Request for Startups in the Rejuvenation Biotechnology Space, 2024 Edition – Fight Aging!

Investors focused on funding biotechnology startups tend to exhibit herd behavior, much like investors everywhere these days. Funding is primarily deployed towards fads and popular trends, not necessarily towards what makes the most sense, even if sometimes the sensible manages to align with the popular. These days that means drug discovery platforms with a strong computational component and partial epigenetic reprogramming. But even in this environment, the path to true success is to work on important projects that few other people are touching. Be the champion for a potential solution to a tough, high-value, comparatively neglected problem.

Considering those tough, high-value problems, we can look at the world as it stands today and count how many people die from this age-related condition or that age-related condition. We could start at the top and work down: atherosclerosis, cancer, viral infection, dementia, kidney disease. All of these categories are vast, worldwide, with room for a sizable number of companies to all achieve significant success. For each of the categories of mortality mentioned above, there is room for many different therapies that address some part of the complex web of mechanisms of aging that lead to disease and death.

More First in Class Treatments for Atherosclerosis

The present state of therapy and development for the treatment of atherosclerosis is dismal. Industry and regulators are fixated on lowering LDL-cholesterol in the bloodstream, an approach that has demonstrably and comprehensively failed to reverse established atherosclerotic plaque, only slowing the progression of the condition modestly. The still-standard small molecule therapies, statins, have meaningful unpleasant, dose-limiting side-effects for a sizable fraction of patients. New development remains near entirely focused on novel ways of lowering LDL-cholesterol, none of which are shown to do any better than statins when it comes to the most important outcome, which is to say reversing the growth of atherosclerotic plaque. Outsider biotech startups like Cyclarity Therapeutics and Repair Biotechnologies cannot continue to be the only groups developing novel, different, ambitious therapies aimed at reversal of atherosclerosis. There is a vast gap in the market, an enormous unmet need in the 26% of humanity that is killed by stroke and heart attack, the direct consequences of unstable atherosclerotic plaques. This ongoing toll takes place in a world in which everyone who can use statins is using statins. We must do better.

More Attempts at a Universal Cancer Therapy

A good number of mechanisms involved in cancer are, if not completely universal to all cancer cells, at least common across a sizable fraction of all cancers. Far too little work is focused on influencing these mechanisms. Finding ways to interfere in alternative lengthening of telomeres (ALT), for example, continues to languish despite being an excellent target for small molecule development, given that ALT only operates in cancerous cells. As the rapid progress of Maia Biotechnology demonstrates, a broadly applicable cancer therapy (targeting telomere extension in their case) will quickly draw the attention of well-funded backers in an industry that has hobbled itself by focusing discovery on uncovering per-cancer and per-cancer-subtype mechanisms without broad application.

Far Better Antiviral Therapies

Present antiviral therapies are a mixed bag, all too few of which are truly effective. Herpesviruses and similar viral infections that persist over years and decades are implicated in the decline of the immune system and development of age-related diseases. The failing immune system also allows influenza and similar respiratory viruses to transiently infect and kill immense numbers of older people every year. There are too few approaches under development, such as the successor to the DRACO methology at Kimer Med, aimed at the production of improved antiviral therapies that are not just more effective for some viral infections, but can also target many different viruses with minimal alteration to the therapy itself.

Means to More Selectively Suppress Excessive Inflammation

The chronic inflammation of aging is highly disruptive to tissue function and drives the progression of many of the common fatal age-related conditions. This maladaptive, unresolved inflammatory response derives from a wide range of processes, everything from the persistent viral infections mentioned above through to a growing burden of senescent cells, bad behavior on the part of visceral fat cells, innate immune reactions to mitochondrial stress and mislocated mitochondrial DNA, and much more besides. So far, research into the biochemistry of inflammatory signaling suggests that both useful, short-term inflammatory reactions and harmful, excessive, unresolved inflammatory reactions run through the same signaling pathways. This is not a certain conclusion, however. If it is the case, then the only way to dampen the chronic inflammation of aging without also suppressing necessary immune function is to fix every dysfunction of aging. Are there short-cuts, however, ways to interfere in only the unwanted inflammatory signaling? Perhaps.

Infrastructure for Faster, Cheaper, Responsible Clinical Trials

There is a huge gap in the options available for clinical development of therapies. Moving forward within the established FDA or EMA system, requiring expensive GMP manufacturing processes and trial infrastructure is excessively costly and far too cautious for near all therapies entering this process. Options such as holding formal clinical trials outside the US, with Australia being a popular location, do not reduce the cost by anywhere near enough. Alternatively one can deploy therapies in clinics outside the US and offer services via medical tourism, suffering all of the consequences thereof, such as lack of public trust and low numbers of patients.

Where is the middle ground between these two points? Sadly, there is no established middle ground whereby responsible clinical trials can be conducted within a system with a good reputation, outside the FDA and EMA systems, making full use of the low cost options of sites such as Próspera in Honduras. Not all medical therapies need GMP manufacture for reasonable degrees of safety. Not all medical therapies need heavy-duty trial infrastructure to provide sufficient proof of safety and efficacy to convince physicians to use them. If we want faster progress, then the costs of medical development must be greatly reduced. Groups associated with the Próspera project are among the few presently attempting to build this middle ground – but there is a great deal of room for competition in the production of a low-cost, responsible, trusted alternative to the FDA and EMA.