Good afternoon, everyone. Thank you for joining the H.C. Wainwright 28th Annual Global Investment Conference. My name is Emily Bodnar, and I am an equity research analyst at H.C. Wainwright. I will be doing a fireside chat with Harout Semerjian, Chief Executive Officer, and Joseph Eid, Chief Medical Officer of Geron. Maybe for those who are newer to the Geron story, if you could start by walking us through your lead asset, imetelstat, or brand name, RYTELO, which is approved for low-risk MDS. Maybe walk us through the mechanism of action, how it differs from other options on the market.
Yeah. Thank you, Emily, and thank you for H.C. Wainwright for this opportunity to share our exciting journey at Geron, which has been a few decades in the making, and finally, we are a commercial stage company over the last couple of years, launching the world's first telomerase inhibitor, helping low-risk MDS patients in the U.S. and hopefully around the world. This is a mechanism that is very unique. It is a Nobel Prize-winning mechanism that really targets the disease itself rather than just masking the symptoms. We launched RYTELO in July 2024, so now it has been about 2+ years and growing. And we are very excited about the potential of this drug, but also about the development that we are doing over the last couple of quarters as well in terms of growth.
Yeah. As you mentioned, RYTELO was approved about two years ago. So how has the launch progressed since then? How have you overcome some of those early launch challenges? And what is your confidence going into the end of 2026 and with your revenue guidance you have provided of $220 million - $240 million?
Yeah, we are confident in RYTELO's potential, but also its trajectory. We have given guidance in the beginning of the year, in the first day of JPMorgan conference, in January, about the overall outlook that we see for this year of a RYTELO net revenue sales in 2026 of $220 million - $240 million. And lately, we have reiterated that, and actually, we have said that we think we are going to be somewhere between the midpoint to the higher end of that guidance, meaning $230 million - $240 million. We have been delivering three quarters of growth back-to-back, which is good. And we know we have more work to do, obviously, but we also like the trajectory that we are on.
As you mentioned, second quarter was your record quarter since launch. What are some of the key marketing and sales force aspects that you are finding are working best, and what is giving you confidence in achieving that higher end of the revenue guidance for the year?
Yeah, and maybe I will give some additional color from a commercial perspective, and Joe, feel free to comment as well from a more medical perspective. It has been a very good journey over the last several quarters, where we have taken the learnings. We are a small biotech. There is a reason why the large pharma start their pre-marketing activities two years, three years in advance. That usually is the case, and certainly, I have done many of those when I was in large pharma. Of course, when you are a more tiny biotech, you are getting to the finish line on fumes in many times. You do not have that luxury. Then what you do is in the first year, you are having to learn what is working, what is not. What is key is to really pivot very rapidly in areas where we can further grow RYTELO.
On the commercialization asset, we are really focused on the second-line patient population in low-risk MDS. How do you know they are a second-line patient population? Well, they were on something else before. Now they are a second line. It is much simpler, especially in a disease where 80% of the business is actually in the community. That is where it is really on us to make the messaging much, much simpler as we get more into the community setting, which we have been doing. The segmentation in terms of where we are focusing, the high volume community accounts is somewhere where we are really now focused. We had to do some work, to be honest, on the academic medical centers over the last 18 months, 24 months, given that a lot of our trials were done ex-U.S.
We wanted to expand on the academic medical centers' experience on RYTELO, which is something that Joe can talk about. But also, that is not just enough to really win in the marketplace, especially in the community. That is where we have been really revamping and honing up our skill sets. As you said, our last quarter, the sales were in the $57.5 million net revenue, which is the highest it has ever been. That is from a more commercialization perspective, but also Joe on the medical.
There are two dynamics. Internally, we obviously focus post-launch on the academic centers to make sure that hands-on experience, mechanism of action, understanding, management of patients, in particular when it comes to the cytopenias, which all of these were new for a new class of drug. As we evolved that pillar, we shifted to the community docs and from CME and small regional hematology meetings to make sure that RYTELO is at the podium and in presentations. The other dynamic, which is external, is NCCN Guideline has been updated twice since the launch of RYTELO, positioning RYTELO as a second line. There is also dynamic change in the treatment paradigm for MDS. Luspatercept having moved from a second line to first line is also creating a positive support for the RYTELO uptake because post-Luspa, serum EPO usually is elevated, so ESA is not an option.
