Metagenomi Therapeutics, Inc 8-K, filed Jan 12, 2026
Metagenomi Therapeutics, Inc. (MGX)
About this 8-K
Metagenomi Therapeutics, Inc filed this 8-K on January 12, 2026.
Items reported
- Item 5.03: Charter or bylaw amendment, or fiscal year change
- Item 7.01: Regulation FD disclosure
- Item 9.01: Financial statements and exhibits
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): |
(Exact name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction |
(Commission File Number) |
(IRS Employer |
||
|
|
|
|
|
|
||||
|
||||
(Address of Principal Executive Offices) |
|
(Zip Code) |
||
Registrant’s Telephone Number, Including Area Code: |
|
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
|
|
Trading |
|
|
|
|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 5.03 Amendments to Articles of Incorporation or Bylaws; Change in Fiscal Year.
Metagenomi Therapeutics, Inc. (the “Company”) filed a certificate of amendment to its Amended and Restated Certificate of Incorporation (the “Certificate of Incorporation”), solely to change the Company’s name from “Metagenomi, Inc.” to “Metagenomi Therapeutics, Inc.” (the “Name Change”), which became effective at 12:01 a.m. Pacific Time on January 12, 2026. The Board of Directors of the Company (the “Board”) approved the Name Change pursuant to Section 242 of the General Corporation Law of the State of Delaware. Pursuant to Delaware law, a stockholder vote was not necessary to effectuate the Name Change and it does not affect the rights of the Company’s stockholders. A copy of the Certificate of Amendment is filed as Exhibit 3.1 hereto and is incorporated herein by reference.
In connection with the Name Change, the Company’s Board also amended and restated its Amended and Restated Bylaws (as amended, the “Second Amended and Restated Bylaws”), effective on January 12, 2026, solely to reflect the Name Change. No other changes were made to the Second Amended and Restated Bylaws. A copy of the Second Amended and Restated Bylaws reflecting the Name Change is filed as Exhibit 3.2 hereto and is incorporated herein by reference.
The Company’s common stock will continue to trade on The Nasdaq Global Select Market under the symbol “MGX”. The CUSIP number for the Company’s common stock will not change in connection with the Name Change.
Item 7.01 Regulation FD Disclosure.
Press Release
On January 12, 2026, the Company issued a press release announcing the Name Change and additional business updates. A copy of the press release is being furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.
Corporate Presentation
A copy of the Company’s January 2026 corporate presentation is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
The information contained in this Item 7.01 (including Exhibits 99.1 and 99.2) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section and shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. |
|
Description |
3.1 |
|
|
3.2 |
|
Second Amended and Restated Bylaws of Metagenomi Therapeutics, Inc. |
99.1 |
|
Press Release Issued by Metagenomi Therapeutics, Inc. on January 12, 2026 |
99.2 |
|
Corporate Presentation of Metagenomi Therapeutics, Inc. dated January 2026 |
104 |
|
Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|
|
|
Metagenomi Therapeutics, Inc. |
|
|
|
|
Date: |
January 12, 2026 |
By: |
/s/ Jian Irish |
|
|
|
Jian Irish, Ph.D., M.B.A. |
Exhibit 3.1
CERTIFICATE OF AMENDMENT
TO THE
AMENDED AND RESTATED CERTIFICATE OF INCORPORATION
OF
METAGENOMI, INC.
Metagenomi, Inc., a corporation organized and existing under the laws of the State of Delaware (the “Corporation”), hereby certifies as follows:
1. Article I of the Amended and Restated Certificate of Incorporation of the Corporation is hereby amended and restated in its entirety to read as follows:
“The name of the Corporation is Metagenomi Therapeutics, Inc.”
2. The foregoing amendment was duly adopted in accordance with the provisions of Section 242 of the General Corporation Law of the State of Delaware.
