Biomea Fusion Inc

Previous wording

We are a clinical-stage biopharmaceutical company focused on the discovery and development of novel oral covalent small molecule drugs to treat patients with metabolic diseases and genetically defined cancers. A covalent small molecule drug is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. Leveraging our extensive expertise in covalent binding chemistry and development, we built our proprietary FUSION™ System discovery platform to advance a pipeline of novel covalent small molecule product candidates. Our goal is to utilize our capabilities and FUSIONTM System to become the leader in developing covalent small molecules to maximize the depth and durability of clinical benefit when treating various diseases. To date we have announced two clinical development candidates, BMF-219 and BMF-500.

Current wording

We are a clinical-stage biopharmaceutical company focused on the discovery and development of novel oral covalent small molecule drugs to treat patients with diabetes, obesity, and genetically defined cancers. A covalent small molecule drug is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. Leveraging our extensive expertise in covalent binding chemistry and development, we built our proprietary FUSION™ System discovery platform to advance a pipeline of novel covalent small molecule product candidates. Our goal is to utilize our capabilities and FUSIONTM System to become the leader in developing covalent small molecules to maximize the depth and durability of clinical benefit when treating various diseases. To date we have announced two clinical development candidates, icovamenib and BMF-500. We expect to announce preclinical data for a third development candidate, BMF-650, a potent, selective, oral small molecule GLP-1 receptor agonist in the fourth quarter of 2024.

Previous wording

Our lead product candidate, BMF-219, is designed to be an orally bioavailable, potent, and selective covalent inhibitor of menin, a ubiquitously expressed scaffold protein that functions in histone modification and epigenetic gene regulation to impact multiple cellular processes including cell cycle control, apoptosis, and DNA damage repair. Menin plays a key role in beta-cell proliferation and function, as previously demonstrated through increased beta-cell mass generation in Men1 knockout mice (Ja et al., 2021). We are developing BMF-219 for the treatment of menin regulated or dependent diseases such as type 1 and type 2 diabetes as well as subtypes of liquid and solid tumors.

Current wording

Our lead product candidate, icovamenib (formerly BMF-219), is designed to be an orally bioavailable, potent, and selective covalent inhibitor of menin, a ubiquitously expressed scaffold protein that functions in histone modification and epigenetic gene regulation to impact multiple cellular processes including cell cycle control, apoptosis, and DNA damage repair. Menin plays a key role in beta-cell proliferation and function, as previously demonstrated through increased beta-cell mass generation in Men1 knockout mice (Ja et al., 2021). We are developing icovamenib for the treatment of menin regulated or dependent diseases such as type 1 and type 2 diabetes as well as subtypes of liquid and solid tumors.

Previous wording

We are currently investigating BMF-219 in diabetes in our Phase 1/2 clinical trial COVALENT-111 (patients with type 2 diabetes) and in our Phase 2 clinical trial COVALENT-112 (patients with type 1 diabetes). In June 2024, the FDA placed a clinical hold on the COVALENT-111 and COVALENT-112 trials. We are working diligently with the FDA to resolve the hold.

Current wording

We are currently investigating icovamenib in diabetes in our Phase 1/2 clinical trial COVALENT-111 (patients with type 2 diabetes) and in our Phase 2 clinical trial COVALENT-112 (patients with type 1 diabetes). In June 2024, we announced that the FDA had placed a clinical hold on the COVALENT-111 and COVALENT-112 trials; this clinical hold was lifted in September 2024.

Previous wording

In October 2022, we announced completion of the Phase 1 portion of COVALENT-111, a Phase 1/2 clinical trial of BMF-219 in healthy volunteers and adults with type 2 diabetes in Canada. In December 2022, we announced FDA clearance of the IND for BMF-219 in type 2 diabetes, allowing us to expand the COVALENT-111 study to sites in the United States. In September 2023, we announced FDA and Health Canada clearance of the expansion cohorts of COVALENT-111, allowing us to evaluate BMF-219, administered at 100 mg and 200 mg, with dosing durations up to 12 weeks in adult type 2 diabetes patients. The expansion portion will consist of approximately 300 patients with 54 subjects treated with BMF-219 and 18 treated with placebo in each arm.

