I think the ultimate goal of longevity biotech is to enable access for anyone, anywhere to safe and affordable drugs that slow down aging to extend healthy lifespan. Anyone should be able to visit their doctor and get a prescription for a longevity drug.
Towards that goal, the strategy most companies have been following is to:
target mechanistic pathways involved in the aging process and secure regulatory approval initially for the treatment of specific diseases and subsequently for the prevention of multiple age-related diseases or for increasing human healthspan.
This is a straightforward answer to a regulatory constraint: there is no clear pathway to bring geroprotectors to market. Although, Loyal is already proving that it can be done.
However, in more than 30 years of history, despite apparently promising science and significant funding raised, no company has succeeded to bring a longevity product to market. Product as in: drug that has been approved by a regulatory agency following thorough clinical trials.
It may be possible to treat an age-related disease by targeting a mechanism of aging and I think some companies will eventually achieve that. However, the treatment would be optimised for treating the disease; and not necessarily for slowing down aging. Running clinical trials to get any drug approved for an indication is by itself extremely difficult. And the best way to increase the chances of success is to optimise every detail. It may be dosage, formulation, biomarkers, protocol, duration or anything in between.
From an investment perspective, given the scientific and historical risks, a drug that targets a specific pathway or mechanism of aging to treat a disease has no superior value than any other drug. Unless that drug can slow down aging. And it is probable that at least some of the drugs from all the longevity biotech startups that are currently active could do that.
Alexandre Orozco taught me that you only get good at what you do. Not at what you say you do, not at what you think you're doing and definitely not at what you hope you will one day do. In his must read book Becoming a Supple Leopard, Kelly Starrett says that practice makes permanent.
If a company is developing drugs that target a mechanism involved in the aging process to treat a disease, that's what they are doing. So that's what they are getting good at. And that's what they will eventually achieve. However, if a company aims at slowing down the aging process and extend healthy lifespan, that's what the they should do. And that's what they will eventually achieve.
So maybe it's worth considering a different product strategy: assume the regulatory risk, target aging itself and do it preventative instead of curative. The challenges are indeed extremely difficult but fundamentally simple:
Identify drugs that can potentially slow down the aging process at a molecular and cellular level that are safe, affordable and easy to distribute. The Interventions Testing Program (ITP) has already found such drugs in mice. We know that at least some of the mechanisms involved in the ageing process are conserved across different species so I'm optimistic that we'll find drugs and combinations that show a big effect for people and their pets. Some strategies include:
- Prioritise already approved drugs with known safety and pharmacology to accelerate the path to human trials
- Test combinations of promising drugs for synergistic effects on aging pathways and biomarkers at safe doses
- Assess effects on a panel of agreed-upon aging biomarkers, not just lifespan, to demonstrate broader healthspan impacts
- Develop partnerships with manufacturers to ensure affordable, scalable production
- Explore shelf-stable formulations that don't require refrigeration for use in developing countries
Understand how to run rigorous longevity clinical trials in a reasonable time at low cost. The Dog Aging Project is running a 3 years long clinical trial to evaluate Rapamycin for pet dogs (TRIAD). The American Federation for Aging Research has proposed a six years long clinical trial to evaluate Metformin for people (TAME). Both are first versions from which we can learn and iterate. Some strategies include:
- Run clinical trials from a preventative perspective instead of a curative one
- Run trials in countries with lower operational costs while upholding data quality standards
- For repurposed drugs, reference existing safety data to justify shorter trials with fewer patients that focus only on new aging-related endpoints
- Validate aging biomarkers that are economical lab tests to use in place of expensive imaging or clinical assessments
- Use consistent core endpoints across different clinical trials
- Enroll patients virtually whenever feasible to improve recruitment and retention
- Take advantage of large pooled medical record databases to identify eligible patients rather than traditional recruiting
- Leverage wearable devices and digital biomarkers to generate real-world data (RWD) at scale, reducing the need for expensive clinic visits
- Publish trial protocols, analysis plans, and data to allow complete auditing and verification of results
Collaborate with regulators to find new pathways to market for geroprotectors. It's essential to overcome the agreed pessimism and skepticism towards regulatory agencies and their willingness to challenge the status quo. Current health care systems cannot survive the growth of the aging population so I'm positive we can work collaboratively with regulatory agencies like the FDA and EMA to cautiously explore responsible ways to evolve our healthcare system towards more preventative medicine. Drugs are already being repurposed for preventative use: colchicine, already approved for gout and other inflammatory conditions, has just been approved for reducing the risk of heart attacks and strokes in people with atherosclerosis. Some strategies include:
- Create specialised teams of regulatory and legal experts with experience in meeting with regulators
- Meet with regulatory agencies early in the development process to align on optimal clinical trial designs and endpoints for longevity clinical trials
- Start with drug candidates that have excellent safety profiles. Unsupported experimental interventions are unlikely to be approved preventatively immediately
- Target initial approval for patients at high risk of age-related decline where benefits may be clearest. Then expand to broader populations
- Propose surrogate endpoints that sufficiently capture potential effects over shorter timeframes
- Provide as much supporting mechanistic and pre-clinical data as possible to build the case for translating effects
- Be transparent about uncertainties and limits of current data to build trust. Paint a vision of future, while maintaining the feet on the ground
- Form coalitions across multiple companies to align on unified aging biomarkers and clinical endpoints. The Biomarkers of Aging Consortium may be just the beginning of a bigger global coalition
Educate people about preventative medicine beyond lifestyle interventions. Doctors already prescribe drugs that prevent specific diseases: vaccines, statins, anticoagulants, anti-hypertensives or anti-malarial drugs. So prescribing a drug that slows down the aging process to prevent multiple diseases at once is just one step away. Some strategies include:
- Create products and brands that help consumers understand the importance of preventative drugs
- Create incentives for doctors and veterinarians to advocate for preventative drugs
- Partner with hospitals and clinics to create preventative programs
- Develop education for doctors and veterinarians on the latest scientific consensus regarding lifestyle and pharmacological aging interventions
- Support content creators with a focus on longevity and preventative medicine
The longevity space will differentiate itself from traditional biotech and thrive (trillions of dollars pouring in every year) if and only if a company manages to commercialise a product that has been clinically proven to slow down the aging process and extend healthy lifespan. Age1 just did a nice estimation of the market potential of such a drug.
For that, a different approach should be considered. It may be fundamentally different than the traditional biotech playbook: spin-out a biotech company around a novel discovery, gather enough pre-clinical data to raise capital for running real world clinical trials or sell the IP to another pharmaceutical or biotech company. Instead of being about how can THIS reach the market; it's about how can a market be created ASAP. And the way to do that is by targeting aging itself preventatively instead of curative and assuming the regulatory risk.