One, I am Imogen Mansfield. I am one of the biotech analysts here at Cantor, and I am delighted to be joined by two members of the management team from Eikon Therapeutics, Roger Perlmutter, the CEO, and Freddie Bowie, the CFO. Thank you for coming.
Thank you.
Thanks for having us.
Yes. We are very happy to have you here. To get us started, Roger, could you give us an overview of Eikon today, a quick snapshot of the company?
Sure. Eikon is a late-stage therapeutics company. We have, right now, four main drug candidates in the clinic. Those include a TLR agonist, which is being developed for advanced melanoma and advanced non-small cell lung cancer. We also have two highly selective PARP1 inhibitors, one of which is brain penetrant and the other which is not brain penetrant. The not brain penetrant one is the most advanced, and is being developed for traditional indications, breast, ovarian, prostate, and perhaps some pancreatic activity as well. The brain penetrant molecule has similar options, but it also can be used in patients with active brain metastases. We also, beyond those three compounds, we have a highly selective Werner helicase inhibitor, which is in clinical trials as well. The most advanced studies are for our TLR agonist, which is in registration enabling studies for melanoma and non-small cell lung cancer. That's the oncology portfolio.
The company is based on super-resolution microscopy, advanced imaging tools that permit us to evaluate targets that elude others and to prosecute targets that others simply can't pursue. Over the long term, it's the most important source of value for the company.
That, however, is a minority of our expense because clinical trial expenses are significant-
...for a late-stage company.
Let's quickly touch on the platform there. Could you tell us more about single molecule tracking and what is Eikon able to do that other people can't do?
Right. Thanks. The entire reason why Eikon Therapeutics was started, why we started it, was to apply these advanced imaging tools, super-resolution microscopy, to drug discovery. Super-resolution microscopy has a long history. Eric Betzig, who helped to develop that field and shared the Nobel Prize for his discoveries in 2014, is the person who was a co-founder of Eikon Therapeutics. I got involved in this actually before he got the Nobel Prize a long time ago, more than 15 years ago, at the time when I met Eric. He explained that he had been working on a method that would permit us to look at individual proteins in living cells in a non-destructive way, and that could, in principle, permit us to evaluate how those proteins were behaving in living cells. The work was fascinating.
When I was at Merck for my second tour of duty there, beginning in 2013, I had Eric come and spend time with our scientists. He's a physicist by training, and he realized that by being able to evaluate what I'll call, in general terms, the motion of individual proteins in living cells, we could learn important things about the interactions of individual proteins, one with another. That turned out to be absolutely true, but in a way that surprised us. In order to make this work, we had to build instruments that permitted us to capture individual proteins that have been labeled with a fluorescent probe, and to watch them move around in living cells. Those tools took some time to build. We have quite a large engineering team. The instruments that we've built are entirely proprietary.
They permit us to evaluate millions of cells per day and typically 10 to 100,000 proteins per cell. We image at a rate usually of about 100 frames per second. We have roughly 10-millisecond time resolution for the motion of proteins in living cells, and roughly 10 to 30 nm, 10 to 30 billionths of a meter, spatial resolution for those proteins. What I say when I'm describing this to lay audiences, I say is what we're really studying is the social lives of proteins. It turns out that individual proteins have very rich social lives. They have friends and family, and they have family members that they like to see a lot of, and others, once a year at Christmas, would probably be okay. They have friendships that are deep and abiding, and others that are quite shallow.
We get to see them all, and we can see the partners. That turns out to be extremely powerful because biochemistry, of course, is a team sport. The motile characteristics of a protein are limited by the interactions of the protein that we have the label on with whatever it interacts with. Drugs typically influence the ability of proteins to interact with their friends and family. That is how they work. What that means is that you can screen for compounds that change motion, and what you find are compounds that change function. You can do that even if you do not know what the function is, as long as you have some kind of phenotype that you can measure.
What that means, of course, is that we can, as I say, we can prosecute targets that others would find impossible to prosecute. The data sets are enormously large because this is imaging data, again, that we are capturing in fractions of a second. We can work at frame rates that are higher than 1,000 frames per second. All I will say to you today is that little Eikon in Milpitas, California, is one of the largest data producers in the world. When our instruments are all running full tilt, which they often are, we produce on the order of a petabyte of data a day, which, as Russ Berman, our lead engineer, often says, is a ridiculous amount of data. A petabyte, just to give the scale, is roughly enough data to fill the U.S. Library of Congress 60 times per day. That is a lot of data.
