Ladies and gentlemen, and this is the operator. Today's conference call will begin in 2 minutes. Until that time, your lines will again be placed on hold. Ladies and gentlemen, Thank you for standing by and welcome to the Q2 2021 Juran Earnings Conference Call. At this time, all participants are in a listen only mode.
As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Ms. Olivia Bloom. Please go ahead.
All right. Thank you very much, Grace, and good afternoon, everyone. Welcome to this conference call to discuss updates on our ongoing imetelstat Phase 3 clinical trials as well as Q2 financial results. I am joined today by Doctor. John Scarlett, Geron's Chairman and Chief Executive Officer Doctor.
Alexander Rizzo, Geron's Executive Vice President and Chief Medical Officer and Anil Kapoor, Geron's Executive Vice President of Corporate Strategy and Chief Commercial Officer. After the market closed today, we announced updates on our IMerge Phase 3 clinical trial will be available on our website for 30 days, including the slides being presented today. Before we begin, Please note that during the course of this presentation and question and answer session, we will make forward looking statements regarding future events, Performance, plans, expectations and other projections, including those relating to the therapeutic potential of and potential regulatory approval of imetelstat, Anticipated clinical and commercial events and related time lines, the sufficiency of Geron's financial resources and other statements that are not historical facts. Actual events or results could differ materially. We refer you to the discussions under the heading Risk Factors in Geron's Quarterly Report on Form 10 Q We undertake no duty or obligation to update our forward looking statements.
And now, I will turn the call over to Doctor. Scarlett. Chip?
Thanks, Olivia, and good afternoon, everyone. I'm very happy to say we've
made a
lot of progress since last quarter, With regard to our ongoing EMERGE Phase 3 trial in lower risk MDS. First, In that trial, we've reached 91% of the planned enrollment. We currently expect to complete enrollment in the Q4 of this year. In addition, we've accelerated the timing of top line results in IMerge Phase 3 by 3 months. We've done this by shortening the follow-up period to the last patients been enrolled from 15 months to 12 months for the primary analysis.
As a result, we now expect top line results Alexander, our Chief Medical Officer, will comment on the progress we've made in both our ongoing Phase III trials. And finally, Anil, our Executive Vice President Strategy and Chief Commercial Officer will discuss the market opportunity in lower risk MDS. So let's get started.
Thanks Chip. The increase in operating expenses for the Q2 year to date period 2021 compared to the same period in 2020 was primarily driven by higher development expenses. This increase in R and D expenses The increase in general and administrative expenses for the Q2 year to date periods of 2021 compared to the same period in 2020 Primarily reflects new costs in connection with pre commercial activities, including modernizing the internal infrastructure to support a commercial launch And higher legal costs. Previously, we provided guidance that our financial resources were sufficient to fund our operations Through the end of 2022, as of June 30, 2021, we had $239,100,000 in cash, Cash equivalents and marketable securities. We now project these financial resources combined with expected future non dilutive funding From the second tranche under our current debt facility, we'll fund our operations through the end of the Q1 of 2023, By which time, top line results from IMerge Phase 3 are expected.
With that, I will now turn the call over to Alexandra, who will review the progress in our Phase 3 clinical trial. Alexandra?
Thank you, Olivia, and good afternoon, everyone. Let me start with 2 important updates related to our IMerge Phase 3 clinical trial for which I'm so pleased that we are nearing completion of enrollment. As Chip commented in his introduction, we have achieved 91% of the planned enrollment as of last week, And we now expect to complete enrollment in the Q4 of 2021. Moving on to another important update about this study. We have determined that the clinical cutoff date For the primary analysis, could occur 3 months earlier by shortening the follow-up period from 15 months to 12 months After the last patient has been enrolled.
