VDP-90 [Assessment] MutagenTech - Somatic mutation sequencing technology

Longevity Dealflow WG team

• Scientific and Business evaluation: 3 venture capitalists, an academic professor, and a start-up founder.
• Shepherd: Ryan Spangler & Paolo Binetti
• Other squad members: Rhys Anderson, Amaury Bekaert, David Wilson, and Ashish Rajput

Project lead

Chris Bradley, MS, Chief Executive Officer

Simple Summary

MutagenTech (a Matter Bioworks Subsidiary): A next-gen sequencing service for somatic mutations discovered in Jan Viig’s lab, a leading geroscience KOL in the DNA damage and repair space.

Problem

Fundamentally, our DNA is the primary source of our entire body’s cellular information. Once our parental DNA fuses to form our own, we then begin the complex journey of unfurling the entire complexity of our organismal dynamics from that single starting point. Naturally, over the course of a lifetime of intrinsic and extrinsic damage, the DNA in our cells inevitably begins to lose its original sequence integrity. This loss of signal takes on many forms, including somatic point mutations, structural variations such as insertions, deletions, and transpositions as well as epigenetic landscape drift.

Despite our overall understanding of human genetics, we still do not fully understand how and which of these errors are most affecting the functionality of cells. Outside of some well documented exceptions such as cancer drivers and suppressor mutations, most of these errors do not yet have predictable and clear consequences. The search for a deeper understanding of this mystery is the foundation of the entire field of somatic mutation sequencing.

Opportunity

Recently, there has been a clear link demonstrated between somatic mutation rate and both organism age and the rate of aging itself (Cagan et al., 2022).

Somatic mutations have been proposed as a core contributor to aging phenotype through loss of function, increasing transcriptional noise, and promoting clonal expansion. Nevertheless, due to a lack of cheap and accurate somatic sequencing methods, the exact mechanisms for these pathological consequences were not fully examined. Until now.

Solution

With MutagenTech's novel SMM-seq technology, developed in the lab of pioneering somatic mutation geneticist Dr. Jan Vijg PhD (Chair of Genomics, Albert Einstein College of Medicine) they can now detect somatic mutations in a cost-effective manner with higher accuracy than ever before. This technology represents a game-changing catalyst in the field of somatic mutations and will help shed light on how somatic mutations contribute to aging and other pathologies.

The current golden standard is duplex sequencing, which is much more costly and less accurate than our SMM-sequencing. In addition to comparing both strands, our approach allows us to amplify DNA fragments by making direct, concatenated copies of the primary DNA. This allows us to differentiate sequencing errors from true point mutations, with an accuracy that has been shown to reach the theoretical maximum after 7 copy cycles. Therefore, we can provide the same service as our competitors in a cheaper, better, and faster way.

Go to Market Strategy

• The team has done extensive market research and we have identified clear customer segments as well as competitors in the space.
• The initial go to market approach is to target labs that already study somatic mutations, since they have already validated the need for the technique.
• Early clients have also confirmed that the approach is beneficial to them and better than the competition.
• The company is already receiving revenue from this segment (with over $300k worth of ARR projected to be closed this quarter), the team feels confident in the product/market fit for this market segment.
• Mid-term, this initial market is relatively small (~$1B) and they are expanding to the pre-clinical genotoxicology market. SMM-seq would be the most accurate method to test genotoxicity, several pharma and governmental institutions have aleady expressed interest.
• Longer-term, they intend to target the larger diagnostic market (>$75B by 2035) through both direct sales and partnerships.
• As part of this they intend to obtain regulatory clearance for our tests by showing the ability to determine disease risk and disease burden using our techniques.
• There are comparable offerings in this space with high value, the largest being Grail (value $8B link) and Guardant Health,(NASDAQ: GH, Market Cap $3.2B) who both use inferior and less cost-effective approaches, and who would benefit from access to our technology through partnership or who could eventually be disrupted by us.