I guess with all that data, should we be expecting an acceleration in the announcement of new drug candidates from the platform? How is that helping you find new drugs faster?
Yeah. I think what we have demonstrated is that, as I said, we can identify potential targets because we can actually visualize them and we can see what happens as we interfere with them. We also do not really need to be structurally enabled in order to pursue a target, although often we become structurally enabled. We come to understand what the protein structure is and how it binds to a particular molecule that we would screen. Our screening assays are very fast. We can screen 1 million compounds or so in roughly 6 weeks. We can analyze those then using the same kinds of imaging tools. We sort of set a land speed record for our Werner helicase inhibitor, which went from the initial lead to a development candidate in about 16 months. That is, of course, in the clinic now.
Initial clinical data, we presented healthy volunteers data at ASCO recently, but the clinical data in patients will be presented at ESMO in October in Madrid. That gives you an idea of how fast it is. Another one of these is the novel androgen receptor antagonist, a Nilutamide, structurally quite different androgen receptor antagonist, that is active against the mutations that emerge in the presence of enzalutamide, the leading androgen receptor antagonist. That molecule, which we had originally planned to file an IND on in 2027, we are going to actually file that IND before the end of this year because we were able to do the analysis so fast. It involves multi-parameter optimization that would be almost impossible to do using traditional biochemistry. We believe, yes. The answer to your question is yes.
Cool. They are ready.
That we will be able to bring forward important new molecules much more rapidly through these tools.
Great. One final question on this. Do you anticipate broadening beyond oncology? You have mentioned neuroscience programs. We do not know the targets yet, but how are you thinking about therapeutic areas you are pursuing there? You also just hired a new CSO who is very accomplished. Does that signal a greater investment in the pipeline or expansion of therapeutic areas that you are-
Yeah
...working on?
Yeah. Well, as you can imagine, because we can visualize processes in living cells, we have expanded our interests into other areas. We can visualize living neurons, and we can watch what happens. We were particularly interested in misfolded proteins in living neurons because there is a great body of evidence that suggests that these misfolded proteins are important in the pathogenesis of neurodegenerative disease. Of course, we would love to have an impact on that. We can visualize that misfolding process in living cells, and we can begin to approach the question. There is, I will just tell you, a biochemistry associated with this, and we would love to be able to identify components that are involved in the correct folding or refolding of proteins that have become misfolded and are toxic as a result.
We have also been active in inflammatory disease, and there are good targets there as well. CP Chang, who just joined us as our new Head of Discovery Research, is a very accomplished leader. He is a molecular cell biologist who has a background in gene expression from his work at Stanford University, where he obtained his PhD degree and also did postdoctoral work. In addition, he is a board-certified cardiologist and was deeply involved in the development of drugs for cardiomyopathies, particularly at MyoKardia, where he worked previously. Then he also led the discovery cardiovascular research arm of Bristol Myers Squibb. So he has quite a lot of understanding about that. He and I have agreed that if there is the opportunity to discover something that addresses the major cause of death for human populations, which is cardiovascular disease, that that would be okay with me.
Okay. Cool. Let's go into your clinical programs, and we'll start with PARP1. You've got the two in-licensed selective PARP1 inhibitors. Tell us about the rationale for PARP1 selective inhibition and why you think that these assets will contribute towards a very meaningful advance for the field.
Right. Thank you, Imogen. We are fortunate at Eikon Therapeutics that we have Roy Baynes as our Chief Medical Officer. Roy and I have worked together for a quarter century or so, long enough to get to know each other. One of the things that we were involved with is while we were leading the clinical programs, Roy was the Chief Medical Officer at Merck. One of the things we were involved in was the development of olaparib or LYNPARZA, which is the leading non-selective PARP inhibitor. It's active against PARP1 and PARP2, and some other ADP-ribosylating enzymes. It's an important drug. It's a meaningful drug, and it is used mainly to preserve the treatment effect that's observed typically with platinum chemotherapy. That's true in individuals, in particular, whose tumors bear certain kinds of mutations in DNA damage repair. So homologous recombination repair defective mutations.
