This proposal asks for 250.000 USD to fund MenoAge - A Glycomics based blood biomarker for detection of perimenopause and menopause transition to enable timely access to therapy.

Shepherds: Maria Marinova, Maximilian Unfried Scientific & IP Evaluation Team: Diane Seimetz, Lutz Kummer, Sebastian Brunemeier, Tovah Wolf

Summary

MenoAge is a perimenopause diagnostic, which is an accurate, rapidly deployable, and cost-effective. It assesses the long-term impact of common therapeutic interventions for management of menopause or of premature ovarian insufficiency impacting women´s health and longevity. Early detection of perimenopause will lead to prompt, personalized treatment, thus preventing and alleviating (peri)menopausal symptoms associated with aging and improving future health by reducing the risk of age-related diseases and mortality.

Motivation

Briefly describe what problem this aims to solve. Why is this a problem worth solving? If this impacts the user, explain how it impacts them. If it helps, frame the problem as a pain point to the VitaDAO community.

While women live longer than men on average, they spend more time in poor health with increased incidence of age-related diseases commonly associated with menopause. Menopause can have severe health and psychological consequences such as heart diseases, osteoporosis, diabetes, and dementia influencing women’s social relationships and overall quality of life and longevity. Women’s reproductive aging, healthy aging and gender equality are therefore inextricably linked, yet female reproductive aging remains an understudied topic. There is a potential for Hormone Replacement Therapy(HRT) to relieve these phenotypes, but we can only get the full effect if the treatment is started on time. If HRT is given after the menopause transition, the patient has already lost a lot of estrogen receptors and will not be able to respond to estrogen as before. The problem is that currently menopause is diagnosed retrospectively, and the HRT administration is not optimal. In the UK, timely treatment of perimenopause could save the NHS over £0.5 billion. A validated prognostic biomarker that would monitor the effectiveness of the personalized therapy, therefore, has a game-changing potential for the menopausal care pathway and could revolutionize the management of female health and aging.

11 million women in the UK alone are in an age of peri(menopause) and 8.8 million experience symptoms. They spend $20 000 in the span of 4-10 years on the menopause journey, including doctor visits, treatments, and other wellness products. Hence the TAM of this project is estimated to be $17.5 billion, with a SAM of $11 billion.

Specification

MenoAge is designed to be a novel biomarker for monitoring highly personalised approach to HRT benefits vs. risks of ongoing therapy, in connection to ageing and long-term health outcomes. It is intended to replace the currently inadequate hormone tests for perimenopause detection and assess the effectiveness of HRT on woman´s healthy lifespan. The retrospective cohort study conducted from 1984-2017 on 105,200 healthy UK women taking HRT, with an average follow- up of 13 years, found a 9-14% reduction in overall mortality for HRT users resulting in longer and healthier lifespan. MenoAge will thus represent a powerful, game-changing, and cost- effective tool aimed at improving female reproductive health and, consequently, supporting woman´s longevity. They propose immunoglobulin G (IgG) glycans as a biomarker of perimenopause onset, and a safe and effective hormonal replacement therapy determination for monitoring of healthy female aging. IgG is a molecule involved in multiple functions of our immune system, one of them being the regulation of the overall immune activation threshold and inflammation level. As a part of the inflammaging process, IgG glycan composition changes towards more inflammatory as we age, with women showcasing a pronounced stepwise decline at menopause, indicating this as a “rapid aging” period. Accordingly, a study on close to 2000 women found that IgG glycosylation pattern “ages” at a higher rate during perimenopause. Most importantly, estrogen supplementation can entirely prevent inflammatory changes of IgG glycome caused by chemically induced menopause.

Project Lead: Who is leading this project? If approved, is that person willing to take on the Team role of lead for the project’s duration? Please mention their Discord username(s) here.

Team: Prof Gordan Lauc, project lead, glauc@genos.hr (founder of Genos research labs, Gordan is the inventor of the GlycanAge test and company CSO)

Dr Julija Jurić, lead scientist, jjuric@genos.hr (employed with Genos for 7+ years)

Dr Marija Pezer, lead scientists, mpezer@genos.hr (employed with Genos for 7+ years)

Dr Frano Vuckovic, lead biostatistician, fvuckovic@genos.hr (employed with Genos for 7+ years)

Dr Louise Newson, principal investigator, louise.newson@newsonhealth.co.uk (research collaborator for 2+ years)

Dr Felix Agakov, AI and machine learning, felix@pharmaticsltd.com (collaborator for over 10+ years)

Dr Samir Khan, health economics and market access, samkhanicgeb@gmail.com (Market access consultant at GlycanAge for 1.5 years)

Nikolina Lauc, commercial director, nikolina@glycanage.com (CEO at GlycanAge for 2+ years)

Zorrie Dimitrova, operations manager, zorrie@glycanage.com (Operations manager at GlycanAge for 4+ years)

Description of what is being funded: The MenoAge test is already developed - it is measuring the same Glycans as the GlycanAge test which is already on the market. The goal of the funded project is mainly about clinical evaluation of the test - for clinicians to evaluate it as a tool in practice and that it is useful and helps decision making.

