want to thank all the patients and the investigators who have helped us get to this level. We still have a lot of wood to chop, as they say. But I feel really, really good going into the next several years where we have some exciting times to come. So thank you all very much, and we look forward to taking the journey with all of you. I think that concludes our call, operator.

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

Okay. Thanks very much.