Current wording

In October 2022, we announced completion of the Phase 1 portion of COVALENT-111, a Phase 1/2 clinical trial of icovamenib in healthy volunteers and adults with type 2 diabetes in Canada. In December 2022, we announced FDA clearance of the IND for icovamenib in type 2 diabetes, allowing us to expand the COVALENT-111 study to sites in the United States. In September 2023, we announced FDA and Health Canada clearance of the expansion cohorts of COVALENT-111, allowing us to evaluate icovamenib, administered at 100 mg and 200 mg, with dosing durations up to 12 weeks in adult type 2 diabetes patients. The expansion portion will consist of approximately 270 participants with 64 participants treated with icovamenib and 23 treated with placebo in each arm.

Previous wording

We have reported several clinical data readouts from the escalation portion of the Phase 2 study (COVALENT-111) in type 2 diabetes patients, supporting the disease-modifying potential of BMF-219 to address a root cause of diabetes: loss of healthy, insulin-producing beta cells. In March 2024, we reported clinical data from the dose escalation phase of COVALENT-111. After just a 4-week treatment period in type 2 diabetes patients who had previously failed standard of care (HbA1c ≥7.0% and ≤10.5%), BMF-219 demonstrated continued glycemic control at 26 weeks, or five months, after cessation of dosing. A general dose response was observed from BMF-219 in type 2 diabetes patients supported by dose-dependent PK response. The 50 mg cohort had the lowest placebo adjusted mean percent change of A1c (-0.04%) while 200 mg with food cohorts achieved the highest change of A1c (-1.4%). A higher proportion of patients treated with once daily (QD) 200 mg (36%) achieved a durable glycemic response (≥1.0% HbA1c reduction) compared to 100 mg QD cohorts (20%) at Week 26 (22 weeks off treatment). Patients with >7 years duration of diabetes and failing dual- or triple-agent therapy (including GLP1 RA and/or SGLT2i) (n=2) also demonstrated improved glycemic control (HbA1c -0.4%, -1.1%, and -1.1% at Weeks 4, 12, and 26, respectively) with BMF-219 dosed at 200 mg with food. An increase in HOMA-B and C-peptide generally correlated with glycemic control, consistent with BMF-219's core mechanism of action: beta-cell proliferation and improved beta-cell function. Dose levels of 100 mg and 200 mg have been selected for the first three Arms of the Expansion Phase, which will dose patients up to 12 weeks (compared to 4 weeks in the Escalation Phase) and extended follow-up to Week 52. BMF-219 was generally well tolerated with no serious adverse events reported and no symptomatic or clinically significant hypoglycemia. Week 26 topline data readout from the Phase 2b of COVALENT-111 is expected to be announced in the fourth quarter of 2024.

Current wording

We have reported several clinical data readouts from the escalation portion of the Phase 2 study (COVALENT-111) in type 2 diabetes participants, supporting the disease-modifying potential of icovamenib to address a root cause of diabetes: loss of healthy, insulin-producing beta cells. In March 2024, we reported clinical data from the dose escalation phase of COVALENT-111. After just a 4-week treatment period in type 2 diabetes participants who had previously failed standard of care (HbA1c ≥7.0% and ≤10.5%), icovamenib demonstrated continued glycemic control at 26 weeks, or five months, after cessation of dosing. A general dose response was observed from icovamenib in type 2 diabetes participants supported by dose-dependent PK response. The 50 mg cohort had the lowest placebo adjusted mean percent change of A1c (-0.04%) while 200 mg with food cohorts achieved the highest change of A1c (-1.4%). A higher proportion of participants treated with once daily (QD) 200 mg (36%) achieved a durable glycemic response (≥1.0% HbA1c reduction) compared to 100 mg QD cohorts (20%) at Week 26 (22 weeks off treatment). Participants with >7 years duration of diabetes and failing dual- or triple-agent therapy (including GLP1 RA and/or SGLT2i) (n=2) also demonstrated improved glycemic control (HbA1c -0.4%, -1.1%, and -1.1% at Weeks 4, 12, and 26, respectively) with icovamenib dosed at 200 mg with food. An increase in HOMA-B and C-peptide generally correlated with glycemic control, consistent with icovamenib's core mechanism of action: beta-cell proliferation and improved beta-cell function. Dose levels of 100 mg and 200 mg were selected for the first three Arms of the Expansion Phase, which dosed participants up to 12 weeks (compared to 4 weeks in the Escalation Phase) and extended follow-up to Week 52. Icovamenib was generally well tolerated with no serious adverse events reported and no symptomatic or clinically significant hypoglycemia. Week 26 topline data readout from the Phase 2b of COVALENT-111 is expected to be announced in the fourth quarter of 2024.

