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Lilly inks obesity deal with seed-stage RNA startup as its genetic medicines effort enters the spotlight

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Eli Lilly is pairing up with a so-called “dark genome” biotech startup to hunt for a new generation of obesity and metabolic drugs.

The Indianapolis-based drugmaker is betting up to $1 billion on seed-stage biotech HAYA Therapeutics, the companies said Wednesday morning. The Swiss and US startup is working on an RNA dark genome platform that complements Lilly’s growing efforts in genetic medicines, which now comprise about one-third of its pipeline.

HAYA will get an upfront payment and equity investment from Lilly, but both companies declined to disclose those figures. Initial checks are becoming a smaller portion of overall biotech-pharma pacts, according to a recent JP Morgan report.

Like a handful of other startups, HAYA is exploring the dark genome, which informs how cells respond to an environment and mediates disease-driving cell state effects, CEO Samir Ounzain said in an interview.

The company considers the dark genome a vastly untapped area of drug R&D. Proteins comprise less than 2% of your genome, and have small therapeutic windows and safety liabilities, but dark genome RNAs are “exquisitely specific,” Ounzain said.

“You can discover these RNAs that are only active in a diseased cell in a specific tissue,” Ounzain said. “So once you develop a medicine to target that RNA, you have really unprecedented precision in disease-modifying activity, and that’s really the reason why we’re so excited about the long non-coding RNAs and the regulatory genome as a new biological target space for drug development.”

Another startup in the space, NextRNA, teamed up with Bayer last week with a focus on two cancer programs.

HAYA’s lead internal program is in cardiac fibrosis in heart failure and is entering the GLP toxicology phase, Ounzain said. Further down the pipeline, it has projects in pulmonary fibrosis and the tumor microenvironment in oncology, he said.

The company is still working off an approximately $20 million seed round announced in May 2021, Ounzain said. It emerged about a year after another startup in the area, ROME Therapeutics, had launched with $50 million in Series A funds from GV and ARCH Venture Partners, among others.

At the time of the seed financing, Ounzain told Endpoints News that HAYA could be in the clinic in two to three years. He declined to give an updated timeframe.

“We’re actually very proud of that, that what we’ve been able to build with our seed financing has validated the value proposition around the platform and the target space,” Ounzain said. The company has about 35 employees across its operations in Lausanne, Switzerland, and San Diego, where it works out of Johnson & Johnson’s JLABS.

As Lilly runs clinical trials of at least half a dozen other experimental obesity medications, with two of those in late-stage testing, the pharma giant is seeking to build out its fourth, fifth and beyond generations of treatments for weight loss and various associated metabolic conditions.

It also teamed up with Fauna Bio last December to apply the California startup’s research on the 13-lined ground squirrel, whose annual six-month dormancy could offer insights into new approaches to the chronic condition. That deal also came with an undisclosed upfront and equity portion and up to $494 million in milestones.


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