3. This Certificate of Amendment shall be effective as of 12:01 a.m. Pacific Time on January 12, 2026.
IN WITNESS WHEREOF, the undersigned officer of the Corporation has executed this Certificate of Amendment to the Amended and Restated Certificate of Incorporation as of January 9, 2026.
By:_/s/ Jian Irish__________________
Name: Jian Irish, Ph.D., M.B.A
Title: President and Chief Executive Officer
Exhibit 3.2
SECOND AMENDED AND RESTATED
BYLAWS
OF
METAGENOMI THERAPEUTICS, INC.
(the “Corporation”)
Stockholders
2
3
4
5
For purposes of this Article I, the term “Proposing Person” shall mean the following persons: (i) the stockholder of record providing the notice of nominations or business proposed to be brought before a stockholders’ meeting and (ii) the beneficial owner(s), if different, on whose behalf the nominations or business proposed to be brought before a stockholders’ meeting is made. For purposes of this Section 2, the term “Synthetic Equity Interest” shall mean any transaction, agreement or arrangement (or series of transactions, agreements or arrangements), including, without limitation, any derivative, swap, hedge, repurchase or so-called “stock borrowing” or securities lending agreement or arrangement, the purpose or effect of which is to, directly or indirectly: (a) give a person or entity economic benefit and/or risk similar to ownership of shares of any class or series of capital stock of the Corporation, in whole or in part, including due to the fact that such transaction, agreement or arrangement provides, directly or indirectly, the opportunity to profit, or share in any profit, or avoid a loss from any increase or decrease in the value of any shares of any class or series of capital stock of the Corporation, (b) mitigate loss to, reduce the economic risk of, or manage the risk of share price changes for, any person or entity with respect to any shares of any class or series of capital stock of the Corporation, (c) otherwise provide in any manner the opportunity to profit, or share in any profit, or avoid a loss from any decrease in the value of any shares of any class or series of capital stock of the Corporation or (d) increase or decrease the voting power of any person or entity with respect to any shares of any class or series of capital stock of the Corporation.
6
7
(5) Notwithstanding the foregoing provisions of this Bylaw, a stockholder shall also comply with all applicable requirements of the Exchange Act and the rules and regulations thereunder, including, but not limited to, Rule 14a-19 of the Exchange Act, with respect to the matters set forth in this Bylaw. If a stockholder fails to comply with any applicable requirements of the Exchange Act, including, but not limited to, Rule 14a-19 promulgated thereunder, such stockholder’s proposed nomination or proposed business shall be deemed to have not been made in compliance with this Bylaw and shall be disregarded.
(6) Further notwithstanding the foregoing provisions of this Bylaw, unless otherwise required by law, (i) no Proposing Person shall solicit proxies in support of director nominees other than the Corporation’s nominees unless such Proposing Person has complied with Rule 14a-19 promulgated under the Exchange Act in connection with the solicitation of such proxies, including the provision to the Corporation of notices required thereunder with timely notice and (ii) if any Proposing Person (A) provides notice pursuant to Rule 14a-19(b) promulgated under the Exchange Act, (B) subsequently fails to comply with the requirements of Rule 14a-19(a)(2) or Rule 14a-19(a)(3) promulgated under the Exchange Act, including the provision to the Corporation of
8
notices required thereunder with timely notice and (C) no other Proposing Person has provided notice pursuant to, and in compliance with, Rule 14a-19 under the Exchange Act that it intends to solicit proxies in support of the election of such proposed nominee in accordance with Rule 14a-19(b) under the Exchange Act, then such proposed nominee shall be disqualified from nomination, the Corporation shall disregard the nomination of such proposed nominee and no vote on the election of such proposed nominee shall occur. Upon request by the Corporation, if any Proposing Person provides notice pursuant to Rule 14a-19(b) promulgated under the Exchange Act, such Proposing Person shall deliver to the Corporation, no later than five (5) business days prior to the applicable meeting date, reasonable evidence that it has met the requirements of Rule 14a-19(a)(3) promulgated under the Exchange Act.
