Core Insights - Metagenomi, Inc. is set to present new preclinical data on APOC3 at the upcoming Nature Conference, highlighting its collaboration with Ionis Pharmaceuticals [1][2] - The company focuses on developing curative genetic medicines through proprietary genome editing technologies, aiming to address various genetic mutations [2] - Metagenomi's lead program, MGX-001, shows a promising preclinical profile for treating hemophilia A, potentially offering lifelong protection from bleeding events [3] Company Overview - Metagenomi is an in vivo genome editing company that utilizes metagenomics to develop novel editing tools for correcting genetic mutations [2] - The company aims to expand its pipeline by leveraging its genetic editing capabilities for site-specific deletion, integration, and correction [2] Product Development - MGX-001 is designed to provide a one-time treatment for hemophilia A, demonstrating competitive potential against existing treatment options [3] - The company is also exploring treatments for other secreted protein deficiencies and cardiometabolic diseases using its genome integration system [3]

Core Insights - Metagenomi's MGX-001 has shown curative factor VIII (FVIII) activity in non-human primates, indicating its potential as a best-in-class treatment for hemophilia A [1][2] - The company plans to submit investigational new drug (IND) and clinical trial application (CTA) submissions by the end of 2026, following a pre-IND regulatory meeting expected in Q4 2025 [1][2] Study Design and Results - The preclinical study involved administering a single dose of AAV containing a B-domain deleted human FVIII gene to 24 non-human primates across six dose cohorts, with doses ranging from 5.0e11 vg/kg to 4.0e13 vg/kg [2][3] - Therapeutically relevant FVIII activity was achieved in the five highest AAV doses, with average FVIII activity ranging from 49% to 81% at a fixed LNP dose of 0.6 mg/kg [4] - The treatment was well tolerated, with no significant elevation of liver enzymes observed, except for transient elevations in the highest LNP dose [4] Implications for Hemophilia A Treatment - MGX-001 represents a potential paradigm shift in hemophilia A treatment, enabling endogenous production of FVIII and potentially providing a lifelong cure [4][5] - The prevalence of hemophilia A is estimated at up to 26,500 patients in the US and over 500,000 globally, highlighting the significant market potential for effective treatments [5] Company Overview - Metagenomi is focused on in vivo genome editing to create curative genetic medicines, leveraging proprietary technologies to address genetic mutations [6][7] - The company aims to expand its pipeline by developing treatments for other secreted protein deficiencies and cardiometabolic diseases [7]

分组1 - Editas Medicine reported a quarterly loss of $0.28 per share, better than the Zacks Consensus Estimate of a loss of $0.38, and an improvement from a loss of $0.75 per share a year ago, resulting in an earnings surprise of +26.32% [1] - The company posted revenues of $7.54 million for the quarter ended September 2025, exceeding the Zacks Consensus Estimate by 365.62%, compared to revenues of $0.06 million in the same quarter last year [2] - Editas shares have increased approximately 94.5% since the beginning of the year, significantly outperforming the S&P 500's gain of 14.4% [3] 分组2 - The current consensus EPS estimate for the upcoming quarter is -$0.19 on revenues of $5.52 million, and for the current fiscal year, it is -$2.12 on revenues of $15.38 million [7] - The Medical - Biomedical and Genetics industry, to which Editas belongs, is currently ranked in the top 36% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8]

Core Viewpoint - AlphaQuest LLC significantly reduced its stake in Intellia Therapeutics by 57.1% in Q2, indicating a shift in investment strategy towards the company [2] Institutional Holdings - Generali Investments Towarzystwo Funduszy Inwestycyjnych increased its position by 23.5%, now holding 100,000 shares valued at $938,000 after acquiring 19,000 shares [3] - D.A. Davidson & CO. raised its holdings by 108.0%, owning 54,120 shares worth $508,000 after purchasing 28,100 shares [3] - VIRGINIA RETIREMENT SYSTEMS ET Al established a new position valued at approximately $166,000 [3] - Harbour Investments Inc. increased its stake by 27.2%, now owning 6,633 shares valued at $62,000 after buying 1,419 shares [3] - CWM LLC grew its holdings by 22.9%, now owning 18,331 shares valued at $172,000 after acquiring 3,419 shares [3] - Institutional investors currently own 88.77% of Intellia Therapeutics' stock [3] Price Performance - Intellia Therapeutics' stock opened at $12.62, with a market capitalization of $1.35 billion and a PE ratio of -2.69 [4] - The stock has a 12-month low of $5.90 and a high of $28.25, with 50-day and 200-day moving averages at $17.12 and $12.38, respectively [4] Earnings Results - For the latest quarter, Intellia reported an EPS of ($0.99), beating the consensus estimate of ($1.03) by $0.04 [4] - Revenue for the quarter was $14.25 million, exceeding analyst estimates of $12.26 million, and reflecting a year-over-year increase of 104.3% [4] - The company had a negative return on equity of 57.48% and a negative net margin of 908.48% [4] Analyst Ratings - Robert W. Baird set a price target of $9.00 for Intellia Therapeutics [5] - Citigroup maintained a "market outperform" rating, while William Blair downgraded the stock from "outperform" to "market perform" [5] - Chardan Capital reduced its target price from $60.00 to $48.00, maintaining a "buy" rating [5] - The consensus rating for Intellia Therapeutics is "Hold" with an average price target of $23.74 [5] Insider Activity - Director William J. Chase acquired 100,000 shares at an average cost of $10.03, totaling $1,003,000, increasing his position by 288.24% [6] - CAO Michael P. Dube sold 1,871 shares at an average price of $17.38, resulting in a total transaction of $32,517.98, representing a 3.27% decrease in his ownership [7] - Insiders currently own 3.10% of the company's stock [7] Company Overview - Intellia Therapeutics focuses on genome editing and the development of curative therapeutics, with programs including NTLA-2001, NTLA-2002, and NTLA-3001 [8]

