Ladies and gentlemen, thank you for standing by, and welcome to the Fourth Quarter 2020 Geron Earnings Conference Call. [Operator Instructions]. I would now like to hand the conference over to Olivia Bloom, Geron's Chief Financial Officer. Thank you. Please go ahead, ma'am.

Thank you, Erica, and good afternoon, everyone. Thank you for joining us for today's conference call. I'm joined today by Dr. John Scarlett, Geron's Chairman and Chief Executive Officer; and Aleksandra Rizo, our Chief Medical Officer. After the market close today, we announced our fourth quarter and year-end 2020 financial results and operational highlights via press release, which is available on our website under geron.com/investors. In addition, a live webcast of this call is available on our website, and an archive will be available 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 expected time lines for completion of enrollment and the results from the IMerge Phase III and IMpactMF clinical trials and submission of an NDA; the potential for positive outcomes from IMerge Phase III and IMpactMF; potential approval imetelstat by regulatory authorities and commercialization of imetelstat; the expectation that Geron's current financial resources will be sufficient to fund its operations until the end of 2022; and that imetelstat has the potential to be disease-modifying and alter the course of MDS and MF. 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 limitations, those regarding that the company may be unable to overcome all the enrollment, clinical, safety, efficacy, technical, scientific, operational, manufacturing and regulatory challenges to meet the expected time line for IMerge Phase III and IMpactMF due to COVID or otherwise; that in the Phase III clinical trial, imetelstat may not prove to be as safe or efficacious as in the Phase II trial and may not demonstrate…

Thanks, Olivia. I'd like to welcome everyone to our fourth quarter and year-end 2020 conference call. Let me start by sharing our vision for Geron, which is to become a leader in the treatment of hematologic malignancies, by changing the course of these diseases, thereby improving and extending the lives of patients. As I look back on 2020, we made significant progress towards realizing this vision. So again, we presented compelling and differentiating data from our IMerge Phase II lower-risk MDS trial. These data showed high rates and exceptional durability of transfusion independence. Of any study in non-del(5q) lower-risk MDS patients who relapsed and refractory to ESAs, the 20-month minimum duration of transfusion independence in IMerge Phase II was the longest reported to date. In our IMerge Phase III lower-risk MDS study, enrollment gains continued with over 50% enrollment achieved by the end of the year. We also presented exceptional overall survival data from our IMbark Phase II trial in JAK eye relapsed or refractory MF patients. In this trial, imetelstat treated patients had a median OS of 28 months, which is almost twice the median OS reported in the medical literature. [Technical Difficulty] and other supporting data and after conferring with FDA, we opened IMpactMF, our Phase III trial in JAK eye refractory MF patients. IMpactMF is the first and to date only Phase III trial with overall survival as the primary endpoint. We also presented strong disease modifying [Technical Difficulty] low-risk MDS and relapsed/refractory MF. In both indications, we saw reductions in key driver mutations of the underlying disease. Furthermore, imetelstat is the only drug in development to establish a correlation of these and other measures of disease modification with key clinical outcomes, including durability of transfusion independence and low-risk MDS and improvement in MF. Such correlations have…

Chip?

And commercially launching this highly differentiated drug in low-risk MDS. Now I'd like to hand the call -- I'd like to call -- hand the call over. Go ahead.

I'm sorry. You were breaking up a bit just back there just right before for Aleksandra?

Okay. So we currently expect the interim analysis for IMpactMF to occur in 2024 and the final analysis to occur in 2025. Looking ahead, our planned strategic priorities for the next 3 years include achieving top line results in IMerge Phase III, gaining regulatory approval of imetelstat and commercially launching this highly differentiated drug in lower-risk MDS. Now I'd like to hand the call over to Olivia to discuss our fourth quarter and year-end financial results and financial guidance for 2021. Olivia?

