Thought Leadership Articles

By Ameet Nathwani, M.D., CEO of Dewpoint Therapeutics
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October 25, 2023
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Category:

Gearing up for the next revolution in medicine

Over the last 5 years, our team at Dewpoint has made astounding progress. We have taken the theoretical ideas of biomolecular condensates and transformed them into tangible science with the potential to create a new class of medicines, condensate-modifying therapeutics (c-mods).

Through our work we have already shown that c-mods can target the pathologic central ‘nodes’ of biologic dysfunction which underpin many diseases – which we have termed a “condensatopathy”. We believe that these advances will allow us to treat many devastating diseases, which were until recently, considered untreatable. As my eminent colleagues put it in a recent milestone publication in Nature Reviews in Drug Discovery: “Biomolecular condensates are emerging as attractive novel targets for drug discovery. Many proteins and nucleic acids of high therapeutic interest, including numerous targets previously considered ‘undruggable’, operate within condensates. Importantly, there is emerging evidence that condensates are ‘druggable’.”

While I am delighted by the progress the team at Dewpoint has made in the last 5 years, I am already setting my sights towards what lies ahead in the next five years.

In five years’ time, I believe that we will be able to answer some of the most pressing questions regarding the ability to effectively understand and target complex, chronic, polygenic diseases through our work on condensate biology. By then, we should have several c-mods in advanced clinical trials across several diseases, and should be well on our way to achieving the first meaningful clinical readouts with our novel therapeutics. The full potential and benefits of c-mods which target the behavior of a community of biomolecules in a condensate rather than individual pathways in complex diseases will become more apparent. Our c-mods, both in our own pipelines and in those being developed with our pharma partners, will provide the evidence to change the way our industry both understands disease and allows us to develop unique therapeutics which are able to address diseases in larger patient populations as defined by their condensate dysfunction.

But delivering on our vision and ambition to revolutionize biology and the scientific drug discovery paradigm comes with immense challenges. At Dewpoint, we have tried to anticipate these and have put into place three core pillars that will put us in a strong position to continue innovating to ensure we have the courage and stamina to do what it takes to achieve our goals.

1. A novel AI-powered drug discovery platform

Condensate science and Artificial Intelligence are destined to forge a tight and symbiotic relationship. Biomolecular condensates have been studied for many years but due to their immense and multi-dimensional complexity, progress in being able to deconvolute and target complex intra-cellular systems has progressed slowly, unlike focused target-based discovery efforts.

The compositional complexity, size and dynamics of biomolecular condensates posed several challenges for drug discovery. First, reliable models reflecting relevant biology and well-defined metrics for characterization of condensates needed to be established. Second, c-mod discovery is heavily dependent on high-resolution cellular phenotypic screening as so much of the biology is captured in the subtle phenotypic changes and properties of the relevant condensates which have only become available recently. Thirdly, the advent of the ‘pan-omics’ and in our case, condensate proteomics and genetics, has also provided an enormous corpus of data from which to build models of systems biology as it pertains to condensates. For those reasons, the identification and deep characterization of the condensate target(s) driving the observed phenotypes will seldom be straightforward. A fourth challenge is how to optimize selective partitioning of the desired c-mod into the disease-relevant condensate, given that the condensate itself creates a unique micro-environment which can affect the function of drugs, and this has also recently shown itself to be amenable to advanced computational predictions.

To overcome these challenges, Dewpoint spent the last 5 years redesigning and reinventing the drug development processes to address the biological and biophysical challenges posed by condensates. We have incorporated cutting edge digital capabilities, including state of the art computer vision approaches, to detect cryptic phenotypes. We have developed multiple advanced analytic approaches to create digital signatures to encompass cellular function and predict chemical perturbations that lead to the desired function change in the cell. Today we have a fully integrated, end-to-end platform powered by a proprietary AI engine (which we lovingly named ERSAi- after the goddess of ‘Dew’), containing nearly 3 Petabytes of proprietary data including over 4 million condensate cell images, which supports and accelerates the discovery of c-mods, from target selection to optimization of lead compounds in disease-relevant models. With our in-house trained models, and customized condensate focused library of compounds, we can now leverage the full complexity of condensate-driven systems biology to unveil novel therapeutic opportunities, and through our proprietary multi-disciplinary drug discovery engine we can deploy condensate-specific assays, and condensate specific chemistry to move drugs rapidly toward the clinic.

The combination of revolutionary biology and the latest AI approaches is a heady mix which will continue to redefine our understanding of disease and drug discovery. It is our mission to continue to fully embed and integrate these disciplines and capabilities into our platform and approach.

