Biomea Fusion, Inc. (BMEA) Earnings Call Transcript & Summary

Good morning and thank you for joining the H.C. Wainwright BioConnect 2022 Conference. My name is Mike King and I'm the Managing Director and Senior Biotechnology sector analyst here at H.C. Wainwright. While we are virtual again this year, we're confident we're going to be able to provide value to you with over 550 presenting companies at this conference. For those of you that don't know us, H.C. Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory and related services to public and private companies across multiple sectors and regions. We have a total of 23 publishing senior analysts and over 630 companies covered across all sectors. You can find more information on our website which is hcwco.com for more information. From a logistics standpoint, please make sure to reference your BioConnect Virtual Conference online portal that provides your -- individual links to your meetings and all presentations. Also, please join us for corporate presentations and panels that will be available live and streaming from January 10 through the 13th. With that, have a productive and enjoyable day. And I'd now like to introduce our next presenting company, which is Biomea Fusion. Presenting on behalf of Biomea is the CEO and Co-Founder Tom Butler. Tom, welcome to the BioConnect 2022 Conference. Appreciate you joining us.

Yes. Thank you very much, Mike. Thanks for having us.

Absolutely. I wouldn't think of having BioConnect 2022 without you guys. So I know you, Tom. I know your colleague, Ramses, very well. We go back to the Pharmacyclics days. But Biomea was one of the quite a number of IPOs in the biotech sector last year. So maybe it would be worth starting just with a quick description of the company, its history, how you guys started it, et cetera and orient us to that and then we'll go from there.

Yes, absolutely. Thank you, Mike. The company started back in 2017 through a reverse inquiry, myself and Ramses coming off the heels of the AbbVie, Pharmacyclics transaction, had set up an innovation fund in Palo Alto, a small office on Emerson Street in downtown. And we were focused on looking at novel mechanisms of action, looking at companies who had initial proof of concepts with their Phase I and we're about to build out their pipeline and their clinical development strategy. And we got a knock on our door one summer afternoon. And in 2017 and it was a company that was computationally chemistry based out of Boston that had this menin program. They started with a reversible inhibitor program and had designed really novel chemical structures and chemical scaffolds that got me really excited as a chemist. At the time, we knew very little about menin. We just knew that the literature had described it both as a tumor activator and a tumor suppressor. So we knew that it wasn't really well understood all the way. And so we knew that we had a little bit of work to do. And we inherited a program that had a lot of virtually designed molecules but synthetically, maybe only a handful and we really set out to be pragmatic about targeting menin. We had always admired folks going after targets that were very patient-centric, that you would really understand the genetics behind the tumor and that you can design a molecule behind those genetics. I came from Gilead in the industry and then I was lucky enough to join an smart team at Pharmacyclics and ibrutinib was a phenomenal drug. We had 6 labels in 18 months. But one thing that we'd always admired was that patient-centric modality of really understanding how to be very precise in the clinic and really be able to be predictive of who's going to benefit the most from your drug. And that's really the hallmark of this type of effort of going after mutations called translocations and others. It just turned out as we explored menin further, we learned that it's not just MLL-r translocations that menin can disrupt, there's a lot of liquid and solid tumors at large, where menin is this key node on the transcriptional level, that's controlling or controlled growth and survival of tumor cells. And then we took it another step further. It also appears that menin acts like the brakes on beta cells, very much like GLP-1 acts like the gas and they actually co-localize together in the pancreas, which is pretty interesting, co-regulate. And so we knew that there was a lot of work to be done in terms of understanding menin and then what's the right way to properly design against the target. And through computational means in SAR, we learned that going after menin with a covalent inhibitor is a very novel way of controlling the pathway in a very consistent way to be ligand efficient and control multiple tumor types and disease types.

Great. Well, I appreciate that overview. I think the answer to my next question is probably a hint of it in your opening statements there. But I'm just curious, as folks don't know, you and I have interacted a number of times while we were at Point Sur. And I just wondered, was it about menin in particular, that made you guys want to do this again, you meaning the company. I think, most people come out of industry and if they start a fund, they're kind of happy with their lifestyle and their ability to kind of pick and choose the things that they do. So what was it about this program in particular, that made you guys either to kind of do it again, so to speak.