Thank you, John. As of December 31, 2020, we had approximately $260 million in cash, cash equivalents and current and noncurrent 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 nondilutive $75 million loan facility that we closed at the end of the third quarter last year. Based on current planning assumptions, we estimate our current financial resources to be sufficient for our operations until the end of 2022. Overall, the financial results for the fourth quarter and year-to-date period were in line with our expectations and our operating expense guidance. Operating expenses for the 3 and 12 months ended December 31, 2020, were generally higher in comparison to the same period in 2019, due to head count increases in 2019 and 2020 across the company, increased activity for the IMerge Phase III clinical trial in low-risk MDS, start-up activities for the IMpactMF Phase III clinical trial in refractory MF and costs associated with ongoing imetelstat manufacturing. These increased costs were partially offset by lower costs related to purchases of raw materials, drug substance and drug products and completion of the IMbark clinical trial. Regarding financial guidance for 2021, we expect our operating expense burn to range from $108 million to $112 million, which includes costs for our 2 ongoing Phase III clinical trials, production of validation batches of imetelstat at contract manufacturers to enable future production of imetelstat for clinical and commercial purposes and preparatory activities for NDA and commercial readiness. 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 will 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 activity. Aleksandra?

Thanks, Olivia. Good afternoon, everyone. As Chip mentioned, we have now achieved 65% enrollment in our IMerge Phase III trial. Also, the first meeting of the independent data monitoring committee was held in December, and the IDMC recommended that the trial continue without modification. We expect the enrollment boosting activities we started last year to become more effective as COVID cases decline and as clinical operations begin to hopefully return to normal over the next several months. As a result, we believe the clinical science liaisons were engaged in the beginning of last year will be able to interact with clinical sites more easily and with greater frequency to help alert site personnel and patients to the potential benefits of participating in IMerge Phase III. In addition, we believe our social media campaign will help drive patient recruitment. Over the next few months, we expect all of the approximately 20 additional sites for IMerge will be open, bringing the total number of sites in this trial to approximately 120. Of course, the best boost to enrollment should come as vaccinations proceed, the number and severity of COVID cases decline and patients, again, become more comfortable leaving their homes to participate in clinical trials. Earlier in this call, Chip mentioned kind of the more mature clinical data from our IMerge Phase II trial in low-risk MDS, on which I would like to expand on briefly. These data are very encouraging. And we continue to differentiate imetelstat from other currently approved or investigational treatments. Foremost, imetelstat achieves its remarkable durability for transfusion independent. In addition to those 42% of patients that achieved the primary endpoint of 8-week transfusion independent, 32% of the imetelstat patients were transfusion free for 24 weeks, which was a key secondary endpoint. Furthermore, 29% of the patients were…

Let's try it, again. Thanks, Aleksandra. Historically, there have been few new treatments for hematologic malignancies, especially myeloid malignancies. However, in 2020, we saw a new approval for luspatercept in low-risk MDS and several new approaches being tested for MF, including many combination therapies. First, let's discuss last year's approval of luspatercept, trade named REBLOZYL in low-risk MDS. This approval took place in April 2020 based on a Phase III trial in non-del(5q) lower-risk MDS patients who are relapsed or refractory to ESAs and naive to HMAs. This trial enrolled only RS+ patients. The launch of REBLOZYL by Celgene and BMS appears to be strong, which validates the high unmet need and the market potential for these RS powers of lower-risk MDS patients. We expect a highly differentiated profile for imetelstat at launch and the lower-risk MDS market. In the patient population of our IMerge Phase II trial that we targeted, as described by Aleksandra, we've seen clinically meaningful transfusion independence across multiple MDS subtypes, including both RS+ as well as RS- patients, low and high transfusion burdened patients in patients with low and high EPO levels. Because of this differentiated and advantageous profile, we continue to expect imetelstat to play a significant role for this lower-risk MDS patient population. For the MS landscape, Jakafi, ruxolitinib, remains the primary frontline treatment. Although the number of investigational treatments, including combination therapies, has increased over time, these treatments are either another JAK inhibitor or a combination with a JAK inhibitor. They continue to be focused on spleen, symptoms or anemia improvement. These are certainly helpful, but do not address the fundamental problem of continued disease progression in these patients, which results in dismal survival. Eventually, the majority of MF patients are or become nonresponsive to a JAK inhibitor. As such, there remains…

[Operator Instructions]. We'll take our first question from Chad Messer with Needham.

I just start with a little bit of drill down on COVID impact, everything you said about patients and sites obviously makes a lot of sense what's going on in the world today. But in your prepared remarks, Chip, you talked a little bit about the primary problem kind of being patients showing up for sites. And then in the press release, there's some additional discussions about site personnel, I guess, site personnel. I was wondering to what extent these 2 things are playing off relative to each other? I mean to me, and maybe I'm naive, it seems the patient interest in showing up is the most obvious to normalize with COVID and that site things may be more complicated, I could even be wrong about that. But just wondering if you could give a little bit more insight on the relative impact of those two things, which are both, in my mind, logically impacted by COVID.

