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

  • Dr. Diogo R. Feleciano

    CO-FOUNDER & CSO

  • Dr. Emanuele Gabellieri

    HEAD OF MEDICINAL CHEMISTRY

  • Prof. Dr. Darci J. Trader

    SCIENTIFIC CO-FOUNDER / ADVISOR

  • Dr. Marianne E. Mertens

    MANAGING DIRECTOR

  • Dr. Sonia Poli

    HEAD OF TRANSLATIONAL SCIENCES

  • Dr. João Ribas

    INTERIM-CBO

  • Dr. Aldemar Degroot

    STRATEGIC ADVISOR

  • 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

We are proud to have the support of leading life sciences investors