AACR April 2025 April 29, 2025 • Targeting SMARCA2-Dependent Tumors with FHD-909 (LY4050784) • Advancing Multiple Additional First-in-Class Anticancer Agents Forward Looking Statements This presentation contains forward-looking statements that are based on management's beliefs and assumptions and on information currently available to management. All statements other than statements of historical facts contained in this presentation are forward- looking statements. In some cases, you can identify forward-loo ...

- FHD-909 (LY4050784) advancing in Phase 1 trial in SMARCA4 (BRG1) mutated cancers, with non-small cell lung cancer (NSCLC) as the primary target population - Preclinical synergistic anti-tumor activity of FHD-909 in combination with pembrolizumab and KRAS inhibitors supports clinical exploration - Selective CBP degrader combination approaches show promise in preclinical ER+ breast cancer models - Further preclinical characterization of the therapeutic potential of the Selective EP300 degrader program to t ...

Core Insights - Etiome has launched an AI-powered platform called Temporal Biodynamics™, which is the first end-to-end solution designed to detect diseases and preempt their progression before they become severe [1][7] - The company has received an initial investment of $50 million from Flagship Pioneering to develop this platform and its initial pipeline of preemptive medicines [1][8] - Etiome aims to shift healthcare practices from reactive to preemptive, focusing on serious and progressive diseases such as metabolic, neurodegenerative, pre-cancerous, and autoimmune diseases [3][4] Company Overview - Etiome was founded as part of Flagship Pioneering's Preemptive Health and Medicine Initiative, which seeks to improve health outcomes by preventing diseases before they manifest [1][6] - The company utilizes a combination of multimodal population-level data and single-cell omics, enhanced by artificial intelligence, to gain insights into disease progression [2][4] - Etiome's founding team includes experts in biology, omics, and AI, with leadership from notable figures such as Avak Kahvejian and Scott Lipnick [4][5] Technology and Innovation - The Temporal Biodynamics™ platform allows for the accurate characterization of disease biostages and the identification of stage-specific biomarkers, known as Biostage Markers [2][3] - The platform's proprietary phenotype-aware AI isolates temporal shifts in genes and proteins, enabling the development of targeted medicines that can alter disease progression [2][3] - Etiome's approach is designed to ensure that patients receive the right treatment at the right time, potentially slowing, stopping, or reversing disease progression [2][3] Market Focus - Etiome is targeting large populations affected by serious diseases with clear unmet needs, aiming to reduce morbidity and healthcare costs while extending healthy lifespans [3][4] - The company envisions a future where preemptive interventions can prevent suffering and save lives, thereby lowering overall healthcare expenses [4][6]

Core Insights - Foghorn Therapeutics is set to present new preclinical combination data for FHD-909, a potential first-in-class selective SMARCA2 inhibitor targeting non-small cell lung cancer (NSCLC) [1][2] - The company will also share updates on its Selective CBP and EP300 degrader programs, along with an overview of the Selective ARID1B degrader program during a virtual investor event on April 29, 2025 [1][2][3] Company Overview - FHD-909 (LY4050784) is an allosteric, orally available small molecule that selectively inhibits the ATPase activity of SMARCA2, showing significant anti-tumor activity in preclinical studies involving SMARCA4 mutant lung tumor models [4] - Foghorn Therapeutics focuses on developing a novel class of medicines that target genetically determined dependencies within the chromatin regulatory system, utilizing its Gene Traffic Control platform to identify and validate drug targets [5]

Core Insights - Foghorn Therapeutics is advancing FHD-909 (LY4050784), a first-in-class selective SMARCA2 inhibitor, in an ongoing Phase 1 trial targeting SMARCA4 mutated cancers, primarily focusing on non-small cell lung cancer (NSCLC) [1][2] - New preclinical data will be presented at the 2025 AACR Annual Meeting, showcasing the potential of FHD-909 in combination with chemotherapy, pembrolizumab, and KRAS inhibitors [1][2] - The company is also presenting preclinical data on its Selective CBP and EP300 degrader programs, which have demonstrated strong anti-tumor activities [2] FHD-909 Details - FHD-909 is an allosteric, orally available small molecule that selectively inhibits the ATPase activity of SMARCA2 over SMARCA4, crucial for the BAF complex's function [6] - Preclinical studies indicate that tumors with SMARCA4 mutations depend on SMARCA2 for their BAF function, highlighting the therapeutic potential of FHD-909 [6] Presentation Information - An oral presentation titled "LY4050784, a selective inhibitor of SMARCA2, demonstrates synergistic activity in combinations with pembrolizumab or KRAS inhibitors" will take place on April 28, 2025 [3] - Poster presentations will cover the Phase 1 trial design for FHD-909 and preclinical data for the Selective CBP and EP300 degrader programs [4][5] Company Overview - Foghorn Therapeutics is focused on developing a novel class of medicines that target genetically determined dependencies within the chromatin regulatory system [7] - The company utilizes its Gene Traffic Control platform to identify and validate potential drug targets, with multiple oncology product candidates in development [7]

