VDP-117 [Assessment] Magnaetus Therapeutics

One liner: Magnaeutus Therapeutics is developing a first-in-class agent for weight loss and metabolic disease.

## Longevity Dealflow WG team

• Scientific evaluation: 2 biotech managers, 2 scientists, 1 pharma consultant
• Shepherd: Jason C. Mercurio, Eleanor Davies
• Other squad members: Maria Marinova, Rhys Anderson
• Sourced by: Jason C. Mercurio

Project PIs:

• Guy Barry, Paul Baldock

Simple Summary

Magnaetus Therapeutics aims to reverse age-related metabolic decline through the development of an exercise mimetic. They intend to develop a therapeutic that will have the effect of weight loss and targeting obesity as well as extending healthspan.

Problem

Obesity and metabolic syndrome have reached crisis levels with almost no effective, patient supported interventions. By 2035, an estimated 50% of the world’s population will be overweight or obese (4.5 billion people).

Currently, patients are offered ozempic, although this is associated with severe side effects including pancreatitis, hypoglycemia and kidney failure amongst others. Alternatively, there are extreme bariatric surgery measures such as gastric banding.

Solution

Magnaeutus Therapeutics is developing a peptide therapy, based on an endogenous protein that mimics the beneficial effects of calorie restriction and exercise. This peptide is thought to reduce fat mass whilst preserving lean tissue.

Opportunity

The weight loss and weight management diet market size was valued at $192 billion in 2019, and is projected to reach $295 billion by 2027. Ozempic (Novo Nordisk) alone had 2022 sales of $8.56 billion.

Following 15 years of research, Magnaetus Therapeutics has identified an endogenous protein that stimulates energy release and consumption, rather than conservation. Serum levels of this protein are suppressed by obesity, but stimulated by calorie restriction and exercise.

Classified as an extracellular matrix molecule secreted into the extracellular space, it acts via interaction with cell surface receptors, and has a wide range of activities. Importantly, it also circulates, consistent with inter-organ actions and metabolic responses. Multiple repeat loops provide specific binding activities.

Elevated levels are thought to be responsible for the downstream health benefits of exercise and dieting including: increased fat burning, reduced food intake, improved insulin sensitivity and secretion, and improved nutrient signalling.

Relevance to longevity

The therapeutic being developed targets metabolism systems thereby directly impacting longevity.

IP Roadmap

The team is working towards a composition of matter patent. The aim is to file a PCT after lead isolation studies with Dominique Bridon and then apply for a full RCT after healthspan and metabolic studies with Brian Kennedy are complete (7-9 months).

The protein is not heavily studied (86 papers with protein in title, 256 total), cancer/cardiac function dominates literature and thus do not anticipate being challenged for priority date.

Experimental Plan

Year 1

• Synthesis of proteins (12 weeks)
• Solid phase synthesis (SPPS) for production, HPLC and MS for characterisation to deliver 2-3 core proteins and their analogues (about 3-5 for each core protein) that mimic protein structure.
• In-vitro screening (12 weeks)
• Cell-based assays to define critical aspects of protein activity profile: weight loss and longevity mTOR/AKT (MCF7, MIN6): Insulin (MIN6): Lipolysis (3T3-E1): Glucose, AMPK (C2C12).
• In-vivo screening (20 weeks)
• Acute murine studies in HFD to define critical aspects of protein activity profile: weight loss and longevity. Weight loss, fat mass, food intake, GTT, ITT, energy expenditure, muscle + adipose (mTOR, AKT, AMPK), serum.

The team has worked through the generation of data on animal studies to determine how their protein of interest operates in the body. They have looked at mouse models and have also determined that their protein of interest is in adipose tissue, muscle and bone. It is not found in the pancreas.

Budget

Year 1 go/no go milestone: USD 500,000

• Incorporated
• Past rounds: They have not raised capital for this company before.
• The team has yet to decide on an exact valuation although it may be around a USD 3-5M post-money valuation.

Financing and VitaDAO Terms

The team is raising a total of USD 500K for the initial seed round. They have allocated USD 100K for the VitaDAO community. The lead investor would fund USD 400K.

Team

• Guy Barry, PhD — CEO 25 years experience with 11 in biotech with an emphasis on metabolic, neural and cardiovascular mechanisms. Worked in academia where he performed research on IPS cells, long non-coding RNA, cancer, G-Protein Coupled Receptors, and bioinformatics.

