KRAS G12D x KRAS G12C x KRAS G12V

REDWOOD CITY, CA, USA I January 17, 2023 I Biomea Fusion, Inc. (“Biomea”) (Nasdaq: BMEA), a biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases, today announced that the first patient has been dosed in COVALENT-102, the company’s Phase I/Ib trial of BMF-219, an oral, selective, covalent menin inhibitor in patients with KRAS-mutated unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC. “We are eager to explore the potential of BMF-219 as a pan-KRAS inhibitor in patients with three of the most prominent KRAS-mutant solid tumor types, including those with tumors that have failed to respond to investigational and approved mutation-specific KRAS inhibitors,” said Steve Morris, M.D., Biomea’s Chief Medical Officer. “As a covalent menin inhibitor, we believe BMF-219 has critical advantages over late stage, mutation-specific inhibitors of KRAS including independence on the KRAS activation state, reduced likelihood for acquisition of resistance mutations, and its potential to address multiple activating KRAS mutations.” KRAS is the most frequently mutated isoform amongst RAS oncogenes in human solid tumors, with high prevalence in NSCLC, CRC, and PDAC. KRAS G12C, KRAS G12D and KRAS G12V are among the most common KRAS mutations. However, there are numerous other known activating KRAS mutations. With only two approved therapies both targeting only KRAS G12C for locally advanced or metastatic NSCLC, KRAS-driven tumors continue to represent a significant unmet medical need. As a covalent menin inhibitor, BMF-219 has manifested a differentiated profile over the commercially approved KRAS-targeted inhibitors LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in multiple pre-clinical studies. As previously reported by Biomea, KRAS-mutant NSCLC, CRC, and PDAC cell lines and ex vivo patient specimens were highly sensitive to BMF-219 in preclinical models. The higher levels of activity of BMF-219 were observed among various KRAS-mutant solid tumor cell lines, but not KRAS wild type, suggesting that BMF-219 broadly inhibited mutant KRAS in these tumor models. A targeted pan-KRAS inhibitor has the potential to treat a large number of NSCLC, CRC, and PDAC patients. About COVALENT–102 COVALENT-102 is an open-label, multi-cohort, multicenter, Phase I/Ib dose escalation and expansion study evaluating the safety, tolerability, and optimal biologic dose of BMF-219 administered orally to adult patients with KRAS-mutated unresectable, locally advanced or metastatic NSCLC, CRC, and PDAC. Additional information about the Phase I/Ib clinical trial of BMF-219 can be found at ClinicalTrials.gov using the identifier NCT05631574. About Non-Small Cell Lung Cancer (NSCLC) NSCLC is the most common form of lung cancer, representing approximately 82% of all lung cancer cases or approximately 200,000 cases in the U.S. each year (Source: NCI SEER Data). The five-year survival rate of NSCLC is approximately 25%. While lung cancer is the third most common form of cancer in the U.S. based on incidence, it contributes to the highest number of annual cancer deaths in the U.S. KRAS is the most frequently mutated oncogene in NSCLC, occurring in approximately 30% of patients. There remains a great unmet need for targeted therapies to address all KRAS driver mutations and avoid known mechanisms of resistance. About Colorectal Cancer (CRC) CRC is the fourth most common form of cancer and the second leading cause of cancer death in the U.S., representing approximately 150,000 cases in the U.S. each year (Source: NCI SEER Data). These cancers start in the rectum or the colon and can be diagnosed/identified early, even potentially as noncancerous polyps. The five-year survival rate of CRC is approximately 65%. Among other mutations, KRAS mutations occur in approximately 40% of patients with CRC. These mutations can not only help predict the absence of response to anti-EGFR therapy, but also result in poorer overall survival. Therefore, there remains a significant unmet need for personalized therapies for patients with KRAS-mutant colorectal cancer. About Pancreatic Cancer (PDAC) Pancreatic cancer is a relatively rare form of cancer in the U.S., representing approximately 60,000 cases in the U.S. each year (Source: NCI SEER Data). Pancreatic cancer is an aggressive cancer with a very low five-year survival rate of approximately 11%, indicating that there is a large unmet need. 80% of patients are diagnosed at an advanced stage, contributing to the low survival rate. KRAS