VDP-120 [Assessment]: Oisín Biotechnologies - Genetic Medicines for Health and Longevity

One-liner: Oisín Biotechnologies is a multi-asset longevity biotech company pioneering genetic medicines to combat sarcopenia and other age-related diseases to promote healthier, longer lives.

Longevity Dealflow WG team

• Senior Reviewers: 2 scientists, 1 pharma professional, 1 VC, 1 biotech entrepreneur
• Shepherd: Eleanor Davies
• Other squad members: Paolo Binetti, Ryan Spangler, Tuan Dinh

Project PI:

• Matthew Scholz, CEO & Co-founder

Simple Summary

Oisin Biotechnologies is a company dedicated to developing genetic medicines that address a range of age-related diseases. Their lead candidate aims to build muscle without exercise, which could be used as a therapy to make older people stronger. The company has assets that selectively kill adipocytes and senescent cells which are believed to play a significant role in the aging process and the onset of age-related diseases. Oisin has generated in-vivo data and has already licensed its technology to pharmaceutical companies.

By leveraging their royalty-free licence to Entos’ Fusogenix Proteo-Lipid Vehicle (PLV) platform, Oisín aims to deliver specific genes to alter cell behavior, or in the case of problematic cells, inducing apoptosis and thereby rejuvenating tissues or improving physical function.

This delivery system is not only safer and more cost-effective than other prevalent systems such as viral approaches, but also ensures consistent and reproducible outcomes. If successful in human trials and upon regulatory approval, this therapy could be a game-changer in the longevity and age-related disease market, potentially becoming available within the next five years.

Problem

As the global population ages, the prevalence of age-related diseases, particularly those linked to physical frailty are on the rise. Physical strength is incredibly important. In more extreme cases, a person in a wheelchair or bedridden is effectively living on borrowed time. If they do not get out soon, they may never get out at all. Conversely, robust physical strength allows for greater activity and exercise, improved mobility, enhanced social interactions and higher quality of life. Increased muscle mass improves metabolism, strengthens bone, protects against injury. The challenge lies in maintaining muscle mass in aging populations, particularly following injury, sickness, or surgery. Current interventions are largely limited to diet and exercise.

Oisín has identified physical frailty as a key target for therapeutic intervention. By directly increasing skeletal muscle mass and physical strength they aim to not only treat but potentially prevent a myriad of age-related conditions, improving healthspan and potentially even lifespan. Pharmaceutical companies have attempted to make therapeutics that target this pathway for years but have failed to solve the manufacturing challenges needed to produce them at scale. Oisín’s approach, rooted in advanced genetic medicine, offers a promising solution in a field that would be both scalable and cost effective.

Solution

Oisín's cutting-edge technology is designed to deliver DNA and RNA with unparalleled distribution and safety at an unprecedented cost and scale. Using their Fusogenix Proteo-Lipid Vehicle (PLV) platform, they can deliver specific nucleic acid cargos to cells across the body that alter the cells behavior, such as making it produce a therapeutic protein, or in the case of unwanted cells causing them to die via apoptosis or other programmed cell death pathways.

Preliminary results from their research have been promising. For combatting frailty, they’ve observed marked increases in muscle size and physical strength from a single treatment. In the case of fat removal, they have shown selective reduction in adipocytes and with their senolytic they've observed a marked reduction in markers of senescence and a noticeable improvement in health parameters and lifespan of treated animals. This approach to genetic medicines enables entirely new therapies that hold immense promise for treating age-related diseases and potentially extending healthy lifespan.

Oisín has already demonstrated it can vastly improve physical strength in mice, selectively clear senescent cells in mice (resulting in improved lifespan and healthspan), and selectively ablate adipocytes in human tissue explants. They have performed tolerability studies in nonhuman primates at doses far higher than are expected to be used in humans. Importantly, their PLV platform has already made it through Phase II human trials in a COVID vaccine with no safety signals. To accomplish this, they had to demonstrate the ability to manufacture PLV-based therapies at human scale.

Opportunity

In 2020 there were ≈36M patients in the U.S. over the age of 60 with moderate to severe sarcopenia. In 2000, the estimated direct healthcare cost attributable to sarcopenia in the U.S. was $18.5B. This number is only expected to increase. Oisín’s follistatin-based therapy is uniquely positioned to address this market. Pharmaceutical companies have tried and failed to manufacture effective follistatin and myostatin targeted therapies in the past, primarily due to manufacturing challenges. Achieving a high enough dose to be therapeutic has been a challenge for other delivery technologies due to toxicity of the vectors. Viral-based gene therapies are too costly to be broadly deployed and would likely encounter significant immunological challenges in a very large patient population.

Oisín plans to initially treat patients prior to surgeries such as ACL repair or hip transplant to protect against disuse atrophy. This allows for a more defined patient population with clear endpoints.

