The noncoding portion that makes up 98% of the human genome is anything but “junk” to HAYA Therapeutics, which said it is partnering with Eli Lilly to identify multiple regulatory genome-derived RNA-based drug targets for obesity and related metabolic conditions through a collaboration that could generate up to $1 billion for the Swiss biotech.
Lilly plans to apply HAYA’s advanced RNA-guided regulatory genome platform to support preclinical drug discovery efforts. The collaboration is HAYA’s first with a biopharma giant, and marks an expansion of HAYA’s therapeutic areas of interest. Until now, HAYA has used its drug discovery engine to target long noncoding RNAs (lncRNAs) that are drivers for fibrotic diseases and other severe health conditions associated with aging, including cancer.
HAYA is a precision therapeutics developer focused on designing tissue- and cell-type-specific genomic medicines by applying its tools and methods intended to interrogate lncRNAs. HAYA uses emerging RNA-targeting modalities, such as modified antisense oligonucleotides (ASOs), to target and inhibit proprietary lncRNAs.
“We really believe that the regulatory genome and these lncRNAs could be central to any cell state transition outside of fibrosis,” Samir Ounzain, PhD, HAYA’s co-founder and CEO, told GEN Edge. “We think it’s a great validation of the work we’ve done in fibrosis that others now would like to deploy that in other areas.”
“This announcement and this collaboration with Lilly gives a flavor of how we see the power of the platform, because we can apply this to many, many disease areas that we’d like to exploit,” Ounzain added.
For Lilly, the collaboration marks interest in yet another approach to fighting metabolic disorders. The Indianapolis-based biopharma launched the world’s first commercially available insulin product for diabetes control in humans in 1923. Nearly six decades later in 1982, Lilly won FDA approval to market Humulin®, the first human healthcare product derived from recombinant DNA (rDNA) technology.
More recently, Lilly has emerged as an arch-rival to Novo Nordisk in the successful development of glucagon-like peptide 1 (GLP-1) drugs, having launched two GLP-1 products based on the same active ingredient tirzepatide—the type 2 diabetes treatment Mounjaro® and obesity drug Zepbound®. During the first half of this year, both have reached “blockbuster” status of more than $1 billion in sales, as have Novo Nordisk’s two GLP-1 drugs containing the active ingredient semaglutide—the type 2 diabetes treatment Ozempic® and the obesity drug Wegovy®.
“Complementing and augmenting”
“We see this as complementing and augmenting the currently available therapies,” Ounzain said. “Obviously, it’s new biology and it’s cell state modifying. So, we have a slightly different approach, which we think is going to be exceptionally well positioned to complement everything that has been developed already in the obesity space.”
HAYA is developing a pipeline of lncRNA-targeting candidates for the tissue-specific treatment of fibrotic diseases in tissues that include lungs, kidneys, liver, and the microenvironment of solid tumor cancers. HAYA’s lead development candidate, HTX-001, is a modified ASO targeting the lncRNA Wisper, a cardiac myofibroblast enriched driver of fibrosis.
The company has not disclosed the targets of its other pipeline candidates.
“What I can disclose is we have targets that we have validated in preclinical models that are regulating fibrosis in the lung and in the tumor microenvironment, for example,” Ounzain said. “We have a number of novel targets that have come from the platform that are demonstrating disease-modifying activity in preclinical animal models.”
HAYA has deployed its platform toward targets in idiopathic pulmonary fibrosis (IPF). “And last but not least, I think it’s important to mention fibroblasts are really important in the tumor microenvironment, in solid tumors,” Ounzain said. “We have a very exciting program looking at these targets to control fibroblast plasticity in the tumor microenvironment, which is also generating some exciting preclinical data.”
Like HAYA, Lilly is also looking to expand its RNA pipeline. In August, the company opened its Lilly Seaport Innovation Center (LSC), an R&D facility in the Boston Seaport focused on advancing Lilly’s efforts to develop RNA and DNA-based therapies. LSC—previously called Lilly Institute for Genetic Medicine—also aims to discover new drug targets for new therapies in diabetes and obesity, as well as cardiovascular diseases, neurodegeneration, and chronic pain.
Lilly has agreed to pay HAYA an undisclosed upfront payment, including an equity investment, as well as up to $1 billion in payments tied to achieving preclinical, clinical, and commercial milestones, plus royalties on product sales.
Lilly is the second big-name biopharma to invest in an lncRNA collaboration in as many weeks.
Bayer joined NextRNA Therapeutics to announce an up-to-$547 million partnership aimed at developing small molecule therapeutics targeting lncRNAs in oncology. Bayer and NextRNA agreed to jointly advance two first-in-class oncology programs: An lncRNA-targeting small molecule program currently in early preclinical development at NextRNA; and a second program in which NextRNA will pursue lncRNA targets identified by its platform, with Bayer holding the option to select one target for joint development.
The up-to-$547 million includes upfront and near-term milestone payments, research funding, and payments tied to achieving development and commercial milestones, plus tiered royalties on net sales.
Sequencing depth yields novel RNAs
HAYA was founded in 2019, five years after Ounzain and colleagues published a paper in Journal of Molecular and Cellular Cardiology that laid the framework for the company’s research by detailing the discovery of hundreds of novel RNAs in the heart.
“The reason we could find them was because of the sequencing depth,” Ounzain told GEN in 2022. “We sequenced to a depth of 250 million paired reads per sample. Even today, most people cap depth at 50 million paired-end reads, but then you’re missing lowly expressed RNAs that are very tissue and cell-specific.”
“One of the questions that always arises is that they’re so lowly expressed, so how can they have a function? We now know you can have super stoichiometric activity of these RNAs because of their ability to induce phase-separated domains, where many of these remarkable biochemical processes happen,” Ounzain added. “That’s how we think about selecting tissues, and cell states: What are the public datasets available, and what can we generate rapidly internally?”
HAYA raised a seed funding round in 2021 that Ounzain said amounted to $25 million. The seed round was led by Broadview Ventures, with participation from Apollo Health Ventures, BERNINA BioInvest, 4See Ventures, Schroder Adveq, and Viva BioInnovator.
The company has yet to complete a Series A financing. “That’s why we’re very proud to have been able to build this value around the platform with this [Lilly collaboration] announcement,” Ounzain explained. “We think hopefully it gives a perspective of the excitement that’s emerging around the non-coding genome is a really interesting target space.”
Headquartered at the life sciences park Biopôle in Lausanne, Switzerland, HAYA also has significant research operations in San Diego, where the company occupies laboratory facilities at the Johnson & Johnson Innovation–JLABS @ San Diego coworking biotech lab space.
HAYA has approximately 35 employees—a number the company expects will increase in the near future.
“There’s definitely going to be some growth at different levels. And hopefully, in the not-too-distant future, there’ll be some announcements around the growth of the team,” Ounzain said.
That growth is expected to be generated both through HAYA’s internal pipeline and external collaborations like the one launched with Lilly.
“Ultimately, we believe long-run coding RNAs are a new wave of medicines,” Ounzain said. “The sooner we can get these targets into the ecosystem and being developed, the better. And for that, I think, we’re always open to specific and exciting collaborations to exploit this biology.”
