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

Good day, ladies and gentlemen, and welcome to the 52-Week Results Conference Call. [Operator Instructions] Please be advised that today's conference call is being recorded. I would now like to hand the conference over to your speaker today, Ramses Erdtmann, President and Chief Operating Officer. Please go ahead. [Technical Difficulty] Ladies and gentlemen, please stand by. Ladies and gentleman, please remain on line, your conference will begin shortly.

Okay. Thank you, operator. Are we live now?

You are live.

Perfect. Okay. All the other speakers that have dialed in, we're going to go live. Maybe you can let Juan Pablo now. Okay. Thank you, operator, and welcome, everyone, to this conference call. My name is Ramses Erdtmann, I'm the President and Chief Operating Officer of Biomea. Today, we'll be sharing the 52-week results from the COVALENT-111 study, a randomized double-blind, placebo-controlled Phase II clinical trial to assess the safety and tolerability profile of icovamenib along with exploratory efficacy endpoints in patients with type II diabetes. Before we begin, let me remind you that today's presentation contains forward-looking statements about the business prospects of Biomea. These statements are subject to a number of risks and uncertainties that could cause our actual results to differ materially from those expressed or implied in this presentation depending on the progress of Biomea's preclinical and clinical development activities, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors, and those factors detailed in Biomea's filings with the SEC, such as the 10-K, 10-Qs and 8-K reports. All forward-looking statements made during the presentation are based on the beliefs of Biomea as of this date only and future events or simply the passage of time may cause these beliefs to change. Please feel aware that you should not place undue reliance on the forward-looking statements made today. Okay. On today's call, you will first hear from me with introductory words. Then Dr. Juan Pablo Frias, Co-Chair of our Scientific Advisory Board, will walk you through the study design and key 52-week data. We are also joined by a very prominent investigator and one of the key opinion leaders in our field, Professor Ralph DeFronzo, who is an expert in the pathophysiology of type II diabetes. Finally, our interim CEO, Dr. Mick Hitchcock, will summarize our findings and discuss next steps before opening the call for Q&A. Let me begin with a few remarks upfront. When we started our menin research back in 2018, we only had academic papers that indicated that menin has a control function in the pancreas. We then conducted animal studies and human pancreatic cadaver islet studies to validate the core assumption others had already observed that the select and partial inhibition of menin may lead to an increase of beta cells and the enhancement of their function. In these early studies, we observed similar improvements with the use of our menin inhibitor, an increase in the number of beta cells and increase in insulin production, better glucose control, which led to lower HbA1c values, and also an increase in GLP-1 receptor expression on the cell surface of beta cells, which potentially enhances the effect of GLP-1 receptor agonist. When we initiated our clinical program and, in particular, our study, COVALENT-111, we wanted to identify which phenotype of patients will respond best to our menin inhibitor, icovamenib, and we also wanted to determine the appropriate dosage. Menin inhibition in diabetes is a brand-new modality for this disease. There were no references or prior clinical studies to lean on. So it was critical that COVALENT-111 helped us answer those 2 questions. I believe we have answers to both questions now that the study is completed. With our 26-week primary readout, we learned that the strongest benefit from icovamenib occurred in those prespecified patients that were considered severe insulin deficiency and taking at least 1 antihyperglycemic agent. And we learned as well that patients already on a GLP-1-based therapy and not achieving their HbA1C target or another strongly responding subgroup. Now after 52 weeks, 9 months post the last dose for these patients, we will provide an update on how these groups have fared. We are confident today that we have isolated our responders and understand the mechanistic reasons for the responses in both of these type II diabetes patient groups. I will now turn the call over to Juan Pablo, who will walk us through the results in detail. You may notice that the slides introduced Juan Pablo as Co-Chair of our Scientific Advisory Board. The reason for this title change is because Juan Pablo is heading back to clinical practice and research and will, therefore, have to reduce his role at Biomea. His support going forward will be more focused on assisting us in clinical trial-related questions, protocol reviews, FDA interactions, presentations and similar activities. Juan? [Technical Difficulty]

Please stand by. Ladies and gentlemen, please stand by.

Operator, are we live?

Yes, we are live. We're waiting for Juan.