This change is due to the significantly longer enrollment period Caused by the COVID-nineteen pandemic, which has allowed enrolled patients on the study to have longer follow-up We'll be similar to the overall median follow-up in the Phase 2 trial, which as you might remember was 24 months. Thus, even with the shorter follow-up, we continue to expect to have mature data set that will allow us to assess the safety And efficacy of somatostat, including durability of transfusion independence. Furthermore, Since we've already enrolled more than 90% of the patients, we believe the impact of this change on our efficacy results will be minimal, if at all. Accordingly, we submitted a protocol amendment to the FDA and have not received any comments on the proposed change. We plan to distribute the final protocol and then to all clinical sites shortly.
With the revised 12 month follow-up period for the primary analysis. We now project that the top line results for IMerge Phase 3 will be available in the Q1 of 2023. Also in July, A regularly scheduled meeting of the independent data monitoring committee for this study occurred, and the committee recommended the trial continue without modification. In conclusion, we are making good progress with this study and I look forward to our announcement when we achieve full enrollment of the trial. Turning to Intrax MF, our 2nd ongoing Phase 3 trial.
The focus for this trial has been on opening sites, which as you know is one of the key factors for patient enrollment. As of last week, 55 sites were open for enrollment. We plan to engage over 180 sites In 30 countries across North, South America, Europe, Australia and Asia. We continue to expect the interim analysis to occur in 2024 and the final analysis in 2025. Just as a reminder, the number of events required to conduct the interim analysis for this study could occur I'll turn the call over to Anil.
Anil?
Thanks, Alex, and good afternoon, everyone. In my prepared remarks today, I'll provide our perspective regarding 2 topics, unmet needs and the market dynamics And low risk MDS that we believe make for an exciting commercial potential for emetelstat. Lower risk MDS, as many of you know, represents approximately 70% of the total MDS patient population. This is an attractive market with a large addressable patient opportunity. There is a significant unmet need For new therapeutics in this setting, as patients are typically elderly, present with chronic anemia, Are dependent on frequent red blood cell transfusions, have poor quality of life, heightened risk of transformation to acute myeloid leukemia And short and survive.
If you look here, we have a schematic of the low risk MDS landscape. You will see that keratopoiesis stimulating agents or ESAs are the mainstay of treatment for the approximately 90% of patients Who have symptomatic anemia and do not have deletion 5Q. Not all patients respond to All are eligible for ESA. And among responders, responses typically last for between 18 24 months. Treatment options are limited for patients who have failed ESAs or are ineligible for ESAs and may include Hypomethylating agents or HMAs and as of recently luspatercept.
Wanted to also quickly note That HMAs are not a preferred option given their limited benefits. Also, they are not broadly approved across the EU for this indication. Luspatercept was recently approved in 2020 for ESA failed Ring Siderogloss Positive Patients. This IS positive segment covers only approximately 25% of patients, Leaving a significant unmet need for effective therapies for the remaining approximately 75% of lower risk MDS patients Moving on to Imetelstat's expected target product profile. In our recent market surveys, Community and academic hematologists reaffirm the unmet needs in lower risk MDS and highlighted How the strengths of Imetelstat can address those needs.
Key aspects of Imetelstat's profile That resonated most strongly with these hematologists are shown on this slide. In particular, I would like to point out That the hematologists appreciated having the ability to treat RS negative patients where there is no approved treatment. In addition, they pointed to the durability of transfusion independence, the 24 week and the 1 year Red blood cell transfusion independent data from the IMerge Phase 2 trial resonated particularly well with physicians as they felt These outcomes to be more clinically relevant than 8 week transfusion independent. In Europe, both regulators and payers Have requested to see 24 week TI data as well. In addition, the potential for disease modification was also very well We expect to achieve broad label coverage for emetelstat in ESA relapsedrefractory, Non deletion 5qlowrisk MDS that includes not only both RS positive and RS negative patients, Therefore, we expect a highly differentiated position for Imetelstat at launch, We expect emetelstat patients to come from 4 main groups, all of whom are eligible to be enrolled In our ongoing IMerge Phase 3 trial, the first group and our key focus is the ESA relapsed refractory RS negative patients.
This is the largest opportunity of about 22 Effective approved therapy available to them. If IMerge Phase 3 is positive, We expect emetelstat will become the standard of care in this segment. The second group is the ESA Relapse and refractory RS positive patients. This group has an addressable patient opportunity of approximately 7,000 patients in the U. S.