mutations are found in nearly all pancreatic cancer patients and are considered as a driver of the malignant process in most of those patients. About Biomea Fusion Biomea Fusion is a clinical stage biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases. A covalent small molecule 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. The company is utilizing its proprietary FUSION™ System to advance a pipeline of covalent-binding therapeutic agents against key oncogenic drivers of cancer and metabolic diseases. Biomea Fusion’s goal is to utilize its capabilities and platform to become a leader in developing covalent small molecules in order to maximize the clinical benefit when treating various cancers and metabolic diseases. SOURCE: Biomea Fusion

BMF-219 is the first menin inhibitor to be clinically studied in patients with KRAS-mutated non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) A pan-KRAS inhibitor targeting multiple KRAS mutations (including G12C, G12D and G12R, among others) has the potential to treat 25-35% of NSCLC patients, 35-45% of CRC patients, and approximately 90% of PDAC patients BMF-219 is now in clinical development across eight liquid and solid tumor types, as well as for patients with type 2 diabetes REDWOOD CITY, Calif., Jan. 17, 2023 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (“Biomea”) (Nasdaq: BMEA), a biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases, today announced that the first patient has been dosed in COVALENT-102, the company’s Phase I/Ib trial of BMF-219, an oral, selective, covalent menin inhibitor in patients with KRAS-mutated unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC. “We are eager to explore the potential of BMF-219 as a pan-KRAS inhibitor in patients with three of the most prominent KRAS-mutant solid tumor types, including those with tumors that have failed to respond to investigational and approved mutation-specific KRAS inhibitors,” said Steve Morris, M.D., Biomea’s Chief Medical Officer. “As a covalent menin inhibitor, we believe BMF-219 has critical advantages over late stage, mutation-specific inhibitors of KRAS including independence on the KRAS activation state, reduced likelihood for acquisition of resistance mutations, and its potential to address multiple activating KRAS mutations.” KRAS is the most frequently mutated isoform amongst RAS oncogenes in human solid tumors, with high prevalence in NSCLC, CRC, and PDAC. KRAS G12C, KRAS G12D and KRAS G12V are among the most common KRAS mutations. However, there are numerous other known activating KRAS mutations. With only two approved therapies both targeting only KRAS G12C for locally advanced or metastatic NSCLC, KRAS-driven tumors continue to represent a significant unmet medical need. As a covalent menin inhibitor, BMF-219 has manifested a differentiated pro the commercially approved KRAS-targeted inhibitors LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in multiple pre-clinical studies. As previously reported by Biomea, KRAS-mutant NSCLC, CRC, and PDAC cell lines and ex vivo patient specimens were highly sensitive to BMF-219 in preclinical models. The higher levels of activity of BMF-219 were observed among various KRAS-mutant solid tumor cell lines, but not KRAS wild type, suggesting that BMF-219 broadly inhibited mutant KRAS in these tumor models. A targeted pan-KRAS inhibitor has the potential to treat a large number of NSCLC, CRC, and PDAC patients. About COVALENT–102 COVALENT-102 is an open-label, multi-cohort, multicenter, Phase I/Ib dose escalation and expansion study evaluating the safety, tolerability, and optimal biologic dose of BMF-219 administered orally to adult patients with KRAS-mutated unresectable, locally advanced or metastatic NSCLC, CRC, and PDAC. Additional information about the Phase I/Ib clinical trial of BMF-219 can be found at ClinicalTrials.gov using the identifier NCT05631574. About Non-Small Cell Lung Cancer (NSCLC) NSCLC is the most common form of lung cancer, representing approximately 82% of all lung cancer cases or approximately 200,000 cases in the U.S. each year (Source: NCI SEER Data). The five-year survival rate of NSCLC is approximately 25%. While lung cancer is the third most common form of cancer in the U.S. based on incidence, it contributes to the highest number of annual cancer deaths in the U.S. KRAS is the most frequently mutated oncogene in NSCLC, occurring in approximately 30% of patients. There remains a great unmet need for targeted therapies to address all