We know the test responds to menopause therapy, it changes before the last cycle stops, etc. , however the time between testing has been generally spaced out. Therefore through this project we will be collecting glycan data at higher resolution, through testing the cohort every 2 months and thereby being able to detect changes that improve the algorithm and make it more sensitive to changes in (peri)menopause.

Reviews

Highlights

• Very Strong Team of Scientists, Clinicians and Entrepreneurs
• MenoAge diagnostic test already developed
• Produces revenue in the near-term, and GlycanAge system can be leveraged for MenoAge
• Large and growing Market with an unmet need, and Early market entry possible
• First encouraging data in humans
• The proposed MenoAge test has the potential to determine long-term average concentrations of sex hormones, which would be a substantial improvement over available test systems focusing primarily on short-lived hormones. This is in analogy to glycated hemoglobin (HbA1c) used as biomarker to determine long-term concentrations of blood glucose.

Risks

• testing of product still in pre-clinical phase
• focus seems to be on UK and potential other countries, so far no plans for EU

Longevity WG scientific evaluation digest:

3/3 senior reviewers have expressed a vote in support of funding this proposal. Here is the digest:

Quantitative reviews:

To quantify the level of conviction, they have provided a score on a scale of 1-5 (with 5 being the highest). The average score was 3.92/5

Brief qualitative review summaries:

Senior Reviewer 1.) Highly relevant for longevity, as the proposed MenoAge test can monitor and optimize hormonal treatment of perimenopause women, which will lead to a healthier lifespan and potentially even longer life span in an aging female population.I recommend funding of this project by VitaDao. The proposed deal terms below, i.e. 250K for 2% on MenoAge revenue up to a 6x return, are considered reasonable.

Senior Reviewer 2.) This is an unmet need in the market and has the potential to enable earlier diagnosis and treatment of menopause / perimenopause. Earlier treatment may reduce the pace of aging and lift the burden on healthcare systems. Knowledge is power! And the team is quite strong.

Senior Reviewer 3.) There is a crucial need for perimenopause diagnostics. Early detection is pivotal so women can receive the personalized treatment they need to decrease the risk of severe health and psychological consequences that can result from menopause. IgG glycans may be the first reliable biomarker of perimenopause onset, which has the potential to help women around the globe start hormone replacement therapy earlier, thus improving their healthspan.

Implementation

Success Metrics:

Patients need to be enrolled and samples collected consistently with timeline described below. When the samples’ glycome is analysed, the result would be compared to clinician reports, questionnaires, and patients’ symptoms to see how well they match. This is both in the case for perimenopause-menopause transition, as well as HRT start and patients’ response to it. If results are promising, the product will generate revenue quickly, starting to sell in private clinics and later on direct to consumers.

Timeline:

Following all applicable ethical guidelines, and aiming at ethnic and socio-demographic variability, we will recruit 100 perimenopausal women from among the waiting list of Newson Health Menopause and Wellbeing Clinic – and follow them up for up to 2 years from the initial visit. Each patient will complete at least 3 assessment visits at 6-12 months intervals. Patients will complete a menopause symptom questionnaire and a quality-of-life questionnaire at each visit. Hormone blood tests (oestradiol, testosterone, and SHBG levels) will be undertaken as clinically indicated. They will be given appropriate hormone replacement therapy, which will include oestradiol, according to their symptoms and health. Their management of perimenopause will be according to the national and international guidance on the management of perimenopause and menopause. The types of hormonal replacement therapy administered will be in line with guidance from the National Institute for Health and Care Excellence (NICE), according to each women’s clinical needs. Dried blood spots will be collected every month for IgG glycosylation analysis: at each visit and, additionally at home by self-test kits.

Budget:

Clinicians $100,000 Project team $50,000 800 IgG glycome analysis: sets (at $7), profiling analysis (at $60 subsidized price). Hormones biochemical blood tests (at $60) blood collection (at $30) $90,000* Shipping costs, Other costs, Overhead $10,000

Total: $250,000

Commercialisation

MenoAge will be Partnering with Intervenn, the first Glycan based ovarian cancer detection test on market - approved as a diagnostic which is generally hard to do independently . Intervenn raised $200M USD and MenoAge plans a joint venture with them and put the MenoAge test through their already established certified regulatory system to get it to a fully certified and approved as traditional diagnostic.

https://www.fiercebiotech.com/medtech/intervenn-biosciences-quintuples-funding-201m-for-ai-powered-cancer-tests

Funding Terms

$250K for a share of 2% of Revenue up to 6x return - in form of a Royalty NFT(facilitated by Molecule).

Supporting Documents

Application form: https://airtable.com/appqo3bPXVQojAtrk/tblE6sjpeUO9vMFRR/viwZNKkwspMtXXN42/rec5sbI80h6na2Fas?blocks=bipf1A1U1w3J7pxR5

MenoAge Community Call with Nikolina Lauc and Dr. Louise Newson: https://www.youtube.com/watch?v=KH2qRMm-QY0