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

All right. And we're back. So it's Michael Schmidt with the biotech team at Guggenheim. The next presenting company is Biomea Fusion. It's my great pleasure to welcome Steve Morris, who is the Chief Medical Officer. Steve, welcome, and thanks for joining us.

Thanks very much, Michael.

So Biomea is focused on the development of covalent inhibitors. Could you please talk a bit about the background of the platform and what makes it so interesting?

The basic approach that Biomea uses with their fusion platform technology is a AI virtual reality modeling and virtual docking approach. And that helps us to avoid compound screening, library compound screening and rather identify virtual molecules that are then synthesized, of course, in the wet lab. We supplement the virtual reality approach with actual chemical structures where available. But using those in tandem, that allows us to synthesize custom scaffolds. One beauty of the approach is that, with it, again, we're not doing library screening, so we're not picking from compounds that are already out there. This approach, the fusion platform approach allows identification of novel chemical space, and, as a result, readily protectable IP. The other beauty of this approach is the time line from identification of target, decision to drug that target until nomination of an IND candidate is very brief. The compounds that are currently in the pipeline, the time line was about 18 months for that process. So very efficient, good way to identify novel IP and also a very quick way to do so.

Very interesting. And then you're enrolling currently the Phase I COVALENT-101 study. Can you just remind us of the clinical trial design? What type of patients are you enrolling and how the study has been progressing?

Certainly. So COVALENT-101 is our heme malignancy first-in-human study. In addition to acute leukemia, we're enrolling diffuse large B-cell lymphoma, myeloma as well as CLL. All of those indications, especially the 3 that I mentioned after acute leukemia, DLBCL, myeloma, CLL, we have generated data indicating, as I mentioned earlier, that covalent menin inhibition has activity in a variety of preclinical models, but not reversible noncovalent inhibition. We commenced COVALENT-101 almost exactly a year ago. The first patient dosed was in January of 2022. That was an acute leukemia patient. We are escalating in the acute leukemia cohort. We're also doing parallel distinct escalations for the other 3 heme malignancy indications.

Okay. And is there a biomarker approach in a plan with the study? That -- are there any particular subtypes if patients that you think might be particularly responsive to 219?

Right. So for acute leukemia, yes, we're enriching for MLL rearranged as well as NPM1 mutant patients. We're not excluding acute leukemia patients with other molecular drivers. But again, we're enriching for those 2 subsets, which have been credentialed to have the greatest both preclinical and clinical data indicating that menin inhibition is effective. For DLBCL, we're especially keen on enrolling a double and triple-hit lymphoma patients. Those are patients who have activation of MYC as well as BCL2 plus or minus in the case of -- plus in the case of the triple-hit lymphomas BCL6. These are DLBCLs that are very aggressive that are poorly served with current standard of care lymphoma therapies. And we think this is a very good population for us within DLBCL to demonstrate 219 efficacy, again, based on preclinical models that we performed with 219. And MYC and CLL, we're accepting all patients irrespective of particular driver mutations because we've seen in the preclinical studies evidence indicative that we will likely see broad spectrum activity with 219.

Okay. And then you've guided to presenting data from the Cohort 1 of the study in the first half of this year. Could you just help set expectations perhaps around the scope of the data that we'll get?

Sure. Definitely. So the data in acute leukemia will report roughly 20 patients. About half of those patients will be acute leukemias with a variety of driver mutations, not necessarily expected to be sensitive to menin inhibition. The other half will be MLL rearranged or NPM1 mutant patients.

And then you're doing also the COVALENT-102 study in solid tumors in a KRAS mutant background. So what is the mechanism of action here, and also talk about what are you trying to show in the study?

Sure. So who knew menin inhibition for KRAS-driven tumors? Well, again, we've generated a large body of data. We presented that over the past year plus at various congresses, AACR, ASCO, et cetera. And it turns out that menin is at the node of several signaling pathways that are critical for cooperation with KRAS during the tumor development process. So KRAS, obviously, is critical for the genesis of KRAS-driven malignancies, but KRAS does not act alone. It requires cooperating genes like MYC, like the EP1 transcription factor JunD, like a guanine nucleotide exchange factor known as RAS-GRF1. All 3 of those cooperate with RAS, are required for RAS to cause tumor development and also to sustain tumor viability. All 3 of those are part of the menin signaling complexes, which we disrupt with 219. So we're not directly inhibiting KRAS, rather, we are inhibiting these cooperating pathways with KRAS. That's one reason why we see a pan-KRAS activity. It's not just G12C-targeted KRAS activity, for example, it's pan-KRAS activity.

Then talk a bit about the Phase I study. I guess, what types of patients are you enrolling in that?

Yes. So COVALENT-102, our KRAS solid tumor study, began enrolling patients the latter portion of last year. We're enrolling 3 types of KRAS-driven solid tumors, non-small cell lung cancer, pancreatic adenocarcinoma, and then, finally, colorectal carcinoma.

Got you. And I guess, what are you looking for in a Phase I and perhaps in terms of the mutational spectrum? And then what level of efficacy are you looking forward to advance this?

Right. So again, the activity that we saw in our preclinical studies was pan-KRAS. That's important to emphasize because in non-small cell lung cancer, as an example, about 15% are G12C mutant. So that's the target population for G12C-targeted inhibitors. G12C by contrast in colorectal is only about 3% of all colorectals. So there's huge unmet need. Because we anticipate pan-KRAS activity, we are accepting any activating mutation of KRAS. The other point I think that is relevant, at least in preclinical models, we've shown that 219 has very potent cytotoxic activity even in cancer cell lines that are KRAS mutant that are resistant to G12C-targeted inhibitors. So we are accepting patients who have seen a G12C-targeted inhibitor, or for that matter, any KRAS investigational agent, have failed that agent, those are accepted into the COVALENT-102 study.

And just again, what are you expecting -- or when do you expect to update investors on the study and...