Core Insights - Lila Sciences is developing the world's first scientific superintelligence platform and fully autonomous labs aimed at accelerating discovery in life, chemical, and materials sciences [1][8] - The company has successfully raised $200 million in seed financing to support the development of its AI platform and infrastructure for rapid scaling [2][8] - Lila's mission is to leverage AI to enhance the scientific method, enabling the design and execution of experiments at unprecedented scales [3][5] Company Overview - Lila Sciences was founded in 2023 within Flagship Pioneering's labs and aims to apply AI across all aspects of the scientific method [1][8] - The company is led by a team with diverse expertise in AI, security, commercial strategy, and various scientific fields, including renowned geneticist George Church as Chief Scientist [7][8] Technological Advancements - The Lila platform combines generative AI with scalable autonomous science units to optimize experimentation across scientific domains [3][4] - The platform has demonstrated superior performance in various areas, including: - Large language models (LLMs) with advanced reasoning capabilities on scientific problems [6] - Generation of optimal genetic medicine constructs that outperform existing therapeutics [6] - Discovery of novel antibodies and catalysts for green hydrogen production [6] - Design of new materials for industrial-scale carbon capture [6] Strategic Partnerships - Lila's platform will be open to partnerships across life and material sciences industries to foster solutions in human health and sustainability [4][5]

Company Performance - Foghorn Therapeutics Inc. reported a quarterly loss of $0.30 per share, slightly worse than the Zacks Consensus Estimate of a loss of $0.29, but an improvement from a loss of $0.57 per share a year ago, indicating a year-over-year improvement [1] - The company posted revenues of $2.86 million for the quarter ended December 2024, missing the Zacks Consensus Estimate by 75.63%, and down from $5.77 million in the same quarter last year [2] - Over the last four quarters, Foghorn Therapeutics has surpassed consensus EPS estimates two times and topped consensus revenue estimates only once [2] Stock Outlook - The stock has lost approximately 1.1% since the beginning of the year, compared to a decline of 0.7% for the S&P 500 [3] - The current consensus EPS estimate for the upcoming quarter is -$0.28 on revenues of $7.4 million, and for the current fiscal year, it is -$1.06 on revenues of $37.62 million [7] - The estimate revisions trend for Foghorn Therapeutics is mixed, resulting in a Zacks Rank 3 (Hold), suggesting the stock is expected to perform in line with the market in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Foghorn Therapeutics belongs, is currently in the top 27% of over 250 Zacks industries, indicating a favorable industry outlook [8] - Empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can impact investor sentiment and stock performance [5]