And the 5 largest European markets. Note also that this is where luspatercept is currently approved. We expect Imetelstat to compete favorably with luspatercept in this setting, Especially in patients with higher baseline transfusion burdens, such as greater than 4 units per 8 weeks, Which is more than 50% of the population in this segment according to our analysis. The 3rd group Is drawn from the first line lower risk MDS patients with high endogenous serum EPO levels Greater than 500 milliunits per ml, who are ineligible for ESAs. This group has an addressable patient opportunity of approximately 3,700 patients in the U.
S. And the 5 largest European markets. Finally, the 4th group of patients for emetelstat will come from those Who have been previously treated with luspatercept. The ultimate size of this segment is yet to be determined And we expect it to grow over time. Just to also point out, as many of you may know, Both luspatercept and ESAs stimulate production of the normal red blood cell via the EPO receptor, Although at different points in the red blood life cycle.
Based on the fact that we have encouraging data in patients who have As a reminder, these patients are eligible to be enrolled in our IMerge Phase 3 trial. Based on our current commercial assumptions and assuming regulatory and payer access to the full patient population I just described, We expect Imetelstat to exceed $1,200,000,000 in potential peak revenue across the U. S. And the 5 largest European markets in lower risk MDS. Lastly, As shown on this slide, I would like to provide a brief update on our commercialization efforts.
With top line results expected in the Q1 of 2023 and assuming priority review, We could potentially launch in the U. S. Market in the first half of twenty twenty four. As an early preparation for launch, We recently hired senior, highly experienced industry professionals to lead our medical affairs and market access functions. With this team, we will be refining our value proposition across all stakeholders, Building a deep understanding of the customer base and executing on our medical affairs plans to ensure a comprehensive understanding of the potential for emetelstat Within the lower risk MDS treatment community.
As we do this, we are applying a stage gated milestone driven investment mindset, which will result in the bulk of our commercial investments coming after top line results are available. We believe Imetelstat has the qualities that strongly differentiated from other drugs currently being marketed All in development today for lower risk MDS. And we are excited about the progress we are making With that, I will now hand over the call to Chip. Chip?
Thanks very much, Aneel. When I turned the call over to Olivia, I said we had a Cover today, now you can see one of the reasons I said that. Aneel just commented that Imetelstat is a potentially transformative product. I'd like to add that with Imetelstat, we expect to transform Geron into a dynamic commercial company over the next several years And to become a leader in the treatment of hematologic malignancies by modifying the course of these diseases in order to improve and extend the lives of patients. As we conclude our call today, shown on this slide, We'd like you to know that we plan to host a virtual event for investors and analysts in November, when management and key opinion leaders will discuss Several broad topics.
The first is Imetelstat's potential for disease modification in lower risk MDS and refractory MF. The next is our expected path to commercializing imetelstat. 3rd is an expansion of imetelstat's development plans, including new studies and additional indications. And the 4th will at least briefly cover our early discovery program in 2nd So please look for further details about this event that will probably come in October of this year. So with that operator, let's please open the call to questions.
Your first question comes from the line of Charles Duncan from Cantor Fitzgerald. Your line is open.
Yes. Good afternoon, John and team. Thanks for taking our questions and congratulations on the enrollment progress in IMerge. So I had just a couple of questions. And Alexander, I guess kind of alluded to this, but with regard to the Primary analysis, Chip and FDA response, I think she said no comment from FDA.
So you take that as Agreement from them that, the analysis you've done to allow for shorter follow-up Is Copacetic with
them? Go ahead, Alex.
Sure. So, Charles, we submitted a protocol amendment to the FDA over 30 days ago, and we have not received any comments on the proposed change. As you know, this is Kind of a regular procedure, if you don't hear from the agency within 30 days, you go ahead and So we are at that stage. The 30 days have passed and no comments received. So
Okay. Very good. And then with regard to the enrollment thus far, yes, nearly complete. To the criteria?