Summary of the Genetic Medicines Conference - Editas Medicine Industry Overview - The conference focused on the genome editing industry, highlighting advancements in technologies and programs related to gene editing therapies [1][2] - The discussion included various companies involved in the field, such as Editas Medicine, Arbor Bio, Prime Medicine, Yultec Therapeutics, and GenEdit Bio [2] Key Points and Arguments Company Introductions - **Yultec Therapeutics**: Focuses on in vivo genome editing therapies with five clinical programs, targeting diseases from ultra-rare to chronic cardiovascular conditions [4] - **Editas Medicine**: An in vivo CRISPR gene editing company with a lead program, EDIT401, showing a 90% reduction in LDL cholesterol levels, aiming for clinical trials by the end of 2026 [6] - **GenEdit Bio**: Developing affordable DNA surgeries for genetic diseases, with a focus on eye diseases and CAR T cell therapies [8][10] - **Prime Medicine**: Specializes in prime editing technology, targeting liver diseases and working on various genetic disorders [11][12] - **Arbor Bio**: Focuses on in vivo genome editing with a broad platform of editing approaches, including programs targeting the CNS [13][14] Technological Advancements - The genome editing field has expanded to include various technologies such as nuclease editing, base editing, and prime editing, with discussions on how these technologies will coexist and evolve [15][16] - The importance of product differentiation and the need for effective delivery systems were emphasized, with a consensus that delivery is as critical as the editing technology itself [28][29] Lessons Learned from Initial Therapies - The technical success rates from preclinical to clinical stages have been unprecedented, highlighting the rapid advancement of gene editing technologies [25][26] - The need for companies to focus on differentiation and the commercial viability of one-time therapies was discussed, with an emphasis on the economic arguments for such treatments [27][46] Commercial Viability and Market Considerations - The commercial case for one-time gene editing therapies was debated, with examples of partnerships and the importance of understanding the rare disease market [50][51] - The potential for gene editing therapies to transform patient care was highlighted, with a focus on the need for effective pricing strategies and understanding the current standard of care [55][61] - The discussion included the importance of low-cost delivery systems to enhance commercial viability and patient access to therapies [59][61] Future Outlook - The panelists expressed optimism about the future of gene editing, predicting multiple approvals and launches in the coming years, alongside an evolving payer landscape that may better accommodate these therapies [68] Additional Important Insights - The variability of clinical responses in edited patients is narrower compared to other therapeutic modalities, which may lead to higher responder rates and lower treatment costs [53][54] - The need for companies to adapt their business models and focus on specific commercial opportunities was emphasized, indicating a more disciplined approach in the industry [65][66] This summary encapsulates the key discussions and insights from the conference, providing a comprehensive overview of the current state and future potential of the genome editing industry.

Group 1 - The article highlights nine research papers published in the journal Cell, with seven authored by Chinese scholars, covering various topics in biology and genetics [2] - A study on the mechano-resistance mechanism in skin adaptation to terrestrial locomotion was published, revealing insights into the SLURP1 gene and its implications for palmoplantar keratoderma [4][7] - A new programmable chromosome engineering technology (PCE) was introduced, enabling precise manipulation of DNA at kilobase to megabase scales, which could enhance crop traits and genetic disease treatments [9][12] Group 2 - Research on composite transposons revealed their role as enhancers in cell fate regulation, highlighting the significance of bivalent chromatin in hematopoietic differentiation and aging [14][17] - A study demonstrated that vagal nerve blockade can alleviate cancer-associated cachexia in mouse models, restoring appetite and extending survival [19][22] - A novel model of mouse embryogenesis was developed using chemically induced embryonic founder cells, providing new tools for studying organ development and regenerative medicine [23][26] Group 3 - A genetic history study of the Southern Caucasus revealed 5,000 years of genetic continuity despite high population mobility, based on ancient DNA analysis from archaeological sites [28][31] - An AI-assisted pipeline was created to identify gut microbial bile acid metabolic enzymes, expanding knowledge of microbial metabolism and its implications for gut health [33][36]

