Metagenomi Therapeutics, Inc. Common Stock Wells Fargo 21st Annual Healthcare Conference

Wonderful. Thank you, Yanan, for having us here. I will start with our forward-looking statement. Metagenomi is an in vivo CRISPR gene editing company capitalizing on its proprietary technologies to create curative genetic medicines. Our lead program, MGX-001 for Hemophilia A, is advancing into the clinic with well-defined development path and clear endpoints. We are also expanding our pipeline with our differentiated site specific gene integration platform and our partnered assets in cardiometabolic indications. Our cash on hand at the end of Q2 was $120.7 million, which we expect will fund our operations through Q4 2027. From our unique metagenomi database, we have discovered more than 20,000 signature gene editing systems capable of effective and durable gene editing, including gene knockout, correction, deletion, and insertion, as well as multiplex editing with excellent specificity. We have published extensively on editing efficiencies, specificity, and functionality.

Beyond that, we have been expanding genome targeting, exceeding spCas9. Applying these technologies, we are focusing our most compelling therapeutic programs that has a high probability of success and near-term value creation. Genome editing is well suited for a potentially curative Hemophilia A therapy. MGX-001 uses site-specific gene integration in the albumin locus. This program is advancing into the clinic on track for IND submission in Q4. Beyond Hemophilia A, this approach has the platform potential across other protein deficiency diseases. In collaboration with our partner, Ionis, we are advancing metabolic indications. We are also pursuing neuromuscular indications with our compact gene editing technologies and pursuing business development to expand the therapeutic applications, including in cell therapy. Now I am going to turn to MGX-001. It is designed to potentially provide a lifelong benefit for patients of all ages, especially children who has the most to gain from a lifelong therapy.

Now, our approach is structurally different from the previous AAV gene therapy attempts. Rather than remaining episomal, factor VIII is directly integrated into the albumin locus that is a stable and active chromosomal site. We achieve that by first deliver a promoterless AAV cassette that contains the factor VIII DNA template. That is followed by the LNP, encapsulated of our novel CRISPR gene editing payload, which will create a targeted specific DNA cut to enable the factor VIII integration into that specific site. The integrated factor VIII then is expressed, driven by the native albumin promoter to reach therapeutic levels at very low integration frequency. We have done two important studies in non-human primates to evaluate this approach. Both studies have delivered desirable factor VIII activities. Let me show you some of those key data.

First study was a dose range finding study, and we are extremely pleased by the outcome of that study. The study demonstrated not only dose-dependent response to both drug product components, AAV and LNP, but most animals in our target dose cohorts achieved normal level of factor VIII. The patients with severe hemophilia have very low factor VIII activity that is typically below 1%. We are targeting 50% to 150%. That is broadly represented as a normal factor VIII level. What is really important, I want to point out, is that the AAV dose level that achieved the normal factor VIII activities is significantly lower, more than tenfold lower than the doses used in the previous AAV gene therapy for Hemophilia A. We believe that is an important safety advantage of our approach. The other study is also important, that was to evaluate the durability of the expression.

In this study, we conducted early with less optimal drug product components. Regardless, achieved the durable expression up to 90 months in the three animals treated. I want to bring your attention to the durability graph, where you can see the factor VIII activity reached the peak within two weeks and then remained stable through the end of the study. Also importantly, the activity level is correlated closely to the integration, which is the result of the mechanism of our approach. This was exactly as we expected our mechanism to do. In closing, I want to say that the totality of the data we have achieved is extremely encouraging and supports a highly differentiated profile in the Hemophilia A space. We have conducted a pre-IND meeting with the agency at the end of last year. The meeting was productive, with favorable outcome. We confirmed the regulatory pathway.

We have been executing, driving for IND submission. Remember, our IND submission is Q4 this year. We are planning to enter the clinical study in 2027. With that, I welcome your questions.

Happy to. We have built a broad and differentiated library of proprietary gene-editing technologies, and we believe that represents a long-term value driver. We can apply our technologies based upon the therapeutic target and to deliver the efficacy and the safety profile as we desire. For example, the first result of our platform was applied in our lead asset, MGX-001, where we use the editing system that is called MG29-1. Not only exhibited high editing efficiency, but in our examining of gene editing safety profile for the purpose of IND submission, we discovered no detectable off-target editing and no translocation, and it is really uniquely clean safety profile.

One additional practical benefit of MG29-1 is that the guide RNA that we use in this system is substantially shorter than the average guide RNA used in spCas9, which really provides the ease of manufacturing and the control of impurity, for instance. The broad profile, we believe, also gives us the potential for partnering collaboration, maximize the application in the therapeutics. For instance, our base editor has demonstrated more than seven plex editing with high efficiency and specificity, which can be used exclusively for cell therapy. As well, early this year, we published on our compact system, which has a much short sequence and structure rather than spCas9 has to break them into two sequences delivered with a different AAV vector for ex hepatic. Our compact system can be packaged into a single AAV, such as for neuromuscular applications. We are very happy with that.

The publication was on Nature and was recognized by the field.