Previous wording

In October 2023, we announced FDA clearance of the IND for BMF-219 in type 1 diabetes mellitus, allowing us to initiate a Phase 2 clinical trial in approximately 150 patients with stage 3 type 1 diabetes (COVALENT-112) at two oral dose levels (50 subjects treated with BMF-219 and 25 treated with placebo for each dose level), 100 mg and 200 mg, for 12-weeks of treatment followed by a 40 week off-treatment period. The trial will also include an open label portion (n=40), enrolling participants in the U.S. and Canada with type 1 diabetes up to 15 years since diagnosis. In December 2023, we announced Health Canada clearance of Clinical Trial Application (CTA) for BMF-219 in type 1 diabetes.

Current wording

In October 2023, we announced FDA clearance of the IND for icovamenib in type 1 diabetes mellitus, allowing us to initiate a Phase 2 clinical trial in approximately 150 participants with stage 3 type 1 diabetes (COVALENT-112) at two oral dose levels (50 participants treated with icovamenib and 25 treated with placebo for each dose level), 100 mg and 200 mg, for 12-weeks of treatment followed by a 40 week off-treatment period. The trial will also include an open label portion (n=40), enrolling participants in the U.S. and Canada with type 1 diabetes up to 15 years since diagnosis. In December 2023, we announced Health Canada clearance of Clinical Trial Application (CTA) for icovamenib in type 1 diabetes.

Previous wording

In April 2024, we highlighted initial data from the first two Stage 3 type 1 diabetes patients dosed with BMF-219 in COVALENT-112, where both patients demonstrated early signs of clinical activity with improved measures correlated with beta-cell function. BMF-219 was generally well tolerated by both patients as of the cut-off date of March 7, 2024. Week 26 topline data readout from the Phase 2a of COVALENT-112 is expected in the fourth quarter of 2024.

Current wording

In April 2024, we highlighted initial data from the first two Stage 3 type 1 diabetes participants dosed with icovamenib in COVALENT-112, where both participants demonstrated early signs of clinical activity with improved measures correlated with beta-cell function. icovamenib was generally well tolerated by both participants as of the cut-off date of March 7, 2024.

Previous wording

In December 2023, we presented data from preclinical ex-vivo human islet experiments of BMF-219. Dependent on dose concentration and also dependent on dose duration, BMF-219 was observed to increase beta cell mass and function, as well as promote controlled proliferation and enhance insulin content in beta cells. Proliferation was observed only under elevated glucose conditions, which mimics diabetic levels, and with continuous drug exposure.

Current wording

In addition, we presented data from preclinical ex-vivo human islet experiments of icovamenib in December of 2023. Dependent on dose concentration and dose duration, icovamenib was observed to increase beta cell mass and function, as well as promote controlled proliferation and enhance insulin content in beta cells. Proliferation was observed only under elevated glucose conditions, which mimics diabetic levels, and with continuous drug exposure. In October 2024, we announced the formation of Global Scientific Advisory Board with 22 world-renowned diabetes experts.

Previous wording

We are currently investigating BMF-219 in oncology in our ongoing Phase 1 clinical trial COVALENT-101 (in patients with liquid tumors) and our ongoing Phase 1/1b clinical trial COVALENT-102 (in patients with KRAS solid tumors).

Current wording

We are currently investigating icovamenib in oncology in our ongoing Phase 1 clinical trial COVALENT-101 (in patients with liquid tumors) and our ongoing Phase 1/1b clinical trial COVALENT-102 (in patients with KRAS solid tumors).

Previous wording

In January 2022, we announced that we had initiated dosing in COVALENT-101, a Phase 1 clinical trial to explore the safety and efficacy of BMF-219 in patients with relapsed/refractory AML and acute lymphoblastic leukemia (ALL), including those with MLL/KMT2A gene arrangements or NPM1 mutations. We also amended the IND to initiate additional cohorts in COVALENT-101 to explore the potential utility of BMF-219 across a range of menin-dependent hematologic malignancies including MM, DLBCL, and CLL.

Current wording

In January 2022, we announced that we had initiated dosing in COVALENT-101, a Phase 1 clinical trial to explore the safety and efficacy of icovamenib in patients with relapsed/refractory AML and acute lymphoblastic leukemia (ALL), including those with MLL/KMT2A gene arrangements or NPM1 mutations. We also amended the IND to initiate additional cohorts in COVALENT-101 to explore the potential utility of icovamenib across a range of menin-dependent hematologic malignancies including MM, DLBCL, and CLL.