In the community, it is still a split between ESA and luspatercept. Luspatercept takes precedent. You will have more patients that come straight in to be treated with imetelstat. There is also a potential for luspatercept moving to non-transfused patients with the ELEMENT study obviously being conducted. All of these dynamics with the NCCN Guideline and our support for the physician awareness and understanding are helpful to understand the disease, imetelstat's role in improving the disease, and taking its place in MDS treatment.
Yep. That is great. You mentioned your focus on moving more into the second-line setting. Maybe just comment on where you currently are penetration-wise in the first and second-line setting, and how do you reasonably expect that to grow in the coming quarters or years?
Yeah. We have been updating the market on multiple KPIs in terms of leading indicators, beyond just the sales, to really show some of the dynamics of those curves. One of them being the percentage of our sales coming from the first-line, second-line setting in patients versus the late-line setting. That has been growing consistently, 1%, 2%. The last number has been 34% of our business is coming from the first-line, second-line patient population with a 12-month look back, which is very good to see. That is what we want to see that happening. That is a very important indicator because IMerge trial has been predominantly a second-line patient population. Our indication is in the second-line population. The NCCN Guidelines support us in the second-line population.
We do understand the dynamics that in the beginning, when you have a new therapy that's launched, a lot of the physicians will use it for the more needy patients, so later lines. That happens in pretty much every oncology asset that I've worked on. The key is to really move rapidly from there into where we've been studied, where we've been used, and that dynamic, we're seeing it more and more, which is really nice. I would say the last piece of that as well is we have commented that in the Q2 earnings call, our last quarter's earnings, predominantly our growth has been from the community as well, which shows that a lot of the education and the partnership that we've done with the academic medical centers, now moving more into the community setting where the vast majority of the patients are.
That's where we're starting to grow. We do expect that number as well to grow over time.
Yeah. Maybe with the increase in accounts, how has the mix been between new accounts versus new patients or existing accounts within those settings that you're already in?
Yeah, that's why we've been giving also quarterly updates on the number of new accounts coming online, and that's been growing between 100 to 200 accounts every quarter of folks who've never ordered RYTELO before and are ordering RYTELO for the first time. That is a very important metric, especially the first couple of years of the life cycle of RYTELO. We do imagine that that, over time, will come down in terms of the breadth, and then what becomes more and more important is the depth, so that we can get more and more patients from the same accounts, especially the high-volume accounts. That's where Joe's team and Nawawi's team both have been very focused on the educational piece across our physician base. Why?
Because we're really leaning into what a good patient looks like, who can benefit the most, and why it's important to be proactive in terms of managing some of the cytopenias that they will see in the beginning. Why is that important based on the ASH data that we have released? The whole story is coming together, but we got to be relentless in our communications and make it as simple as possible, especially as we move into the community setting, because the average time that those physicians have is very limited, and they see very different types of cancer patients, from a lung cancer patient in the morning to a prostate cancer at noon, and a low-risk MDS patient in the evening.
We really want to make sure that we're really part of that conversation rather than keeping the high-end science in our academic medical centers, and whoever else is needed, it's always there. But we also have very punchy and effective messaging so that they can treat the patients that they see in the way that they see it in the time that they have. That's what we're doing.
How do you characterize the addressable patient population in the U.S. currently, where RYTELO is approved, and what could the peak opportunity look like from here?
Yeah. We haven't given any guidance on the peak opportunity. But at the same time, I think there is a few different metrics out there in terms of showing the size of what can be. One is the size of the business in low-risk MDS. We know that there is another therapy with luspatercept that's around $2.5 billion and growing, only in low-risk MDS. Obviously, they have the first-line set indication and the second-line, but usually a drug is not used in both indications. If you're moving more and more in the first-line indication, that opens the opportunity for us in the second-line, but it is a significant patient population, so that's really something that is out there and important. And if we are true to our guidance of $230 million - $240 million of net revenue this year, that would be in the full second year of launch.