Yes, we're drug developers by training. That's our bread and butter. That's our core skill set, is to is to do this type of work. I started out in the industry as a medicinal chemist, organic chemist working at Gilead at the bench. I started working on HIV, designing polymerase inhibitors and then was fortunate enough to work on the [ Hep C cure program ]. And that's where I met Thorsten, our Head of Chemistry. And what made us do it is just that potential to do something different and be able to have high impact. For us, it's all about an impact and we want to put a molecule forth into the clinic. But also know that whatever we're doing in the clinic has high commercial potential success. And menin had that written all over it. We knew that because it wasn't well understood, we had the time as a small company to understand the menin program. If there were too many participants in menin, it would be very difficult as a young, small company to try to catch up. And it was just fortuitous that we found menin when we did and we found the potential of a covalent inhibitor when we did and it was really -- what the literature was telling us and one of the first things we did was kind of reach out to our network and we reached out to a KOL that really had a big impact on ibrutinib's clinical development. And he told us as we were describing the menin program, he said, look, I think this target is great. I think you guys are on the right track and that it should be a wonderful target for leukemia, you better develop this in diabetes. And we thought, wow, medical oncology, that's pretty interesting.

Right, right. So without exaggerating, but I guess it's fair to say that you felt there was another opportunity to kind of recapitulate the ibrutinib experience that you had at PCYC?

That's exactly right.

Okay. So yes, speaking of menin and there you do have some competitors in the space. The science have been around for decades but only recently has the industry started to catch up. Why do you think this is the case? Is the -- is menin hard to drug? Or is there some other reason?

Menin is very difficult to drug. The pocket that we all target is relatively featureless in the bud sense and comparatively to a kinase, it is quite shallow. And so with those type of properties as a target, you typically have to build a very large molecule, a lot of real estate, right, because you're engaging with noncovalent interactions. And you can't build a reversible inhibitor that's 300 or 400 molecular weight. You have to go much bigger because of its relatively featureless attributes. And I think you don't really understand the potential of a target until you get a great molecule to study it. And there just weren't great molecules until a recent day that you could actually properly study menin. And I think the book on menin is just, we're in the first chapter to be honest.

Well, this featureless aspect of the target sounds a bit like KRAS. And it sounds like you took some of the learnings maybe from KRAS discovery to apply here. Can you maybe talk a little bit about that?

Yes. That's right. And when we first started building and designing our small molecule, you can do certain things even if you think about just from a physical property perspective, you can build propellers to try to wedge yourself into this dynamic protein. That's what the KRAS developers did, is build these kind of propellers. And we did the same for menin to try to create a reversible molecule that was too -- that was a little bit more sticky, that had a longer [indiscernible]. But then as we explore the PK/PD properties of reversible inhibition, we knew that this isn't going to work well. It's going to very -- it's going to limit the potential of your molecule and it's going to be difficult to study in the clinical setting. It will be virtually impossible in the commercial setting. And so we wanted to build, again, a molecule that just demonstrated strength from a pathway control perspective but also consistency across multiple tumor types. And through the advent of the cysteine that sits deep in the pocket, you're afforded that capability. And really, that's how we get this deep target and activation but also really strong selectivity specificity of BMF-219.

Right. Okay. Right. So we can take this in kind of 2 directions. The first direction would be irreversible inhibitor in menin. Talk about what may be confident that you need a irreversible inhibitor. And maybe we can talk more about this after that about sort of philosophically that Biomea is focused on irreversible inhibitors. But about to back up a second, menin is expressed widely, how confident were you that you could drug the target without inducing tox? And were there some experiments that you needed to do to understand the biology better like knocking it out with CRISPR or some other methodology to make sure that you aren't going to do any harm by irreversibly binding the target?

Yes. We did all the initial work that you guys on the other side would do in understanding the target. What happens when you have a knockout scenario, very similar to when you study BTK, there does exist this knockout scenario. How do you study this? The good news is that a covalent inhibitor never recreates the knockout scenario and ibrutinib didn't do it with BTK and we don't believe BMF-219 does it with MEN1 but you do show strong pathway control but the protein is there and it is available. And so you never completely recreate the knockout scenario. But -- and menin is ubiquitously expressed, however, its strength or the way it's used is quite focused. And whether it's in the pancreas or in other target organs, one can quickly understand where menin can have its strength. And when you start to apply into these menin-driven tumors, really, these tumors are addicted to menin and it's complex. And whether it's MLL, that's part of the complex or another protein like MYC, really menin is the core scaffold protein that's kind of keeping it all together on the chromatin level.

Right. Let's go a little deeper on that because I think it's important for the validation of the target to understand the biology of menin in a deeper fashion. And that is, again, in the same -- similar, certainly not the same, similar to BTK, where we had human knockout validation, we have sort of the same thing with menin. Can you elaborate on that?