Yes. That's a really perceptive question. Thanks, Chad. I think I'm going to turn it over to Aleksandra, who's certainly the closest of all the people on the call to the question. She's in rather constant contact with these sites and our team is, of course. So Aleksandra, maybe you'd like to comment on these 2 different variables that Chad brought up.

Sure. Thanks for the question, Chad. I mean you are spot on. The 2 main issues that we are seeing is really the patient reluctance to participate in clinical trial, which actually may require more frequent visits to the hospital, right, than they would like to during COVID time. And the second one is really the availability of site personnel, which appear to be busy maintaining trials with, again, multiple procedures during COVID time. So it's really a mixture of these two variables. And it's -- we do expect that as we spoke as the COVID pandemic winds down and with the vaccination, hopefully, patients feel again comfortable to come to clinical -- to come to the clinic and participate in clinical trials. But those are the two key reasons. Yes.

Okay. Yes. No, that makes a lot of sense. And then this next one, well, I definitely have a comment. Maybe there's a question in there. So it's really interesting that -- especially when we hear about your ASH data and you talk about justifying OS as the OS benefit that you've seen, and I get it, it's single-arm, so that maybe the justification comes with kind of validating it in that context. But with things like spleen volume and symptom scores, in one way of thinking spleen volume and symptom score should be out there justifying their value in terms of OS, in my mind. So I guess that was the comment. And then the question, and you guys -- you touched on this a little bit. But I mean, talk a little bit more, and I know MF is such a unique disease in terms of the endpoints that are looked at for JAK inhibitors and other standard of care therapies, but why is it that where you have to work so hard here to convince people that OS benefit is important.

I'll take the first part, and then I think Aleksandra, again, would like to probably comment on this. I don't think we feel that there's any need to justify the OS benefit. I think it's plain and simple and incredibly obvious. I think we make the point and perhaps our continued commentary on this could be taken the wrong way. But I think we're trying to make the point that we're the only drug that we're aware of that is actively engaged in the Phase III trial that will, in fact, use OS as an outcome. And it takes some courage to do that, right? These are long trials. You have heard the date, they require a fairly large number of patients. And it's breaking out of the mold. Most people just do a landmark analysis at a certain number of months after being treated with a combination, usually containing a JAK inhibitor and a new drug or simply new JAK inhibitor alone, and you're kind of done. But what you don't see are the real benefits of changing the course of the disease. And Chad, we think that, that's the big news, big story and frankly, the big benefit of this drug. I don't think anybody else has any kind of data like we do in that regard. So that's been our primary focus on why we've tried to talk about OS more than anyone else because we -- and we also have the correlations of the changes in the course of the disease both clinical and more importantly, perhaps, in some ways, molecularly with the actual improvement in OS in our Phase II study. So I hope that, that puts it in some context. Aleksandra, I don't know if there's anything else to add or Chad, if you would like to jump back in, that's fine.

Your next question is from Justin Walsh with B. Riley Securities.

Can you provide any color on feedback that you've received from your initial marketing research and outreach efforts. How either our MDS versus MF physicians and patients for new treatment options? And how they reacted to in the imetelstat's profile?

Right. Well, I'm going to let Aleksandra talk about the individual physicians that we've spoken to. We've done market research, and we're in the process of planning for additional market researches here that will really drive into those points, Justin. But I think that the benefits of MDS -- in MDS are really quite evident to a lot of physicians, particularly those who take care of more ill patients. Remember that all of our patients have very high transfusion burdens. And that's an area that can be particularly difficult for these physicians to get traction with. Now they've certainly adopted or they're in the process of adopting luspatercept. And we, again, we call that out, and we think that's good because prior to luspatercept coming on the market, there hasn't been anything new since the HMAs over 10, 12 years ago. So I think that the rapid uptake has been good, but there's a lot of room left for a drug like an imetelstat that does a bunch of things. One, we treat RS- patients as well as RS+; two, we can treat patients with very high baseline transfusion burdens and still get excellent outcomes; three, the durability, repeat it, the durability, the durability of imetelstat's activity in these patients is really dramatic and far greater than anything we've seen, at least in print or at meetings from the folks studying luspatercept. So I think that those then factor into the underlying cause of all of this, which is when we see decreases in SF3B1 and decreases inside genetic abnormalities, it's pretty clear that we have disease-modifying activity going on. I won't characterize other products in low-risk MDS, but all of those are really powerful differentiating factors. And I think that they'll play very, very well. Aleksandra, do you want to comment on the specifics of investigator interaction and KOL interaction because you're very close to a number of resource.

