Nested Therapeutics Raises $90M to Crack New Proteins in Precision Oncology

Klaus Hoeflich_Nested Therapeutics

Nested CSO Klaus Hoeflich, Ph.D./courtesy Nested Therapeutics

Nested Therapeutics, a precision oncology company targeting previously undruggable cancer targets, closed on a $90 million Series A financing Thursday, bringing total financing to $125 million since its inception in 2021. 

Nested CEO Darrin Miles and co-founder and CSO Klaus Hoeflich, Ph.D. spoke with BioSpace about the company's approach ahead of the official company launch.

Nested developed a “proprietary approach to comb through a compendium of the current mutations associated with cancer and was able to identify driver mutations," Miles said.

Darrin Miles_Nested TherapeuticsBehind the company is a “team of highly experienced drug hunters who have collectively brought over 35 candidates to the clinic," he added. 

“We’re in this unique opportunity where we know the current mutations in cancer, but we don’t know what those mutations do, and which of those are driver versus passenger mutations," Hoeflich said. "So we decided to take an entirely differentiated approach and employ a structure-based lens to the channel.”

Discovering Mutations and Cracking New Proteins

This allows the company to discover newly uncovered driver mutations and pockets in cancer targets dubbed “high-conviction," as the evidence suggests they are likely to be effective approaches to treating the disease.

Nested’s technology platform has three pillars: mapping mutational clusters onto the structural proteome, identifying druggable pockets and cancer-driving mechanisms and designing novel drugs optimized for those pockets.

As a result of this approach, Hoeflich said the company is "cracking new proteins for which we didn’t have insights before."

In addition, "there are a lot of AI-based methodologies that have come out in the past few months that we employ to fill some of the gaps, not just gaps in what an individual protein structure would look like," but Nested also uses AI to understand how proteins can best get together to form a sequence.  

The company aims to find relationships between cancer mutations that were not previously known, and in some cases, those mutations map “as a cluster to a very discrete region of a protein target,” Hoeflich said.

“It may be a pocket or part of a loop of a signaling domain that is important for signaling dynamics, and in those instances, we’re very interested.”

Nested wants to “be known as the company that has the best targets and novel differentiated mechanisms," Hoeflich said. 

In that respect, the company's platform has given it a runway of over 300 of those types of target opportunities. 

What's Next for Nested

The Series A round was led by the Life Sciences Investing business within Goldman Sachs Asset Management. New investors included Foresite Capital, Avidity Partners, Cowen Healthcare Investments and Section 32. Nested was founded by Versant Ventures.

The funds raised will help to advance Nested's pipeline programs, with its lead program, NEST-1, and another program, NEST-2, a little further behind. NEST-1 is a non-degrading dual molecular glue targeting several components of the MAPK pathway.

Miles indicated the company is moving forward on selecting its development candidate for NEST-1 by the first quarter of 2023, with plans to submit an Investigational New Drug application about a year later. “We would expect then to be in the clinic by 2024,” Miles said.

The pathways Nested is focused on, MAPK and RAS, are common in at least one-third of cancer types. Miles and Hoeflich were hesitant to announce specific indications they hope to treat, but Hoeflich said the company was “very focused on the biomarker piece in order to find those patients most dependent and most likely to benefit from our medicine."

Miles also emphasized Nested is not just a “platform company,” although he noted the platform is highly differentiated which allows it to “uncover a whole host of new targets.”

Miles said the current funds will take Nested into 2025.

As far as future partnerships go, “We’re flexible. We’re not taking any options off the table," he said.  

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