Okay. Juan is traveling, and he is unfortunately in a position where he just lost cell coverage, and I hope he's getting back to us with the Q&A section. If everybody doesn't mind, I'm going to read his section, just assume it's Juan speaking, okay? He's going to come right back, hopefully, for the Q&A section. Okay. So I would like to focus the majority of my prepared remarks today on the 52-week results of the COVALENT-111 study and what they mean for -- what they mean for endocrinologists and diabetologist like myself. During my remarks, I will not cover every slide that you'll find online but instead highlight the key takeaways. Let's start with Slide 5, which is an important slide. It illustrates the 2 key effects we see with the orally bioavailable menin-inhibitor, icovamenib. These effects were first observed in preclinical studies, and we now have clinical evidence of this proposed dual mechanism of action. It's particularly important to understand the effect shown on the right side of the slide, which can be easy to be overlooked. Icovamenib increases GLP-1 receptor expression on the surface of beta cells. Preclinical data demonstrating this were presented at the ADA scientific sessions in June of this year and again at the EASD Congress a couple of weeks ago. Clinically, we believe this may help people with diabetes who are not achieving glycemic targets on GLP-1 therapies. Based on our preclinical data, we believe there may be potential for icovamenib to have an impact on body weight and, importantly, the quality of weight loss through preservation of muscle mass. The slide lays out where we are observing patient benefits and helps us understand the clinical development path for icovamenib. Slide 6 to 10 summarize our trial design and patient enrollment. With this study, we aim to better understand icovamenib's safety and tolerability profile to assess for optimal dose and the durability of patients response to icovamenib. Additionally, we aim to identify the patient population most likely to benefit from selective and partial menin inhibition. Remember, before Biomea, no 1 had ever dosed a person with type II diabetes with a menin inhibitor. We had no benchmark for what to expect across different patient subtypes. Slide 11 shows the 4 generally accepted and well-characterized subtypes of type II diabetes. The statistical analysis plan prespecified that our analysis include an assessment of HbA1c change within these subtypes for the readout at Week 26 and Week 52. When a patient with severe insulin deficient diabetes comes into my practice, I can usually recognize them. These patients are typically not obese, they present with a high HbA1c and they are often difficult to control on non-insulin therapies. They generally progress quickly to requiring insulin therap. By contrast, from my professional experience, insulin-resistant patients usually produce sufficient insulin, but need weight reduction to lower resistance, enabling their own insulin to work more effectively. These patients often respond very well to GLP-1-based therapies, especially given the weight lowering effect. Roughly 20% of type II diabetes patients in the Western world fall into the insulin-deficient subtype, whereas in Asia it is closer to 40% or even higher. Moving to Slide 12. At 26 weeks, we observed that icovamenib performed better when dosed for 12 weeks versus 8 weeks. In the two 12-week arms, arms B and C, icovamenib has particularly good efficacy signals in insulin-deficient patients. Importantly, this effect was durable with benefit persisting more than 3 months after the last dose. In addition, patients already on chronic GLP-1 therapies at baseline but who have not achieved HPLC below 7, also showed a notable reduction in HbA1c. Here, independent of dosing regimen, icovamenib's response persisted to Week 26 as well. This was a post hoc analysis. The key question was what would glycemic control looks like at Week 52, 9 months after the last dose? In the severe insulin-deficient subgroup treated