• Paul Baldock, PhD — CSO 25 years experience with extensive time in academia — researcher with an emphasis on in-vivo models, metabolic, musculoskeletal, glycaemic, neural, endocrine, and cancer. Identified the unique protein that serves as a longevity target through metabolism optimization.

• Brian Kennedy, PhD — Advisor

• Dominique Bridon, PhD — Advisor**

Additional information

Deck: Magnaetus Therapeutics Presentation

Newer deck available with NDA

Highlights

As above

Risks

Customer Risks The potential for causing more harm than benefit or adversely affecting daily life is low. This is largely because the protein in question is naturally occurring in the human body. Interestingly, the high cost is not seen as a risk. Insurance companies are generally willing to cover the costs of medications that benefit patients, and the FDA often grants exclusive rights to newly approved drugs.

Product Risks There could be side effects from the developed drug although this is minimal since the body already contains the protein and it’s natural.

Go-To-Market & Business Model Risks There could be competing products when going to market with an exercise mimetic and weight loss drug.

Team Risks The founders have been working together for many years. There is a risk of getting more team members efficiently as their organization grows.

Bibliography

• Eli Lilly and Company Lilly to Acquire Versanis to Improve Patient Outcomes in Cardiometabolic Diseases

Senior Review Digest - Quantitative

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

Average Scores:

• Novelty & Impact 3.6
• Feasibility & Data 3.6
• Relevance 4
• Science Team 3.8
• Market Advantage 3
• IP Potential 3.25
• General Conviction Score 3.6

Senior Review Digest - Qualitative

Reviewer 1 My questions have been answered very well, and took away some of the worries I had on IP and general approach. I think the team has provided quite some convincing data in one of the hottest fields of pharma at the moment, which is also one of those fields that is relevant for longevity. There are 2 major points that I’d like the community to be aware of for the voting:

1. It is a serious problem the receptor is not identified. Pharmacological modelling will be practically impossible, making dose-predictions etc a true headache. In pharma companies, this would be an early kill for the project and will make your partnering possibility at early stage very challenging. I would advise to include a biopharmaceutical pharmacologist very early onwards in the project to work on this.

2. To me, the mTOR effect is still a serious worry for this project. Although I think the experiment they’ve done is interesting, perhaps just doing a prolonged treatment in elderly mice and monitoring pmTOR in leukocytes (as a proxy) would be a good way to address this?

Reviewer 2 Although no direct relationship or direct mechanistic action with aging, I am enthusiastic about their idea to use parts of the ECM and the protein of interest to target obesity (and metabolic dysregulation), which definitely will have a big impact on the aging society. Also, if they succeed, Novo Nordisk or Eli Lilly is likely to acquire them.

Reviewer 3 After reevaluating the data based on the company’s answers, they do indeed look promising and would allow VitaDAO to enter the weight-loss market. From a commercial perspective, my key concerns are the limited knowledge by the team of what is being developed outside of the two weight-loss drugs that are already commercialized and the lack of a Target Product Profile to be presented to physicians for feedback. I would also recommend as soon as it is feasible to generate head-to-head data vs semaglutide (Novo Nordisk) and tirzepatide (Eli Lilly). Also, given the size of the market, this is not a drug that can be developed and sold on its own, and Business Development activities targeted at Big Pharma must be initiated as soon as possible

Reviewer 4 All of my questions are answered thoroughly and satisfactorily. I believe the approach Magnaetus Therapeutics is taking and experiments planned together with their research collaborators is very well designed and will be helpful to gain a lot of insights during the study. Fast IP protection should be considered in this project. I would further recommend providing funding to this project by VitaDAO given its direct application on longevity and age related diseases.

Reviewer 5 Magnaetus is proposing a very diligent approach to identify the most promising elements to achieve the intended functionality. A step-by-step program is proposed and one may question if some work could be speeded-up by a more intertwined planning and execution. In fact, the team agreed during the Q&A session that shortening of the plans is feasible. It is noted that it took the team fairly long to provide answers to the questions raised by the VitaDAO team. Execution speed is a concern.

The team has a strong background in research, medicinal chemistry and early stage drug development. The team would benefit from entrepreneurial expertise and speed to ensure that research efforts are well aligned with business needs to attract further funding and build the company for success towards an exit strategy. At this stage, limited information is available. The team is currently planning for a 6 monthly implant, which is a demanding pharmaceutical presentation. Except for the TPP, appropriate responses to my questions were provided. In summary, I recommend funding of this project by VitaDAO.

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