That includes, of course, breast cancer and ovarian cancer with BRCA1 or BRCA2 mutations, as well as a whole set of others, PALB2 and RAD51 and et cetera. In those cases, there is synthetic lethality because they're already defective in an aspect of homologous recombination repair, and the inhibition of a poly ADP-ribose polymerase involved in that, PARP1, largely, we believe, is what's responsible for the treatment effect. We believe that PARP2 is not necessary for the treatment effect, and that's in part from studies in preclinical models. PARP2 inhibition does contribute to some of the adverse effects that are seen with olaparib, LYNPARZA, or other PARP inhibitors among the four registered PARP inhibitors. These are important drugs. They have a meaningful impact for patients, particularly with ovarian, breast cancer, prostate cancer, but also some other tumors, including pancreatic cancer.
What we would like to do, of course, is to have a highly selective PARP1 inhibitor that preserved the treatment effect but reduced the hematologic toxicity that's associated with PARP2 inhibition. We decided, because of our experience with LYNPARZA, that we could use Eikon's biochemical tools, to scour the Earth for the most selective PARP1 inhibitors, and to truly test the hypothesis that a selective PARP1 inhibitor would be, in fact, a better therapeutic molecule because it would have a better therapeutic index. So we did that, and we found a set of molecules at a small company called IMPACT in China, run by Dr. Cai, whom I'd known in a previous life, a medicinal chemist. These compounds are really quite distinctive. They have different sorts of structures from the existing PARP inhibitors, and they are very selective.
Two of those molecules, we filed the INDs and advanced two molecules. One, as I said, is brain penetrant, and the other is non-brain penetrant. The non-brain penetrant is called EIK1003 and is the most advanced. It's about 650-fold selective for PARP1 over PARP2. The brain penetrant is even more selective, about 800-fold selective at the enzymatic level. These molecules have the characteristic of having less myelosuppression, less reduction in production of red and white blood cells and platelets as compared to the dual PARP1/PARP2 inhibitors. We've demonstrated that in more than 250 patients who've been treated with EIK1003. The impression is that the result of that is really quite powerful.
For example, we've been able to show, and we presented these data at ASCO in June, that we can use EIK1003 in combination with paclitaxel chemotherapy at full dose in the treatment of ovarian and breast cancer in the second line. It has not been possible, to my knowledge, ever before to combine a PARP inhibitor with paclitaxel, because the combined toxicities in terms of myelosuppression were simply intolerable. We tried with LYNPARZA very hard to develop a protocol that would permit that. We were not able to do so. That's quite remarkable data. What we've shown is that EIK1003 is an active drug, that PARP1 inhibition is associated with activity in the susceptible tumor types at roughly the frequency one would expect. These are based on single-arm studies, but quite robust single-arm studies.
We've shown in the combination studies that you see quite impressive responses and a favorable safety profile. The next set of data will be a combination study with abiraterone, a novel hormonal modulating agent in prostate cancer. Those data will be presented at ESMO. We're pretty excited about those data. So looking forward to having the opportunity to talk with people about them. Meanwhile, the brain penetrant molecule has now been studied in around 75 patients or so. We've completed multiple ascending dose studies. Those data, broadly speaking, support the fundamental hypothesis that selective PARP1 inhibition spares the hematopoietic system. Selective PARP1 inhibition spares the hematopoietic system. That opens up the possibility to go beyond maintenance treatment, which is what PARP inhibitors are used for now, to actually treatment in the second line, as we showed with paclitaxel, and possibly in the first line as well.
We think that could transform the use of PARP inhibitors for susceptible tumors and potentially broaden the therapeutic index in other tumors as well. I think it's a pretty exciting time for the PARP inhibitor program, and our PARP inhibitors are certainly the most advanced, highly selective PARP1 inhibitors right now in clinical development.
Cool. We are going to get updates on both of them at ESMO. Could you just walk us through, at a high level, what are we going to see at ESMO, and how will these updates impact Eikon and your decisions for progressing both programs?