Previous wording

In July 2023, we then reported initial topline data from ongoing Phase 1 clinical trial COVALENT-101 showcasing initial responses in relapsed/refractory AML patients with menin-dependent mutations. New data revealed two Complete Responses (CRs) (1 CR, 1 CRi (complete remission with incomplete count recovery)) out of five relapsed/refractory AML patients carrying menin-dependent mutations treated at Dose Level 4. BMF-219, the first and only investigational covalent small-molecule menin inhibitor in clinical development to our knowledge, was generally well tolerated with no dose-limiting toxicities observed, and no QTc prolongation reported. Dose Level 4 exposure correlates with initial activity seen in BMF-219’s preclinical studies. We believe that this data supports further dose escalation.

Current wording

In July 2023, we then reported initial topline data from ongoing Phase 1 clinical trial COVALENT-101 showcasing initial responses in relapsed/refractory AML participants with menin-dependent mutations. New data revealed two Complete Responses (CRs) (1 CR, 1 CRi (complete remission with incomplete count recovery)) out of five relapsed/refractory AML participants carrying menin-dependent mutations treated at Dose Level 4. icovamenib, the first and only investigational covalent small-molecule menin inhibitor in clinical development to our knowledge, was generally well tolerated with no dose-limiting toxicities observed, and no QTc prolongation reported. Dose Level 4 exposure correlates with initial activity seen in icovamenib’s preclinical studies. We believe that this data supports further dose escalation.

Previous wording

In December 2023, we reported the achievement of minimal residual disease negativity (MRD-neg) in first complete responder in a patient with AML. Within the total of seven patients selected as evaluable for efficacy, two CRs were observed with a mean time to response of 1.8 months. We believe that pharmacodynamic data from a case study of an AML patient containing NUP98-NSD1 mutation further supports the proposed mechanism of action of BMF-219 as a menin inhibitor; in-line with preclinical models, BMF-219 downregulated key leukemogenic genes (e.g. HOXA9, MEIS1) as well as MEN1. BMF-219 was generally well tolerated with no dose-limiting toxicities observed and without adverse event (AE) related treatment discontinuations. Four participants experienced Differentiation Syndrome (DS) ≤ Grade 3, managed by cytoreductive therapy (hydroxyurea and steroids). Two participants recovered without dose modification or interruption, and none of the participants discontinued due to DS. Clinical data to date support protocol enhancements to COVALENT-101 to include focusing exclusively on patients with menin sensitive mutations such as MLL-r and NPM1 mutant acute leukemias and higher dose levels for CYP3A4 inhibitor Arm (Arm B).

Current wording

NUP98-NSD1 mutation further supports the proposed mechanism of action of icovamenib as a menin inhibitor; in-line with preclinical models, icovamenib downregulated key leukemogenic genes (e.g. HOXA9, MEIS1) as well as MEN1. icovamenib was generally well tolerated with no dose-limiting toxicities observed and without adverse event (AE) related treatment discontinuations. Four participants experienced Differentiation Syndrome (DS) ≤ Grade 3, managed by cytoreductive therapy (hydroxyurea and steroids). Two participants recovered without dose modification or interruption, and none of the participants discontinued due to DS. Clinical data to date support protocol enhancements to COVALENT-101 to include focusing exclusively on patients with menin sensitive mutations such as MLL-r and NPM1 mutant acute leukemias and higher dose levels for CYP3A4 inhibitor Arm (Arm B).

Previous wording

We anticipate that the dose escalation for COVALENT-101 and COVALENT-102 will be completed by year end 2024. We decided to discontinue two cohorts, CLL and DLBCL of COVALENT-101 due to insufficient enrollment.

Current wording

We anticipate that the dose escalation for COVALENT-101 and COVALENT-102 will be completed by year end 2024. We chose to discontinue two cohorts, CLL and DLBCL of COVALENT-101 due to insufficient enrollment.

Previous wording

Including the discovery and development of BMF-219, we are utilizing our novel FUSIONTM System to pioneer covalent treatments against other high-value genetic drivers of disease. In May 2022, we announced the nomination of our second development candidate, BMF-500, a third-generation oral covalent small molecule inhibitor of activating mutations of the FMS-like tyrosine kinase 3 (FLT3), which are the most frequent genetic alteration in AML and are associated with poor prognosis. We believe that, despite available therapies, the treatment of patients with FLT3-mutated AML continues to be considered a significant unmet medical need. In December 2022, we presented initial preclinical data at the American Society of Hematology Annual Meeting (ASH) demonstrating BMF-500’s picomolar affinity to activating FLT3 mutations including FLT3-ITD and various tyrosine kinase domain (TKD) mutations, multi-fold higher potency and increased cytotoxicity than commercially available non-covalent FLT3 inhibitor gilteritinib, as well as complete tumor regression in mouse models of FLT3-ITD acute myeloid leukemia (AML) and maintenance of effect without the need for continued exposure. In May 2023, we announced FDA clearance of our IND to study BMF-500 in a Phase 1 study (COVALENT-103) examining safety and efficacy in patients with relapsed or refractory acute leukemia with FLT3 wild-type and FLT3 mutations, including those with MLLr/NPM1 mutations. In October 2023, we announced the first patient had been dosed with BMF-500 in relapsed or refractory acute leukemia. We anticipate that the dose escalation for COVALENT-103 will be completed by year end 2024.

