Epigenetics is the study of changes in organisms caused by modification of gene expression. By targeting epigenetic mechanisms, epigenetic therapies alter gene expression patterns to treat diseases.

Some of these mechanisms include DNA methylation and histone modifications. DNA methylation is the attachment of chemical compounds called methyl groups to DNA so as to activate or silence a gene, whereas histone modifications aim to reduce gene expression by altering chromatin structure, which is the mixture of DNA and proteins that form the chromosomes.

In this article, we take a look at six epigenetics biotech companies that are significant as well as up-and-coming players in the industry.

Chroma Medicine

Massachusetts-based Chroma Medicine has come up with programmable epigenetic editors that target genes and control chromatin conformation. These editors have a DNA binding domain to silence or activate a specific gene and a modular epigenetic effector domain that creates durable methylation patterns to control chromatin conformation and check whether a gene is accessible for transcription. Chromatin conformation is the process that regulates the coordination between DNA replication and transcription.

Chroma’s epigenetic editors are able to fully eliminate the expression of the targeted gene as opposed to other current methods that regulate gene expression by cutting the DNA, which in turn may cause unpredictable DNA repair pathways to become activated.

Recently, the biotech partnered with the Whitehead Institute for Novel Epigenetic Editing Technology to access a novel technology called CHARM, which is short for coupled histone tail for autoinhibition release of methyltransferase. CHARM uses an epigenetic editing effector domain to recruit and activate endogenous DNA methyltransferases to silence target genes.

Earlier this year, it sponsored a preclinical study that found that epigenetic gene silencing can suppress a target gene – in this case, the Pcsk9 gene linked to high cholesterol – further strengthening the science behind epigenetic therapeutics.

Last year, the epigenetics company was among The Endpoints 11, and named a top startup to hit the biotech scene with its novel science and technology.

Storm Therapeutics

RNA is a key player in cellular decision-making, especially non-coding RNA. RNA-modifying enzymes can change the course of key cellular processes, changes to RNA can result in the development of diseases like cancer, making these enzymes an ideal drug target.

British spinout Storm Therapeutics is developing RNA-modifying enzyme inhibitors to tackle a range of diseases. Storm’s lead candidate STC-15 is the first RNA methyltransferase inhibitor to enter the clinic. STC-15 inhibits METTL3, an RNA methyltransferase associated with cancer and other diseases. Phase 1 interim results presented at ASCO found that the drug was well-tolerated and clinical activity was measured. An 11% overall response rate and 63% disease control rate were observed.

Preclinical data has shown that the drug stimulates immune cells and enhances anti-tumor properties in combination with checkpoint inhibitors. Storm also has preclinical candidates being designed to treat Alzheimer’s disease and other neurodegenerative conditions as well as looks to target coronavirus.

In 2022, the British biotech was ranked among Fierce Biotech’s 2022 Fierce 15. This was also the year it bagged $30 million in series B funding to push STC-15 into the clinic.

K36 Therapeutics

Founded three years ago, American startup K36 Therapeutics is on a mission to treat multiple myeloma, a type of bone marrow cancer. Around less than a quarter of patients with multiple myeloma have a genetic translocation between chromosomes 4 and 14 that forms two abnormal chromosomes. This leads to the overexpression of the MMSET gene and protein. This further aids in converting normal blood cells to cancer cells.

Leveraging epigenetic technology, K36’s lead candidate KTX-1001 is a small molecule that inhibits the overexpression of MMSET. It is the first investigational drug that targets MMSET to enter the clinic, which it did last year.

Last year, it was awarded the Overall BioPharma Startup of the Year title by BioTech Breakthrough. It also secured $70 million in series B backed by pharma giant Bristol Myers Squibb. This funding came more than two years after it launched with $30 million in 2021.

Omega Therapeutics

Insulated genomic domains (IGDs), as Omega Therapeutics calls it, are 3-dimensional loops of DNA that possess genes and regulate genomic activity. With the intent to control gene regulation and cellular expression, the Massachusetts-based company has engineered mRNA therapeutics called epigenomic controllers to address a range of diseases. The epigenetics company has identified around 15,000 IGDs across 23 chromosomes in every cell.

Its lead candidate OTX-2002 is in a phase 1/2 study to treat liver cancer, which is responsible for over 12,000 deaths every year in the U.S. Based on preliminary clinical data announced last year, the drug achieved on-target genomic engagement and downregulation of the undruggable target gene MYC. The trial saw durable decreases in MYC mRNA expression levels.

It also presented preclinical data demonstrating the regulation of gene expression in cellular models at the pre-transcriptional level at the American Society of Gene and Cell Therapy (ASGCT) in the U.S. earlier this year.

It has collaborated with Danish multinational Novo Nordisk to develop a therapy to manage obesity. As part of the deal, Omega will receive $532 million in upfront, development, and commercial milestone payments, as well as tiered royalties.

Inherent Biosciences

American biotech company Inherent Biosciences is on a mission to address reproductive health through epigenetics. Inherent’s platform assimilates artificial intelligence (AI) to look at DNA and how modifications are linked to certain diseases.

It has developed Path SpermQT, an epigenetic sperm quality test that is designed to predict poor fertility outcomes – typically not detected in semen tests alone. It categorizes sperm as excellent, normal, or poor sperm quality based on epigenetic patterns. The test aims to shed light on the quality of a sperm sample, and help fertility doctors and patients gather more information about the sperm’s function.

The non-invasive test can use an at-home kit after which samples are shipped off to the lab for analysis and results are delivered within two weeks. The technology analyzes the sperm’s genes to measure its ability to find, bind, penetrate, and fertilize an egg. It assesses the dysregulation in the DNA methylation patterns of over 1,200 genes that are necessary for sperm function. The company also looks to develop epigenetics-based therapies to treat infertility.

Inherent has partnered with Genomic Prediction to advance reproductive health. The SpermQT test will be integrated with Genomic Prediction’s clinical tests to gain more insight into fertility challenges.

Epic Bio

California-based Epic Bio aims to control the epigenome without making permanent edits to their DNA with the help of its platform the Gene Expression Modulation System (GEMS).

Each construct of the GEMS platform has three basic components: a DNA-binding protein, one or more guide RNAs, and modulators. When paired with a custom guide RNA, the DNA-binding protein recognizes and binds to the target sequence. Then, the modulators alter gene expression, be it to activate or silence gene transcription.

This platform has been employed to create Epic Bio’s pipeline, its lead candidate being EPI-321. The drug, which is currently undergoing Investigational New Drug (IND)-enabling studies, targets a genetic muscle disorder called facioscapulohumeral muscular dystrophy (FSHD). It is designed to suppress DUX4 protein expression to stop muscle cell death. It was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) late last year, and is set to enter the clinic soon.

Last year, the epigenetics company was named a Fierce 15 Company by Fierce Biotech for its speedy pipeline creation since its launch in 2022.

Epigenetics market on a high

The global epigenetics market was valued at $1.56 billion in 2021 and is growing steadily, according to Polaris Market Research. As AI has been integrated into drug discovery lately, it is also being applied to epigenetics. Moreover, big pharma like British-Swedish multinational company AstraZeneca is building a portfolio of epigenetics therapies to target cancer. And, more and more partnerships in the field suggest that things are moving forward in cancer therapeutic research as well as other therapeutic areas.