Well, I can tell you about what we are going to get updates on. How they will impact Eikon, well, that we will see.
Okay, we will talk about that after. So what are we going to get updates on?
What we will get updates on, for EIK1003, the most important update, as I mentioned, is the chance for the first time to see the abiraterone combination data. The thing that I think investigators will be looking at, all of those people whom we work with and whom we know, is the question of, in prostate cancer patients who are being treated with abiraterone, does the addition of a PARP inhibitor have an untoward effect on red blood cell production in particular, but as well, white blood cell production and platelet production? That is important because while there is good data now available from the use of other non-selective PARP inhibitors in combination with abiraterone, and in the treatment of prostate cancer more generally, hematologic toxicity is a significant problem.
I won't sum over all of the studies, but just say, in general, the rate of blood transfusion in patients treated with novel hormonal agents in combination with PARP inhibitors is on the order of 50%. That is not trivial, and it is challenging for patients to continue to take a drug that reduces their hemoglobin levels to points where they feel fatigued and cold, and fundamentally, it interferes with their quality of life in a pretty significant way. If we can show the sorts of responses that we expect to show, and less hematologic toxicity, I think that's very powerful for the world and clearly very important for Eikon and for our future development plans. The reality is that being able to move from a maintenance therapy program to treatment opens up a world of possibilities.
When Roy and I sit down and look at the set of things that we could study with our PARP inhibitors, it's easy to see that we could approach, for example, first-line treatment in combination with platinum. We have no data there, but right now we could say, gee, the likelihood that there would be tolerability from a hematologic perspective is pretty high. Any time you move upstream in a treatment paradigm, you're likely to see larger treatment effects. We know that our EIK1003 molecule is active. There's no question. We can say the same thing, or will say the same thing, with respect to EIK1004, unsurprisingly, because of course, it's active against PARP1.
All of that suggests that in the first-line treatment, potentially in the second-line treatment, in a variety of different indications, in individuals who are selected by a variety of genetic criteria or in unselected populations, and in combination with a whole variety of different agents, that we can have a meaningful effect on treatment of malignancy, and that just gives us enormous enthusiasm for the field.
Roger, if I was to force you to pick one indication to pursue first for EIK1003, what would you do first? There was so many different options and settings that you could go.
I would dodge the question.
Ha ha.
The reason is we are right now in the midst of doing a very detailed analysis of all the places where we could go.
Just to give you a sense, the axes are complex because there are areas where we already have data.
When you already have data, that is of course, the most positive thing you can have in terms of advancing to the next study. There are areas where we are likely to get data soon. There are areas where we do not have data, but we think we will have data in a reasonable period of time. There are areas where we can project. There is early lines of therapy, late lines of therapy. There is monotherapy, maintenance combination therapy. So there is a fairly broad range.
We have distilled that down not to one,
Okay
but to 12.
Okay.
We have distilled it down to 12 studies.
Yep.
Some of those studies can be done faster
because enrollment is relatively straightforward, and there are no other options. Some of them take a longer period of time. Any maintenance study takes quite a long period of time.
A treatment intervention is faster. I think I've given you a sense of how we are working through the tiling path-
Yep
...that gets us to a small set of registration-enabling studies that will bring EIK1003 and EIK1004, we hope, ultimately to the marketplace, because we think they can provide a lot of benefit.
We'll have the data at ESMO. Will you be telling us what the next steps are? When will we know which indications you're going to go into first for EIK1003?
We will announce, of course, when we design the registration-enabling studies, but we may not announce those at ESMO in association with these trials.
The reason is, of course, that we want to have appropriate discussions with regulatory agencies before we make ourselves look foolish. We'll have those discussions. It takes time to orchestrate them and then to initiate the trials. Suffice it to say that we have a lot of experience in this area.
Yep. EIK1004, is it a more simple plan, given the very clear opportunity in breast cancer?
Well, I think it is both more simple and more complex. The idea of being able to pursue a brain-penetrant molecule. Fundamentally, a key issue that people will look for in our data is what evidence is for toxicity of the special kind that's related to the human nervous system. One of the problems you have as a drug developer, anytime you introduce a drug that penetrates the central nervous system, is are there disorders that are reported with some frequency that you can't evaluate pre-clinically? Headache, sensory disturbances, mood disturbances, even seizure disorders, all kinds of things like that. At the moment, we're very comfortable with the safety profile for EIK1004. We've been in quite a few patients, but that's always something to think about.