Sure. Sure. I can talk about that. I mean we obviously are in very close contact with participating PIs as well as key opinion leaders. So -- and I can just reiterate. There is really a great enthusiasm for a drug that works across different subtypes of low-risk MDS. That's to start with, right? So for them, there's just the fact that they don't need to subsize whether you RS+ or RS-, makes their clinical and every day work, very easy, right? I mean we were not subtyping for RS positivity prior to REBLOZYL's approval, let's put it that way. So this kind of is one convenience for that, right? And then, I mean, the fact that we have durability of 20 months versus 7 months of our already approved drug that is doing very well on the market is really another convenience, if you will, for patients. You don't have to come back to the clinic for multiple transfusions to which they're used to prior to treatment. And I have to say something and really often discuss this internally. I mean, what really makes investigators excited is the molecular data. It's really -- and this was -- that's maybe even the best reason why the paper ended up in JCO. So it's really the decrease in not only SF3b1. SF3b1 is just an example that we are using here to illustrate the effect. But it's really multiple mutations that we've seen and also cytogenetic rate decrease in these patients that may believe our KOLs, NPIs that imetelstat is really altering the course of disease in low-risk MDS patients. Same goes, Chip, you answer for MDS. I don't know, Jason, if you wanted to cover for MS, but it is the same pretty much is really the molecular data. And I mean and Chad also a little bit to go to your question, right, about the OS. I mean data has been evolving and the agencies has been more receptive to different endpoints, right? We started with SVR as Jakafi was on the market for so long. But as new data with new compounds, right, show that we can improve anemia with one drug. We can improve symptoms, right? New endpoints has been established. And now we come with OS. We had a question, that the crown of the endpoint, I mean, the ultimate endpoint of every clinical trial, right? So when you show such data granted at the moment, it's just from 2 different doses of imetelstat, enthusiasm is high. I don't think we had leads to justify the OS as an endpoint to any of our investigators nor to regulators so far. So we remain enthusiastic. It's long, and that's what makes it a challenge. It's a long study, right? It's a different endpoint. But other than that, there's really no other reason to believe that we have any questions about the data.

That's very helpful. Maybe just a quick follow-up to that. So one, could you maybe quickly just remind us of how many of the low-risk MDS patients RS+ positive versus RS-? And do you think that there could be potential for patients to use luspatercept and imetelstat in sequence if they fail therapy with one or the other?

So typically, the numbers for RS+ patients in the literature range anywhere from 10% to 25%, right? It depends which paper you take, right? So let's say most, if 1/4 of the patients are RS+, right? So major -- a lot of the patients are RS-. And again, as we've spoken multiple times, we work across both post subsides. So I think that was one quick question. And can you remind me what was the second part of your question?

Yes. Is there a potential to use luspatercept from subtyping treatment?

So for RS+ patients, right, potentially, right, but for patients that are heavily transfused, no, I really don't know, right, what would be the clinical preference, I would say.

Your next question is from Stephen Willey with Stifel.

So maybe just with respect to the IMpactMF guidance. So I'm just kind of curious as to there's obviously a lot of competitive happenings within the space. And I'm just kind of curious as to how the guidance if at all contemplates the competitive environment in terms of competition for some of these post-RUX patients? I guess specifically just given the number of trials we're kind of seeing within that setting.

Yes. That's a great question, Steve. I mean just since we announced the study, there had been 3 new trials -- Phase III trials in MS, right, that had been started. So competition is really high. For us, at this moment, it's difficult to give a very precise guideline. But as you can imagine, we have conducted a study feasibility. And base -- and that visibility takes into account COVID as well as competitive trials. So that's how -- based on the current knowledge we have, our current planning assumptions are that we will reach the full enrollment in 2024, which is a different guidance than what we've given so far.

Okay. And then maybe just going back to IMerge for a minute. And Chip, you had made the comment with respect to luspatercept availability potentially impacting patient enrollment into the study. So is there a scenario whereby IMerge maybe ends up representing kind of over enrichment of RS- patients? And do you think that there is any potential labeling or unifications as a result of that? I'm just kind of curious to get your opinion there. And just whether or not you have kind of real-time insight into the baseline characteristics of patients that are coming into the study if that's something that you're seeing?

