Leading the race to stop neurodegenerative disease progression
NR Times meets Coya Therapeutics’ founder and CEO Howard Berman as he closes in on his mission to halt ALS / motor neurone disease and other neurodegenerative conditions.
“Even if we see results that are half as good as what we’ve already seen, this is going to change the way ALS is treated,” says Howard Berman, founder and CEO of Coya Therapeutics.
The results he points to, which caused much excitement in the neuroscience research community last month, showed four people with ALS treated with Coya’s immune modulating therapy experienced a significant slowing of disease progression.
ALS is the most common form of motor neurone disease (MND), while, in the US, it is also the umbrella term for MND.
Coya’s therapy has emerged from the Nasdaq-listed firm’s pursuit of treatments based on the enhancement of the function of regulatory t cells (Tregs) in the immune system.
Dysfunctional Tregs underlie numerous conditions including neurodegenerative, metabolic, and autoimmune diseases.
They can lead to sustained inflammation and oxidative stress, preventing the immune system from working properly.
Coya’s investigational product pipeline is aimed at restoring the anti-inflammatory and immunomodulatory functions of Tregs.
In the small proof-of-concept ALS study, the treatment was delivered over 48 weeks.
The average ALS patient decline, as measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS FRS-R), is approximately -1 point/month.
But in the Coya study, there was no average decline from baseline to 24 weeks and only a minimal average decline from baseline to 48 weeks.
This, said the company, suggests that the approach “may provide a potentially meaningful approach for the ‘unmet need’ in ALS”.
Berman says: “We were able to stop progression of the disease at six months and that’s remarkable because most patients decline month upon month. At one year, we dramatically slowed the progression.
“This is a hypothesis that we are excited about and one which also translates into Alzheimer’s disease and potentially Parkinson’s and others.
“We have clinical data coming out in May on the use of our biologic therapies to enhance these Tregs in Alzheimer’s disease with the goal of hopefully slowing [the disease] or even possible enhancement of cognitive function.”
The proof-of-concept Alzheimer’s study involves eight patients with mild to moderate Alzheimer’s who received the therapy over four weeks.
On the ALS front, the early trial presents exciting possibilities about future treatment options, although the study size and the barriers ahead in developing an available therapy should not be understated.
Berman hopes in years to come, people with ALS might have access to a treatment regime akin to that available to those with HIV / AIDS.
“The current approved drugs for ALS can only slow progression very slightly and only improve survival by a few months. So, patients are still dying pretty rapidly and those [treatments] are not very impressive.”
“What we’re doing could stop progression at six months, or a year. That would be like what they’ve achieved for HIV and AIDS by putting three drugs together and [developing] viral therapy.
“Now patients can live with it for the rest of their lives, and that’s what we’re trying to accomplish here.”
Coya’s progress is underpinned by a growing understanding of the role of inflammation in brain conditions, as Berman explains.
“Neurologic diseases have many different causes and underlying pathologies. There could be neurons getting in trouble because of misfolded proteins, perhaps because of the waste disposal system of the cell or genetic predispositions. And we know the many causes of stroke, traumatic brain injury and spinal cord injury.
“But one commonality is inflammation. Inflammatory processes occur because the immune system is responding to the damage done to the neurons. This inflammatory process is essentially one of the important reasons why the patient deteriorates and declines.
“This is a phenomenon that has recently been recognised and is critically important. If you could control inflammation, if you could slow it down or stop it selectively, then the thought is that you could slow or stop many of these diseases from progressing, and maybe even have some disease modifying capability.
“In Alzheimer’s disease, for example, the immune system goes to the sites of the damage of the of the neurons, and the neurons are saying, ‘please help me out I’m sick’. So initially the immune system is helpful, but ultimately becomes the pathologic process.
“We are developing drugs that can slow or stem that inflammatory process, with the goal of slowing or stopping the disease from progressing.”
Coya’s potential solution is built on a focus on Tregs and the bioscience advancements needed to manipulate and modulate them.
“The Treg is the most important cell in your body that controls inflammation. When they are not working properly, the inflammatory process is heightened.
“In these diseases the Tregs are compromised and, in fact, in many instances they correlate with the degree of decline. We’ve shown in ALS that the worse the Treg function is, the faster the decline and the shorter the survival.
“In using biologics which we’ve developed and licensed, we are able to ramp up the Tregs in the bloodstream. We are also able to have biologic combinations.
“We can add drugs that stop another aspect of the immune system. By doing that, we have a synergistic impact in stopping the inflammatory process.”
Following the early ALS trial, the next stage is a larger, double-blind, placebo-controlled trial in the second half of this year.
“The FDA requires a six-month period to show the benefit of our therapy versus placebo. That trial should take around 18 months in total to complete.”
Coya’s drive to develop these potentially game-changing treatments is backed by world-leading experts.
Included on its scientific advisory board, for example, is Dr Shimon Sakaguchi, of Osaka university, who is credited with the discovery of Tregs.
Also among several other luminaries on board is Dr Stanley Appel, of Houston Methodist Hospital and Cornell University, who Berman describes as “the father of modern ALS” research, having been a pioneer of cell therapy around the condition.
His seminal research documented the intimate relationship of neurodegeneration and ALS progression with dysfunctional and decreased levels of Tregs.
He also discovered cryopreservation of Tregs, demonstrating the ability to expand, freeze and re-thaw Tregs, while maintaining viability and suppressive function.
Beyond its focus on the bioscience of Tregs, Coya has “evolved to develop biologics”; proteins that can be easily injected.
“This makes us much more scalable and you’re able to treat many, many more patients, much more cost-effectively,” says Berman.
Also speeding its progress is an increasingly proactive, determined and united ALS community. This, says Berman, is important as Coya works through the journey towards patient usage, including in gaining FDA approval.
“ALS patient advocacy groups have been very vocal in pushing the FDA to be more aggressive in terms of reviewing and allowing for more creative trials and being at the forefront of helping patients.
“It’s a disease where, if patients aren’t treated, or if they’re treated on a placebo, they die very quickly. When they don’t get therapy, they decline over a period of time. The FDA is very much more receptive to trials and the processes involved [now].”
Approval in the US will just be the start for Coya, Berman believes, with the company aiming to eventually roll out its therapy to the rest of the world.
“Right now we’re centered around the approval process here in the States. But of course, just as with most pharma companies, once you get approval in one location, like the US, you want to go into Europe, and other places, and really expand the use of these therapies.
“People die every day from the neurodegenerative diseases, so we will expand, but we want to show the early successes here first.”