for 12 weeks in arms B and C, shown on Slide 17, we observed a mean HbA1c reduction of 1.2%, both clinically and statistically significant with a p-value of 0.01. That is remarkable. Slide 18, focusing on RMB alone in the same severe insulin-deficient subgroup shows an even greater reduction of 1.5% versus placebo, also statistically significant. Overall, we saw durable HbA1c reductions to Week 52 in this predefined subgroup. We then asked whether response was related to exposure, if higher PK levels correlate with greater HbA1c reduction. Looking at Slide 19, you can see that mean PK exposure in arm C was actually lower than in Arm B., which we believe helps explain why arm C not performed quite as well. As shown in Slide 20, greater exposure was correlated with greater HbA1c reduction patients with the highest PK exposure achieved the greatest improvement, a point also summarized on Slide 21. Our data suggests that readily achievable exposure levels may support HbA1c reductions of at least 1.5% in patients with type II diabetes. One additional observation, we believe that food type and timing impact icovamenib PK. We have started a dedicated food effect study to optimize dosing instructions and expect this to further improve exposure. Turning now to a post hoc analysis, we also show -- which also shows some very interesting findings on Slide 23. Here we are showing the reduction in HbA1c for all patients that enrolled into the study while on a GLP-1-based therapy and who had not achieved their target HbA1C level of below the 7% range at enrollment. You can see the profound impact that icovamenib has on these patients with over 1.8% in placebo-adjusted HbA1c reduction 9 months post dosing, very impressive considering that these patients were on very potent agents at baseline that are not getting them to target. We just presented more preclinical information at ADA and EASD this year, showing that when you selectively and partially inhibit menin, do not only achieve a regeneration of the beta cells and a recovery of beta cell function but we also observed an increase in GLP-1 receptor expression, which then led to a higher insulin release, glucose control and, in the preclinical models, also to enhance weight loss and muscle preservation. We believe that the increase in receptor expression is a key reason for the effect we are observing in this patient population shown on Slide 23. Slide 24 provides context by comparing these outcomes with widely used therapies, which require chronic use and, in some cases, injections. On Slide 27, our safety assessment is summarized. We observed icovamenib's safety profile to remain stable post dosing. The results here are consistent with earlier findings. Icovamenib has been generally well tolerated with no treatment-related serious adverse events or discontinuation. This is consistent with partial and selective inhibition of menin. In summary, icovamenib was generally well tolerated, demonstrated sustained reduction in HbA1c at 52 weeks in severe insulin patients taking at least 1 anti-hyperglycemic agent, and showed promising benefit in GLP-1 treated patients who are not at goal. I would now like to turn the call over to my colleague, Dr. Ralph DeFronzo, who many of you know for his relentless work around the early pathways to address diabetes, which led to the approval of metformin, SGLT2 inhibitors and several others. Dr. DeFronzo, is a Professor of Medicine and Chief at the Diabetes Division at the University of Texas Health Science Center in San Antonio. He is also the Deputy Director of the Texas Diabetes Institute, which is one of the largest institutions in the U.S. They see about 10,000 unique diabetic patients annually. He has published nearly 1,000 peer-reviewed papers and has received lifetime achievement award from both the ADA and EASD, amongst many honors and accolades. Ralph? And I'm not sure if Ralph is able to handle his -- and you know what, I think it's up to me to continue reading. Okay? Operator, is that what we're doing?

