Dewpoint: the leader in condensate biology that is breaking new ground in drug discovery

Plenty of biotech companies claim to be leading a revolution with their approach to disease.

The difference with Dewpoint Therapeutics is that it is spearheading a revolutionary shift in drug discovery with its focus on the role of biomolecular condensates in disease pathogenesis. Leveraging ground-breaking new insights into cell biology, Dewpoint is decoding the intricate mechanisms of diseases to pioneer novel treatments.

“Dewpoint Therapeutics was founded on the ground-breaking realization that biomolecular condensates - dynamic, membraneless cellular structures that compartmentalize biological processes - are not only crucial to normal cellular functions, but are also implicated in disease manifestation, including cancer, neurodegeneration and cardio-metabolic disorders,” Dr Ameet Nathwani (pictured, inset image below), chief executive of Dewpoint shared with The Pharma Letter.

“Essentially, condensates may form the missing link between genetics and the origin of the cellular dysfunction underpinning many disease processes. This concept is redefining cell biology and the insights stem from seminal work first described by Dewpoint’s co-founder Dr Tony Hyman in 2009. Since then, this field has been amplified by contributions by our other scientific founders, including Dr Rick Young from the Whitehead Institute and Nobel Laureate Dr Phillip Sharp from the Massachusetts Institute of Technology (MIT).

“Together, their pioneering research has reimagined the way we think about drug targets, suggesting that dysregulated biomolecular condensates underlie many complex diseases - termed condensatopathies - providing unique ways to discover and design novel drugs that are capable of specifically and selectively modulating aberrant condensates. By re-conceptualizing the drug target as a molecular community with a unique micro-environment within a condensate as opposed to a single protein, our strategy aims to precisely modulate the function of the target condensate and, thereby, affect the multi-pathway processes involved in a disease. Remarkably, proteins and nucleic acids previously deemed ‘undruggable’ are now within reach thanks to their operation within condensates.

Emerging evidence supports the notion that condensates are indeed ‘druggable,’ igniting hope for treating diseases once thought intractable.”

Dewpoint was founded five years ago, when the scientific visionaries teamed up with Amir Nashat, a pioneering biotechnology investor from Polaris Partners, to tackle this extraordinary and complex concept.

The understanding that condensates are membraneless compartments in cells with dynamic properties, often forming by liquid-liquid phase separation, and could be responsible for disease processes was first described by multi-award-winning scientist Tony Hyman, co-founder of Dewpoint and currently director and group leader at Germany’s Max Planck Institute of Molecular Cell Biology and Genetics, in a pivotal paper published in 2009. Most recently, Mr Hyman was awarded the 2023 Breakthrough Prize in Life Sciences for the discovery.

‘Revolution in drug discovery’

“The research after 2009 started to pick up because people started to recognize the role of condensates everywhere in cellular processes,” Dr Nathwani said. “People began to think that this biology could offer a different way to understand complex disease biology, the central roles of difficult to drug transcription factors to be able to discover and design new drugs.”

Dr Young, a member of the Whitehead Institute and professor of biology at MIT, is regarded as a pioneer in the systems biology of gene control and expression and has harnessed the emergent understanding of biomolecular condensates and phase separation for new insights in his field. Like Dr Hyman, he has won multiple top scientific awards for his research.

“In the past five years since the idea was born around this extraordinary science, we have taken the traditional drug discovery process and redesigned the end-to-end approach customized to working with this ‘mesoscale’ biology,” Dr Nathwani said.

Dewpoint hired the world’s leading condensate scientists from Max Planck and Whitehead, seeking to build a platform that identifies where a condensate becomes aberrant, helping to predict diseases.

New thinking on developing therapeutics

“We use a genetics-first approach to uncover the intricate relationship between gene mutations and disease manifestation, with a particular focus on the role of biomolecular condensates,” Dr Nathwani explained. “Often, the path from genetic mutation to disease passes through alterations in condensates, leading to aberrant cellular states and diseases.”

The identification of condensates as key players in disease has opened up a new frontier for therapeutic intervention. In the realm of oncology, for instance, insights into the dysregulation of cellular condensates have spurred innovative strategies for drug development. Dewpoint is redefining the drug discovery paradigm, shifting the focus from interactions with individual proteins to targeting the dysfunctional condensates, aiming to restore normal cellular functions.

Dewpoint is leveraging advanced computational tools to expedite the exploration of condensate biology's link to human diseases, establishing a comprehensive discovery platform and advancing a drug pipeline that positions them at the forefront of developing new medicinal therapies.

Since the founding of Dewpoint, other companies are exploring the science of condensates, but Dewpoint remains a leader and continues to publish groundbreaking research in the space.

