Re-inventing drug discovery by targeting biomolecular condensates

We gained exponential growth in technology over the past few decades, but the field of drug discovery has remained relatively stagnant. There is a need for re-inventing the drug discovery process with disruptive innovations. The term “disruptive innovation” first coined by Clayton M. Christensen in 1995, describes the innovations that significantly affect the way a market or industry functions and changes the dynamics of the competitive market. These innovations are imperative to bring new players to the competition captured by big companies reluctant to innovate and few of these players successfully create their niche eventually creeping their way upmarket to topple the incumbent.

Focusing on biomolecular condensates as a druggable target is one such disruptive advancement which re-ignited the curiosity in drug discovery. Recently, drug-discovery particularly in the field of neurodegenerative diseases hit numerous roadblocks. Big pharma companies halted their ongoing drug discovery programs after successive disappointments to discover any lead molecule targeting amyloid plaques implicated in neurodegenerative diseases. The emergence of biomolecular condensates field changed the way we approach amyloid disease treatment.

Biomolecular condensates are membraneless organelles enriched in proteins and nucleic acids. These are involved in the diverse cellular processes and also implicated in diseases. Even though Prof. Edmund Beecher Wilson first mentioned liquid-like organelles in 1899, it took more than a century to clarify the concept of liquid-liquid phase separation (LLPS) as a fundamental physicochemical mechanism for cytoplasm organization described in Science paper (2009) by the lab of Prof. Anthony Hyman. This landmark discovery leads to the emergence of the biomolecular condensate field which is now explored by hundreds of labs across the world. Driven by multivalent interactions, these biomolecular condensates or phase-separated membraneless organelles play a critical role in regulating diverse cellular processes. a growing body of research suggests that these condensates are not only important for normal cellular homeostasis but implicated in complex conditions like neurodegenerative diseases, viral infection, and cancer. This opened up the new avenue for the drug discovery for targets considered as undruggable. With huge potential to identify entirely novel targets and unexplored ways to modulate these targets hidden within condensates brought new excitement to the field. With many pharma companies on the verge of closing their ongoing drug discovery programs especially for neurodegenerative diseases, the emergence of biomolecular condensate field is a breather much needed at this time than ever. With the intent to disrupt these condensates now considered as hot spots, many pharma companies jumped into the race without taking risks directly.

Currently, two startups Aquinnah Pharmaceuticals and Dewpoint Therapeutics are leading the drug discovery race for targeting biomolecular condensates. Aquinnah pharmaceuticals was founded in 2014 by Dr. Glenn Larsen and Prof. Ben Wolozina. Company rely on their discovery of the connection between stress granules and neurodegenerative disease. It received funding from Takeda Pharmaceuticals, Pfizer, Abbvie and grants from National Institute of Neurological Disorders and Stroke (NINDS) and The Tau Pipeline Enabling Program (T-PEP) for developing new therapies for Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Despite early start, Aquinnah failed to impress investors over the past six years and probably missed to achieve milestones. With small funding at their dispel, the company struggled to push any molecule to clinical trials and no official updates on current status from the company since January 2019.

Aquinnah Pharmaceuticals (Timeline picture created using visme)

Another startup Dewpoint Therapeutics founded in 2018 by Prof. Richard Young and Prof. Anthony Hyman is making inroads at a faster pace. With already two big deals with Bayer and Merck for different modalities encompassing cardiovascular, gynecology and viral diseases apart from an exciting future portfolio including neurodegeneration, cancer, inflammation, infectious disease, metabolic disease and rare genetic disorders. With a growing team of scientists based in Boston and Dresden and good financial support, Dewpoint is setting up an example by “translating the condensate biology into much-needed medicines”.

Dewpoint Therapeutics (Timeline picture created using visme)

With ample opportunities available for drug discovery, over time, the usefulness of targeting biomolecular condensates will be undermined. As we know that not every disruptive path leads to a triumph, it will be interesting to see whether this emerging curiosity in targeting biomolecular condensates will sustain and prove to be a disruptive innovation.

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