“The next wave of regenerative medicine”

Frequency Therapeutics CSO on the development of drugs that selectively activate the body’s innate regenerative abilities.

Regenerative medicine company Frequency Therapeutics develops new drugs that activate our innate abilities to restore function and reverse degenerative diseases. The company is working on small molecules that selectively activate progenitor cells already present in our bodies to create healthy, functioning tissues. Frequency is initially focused on hearing loss and multiple sclerosis, and the company has just completed enrollment for a Phase 2b trial in adults with acquired sensorineural hearing loss (SNHL).

Longevity.Technology: Frequency focuses on progenitor cells, which resemble stem cells but can only produce cells belonging to the same tissue or organ. While progenitor cells remain active in some of our organs and tissues, they can become dormant in others. Frequency’s small molecules are designed to selectively target and induce dormant progenitor cells to create specific cell types to restore tissue structure and function. We caught up with Frequency’s Chief Scientific Officer, Dr. Chris Loose, to find out more.

Dr Chris Loose, CSO – Therapeutic Frequency

Nasdaq-listed Frequency was founded in 2014, licensing technology developed by professors Robert Langer of MIT and Jeffrey Karp of Harvard Medical School.

“They were studying the lining of the gut, which is one of the most regenerative parts of the body, it actually recreates itself every five days,” Loose says. “And it will for over 100 years, your whole life – staying super active and hardy all the time.”

Activation of progenitor cells

The professors discovered a type of progenitor cell in the intestine called Lgr5, which takes its “signals” from neighboring cells to create new intestinal tissue. In the intestine, these progenitor cells seem to remain active throughout our lives.

“As they were publishing this finding, it was discovered that there are also dormant versions of the same progenitor cells in your cochlea. [inner ear] – but they are not activated,” says Loose. “So the big question was, can we turn this system back on and reverse the hearing loss?”

Frequency was formed with the aim of answering this question, using an approach the company calls “progenitor cell activation”.

“We basically use small molecules to activate progenitor cells that are already in your body,” Loose explains. “Rather than removing cells from the body and trying to restore them with cell therapy, or altering the genetics of the body, as with genetic engineering, we are simply trying to use small molecule signals that reactivate the cells. native progenitors to restore tissue.”

Target hearing loss

Sensorineural hearing loss is usually caused by the permanent loss of sensory hair cells in the cochlea of ​​the ear and accounts for 90% of all cases of hearing loss. This type of hearing loss is often acquired with age, affecting more than 40 million people in the United States and more than one billion worldwide. There are currently no FDA-approved treatments to repair SNHL.

“One of our most exciting early discoveries came from studying hearing loss in animals,” Loose says. “When birds and reptiles lose their hearing, they also lose those hair cells, but they turn on their progenitor cells, create a new set of hair cells, and can hear again within weeks.

“So if other animals are doing this, and we are already doing this elsewhere in our bodies, we wanted to see if we could reactivate this in our cochlea using small molecules.”

According to Loose, one of the main advantages of Frequency’s approach is that it exploits the tissue architecture already present in our bodies.

“Progenitor cells are often exactly where they need to be,” he says. “In the cochlea, for example, it’s very carefully organized – which cells should sit where – and our goal is to activate the system that’s already in place.”

Another key advantage of a small molecule approach relates to drug delivery.

“The cochlea is sealed inside the hardest bone in the body, so with a standard local injection, small molecules can enter the cochlea,” says Loose. “We have proven it both preclinically and clinically. Using gene vectors and bigger things, then you need much more invasive approaches, which won’t be applicable to large populations.

Frequency’s lead product candidate, FX-322, is designed to regenerate hair cells by activating progenitor cells already present in the cochlea. The company moved FX-322 quickly through its preclinical phases and it is now well advanced in human studies, including the ongoing Phase 2 trial.

“We’ve had several trials now where we’ve shown significant improvements in hearing performance in patients who had long-standing stable hearing loss,” Loose says. “With 142 patients, our Phase 2 trial is the largest healing restoration trial that has been conducted. And we think it has the best rigors ever put in place for a hearing restoration trial, so we’re really excited about it. We have just completed registration and will be reading in the first quarter of next year. »

Potential in MS and beyond

Although the primary focus of Frequency’s work is clearly on hearing loss, Loose is keen to point out that the company believes its approach has potential in many other areas of the body.

“This is a disease modification platform to achieve the benefits of regenerative medicine with small molecules, using a progenitor cell activation approach,” he says. “There are progenitor cells all around your body and your body needs to control them during development. This was done in a very specific way – by activating one tissue at a time in a coordinated fashion – so there are unique signals or combinations of signals for many of these cells.

This thinking led Frequency to wonder where its approach could have a significant impact, and multiple sclerosis emerged as an obvious target.

“Currently, all of the highly successful multiple sclerosis drugs have slowed the body’s immune attack on myelin, the covering of the neurons in your brain,” says Loose. “But nothing is restorative yet, and that’s why there’s a huge unmet need.”

“There is also a large population of progenitor cells in the brain. This is about 5% of your brain cells, and their job is to remyelinate. In healthy individuals, even in the early stages of MS, they do quite well at repairing the damage, but eventually they can’t keep up.

Based on his successful work in hearing loss, Frequency studied different small molecules that target distinct remyelination pathways.

“Part of what encouraged us was that a few groups went to the clinic and saw encouraging human signals, but which we felt had quite modest preclinical and clinical efficacy,” Loose says. “We were looking for something that is fundamentally much more efficient. And that’s what we’ve seen, so we’ve started sharing preclinical, head-to-head data that we think really shows that we’ve made a big step forward. We are very excited to bring this to patients.

So, according to Loose, what is the future potential of Frequency’s approach?

“There are progenitor cells in most tissues of the body,” he says. “For us, it was about where the biology is best understood, where in the stage of the disease it could have the greatest impact, and understanding the development and the clinical pathway. We have looked at a number of areas and believe that harnessing the body’s potential using small molecules is the next wave of regenerative medicine.