Many medication accessible and in growth work by focusing on proteins, an strategy that comes with limitations. For one, proteins are usually not the basis reason for illness, stated Samir Ounzain, co-founder and CEO of HAYA Therapeutics. The driving force of illness is the response of cells to their atmosphere. Regulation of this response occurs in part of the genome as soon as neglected and even dismissed by many scientists as junk.
The overwhelming majority of the genome, some 98%, consists of DNA that doesn’t code for proteins. Referred to as “junk DNA” as a result of scientists thought it had no operate, analysis prior to now decade has discovered this non-coding DNA does play a key function in regulating gene expression, together with states of illness, Ounzain stated. Whereas non-coding DNA is also known as the darkish genome, Ounzain stated it’s extra appropriately known as the regulatory genome. This portion of the genome — not proteins — is what controls cells and results in illness.
HAYA, which is predicated in Lausanne, Switzerland, and maintains U.S. operations in San Diego, is growing medication meant to handle targets at midnight genome to be able to reprogram disease-driving cells. On Thursday, the startup unveiled $65 million to start human testing with a lead therapeutic candidate that would display this strategy in a kind of coronary heart failure.
“We want to consider the basic unit of illness development, and illness driving, because the cell — not a gene, not a pathway, it’s mobile states,” Ounzain stated. “The cells are what manifest the pathophysiology underpinning many of those indications. And should you ask the query the place is the basis trigger, causal biology that controls cell states, it’s all at midnight genome. That’s actually what we’re attempting to display to the world, and now with this Sequence A financing, we’re excited to hopefully show that clinically as properly.”
HAYA is the product of Ounzain’s tutorial analysis, most not too long ago at Lausanne College Hospital. He stated he spent his tutorial profession attempting to decipher and unlock the that means of junk DNA. Ounzain printed a number of the first scientific papers demonstrating that the darkish genome produces lengthy non-coding RNAs (lncRNAs) that regulate genes particular to sure ailments. The analysis led him to cell states within the cardiovascular system, together with problems pushed by fibrosis, the formation of scar tissue that impairs coronary heart operate.
Antifibrotic medication that concentrate on proteins face a selected problem. The identical protein that causes illness in a single cell sort can also be discovered on different cell sorts within the physique, Ounzain stated. Consequently, a drug designed to handle that protein may hit off-target tissues, sparking security issues. However utilizing a decrease dose to cut back that complication threat means a drug received’t be efficient.
HAYA has developed a platform know-how that applies computational biology and machine studying methods to affected person biopsies. Evaluation of those samples allows HAYA to construct built-in datasets that Ounzain calls an “atlas” of the regulatory genome. With this atlas, the corporate develops RNA-guided medication to reprogram the cells driving a illness. By finding out the darkish genome, HAYA has recognized the lncRNAs that management fibrosis in a tissue, Ounzain stated. HAYA has been growing medication that go after particular targets to reprogram fibroblasts, the cell sort that results in fibrosis.
HAYA’s medication are primarily antisense oligonucleotides however the firm can also be researching small interfering RNA therapies, each of that are established modalities. Lead program HTX-001 is an oligonucleotide designed to focus on Wisp2 super-enhancer-associated RNA (Wisper), a lncRNA that regulates fibroblast exercise. Preclinical analysis confirmed this strategy can block and probably reverse cardiac fibrosis, Ounzain stated. As a result of Wisper is discovered solely in cardiac tissue, focusing on it mustn’t result in hostile results elsewhere within the physique.
“On the right track tox[icity] in off-target tissues, it’s a function we don’t see,” Ounzain stated. “You’ll by no means have interaction these targets exterior of the disease-driving cells they as a result of they’re not expressed, they’re not lively.”
The flexibility to supply higher efficacy and security in a genetic drugs allows HAYA to pursue frequent, persistent ailments. The lead illness goal is non-obstructive hypertrophic cardiomyopathy (HCM), a genetic situation during which coronary heart muscle thickens however doesn’t block blood circulation out of the organ. Whereas this dysfunction doesn’t impede blood circulation, it nonetheless makes it tougher for the guts to pump blood and might result in coronary heart failure. Non-obstructive HCM emerged as HAYA’s lead indication as the corporate’s analysis confirmed a really sturdy affiliation between fibrotic burden and the guts dysfunction skilled by sufferers with this illness.
Commonplace HCM drug therapy contains older coronary heart medication, akin to beta blockers. Bristol Myers Squibb drug Camzyos, an oral small molecule designed to dam a protein that results in the thickening of coronary heart muscle, was accepted in 2022 as a therapy for obstructive HCM. However the drug not too long ago failed a Section 3 check meant to assist increasing use of the drug to non-obstructive HCM. Imbria Prescribed drugs goals to deal with non-obstructive HCM with a drug known as ninerafaxstat. The startup final month raised $57.5 million to advance this oral small molecule to Section 2b testing.
Ounzain stated reaching proof of idea in non-obstructive HCM may pave the way in which for HAYA to pursue different sorts of coronary heart failure. The startup additionally has a separate program addressing pulmonary fibrosis. HAYA goals to maintain the guts failure and pulmonary fibrosis analysis in-house, however Ounzain is just not ruling out partnerships if they may deliver therapies to sufferers sooner. Exterior of these lead indications, the startup has a analysis alliance with Eli Lilly. Final September, Lilly inked a deal to collaborate with HAYA to find medication for metabolic indications, together with weight problems. Particular monetary particulars have been undisclosed, however the firms stated the upfront fee, fairness funding and milestone funds may attain as much as $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 brand new financing introduced Thursday was led by Sofinnova Companions and Earlybird Enterprise Capital. Different members within the financing embrace Eli Lilly, ATHOS, +ND Capital, Alexandria Enterprise Investments, and LifeLink Ventures. Earlier traders Apollo Well being Ventures, Longview Ventures (an affiliate of Broadview), 4see ventures, BERNINA Bioinvest, and Schroder Capital additionally participated within the newest financing.
With the brand new capital, HAYA goals to start Section 1 testing of HTX-001 within the first half of 2026, Ounzain stated. Within the nearer time period, HAYA is making ready to current preclinical information for its Wisper-targeting lead program in New Orleans subsequent week in the course of the annual assembly of the American Society of Gene & Cell Remedy. HAYA may have one other presentation targeted on its know-how platform. The assembly will even give Ounzain the chance to elucidate to the scientific group the corporate’s title, which is impressed by “hayah,” a phrase with the identical that means in each Hebrew and Arabic.
“It truly means life, so [the name is] actually ‘Life Therapeutics,’” Ounzain stated. “We’re hoping to increase well being span and produce life to sufferers who sadly are affected by most of the frequent persistent ailments which can be plaguing society.”
Photograph: champpixs, Getty Pictures
