HAYA Therapeutics is using its unparalleled regulatory genome atlas and innovative proprietary platform to identify novel long non-coding RNAs and develop drug candidates that return diseased cells back to healthy states.
Heart failure and many other common and chronic diseases that have a huge impact on society can be driven by lifestyle-related risk factors. A combination of genetic variants and environmental stressors—unhealthy eating habits or exposure to cigarette smoke and other toxins, for example—can change the behavior of cells, causing disease. The conductors of this activity are found in the ‘dark genome’, now recognized as the ‘regulatory genome’ due to its key regulatory functions. This large and previously overlooked area encompasses dynamically active regions that generate thousands of long non-coding RNAs (lncRNAs). These play a key role in the epigenetic processes that respond to environmental inputs, controlling the expression of genes, proteins and other RNAs in much the same way that software instructs a computer to respond in a meaningful way to our input.
Leveraging the power of the regulatory genome, HAYA Therapeutics is pioneering precise and potent RNA-based therapeutics for chronic diseases. “Epigenetic programming and interfacing with the environment are happening in the regulatory genome, so therapeutic strategies that target lncRNAs could be the most viable option for a multitude of hard-to-treat chronic diseases and other indications, for which solutions are currently very limited,” said Samir Ounzain, HAYA’s CEO and co-founder. “By modulating lncRNAs we can tackle disease where it matters—at its source.”
The company has developed a proprietary regulatory genome platform and a large suite of cutting-edge omics and computational tools for the identification of first-in-biology high-value lncRNA targets. HAYA has built the world’s largest and best curated regulatory genome database, and is developing effective therapies that address the root cause of disease by reprogramming diseased cells back to healthy states (Fig. 1).
Fig. 1 | The multi-functional platform at HAYA Therapeutics. LncRNAs, long non-coding RNAs; MoA, mechanism of action.
Using its expertise in antisense oligonucleotide therapies, it takes only 18–24 months—compared to 4 or 5 years for a small molecule—for HAYA to design cell state-reprogramming, lncRNA-targeting drug candidates with the potential to be safer and more effective than currently available therapeutics. “In contrast to widely-expressed mRNAs and proteins, lncRNAs are exquisitely specific, acting only in particular tissues and cells and with low expression and fast turnover. This potentially facilitates faster acting and more-efficacious RNA-targeting therapies using lower doses, resulting in reduced toxicity and fewer side effects,” explained Sudhir Agrawal, antisense leader on HAYA’s scientific advisory board. “Moreover, the precise pairing between antisense oligonucleotides and their lncRNA targets results in the highly specific binding that is essential for therapies that aim to modulate gene expression.”
Tackling fibrosis where it matters
HAYA’s initial in-house focus is on fibrosis—a process involved in many chronic diseases, including cardiovascular disorders—which accounts for one in three deaths globally. Environmental responses and associated changes in lncRNA expression can activate fibroblasts to produce large amounts of potentially deleterious extracellular matrix proteins, including collagen. The progressive build-up of activated fibroblasts and collagen deposition in a tissue result in fibrosis that can eventually lead to organ failure. Unfortunately, many fibrotic diseases have no effective treatments. Those that do exist target proteins related to the activity of fibroblasts which—because they are also present in other tissues—often results in limited effectiveness, unwanted toxicities and severe side effects.
HAYA’s lead therapeutic candidate, HTX-001, targets a cardiac fibroblast-specific lncRNA for the treatment of non-obstructive hypertrophic cardiomyopathy, with the potential to reduce the pathological development of fibrosis and prevent associated adverse remodeling in the heart. Clinical trials are expected to begin by early 2026, according to Ounzain, with the ultimate goal of treating heart failure.
Unlocking new disease areas
As fibrosis is also involved in the lung and in the microenvironments of some tumors, HAYA’s research and development pipeline includes potential lncRNA-targeting precision candidates for conditions such as idiopathic pulmonary fibrosis, solid tumor cancers and a broad range of diseases in other tissues where fibrosis can occur. Additionally, the company is planning to leverage lncRNAs as biomarkers to inform drug discovery, de-risk clinical trials, and develop and deploy diagnostics in clinical practice.
Moreover, HAYA’s platform extends beyond fibrosis; the company has already struck a multi-year collaboration with Eli Lilly to use it to identify, characterize and validate multiple novel lncRNA targets for the potential development of new treatments for obesity and related metabolic disorders—a deal in which HAYA could receive up to $1 billion in milestone payments alone. Keen to exploit the regulatory genome platform to fulfil its mission of helping the thousands of patients without a current therapeutic option, HAYA is open to additional collaboration with biopharma companies that have complementary disease or modality expertise.
“lncRNAs are versatile molecules, attractive targets, and therapeutically unexplored, and we have a revolutionary platform for reprogramming disease-driving cell-states to treat rare, common and chronic diseases,” said Ounzain. “Together we can accelerate the development of next-generation RNA therapies and provide patients with safer and effective medicines, supporting their path to healthier aging and ultimately enabling an extended health span for all.”