Again, I think Aleks is in the best position to answer those questions. Go ahead.

Yes. So I'll start with the last one, Steve. I mean we have no insight into what type of patients are being enrolled in the study because it's a double-blind, placebo controlled study, right? So it's very difficult to -- not very difficult, it's impossible to comment or to know what patients are enrolled. Now your first question if luspatercept might or luspatercept approval might have the impact on luspatercept, right, might have impact in a way that we now enroll RS+ patients only -- sorry, RS- patients, the other way because they will be treating. I don't think so. Remember, luspatercept has just been approved. It will be used on patients, I assume, for the RS+ patients. They would initially be treated with luspatercept and [indiscernible]. So I honestly do not think, right, that we will end up in reaching for one or for another patient population. And therefore, I don't see a problem in the labeling I mean, at the moment.

Steve, I think also...

And Chip, I don't know -- yes.

Yes. Yes, Steve, I think also we should comment that when we talk to investigators, their views on the -- these are really quite different drugs, right? I mean the effects of imetelstat in high-transfusion burden patients, greater than 4 units and especially greater than 6 units is quite dramatically different, at least if you look at sort of the Phase II comparisons to Phase III comparisons between the 2 drugs. So I think that there's probably so many different ways to cut this. I agree with Aleksandra. We're -- I think we'll be surprised to see a meaningful enrichment of one RS+ versus RS-. And I think we'll be surprised. But we don't know yet, and we'll see.

And I would just -- as you were talking Chip, -- sorry, Steve, I just want to answer. I mean we involved about 50% on our trial before luspatercept became available or reimbursed in the European country, where most of our sites are. So I bet, we do have sufficient number in those stations that are RS+ as well RS-.

Your next question is from Tom Shrader with BTIG.

You kind of just talked about my question, but you see no reason to stratify for RS+ versus RS-. Kind of Chip to your point that these patients either physicians would know are going to get almost nothing out of luspatercept or probably did get almost nothing out of luspatercept. Is that accurate? And you just don't think it confounds your study much?

I think the question, if I understand it, Tom, is whether we're stratifying in the analysis for RS+ versus RS-, and stratification, in this case, usually, would mean if you were stratifying in the randomization. We're not stratifying at least in the randomization. Will we look at the effects of the subtypes? Absolutely, of course, we will. So we'll look at it, but we're not preferentially making sure that we take a specific group. I mean I need to say this, we don't completely understand why luspatercept has this effect in -- and appears to have this effect, a big enough effect that Acceleron and Celgene decided to really restrict their Phase III -- their initial Phase III trial MEDALIST study to RS+. But what I can tell you is that when we look at our data, it doesn't really matter whether you're RS+, RS-, you get very similar results. So I think that's the real bottom line for us. And I think that will show equally good results in either group.

Okay. And then there's kind of an interesting comment about a reasonable R&D build going forward. Is -- are you still looking -- looking for a way forward in AML? Is that still on the table? Are you looking for a subgroup that makes a lot of sense? Or am I misreading the...

Yes. No. I mean let's just say this. I don't know that the R&D build necessarily reflects that. But what it does reflect is a maturing development organization for a drug that's going to be on the market and however many years. And one that we think has a very unique mechanism of action as well and has properties and capabilities that aren't shared by other products. So we'd be crazy not to try to take advantage of that. And I think that's kind of the real answer. I don't think we're prepared to talk today about the specifics of what the next indication would be or when it would come or how much it will cost or any of that or how many people will be required to support it. But we certainly have are going through the Asteria line of hematologic malignancies we're certainly interested in putting more in our plates and simply low-risk MDS and MF and relapsed/refractory MF, for that matter. So I think that you can assume that we have a very keen interest in that. But we'll just have to wait a little bit longer for us to really come out and do the -- have the commentary that I think you're looking, Tom.

This concludes our Q&A session. I will now turn the call back over to Dr. Scarlett for closing remarks.

Well, thanks a lot. That was a very spirited discussion, which I think we really appreciate and thank everyone who participated. We thank all the people who listened to the call, and we hope you have a good rest of this week and onward. And we will talk to you again truly at the next quarterly earnings call. Thank you all very much for participating. Bye-bye.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.