KRAS driver mutations and avoid known mechanisms of resistance. About Colorectal Cancer (CRC) CRC is the fourth most common form of cancer and the second leading cause of cancer death in the U.S., representing approximately 150,000 cases in the U.S. each year (Source: NCI SEER Data). These cancers start in the rectum or the colon and can be diagnosed/identified early, even potentially as noncancerous polyps. The five-year survival rate of CRC is approximately 65%. Among other mutations, KRAS mutations occur in approximately 40% of patients with CRC. These mutations can not only help predict the absence of response to anti-EGFR therapy, but also result in poorer overall survival. Therefore, there remains a significant unmet need for personalized therapies for patients with KRAS-mutant colorectal cancer. About Pancreatic Cancer (PDAC) Pancreatic cancer is a relatively rare form of cancer in the U.S., representing approximately 60,000 cases in the U.S. each year (Source: NCI SEER Data). Pancreatic cancer is an aggressive cancer with a very low five-year survival rate of approximately 11%, indicating that there is a large unmet need. 80% of patients are diagnosed at an advanced stage, contributing to the low survival rate. KRAS mutations are found in nearly all pancreatic cancer patients and are considered as a driver of the malignant process in most of those patients. About Biomea Fusion Biomea Fusion is a clinical stage biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases. A covalent small molecule 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. The company is utilizing its proprietary FUSION™ System to advance a pipeline of covalent-binding therapeutic agents against key oncogenic drivers of cancer and metabolic diseases. Biomea Fusion’s goal is to utilize its capabilities and platform to become a leader in developing covalent small molecules in order to maximize the clinical benefit when treating various cancers and metabolic diseases. Forward-Looking Statements Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding our cash runway, the clinical and therapeutic potential of our product candidates and development programs, including BMF-219, the potential of BMF-219 as a treatment for various types of cancer and diabetes, our research, development and regulatory plans, including our pursuit of BMF-219 in KRAS-mutant solid tumors in our ongoing Phase I/Ib COVALENT-102 trial, the availability of clinical data for BMF-219 in oncology and diabetes, and the timing of such events, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays or unforeseen results in preclinical development, IND-filing and acceptance, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research, development and regulatory activities. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law. Contact: Sasha Blaug SVP, Corporate Development [email protected] (650) 460-7759

IND filing for IMM-1-104, which has displayed broad preclinical pan-KRAS/NRAS activity, expected this quarter; Enrollment of first patient in planned Phase 1/2a clinical trial expected in Q4 2022 IND filing for IMM-6-415, designed to sensitize resistant tumors to select immunotherapies, expected in 2023 Cash, cash equivalents and marketable securities of $128.1M is expected to provide cash runway into Q3 2024 CAMBRIDGE, Mass., Aug. 10, 2022 (GLOBE NEWSWIRE) -- Immuneering Corporation (NASDAQ: IMRX), a biopharmaceutical company using translational bioinformatics to advance a pipeline of product candidates designed to benefit large populations of patients with cancer and other diseases, today reported financial results for the second quarter ended June 30, 2022 and provided recent business highlights. “We believe IMM-1-104 has great potential to benefit the many cancer patients with tumors driven by KRAS or NRAS mutations,” said Ben Zeskind, Ph.D., MBA, chief executive officer of Immuneering Corporation. “We are thrilled to be gearing up to file our IND for IMM-1-104, which remains on track to be filed this quarter, and we expect to enroll the first patient in our planned Phase 1 clinical trial in the fourth quarter of 2022. To date, we have generated strong preclinical results across a broad range of animal tumor models including KRAS-G12C, KRAS-G12D, KRAS-G12S, KRAS-G12V, NRAS-Q61R, and BRAF-V600E mutations. This compelling preclinical data package demonstrates IMM-1-104’s potential as a third generation MEK inhibitor to have broad activity that is independent of the specific mutation activating the MAPK