Financial Performance - The company reported net losses of $98.4 million for the year ended December 31, 2023, and an accumulated deficit of $558.2 million as of December 31, 2024 [346]. - The net loss for the year ended December 31, 2024, was $86.6 million, an improvement of $11.8 million compared to a net loss of $98.4 million in 2023 [375]. - For the year ended December 31, 2024, the company reported a net loss of $86.6 million, compared to a net loss of $98.4 million for 2023, indicating a 12.5% improvement in losses year-over-year [421]. - The company experienced a net cash used in operating activities of $100.4 million for 2024, a decrease from $118.1 million in 2023, reflecting a 15% reduction in cash outflows [421]. Revenue and Collaboration Agreements - The company has not generated any revenue from product sales and does not expect to do so in the near future [351]. - The company recognized total deferred revenue of $337.8 million related to the Lilly Collaboration Agreement, including a $300.0 million upfront payment [357]. - The company recognized $22.6 million and $17.1 million of revenue under the Lilly Collaboration Agreement for the years ended December 31, 2024 and 2023, respectively [357]. - Collaboration revenue for the year ended December 31, 2024, was $22.6 million, down from $34.2 million in 2023, a decrease of $11.6 million attributed to the termination of the Merck Collaboration Agreement [376]. - The Merck Collaboration Agreement was terminated effective November 7, 2023, resulting in the recognition of all remaining deferred revenue [500]. - The Company recorded $17.0 million of revenue under the Merck Collaboration Agreement for the year ended December 31, 2023 [499]. Operating Expenses - The company expects to incur significant operating losses and increasing expenses for at least the next several years as it advances its product candidates [346]. - Total operating expenses decreased to $125.3 million in 2024 from $142.1 million in 2023, a reduction of $16.8 million [375]. - Research and development expenses were $94.5 million for the year ended December 31, 2024, compared to $109.7 million in 2023, reflecting a decrease of $15.2 million [377]. - General and administrative expenses decreased to $28.4 million in 2024 from $32.4 million in 2023, a reduction of $4.0 million [378]. - The company expects substantial increases in expenses related to ongoing clinical activities, including the Phase 1 clinical trial of FHD-909 partnered with Lilly [393]. Cash and Financing Activities - As of December 31, 2024, the company had cash, cash equivalents, and marketable securities totaling $243.7 million [385]. - The company expects its cash, cash equivalents, and marketable securities to be sufficient to fund its operating expenses and capital expenditures for at least the next 12 months [421]. - The company raised net proceeds of $102.8 million from a public offering that closed on May 22, 2024, selling 12,743,039 shares at a public offering price of $5.51 per share [420]. - The company reported a net cash provided by financing activities of $105.4 million in 2024, a significant increase compared to $1.8 million in 2023 [421]. Impairments and Taxation - The company recorded a non-cash impairment of long-lived assets of $2.4 million in 2024, with no impairment charges in 2023 [382]. - The provision for income taxes was $0 in 2024, compared to $4.2 million in 2023, primarily due to the recognition of taxable income from the Lilly Collaboration Agreement [384]. - The valuation allowance against net deferred tax assets increased by $23.5 million and $31.1 million for the years ended December 31, 2024 and 2023, respectively [505]. - The Company has established a full valuation allowance against net deferred tax assets due to uncertainty in realizing benefits from these items [504]. Research and Development - The company has a pipeline that has the potential to help more than 500,000 cancer patients [339]. - The company incurred research and development expenses, which include salaries, bonuses, and external vendor costs, reflecting its commitment to innovation and development [446]. - Personnel expenses for research and development decreased to $22.5 million in 2024 from $29.5 million in 2023, a reduction of 23.6% [524]. Marketable Securities and Assets - As of December 31, 2024, the company reported total available for sale marketable securities of $188.293 million, with U.S. treasury notes valued at $35.394 million and corporate notes and bonds totaling $107.905 million [467]. - The company's property and equipment, net, increased to $9.964 million in 2024 from $12.956 million in 2023, with a depreciation and amortization expense of $3.1 million for 2024 [469]. - Total liabilities decreased from $363.1 million in 2023 to $329.5 million in 2024, while stockholders' deficit improved from $(77.2) million to $(45.5) million [408]. Stock-Based Compensation - The company incurred stock-based compensation expense of $11.9 million in 2024, down from $16.2 million in 2023, reflecting a 26.5% decrease [421]. - The weighted average grant-date fair value of stock options granted was $3.14 per share in 2024, down from $6.12 per share in 2023 [484]. - Total unrecognized compensation cost related to unvested options was $16.3 million as of December 31, 2024, expected to be recognized over a weighted average period of 2.1 years [485].

