Startup Haya Hauls spends $65 million to reveal dark genome with lead drug for heart failure
Many drugs can be targeted by proteins, which is a limited approach in development efforts. First, protein is not the root cause of the disease, says Samir Ounzain, co-founder and CEO of Haya Therapeutics. The driving force of disease is how cells respond to their environment. Regulation of this response occurs in a part of the once neglected genome and is even seen as garbage by many scientists.
The vast majority of the genome (about 98%) consists of DNA that is not encoded for proteins. Over the past decade, scientists have believed it has no function and therefore called “junk DNA”, and found that this non-coding DNA does play a key role in regulating gene expression, including disease states, Ounzain said. While non-coding DNA is often called the dark genome, Ounzain says it is called the regulatory genome. This part of the genome, not proteins, is what controls cells and causes disease.
Headquartered in Lausanne, Switzerland, Haya, maintains operations in the United States in Santiago, is developing drugs designed to address targets in the dark genome to reprogram cells that drive disease. On Thursday, the startup announced $65 million to start using lead treatment candidates to start human testing that could prove the method with a heart failure.
“We need to consider the basic unit of disease progression and the basic unit of disease-driven, because cells are not genes, not pathways, but cellular states,” Ounzain said. “These cells show a lot of pathophysiology of these signs. And if you ask the root cause of the question, where is the causal biology that controls the state of the cell, it’s all in the dark genome. That’s really what we’re trying to show the world, and now with this series of financing, we’re excited to have that interest in clinically.”
Haya is the product of Ounzain’s academic research, most recently the University Hospital of Lausanne. 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 showing that the dark genome produces long non-coding RNAs (LNCRNAs) that regulate genes specific to certain diseases. The study led him to enter cellular states in the cardiovascular system, including fibrosis-driven diseases, which are the formation of scar tissue that impairs the function of the heart.
Antifibrotic drugs targeting proteins face particular challenges. Ounzain said the same proteins that cause disease of one cell type are also found on other cell types in the body. Therefore, a drug designed to address the protein may also encounter off-target tissue, causing safety issues. However, using lower doses to reduce the risk of complications means that the medication will not work.
Haya has developed a platform technology that applies computational biology and machine learning techniques to patient biopsy. Analysis of these samples allowed Haya to build an integrated dataset called “atlas” by Ounzain. With this atlas, the company has developed RNA-guided drugs to reprogram cells that drive disease. By studying the dark genome, Haya identified LNCRNAs that control fibrosis in tissues, Ounzain said. Haya has been developing drugs for pursuing specific targets to reprogram fibroblasts, the type of cell that causes fibrosis.
Haya’s drugs are primarily antisense oligonucleotides, but the company is also investigating small interfering RNA therapies, both of which are built. The LEAD program HTX-001 is an oligonucleotide designed to target WISP2 superenhancer-associated RNA (Wisper), an lncRNA that regulates fibroblast activity. Preclinical studies have shown that this approach can prevent and possibly reverse cardiac fibrosis, Ounzain said. Since wood is found only in cardiac tissue, targeting it should not lead to adverse reactions elsewhere in the body.
“On the Target Tox[icity] In off-target tissue, this is a feature we cannot see. “You will never touch them outside the cells that drive the disease because they are not expressed, they are not active.” ”
The ability to provide better efficacy and safety in genetic medicine allows Haya to pursue common chronic diseases. The target of lead disease is non-irritating hypertrophic cardiomyopathy (HCM), a genetic disease in which the heart muscles thicken but do not prevent blood from flowing out of the organs. Although the disease does not hinder blood flow, it still makes it harder for the heart to draw blood and can lead to heart failure. As the company’s research shows that there is a very strong association between the burden of fibrosis and the cardiac dysfunction experienced by patients with the disease, non-target HCM becomes the lead indicator of Haya.
Standard HCM medications include older cardiac drugs, such as beta blockers. Bristol Myers Squibb Drug Camzyos, an oral small molecule designed to block proteins that cause myocardial thickening, was approved in 2022 as a treatment for obstructive HCM. But the drug has not recently passed the 3-phase test, aiming to support the expansion of the drug to non-target HCM. The purpose of Imbria Pharmaceuticals is to treat non-target HCM with a drug called NinerafaxStat. The startup raised $57.5 million last month, pushing the small molecule to phase 2B testing.
Ounzain said implementing proof of concept in non-target HCM could pave the way for Haya to pursue other types of heart failure. The startup also has a separate procedure that can resolve pulmonary fibrosis. Haya’s goal is to keep heart failure and pulmonary fibrosis studies, but Ounzain does not rule out partnerships if it can bring treatment to patients faster. Apart from these main signs, the startup has conducted a research alliance with Eli Lilly. Last September, Lilly signed a deal to partner with Haya to find medications that show metabolic signs, including obesity. Specific financial details are not disclosed, but the companies said advance payments, stock investments and milestone payments could reach $1 billion.
Haya appeared from Stealth in 2021, with a seed financing of CHF 18 million (about US$20 million) led by Broadview Ventures. The new financing announced Thursday is led by Sofinnova Partners and Early Bird 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 (a branch of Broadview), 4See Ventures, Bernina Bioevest and Schroder Capital also participated in the latest financing.
With the new capital, Haya aims to start the first phase of testing of HTX-001 in the first half of 2026, Ounzain said. In the recent semester, Haya is preparing to conduct temporary data in New Orleans next week during the annual meeting of the American Society of Gene and Cell Therapy to present its Smart Lead Lead Program for New Orleans. Haya will focus on its technology platform. The conference will also provide Ounzain with the opportunity to explain the company’s name to the scientific community, inspired by “Hayah,” which has the same meaning in both Hebrew and Arabic.
“It actually means life, so [the name is] “We hope to extend our health and extend our lives to those who are unfortunately suffering from common chronic diseases that are troubled by society,” Ounzain said.
Photos: Champpix, Getty Images