Given how much the tech industry itself is encroaching into disease and drug research, we understand the need to collaborate and partner with the leading minds in tech. Just last month, we announced a novel partnership between Dewpoint and an emerging digital chemistry company, Chemify, to develop a suite of digitally discovered and automatically synthesized novel molecules against condensate targets of interest in our oncology and neurodegeneration pipeline. I am also excited about a number of other cutting-edge technology orientated partnerships which I hope to bring to fruition and announce soon.

2. A new generation of scientific pioneers working in a flexible culture

As I walked through our Boston lab recently and spoke with some of our young scientists, I was struck by the thought that there is a new generation of scientists who are just starting their careers and already working on cutting-edge c-mod discovery. If this is their starting point, I can only imagine where their expertise and evolution of the approach they will help shape will take us in the next decade.

At Dewpoint, we feel the weight of responsibility to give our teams and other young scientists working in the field of condensate research the tools and support they need for both them and science to thrive.  After all, drug discovery is a lengthy process, and it will still take close to a decade for discoveries in the lab to potentially reach patients, and we need to help set the foundation of growth for the young scientists who wish to build their career and knowledge with us. For this we take a twofold approach.

The first is to ensure ours is a company where a diversity of ideas are fully encouraged and appreciated, where each employee is empowered to push the limits – not fearful of failing and where every person feels valued as their authentic self. Great science is a collective effort, and drug discovery is a team ‘sport’ requiring diverse skills. We know that to maintain this culture takes hard work and a willingness to listen and adapt. To find out more about how we are doing this, you can read the latest article from my colleague and Dewpoint’s Chief People Officer Lori Escobedo – HERE.

The second way in which we are supporting the next generation of scientific leaders is through our ongoing partnerships with academia, and we are proud of the strong links we have with the academic homes of our founders, the Max Plank Institute in Dresden (Germany) and MIT in Boston, Massachusetts (USA). As interest in the study of condensates grows, we are excited to look for new ways to collaborate with these institutions and even to extend our partnerships outside of North America and Europe.

3. An ecosystem of visionary partners

For any biotech, financing is the Sword of Damocles. As long as your investors keep faith in your promise, feel confident in your vision, and can see tangible progress against the commitments you have made, they will continue to provide you with the financial support and strategic guidance to run the company. Every investor knows the risks we face in our industry and that includes the high potential of failure or results which fail to live up to the potential of the science.

At Dewpoint, from the outset, we have been fortunate to work with committed investors who understood the challenge of exploring new biology and the time the journey could take. The original scientific concepts and the approaches we developed confirmed the potential of the biologic approach, and the continual flow of increasingly compelling data and novel drug-like c-mods has moved the scientific question of the relevance of condensates from “if” to “when”. Our initial focus on biology was backed by partners who understood condensates are not a “new pathway” and c-mods are not a “new mechanism of action” -rather that they compose an audacious new paradigm in the drug discovery ecosystem, with an unimaginable breadth of possibilities in terms of diseases which have condensate-driven biology (condensatopathies).

Now that we are entering a new phase where systems biology meets advanced computational science, this will allow us to interact with new players and investors from the tech sector who are increasingly looking to apply these technologies to the challenge of improving healthcare.

The collaborative approach we have encouraged from our early days will become even more crucial and we will need to continue to foster partnerships with major pharmaceutical companies, to help exploit the biology and disease opportunities, as well be agile enough to work with a suite of diverse novel technology companies to complement our capabilities and modernize our approach in a manner befitting a next generation of Biotech company.

Our unique platform, our pioneering team and our visionary partners are three powerful levers to achieve our goals, and I feel both excited and humbled, knowing that we hold the keys to unlock the benefits of a truly revolutionary science in our hands.

I am confident that when I write on the occasion of our 10-year anniversary in 2028, we will be celebrating the success and clinical impact that our leading, home-discovered and home-developed c-mods have had in difficult to treat diseases, and the shared success that our collaborations have had to the partnered programs where our science has helped to discover transformative drugs which our Pharma partners have progressed and are excited about.  By then, we should be on our way to having an impact on millions of lives across multiple diseases which the company set out 5 years ago.

In the meanwhile, while we can be wistful regarding our future wishes, the journey today matters as much as the destination. I am very excited by the challenges of building a company charged with transforming science, adapting drug discovery to accompany science, integrating the emergence of AI into our core substrate. We are developing new business models which embrace these challenges in a market environment which remains unforgiving, except to companies which can show they are innovative, exceptional, adaptable, and efficient. Our metamorphosis as a company will be continual, although what the end result will look like is something only our vision, drive and data will determine.

Media Contact

media@dewpointx.com

Investor Contact

Michael Fenn, PH.D.
Head of External Innovation
Dewpoint Therapeutics
mfenn@dewpointx.com
Dewpoint Therapeutics
451 D Street, Suite 104
Boston, MA 02210
USA
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