Fight Aging!

Biopharma Dealmakers is a research news publication used by biotech and pharmaceutical startups to promote themselves and explain their work, published in association with editorial commentaries on the present state of the industry, as well as on specific areas of focus in research and development. It is published by Nature, and the way in which his typically works, under the hood, is that the editors decide on areas of focus for each issue and then reach out to selected companies related to that area of focus in order to invite them to pay a modest amount for inclusion. Technically this is a form of advertising wherein the Nature staff assists the selected companies in writing articles to discuss their research and development programs. The intended audience of that advertising is made up of life science investors and Big Pharma - publicity is ever useful!

However, this is also one of the few ways in which busy company leaders can be induced to explain their work in a format accessible to laypeople, and which is freely available to readers of any affiliation. So it can be an interesting read for industry observers. The last issue of 2023 includes a section on the longevity industry, and coverage of a few of the companies targeting age-related disease and mechanisms of aging that are currently interested in launching new initiatives or raising significant funding in the near future: Bioviva Science; Deciduous Therapeutics, a senolytics company; NIBEC; Rejuveron Life Sciences; and Repair Biotechnologies, the company that I co-founded. A few selected quotes follow, but I encourage you to take a look at the whole issue.

Biopharma Dealmakers, Volume 17 Issue 4, December 2023

Biopharma Dealmakers - a Nature Research publication - brings together life scientists, biotech and pharmaceutical professionals, and investors from across the globe. Biopharma Dealmakers offers readers themed editorial features that provide insights into dealmaking and industry trends. Regular editorial content includes biopharma deal round-ups, financing news and a collection of 'business of science' articles from the Nature Research catalogue. Biopharma Dealmakers also includes profiles of companies looking to partner or seek investment that showcases their pipeline products, technologies, therapeutic focus and partnering strategies. In this issue: Top 20 biopharma deals of 2023. Live forever: approaches to reverse aging. What are the drivers behind CNS deal flow? Oligonucleotide therapies broaden their reach. Make way for gene editing.

Editorial: The quest to turn back the clock

Delaying aging, restoring youth, regenerative medicine... whatever term is used, research aiming to target fundamental mechanisms of aging to increase life expectancy and quality has flourished in recent years. Ten years ago, researchers wrote a review that described hallmarks of aging, including genomic instability, stem cell exhaustion, deregulated nutrient sensing, mitochondrial dysfunction, and cellular senescence. Among efforts to target these hallmarks with potential therapies, those focused on cellular senescence have been at the forefront of industry activity, with more than 20 companies established in the past decade. In this piece, we highlight some of the progress and challenges for a selection of these companies.

Repair Biotechnologies: Developing therapies to degrade free cholesterol

Cholesterol is largely manufactured in the liver and transported throughout the body via a system of carrier molecules such as low-density lipoprotein (LDL) particles. Inside cells, cholesterol is esterified to provide protection from the toxicity of free cholesterol. Local excesses can overwhelm this protective mechanism and cells have no internal mechanism for degrading cholesterol. "When your system of transport breaks down, which happens in obesity and aging, localized excesses of cholesterol form. Our data show that the consequent toxicity is an important cause of downstream damage and disease." No current therapeutics directly target free cholesterol. While lifestyle changes, statins, or PCSK9 inhibitors can dramatically reduce LDL cholesterol levels to lower risk of atherosclerosis and slow its progression, they do not significantly impact free-cholesterol excess or reverse the damage caused by free cholesterol. "Getting rid of excess free cholesterol was impossible until our approach to effectively target it."

Established therapies focused on lowering LDL cholesterol cannot meaningfully remove established plaques, but Repair's animal studies have shown a sizeable reversal of plaques following gene therapy mediated clearance of free cholesterol. The company is now finalizing its formulation and preclinical studies. Repair is also developing a therapy for NASH, which affects 3% to 6% of the US population, being more prevalent in patients with metabolic disease and obesity. It progresses from inflammation and fibrosis to cirrhosis in approximately 20% of cases and is associated with increased overall mortality. There is no US Food and Drug Administration (FDA)-approved therapy for NASH, and, like atherosclerosis, its progressive pathology is largely irreversible. Repair's gene therapy reduced liver-tissue free cholesterol in mouse models significantly after only a few days, rapidly reducing key serum markers of liver damage. Moreover, hallmarks of NASH pathology including liver inflammation, insulin resistance and, most importantly, liver fibrosis were all significantly reduced following an 8-week therapy.

Deciduous Therapeutics: Restoring immune surveillance to tackle age-related diseases

Researchers discovered that a subtype of cells that sit between the innate and adaptive immune system were dramatically dysfunctional where senescent cells were accumulating. They m showed in two different mouse models of disease that the number and function of these invariant natural killer T (iNKT) cells was significantly reduced in tissues with high levels of senescent cells. Initial work showed that a tool compound, alpha-galactosylceramide (αGalCer) could be used to activate iNKT cells and reduce senescent cells in adipose tissue, leading to durable improvements in blood glucose levels, insulin resistance and HbA1c levels in diet-induced obese mice.

Subsequently, to demonstrate the widespread utility of immune-based senolysis, the company applied the approach to a severe model of pulmonary fibrosis. In this study, a single treatment at the peak of disease resulted in the ablation of senescent cells in the lung and attenuation of key fibrotic and inflammatory markers, which ultimately resolved fibrosis. Deciduous Therapeutics has used computational assisted design to synthesise a suite of proprietary therapies that could be used in the clinic to re-activate tissue-resident iNKT cells. To date, the company's lead program has shown single-dose efficacy in resolving both metabolic and fibrotic diseases along with a favorable safety profile at doses significantly higher than the efficacious dose.