Please continue.

Okay. I'm now going to the section of Ralph DeFronzo, and I'm going to read his section. Thank you, Juan, for the introduction. Let me start with a bit of background before we put icovamenib's results in perspective. As you indicated, I've spent most of my career really trying to understand what causes type II diabetes and how we can address it effectively. Looking at the American Diabetes Association standards of care, they say very little about pathophysiology. To me, that is essential. If you don't understand what causes the disease, you're not going to understand how to treat it. So very simply, we have 2 problems. On the one hand, we have insulin resistance, and on the other hand, we have beta cell failure, as Juan pointed out earlier. The epidemic of diabetes we're dealing with today is being driven by the epidemic of obesity, basically lipotoxicity leading to insulin resistance. But we tend to forget that there is also a large number of people who actually have primary beta cell failure. These are severely insulin-deficient patients. They are usually leaner patients, their A1c is fully controlled. They progress rather quickly to severe hyperglycemia. And for them, we really don't have the kind of medications that we need to stop this progressive beta cell failure. The very obese patients with BMIs 35 to 40 are the insulin-resistant ones. In these individuals, type II diabetes eventually develops because of beta cell failure. And the leaner group progresses much more rapidly and they are the most difficult to treat. Most of them end up on insulin therapy. Yet insulin therapy for type II diabetes is very, very difficult and can be associated with serious side effects. For example, hypoglycemia, that interfere with effectively controlling blood glucose. Let me remind you that 80% of people with diabetes will die from this disease and premature mortality caused by diabetes results in an estimated 12 to 14 years of life loss. So we are dealing with a real health care problem. As diabetes progresses, you initially start to lose beta cell function and then eventually beta-cell mass. When you lose a critical level of beta cell mass, about 70% to 80% of people become insulin-dependent. GLP-1 receptor agonists are actually very good at improving beta cell function, but they don't increase beta cell mass. If you have lost 70% to 80% of your beta cells, they're not going to regenerate them. What we would like to have is a therapy that both increases beta cell mass and improves function. Menin inhibitors are a class that actually has the potential to do this. They also increased GLP-1 receptor expression on beta cells, which allows the body's own GLP-1 to work more effectively. Looking at the data slides presented here today, I'm very impressed with -- by these results. The 52-week follow-up is rather striking in both groups. In the severe insulin-deficient group, which was prespecified in advance, the A1c was not just declining during the 12 weeks of dosing but continued from 12 to 26 weeks to now 52 weeks, even when there was no further treatment. This suggests an effect on increasing beta cell mass and/or function. These are very insulin deficient patients, the most difficult to treat. The drugs we currently have do not work for them, including GLP-1 RAs. And now we see an absolute mean A1c drop of 1.5% in Arm B and across all patients dosed for 12 weeks arms B and C when placebo is going steadily up. This is an enormous positive effect. this is very encouraging because we know from animal studies that menin inhibitors markedly increase beta cell mass. They cause beta cell proliferation and likely also improve function by increasing GLP-1 receptor expression. So if we see a big drop in HbA1c in humans, that's quite meaningful. Also looking at the trends of these graphs, the A1c is still clearly trending downwards, so we do not know how long the effect will last, likely until the beta cell toxicity is controlled in these patients. As I mentioned earlier, menin inhibition leads to an increase in GLP-1 receptor expression on beta cells, which, under conditions of pregnancy or obesity, makes good sense. In these natural occurrences, it helps the body to be more effective with its own GLP -- with its own GLP-1, to manage the stress and the demand for insulin. So how did this GLP-1 effect help type II diabetes patients in this study? When icovamenib was used in combination with a GLP-1-based therapy, the data was equally striking, showing an improvement of 1.3% in A1c reduction. This effect was achieved in typical insulin-resistant patients where the menin inhibition alone without the use of GLP-1 is not working. But in combination with the GLP-1-based therapy, we see impressive diabetes control. The effect started during dosing, as you can observe in these slides, and continued through the dosing and even 9 months post dosing. Striking, really striking. Menin inhibitors can give you more beta cells and GLP-1s can make those beta cell function better and likely promote weight loss. These 2 effects together combined show a huge effect. I would predict with a strong certainty that the GLP-1 plus menin inhibitor combination will be a very powerful therapy. Let me also address safety concerns. At higher doses of 200 to 400 milligrams, there were some liver enzyme elevations, so the study was paused. But at 100-milligram daily, there has not been any meaningful liver signal. The side effect profile post 52 weeks looks quite manageable: some nausea and a little diarrhea, Grade 1 events. Menin mutations that cause abdominals are lifelong genetic defect. Here we are treating for 12 weeks, not a lifetime. The company is monitoring quite vigorously, and with further long-term observation, we will fully answer all these safety questions. But at this stage, I'm very pleased with the safety profile. A question I get asked frequently is how this therapy will get approved. Here I can only say that good therapies typically find a way. I feel the company's approach of episodic treatment is quite reasonable: treat for 12 weeks and then the A1c stays controlled for the rest of the year. Whether it lasts 2 or 3 years or even longer, we don't know yet. But we'll learn over time. This would generally be the first therapy that is not chronically dosed and the first that would be addressing diabetes at the root cause level. I've been involved with diabetes research for over 50 years, and I believe that having a medication that increases beta cell mass is a major advancement. If we can increase beta cell mass and function, that's a huge step forward for patient care. It is a game changer. For the severe insulin-deficient group, the most difficult patients to treat, who don't respond to basically anything, if we can normalize A1c for these patients, that is a huge step forward. Even in insulin-resistant patients, eventually, their beta cells will fail, and then they'll need the therapy as well. So in summary, I think menin inhibitors can become a major pillar for diabetes therapy.