Current wording

Including the discovery and development of icovamenib, we are utilizing our novel FUSIONTM System to pioneer covalent treatments against other high-value genetic drivers of disease. In May 2022, we announced the nomination of our second development candidate, BMF-500, a third-generation oral covalent small molecule inhibitor of activating mutations of the FMS-like tyrosine kinase 3 (FLT3), which are the most frequent genetic alteration in AML and are associated with poor prognosis. We believe that, despite available therapies, the treatment of patients with FLT3-mutated AML continues to be considered a significant unmet medical need. In December 2022, we presented initial preclinical data at the American Society of Hematology Annual Meeting (ASH) demonstrating BMF-500’s picomolar affinity to activating FLT3 mutations including FLT3-ITD and various tyrosine kinase domain (TKD) mutations, multi-fold higher potency and increased cytotoxicity than commercially available non-covalent FLT3 inhibitor gilteritinib, as well as complete tumor regression in mouse models of FLT3-ITD acute myeloid leukemia (AML) and maintenance of effect without the need for continued exposure. In May 2023, we announced FDA clearance of our IND to study BMF-500 in a Phase 1 study (COVALENT-103) examining safety and efficacy in patients with relapsed or refractory acute leukemia with FLT3 wild-type and FLT3 mutations, including those with MLLr/NPM1 mutations. In October 2023, we announced the first participant had been dosed with BMF-500 in relapsed or refractory acute leukemia. We anticipate that the dose escalation for COVALENT-103 will be completed by year end 2024.

Previous wording

As of June 30, 2024, we had an accumulated deficit of $325.2 million. We incurred net losses of $76.3 million and $53.9 million for the six months ended June 30, 2024 and 2023, respectively. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future, and our net losses may fluctuate significantly from period to period, depending on the timing of and expenditures on our planned research and development activities.

Current wording

As of September 30, 2024, we had an accumulated deficit of $357.9 million. We incurred net losses of $109.1 million and $82.4 million for the nine months ended September 30, 2024 and 2023, respectively. We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future, and our net losses may fluctuate significantly from period to period, depending on the timing of and expenditures on our planned research and development activities.

Previous wording

conduct our ongoing preclinical studies and Phase 1 clinical trial of BMF-219 in various types of liquid tumors, our planned Phase 1/1b clinical trial of BMF-219 in solid tumors with KRAS mutations, and, pending resolution of the clinical hold, our Phase 1/2 clinical trial of BMF-219 in type 2 diabetes and our Phase 2 clinical trial of BMF-219 in type 1 diabetes;

Current wording

conduct our ongoing preclinical studies and Phase 1 clinical trial of icovamenib in various types of liquid tumors, our planned Phase 1/1b clinical trial of icovamenib in solid tumors with KRAS mutations, our Phase 1/2 clinical trial of icovamenib in type 2 diabetes and our Phase 2 clinical trial of icovamenib in type 1 diabetes;

Previous wording

conduct preclinical studies and initiate and conduct clinical trials;

Current wording

conduct preclinical studies and initiate and conduct additional clinical trials;

Previous wording

We may need to raise additional capital in the future to fund our operations, including to conduct and complete clinical trials for any product candidates. If sufficient funds on acceptable terms are not available when needed, we could be required to significantly reduce our operating expenses and delay, reduce the scope of, or eliminate one or more of our development programs.

Current wording

We will need to raise additional capital in the future to fund our operations, including to conduct and complete clinical trials for any product candidates. If sufficient funds on acceptable terms are not available when needed, we could be required to significantly reduce our operating expenses and delay, reduce the scope of, or eliminate one or more of our development programs.

