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

Hello. I'm Steve Morris, Chief Development Officer at Biomea Fusion. On behalf of all authors, I'm pleased to present a short summary of our poster, a Phase I/II trial of BMF-219 in patients with type 2 diabetes, COVALENT-111, describing durable glycemic control with a covalent menin inhibitor BMF-219 during the off-treatment follow-up period at week 26, a full 22 weeks after the last dose of the small molecule. By way of background, the root cause of type 2 diabetes is beta cell dysfunction, which is present at diagnosis and progressively worsens over time. Specifically, at the time of diagnosis, a type 2 diabetes patient has already lost approximately 50% of their beta cell pool and about 5% of the pool is lost thereafter each year. Menin is a scaffold protein and is an important physiologic regulator of glucose metabolism. Inhibition of menin in normal physiologic conditions, such as during pregnancy, results in an increased beta cell mass and enhanced function. BMF-219 is an oral covalent menin inhibitor under clinical development for the treatment of both type 2 and type 1 diabetes. We have previously reported improved glycemic control with only 4 weeks of BMF-219 administration and persistence of this control in over 1/3 of patients for up to 22 weeks after stopping therapy. Here, we present week 26 follow-up data in additional patients subsequent to 4 weeks of either 100 or 200 milligrams, BMF-219 therapy in patients with type 2 diabetes poorly controlled with up to 3 antidiabetic agents. As before, these additional patients were treated for 4 weeks then followed for 22 weeks after discontinuation of therapy. In the 32 patients treated at these doses, at week 26, a minimum 1% reduction in hemoglobin A1c was seen in 20% of patients in the 100-milligram cohorts, while 36% of patients in the 200-milligram cohorts achieved an A1c reduction of at least 1%. After 4 weeks of once daily dosing, responders defined as patients with a hemoglobin A1c reduction greater than or equal to 0.5% at week 26 and with a baseline HOMA-B less than 200 at study entry, achieved a substantive increase in HOMA-B and C-peptide at both dosing levels, compared to nonresponders and placebo patients, indicative of improved beta cell function following BMF-219 administration. In addition, the increases in HOMA-B and C-peptide levels at week 26 were consistent with the magnitude of reduction in hemoglobin A1c in patients with a baseline HOMA-B less than 200, following BMF-219 200 milligrams once daily for 4 weeks. An illustrative patient case is presented in the poster describing a 51-year old male with a 5-year history of type 2 diabetes. The patient was poorly controlled with a hemoglobin A1c of 8.9% despite receiving metformin. He was treated with BMF-219 100 milligrams once daily for 4 weeks. His hemoglobin A1c progressively improved over the study period. At the 26-week time point, a 1.8% hemoglobin A1c reduction was noted. In addition, time and range, measured by CGM, increased to 70% at week 26 from 44% time in range at baseline. In summary, 4 weeks of treatment with BMF-219 in patients with poorly controlled type 2 diabetes resulted in a durable glycemic response. At week 26, 22 weeks after completion of treatment, a 1% or greater hemoglobin A1c reduction was seen in 20% and 36% of patients in the 100- and 200-milligram BMF-219 cohorts, respectively. Across all of the 100 and 200-milligram cohorts, 39% of patients safely achieved at least 0.5% or greater reduction in hemoglobin A1c observed approximately 5 months after the final BMF-219 dose, highlighting the durability of the effect. In the ongoing next stage of COVALENT-111, the Expansion Phase, patients with poorly controlled type 2 diabetes are being treated with up to 12 weeks of once daily BMF-219 then followed for up to 52 weeks. Data from this stage of the study will be presented at an upcoming scientific conference. Thank you for your attention.

