Again, my name is James Molloy, biotech and specialty pharmaceutical analyst here at AGP. In this chat, we're talking with another of my coverage companies, one of the more exciting of my coverage companies, SELLAS Life Sciences. We have buy rated a $10 price target, which they're rapidly approaching. They have two compounds in late-stage clinical trials, SLS-009, a CDK9 inhibitor for AML and other hematological and solid cancers currently in phase II, and also GPS in the phase III REGAL trial as a monotherapy in AML patients following second complete remission. With us today from SELLAS is CEO Angelos Stergiou. Thank you for joining us here today, Angelos.
Thank you very much for having us, Jim.
Well, would perhaps you give us a brief overview of SELLAS for our listeners?
SELLAS, we are a late-stage oncology company with a focus on the development of galinpepimut-S or GPS, an innovative and potentially first-in-class Wilms' Tumor 1 or WT1 targeting heteroclitic immunotherapy, as well as our highly selective CDK9 inhibitor, SLS009, in phase II currently. We're focusing on acute myeloid leukemia with both of our assets. Quite exciting because we may be able to shift the AML treatment paradigm, among others, from induction all the way through maintenance with SLS009 and GPS respectively. As for GPS, we licensed this exciting technology from Memorial Sloan Kettering Cancer Center, and we're in a pivotal phase III trial in acute myeloid leukemia, the REGAL trial, and that is in patients after the second complete remission. SLS009 is a selective CDK9 inhibitor, which really gives us an opportunity to potentially, again, be first and best in class, just like with GPS.
We're currently in phase II here in frontline AML, utilizing our extensive transcriptomics, genomics, and proteomics work down really the path of precision medicine to identify patients most likely to respond with our treatment. I think maybe if I can just add that from day one, I've been convinced when I founded the company that science, when pursued with focus and integrity, can truly transform patients' lives. We set out to build an oncology company that blends breakthrough innovation with rigorous execution and strong capital allocation discipline. This diversification, and the complementary nature of both assets from frontline with the SLS009 to maintenance with GPS in AML, as I mentioned earlier, really positions SELLAS as an emerging leader in targeted cancer therapeutics.
All right. Well, let's dive into the lead compound, GPS, in the phase III REGAL trial, in AML. This is a challenging disease state. I think last year we saw any number of companies that had failures in this disease state. Where is SLS finding success where many others have failed? You guys are at 78 of 80 events. It's taking much longer than you would think. It seems to be remarkably effective. What are your thoughts?
Yeah. GPS has shown consistent positive trends in overall survival, durable immune responses, and the favorable safety profile across a broad range of indications, not just in AML, but also in mesothelioma, ovarian cancer, and multiple myeloma. Indeed, survival times in the REGAL study appear unexpectedly long, from a mathematical standpoint and understanding real-world clinical evidence and the fact that we administer GPS to patients even 3 years out. Every passing month, as I've often said, may increase the probability of a successful study due to a potential GPS effect, as we have seen in our previous CR1 and CR2 studies, really far surpassing median overall survival versus standard of care.
Obviously, this disease state is a terrible, AML is still a deadly disease. It's not curative, but extending life vastly beyond the standard of care. It's an 80 events, 80 deaths to unblind the trial. Presently 78 events have occurred. When are you now anticipating sort of the final events and the unblinding and sort of get to the bottom of what seems to be remarkable extension of life here?
Yeah. When the 80th event materializes, and as you said, we currently stand at 78 events, we will inform the public, which obviously represents a very important near-term catalyst for SELLAS. Obviously a subsequent positive outcome could really position GPS as the first-in-class maintenance therapy in AML and unlock significant commercial potential in the CR2 setting.
How could GPS, again, waiting to see what the data looks like, but if things look as it seems like it might, how could GPS change the treatment paradigm in AML if it is, in fact, as effective as it seems to be showing?
As you know, there's nothing approved in the AML CR2 maintenance setting, and GPS being an effective immunotherapeutic with a favorable safety profile would indeed set the stage, I believe, to possibly become the maintenance therapy in AML after patients are in remission, not just in CR2, but potentially also in the CR1 setting. There's been significant interest in evaluating GPS in combination with bone marrow transplant in AML. Last but not least, as you know, GPS targets the number 1 ranked cancer antigen by the NCI, Wilms' Tumor 1, which interestingly in the fetal state is responsible for kidney formation, among other functions. Then it disappears, comes back again when it causes cancer. It's a fetal oncoprotein. There are about 20 tumor types that have this WT1 expression. Assuming positive data, GPS could potentially be developed in other WT1-expressing tumor types as well.