In 2022, Dewpoint was granted two ground-breaking foundational platform technology patents, cementing their leadership in condensate drug discovery.

An ambitious pipeline of ‘affordable’ medicines

Another advantage to Dewpoint’s approach is aiming to develop primarily small molecule lower cost therapies, and the pre-clinical results to date have been very encouraging.

“In an era of complex and expensive biologics and cell and gene therapies, the fact that we can tackle potentially complex diseases in large populations with small molecules, is really attractive for us to make affordable and accessible medicines,” Dr Nathwani said.

Dewpoint has discovery programs across an ambitious pipeline, with a proprietary pipeline focused primarily on cancer and neurodegeneration at present, though big pharma has shown interest in the company’s exploration of modulating condensates to target diseases through multi-program collaborations across many different therapeutic areas.

Currently, Dewpoint has partnerships with Bayer (BAYN: DE) to use its platform in cardiovascular and renal diseases and with Novo Nordisk (NOVN: VX) to use it for the treatment of insulin resistance.

The collaborations are part of a broader strategic approach that Dewpoint is taking to accelerate the momentum and demonstrate the impact of condensate derived drug discovery.

Partnering with and learning from the best

“Science is a team sport,” Dr Nathwani said. “The reason that we have Max Planck, the Whitehead Institute and MIT as academic collaborators is because we know that the scientific excellence that drives some of these concepts emerges from many places. We want to be at the frontier. We have great scientists internally, and we think collaborating with world class academic centers and scientific advisory groups strengthens our innovation.

“We wanted to emulate the most successful biotech companies that had to demonstrate the impact of cutting-edge science. And many of these innovators, for example, Moderna (Nasdaq: MRNA), Alnylam (Nasdaq: ALNY) and Regeneron (Nasdaq: REGN), all started with not just new biological concepts, but formed strategic partnerships early on. This approach rapidly creates momentum and provides multiple points of external scientific validation. You gain deep insights into redesigning the drug development and discovery process from these partnerships. We’ve taken the same approach and I am positive it will allow us to accelerate and showcase our science more broadly.”

Dr Nathwani continued: “We’ve forged partnerships with leading global pharmas in disease areas that we, as a small company, could not afford to develop ourselves. As a small company, we do not have the resources to develop drugs in cardiology or in diabetes. We viewed Bayer as a leader in the in the cardiovascular space and Novo Nordisk as a leader in the metabolic space—what great partnerships to develop breakthrough drugs in these areas. This will allow us to focus and continue to build our own pipeline in oncology, as well as very targeted diseases in neurology. Those are more manageable initially for a company of our size.”

Deep consortium of investors

Dewpoint is also evaluating other strategic partnerships in different therapeutic areas. But the validation of its platform comes not just from partners in pharma, but also from investors, which have participated generously in three separate rounds since 2019 during what has been a turbulent time in biotech fundraising.

These rounds have raised a total of $287 million, led by founding investor Polaris Partners as well as ARCH Venture Partners and SoftBank Vision Fund 2, with repeat participants including Leaps by Bayer, Samsara BioCapital, EcoR1 Capital and Maverick Ventures.

“We’ve been deeply fortunate to have secured substantial backing from a very deep consortium of biotech investors,” Dr Nathwani said. “They see this as transformative science and are very excited about its novelty and potential.”

“And what’s important is that they’re not impatient. They know this is going to require time and we have to create the discovery platform and the process first, and the novel medicines will quickly follow.”

The support of these investors will be important again as Dewpoint looks to raise further capital in the next 18 months.

“We have the money to get into the clinic,” Dr Nathwani said. “We want to make sure that we can fund through the completion of the early studies because we want to make the readouts compelling.

“We also now have a significant proprietary data and an accompanying AI approach to amplify our discovery efforts, so hopefully the next round will attract a more diverse set of investors, including from the tech side.”

Big plans in a short time

With strong interest in and support for the company, and leading scientists based in Boston (USA), Dresden and Frankfurt (Germany), it is no wonder that Dr Nathwani and his colleagues are optimistic when they consider where the company might be in five years’ time.

“The first thing is we want to make sure that we bring several of our breakthrough therapies into the clinic,” he said. “While five years is too short a time to get a new medicine to the market, we expect to be in the late clinical phase with some of our breakthrough therapies in cancer and neurodegeneration, as well as have the next generation of oncology programs about to enter the enter the clinic.

“At the same time, we want to see partnership successes. We have several milestones with both Bayer and Novo Nordisk across the five years. If we meet those, it will be remarkable for those companies, and remarkable for us, and would further validate the impact of condensate science.

“Our ultimate goal is unchanged. We aim to leverage this ground-breaking science to create breakthrough and cost-effective medicines and change the disease understanding along the way.”