That's the kind of revenue coming in, and we haven't even scratched the surface of all the additional markets where we can serve more and more patients. We have RYTELO worldwide rights. We haven't done any deal. That's another area for us from a geographical growth perspective. The third, I would say, is the shape of the curve. There are certain therapies that have very rapid uptake, especially if a single point mutation or some sort of a companion diagnostic where we can identify the patient and put them on. Typically, what we've seen is a fast uptake of this, but then more of a gradual stability of that curve. While in hematology assets, in areas such as in MDS, what we've seen is growth over time.
We do believe that the curve over here would probably be more of a mimicking continuous growth quarter- over- quarter, and do that for a long period of time. So we're very excited about the potential of RYTELO in lower-risk MDS, where with the launch in the U.S., we're already breaking a lot of that more small company or small net revenue aspect, where we see a lot of other companies sometimes get stuck in that $70 million - $80 million or $100 million. We're already blown through that. Why not be a product that is in line with a luspatercept within our indication, obviously. So that can still be a significant revenue generating folks outcome, especially that we're only getting started.
Yeah. As you mentioned, you do have approval in ex-U.S. markets. What have you communicated about timing for expanding ex-U.S., and what are some of the options that you're looking at?
Yeah, basically we're guided by the mission of RYTELO needs to be everywhere helping patients. We don't necessarily need to be everywhere across the world. That's important because we've all in, especially in our executive leadership team, we have a lot of folks who have actually launched assets around the world. So we know how to do that, but at the same time, we want to also make sure that we're doing the right thing for the patients and also for the company. What we have said is that we're looking at all different options. What we are not going to be doing is doing the classical put 60 people in Germany and 50 people in France, and that's really not for us.
But at the same time, in the world of MFN and other kind of market forces that are reshaping the way how launches happen in the world and launch sequencing, I think everybody's having to relearn that perspective. It's not like somebody has mastered it because there's MFN, and then you hear about GLOBE and GUARD, and then you hear about certain things that will be in and certain things that will be out. What is important is that we're prepared for all these different permutations of it, and what we had committed is before end of year, that we come back to the market with an ex-U.S. strategy, particularly a European strategy.
Meanwhile, we're having those conversations and making sure that we are in a good place with the payer component, because from an advocacy perspective, we actually have even more advocacy ex-U.S. than we had in the U.S. initially. Why? Because our trials were predominantly European trials. So we had a lot of those KOLs who would love to see RYTELO helping their patients. And that's something we want to capitalize on, but we also want to do it in a way that makes sense for the company, for patients as well. So stay tuned.
Great. Maybe moving on to your myelofibrosis program. You have an interim OS readout coming in the second half of the year for your IMpactMF trial. So maybe talk to us about that study a bit. What are the kind of expectations for the interim readout, and is there anything you can share on what would be considered positive?
Yeah. Joe, do you want to comment?
Yeah. This trial, as we have mentioned, has completed enrollment last September. It's a large study, 327 patients, in a relapse refractory to JAK inhibitor population, with imetelstat versus best available therapy. That trial started in 2020, and is continuing to, obviously is ongoing in terms of treating patients that are still on study, and had an interim analysis planned as part of the design. What we have shared at the last earnings call is the discussion that we have proactively started with the regulators, both in Europe and in the U.S., to make sure that any interim analysis that is triggered leads to a positive outcome, meaning that the regulators would accept the parameters in 2026, given the changes in the treatment paradigm for MF, as well as the changes in FDA personnel, policy making, et cetera.
We want to make sure that before we trigger an interim analysis and be unblinded, that we have an alignment. The projection that we have laid out before, as of now, continue to be the same. If there's any outcome from the discussion with the regulator that will alter that projection, we will let the market know.