Yes, you do. And when you knockout menin all the way and they studied this in animals and humans, when you have complete knockout, what happens is, over the course of many years, humans develop benign tumors in the majority setting. And in the very few they form malignant tumors in very small percentages after a 20-plus year experience of having continuous menin knockout. In animals, in mice and rats, when you do a MEN1 knockout, you see formation of these tumors after 1 year. But again, 1 year in a [indiscernible] in a mouse is like 25 years plus in a human. So again, the phenotype that's seen doesn't have -- any negative effects doesn't happen for many years down the road. That's very important. And when it does happen, they're benign resectable tumors.

But it does manifest in pathology. So we know that. There's your genetic validation there.

That's right. There is genetic validation, absolutely. And then at least you know your boundaries, right? And you can tailor-make your molecule to make sure that you're operating within those boundaries.

Right, right. Okay. Well, let's go a little further into current plans. I know your IND is active. You had an announcement this morning about your development strategy. Why don't you take an opportunity here to kind of summarize the release that came out this morning and tell us about the plans for 219.

Yes. And so for us, it's all -- we understand the benefit of speed of going in parallel. And so what we announced this morning is that we are going in parallel up to 7 tumor types this year. We will be enrolling up to 7 tumor types this year in 2022. And what that allows us to do is to properly explore BMF-219 in parallel, or in as close to parallel as possible. We will also be exploring 219 in type 2 diabetes patients this year. Again, the preclinical work that we've done, both on the safety side, first and then also complemented with the efficacy side is just a molecule that is unparalleled for diabetes. We're looking for an oral long-acting medicine that we want to study this in type 2 but certainly type 1, certainly, the door is still open. We have to explore it. But to be able to have a molecule that has a long-lasting effect on patients after a short-term duration of treatment, I think, would be a game changer for diabetes. So we're extremely excited about this potential and we'll be announcing -- presenting data later this year on our preclinical findings.

Okay. And talk about the [indiscernible] on oncology side, talk about the liquid and the solid tumors you've chosen and maybe a little rationale why in terms of the ones you've chosen?

Yes. The reason why we chose it again is to take a step back and even why we decided to go after this program was because we admired this patient-centric approach. We really wanted to pick tumor types where we knew the subtyping ahead of time. We knew, meaning what patient would have the highest probability of success with a menin inhibitor that shows this type of effect on the pathway, which BMF-219 does. And that's how we put together our clinical development plan in DLBCL, in multiple myeloma. And then in KRAS-activated tumors is, you got to make sure the drug gets there at sufficient concentration. You got to make sure that you have your therapeutic window. And you got to make sure that you have a deep understanding of the biology and the rationale which has been wonderful for 219 and for our clinical development. We're very excited to be able to explore this broadly because of what we think menin can do for these patients in need.

Right. Maybe digging down a little further. You talk about -- so you've got DLBCL, AML, double-, triple-hit lymphoma, double-expressor lymphoma and multiple myeloma are at least initially and then also in KRAS-driven cancers, are you looking for sort of biomarker-driven strategies? Or will you employ them once you've got some idea about PK/PD safety in these different tumor types?

Yes, that's right. So at the end of the day, we know the subtyping, where we believe we have a strong rationale for being specific with particular subtypes within DLBCL and MM, as well as leukemia. It's very, very synonymous with going after MLL rearrangement or NPM1. For DLBCL, it's a double hit, triple hit and double-expressor, these are all tumor types or subtypes of DLBCL that have strong MYC control. And we've seen that if you have MYC as a major driver, then BMF-219 has a very strong impact on your tumor. And so...

That would be somewhat self-selecting from the genetic profile of tumor types.

That's right. And we'll do full paddling as well so that we understand what else is going on with that particular tumor type. But we want to be smart about it and be patient-centric upfront.

Right. And then I think you had said in -- I may be misquoting but I thought that there may be some data available on some of these studies in the first half or maybe I'm wrong on that front?

Yes. So during Q4, we published some of our DLBCL work. We'll continue to publish DLBCL, multiple myeloma and KRAS-activated tumor preclinical data. You'll get that work as well that supports the rationale. And what's so profound is that at the same concentrations that we're disrupting acute leukemia, we're disrupting these other tumor types. And that's what gets us so excited. So as we go through the dose escalation in our acute leukemia, we will understand the proper exposure to control tumor growth and control the cancer in that patient setting. We'll be able to then translate that into the other tumor types as well as we're enrolling them.

