POWER TO THE PROTEASOME
Pioneering a new class of medicines that fully activate the cell’s natural quality control machinery to treat a range of complex indications
Overwhelmed proteasomes lead to complex cell dysfunction. No one has known how to restore their activity.
Until now.
Proteasomes degrade damaged, misfolded, or unnecessary proteins. To date, protein degradation therapeutics have mainly focused on tagging individual proteins of concern with a protein called ubiquitin, inducing their degradation. While this approach holds promise, it does not address the broader issue of natural proteasome dysfunction which affects many protein pathways and contributes to many major diseases. Our approach is designed to restore the proteasome’s full potential with therapeutics to address complex diseases.
In healthy cells, proteasomes play a critical role in maintaining cellular protein homeostasis, the correct balance between production and degradation of proteins.
HOMEOSTASIS
DISEASE STATE
With age and disease, impaired proteasome function causes a progressive stress cascade as “cellular junk” accumulates and impacts many pathways.
20S PROTEASOME ACTIVATION
Our small molecules are designed to directly boost the activity of 20S proteasomes to restore the body’s ability to clear disease-causing proteins.
Finally in the spotlight:
The 20S Proteasome
Conventional protein degradation methods target proteins implicated in single-factor diseases by tagging them with the marker protein ubiquitin. This leads to their degradation by 26S proteasomes.
By contrast, Booster’s approach directly activates the natural 20S proteasome, which:
recognizes disordered proteins without the need for ubiquitin tagging,
degrades disease-associated proteins known to accumulate abnormally,
reverses proteasome dysfunction in general, and
20S proteasome activity decreases with age, underscoring the potential to restore their activity against a range of diseases that increase in incidence as we age.
Activating the ‘universal surveillance’ of the 20S proteasome thus leads to a holistic restoration of quality control activity that makes cells more resilient to stress and faster at degrading and removing large numbers of varied misfolded proteins throughout the cell.
When 20S proteasomes are working properly, the body is better at keeping diseases at bay. Research in both humans and animals demonstrates a correlation between increased 20S proteasome function and cellular resiliency, and longer lifespan. Experimental data showing restored proteasome function with our activators support this hypothesis. Our compounds accelerate toxic protein removal and rebalance cellular homeostasis. The implications for solving complex degenerative conditions associated with age, such as neurodegenerative diseases, are enormous.
–Dr. Diogo R. Feleciano, Co-Founder & CSO
Leading the Way
Booster’s progress in proteasome-based drug discovery is built on deep scientific expertise on proteasome function and the untapped potential to deploy proteasome activation against a range of difficult-to-treat diseases. Through our structure-based DGRADX™ platform, combining proprietary methods for automated high-throughput screening and X-ray crystallography, coupled with advanced computational tools, we have built an extensive library of activator compounds with therapeutic potential and assembled compelling data supporting our approach.
Clinical Opportunity
Booster is building a multi-disease pipeline to address diseases associated with a breakdown in proteasome function. We are initially focused on neurodegenerative diseases.
Meet the Booster Team
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Dr. Diogo R. Feleciano
CO-FOUNDER & CSO
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Dr. Emanuele Gabellieri
HEAD OF MEDICINAL CHEMISTRY
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Prof. Dr. Darci J. Trader
SCIENTIFIC CO-FOUNDER / ADVISOR
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Dr. Marianne E. Mertens
MANAGING DIRECTOR
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Dr. Sonia Poli
HEAD OF TRANSLATIONAL SCIENCES
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Dr. João Ribas
INTERIM-CBO
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Dr. Aldemar Degroot
STRATEGIC ADVISOR
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Dr. Niels Plath
SENIOR ADVISOR
Board of Directors
Chair of the Board,
Booster Therapeutics
Chief Executive Officer,
TRIANA Biomedicines
Dr. Patrick Trojer
Managing Director,
Booster Therapeutics
Partner, Apollo Health Ventures
Dr. Marianne E. Mertens
Interim Chief Business Officer,
Booster Therapeutics
Principal, Novo Holdings
Dr. João Ribas
Dr. Jan Adams, MBA
Partner, Apollo Health Ventures