Thank you, Ralph, for your insightful comments. Before we move to Q&A, I would like to reiterate the key points highlighted on the summary slide, Slide 33. Icovamenib achieved clinically meaningful and durable HbA1c reductions out to 52 weeks. The effect was strongest in severe insulin efficient diabetes patients where we observed HbA1c reductions up to 1.5%. We also saw marked improvements in patients on GLP-1 therapy who had not achieved their HbA1c target, with mean HbA1c reductions of 1.3%. Importantly, icovamenib continued to show a favorable safety profile, with no treatment-related discontinuations or serious adverse events. Turning to Slide 34, let me briefly outline the next steps. We are currently running a food effect study to optimize icovamenib exposure and defined dosing criteria, with results expected in December of 2025. Based on interactions with FDA, we believe the path forward is to conduct larger studies, specifically enrolling the 2 target type II diabetes populations that we have identified as responding to icovamenib therapy: patients with severe insulin-deficient diabetes and patients currently on a GLP-1 receptor agonist but not achieving their target HbA1c levels. Given the responses to icovamenib's observed in the COVALENT-111 study, we believe these studies can be conducted in fewer than 100 patients each and will give both us and the FDA a clear understanding of the risk versus benefit profile of icovamenib. We plan to initiate these studies in the fourth quarter of this year. Finally, on the obesity side, we are advancing BMF-650 an oral GLP-1 receptor agonist candidate. Preclinical data showed robust weight loss and appetite suppression. With IND clearance now in hand, we have initiated a Phase I study in obese, otherwise healthy, volunteers. We expect to report initial results from this program in the first half of next year. This morning, you will also see that we announced the pricing of our underwritten public offering. This financing strengthens our balance sheet and extends our cash runway into the second half of 2027. With this additional capital, we are well positioned to advance icovamenib and BMF-650 through key upcoming milestones and continue driving towards our goal of delivering meaningful disease-modifying treatments for patients with diabetes and obesity. I would now like to turn -- I would now like to turn the call over to the operator to start the Q&A portion of the call.

[Operator Instructions] Our first question will be coming from Matt Biegler of OpCo.

Everyone, can you hear me?

Yes.

Thank you, Ramses, for that nice presentation and, obviously, for dealing with the technical issues. But just maybe a quick one on COVALENT-111, the design and the eligibility here. Are you restricting it now just the severe insulin deficient patients? Or are you also seeking to include other insulin-deficient subtypes such as age-related deficiency like MARD? I know in the past you've kind of grouped both SIDD and MARD together, but it seems like now the focus really just is on SIDD. So I just wanted to clarify that.

Maybe, I don't know, Juan, how is your connection now? Can you speak, Juan? Is Juan on? Okay, no. And I'm really sorry that we had this technical difficulty. Juan one is traveling, he's presenting in Bangladesh. And so that may be the reason why we couldn't reach him. And then Ralph is on -- I know he's on. I talked to him earlier, but we couldn't get his script to him. So I apologize. But to answer your question, Matt, yes, the purpose, as we highlighted in the prepared remarks, was primarily with the 111 study just to where is menin working, what are the patient subtypes where it is working. We identified that now. And so we are teasing -- we've teased it out and we're now going to the FDA with that certainty in a Phase II design study, primarily for severe insulin-deficient patients, as you indicated, the Study 211, and the study 212 is in combination with GLP-1. There the enrollment criteria is very easy. You fail the GLP-1 receptor agonist, your HbA1c is rising, you're a type 2 diabetic patient. That's very simple. In the severe insulin deficiency, you could argue, well, what defines the severe insulin-deficient patient? And you can see that the criteria that are being used by the German group or the [indiscernible] group are very, very similar. And so the criteria will be a person that is failing, obviously, his current therapy, and that is of lower BMI and of upper end of the HbA1c, so above 8, below 30. So below 30 basically means you're not obese. Above 8 means you have a problem with your pancreas. And the other criteria such as age very likely will not fall into it because we couldn't really see that as a signal. And lastly, probably the time or the duration of length since when you've had diabetes will also be an influencing factor. The longer you've had it, say, greater than 3 years, we've seen has an influence. So 211 is focused on these type of patients.

