Proteasome activation offers important advantages over more limited conventional protein degradation approaches and provides a powerful lever to combat the effects of the many types of deviant proteins that can accumulate in cells when proteasome function declines through age or disease. The implications for solving major degenerative conditions, such as Parkinson’s and Alzheimer’s, are enormous, said Dr. Diogo Feleciano, Co-Founder and Chief Scientific Officer. We’re grateful for the support of our investors, who have enabled us to assemble a world-class team to realize the untapped potential of proteasome activation against a range of difficult-to-treat diseases.

Proteasomes, the cell’s natural quality control machinery, play a critical role in removing damaged or misfolded proteins. When their function is impaired, misfolded proteins accumulate and increase the risk of serious disease. Booster’s approach is a departure from current targeted protein degradation methods, which tag single disease proteins with the marker protein ubiquitin, leading to their degradation via 26S proteasomes. This can be effective, particularly in diseases driven by a single errant protein. But complex diseases are often driven by multiple protein dysfunctions. To achieve more widespread degradation of unwanted proteins, Booster’s compounds directly activate 20S proteasomes, which naturally recognize disordered proteins without the need for ubiquitin tagging.

Booster exploits the cell’s universal protein surveillance machinery to drive restoration of protein homeostasis in various disease contexts, said Dr. Patrick Trojer, Chair of Booster’s Board of Directors and Chief Executive Officer of TRIANA Biomedicines. “The application potential of this therapeutic frontier is highly attractive, and given the broad-spectrum activity of proteasome activators, we see opportunities for both monotherapy and combination approaches where increased proteasome activity may enhance the efficacy of other therapeutics. 

Booster is discovering small molecules through its DGRADX platform, which combines proprietary methods for automated high-throughput screening with advanced structural and computational tools. The company has built an extensive library of activator compounds with therapeutic potential and aims to develop a multi-disease pipeline to address proteinopathies. 

Emerging from Apollo's company creation engine, Booster has made remarkable strides in pioneering this exciting new field of medicine. Booster’s focus on activating the 20S proteasome directly addresses a critical mechanism involved in the cellular stress of aging, offering us a new therapeutic perspective on major disease areas, said Dr. Marianne Mertens, Partner at Apollo, Managing Director, and Board Member of Booster Therapeutics. “We look forward to working with the team and the strong syndicate to advance toward proof-of-concept and develop a pipeline of potential first-in-class medicines.

The pioneering work of Prof. Trader and Dr. Feleciano completely transformed our approach to protein degradation in proteinopathies. Booster’s data support the ability of the 20S proteasome to safely, effectively and specifically degrade a wider set of pathological proteins. said Dr. João Ribas, Principal at Novo Holdings, Seed Investments and Interim Chief Business Officer and Board Member, Booster Therapeutics. “Proteinopathy is core to many of the most challenging complex diseases, so the potential to address them with a single agent is incredibly promising and could reshape the treatment landscape. We’re excited to join Apollo and help advance this novel therapeutic concept to the clinic. 

Source: https://www.businesswire.com/news/home/20241010031303/en/Booster-Therapeutics-Launches-to-Pioneer-New-Class-of-Proteasome-Activator-Medicines-for-the-Treatment-of-a-Range-of-Complex-Diseases