(7) The number of nominees a stockholder may nominate for election at the Annual Meeting (or in the case of a stockholder giving the notice on behalf of a beneficial owner, the number of nominees a stockholder may nominate for election at the Annual Meeting on behalf of such beneficial owner) shall not exceed the number of directors to be elected at such Annual Meeting.
9
10
11
12
Directors
13
14
Officers
15
16
17
Capital Stock
18
19
Indemnification
20
21
22
23
24
25
Miscellaneous Provisions
26
27
Effective as of January 12, 2026.
28
Exhibit 99.1
Metagenomi Announces Corporate Name Change to Metagenomi Therapeutics, Inc. and Highlights Recent Business Milestones and 2026 Corporate Outlook
New name reflects the Company’s strategic evolution focused on later-stage preclinical assets leveraging its most advanced, signature gene-editing capabilities
Pre-IND meeting held in 4Q 2025 following MGX-001 preclinical data demonstrating curative FVIII activity in non-human primates (NHPs); MGX-001 on track for IND/CTA submissions in 4Q 2026
Cash runway anticipated through 4Q 2027
EMERYVILLE, Calif., January 12, 2025 (GLOBE NEWSWIRE) – Metagenomi Therapeutics, Inc. (Nasdaq: MGX) (the “Company”), an in vivo genome editing company capitalizing on its proprietary technologies to create curative genetic medicines for patients, today announced that it has completed its corporate name change to Metagenomi Therapeutics, Inc. to reflect the Company’s strategic evolution focused on driving forward the Company’s lead program in hemophilia A and other compelling programs and technologies that have the highest probability of near-term success. The Company also provided a summary of milestones achieved across its therapeutic development programs and technology platforms in 2025 as well as anticipated milestones in 2026.
“I am excited by the direction we are headed as we enter 2026, led by MGX-001, our wholly owned hemophilia A program. MGX-001 recently demonstrated curative factor VIII (FVIII) activity in non-human primates with clear dose-dependent activity and no identifiable off-target editing, representing a therapy with best-in-class treatment potential,” said Jian Irish, Ph.D., M.B.A., President and Chief Executive Officer of the Company. “The study informs our anticipated clinical dose regimen and based on recent regulatory engagement, we feel well positioned to file our IND/CTA submissions before year end 2026 and initiate a first-in-human study in 2027. The recent steps we took to strategically reprioritize our pipeline provide us a strengthened balance sheet with runway anticipated into the fourth quarter of 2027. Looking ahead, our new corporate name represents our focus and commitment to delivering curative genetic medicines to patients and accelerating development of these medicines by strategically deploying our most advanced, proprietary technologies built on our foundational science of metagenomics.”
Recent Pipeline Advancement and Corporate Updates
MGX-001 - Hemophilia A Program:
2025 Achievements
2026 Anticipated Milestones
Secreted Protein Deficiencies
2025 Achievements
Cardiometabolic Programs:
2025 Achievements
Corporate Highlights
About Metagenomi Therapeutics, Inc.
Metagenomi Therapeutics, Inc. is an in vivo genome editing company capitalizing on its proprietary technologies to create curative genetic medicines for patients. The Company was founded on the science of metagenomics, the study of genetic materials recovered from the natural environment, to discover and develop a suite of novel editing tools potentially capable of correcting any type of genetic mutation found anywhere in the human genome. The Company focuses on high value programs in disease indications with well-understood biology and clearly defined clinical development and regulatory pathways. Going forward, the Company intends to continue to expand its pipeline by leveraging its proprietary genetic editing capabilities in site specific deletion, integration and correction.
MGX-001, the Company’s lead, wholly-owned development program in hemophilia A, has demonstrated a preclinical profile potentially competitive with best-in-class treatment options, including targeted genome editing and durable gene expression in a one-time treatment. MGX-001 is designed to provide curative, life-long protection from bleeding events and joint damage in adults and children with hemophilia A. The Company is also currently pursuing other secreted protein deficiencies leveraging the MGX-001 site-specific genome integration system and partnered assets targeting cardiometabolic diseases. For more information, please visit https://metagenomi.co.