Our next question will be coming from Joe Pantginis of H.C. Wainwright.

Very nice to see the sustained data post treatment cessation. So a couple of questions, if you don't mind. I know you're doing the food effect study to look at the, well, basically see what you're going to find. But with regard to B versus C exposures that you were talking about, A, when did you measure your PK time point? And B, what anecdotes could you share right now with regard to what patients or some patients may have been eating or types of food at time point?

Thank you, Joe, for the question. Just a little background here on the way the study was done. The PK was taken like during the first administration and then a month later and then a month later, et cetera. So it's not systematic; it's periodic. And sometimes what we noticed was the exposure was very good. And sometimes we noticed the exposure was very bad. And we think that the issue ultimately relates to the solubility of the drug at low PH. We know it's much more soluble at PH. We know that the best way to get a low PH in the summer is to have food there. And food not only provides for low PH but also sustains the drug in the stomach for a longer period of time. So the current study that we're doing is to basically look at what would be the best time to have the drug after we've eaten. And then we're also looking at things like high-fat and low-fat meal and half an hour after starting the meal versus 1 hour after starting the meal. We'll try and nail down what's the best approach is to increasing the exposure and getting it more consistent from one patient to the next.

No, it certainly does. And I'm just curious, would you wait for the results of the food effect study before starting various studies you talked about in your last slide?

Yes. We don't have to wait actually because of the way the timing is set up. The data will be coming out in cohorts, and we will assess the data all the way through food effect study. By the time we are ready to start 211 and 212, those data will be in the book.

No, that's helpful. And just lastly, if you don't mind, just curious, with regard to the dosing beyond the food effect impact that you're potentially looking at, are there any other dose learnings that you may apply or have seen for the next studies? And then secondly, are you looking to disclose any C-peptide data from this data set?

From the current data set, we will have C-peptide data. Is that what you mean? Or did you mean...

Yes.

Yes, 52 weeks, yes. We don't have it yet but we should and we will probably publish that on the conferences. And then there was another question on...

Yes. The other question was about are there any other things we can learn about how to give the drug?

Yes, beyond the food impact.

No. It's -- we really think the food effect, based on what we've seen so far, will be the overarching effect. And once we nail that down, we feel like we'll be able to get consistent exposure.

And our next question will be coming from Yigal Nochomovitz of Citigroup.

Yes. Ramses, so with regard to this comment around the food effect and the better exposure at the 100-milligram QD for 12 weeks, are you saying that you're not going to look at 100-milligram QD and then 4 weeks of BID? Or is that still something you would consider, because if you solve for the food effect question and that Arm C regimen may, in fact, be something worth pursuing?

Yes. We didn't see anything outstanding in Arm C that would enable us to be excited about pursuing that at this point. We feel that the simplicity of keeping the dose the same all the way through is probably more important than getting a marginal amount of improvement in the PK. So right now, we're going to push forward with the 12 weeks of 100 mg QD. And we'll see what that provides us. Down the road, I'm sure that other people will want to look at other ways of giving the drug. But I don't think at this stage it makes sense for us to go into many directions.

Okay. And then can you also talk a little bit about the GLP-1 up-regulation with the menin inhibition? How quickly are you seeing that in your preclinical work? What is the degree of up-regulation? If you could just explain a little bit more what you're observing.

Yes. Maybe let's see, Steve. Steve, are you on? Can you handle that question, Steve Morris?

Yes, indeed. I am, Ramses. Thank you. We do see it preclinically very rapid within minutes, an hour at most, you see up-regulation, the up-regulation occurs both transcriptionally and translationally, i.e., we see up-regulation of both the mRNA expression of the receptors as well as the protein. The up-regulation is multifold and it is sustained. By the way, this has been also described in the peer review literature by several groups. So it's not a finding that is unique to Biomea. Does that answer your question?

Yes. Thank you very much.

Our next question will be coming from Cha Cha Yang of Jefferies.

Can you hear me?

Yes.

This is Cha Cha on for Roger Song. I had 2 questions. One is I want to know if you're going to be continuing to study these patients in 111 and what future time points you'll be reporting. And then my second question has to do with your Phase IIb and pivotal study design. If you could give some more color on your current thinking about this design, whether that's about patient population, endpoints or duration.