Right. Okay. Terrific. Maybe we can switch gears a little bit to diabetes. You had some preclinical data out last week that appears to validate the biologic hypothesis. Maybe talk a little bit about that for us at first and we'll pick up from there.

Yes. So there's a growing body of evidence that supports the use of a menin inhibitor in diabetes. And the premise is that, as I mentioned before, that menin is acting like the brakes. And so your beta cells, which are consistently exposed to a hyperglycemic state in diabetes, they get exhausted and they just can't pump out enough insulin. Now you can try to use GLP-1 and other agents that try to squeeze more insulin out of them. But at the end of the day, when you continuously exhaust your beta cells, it's just a degressing type of situation. And so the reason why you don't have rapid turnover of your beta cells is because you have this gatekeeper menin that's preventing it's turnover. And all we're doing is taking the brakes off of this gatekeeper and allowing the beta cell to turn over and reestablish a pool of healthy beta cells. And there's several pieces of literature that suggests this can be done. We've been doing our own preclinical work that suggests it is being done. And if you think about that fundamentally, you don't have to continuously grow a pool of beta cells. You just have to regrow it completely because diabetes doesn't happen overnight. Type 2 diabetes doesn't happen over a week's time. It happens over many years. So if I give you now a pool of fresh beta cells, we're kind of resetting the clock on your disease.

Right. And the thing you can -- I think obviously remains to be determined but it would seem that beta cell can regulate itself normally, so you wouldn't have to be too concerned about hypo or hyperglycemia.

That's exactly right. And that's the beauty of menin as a gatekeeper, is that it doesn't tell the body to now create a hypoglycemic state. You just get to normalized glucose levels.

Right. I got to ask the obvious question, which is to develop 219 for both diabetes and oncology, you eventually run into the issue of giving a cancer drug to treat diabetes, pricing differentials, things like that. Do you contemplate at some point, perhaps after you improve concept with 219 that related molecule or a new molecule could come through and be the one that carries forward for diabetes? Or what kind of decisions are you making there on that?

Yes. It's a great point. And just take a step back, an oncology drug as a profile, if you look at most oncology drugs, even if they could do it, they can't go into non-oncology settings because their safety profile is not clean enough. They would never pass the non-oncology studies, 219 can. And that's how special BMF-219 is. So imagine if you have an oncology drug that can pass non-oncology toxicity studies, well, that's pretty special. And think about what impact it can have in oncology patients then if you have a drug that has that type of profile. So flip it the other way, it's got to be a tremendous molecule, first of all and it can maybe provide tremendous benefit for oncology patients. On the other end, to be able to pass those hurdles and get into non-oncology, again, the reason why we would do it is because there's potential for a breakthrough. And to have finite treatment for diabetes and to turn the treatment paradigm on its head is an opportunity that we'd love to take. And that's why we...

Yes. I assume you'll be monitoring glucose levels in your oncology patients.

Certainly, certainly. And at the end of the day, from a team perspective, from a patient targeting and how do you manage through that, at the end of the day, breakthrough medicine takes care of all those things and...

Yes, I understand. But there are pragmatic considerations there. Obviously, diabetes much more expensive, much more elaborate long-term studies, different dynamics in the marketplace. I mean, it seems like you could partner that program off with a separate molecule or family of molecules.

Well, again, keep in mind that the reason why the sizing of clinical trials in diabetes and the time is usually predicated that you're giving this drug to people chronically for the rest of their lives. That's not what we're doing, right? So we'll be doing finite treatment for a short period of time. And obviously, we need to learn more about what those guidance trials would look like, what the sizing and timing look like. But we're doing something that's never been done before.

Right. It'd be interesting to see a small company bring a diabetes drug all the way to market on its own. I think that would be -- I don't even know if -- maybe Amylin did it but that's about all I can think of at the moment. But anyway, unfortunately, we're out of time. This is a fascinating story, folks. I urge you to take another look at Biomea. I know there were flood of names in the marketplace last year. This one is certainly worth your consideration, especially given the experience and track record of the team. So let me thank Biomea. Thank you, Tom, for taking the time and effort to preparing your talk. And hopefully, the next conference we do here will be where COVID is endemic rather than pandemic and we can do it in person rather than virtually. But in the meantime, we're grateful for your flexibility and your presence online this year. So thanks again for myself as well as the H.C. Wainwright team and enjoy the rest of your day.

Absolutely. Thank you guys very much. It was a pleasure.

Thanks, Tom.