Cautionary Note Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions include, but are not limited to, any statements relating to our product development programs, including the timing of and our ability to conduct IND-enabling studies and make regulatory filings such as INDs, expectations regarding MGX-001 including the preclinical profile being potentially competitive with best-in-class treatment options and timing to submit the IND/CTA package, statements regarding the Company’s plans to prioritize its preclinical pipeline and potential for value creation and sustainable growth, statements regarding upcoming milestones including the nomination of development candidates, statements concerning the potential of therapies and product candidates, statements concerning the impact of the organizational restructuring, statements concerning our anticipated cash runway, and any other statements that are not historical facts. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition, and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of IND submissions and starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation and the current regulatory environment; patent and intellectual property matters; competition; the volatility of capital markets and other adverse macroeconomic factors; as well as other risks described in “Risk Factors,” in our most recent Form 10-K and other risk factors set forth from time to time in our filings with the Securities and Exchange Commission made pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.
Investor Contact:
Stephen Jasper
Gilmartin Group
stephen@gilmartinir.com
Corporate Presentation January 2026
This presentation includes forward-looking statements, including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation are forward looking statements, including statements regarding our cash runway, strategy and plans, industry environment, potential growth opportunities, and the therapeutic potential of our programs. The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “design,” “expect,” “could,” “plan,” “potential,” “predict,” “seek,” “should,” “would,” or the negative version of these words and similar expressions are intended to identify forward-looking statements. We have based these forward-looking statements on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, strategy, short- and long-term business operations and objectives, and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including but not limited to, our ability to develop and advance our programs and product candidates, our ability to maintain and establish collaborations or strategic partnerships, our regulatory approvals and filings, and other risks, uncertainties and assumptions identified in our filings with the Securities and Exchange Commission (the “SEC”), including our most recent Form 10-K and Form 10-Q filed with the SEC, and any subsequent filings with the SEC. Moreover, we operate in a very competitive and rapidly changing environment, and it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking statements and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations, unless required by law. This presentation contains estimates and other information concerning our industry, our business and the markets for our products. Information that is based on estimates, market research or similar methodologies is inherently subject to uncertainties, and actual events or circumstances may differ materially from events and circumstances that are assumed in this information. Unless otherwise expressly stated, we obtained this industry, business, market and other data from our own internal estimates and research as well as from reports, research surveys, studies and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data and similar sources. These sources include government and industry sources. Industry publications and surveys generally state that the information contained therein has been obtained from sources believed to be reliable. Although we believe the industry and market data to be reliable as of the date of this presentation, this information could prove to be inaccurate. Industry and market data could be wrong because of the method by which sources obtained their data and because information cannot always be verified with complete certainty due to the limits on the availability and reliability of raw data, the voluntary nature of the data gathering process and other limitations and uncertainties. While we believe our internal company estimates and research as to such matters is reliable and the market definitions are appropriate, neither such research nor these definitions have been verified by any independent source, and no reliance should be placed on or should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. Forward-looking statements
From novel genome editing systems to curative therapies An in vivo genome editing company capitalizing on its proprietary technologies to create curative genetic medicines Focusing on wholly owned programs in hemophilia A and secreted protein disorders, and partnered assets targeting cardiometabolic indications
Overcoming limitations of CRISPR/Cas9 Nucleases Enabling gene knockdown, large deletions and large gene integration RIGS Enabling gene correction CAST Enabling large gene insertion Higher specificity No off-target cuts or translocations seen in genome-wide screens Multiplexed editing Using multiple editing systems to create new functionality in primary cells without translocations Durable large-gene integration Overcoming one of the major issues in AAV gene therapies Broad genomic targeting Increased ability to edit targets of interest N RIGS CAST 20,000+ signature editing system from Metagenomi's database Base editors Enabling single base correction BE Proprietary genome editing Attributes demonstrated in preclinical translation: With novel nucleases and other proprietary systems, we improve editing precision and expand genome targeting and editing functionality beyond CRISPR/Cas9 to effectively address genetically-driven diseases.
