European Biotech Targeting Anti-ageing

Barton,Cheryl;

European Biotech Targeting Anti-ageing

October 2, 2024

By Cheryl Barton

News

Article

Pharmaceutical TechnologyPharmaceutical Technology, October 2024

Volume 48

Issue 10

Pages: 14–15, 18

Novel mitophagy inducers and gene therapies that restore cellular function and decelerate the ageing process.

cosmetic molecule and chromosome background | Image Credit: ©Thongden_studio - stock.adobe.com

Over the past century, life expectancy has dramatically increased in most parts of the world, but humans are spending more years in poor health than at any point in history (1). However, technological and scientific advances have increased our understanding of the ‘hallmarks of ageing’ resulting in molecular and cellular changes that lead to the modulation of mitochondrial dysfunction, inflammation, and cellular senescence (2).

Editor's Note

This article was published in the October 2024 print issue of Pharmaceutical Technology® Europe.

Ageing is emerging as a druggable condition with multiple pharmaceuticals able to alter the pace of ageing in model organisms. Anti-ageing activity has been demonstrated in some US Food and Drug Administration (FDA)-approved drugs such as the immunosuppressant rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, and the anti-diabetic agent, metformin, an AMP-activated protein kinase (AMPK) activator (3). US-based Aeovian Pharmaceuticals and Amplifier Therapeutics are looking to develop next-generation AMPK and mTOR inhibitors in age-related diseases (4,5).

Biopharma prioritizing ageing research

Many biopharmaceutical companies are now prioritizing ageing research for early-stage discovery or therapeutic pipeline development. BioAge Labs, Fauna Bio, and Insilico Medicine are deploying artificial intelligence (AI)-enabled multi-omic platform technologies to identify novel anti-ageing targets. Several experimental drugs—dasatinib, fisetin, navitoclax, and quercetin—have demonstrated senolytic activity, and inhibitors targeting Bcl-2, HSP, tyrosine kinase or P53, are now being evaluated by biopharma as potential senolytics (6). One of the most advanced programmes is Unity Biotechnology’s UBX1325 (foselutoclax), a Bcl-2 inhibitor in Phase II development for the treatment of age-related macular degeneration (AMD) (7).

Several European start-ups are actively pursuing anti-ageing research including Swiss-based Vandria and UK-based clook.bio and Genflow Biosciences.

Vandria mitochondrial therapeutics look promising in neurodegenerative disease models

Vandria is developing novel mitophagy inducers that rejuvenate cells to treat age-related and chronic diseases. The decline in mitochondrial function has been implicated in many age-related diseases including mild cognitive impairment (MCI), neurodegenerative diseases, and muscular disorders. Vandria has demonstrated that removing damaged mitochondria via mitophagy can rejuvenate cells leading to an improvement in cellular functions and the generation of energy or ATP (adenosine triphosphate) (8).

Vandria has built a proprietary in vitro screening platform and generated a novel pipeline of small-molecule mitophagy inducers to target different tissues and address specific unmet medical conditions. Its lead programme, VNA-318, has completed investigational new drug (IND) studies for central nervous system (CNS) indications including MCI, Alzheimer’s, and Parkinson’s diseases, and other forms of dementia. Its other preclinical programmes include VNA-052 for sporadic inclusion body myositis, VNA-438 for Metabolic Dysfunction Associated Steatohepatitis (MASH), VNA-710 for idiopathic pulmonary fibrosis (IPF), and VNA-897 for an undisclosed target (9).

In February 2024, Vandria was awarded a CHF 2.5 million (US$2.8 million) research grant from the Swiss Innovation Agency Innosuisse to help advance the development of VNA-318 (10). The funds will be matched with CHF 4.6 million from the company initiative to progress VNA-318 into Phase I/IIb clinical trials in 2025. In preclinical animal models, VNA-318, has been shown to improve memory and learning. Additionally, VNA-318 has strong disease-modifying effects in Alzheimer’s and Parkinson’s disease models and has a wide safety window. The company has been issued a composition of matter patent by the US Patent Office covering VNA-318 and other compounds (10).

The company is also advancing the development of another mitophagy lead candidate, VNA-052, for muscle diseases. This clinical programme was awarded a research grant, totaling €1.1 million (US$1.2 million) from Eurostars, a programme co-funded by the European Union (10). In August 2024, Vandria announced the second closing of its Series A financing raising CHF 28.3 million (US$30.7 million). The funds will be used to support its clinical development programmes (11).

Pioneering gene therapies to decelerate the ageing process

Recent advances in gene editing and delivery have allowed scientists to partially reprogramme cells and reverse the effects of ageing (12). Two UK start-ups, clock.bio and Genflow Biosciences, are leveraging human inducible pluripotent stem cells (hiPSC) to prevent and treat age-related diseases:

clock.bio was founded in 2020, by Mark Kotter and has attracted more than US$4 million (€3.6 million) in funding (13). The company has developed an ageing model that force-ages hiPSCs to trigger self-rejuvenation. The company deploys unbiased clustered regularly interspaced short palindromic repeats (CRISPR) screens to identify gene candidates that are causally linked to cell rejuvenation. Clock.bio aims to decode the biology of human rejuvenation across the entire human genome and generate a comprehensive atlas of disease and rejuvenation targets for clinical translation (14).
Genflow Biosciences was founded in 2020 and has R&D facilities in Belgium. Its lead compound, GF-1002, a suspension of an adeno-associated virus vector-based (AAV-based) gene therapy that delivers the centenarian variant of the sirtuin 6 (SIRT6) gene, a gene intricately linked to cellular stress responses that can promote longevity in mice. GF-1002 has demonstrated promising preclinical results and is due to enter clinical development in 2025 for the treatment of MASH (15). In January 2024, Genflow established two technological innovation partnerships with Revatis SA and with EXO Biologics to develop advanced therapy medicinal products (ATMPs) in sarcopenia and Werner Syndrome, respectively (16). In April 2024, Genflow raised £715,000 (US$959,000) through the placing and subscription for new stock organized by Capital Plus Partners (17). Genflow has been awarded a European Patent with the University of Rochester, New York, for SIRT6 in the prevention and treatment of age-related diseases (18).

In the United States, numerous companies are also pursuing cellular reprogramming strategies including Altos Labs, Longeveron, Retro Biosciences, Rejuvenate Bio, and Turn Biotechnologies (19–23).

Future opportunities

Great strides have been made in anti-ageing longevity research, numerous drug targets have been identified, and several agents are progressing steadily through the clinic. In 2021, venture capitalists invested $9.26 billion (€8.3 billion) in this area, with cellular reprogramming and rejuvenation attracting the most attention (24). Pharma has announced several partnerships in this space including Eli Lilly/Fauna Bio, Sanofi/Insilico Medicine, and Pfizer/VitaDAO. While US biotechs dominate the scene, European and UK start-ups are gaining traction, and there are significant opportunities for pharma to expand their foothold and take a more proactive approach in the treatment of chronic age-related diseases.