Company Performance - Immunome, Inc. reported a quarterly loss of $0.5 per share, which was better than the Zacks Consensus Estimate of a loss of $0.52, representing an earnings surprise of +3.85% [1] - The company posted revenues of $4.02 million for the quarter ended June 2025, exceeding the Zacks Consensus Estimate by 62.88%, compared to revenues of $2.36 million in the same quarter last year [2] - Over the last four quarters, Immunome has surpassed consensus EPS estimates two times and topped consensus revenue estimates twice [2] Future Outlook - The sustainability of Immunome's stock price movement will depend on management's commentary during the earnings call and future earnings expectations [3] - The current consensus EPS estimate for the upcoming quarter is -$0.56 on revenues of $2.48 million, and for the current fiscal year, it is -$2.21 on revenues of $5.47 million [7] - The estimate revisions trend for Immunome was unfavorable ahead of the earnings release, resulting in a Zacks Rank 4 (Sell) for the stock, indicating expected underperformance in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Immunome belongs, is currently ranked in the bottom 42% of over 250 Zacks industries, suggesting that stocks in the top 50% outperform those in the bottom 50% by more than 2 to 1 [8] - Another company in the same industry, Precision BioSciences, is expected to report a quarterly loss of $0.09 per share, reflecting a year-over-year change of -102.6%, with revenues anticipated to be $13.7 million, down 72.6% from the previous year [9][10]

Core Insights - Editas Medicine reported a quarterly loss of $0.43 per share, better than the Zacks Consensus Estimate of a loss of $0.51, and an improvement from a loss of $0.76 per share a year ago, resulting in an earnings surprise of 15.69% [1] - The company generated revenues of $4.66 million for the quarter ended March 2025, exceeding the Zacks Consensus Estimate by 385.21%, compared to $1.14 million in the same quarter last year [2] - Editas shares have increased by approximately 14.2% since the beginning of the year, contrasting with a -3.8% decline in the S&P 500 [3] Earnings Outlook - The current consensus EPS estimate for the upcoming quarter is -$0.40 on revenues of $0.98 million, and for the current fiscal year, it is -$1.53 on revenues of $6.74 million [7] - The estimate revisions trend for Editas is currently favorable, leading to a Zacks Rank 2 (Buy) for the stock, indicating expected outperformance in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Editas belongs, is currently ranked in the top 34% of over 250 Zacks industries, suggesting a positive outlook for stocks within this sector [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5]

Core Insights - Metagenomi, Inc. reported significant advancements in its hemophilia A program, demonstrating sustained Factor VIII (FVIII) activity in nonhuman primate studies for over 16 months, supporting the durability of its gene editing therapy [1][7] - The company is well-capitalized with $248.3 million in cash and equivalents as of December 31, 2024, providing a cash runway anticipated to support operations into 2027 [1][10] - Metagenomi plans to submit its first Investigational New Drug (IND) application for hemophilia A in 2026 and aims to nominate one to two development candidates from its Wave 1 Ionis collaboration programs in 2025 [2][14] Hemophilia A Program - The company has declared MGX-001 as a development candidate for hemophilia A, which includes a bioengineered FVIII construct with higher activity levels compared to the wild type [7] - An oral presentation at the American Society of Hematology (ASH) highlighted the sustained FVIII activity in nonhuman primate studies, reinforcing the potential of MGX-001 [7] - Plans are in place to release final FVIII durability and related preclinical study data in the first half of 2025 [14] Secreted Protein Deficiencies - Metagenomi has identified targets for wholly-owned therapeutic programs leveraging the gene integration approach used in MGX-001, achieving in vivo proof-of-concept in rodents across three secreted protein targets [4] - The company plans to demonstrate nonhuman primate proof-of-concept for its lead secreted protein deficiency target in 2025 and nominate a development candidate in 2026 [9] Cardiometabolic Indications - The company advanced four Wave 1 Ionis collaboration programs to lead optimization, including targets for transthyretin amyloidosis and refractory hypertension, achieving in vivo proof-of-concept in rodents [8] - Demonstrated a 95% protein knockdown in spontaneous hypertensive rats, showcasing the progress made in the collaboration [8] Financial Performance - For the full year ended December 31, 2024, Metagenomi reported research and development expenses of $109.2 million, an increase from $94.4 million in 2023 [10] - General and administrative expenses rose to $32.0 million in 2024 from $28.8 million in 2023 [11] - The net loss for 2024 was $78.1 million, compared to a net loss of $68.3 million in 2023, with a net loss per share of $2.36 [20]

Table of Contents As filed with the Securities and Exchange Commission on January 5, 2024. Registration No. 333– UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Metagenomi Technologies, LLC (to be succeeded by Metagenomi, Inc. in the reorganization) (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Delaware 2836 83-2735153 (Primary Standard Industrial C ...