Frank Vinluan , 2025-05-08 12:00:00
Many drugs available and in development work by targeting proteins, an approach that comes with limitations. For one, proteins are not the root cause of disease, said Samir Ounzain, co-founder and CEO of HAYA Therapeutics. The driver of disease is the response of cells to their environment. Regulation of this response happens in a part of the genome once overlooked and even dismissed by many scientists as junk.
The vast majority of the genome, some 98%, consists of DNA that does not code for proteins. Called “junk DNA” because scientists thought it had no function, research in the past decade has found this non-coding DNA does play a key role in regulating gene expression, including states of disease, Ounzain said. While non-coding DNA is often referred to as the dark genome, Ounzain said it’s more appropriately called the regulatory genome. This portion of the genome — not proteins — is what controls cells and leads to disease.
HAYA, which is based in Lausanne, Switzerland, and maintains U.S. operations in San Diego, is developing drugs intended to address targets in the dark genome in order to reprogram disease-driving cells. On Thursday, the startup unveiled $65 million to begin human testing with a lead therapeutic candidate that could demonstrate this approach in a type of heart failure.
“We need to think about the fundamental unit of disease progression, and disease driving, as the cell — not a gene, not a pathway, it’s cellular states,” Ounzain said. “The cells are what manifest the pathophysiology underpinning many of these indications. And if you ask the question where is the root cause, causal biology that controls cell states, it’s all in the dark genome. That’s really what we’re trying to demonstrate to the world, and now with this Series A financing, we’re excited to hopefully prove that clinically as well.”
HAYA is the product of Ounzain’s academic research, most recently at Lausanne University Hospital. He said he spent his academic career trying to decipher and unlock the meaning of junk DNA. Ounzain published some of the first scientific papers demonstrating that the dark genome produces long non-coding RNAs (lncRNAs) that regulate genes specific to certain diseases. The research led him to cell states in the cardiovascular system, including disorders driven by fibrosis, the formation of scar tissue that impairs heart function.
Antifibrotic drugs that target proteins face a particular challenge. The same protein that causes disease in one cell type is also found on other cell types in the body, Ounzain said. Consequently, a drug designed to address that protein can also hit off-target tissues, sparking safety problems. But using a lower dose to reduce that complication risk means a drug won’t be effective.
HAYA has developed a platform technology that applies computational biology and machine learning techniques to patient biopsies. Analysis of these samples enables HAYA to build integrated datasets that Ounzain calls an “atlas” of the regulatory genome. With this atlas, the company develops RNA-guided drugs to reprogram the cells driving a disease. By studying the dark genome, HAYA has identified the lncRNAs that control fibrosis in a tissue, Ounzain said. HAYA has been developing drugs that go after specific targets to reprogram fibroblasts, the cell type that leads to fibrosis.
HAYA’s drugs are mainly antisense oligonucleotides but the company is also researching small interfering RNA therapies, both of which are established modalities. Lead program HTX-001 is an oligonucleotide designed to target Wisp2 super-enhancer-associated RNA (Wisper), a lncRNA that regulates fibroblast activity. Preclinical research showed this approach can block and potentially reverse cardiac fibrosis, Ounzain said. Because Wisper is found only in cardiac tissue, targeting it should not lead to adverse effects elsewhere in the body.
“On target tox[icity] in off-target tissues, it’s a feature we do not see,” Ounzain said. “You will never engage those targets outside of the disease-driving cells they because they’re not expressed, they’re not active.”
The ability to offer better efficacy and safety in a genetic medicine enables HAYA to pursue common, chronic diseases. The lead disease target is non-obstructive hypertrophic cardiomyopathy (HCM), a genetic condition in which heart muscle thickens but does not block blood flow out of the organ. While this disorder does not impede blood flow, it still makes it harder for the heart to pump blood and can lead to heart failure. Non-obstructive HCM emerged as HAYA’s lead indication as the company’s research showed a very strong association between fibrotic burden and the heart dysfunction experienced by patients with this disease.
Standard HCM drug treatment includes older heart drugs, such as beta blockers. Bristol Myers Squibb drug Camzyos, an oral small molecule designed to block a protein that leads to the thickening of heart muscle, was approved in 2022 as a treatment for obstructive HCM. But the drug recently failed a Phase 3 test intended to support expanding use of the drug to non-obstructive HCM. Imbria Pharmaceuticals aims to treat non-obstructive HCM with a drug called ninerafaxstat. The startup last month raised $57.5 million to advance this oral small molecule to Phase 2b testing.
Ounzain said achieving proof of concept in non-obstructive HCM could pave the way for HAYA to pursue other types of heart failure. The startup also has a separate program addressing pulmonary fibrosis. HAYA aims to keep the heart failure and pulmonary fibrosis research in-house, but Ounzain is not ruling out partnerships if they could bring therapies to patients faster. Outside of those lead indications, the startup has a research alliance with Eli Lilly. Last September, Lilly inked a deal to collaborate with HAYA to discover drugs for metabolic indications, including obesity. Specific financial details were undisclosed, but the companies said the upfront payment, equity investment and milestone payments could reach up to $1 billion.
HAYA emerged from stealth in 2021 backed by 18 million Swiss francs (about $20 million) in seed financing led by Broadview Ventures. The new financing announced Thursday was led by Sofinnova Partners and Earlybird Venture Capital. Other participants in the financing include Eli Lilly, ATHOS, +ND Capital, Alexandria Venture Investments, and LifeLink Ventures. Earlier investors Apollo Health Ventures, Longview Ventures (an affiliate of Broadview), 4see ventures, BERNINA Bioinvest, and Schroder Capital also participated in the latest financing.
With the new capital, HAYA aims to begin Phase 1 testing of HTX-001 in the first half of 2026, Ounzain said. In the nearer term, HAYA is preparing to present preclinical data for its Wisper-targeting lead program in New Orleans next week during the annual meeting of the American Society of Gene & Cell Therapy. HAYA will have another presentation focused on its technology platform. The meeting will also give Ounzain the opportunity to explain to the scientific community the company’s name, which is inspired by “hayah,” a word with the same meaning in both Hebrew and Arabic.
“It actually means life, so [the name is] really ‘Life Therapeutics,’” Ounzain said. “We’re hoping to extend health span and bring life to patients who unfortunately are suffering from many of the common chronic diseases that are plaguing society.”
Photo: champpixs, Getty Images