Then you have to ask yourself if there is room for a selective PARP1 inhibitor because it can improve therapy, is there really room for two? We have the advantage of having two, and they have slightly different properties.
They could be used in different places. Clearly, one place where EIK1004 is especially useful is in breast cancer patients who are at high risk for developing intracranial malignancy. Right now, we don't have a treatment, a brain-penetrant PARP to use in those patients. This, if it continues to be active and well-tolerated as we see it, that's a good place to go with that molecule. It could turn out that there's a much broader set of indications, but that's certainly a good place to look. We are enrolling in our studies, and we'll talk about this at ESMO, patients who are at risk for active brain metastases.
Quickly, on your TLR7/8 agonist program, EIK1001, you've got two quite big sort of integrated phase II/III rolling studies ongoing. When could we see top-line data for each of those in first-line melanoma and first-line non-small cell lung cancer?
Well, as you say, these are seamless Phase II/III programs, which are under, broadly speaking, the supervision of an independent data monitoring committee. We don't see unblinded data. We are entirely blinded internally throughout the company to the data. So we only see blinded data. The other thing to say is that these are event driven.
In some ways, what that means, of course, is that the stronger your treatment effect, the longer it takes you to get to pivotal results. We don't have a good sense of event rates yet, even though we've enrolled a lot of patients. We've been through the first interim analysis for the melanoma study, which permitted us to collapse the dose from two doses to one. So we now have a two-arm study where we previously had a three-arm study. That study will proceed. Sometime during the first half of next year, we'll have the second interim analysis. That interim analysis will provide the first indication of efficacy in the sense that we charge the data monitoring committee with making a recommendation to us as to whether we should expand the trial still further in Phase III or should pause and evaluate the data from Phase II.
I can't predict the outcome. We will know, and we'll announce it to the world within days of knowing ourselves, what that outcome is, and it will be sometime during the first half of 2027. The enrollment rates are so high, my expectation is that we will be able to complete enrollment, and have the opportunity then, depending on event rate, to complete the melanoma study first. At the same time, our non-small cell lung cancer study, which is just spooling up, is probably going to enroll even faster.
That's because there we have phase II data that look quite attractive. We will provide an update on those phase II data at ESMO.
People will have a chance to see the really what is quite mature data. We have patients who've been on the study for 2 years. There's a lot of information there about response rates, durability of response, and the safety program. It all looks really quite good. I can tell you enrollment in the non-small cell lung cancer program is going to be quite rapid. Because of the rapid progression, unfortunately, of non-small cell lung cancer, which the study is a combination with KEYTRUDA and chemotherapy, so it's standard of care plus EIK1001 versus standard of care alone for both squamous and non-squamous, non-small cell lung cancer. I can tell you, unfortunately, it is the case that progression, even with the best available therapy, is fairly rapid. We will probably catch up with the melanoma study, with the non-small cell lung cancer study.
That, frankly, was our design. We hope we'll have results for the two of them at a similar timeframe. Event driven, we'll see what happens. Stay tuned and we'll provide updates as they happen.
Great. In the final 1 minute, Freddie, could you just remind us of the cash position, your burn rate, and where the cash will take you to?
Yeah. Thanks, Imogen. At 6:30 AM, we posted our half-year results. We had $531.2 million of cash, not to put too fine a point on it. The way I think about it is we are burning roughly $75 million of cash every quarter supporting these studies. The bulk of that, or two-thirds, is really directed to the clinical work.
As we talked about previously, we are at a state where we are really just supporting the platform. Year- over- year, actually, we have gotten more efficient with that spend. The spend on the kind of research and engineering has actually gone down, and we have been more effective, as Roger said, developing candidates that are headed to the clinic. We are in a great position, and we look forward to providing further updates.
Wonderful. Well, that is all we have time for today, but thank you so much for joining us, both of you, and thank you everyone in the audience.
Thank you.
Yeah. Thanks, Imogen.
We really appreciate it. Thank you.