Great. Assuming the interim, if it was not positive and the trial continued to full analysis, what's your confidence level in the final analysis being positive based on the IMbark trial results you had?
The OS endpoint projection and confidence are still based on the same science. That hasn't changed. The base case for us has been going to the final analysis, given that typically for overall survival trials, interim analysis are a high bar to hit. That's how it's a matter of science and data and events.
Yeah. Maybe just talk a bit about the competitive landscape in relapsed/refractory myelofibrosis. Assuming imetelstat were to get approved, what could the market look like in the post JAK setting?
At this juncture, there's a lot of, obviously, MF noise in the market from acquisitions, new mechanism of action. A lot of that is interesting, but as of now, the only drug that has a potential for approval in the next 24 months is imetelstat. The other aspect of our MF program is the combination with the JAK inhibitor, because we believe that the relapse refractory monotherapy is dependent on IMpactMF. A lot of the patients are being kept on JAK inhibitor because there's a rebound once you take patient off JAK. So that data will be complementary to the IMpactMF as well.
Yeah, and in the phase II, we've seen almost a tripling of the survival signal, right? That's why we have started this large phase III trial in this relapse refractory patient population with an overall survival primary endpoint. It's been six years in the making, which for a small biotech, that's a big undertaking.
Now it's fully enrolled. It's been almost a year. We're aligning with the FDA just in case, even with that higher bar in the interim, if it hits, let's make sure that we have the conversations before we're unblinded rather than having those uphill battles. No one wants to do that. As Joe said, for us, from a planning perspective, we think a lot of these trials will continue to go and mature. They will need more of the time to mature. Meanwhile, we want to grow our base business. We want to be prepared for myelofibrosis, but we also have $300+ million of cash on our balance sheet. The idea is that we put that also to use. So, eight weeks ago, we've hired our first chief business officer.
We're also getting ourselves ready and starting to imagine, as we get our base business in a good shape with hundreds of millions of dollars coming, this year, we grow our business to where it's $230 million - $240 million net revenue. We have reiterated our OPEX guidance of $230 million and $240 million. It doesn't take a genius that we're kind of starting to get to that point where we have optionality to do more as well. That's kind of what is exciting about our journey, Emily, that a lot of our base business, helping those folks and saying that there's about 8,000 of them in the U.S., low risk MDS in the second line setting. Many people, to be honest, tell us, well, there are more low risk MDS patients. And we agree.
We wanted to have a conservative number because even with a conservative number, with our pricing, it just shows what the possibility can be as a base business. Then you have our cash, and then you have now that we're going in the right direction. All this are really seeds for us to plant for making a hematology oncology company for many, many years to come, today with RYTELO and tomorrow beyond that as well.
Yeah. I think that leads well into my last question. Maybe just sum up for us some of the upcoming catalysts that investors should be looking out for into the end of next year.
Yeah, a lot of what it is quarterly building up our business quarter-over-quarter. That's important, especially in the U.S. Finding new ways where we can bring RYTELO's benefit to patients around the world. That's also something very important. Being ready for myelofibrosis, right? You start these trials years ago, and we started in 2020, and then you hope for the best, right? It's fully enrolled now, so a lot of the heavy lifting that our clinical team did over the last six years, now it changed into more of the follow-up, making sure that the cleanup of the data happens. There's a lot of chasing ground that happens for all these different sites, making sure that we're having a very clean database over there, but also now with the BD kind of lens to say, okay, how would we do due diligence?
How would we pay for some of these things? Really making sure that we're having those conversations so that at any given time, we have the optionality to really implement a long-term growth strategy, but really move carefully from the base to beyond that as well and continue to communicate to the marketplace. I think that this team has shown that we're able to do that and we will continue to do that. So multiple different levers from large phase III's that we'll be reading out, but also as a company, putting it in a good shape that with that, without that, we're able to build on RYTELO's base business today and beyond.
Perfect. Thank you very much, Harout Semerjian. Thank you, Joseph. Thanks everyone who's been listening in. Hope everyone has a great rest of their day.
Thank you very much, Emily.