Oncology Programs - Foghorn is advancing multiple programs targeting SMARCA4 mutant cancers, with FHD-909 (Selective SMARCA2 Inhibitor) currently in Phase 1 trial[28]. - The potential market for Foghorn's therapies includes up to 10% of Non-Small Cell Lung Cancer (NSCLC) and up to 5% of all solid tumors[33]. - The company is developing a pipeline of first-in-class precision therapeutics with potential for broad application in oncology[19]. - Foghorn has progressed multiple programs against challenging targets, including selective inhibitors and degraders for various cancers[8]. - FHD-909 monotherapy demonstrated a 96% tumor growth inhibition (TGI) in A549 and RERF-LC-Al mutant NSCLC models[43]. - In vivo studies showed FHD-909 resulted in significant tumor volume reduction in H2126 and H1793 SMARCA4 mutant NSCLC models[41][46]. - The selective SMARCA2 degrader achieved complete SMARCA2 degradation and cell growth inhibition in vitro[51]. - The selective CBP protein degrader targets EP300 mutated cancers, with an IND planned for 2026[61]. - Selective EP300 degradation resulted in significant anti-tumor activity across multiple hematological malignancies[74]. - Foghorn's selective EP300 degrader has demonstrated complete tumor regression in multiple myeloma models, showing improved therapeutic windows with no thrombocytopenia[82][83]. - The ARID1B program targets ARID1A mutated cancers, with over 175,000 addressable patients per year in the U.S., EU5, and Japan[89]. - The selective ARID1B degrader program is expected to provide an update in 2025, with degradation already achieved[89][98]. - The selective SMARCA2 inhibitor, FHD-909, is currently in Phase 1 trials, partnered with Lilly[102]. Financials and Collaborations - Foghorn's collaboration with Lilly includes a 50/50 global R&D cost share and U.S. economics in the low double-digit range, escalating into the teens[28]. - The collaboration with Lilly includes a $380 million upfront payment for two programs, with a 50/50 economic split in the U.S.[106][107]. - Foghorn has $243.8 million in cash and equivalents as of December 31, 2024, providing a cash runway into 2027[102]. Research and Development - Foghorn's Gene Traffic Control® Platform is designed to deliver integrated, scalable, and efficient therapeutics[10]. - Foghorn's platform has potential for therapeutic area expansion beyond oncology, including immunology and inflammation[24]. - The company anticipates multiple near-term value inflection points through 2026, including IND and Phase 1 initiations for several programs[21]. - The company is advancing multiple preclinical assets, including selective SMARCA2, CBP, EP300, and ARID1B degraders towards INDs[102]. - Foghorn's chromatin biology platform potentially impacts around 2.5 million patients, addressing more than 500,000 patients with its current pipeline[100]. - The company has identified multiple ARID1B binders with nanomolar affinity and selectivity, enhancing its drug development capabilities[90][91]. Clinical Trials and Data - FHD-909 is currently in a trial design that includes dose escalation and expansion, focusing on SMARCA4 mutated tumors[49]. - The company plans to present preclinical combination data of FHD-909 with pembrolizumab at the Annual Meeting on April 20[50].

Core Insights - Foghorn Therapeutics is advancing its clinical pipeline, particularly focusing on FHD-909, a first-in-class oral selective SMARCA2 inhibitor targeting SMARCA4 mutated cancers, with non-small cell lung cancer (NSCLC) as the primary target population [1][2][5] - The company has achieved selective degradation of ARID1B and plans to provide updates on this program in 2025 [1][3][14] - Foghorn's financial position remains strong, with cash, cash equivalents, and marketable securities totaling $243.7 million as of December 31, 2024, providing a cash runway into 2027 [1][21] Clinical Development - The Phase 1 trial for FHD-909 is currently enrolling patients, with the first patient dosed in October 2024 [3][5] - Preclinical combination data for FHD-909 with pembrolizumab and KRAS inhibitors will be presented at the AACR Annual Meeting in April 2025 [1][5] - The Selective CBP and EP300 degrader programs are progressing towards Investigational New Drug (IND) applications, with additional preclinical data to be shared at the AACR [2][12][13] Financial Performance - Collaboration revenues decreased to $22.6 million for the year ended December 31, 2024, down from $34.2 million in 2023 [11][23] - Research and development expenses were $94.5 million in 2024, a decrease from $109.7 million in 2023, primarily due to reduced headcount [21][23] - The net loss for 2024 was $86.6 million, compared to a net loss of $98.4 million in 2023, indicating improved financial performance [21][23] Strategic Collaborations - Foghorn is engaged in a strategic collaboration with Lilly, which includes a 50/50 co-development and co-commercialization agreement for the selective SMARCA2 oncology program [6] - The collaboration also encompasses agreements for a selective inhibitor and a selective degrader, along with three discovery programs from Foghorn's Gene Traffic Control platform [6] Research and Development Focus - FHD-909 targets SMARCA4 mutations, which are present in up to 10% of NSCLC cases, and aims to induce tumor death while sparing healthy cells [5][16] - The Selective ARID1B degrader program targets ARID1A-mutated cancers, with updates expected in 2025 [9][14] - The company continues to invest in its chromatin biology and degrader platform, focusing on novel ligases and oral delivery systems [10]