Traction

• Early revenue from several paying clients with $300k in ARR projected to be closed this quarter
• Multiple pharma companies and research orgs expressing strong interest as customers
• Expected to be strongly revenue generating / profitable in 6-12 months
• Contracted incubator/lab space

Upcoming Milestones

Update on milestones

Overall MutagenTech is tracking well with their timeline and have hit substantial milestones, including:

• Has successfully contracted our incubator space
• Has hired our lab technician
• Has agreed on licencing terms (full license being finalized)
• Has ramped up sales with revenue being generated and 4 new clients, with several more in process of closing. These existing clients represent over $300,000 in ARR
• They are in advanced planning for a co-marketing push with a large sequencing company and a sales channel partnership with a different company.
• They are in additional partnership talks with several very large, well known companies.

Intellectual Property

The work has been recently published in Science Advances (Maslov et al. 2022). The IP has been produced out of Dr. Jan Vijg’s lab and is patented by the Albert Einstein College of Medicine. Mutagentech is licensing the IP and we are ready to commercialize this technology in the market today.

Team

• Chris Bradley, MS, Chief Executive Officer
• Alex Maslov MD, PhD, Scientific Cofounder
• Jan Vijg, PhD, Scientific Cofounder
• Sam Sharifi, PhD, Chief Scientific Officer

Financing

Matter Bioworks and its subsidiaries have raised over $10M in non-dilutive capital and $3M in dilutive capital, primarily through angel investors and family offices. Existing investors include: Formic Ventures, ODX Fund, and Balaji Srnivasan.

MutagenTech is the newest of Matter Bio’s subsidiary and has been primarily bootstrapped, and is already generating revenue.

Funding

MutagenTech is raising an equity round and has $50,000 USD allocated for the VitaDAO community.

The use of capital would be for expanding MutagenTech’s market footprint in scientific and industry labs. The budget will include personnel, laboratory, and bench costs, as well as marketing, sales expenditures, and IP prosecution costs.

MutagenTech’s goal is to achieve scalable, repeatable revenue growth this year, which will prove product-market fit as well as begin growing our somatic mutation database.

Highlights

1. Novel sequencing technology enabling the accurate sequencing of somatic mutations for the first time ever from Jan Viig’s lab, leading key opinion leader in the geroscience field and DNA damage/repair.
2. Company already has strong investor base and financing with high profile VCs and angel investors.
3. Existing clients already identified (300k in ARR), and many market applications identified (with Pharma interest)

Risks

1. Successful market identification/customer acquisition will be key
2. Other competitors could enter the market with superior technology.

Senior Review Quantitative

Below is the average scores out of 5 per category from 5 reviewers.

Average Score

• Novelty 3.4
• Feasibility 4.0
• Relevance 3.6
• Science Team 4.3
• Market Advantage 3.0
• IP Potential 3.7
• Conviction score 3.4

Senior Review Qualitative

Reviewer 1

• Strong CEO with startup and exiting experience. The focus is on something at the core of aging.
• Unclear whether the DNA diagnostic will be a lifestyle or investible business. Not clear if we want to invest in the holding company or MutagenTech by itself.

Reviewer 2

• I am not in favor sponsoring fee for service research projects, unless the upside was significant.

Reviewer 3

• The technology is apt for the intended use. The bottleneck for the project is the commercialization. Although little data is provided I do think the team oversees the difficulties they are facing, but, I can not properly judge if they also have the tools and team in place to overcome this commercial hurdle. Also, the licenses for the technology have not been shared with vitaDAO, hence, vitaDAO would invest in a project without knowing the exact commercial terms, which I would advise against. In case vitaDAO wants to support a service-based biotech this is a very good candidate.
• So altogether: in case vitaDAO can secure a good % of revenue for this project we will have to take the unknowns and move forward.

Reviewer 4

• Technology claims to be better and cheaper than the competition
• Scientific team who developed the technology is strong
• If a "killer application" were to be found, this IP might see a quick acquisition by a bigger company

Reviewer 5

• Demonstrated to be more accurate
• More efficient data utilization compared with duplex sequencing - hence cheaper
• Single molecule mutation sequencing is 2x more accurate compared to duplex sequencing like Nanoseq
• MT tech only needs single strand while duplex sequencing requires both strands
• MT tech allows analysis of any tissue, including circulating free DNA, exomes, mitochondrial DNA.
• Strong technical founding team

Additional Information

Website: https://www.matterbio.com/ Pitch Deck

Publications

1. https://www.nature.com/articles/s41586-022-04618-z
2. https://www.science.org/doi/10.1126/sciadv.abm3259

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