Hello, I am Juan Pablo Frias, Chief Medical Officer and Head of Diabetes of Biomea Fusion. On behalf of all authors, I'm pleased to provide a short summary of our poster describing key observations from the dose escalation portion of study COVALENT-111, a Phase I/II trial assessing the oral covalent menin inhibitor, BMF-219, in patients with poorly controlled type 2 diabetes. By way of background, the root cause of type 2 diabetes is beta cell dysfunction, which is present at diagnosis and progressively worsens over time. Menin is a scaffold protein, which is an important physiologic regulator of glucose metabolism. Suppression of menin, such as during pregnancy, results in enhanced beta cell mass and function. BMF-219 is an oral covalent menin inhibitor under development for the treatment of both type 2 and type 1 diabetes. We have previously reported improved glycemic control with 4 weeks of BMF-219, which persists in over 1/3 of patients for up to 22 weeks after stopping therapy. Here, we present additional key observations of 4 weeks of 50, 100 and 200 milligrams daily BMF-219 in patients with type 2 diabetes poorly control with up to 3 antidiabetic agents. Again, treated for 4 weeks and then followed for an additional 22 weeks after discontinuation of therapy. Across the initial 100- and 200-milligram cohorts 39% of patients had at least a 0.5% reduction in hemoglobin A1c at week 26. These patients achieving a mean reduction in A1c of 1.3%. In looking at the pharmacokinetic response, there was a dose-dependent response with the 200-milligram dose taken with food, resulting in the highest PK exposure. The hemoglobin A1c response at week 26 across cohorts suggest a durable response after 4 weeks of treatment. Importantly, in looking at the combined 100-milligram and the combined 200-milligram cohorts, 20% of the 100-milligram treated patients had a greater than 1% hemoglobin A1c reduction at week 26 and almost double, 36%, achieved this threshold at week 26 with the 200-milligram dose. None of the placebo-treated patients achieved this greater than 1% threshold. In looking at the combined 100- and 200-milligram cohort, 26% of patients had a hemoglobin A1c reduction of greater than 1% at week 26, with a mean reduction of 1.5%. The brief patient case illustrated in the poster describes a 61-year-old woman with a 10-year history of type 2 diabetes. She was poorly controlled with a hemoglobin A1c of 7.9% despite triple agent therapy metformin, a GLP-1 receptor agonist and an SGLT2 inhibitor. She was treated with BMF-219 200 milligrams once daily for 4 weeks. Her hemoglobin A1c progressively declined over the 26 weeks, a 1.1% reduction and time in range, measured by continuous glucose monitoring, increased almost 90%, a 30% increase for baseline. Again, this was with 4 weeks of treatment in over 5 months or 22 weeks off of BMF-219. In summary, at week 26, 22 weeks after completing 4 weeks of treatment with BMF-219, patients in study COVALENT-111 are displaying improved glycemic control while off therapy supporting improved beta cell function. A higher proportion of patients treated with BMF-219 200 milligrams daily achieved a clinically significant reduction in hemoglobin A1c of greater than 1% compared to the 100-milligram dose at week 26. These data demonstrate the novel disease-modifying potential of short-term BMF-219 therapy in patients with type 2 diabetes. In the ongoing next phase of this study, the Expansion Phase, patients with poorly controlled type 2 diabetes are being treated with up to 12 weeks of once daily BMF-219 and followed for up to 52 weeks. Thank you.

Hi, I'm Sanchita Mourya, Executive Medical Director at Biomea Fusion. On behalf of all authors, I'm pleased to provide a short summary of our poster describing case-studies from COVALENT-111 trial, a Phase I/II trial of BMF-219, a covalent menin inhibitor in patients with type 2 diabetes. By way of background, the root cause of type 2 diabetes is gradual decline in beta cell number and function. Type 2 diabetes patients have only 50% of beta cell pool remaining in their pancreas at the time of diagnosis, with 5% to 10% annual decline post diagnosis. Menin, a scaffold protein, is an important regulator of glucose control. In normal physiological conditions such as pregnancy, inhibition of menin results in enhanced beta cell mass and function. BMF-219, an oral covalent menin inhibitor, is under clinical development for the treatment of type 2 and type 1 diabetes. We have previously reported improved glycemic control with only 4 weeks of BMF-219 treatment as 100- and 200-milligram once-daily dosing and persistence of glycemic control in over 1/3 of patients for up to 22 weeks after stopping therapy. Here, we present week 26 follow-up data in 2 patients, subsequent to 4 weeks of either 100-milligram or 200-milligram BMF-219 treatment in patients with type 2 diabetes, poorly controlled with up to 3 antidiabetic agents. As before, both patients were treated for 4 weeks and then followed for additional 22 weeks after completion of treatment. In the 32 patients treated at these doses at week 26, at least 0.5% reduction in HbA1c was seen in 39% of patients. These patients achieving a mean reduction in HbA1c of 1.3% at week 26. The brief case illustrated in the poster described a 29-year old man with a 4-year history of type 2 diabetes. He was poorly controlled with HbA1c of 9.5% despite being on dual-agent therapy with forming an SGLT2 inhibitor. He was treated with BMF-219 200-milligram daily dosing for 4 weeks. His HbA1c progressively improved over 26 weeks, a 2.5% reduction at week 26. And the time in range, measured by continuous glucose monitoring, increased to almost 90% during the follow-up of 56% increase from the baseline. There was an increase in HOMA-B by 190% and a C-peptide increase of 71% at week 26, which well correlates with glycemic control. Again, this was 4 weeks of treatment and over 5 months of treatment period. Another illustrative patient case in the poster describes a 49-year old man with a 10-year history of type 2 diabetes. The patient was poorly controlled with HbA1c of 8.6% despite receiving metformin. He was treated with BMF-219 100-milligram once daily for 4 weeks. His HbA1c improved over the 36-week study period. At week 26 time point, 1.1% reduction in Hb1Ac was noted. In addition, time in range, measured by continuous glucose monitoring, increased to almost 80%, a 75% increase from the base line. There was an increase in HOMA-B by 12% to 33% and C-peptide increase of 59% at week 26, which then correlates with glycemic response. In summary, these case studies illustrate potential disease modifying and durable effect of short-term BMF-219 treatment in patients with uncontrolled type 2 diabetes. Patient experience, a continuous improvement in HbA1c, an improvement in time in range on CGM during the follow-up period. Increase in HOMA-B and C-peptide well correlates with glycemic control supporting BMF-219 core mechanism of action of beta cell proliferation, improving beta cell function in patients with type 2 diabetes. In the ongoing next phase of the study, that is the Expansion Phase, patients with poorly controlled type 2 diabetes are being treated for up to 12 weeks of day BMF-219 treatment and follow up for up to week 52 or 1 year. Data from this stage of the study will be presented at upcoming scientific conference. Thank you for your time.