Oisín’s technical and IP strengths position it well to aggressively pursue this growing market in particular. Given the vast potential market for effective anti-aging therapies and increasing interest in longevity research, Oisín's approach could capture a significant share of this market. Their therapies could become a cornerstone treatment for age-related diseases, offering both societal and commercial value. In addition, Oisin has exclusive rights to use the Entos’ Fusogenix technology in the field of longevity, giving them an edge in drug delivery.

Relevance to longevity

Sarcopenia and dynapenia are significant drivers of physical frailty and morbidity. Follistatin directly counteracts this as a direct driver of skeletal muscle hypertrophy. They have shown that increasing muscle mass with our follistatin therapy increases physical strength. Increasing physical strength improves healthspan by facilitating greater activity levels, improved metabolic function, and higher quality of life. Increased muscle mass leads to increased bone density and protects against injury. Others have even recently published that follistatin gene therapies can even extend lifespan in animals.

Beyond follistatin, Oisín has a robust pipeline and is positioning itself to become a large pharmaceutical company focused on healthspan and longevity. Their initial focus on validated targets and FDA-centric endpoints is designed to allow for early licensing deals with large pharmaceutical companies. The objective is to bring in enough revenue with these deals to take their own therapies to approval and eventually even commercialization. Their IP position is broad enough to facilitate product development far into the future and capitalize on new science as it emerges.

IP Roadmap

Oisín Biotechnologies has been proactive in protecting its IP pipeline. They have broad exclusive rights to the Fusogenix PLV patent portfolio and hold several patents related to their specific cargos and therapeutic applications. They continue to file new applications as they develop them and have rights to improvements of the PLV delivery technology. This robust IP portfolio positions them well against competitors and ensures they can capitalize on their innovations.

As they continue their research and development, it is expected that Oisín will further expand its IP holdings, ensuring a dominant position in the longevity biotech sector.

Budget

12 Month Budget:

• Research and Development: $1,666,229
• Payroll and Related Expense: $1,715,063
• Consulting: $349,013
• Lab Rent & Insurance: $166,713
• Legal: $106,015
• Intellectual Property: $383,045
• General and Administrative: $232,624

Total: $4,618,702

Financing and VitaDAO Funding Terms

Oisín Biotechnologies is actively seeking funding to propel their research forward. They recognize the value that VitaDAO members bring, both in terms of financial support and expertise. Oisín has allocated 50k for the VitaDAO community under their current SAFE (standard SAFE document, raising up to $5M with a $100M cap, and 15% discount to the next round), ensuring a mutually beneficial partnership. The previous round was in 2021 and also a SAFE. It had a $70M cap and 15% discount. They have verbal commitments for a significant portion of this SAFE and anticipate closing it soon. This closure will also be based on the outcome/time frame resulting from current discussions with pharmaceutical partners.

Oisín was incorporated in February 2014 as a Delaware C corporation and has raised $11.2M. Notable investors include SENS Foundation, M Fund, Althea, Kizoo, Healthspan Ventures, and several prominent angel investors in the longevity community. They have already identified a putative lead investor for their subsequent Series A.

Team

Leadership

• Matthew Scholz - CEO & Co-founder: 20+ years experience starting and running biotech companies. Founder of Immusoft, creator of the first engineered B cell therapy allowed to enter human trials and Sigma Genetics, a YC-backed company developing a novel nucleic acid delivery technology.

• John D. Lewis, Ph.D. - CSO & Co-founder: Endowed Chair, Prostate Cancer, University of Alberta. Founder of Entos Pharmaceuticals, the owners of the PLV technology and Nanostics, a ML-based cancer diagnostics company.

• Gary C. Hudson - Executive Chairman: 50+ years experience biotech and aerospace.

• Steve Hilbert - Chief Business Officer: 19+ years experience finance and business JP Morgan/Charles Schwab.

• Eric Garcia - Chief Operating Officer: 15+ years experience, COO, CFO in biotech.

• Hank Garcia, Ph.D. - Head of Aging R&D: 10+ years experience in aging, oncology, and gene therapy.

Key Collaborators

• Joseph Bonventre, M.D., Ph.D. - Advisor: Chief of the Renal Unit & Engineering in Medicine Division, Brigham and Women’s Hospital.

• Marco Demaria, Ph.D. - Advisor: Faculty of Medical Sciences, Leader of the Laboratory of Cellular Senescence and Age-related Pathologies.

• Peter Elias, Ph.D. - Advisor: Professor Emeritus, Department of Dermatology UCSF, Staff Physician at the VA San Francisco

• Ed Simcox J.D. - Advisor: CSO, LifeOmic; Fmr. CTO, U.S. Department of Health and Human Services; Launched KidneyX

Slide deck

Slide Deck

Highlights

• Fusogenix Proteo-Lipid Vehicle (PLV) Platform: Oisín's proprietary Fusogenix PLV platform allows for the delivery of specific nucleic acid cargos to cells, altering their behavior or inducing apoptosis in problematic cells. This allows for the targeted delivery of genetic material, ensuring precision in addressing problematic cells without affecting healthy ones.

