Geron Corp H.C. Wainwright 28th Annual Global Investment Conference

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 plus 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, 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 to $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 to $240 million. We have been delivering 3 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.

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 2 years, 3 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.

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.