I don't think so. I don't think there's any geographic pattern here. We've Seems especially for the elderly patients that are enrolled in our trials has helped. So with that, The enrollment has really picked up very well. But no, to go back to your question, I don't think there's any pattern there.
Okay. And then regarding the blinded efficacy or blinded interim, look, the IDMC look in July, Was there any criteria for trial, I guess changes, Any efficacy criteria or anything else that really could have come out of that meeting
Right. So all we hear from the IDMC, per all of the documents, per the charters This is whether the study should continue with or without modifications. So just like last time, this time they said
Probably have to wait till November to get the answer to this. But when you contemplate commercialization of imetelstat across the globe, Do you think that you'll end up working with a partner for ex U. S? I mean, what is your preferred strategy there?
Chas, it's Chip. Yes, we're actually deep in consideration of that question, Doing a lot of analyses, a lot of background work, a lot of work specifically with regard to the drug and the markets. And so I think today we're not ready to make that have that comment on it, but that is our That's kind of our plan and stay tuned as they say.
Okay. Thanks for taking my questions. Congrats on the progress.
Thank you. And your next question comes from the line of Justin Walsh from B. Riley Securities. Your line is open.
Hi, thanks for taking the questions. I'm sure we'll hear more details in November, but maybe you could provide some color on why now is a good time to expand Imetelstat's Development plans and how the 2nd generation telomerase inhibitors are expected to fit into the Geron story?
I'll let Alex take the first part and I'll take the second part. So additional development plans, you want to just comment about that?
I think that at this point, Justin, we are certainly considering to expand in areas where we have a good Preclinical data, we believe in our data, we believe it's a strong data and there's always it's always a good time to And in traditional indications, if you have good data. Yes.
I think I'd add to that, Justin. If you look back at A consistent theme that we've had for quite some time has been the exploration of the effect of imetelstat on The molecular basis of disease and in particular on malignant stem and progenitor cells. And I think we've put together an amazing Cascade of data that's really strongly supported that what's going on is that we're selectively targeting and killing the lignin stem and progenitor cells in the marrow. And these are the cells and the clones that are responsible for the disease. So when we see in both of our big Phase 2 programs, Really good evidence that there is a significant and selective killing Of these malignant stem and progenitor cells and ultimately the marrow depopulates with more normal I think that really encourages us to look at additional indications in heme malignancies.
This is kind of what's really needed, right? And so now that we've got both of these Phase 3 studies up running, one almost completed in terms of enrollment, I I think it's the right time to look at other opportunities. And of course, as Alexander says, we have preclinical data, Non clinical data, some of which is public, some of which is not yet public that really encourage us. So stay tuned for November. I think we're Excited to tell you about some of this.
Got it. And how about the 2nd generation inhibitors? How do those fit in?
Well, I think it's a fair statement to say that Imetelstat is really a 1st generation telomerase inhibitor. It's the only one that we're really aware of that is in the clinic today and has advanced thus far. There are a lot of things we would love to do that you can imagine that would incorporate, an even more attractive profile. And I think we won't get into that today. I want to save a little bit of the powder for November, but we just We decided some time ago that it was really the right time to go off and begin the early stages of a medicinal chemistry effort To identify other scaffolds that would be potentially attractive.
And We'll go into that in a little more detail. Obviously, a lot of it remains proprietary, but we did want people to know that we're not just sitting back with Natelstat is our only idea towards telomerase inhibition. We think that the data really strongly supports Going forward in multiple different areas and having a new drug, new indication our new IP, new everything Would be very potentially attractive.
Got it. Well, I'm looking forward to hearing more in November. Next question. So what if anything, do you guys think that the recent acquisition of Constellation could tell us about the deal appetite and continued interest in the MS space?
Well, whenever you see one of your colleagues who is involved in similar areas that you are get Acquired and at a very nice premium. I don't think that it makes any of us feel anything but good, right? I mean, that's Just a shareholder, a broad shareholder perspective and one that I'd be hard for anybody to argue against. I think that it's an interesting deal. We won't go into how we view various elements of the deal itself.