Progressing wholly-owned and partnered programs toward the clinic Protein replacement via gene insertion Protein reduction via gene knockout ALB MGX-001 Hemophilia A Editing platform: Editing target: Discovery Lead optimization IND-enabling Clinical Undisclosed Undisclosed secreted protein diseases TTR Transthyretin Amyloidosis AGT Refractory Hypertension APOC3 Severe Hypertriglyceridemia Undisclosed Undisclosed cardiovascular disease Metagenomi is exploring opportunities to pursue neuromuscular disease targets & liver disease targets such as A1AT and Wilson Disease, as well as business development to expand therapeutic applications including cell therapy. Indication:
Focused on generating clinical data in 2027 2026 2027 2025 MGX-001 Hemophilia A Secreted protein deficiencies Cardiometabolic programs Other therapeutic programs Complete NHP durability and dose range finding (DRF) studies Disclose lead indication for secreted protein deficiency platform File IND and CTA; Prepare for 2027 clinical entry Initiate clinical trial Conduct Pre-IND regulatory meeting Achieve NHP PoC to validate broad platform applicability Named APOC3 as a clinical target and shared in vivo proof of concept data Explore opportunities to pursue neuromuscular disease targets & liver disease targets such as A1AT and Wilson Disease, as well as business development to expand therapeutic applications including cell therapy
MGX-001 in hemophilia A advancing toward clinic Demonstrated curative Factor VIII activity with best-in-class treatment potential Dose-dependent efficacy of both AAV and LNP Therapeutically relevant FVIII activity in each animal treated in all but the lowest dose Data informs clinical dose regimen strategy Potential competitive advantages of MGX-001 Enables endogenous production of FVIII for hemostatic regulation Potential to effectively treat both adults and children One-time potentially curative therapy allowing patients a hemophilia free mindset Builds on previous data Durable FVIII activity over an approximately 19-month study Encouraging safety profile, with minimal steroid use at the time of dosing No off-target editing IND submission on track for Q4 2026 Completed pre-IND meeting in December 2025 Ongoing KOL and patient advocacy engagement
Hemophilia A: a validated target waiting for a durable cure Hemophilia A is the most common X-linked inherited and de novo bleeding disorder, largely affecting males. Caused by variety of mutations in the Factor VIII (FVIII) gene leading to loss of functional FVIII protein. Current SOC: ~26,500 patients in the U.S.1 ~500,000 worldwide2 - Soucie, J.M., et al, 2020. Haemophilia. Vol. 26, no. 3, pp. 487–493. - Stonebraker, J. S., et al, 2010. Haemophilia. Vol. 16, pp. 20–32. - ICER. Gene Therapy for Hemophilia B and A: Final Evidence Report. Dec 22, 2022. - Curtis R et al. Poster presented at: 65th ASH Annual Meeting & Exposition; December 11, 2023; San Diego, CA. - Zemplenyi A et al., Pharmacoeconomics (2024) 42(3):319–328. Hemophilia joint bleeds image: International Hemophilia Training Center. Factor VIII replacement therapy IV typically dosed 1 - 3 times/week Significant adherence challenges Risk of breakthrough bleeding Chronic treatment, non-curative Bi-specific antibody "mimetic" SQ dosed 1, 2 or 4 weeks post loading Risk of breakthough bleeding Treatment burden, non-curative Gene therapy Variable initial efficacy Significant decline in FVIII levels over time High risk of prolonged corticosteroid use Not suitable for pediatric patients Annual treatment cost3: ~$565K - $750K Lifetime treatment cost: ~$18M - $24M4 One-time treatment cost3: $2.9M5 FVIII
