Welcome to today’s Biotech Spotlight, a series featuring companies creating breakthrough technologies and products. Today, we’re looking at Tune Therapeutics, a preclinical biotech pioneering a next-generation genetic therapy by tuning the epigenome.
In focus with: Lucas Thompson, senior director of the ex vivo program at Tune Therapeutics
Tune Therapeutics’ vision: Tune launched in 2021 with $40 million in funding and is one of several companies — including Chroma Medicine and Epic Bio — riding a wave of investor enthusiasm for epigenetic editing. The approach modifies gene expression using the epigenome, a system of marks that provide instructions for how DNA is read and used. By modifying these marks, epigenetic editing can alter gene expression while leaving the underlying DNA untouched. Touted as a safer and more precise way to carry out genetic therapy, it could help treat a broad variety of diseases, from cancer and autoimmune diseases to chronic health conditions.
“The premise of our vision is to leverage our genetic tuning technology platform in ways that uniquely address unmet medical needs across various indications,” Thompson said. “We have the potential to address a large number of disease settings.”
Why it matters: Epigenetic editing is an alternative to CRISPR-enabled gene editing, which has some critical drawbacks. Gene editing technologies that snip and splice strands of DNA may accidentally insert dangerous, permanent errors into a patient’s genetic sequence. Genetic tuning through epigenetics could wield similar power with less risk.
Tune’s Tempo platform adjusts the epigenome, not just turning genes on or off but acting as a dimmer switch, turning down genes stirring up trouble or amplifying others to reverse a deficiency.
“Instead of addressing genetic issues in disease by causing DNA breaks, we can go in and tune the genes using natural mechanisms — we harness endogenous gene regulatory networks in a controlled, targeted manner,” Thompson said. “This means we can avoid unintended consequences of some of the other modalities of either knocking in are knocking out genes that can break DNA and cause issues with recombination and other sort of mutational genomic toxicities.”
“It is really difficult or impossible to achieve these types of outcomes with other modalities.”
Senior director, ex vivo program, Tune Therapeutics
A more precise mechanism also allows the company to simultaneously target multiple gene pathways, opening the door to treating complex conditions that were previously out of reach, Thompson said. Other technologies can also carry out multiple modifications, but this increases the risk of potentially dangerous translocations. Tune’s process does not.
“This is really unique, this ability to go up and down with genes in the same cell, and this can unlock some very complex mechanisms that control cellular behavior,” Thompson said. “It is really difficult or impossible to achieve these types of outcomes with other modalities.”
A major milestone: Tune’s technology cleared a major hurdle in May when the company revealed its success modifying a well-known gene target called PCSK9, which can elevate levels of artery-clogging LDL-cholesterol in the blood. The goal was to show that epigenetic editing could alter this gene’s expression and lower cholesterol in animal models.
Researchers performed a single infusion of the Tempo epi-repressor targeting the gene using a lipid nanoparticle and not only dropped cholesterol levels by 56% but still showed repression of the PCSK9 gene at seven months. Company officials said this provided validation for the field by showing that epigenetic editing can durably modify gene expression in non-human primates. However, researchers are still tracking how long this effect will last.
How the technology will be used: “We're still in a range of discovery and preclinical stages across multiple programs. At this point, we aren't disclosing our pipeline,” Thompson said, noting that although Tune yet to announce clinical targets, the company is hoping to move rapidly toward a preclinical development candidate.
“Once we start working toward candidates for any kind of indication, the process of discovery, and getting to develop a candidate is pretty quick,” he said. “We do have candidates that are fairly advanced in that process.”
The program will likely use two major therapeutic approaches, including direct gene modulation in patients.
“That's where an epi-editor product would be infused into the patient to target certain organs and other cells that have an inborn error in gene expression and address it,” Thompson said. “The other major modality is using this for ex vivo therapies. And that's the CAR-T cell-type approach where we take cells, program them to our liking in vitro using gene tuning and other methods and then infuse them back into the patient as a drug.”
This approach could boost the therapeutic potency and clinical durability of CAR-T cell therapy and reduce detrimental side effects for patients, possibly enabling earlier treatment, Thompson said.
Navigating the obstacles ahead: One of the main challenges will be hitting the right notes with the gene-tuning technology.
“I think probably the most significant hurdle is trying to understand what kind of durability of effect we need for our epi-editors to achieve the outcome in vivo,” Thompson said.
In cancer treatments for instance, the therapy may need to maintain an effect long enough to destroy tumor cells but not so long it produces dangerous side effects. But the payoff could be big if they get the timing right.
“We believe that we can precision target key epigenetic modalities, and this unlocks a pretty large untapped resource for some of these next-generation therapeutic strategies,” Thompson said.
Distinguishing themselves in a crowded market: Tune is not the only company looking to harness the power of the epigenome.
“This is a pretty exciting new field, so it’s a fruitful area for competition,” Thompson said. Other companies in the space include Modalis Therapeutics, Rejuvenate Bio, Navega Therapeutics, and Sangamo Therapeutics, among others.
“But I think our outlook here is that this is a great time to be in this field,” he said. There are a lot of really smart people working here and investors are excited.”
Tune hopes to distinguish itself from competitors through its unique approach to tuning genes by turning them up or down, its ability to modulate genes in different ways and to target and combine epigenetic editors to achieve unique outcomes.
“We're really excited to be at the forefront of this,” Thompson said.