Biomea Fusion, Inc. Common Stock H.C. Wainwright 28th Annual Global Investment Conference

Welcome. Thank you. Thank you for hosting.

This is actually, you typically do fireside chats, and now you make me present. You had me work this presentation, and I hope I can make it in 20 minutes. There's a lot to cover. The company was founded in 2017. Today, we have two assets that we're pursuing. We're no longer having our research department. We basically are 35 people strong, and we're focused on two assets. One, a first-in-class beta cell restorative therapy. We are the first menin inhibitor that targets diabetes, and this pathway was detected in 2005. 2007, 2010, early academic papers came out, and when we started the company in 2017, we read those papers and thought, if ever menin, which was originally identified for cancer, if ever that target can be addressed safely with a menin inhibitor, we should go after diabetes.

The market is so huge and nothing in diabetes restores. Everything is trying to sort of bring down the sugar. We thought it was a phenomenal opportunity, so we spent a lot of time working through pre-clinical animal models, and now we have a first-in-class, and potentially best-in-class, type 1 and type 2 diabetes agent. We're in phase II, and I will show you where we are exactly. Then we have, with the team, about 4 or 5 years ago, we started, and we said, "This GLP-1 space is just heating up. Is there a way to make it better? Can we, as drug developers, come up with a scaffold or improve a scaffold that threads the needle just a little better?" Right now you're fighting between the persistence of patients. Patients are not staying on drug. Why? Because they have GI side effects. Okay. You're fighting that on the one hand with, "I need to get this weight down, but not only through vomiting." That would not be a good outcome. 7 out of 10 patients, in the worst of all studies I have read, drop within the first year, even though you pay for them.

So what kind of drug is that? That's not a good drug. The class is great, the effects are great, but can we improve this profile to keep patients on drug? I will talk about that as well. So that's our next generation all GLP-1. We have multiple phase II readouts. We have a fairly experienced leadership team with a clear vision and execution plan. Probably every biopharma says that. Then we have a cash runway through key upcoming inflection points. That's a very important graph, and I'll show you that as well.

Okay. Here is the milestone slide. It is very busy. I will walk you through each one of those important findings. One, we saw our pathway has phenomenal impact. Literally unusual impact in type 1 patients. That blew me away when I saw this data. We are showing C-peptide increases in a patient where the immune system is attacking those cells, and we see that the C-peptide, meaning the output of those cells that are being attacked, is going up, which means the mass is growing. That is our targeted approach. We want this mass to grow, and C-peptide is the marker for that. We saw that. We were really excited about this opportunity. We have 2 studies planned in type 1.

We have a study where we show the benefits of the use of our menin inhibitor in combination with the GLP-1 agonist in obesity because we saw muscle preservation, additional weight loss, and general health benefits when combining menin inhibition with GLP-1 agonism. That study will read out by the end of next year. The type 1 study will engage at the beginning of next year. We will have a first patient in, and we will read out by the end of next year as well. We have our core, which are the 2 studies here. The ones in type 2 diabetes, where the subsets are identified here. One finished enrollment, and they are on track to read out next year as well. The primary goal for a company like ours is what?

The primary goal is finish your phase II, show to the FDA that we have the data sets necessary to go into a commercial study, which is a phase III, and that is the primary goal. That is why we are here. We are here. After that, anybody can do this work because to translate a 2 to a 3 is difficult, but is not overly complex. You just take the protocol. If the protocol is acceptable to FDA, which we hope it is, and replicate it in your phase III studies. We already talked about how many patients are needed for these phase III studies. So we feel comfortable if we produce the data, we will be in end of phase II meetings with FDA by the end of next year.

Here down there, you can see the GLP-1 is the BMF-650, is the next generation GLP-1 that we created, which will read out by the end of this quarter. Lots going on. Okay, let us go into it. Most people do not know that diabetes is actually a disease that is not approached at its root cause level with the medicines we have. What does that mean? That means you go to the doctor, you say, "Oh," the doctor indicates to you you have diabetes. What is he going to give you? He is going to give you a drug or one of a drug class of drugs, and they typically have a lifespan of 2-5 years, whatever the literature you can find.

He is going to give you another drug and another drug, but all these drugs are doing is they are addressing the sugar that is circulating in your blood. Diabetes is an indicator that your pancreas that has beta cells are fitted to you at birth, but they do not fit your current lifestyle. Your current lifestyle is maybe sedative, maybe you eat the wrong things, maybe too much sugar intake, which is very likely your lifestyle, and thereby you are depleting these cells. When you hit about 50%, your body signals side effects, and these side effects are indicators that you have too much sugar circulating and the pancreas is incapable of managing that sugar. The insulin production is insufficient. So you typically have lost 50% of that capacity. Losing means losing, they do not come back. You do not make new cells, generally speaking.

Only under two circumstances, and I will get to those. If you get this indication, the doctor addresses this disease by addressing the symptom, which is sugar, and he addresses it with different drug classes. As you cycle through these classes, you will end up on insulin. 1 out of 3 patients ends up on insulin. Did you know that you lose 12 years of your life by being a diabetic? This is a really severe disease. I worked in oncology for over 10 years. I have never had a statistic as clear as this, the premature mortality. It is brutal. You have diabetes, you lose 10 years of life. So what can we do to change these dynamics as you see them here? The only thing we can try to do is not get a better agent to address the sugar.

Could be one way, but there are so many ways people have tried to get the sugar out of your blood. The better way is your pancreas. Why do not we restore the cells in your pancreas so they can address the sugar? So what the body does is, and I am going to show you some This is just basically high level. It is a big disease, we know, diabetes and obesity. What was found is, and this is the paper of 2005 I mentioned earlier, is in your pancreas, there is a control switch called menin. When you go through obesity as a male or you go through pregnancy as a female, your body upregulates a hormone called prolactin. This hormone, when upregulated, downregulates menin, which is a protein. When menin is downregulated, the body can now address the need for more insulin by increasing the cells of your pancreas.

A pregnant woman who died during pregnancy has an enlarged pancreas. Women who have gone through more than one pregnancy have less probability of diabetes. Women who have gone through breastfeeding have less probability of diabetes. If you put these facts together, and this pathway has now been found in animals as well, menin regulates pancreatic islet growth. Can I address this menin protein and allow the body to respond in a diabetic circumstance and bring these beta cells and restore the pool of beta cells? That is the question we asked. What we found is that icovamenib has been shown to directly inhibit menin, and I will show you this example here. There were so many stories about us early on because what we are doing here is actually too good to be true. I can restore your health with a medication. How is that possible? Well, what you can see here on the left is the protein menin gets reduced in donor islet cells.

That is where you typically show, are you having an effect on the target, left side. On the right side, you can see here, under high glucose condition, the proliferation rate of more menin inhibition, higher green bar, is higher in a high glucose environment. If you have standard glucose conditions, even though we inhibit menin, the body does not proliferate these beta islet cells. Very interesting finding. We know we are on target left, and we know while we are on target, the effect is improved the more we inhibit the target, if you are in a high glucose environment. Meaning, if your HbA1c is above 7, you are not controlled, the physician will give you a drug to address your diabetes. That is this high glucose environment.