pathway.” Corporate Highlights IMM-1-104 strongly inhibits tumor growth in an animal model of KRAS-G12V Mutant Pancreatic Cancer: In May 2022, Immuneering reported preclinical data at the ASCO 2022 meeting titled “Head-to-head comparison of the dual-MEK inhibitor IMM-1-104 versus sotorasib or adagrasib in KRAS mutant pancreatic tumors” in an online publication. In the Capan-2 PDAC KRAS-G12V xenograft animal model, all doses and schedules of IMM-1-104 (75, 100, 150mg/kg BID p.o. or 150mg/kg QD p.o.) showed tumor growth inhibition (TGI) of 49-84% after 21 days of treatment. Taken together with IMM-1-104’s demonstrated preclinical activity across KRAS-G12C, KRAS-G12D, KRAS-G12S, NRAS-Q61R and BRAF-V600E, this new data in KRAS-G12V shows the potential to offer a unique advantage in pancreatic cancer where a broad range of KRAS mutations occur.IMM-1-104 translational modeling shows models sensitive to IMM-1-104 were enriched for MAPK Driver Mutations: In May 2022, Immuneering reported a second preclinical abstract at the ASCO 2022 meeting entitled “Translational modeling for patients with RAS mutant tumors: Profiling the dual-MEK inhibitor IMM-1-104 in a humanized 3D assay” in an online publication. IMM-1-104’s pharmacological activity was profiled across 52 human tumor cell lines spanning a variety of mutations in a 3D tumor growth assay (3D-TGA). KRAS mutant pancreatic cancer and NRAS mutant melanoma demonstrated broad sensitivity followed closely by KRAS mutant NSCLC and KRAS mutant CRC to IMM-1-104 in the 3D-TGA, and thus are included in Immuneering’s expected Phase 1/2a clinical trials. Key Development Highlights IMM-1-104 IND submission expected this quarter: Immuneering remains on track to file its IND for IMM-1-104 this quarter. IMM-1-104 first patient enrolled expected in Q4 2022: Immuneering expects to enroll the first patient in its Phase 1/2a clinical trial evaluating IMM-1-104 in advanced solid tumors in patients with tumors driven by RAS mutations in the fourth quarter of 2022. Second IND submission for IMM-6-415 expected in 2023: IMM-6-415, the company’s MEK-io program, is currently in IND-enabling studies. Immuneering expects to file an IND application for IMM-6-415 in 2023. IMM-6-415 is a dual-MEK inhibitor that has drug-like properties optimized for immune normalization and may enhance and/or expand clinical responses to checkpoint inhibitors. Second Quarter 2022 Financial Highlights Cash Position: Cash and cash equivalents and marketable securities as of June 30, 2022 were $128.1 million, compared with $150.2 million as of December 31, 2021. Research and Development (R&D) Expenses: R&D expenses for the second quarter ended June 30, 2022 were $8.0 million, compared with $7.0 million for the same period in 2021. The increase in R&D expenses was primarily attributable to higher preclinical costs related to the company’s lead programs and increased personnel to support ongoing research and development activities. General and Administrative (G&A) Expenses: G&A expenses for the second quarter ended June 30, 2022 were $3.7 million, compared with $1.3 million for the same period of 2021. The increase in G&A expenses was primarily attributable to an increase in headcount to support the company’s business and to costs related to operating as a public company. Net Loss: Net loss attributable to common stockholders was $11.5 million, or $0.44 per share, for the second quarter ended June 30, 2022, compared to $8.0 million, or $1.61 per share, for the second quarter ended June 30, 2021. 2022 Financial Guidance Immuneering reiterates full year GAAP operating expenses to be between $55.0 million and $60.0 million including estimated non-cash stock-based compensation. Based on cash, cash equivalents and marketable securities as of June 30, 2022, and current operating plans, the company expects its cash runway to extend into the third quarter of 2024.  