Previous wording

We expect our research and development expenses to increase substantially during the next few years as we seek to initiate and complete clinical trials, pursue regulatory approval of BMF-219 and BMF-500, pursue a resolution of the clinical hold on the Phase 1/2 clinical trials of BMF-219 in type 2 and type 1 diabetes mellitus, and advance our other programs through preclinical and clinical development. Predicting the timing or the final cost to complete our clinical program or validation of our manufacturing and supply processes is difficult and delays may occur because of many factors. The process of conducting the necessary preclinical and clinical research to obtain regulatory approval is costly and time-consuming. To the extent that our product candidates continue to advance into clinical trials, as well as advance into larger and later stage clinical trials, our expenses will increase substantially and may become more variable.

Current wording

We expect our research and development expenses to increase substantially during the next few years as we seek to initiate and complete clinical trials, pursue regulatory approval of icovamenib and BMF-500 and advance our other programs through preclinical and clinical development. Predicting the timing or the final cost to complete our clinical program or validation of our manufacturing and supply processes is difficult and delays may occur because of many factors. The process of conducting the necessary preclinical and clinical research to obtain regulatory approval is costly and time-consuming. To the extent that our product candidates continue to advance into clinical trials, as well as advance into larger and later stage clinical trials, our expenses will increase substantially and may become more variable.

Previous wording

the scope, rate of progress, expense and results of our ongoing preclinical development activities and clinical trials of BMF-219 and BMF-500 in various types of cancer and metabolic diseases, of any future preclinical development and clinical trials of our product candidates and other research and development activities we may conduct;

Current wording

the scope, rate of progress, expense and results of our ongoing preclinical development activities and clinical trials of icovamenib and BMF-500 in various types of cancer and metabolic diseases, of any future preclinical development and clinical trials of our product candidates and other research and development activities we may conduct;

Previous wording

the number of patients who participate in the trials;

Current wording

the number of participants who participate in the trials;

Previous wording

the length of time required to enroll eligible patients;

Current wording

the length of time required to enroll eligible participants;

Previous wording

the drop-out or discontinuation rates of patients;

Current wording

the drop-out or discontinuation rates of participants;

Previous wording

Comparison of the three and six months ended June 30, 2024 and 2023

Current wording

Comparison of the three and nine months ended September 30, 2024 and 2023

Previous wording

Research and development expenses increased by $19.3 million during the six months ended June 30, 2024 compared to the six months ended June 30, 2023. The increase of $14.1 million in external costs was primarily driven by an increase of $11.8 million related to clinical activities resulting from the completion of enrollment of first 3 arms in the expansion cohort of COVALENT-111, and continuing enrollment in COVALENT-112 and COVALENT-103 during the six months ended June 30, 2024. Preclinical activities related expenses increased by $2.5 million primarily driven by an increase in other exploratory programs. Other external costs increased by $1.5 million primarily driven by external consultants and professional services to support clinical and preclinical activities. Manufacturing related costs decreased by $1.8 million primarily driven by timing of services performed by our contract manufacturers. Personnel-related expenses, including stock-based compensation, increased by $4.9 million due to an increase in headcount.

Current wording

Research and development expenses increased by $1.9 million during the three months ended September 30, 2024 compared to the three months ended September 30, 2023. The increase of $0.9 million in external costs was primarily driven by an increase of $1.7 million of clinical activities related expenses related to increased enrollment of our diabetes and oncology trials. Preclinical activities related expenses decreased by $1.4 million primarily driven by timing of our exploratory programs. Other external costs increased by $2.7 million primarily driven by external consultants and professional services to support clinical and preclinical activities. Manufacturing related costs decreased by $2.1 million primarily driven by timing of services performed by our contract manufacturers. Personnel-related expenses, including stock-based compensation, increased by $1.2 million due to an increase in headcount.

Previous wording

Research and development expenses increased by $9.9 million during the three months ended June 30, 2024 compared to the three months ended June 30, 2023. The increase of $8.0 million in external costs was primarily driven by an increase of $7.2 million related to clinical activities resulting from the completion of enrollment of first 3 arms in the expansion cohort of COVALENT-111, and continuing enrollment in COVALENT-112 and COVALENT-103 during the three months ended June 30, 2024. Preclinical activities related expenses increased by $1.6 million primarily driven by an increase in other exploratory programs. Other external costs increased by $0.9 million primarily driven by external consultants and professional services to support clinical and preclinical activities. Manufacturing related costs decreased by $1.7 million primarily driven by timing of services performed by our contract manufacturers. Personnel-related expenses, including stock-based compensation, increased by $1.8 million due to an increase in headcount.