• Broad Therapeutic Pipeline: Beyond muscle growth, Oisín has shown the ability to selectively clear senescent cells in mice and ablate adipocytes in human tissue explants, positioning it as a comprehensive solution for age-related conditions.

• Proven Preliminary Results: Early studies have shown significant results, such as mice treated with their follistatin therapy showing a 50% increase in size and a 100% increase in strength compared to controls.

• Traction: Oisin has already sold a license option of its follistatin application to a large pharmaceutical company providing further validation of the approach and existing preclinical data. If successful in human trials and subsequent regulatory approval, this therapy could become available within the next five years.

• Market Opportunity: With sarcopenia-related healthcare costs in the U.S. already at $18.5B in 2020 and rising, Oisín's follistatin-based therapy, combined with exclusive rights to the Fusogenix technology, positions the company to capture a portion of this market. This may offer a revenue stream where previous pharmaceutical efforts have been unsuccessful.

• Strong IP Position: With broad exclusive rights to the Fusogenix PLV patent portfolio and several patents related to specific cargos and therapeutic applications, Oisín stands protected against competition.

Risks

• Manufacturing Challenges for Follistatin and Myostatin Therapies: Historically, the biotech industry has struggled with producing follistatin and myostatin-targeted therapies at scale. While Oisín's Fusogenix PLV platform promises to overcome these challenges, the actual large-scale production may present unforeseen difficulties, potentially affecting the timeline for therapy availability and cost-effectiveness.

• Regulatory Hurdles: Oisín's Fusogenix PLV platform introduces a new paradigm in genetic material delivery. The safety of genetic therapies, not to mention Oisín’s novel delivery mechanism, may be subject to regulatory scrutiny and rigorous evaluation, especially in regions where genetic medicine policies are still being formulated or updated.

• Competitive Landscape: As Oisín focuses on genetic medicines for sarcopenia and senescent cell clearance, they face competition from other biotechs targeting the same pathways or using alternative methods. The race to develop effective follistatin and myostatin-targeted therapies has seen multiple entrants, and Oisín's Fusogenix PLV platform, while unique, will need to demonstrate superiority in efficacy, safety, and scalability to maintain a competitive edge.

• Potential Side Effects: While showing promise in preliminary studies, Oisín’s technology is still in the investigational stage. As with all genetic therapies, there's a possibility of unforeseen side effects emerging during later-stage clinical trials. These could arise from the targeted delivery of genetic material or the induced cellular responses, potentially impacting the therapy's broader applicability and acceptance.

Bibliography

1. Brown, D. W. et al. Safe and Effective Delivery of Nucleic Acids Using Proteolipid Vehicles Formulated with Fusion-Associated Small Transmembrane Proteins. SSRN Electron. J. (2022) doi:10.2139/ssrn.4241169.

2. Top, D. et al. Liposome reconstitution of a minimal protein-mediated membrane fusion machine. EMBO J. 24, 2980–8 (2005).

3. Ciechonska, M. & Duncan, R. Reovirus FAST proteins: virus-encoded cellular fusogens. Trends Microbiol. 22, 715–24 (2014).

4. Top, D., Barry, C., Racine, T., Ellis, C. L. & Duncan, R. Enhanced fusion pore expansion mediated by the trans-acting Endodomain of the reovirus FAST proteins. PLoS Pathog. 5, e1000331 (2009).

5. Mendell, J. R. et al. A Phase I/IIa Follistatin Gene Therapy Trial for Becker Muscular Dystrophy. Mol. Ther. (2014) doi:10.1038/mt.2014.200.

6. Kota, J. et al. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci. Transl. Med. 1, 6ra15 (2009).

7. Tang, R. et al. Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet-induced obesity. Sci. Adv. 6, eaaz7492 (2020).

8. Rodino-Klapac, L. R. et al. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve 39, 283–96 (2009).

9. Lee, S. J. & McPherron, a C. Regulation of myostatin activity and muscle growth. Proc. Natl. Acad. Sci. U. S. A. 98, 9306–11 (2001).

10. Jaijyan, D. K. et al. New intranasal and injectable gene therapy for healthy life extension. bioRxiv 2021.06.26.449305 (2021) doi:10.1101/2021.06.26.449305.

Senior Review Digest - Quantitative

Below is the average scores out of 5 per category from 5 reviewers, who all recommended the project should be advanced for community feedback.

Average Scores

• Novelty: 4.2
• Feasibility: 3.6
• Relevance: 4
• Science Team: 4.2
• Market Advantage: 3.6
• IP Potential: 4.2
• Conviction score: 3.8

Senior Review Digest - Qualitative

Please find the qualitative digest in the corresponding Discourse proposal.

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