Is there potential, you mentioned in complete remission, but complete response, is there a potential for a first-line therapy, first-line usage, maybe even off-label? I know that certainly you wouldn't market it off-label, but doctors will use things as they will.
Yeah. The multivalent approach of GPS targets 25 carefully selected WT1 epitopes that are predicted to have optimal MHC class I and II presentation and to be really maximally immunogenic and targets both CD4 and CD8. They're much more prone to elicit an antigen-specific immune response, including cell immunity-based memory and helper function via CD4 and, of course, cytotoxic CD8. Our GPS monotherapy studies are in patients with very low burden of residual disease, such as complete remission status in AML, because the tumor microenvironment could be a major barrier. Nonetheless, in our combination approach, for example, with PD-1 blockers, we have successfully administered GPS both in frontline as well as maintenance settings. In the former scenario, attacking measurable microscopic metastatic disease. I do believe that as a monotherapy, patients in remission ought to benefit from our treatment.
If we go into solid cancers, I think a combination, because of the tumor microenvironment, ought to be warranted, where we can go in frontline as well as then maintenance.
I'd love to touch on some other potential indications, but when the 80th event occurs, when would you anticipate having data subsequent to that, and when would you anticipate potentially a BLA? Again, should the data look as promising as it seems to look.
When the 80th event materializes, obviously we'll inform the public, which again represents a very important near-term catalyst for SELLAS and, of course, the disclosure of the top-line data shortly thereafter. With top-line data available, we will do the necessary work for a pre-BLA meeting with the agency, and assuming positive outcome, we'll be in a position to file shortly thereafter.
Good. You touched on potentially some other indications. Would you care to touch on any others here for our listeners?
I think, obviously AML is sort of, if you will, the flagship indication, and it's not by chance when the discovery work was done at Memorial Sloan Kettering Cancer Center. It was done by the former chief of leukemia, David Scheinberg, who is also the Chair of the Center for Experimental Therapeutics at Memorial Sloan Kettering Cancer Center. Inevitably all patients with AML express WT1. There are other indications, as I mentioned, we've done work in ovarian cancer, mesothelioma, multiple myeloma, and there are about 17 other types of cancers where galinpepimut-S could be effective. I think there is, assuming positive data, there's obviously a whole gamut of indications that one could go after.
I think I forgot to mention as well that GPS has both Fast Track and Orphan designation. Obviously hopefully a quicker path through the FDA should you get there. Let's switch over to the next indication, SLS009 for AML in combination with Azaven, that also has Orphan, Fast Track for AML, and relapse remaining PTCL, as well as rare pediatric for ALL and AML in children. Could you walk our listeners through SLS009, please?
Sure. CDK9, as you know, is a major cancer target. It's well-known that many cancers that depend on rapid production of proteins to promote cancer growth, like MYC, and/or to protect cancer cells from shutting down once they're damaged by environmental factors or anti-cancer drugs like MCL1. To rapidly forge those proteins, cancer cells crucially depend on the activity of certain factors, and one which is CDK9, that allows elongation of RNA transcripts necessary for production of proteins that keep the cancers alive. By shutting down CDK9, SLS009 blocks production of cancer-promoting and protecting proteins, resulting in death of cancer cells.
I think what is important to note here is that speed is of the essence for cancer cells, as some of the key stimulating and protecting proteins, importantly the aforementioned MYC and MCL1, they have short lives and have to be constantly replenished for a cancer cell to survive. In fact, it's so important that we see that mechanism employed across a wide variety of cancer types, both hematologic and solid cancers. CDK9 is a member of the larger CDK family, and therefore there's a high level of similarity between CDK9 and other kinase proteins that play a key role in survival of not only cancer cells, but normal cells. Therefore, to avoid severe toxicities that eventually curtail duration of treatment and therefore efficacy, the selectivity of CDK9 inhibitor is crucially important, especially for those strongly binding new generation of molecules.
AstraZeneca, our biased drug, for example, who by the word discontinued their programs due to toxicity and efficacy reasons, suppresses other kinase proteins, whereas SLS-009 is quite selective and specific to CDK9. Unsurprisingly, the other drugs were tolerated up to 30 milligrams, yet we could dose SLS-009 up to 100 milligrams, and even then we could go higher, but chose not to, as we have reached optimal efficacy long before that. Basically, SLS-009, Jim, is in the body long enough to kill cancer cells, but not long enough to cause severe toxicities as other CDK9 inhibitors have shown.
How did it come about? This is one that more recently came into SLS. How did that come about, you guys brought in SLS009?