Current wording

Research and development expenses increased by $21.2 million during the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023. The increase of $15.0 million in external costs was primarily driven by an increase of $13.5 million of clinical activities related expenses related to increased enrollment of our diabetes and oncology trials during the nine months ended September 30, 2024. Preclinical activities related expenses increased by $1.2 million primarily driven by an increase in other exploratory programs. Other external costs increased by $4.3 million primarily driven by external consultants and professional services to support clinical and preclinical activities. Manufacturing related costs decreased by $3.9 million primarily driven by timing of services performed by our contract manufacturers. Personnel-related expenses, including stock-based compensation, increased by $6.1 million due to an increase in headcount.

Previous wording

General and administrative expenses increased by $1.4 million during the three months ended June 30, 2024 compared to the three months ended June 30, 2023. The increase is primarily due to increase in personnel-related expenses, including stock-based compensation of $1.0 million, resulting from an increase in headcount and increase in professional services of $0.5 million related to general external consultants.

Current wording

General and administrative expenses increased by $1.0 million during the three months ended September 30, 2024 compared to the three months ended September 30, 2023. The increase is primarily due to increase in personnel-related expenses, including stock-based compensation of $0.9 million, resulting from an increase in headcount and increase in professional services of $0.2 million related to general external consultants.

Previous wording

General and administrative expenses increased by $3.0 million during the six months ended June 30, 2024 compared to the six months ended June 30, 2023. The increase is primarily due to increase in personnel-related expenses, including stock-based compensation of $2.1 million, resulting from an increase in headcount, increase in professional services of $1.3 million related to general external consultants and legal related expenses. The increase is offset by a decrease of $0.3 million related to insurance.

Current wording

General and administrative expenses increased by $4.0 million during the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023. The increase is primarily due to increase in personnel-related expenses, including stock-based compensation of $3.0 million, resulting from an increase in headcount, increase in professional services of $1.6 million related to general external consultants and legal related expenses. The increase is offset by a decrease of $0.3 million related to insurance and decrease of $0.2 million in facilities related expenses.

Previous wording

As of June 30, 2024, we had cash, cash equivalents, and restricted cash of $113.7 million and an accumulated deficit of $325.2 million. We have incurred substantial operating losses and have used cash in our operating activities since inception. Without any future financing, the current operating plan under the existing cash and cash equivalents, and restricted cash as of June 30, 2024, will not be sufficient for us to fund our operating expenses and capital expenditure requirements for at least twelve months following the issuance date of the unaudited condensed financial statements. Our ability to continue as a going concern will require us to obtain additional financing to fund our operations and there can be no assurance that additional financing will be available to us or that such financing, if available, will be available on terms acceptable to us. Accordingly, there is substantial doubt about our ability to continue as a going concern.

Current wording

As of September 30, 2024, we had cash, cash equivalents, and restricted cash of $88.3 million and an accumulated deficit of $357.9 million. We have incurred substantial operating losses and have used cash in our operating activities since inception. Without any future financing, the current operating plan under the existing cash and cash equivalents, and restricted cash as of September 30, 2024, will not be sufficient for us to fund our operating expenses and capital expenditure requirements for at least twelve months following the issuance date of the unaudited condensed financial statements. Our ability to continue as a going concern will require us to obtain additional financing to fund our operations and there can be no assurance that additional financing will be available to us or that such financing, if available, will be available on terms acceptable to us. Accordingly, there is substantial doubt about our ability to continue as a going concern.

Previous wording

the cost, timing and outcome of regulatory review of our product candidates, including the timing and outcome of our efforts to resolve the clinical hold of BMF-219 in type 2 and type 1 diabetes mellitus;

Current wording

the cost, timing and outcome of regulatory review of our product candidates;

Previous wording

the impact of the COVID-19 pandemic and adverse global economic conditions on our business, which may exacerbate the magnitude of the factors discussed above.

Current wording

the impact of any public health emergencies such as the COVID-19 pandemic and adverse global economic and geopolitical conditions on our business, which may exacerbate the magnitude of the factors discussed above.

Previous wording

Net cash used in operating activities was $64.7 million during the six months ended June 30, 2024 and consisted of a net loss of $76.3 million and decrease in net assets of $0.4 million, offset by non-cash adjustments of $12.1 million. The decrease in net assets consisted primarily of an increase in prepaid expenses and other current assets of $0.7 million, an increase in other assets of $1.2 million, a decrease in accounts payable of $1.1 million offset by an increase in accrued expenses and other current liabilities of $2.5 million. Non-cash adjustments consisted primarily of stock-based compensation expense of $9.9 million, operating lease expense of $1.4 million and depreciation expense of $0.8 million.