DNA FVIII protein DNA DNA sgRNA promoter MG29-1 RNP complex LNP DNA sgRNA MG29-1 AAV cell nucleus DNA MGX-001 mechanism leverages natural promoter AAV delivers promoterless FVIII gene. AAV enters hepatocytes and the donor FVIII cassette localizes to the nucleus. LNP delivers MG29-1 nuclease mRNA + guide targeting albumin promoter. The mRNA is released in the cytoplasm. The mRNA is translated into MG29-1 nuclease, which binds the guide RNA to form a ribonucleoprotein (RNP) complex. The guide pairs with the matching bases and MG29-1 nuclease cuts at the albumin locus. The FVIII cassette integrates at the albumin cut site via natural end-joining. The albumin promoter drives the expression of FVIII, which triggers the production of FVIII protein. AAV delivers FVIII gene (donor DNA): promoterless FVIII gene MGX-001 components: guide RNA to albumin gene (sgRNA) nuclease mRNA (MG29-1) LNP delivers nuclease mRNA & sgRNA targeting albumin site: 1 2 3 4 5
Animal 1001 Animal 1002 Animal 1003* NHP study designs N=3 Durability study AAV LNP Baseline Step 1 Step 2 Dose range finding study Human FVIII Pre-development candidate Development candidate Study duration: 19 months NHP FVIII N=24 Study duration 3 weeks FVIII evaluation: days 5, 8, 11 Group 1: N=4 Group 2: N=4 Group 3: N=4 Group 4: N=4 Group 5: N=4 Group 6: N=4 AAV dose LNP dose (vg/kg) (mg/kg) 2.0 x 1013 1.0 5.0 x 1012 0.6 5.0 x 1012 2.0 4.0 x 1013 0.6 1.6 x 1012 0.6 5.0 x 1011 0.6 5.0 x 1012 0.2 AAV dose LNP dose (vg/kg) (mg/kg)
Dose dependent FVIII activity in NHP: minimally efficacious and clinically relevant doses identified bleeding risk normal FVIII range thrombosis risk FVIII activity for each animals is the mean of values on d5, d8, d11 post LNP measured with a capture-chromogenic assay. hFVIII activity was stable from d5 to d11 post LNP. Xyntha was used for the standard curve. Means and standard deviation per group are shown. AAV dose response identified the optimal efficacious dose of 5x1012 vg/kg: LNP dose response identified 0.2 mpk as the minimally efficacious dose and 0.6 mg/kg as optimal dose: Development candidate 25 15 0 50 75 100 125 150 hFVIII Activity (IU/dL) Group 6 Group 5 Group 2 Group 4 AAV dose (vg/kg): 5x1011 1.6x1012 5x1012 4x1013 LNP dose (mg/kg): 0.6 hFVIII Activity (IU/dL) 25 15 0 50 75 100 125 150 Group 2 Group 3 5x1012 0.6 2.0 Group 1 0.2
Durable, therapeutic levels of FVIII achieved in NHP NHP durability study: Plasma FVIII activity levels unchanged between 3-6 months and 12-19 months and correlate to integration: FVIII activity values are the mean and standard deviation of at least 3 independent assay runs with each sample run in at least duplicate in each assay. Animal 1003 died on day 540 (17.8 mo) post LNP, assessed as unrelated to the treatment. 1 - Integration in forward orientation (copies per 100 haploid genomes, average of 5 liver lobes). Pre-development candidate 0 20 40 60 80 100 cFVIII Activity (IU/dL) 1001 3-6mo 12-19mo 1002 3-6mo 12-19mo 1003 3-6mo 12-18mo Ratio FVIII activity/ /integration Animal ID 0 5 10 15 1001 1002 1003 0 50 100 150 200 250 300 350 400 450 500 550 600 100 75 50 25 0 125 1001 1003 40% 15% 1002 cFVIII Activity (IU/dL) Days post LNP dosing
No genotoxicity observed with MGX-001 Discovery of potential off-target sites No validated off-target sites observed 2. Biochemical off-target discovery: 3. In cell off-target discovery: No potential off-targets were found. No potential off-targets were discovered in cell-based assays. No validated off-target editing observed. Development candidate High genome integrity maintained as observed in off-target editing, and AAV integration assays. 1. In silico off-target discovery: Three independent primary human hepatocyte donors: Untreated Indel % Treated Indel %
Strong advocacy and infrastructure Robust preclinical models and regulatory familiarity Clearly defined target threshold of curative FVIII level & wide safety range Monogenic and well-characterized biology with clear biomarker De-risked and clear opportunity for genome editing in hemophilia A proprietary Type V nuclease IND-enabling stage Technology: Durability: Regulatory status: Pediatric potential: Hemophilia A is an ideal indication for genome editing approach: MGX-001 is uniquely suited for patients of all ages: MGX-001 is a potentially durable, curative approach for adults and children – the population with the most to gain.