About Immuneering Corporation Immuneering aims to improve patient outcomes by advancing a pipeline of product candidates designed to benefit large populations of patients with cancer and other diseases, developed using its translational bioinformatics platform. Immuneering has more than a decade of experience applying translational bioinformatics to generate insights into drug mechanism of action and patient treatment response. Building on this experience, Immuneering's disease-agnostic discovery platform enables the company to create product candidates based on 1) biological insights that are both counterintuitive and deeply rooted in data, and 2) novel chemistry. Immuneering's lead product candidate, IMM-1-104, aims to achieve pan-KRAS/NRAS activity that selectively impacts cancer cells to a greater extent than healthy cells. IMM-1-104 is designed to be a highly selective dual-MEK inhibitor that further disrupts KSR to modulate the signaling dynamics of the MAPK pathway by driving deep cyclic inhibition that deprives tumor cells of the sustained proliferative signaling required for rapid growth, while providing a cadenced, moderate level of signaling sufficient to spare healthy cells. IMM-1-104 is being developed to treat advanced solid tumors in patients harboring RAS mutations, and is translationally guided by Immuneering's proprietary, human-aligned 3D tumor modeling platform combined with patient-aligned bioinformatics. In addition to IMM-1-104, Immuneering is evaluating its MEK-io product candidate, IMM-6-415, in IND-enabling studies, and has five other oncology programs in the discovery stage that are designed to target components of the MAPK or mTOR pathway, as well as two discovery stage neuroscience programs. Forward-Looking Statements This press release includes certain disclosures that contain "forward-looking statements," including, without limitation, statements regarding Immuneering’s expectations regarding the sufficiency of Immuneering’s cash, cash equivalents and marketable securities, its full year GAAP operating expenses for 2022, the treatment potential of IMM-1-104 and IMM-6-415, the timing of submission of the IND and commencement of clinical trials for IMM-1-104 and IMM-6-415, and Immuneering’s ability to advance its pipeline and further diversify its portfolio and make progress towards its longstanding goal of creating better medicines for cancer patients. Forward-looking statements are based on Immuneering’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the risks inherent in oncology and neuroscience drug development, including target discovery, target validation, lead compound identification, lead compound optimization, preclinical studies and clinical trials. These and other risks and uncertainties are described more fully in the section titled "Risk Factors" in Immuneering’s most recent Form 10-Q filed with the U.S. Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Immuneering Corporate Contact: Rebecca Kusko, Ph.D. Immuneering Corporation [email protected] 617-500-8080 Investor Contact: Susan A. NoonanS.A. Noonan [email protected] IMMUNEERING CORPORATION CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) Three Months Ended June 30, Six Months Ended June 30, 2022 2021 2022 2021 Revenue $94,419 $660,040 $278,117 $1,408,240 Cost of revenue 47,933 318,601 138,778 727,763 Gross profit 46,486 341,439 139,339 680,477 Operating expenses Research and development 7,981,075 6,991,965 17,031,517 12,382,985 General and administrative 3,704,143 1,340,398 7,664,112 2,524,422 Amortization of intangible asset 7,317 — 15,420 — Total operating expenses 11,692,535 8,332,363 24,711,049 14,907,407 Loss from operations (11,646,049) (7,990,924) (24,571,710) (14,226,930) Other income (expense) Interest income 142,799 3,259 275,304 9,614 Other expense (24,053) — (127,271) - Net loss $(11,527,303) $(7,987,665) $(24,423,677) $(14,217,316) Net loss per share attributable to common stockholders, basic and diluted $(0.44) $(1.61) $(0.93) $(2.87)Weighted-average common shares outstanding, basic and diluted 26,386,343 4,954,553 26,372,787 4,952,352 Other comprehensive loss: Unrealized losses from marketable securities (14,166) — (132,552) — Comprehensive Loss $(11,541,469) $(7,987,665) $(24,556,229) $(14,217,316) IMMUNEERING CORPORATION CONSOLIDATED BALANCE SHEETS (Unaudited) June 30, 2022 December 31, 2021 Assets Current assets: Cash and cash equivalents $87,937,479 $74,888,145 Marketable securities, current 40,163,875 74,311,203 Accounts receivable 178,425 246,040 Prepaids and other current assets 890,409 2,888,608 Total current assets 129,170,188 152,333,996 Marketable securities, non-current — 996,560 Property and equipment, net 985,007 807,223 Goodwill 6,690,431 6,701,726 Intangible asset 423,580 439,000 Right-of-use assets, net 4,691,157 5,324,198 Other assets 89,579 102,129 Total assets $142,049,942 $166,704,832 Liabilities and Stockholders' Equity Current liabilities: Accounts payable $1,240,241 $1,394,340 Accrued expenses 2,226,687 3,965,447 Other liabilities, current 47,213 — Lease liabilities, current 286,374 274,039 Total current liabilities 3,800,515 5,633,826