Current wording

Net cash used in operating activities was $89.9 million during the nine months ended September 30, 2024 and consisted of a net loss of $109.1 million offset by increase in net assets of $1.3 million and non-cash adjustments of $18.0 million. The increase in net assets consisted primarily of an increase in prepaid expenses and other current assets of $3.3 million, a decrease in other assets of $0.9 million, an increase in accounts payable of $2.1 million, an increase in accrued expenses and other current liabilities of $2.4 million and a decrease in operating lease liabilities of $0.7 million. Non-cash adjustments consisted primarily of stock-based compensation expense of $14.6 million, operating lease expense of $2.1 million and depreciation expense of $1.3 million.

Previous wording

Net cash used in operating activities was $49.9 million during the six months ended June 30, 2023 consisted of a net loss of $53.9 million, offset by a decrease in net assets of $4.5 million and non-cash adjustments of $8.6 million. The decrease in net assets consisted primarily of a decrease in prepaid expenses and other current assets of $1.7 million, decrease in accrued expenses and other current liabilities of $4.2 million and a decrease in operating lease liabilities of $1.2 million. The decrease is offset by an increase in other assets of $0.8 million. Non-cash adjustments consisted primarily of stock-based compensation expense of $6.7 million and operating lease expense of $1.3 million.

Current wording

Net cash used in operating activities was $73.8 million during the nine months ended September 30, 2023 and consisted of a net loss of $82.4 million, offset by a decrease in net assets of $4.7 million and non-cash adjustments of $13.3 million. The decrease in net assets consisted primarily of a decrease in prepaid expenses and other current assets of $1.4 million, decrease in accounts payable of $1.1 million and decrease in accrued expenses and other current liabilities of $1.5 million and a decrease in operating lease liabilities of $1.8 million. The decrease is offset by an increase in other assets of $1.7 million. Non-cash adjustments consisted primarily of stock-based compensation expense of $10.3 million and operating lease expense of $2.0 million.

Previous wording

Net cash used in investing activities was $0.1 million during the six months ended June 30, 2024 and was primarily related to the purchase of property and equipment.

Current wording

Net cash used in investing activities was $0.3 million during the nine months ended September 30, 2024 and was primarily related to the purchase of property and equipment.

Previous wording

Net cash used in investing activities was $2.2 million during the six months ended June 30, 2023 and was primarily related to the purchase of property and equipment partially offset by maturities of investments.

Current wording

Net cash used in investing activities was $2.2 million during the nine months ended September 30, 2023 and was primarily related to the purchase of property and equipment partially offset by maturities of investments.

Previous wording

Net cash provided by financing activities was $1.2 million during the six months ended June 30, 2024 and relates to proceeds received from stock option exercises and purchases under the 2021 Employee Stock Purchase Plan, or the ESPP.

Current wording

Net cash provided by financing activities was $1.3 million during the nine months ended September 30, 2024 and relates to proceeds received from stock option exercises and purchases under the 2021 Employee Stock Purchase Plan, or the ESPP.

Previous wording

Net cash provided by financing activities was $163.0 million during the six months ended June 30, 2023. Cash provided by financing activities was related to $161.8 million net proceeds received from the public offering of our common stock and $1.2 million of proceeds received from stock option exercises and purchase under the ESPP.

Current wording

Net cash provided by financing activities was $163.2 million during the nine months ended September 30, 2023. Cash provided by financing activities was related to $161.8 million net proceeds received from the public offering of our common stock and $1.4 million of proceeds received from stock option exercises and purchases under the ESPP.

Previous wording

Our critical accounting policies are described in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Use of Estimates” in our Annual Report on Form 10-K filed with the SEC on March 28, 2024 and the notes to the financial statements appearing elsewhere in this Quarterly Report on Form 10-Q. During the six months ended June 30, 2024, except as described in Note 2 to the unaudited condensed financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, there were no material changes to our critical accounting policies from those discussed in our Annual Report on Form 10-K filed with the SEC on March 28, 2024.

Current wording

Our critical accounting policies are described in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Use of Estimates” in our Annual Report on Form 10-K filed with the SEC on March 28, 2024 and the notes to the financial statements appearing elsewhere in this Quarterly Report on Form 10-Q. During the nine months ended September 30, 2024, except as described in Note 2 to the unaudited condensed financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, there were no material changes to our critical accounting policies from those discussed in our Annual Report on Form 10-K filed with the SEC on March 28, 2024.