Potential cure for adults and children living with hemophilia A Designed to enable the body's own ability to produce FVIII Expected durable FVIII activity via gene integration Established regulatory and clinical pathways for advancement to pivotal study Our goal: to provide patients with a hemophilia-free mind
Beyond Hem A: pursuing secreted protein diseases with site-specific large gene insertion Expanding MGX-001 site-specific gene integration system into additional secreted protein deficiency therapeutics Normal circulating levels of target protein achieved in mice with multiple construct designs LNP delivers nuclease mRNA and guide targeting albumin site Above normal human protein expression achieved in mouse plasma Insertion assessed with multiple DNA template constructs LNP and AAV dose titration can be used to fine tune therapeutic window Mean Normal Human Range 140 µg/mL Target protein 1 (μg/ml) 0 100 200 300 400 Construct 1 Construct 2 Control Construct 3 AAV delivers Transgene (donor DNA)
Animal 1001 Animal 1002 Animal 1003 In vivo PoC in AT-III achieved with MGX-001 site-specific large gene integration system N=3 AAV LNP Baseline Step 1 Step 2 In-life, study Ongoing at 46 days AAV dose LNP dose (vg/kg) (mg/kg) 1.0 x 1013 1.0 1. Lane DA, Bayston T, Olds RJ et al. Antithrombin mutation database: 2nd (1997) update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International 2. Conard et al (1983). Molar antithrombin concentration in normal human plasma. Haemostasis.13:363–8 Achieved circulating AT-III protein exceeding curative target of 50% of normal human levels Severe antithrombin (AT-III) deficiency increases risk of venous thromboembolism (VTE) On average patients with severe disease have 50% of the normal amount of AT-III in their blood (70 ug/ml) 1,2 Replacing the missing AT-III with at least 50% of normal is expected to be a functional cure Minimal target level (50% of normal human ATIII) * *Data are the mean of day 8 and 11 post-dosing minus the mean of days 0, 4 and 7 pre-dose.
Pursuing cardiometabolic indications in partnership TTR AGT APOC3 Undisclosed Current indications: MGX's in vivo genome editing complements Ionis leadership in cardiometabolic space. 4 targets: two co-development and co-commercialization options. Multibillion dollar TAM.
Team Jian Irish, PhD, MBA President and CEO Pamela Wapnick, MBA CFO Katalin Kauser, PhD, MD, Sc.D SVP, Translational Biology Board of Directors: Executive Leadership: Willard H. Dere, MD Professor Emeritus, Internal Medicine, University of Utah Eric Bjerkholt, MBA CFO, Mirum Pharmaceuticals, Inc. Jürgen Eckhardt, MD, MBA EVP Global Head, Business Development and Licensing, Head of Leaps by Bayer Laurence Reid, PhD Former CEO, Decibel Therapeutics Brian C. Thomas, PhD Founder, former CEO of Metagenomi, Inc. Jian Irish, PhD, MBA President and CEO, Metagenomi Therapeutics, Inc. Matthew Wein, JD General Counsel and Corporate Secretary Alan Brooks, PhD SVP, Research Mark Leonard, PhD SVP, Technical Operations
Thank you