Frequency Therapeutics CSO on developing drugs that selectively activate the body’s innate regenerative capabilities.

Regenerative medicine company Frequency Therapeutics is developing 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 within our bodies to create healthy, functional tissues. Frequency’s initial focus is on hearing loss and multiple sclerosis, and the company has just completed enrolment of a Phase 2b trial in adults with acquired sensorineural hearing loss (SNHL).

Longevity.Technology: Frequency is focused on progenitor cells, which are like stem cells but can only make cells that belong 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 learn more.

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

“They were studying the lining of the intestine, which is one of the most regenerative parts of the body, it actually recreates itself every five days,” says Loose. “And it’ll do that for 100 plus years, your entire life – staying super active and robust the whole time.”

Progenitor cell activation

The professors found a type of progenitor cell in the intestine called Lgr5, which takes its “cues” from neighbouring cells to create new intestinal tissue. In the intestine, these progenitor cells appear to stay active throughout our lives.

“As they were publishing that discovery, it was found that there are also dormant versions of the same progenitor cells in your cochlea [inner ear] – but they aren’t getting activated,” says Loose. “So, the big question was, can we reactivate that system and reverse hearing loss?”

Frequency was formed with the goal of answering that question, using an approach that the company is calling “progenitor cell activation.”

“We’re essentially using small molecules to turn on progenitor cells that are already in your body,” says Loose. “Rather than removing cells from the body and trying to deliver them back with a cell therapy, or changing the genetics of the body, like with genetic engineering, we’re simply trying to use small molecule cues that reactivate the native progenitor cells to restore tissue.”

Targeting hearing loss

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

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

“So, if other animals do this, and we already do it elsewhere in our body, we wanted to see if we could turn this back on in our cochlea using small molecules.”

One of the key advantages to Frequency’s approach, says Loose, is that it leverages the tissue architecture already in our bodies.

“The progenitor cells are often in exactly the spot they need to be in,” he says. “In the cochlea, for example, it’s very carefully organised – which cells have to sit where – and our focus is to turn on the system that’s already in place.”

Another key advantage of a small molecule approach is when it comes 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’ve proven that both preclinical and clinically. Using gene vectors and larger things, then you need much more invasive approaches, which will not be applicable to broad populations.”

Frequency’s lead product candidate, FX-322, is designed to regenerate hair cells through the activation of progenitor cells already present in the cochlea. The company moved FX-322 swiftly through its preclinical phases and it is now well on its way through human studies, including the current Phase 2 trial.

“We’ve had multiple trials now where we’ve shown meaningful improvements in hearing performance with patients that had long standing stable hearing loss,” says Loose. “At 142 patients, our Phase 2 trial is the largest healing restoration trial that’s been done. And we think it has the best rigours that have ever been put in place for a hearing restoration trial, so we’re really excited about it. We’ve just completed enrolment, and we’ll be reading out in Q1 next year.”

Potential in MS and beyond

While the main thrust of Frequency’s work is clearly on hearing loss, Loose is keen to stress that the company believes its approach has potential in many other areas of the body.

“This is a disease modifying 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 needed to control them during development. This was done very specifically – turning on 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 consider where else its approach could have a significant impact, and multiple sclerosis emerged as an obvious target.

“All the MS drugs right now, which are very successful, have been slowing down the body’s immune attack on myelin – the covering of the neurons in your brain,” says Loose. “But nothing is yet restorative, and that’s why there is a huge unmet need.”

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

Based on its successful work in hearing loss, Frequency has been looking at different small molecules that target distinct pathways for remyelination.

“Part of what encouraged us is that a few groups have gone to the clinic and seen some human signals that were encouraging, but had, in our view, fairly modest preclinical and clinical efficacy,” says Loose. “We were looking for something that is fundamentally much more effective. And that’s what we’ve seen, so we’ve started to share some preclinical data, head-to-head that we really think shows we’ve taken a big step forward. We are very enthusiastic about bringing this to patients.”

So what does Loose believe is the future potential of Frequency’s approach?

“There are progenitor cells in most tissues throughout the body,” he says. “For us, it’s been a question of where the biology is best understood, where in the stage of disease it could have the biggest impact and understanding the development and clinical path. We’ve been looking at quite a number of areas, and we believe harnessing the body’s potential using small molecules is the next wave of regenerative medicine.”