But I will say that it was a healthy price. It was still a relatively early And I should just say more opportunities will come the way For patients to get better therapy as more resources are put into any of these drugs. So Good for them and good for the business and most of all good for patients.
Got it. Now last question from me. Now that we have patients enrolling in IMPACT MF, do you have a sense if most of these patients have seen treatment with fedratinib as well as rasolitinib and How that could possibly affect any read through from IMbark?
So I can take that question. I think that at the moment, I mean, it's a randomized study. It's meant for registration and we're really not looking into the data, Patient disposition or anything like that. So I think it's very early for us to give a comment on that, Justin.
Yes. I would agree. I would make a separate comment. Our perception is that fedratinib does not have a huge uptake in the market, But that's really not for us to make comments about. And as Alex said, this is a blinded big blinded study and hands off for most of this.
And not blinded, but it's randomized and Phase 3 registration. Yes, exactly. So we should not be looking at any of
comes from the line of Stephen Willey from Stifel. Your line is open.
Yes. Good afternoon. Thanks for taking the questions and congrats on the enrollment progress.
I was wondering, so I know
that you're speaking to, I guess this subgroup of potentially frontline patients that are ESA And I know that they were, I think, a fractional component of the Phase II patient population. I'm not sure if we've ever Seeing activity or clinical data broken out on the as a function of ESA Eligibility or ineligibility, but just wondering if you've had any regulatory conversations around your ability to procure The distribution of ESA ineligible patients looking similar to the Phase 2 experience.
Yes. It's a great question, a very thoughtful question. Thank you. Alex will start.
Yes. So This is actually data that's published in the JCO and also in couple of our abstracts or conference presentations Where we've been reporting data with in different subgroups, so patients with Lower or higher than 500 micro units per ml of nickel. And What we've shown is that actually you can achieve transfusion 8 week transfusion independence or HIE Irrespective in which subgroup you belong, right? So you're talking specifically for those that are the high EPO, right? So the refractory to EPO patients that have never seen an EPO before, they've never seen any treatment so far.
So based on our data, I believe that this patient population can be included in our label. And we had a good proportion of patients even in our Phase 2 study that were in this bucket, I would say. So I don't know, Chip, if you want to add something to that. So Yes, we don't
usually get into conversations that we've Had or haven't had with regulators and it's always speculative, right, how this works out. But I think the critical element is that there is a small but meaningful Percentage of patients who never respond to ESAs and those patients were included in the MEDALIST study, as I recall. And we've seen some patients in our Phase 2. So I think we feel pretty comfortable with the idea that we'll be able to access that patient population. How it actually comes out and whether it gets labeled, whether it's via NCCN guidelines, there are a lot of different ways this can play out, but the most important thing is to have data.
So we would expect to have data that would bear on your question, Steve.
Okay. And then maybe just, I guess a follow-up from one of the earlier questions with respect to next gen telomerase inhibitors and again maybe this is a November Investor Day topic. But Are some of these next gen compounds that you're looking at, are they also, I guess, oligo based in terms of structure? Or Is there a way, I guess, from a MedChem perspective that we should think about next gen telomerase inhibitors as being, I think, a little bit maybe more in the Traditional small molecule mold. Thanks.
Well, you're right. This is I'm going to just tease you on this and not tell you anything more. We will talk about a little bit more in November. We wanted to make sure people had a good reason to come to that call and that was one of them was we thought this would have some real interest. It's let us suffice to say right now that we would like to see a whole host of things that obviously if you start a discovery program many years after your initial discovery was started, there are lots of things that you would change.
And we'll talk about some of those and some of the scaffolds and what they look like. So it's de novo medicinal chemistry work that we're doing. Let's put it that way.
Okay. Very interesting. Thanks for taking the questions.
Thank you.
Thank you. This concludes the
Thanks everybody for joining us today. We really appreciate you taking the time to dial in and participate. And we do expect to present at 3 healthcare conferences in September And webcast details for those events will be available at the beginning of next month. So keep an eye out for that. And we also obviously look forward to virtually seeing many of you at our Investor Day in November.
Thank you. Everybody have a good afternoon.