Starting with the 111 study. Because we haven't figured out exactly what was going on and we had to wait for the 52-week data to potentially get enthusiastic about how well the drug was working, we did not pursue the study patients beyond Week 52. So that trial is now finished and closed down, and we will not be getting any additional data from it. However, the next studies going forward where we have a better idea of what we're likely to get out of it, whilst we will do a 26-week and 52-week endpoint, I would hope that we'll also keep those patients around and see how well they do over time beyond that and see how long this response ultimately is going to last for. Could you repeat the second part of the question too?

Yes. Just about Phase IIb and pivotal study design.

So the Phase IIb that we're working on right now will give us a point to where we need to go, what sort of sample size we'll need, what sort of specification around the patients, et cetera. And I think that we'll have a good idea about how to design a Phase III once we've gotten even the 26-week data, if we can extrapolate to what 52 is going to bring us and set up meetings with clinicians and the FDA before the 52-week data comes in so that we have a good idea about how to move forward with those trials. And when the 52-week data comes in, we should be then ready to sort of kick them off fairly quickly after that.

Maybe a flavor, Cha Cha, if you look at the guidelines of FDA, the first question is, well, the guidelines are written for chronic agents. And if you look at the marketplace and I've done that work, you will find there are 60 approved agents or combination of agents, a lot of injections with a lot of side effects that are being used to treat diabetes. That's our landscape today. So here we come along, and we propose to the FDA and the space, hey, by the way, there is this protein in your body that, if we inhibit it, it reacts almost like mother nature where mother nature when it addresses either pregnancy like Ralph DeFronzo mentioned, or obesity, it has this regulating mechanism. And if you take out or if you inhibit this protein, you may have the benefits of that mechanism. But we don't need to do it chronically; we only need to do it for 12 weeks. And so what we asked the FDA and we feel and, obviously, you never get a perfect answer from a government agency that hasn't seen everything and where there's, obviously, large studies lacking but you get an indication, we feel comfortable with the understanding that we will not be treated under the guidelines of a chronic agent because we're not treating chronically. So the endpoints that were agreed upon for the study COVALENT-111 will likely be the influence that we think the protocol -- we already know that the protocols for 211 and 212, the 2 studies we mentioned in the deck, will have the same endpoint, 26 and 52 weeks, as Mick mentioned. But I also think that the FDA will look for those for a Phase III design, meaning you'll look at HbA1c reduction at -- your primary is 26 weeks and your secondary is 52 weeks with -- in concurrence with a safety review. And that -- those are the primary things we look for. And if you take that into consideration, well, what does that mean? That means I may not have to do with the thousands of patient studies because I'm not having to follow the guidelines for chronic agents and chronic treatment of type 2 diabetes. So those large Phase III studies in -- that you are accustomed to, we think we will not need. We are more in the hundreds of patients for our Phase III design. Yet, obviously, we have to prove it in the Phase IIs that we're now embarking upon. Is that okay?

[Operator Instructions] Our next question comes from Edward Tenthoff of Piper Sandler.

Congrats on very compelling data. Just a quick follow-up and maybe a little bit more detail on this next study. You said you would follow patients up for 52 weeks and/or longer. Would -- and I apologize if I missed this but would these trials have longer-term dosing with icovamenib? And do you think that's even -- do you think that's even necessary?

Yes. Right now, I feel like we already know we're going to get good results with 12 weeks of dosing. And we're going to pursue that as a sort of strategy for registration at this stage. Whether we will need to come back later with additional dosing, obviously, we'll need to see what data happens over time. And I think right now, it's not, as I said before, it's not sensible for us to go into many directions. So I think we want to make sure that we can drive forward with a 12-week therapy, and then if we get a registration and we get on the commercial side, then we can investigate some of these other pieces.

Great. That's super helpful, and very differentiated profile.

Thanks a lot.

And I am showing no further questions at this time. I would like to hand the call back to Mick, CEO, for closing remarks.

Thank you very much for joining the call today. We appreciate your continued interest and support. This now concludes the call. Thank you.

And we do appreciate your patience. Thank you for participating. You may now disconnect.