Yeah, this came about a few years back where we wanted to have an additional asset, yet complementary to GPS, but also to look for other indications. We partnered with GenFleet Therapeutics, who are really experts, if you will, in going after drugs that are after targets that are not druggable or are really exciting targets, but where efficacy or safety issues have been a problem with other drugs. We partnered with them. If you will, they are experts in this type of development work, and through our network, we're able to bring the asset in.
This is first-line treatment. In December, you presented some interesting data at the American Society of Hematology, the ASH meeting. Could you walk our listeners through that data, and sort of any updates on how the current study's going?
Yeah. In December, as you mentioned, at the ASH conference, the phase II expansion study showed a 44% overall response rate across all relapsed/refractory AML-MR cohorts and close to 60%, specifically 58% OR in patients with 1 prior line of therapy treated with 30 mg twice a week. Those responses, they far exceed the targeted 20% benchmark. Furthermore, we showed that the median overall survival of 8.9 months in patients with relapsed/refractory to venetoclax-based treatment, AML-MR and 8.8 months in all relapsed/refractory to venetoclax-based treatments with a median of 1 prior line of treatment, which far surpassed the historical benchmark of 2.4 months. What we then did with elite academic center here in the U.S. Oncology Center, we dove in doing really extensive transcriptomic, proteomics, genomics work. With guidance by the FDA, moved into the frontline setting.
The results to date, as I mentioned, have been extremely encouraging and may represent really an important advancement for SLS-009. Indeed, our current trial, with input by the FDA, focus on newly diagnosed patients where we'll administer, or we are administering SLS-009 in the frontline setting, truly frontline, as well as in patients who did not respond to azaven after 2 cycles by utilizing our biomarker approach through our omics work that we have done. The things that we would want to see or the goals of the study, in addition to safety, of course, is, 1, to assess the efficacy of SLS-009 as an add-on therapy measured by substantial increase in complete response rate compared to control arm percentage. Also to increase overall survival considerably compared to control arm.
Lastly, to confirm our predictive properties of biomarkers identified and to compare and confirm those really with further work that we're doing in transcriptomics, genomics, and proteomics.
How is the trial recruitment going? How's the environment for recruiting for this trial in general? I know there's obviously a lot of oncology trials out there in the world.
I think there's a lot of excitement, Jim, because I think in the CDK9 space, humbly speaking, we're sort of ahead of the curve, not just because of the data, but with all the biomarker work that we have done. We started enrollment in March already in the U.S., and we will add Europe into the study here very soon. What I expect is to have top-line data available from this study sometime later this year. Obviously, we're very extremely excited about the potential to use the data towards potential accelerated approval path and/or quickly move into registrational study with SLS009 based on the predictive work that we have done, the biomarker work that we've done and identified, in addition to other solid cancer indications that these biomarkers express.
The first patient was in March 12th. Maybe for some listeners who aren't as familiar, could you walk through azaven and how that's a standard usage in AML?
Yeah, I believe in the Western world for sure, I think there will be no patient moving forward will not have seen venetoclax type of treatment. It is sort of the standard treatment. The issue with venetoclax is, I think, twofold. One is just like other drugs, it is myelosuppressive, and it has severe toxicities, and that's why I've said for many years that I really believe that over the next five, 10 years, immunotherapeutics will really bypass other types of modalities. Coming back to venetoclax, the other issue is also that the vast majority of patients, at some point, may either relapse and/or, well, or they're refractory to venetoclax to begin with. We need treatments either as a monotherapy or to reverse that setting of being refractory or patients who have relapsed on venetoclax to make them and get them sensitized towards an efficacious treatment.
I think that's exactly where SLS009 really is ahead of the curve.
azacitidine, venetoclax is the sort of the standard combo therapy everyone gets who's unfit for intensive chemotherapy. All right. We're getting down to the last minute and a half here. You guys just reported your first quarter, $110 million in cash, very well capitalized. What sort of milestones does that get you through, and what run rate do you have?
Yeah, we are extremely pleased to be in such a strong financial position, which really enables us, Jim, to reach all our important upcoming milestones.
The next key catalyst we should be watching for, I guess, data in SLS009 end of this year, and then obviously the 80th event, and then the data release from that.
That's accurate, yeah. The announcement of the 80th event, then followed shortly thereafter with top-line results and on galinpepimut-S and SLS009 top-line results by year-end.
Excellent. Well, thank you very much, Angelos. With that, we're at the end of our Fireside Chat. I'd like to thank Angelos from SELLAS for joining us today and for all of you for listening. This ends our SELLAS Fireside Chat. Please stay tuned for our next Fireside Chat coming up right after this. Thank you very much.