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After two meetings with the U.S. Food and Drug Administration (FDA), <a href="https://coyatherapeutics.com/">Coya Therapeutics</a> says it&#8217;s received constructive feedback — and has reached an alignment with the agency regarding development plans for COYA 302, its therapy candidate for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The company held the two meetings — a pre-investigational new drug (IND) meeting and a type C meeting — to seek advice from the FDA. Now, according to COYA, the two parties are in agreement regarding key areas of COYA 302&#8217;s development, to include its manufacturing, preclinical research, and clinical studies, which should support the filing of an IND application seeking clearance to start clinical trials.
That application is expected to be submitted in the first half of 2024, the company said in a <a href="https://www.businesswire.com/news/home/20240105424614/en/Coya-Therapeutics-Announces-Successful-Pre-IND-and-Type-C-Meetings-with-the-FDA-to-Advance-the-Development-of-COYA-302-for-Treatment-of-Amyotrophic-Lateral-Sclerosis-ALS">press release</a>.
If it&#8217;s accepted, Coya will soon thereafter launch a double-blind clinical trial to test COYA 302 in people with ALS. In a double-blind study, neither researchers nor participants know what treatment, if any, patients are receiving.
“This important feedback allows us to advance our development program in ALS with a planned double-blind controlled study, with the potential for bringing forward a much-needed therapy for ALS patients,” said Fred Grossman, Coya’s president and chief medical officer.
[recommended-reading id=82985]
<h3>In proof-of-concept study, COYA 302 showed marked benefits</h3>
ALS is characterized by progressive damage to motor neurons, the nerve cells that control voluntary movements. It renders the brain less able to control muscle movements.
<a href="https://coyatherapeutics.com/science-and-technology/">COYA 302</a> is an experimental approach that combines a low dose of the immune signaling molecule interleukin-2 (IL-2) and a fusion protein named CTLA-4 Ig (abatacept).
IL-2 is intended to reduce inflammation by increasing the levels and activity of anti-inflammatory immune cells called regulatory T-cells, or Tregs. CTLA-4 Ig, meanwhile, aims to decrease the activity of immune cells that promote inflammation and damage in ALS.
The therapy, administered via a subcutaneous or under-the-skin injection, has already been tested in four ALS patients in a proof-of-concept clinical trial. The participants received treatment for 48 weeks, or nearly one year, and were followed for eight more weeks after stopping COYA 302.
Results of the small study showed that ALS progression was markedly slowed during the treatment period, with patients experiencing similar levels of disability after 48 weeks compared with before treatment.
Prior to treatment, participants were losing a mean of 1.1 points per month in their ALS Functional Rating Scale (ALSFRS-R) scores, indicating a lower ability to perform daily tasks each month. During the entire study period, scores dropped a total of 1.5 points, on average.
However, once patients stopped COYA 302, progression rates returned to those observed before the trial started, indicating a need for continuous treatment.
Similarly, there was a statistically significant increase in Treg anti-inflammatory activity during the treatment, which also decreased to starting, or baseline, levels eight weeks after treatment discontinuation.
The study also evaluated biomarkers of inflammation and oxidative stress — a type of cell damage associated with inflammation. Available data up to 16 weeks, or about four months, suggested a decrease in these biomarkers, consistent with the observed increase in Treg function.
[quote=&#8221;center&#8221;]We believe that gaining alignment with FDA through multiple regulatory meetings on the path to filing an IND in [the second quarter of] 2024 is an important next step in advancing the program in patients with ALS.[/quote]
The therapy was generally well tolerated, with no serious side effects reported and no treatment discontinuations. The most common side effects were mild reactions at the injection site.
Coya plans to continue working closely with the FDA throughout COYA 302&#8217;s development program, the company said.
“We believe that gaining alignment with FDA through multiple regulatory meetings on the path to filing an IND in [the second quarter of] 2024 is an important next step in advancing the program in patients with ALS,” said Howard H. Berman, PhD, Coya’s CEO.

Coya aligns with FDA on plans for developing COYA 302 for ALS

Under a new agreement, Coya Therapeutics&#8217; <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) treatment candidate COYA 302 — which aims to suppress chronic and sustained inflammation — will now be exclusively marketed by <a href="https://www.drreddys.com">Dr. Reddy’s Laboratories</a> in the U.S., Canada, and the U.K., as well as in the European Union, should it be approved in those countries.
<a href="https://coyatherapeutics.com">Coya</a> will retain the rights to market COYA 302 in Japan, Mexico, and countries of South America. Additionally, the company will remain responsible for moving the experimental therapy through clinical development in the U.S. and dealing with regulatory matters.
The company is <a href="https://alsnewstoday.com/news/coya-meet-fda-about-phase-2-trial-coya-302-als/">preparing a meeting</a> with the U.S. Food and Drug Administration (FDA) to discuss its development plans for COYA 302 in advance of an investigational new drug (IND) application, which it plans to file in early 2024. That IND will seek FDA clearance to launch a Phase 2 clinical study of the combination therapy.
Under the terms of the agreement, India-based Dr. Reddy’s will make an upfront payment of $7.5 million. Additional payments of up to $40 million will follow should a number of development and regulatory milestones be achieved. Coya also could receive additional payments of up to $677.25 million based on sales milestones, as well as royalties on net sales.
“While the agreement provides the financial resources to execute on the Phase 2 clinical program for COYA 302 in ALS, the strategic value of the partnership contributes much more than capital,” Howard Berman, PhD, Coya’s CEO, said in a <a href="https://www.businesswire.com/news/home/20231206037106/en/Coya-Therapeutics-Inc.-and-Dr.-Reddy%E2%80%99s-Laboratories-Enter-into-an-Exclusive-Collaboration-for-Development-and-Commercialization-of-COYA-302-an-Investigational-Combination-Therapy-for-Treatment-of-Amyotrophic-Lateral-Sclerosis-ALS">press release</a>.
[recommended-reading id=82985]
<h3>2nd deal between Coya, Dr. Reddy&#8217;s this year on COYA 302</h3>
This agreement comes in addition to an <a href="https://ir.coyatherapeutics.com/news/news-details/2023/Coya-Therapeutics-Inc.-Announces-an-Agreement-with-Dr.-Reddys-Laboratories-Ltd.-to-License-its-proposed-biosimilar-Abatacept-for-the-Development-and-Commercialization-of-COYA-302-for-the-Treatment-of-Neurodegenerative-Diseases/default.aspx">in-licensing agreement</a> signed earlier this year, in which Dr. Reddy’s has allowed Coya to use its proposed biosimilar of abatacept — a fusion protein — as one of the components in COYA 302.
“We will benefit from and leverage Dr. Reddy’s manufacturing expertise and growing commercial infrastructure both in the USA and worldwide as we plan together for the future of COYA 302 in ALS,” Berman said.
ALS occurs due to damage to motor neurons, the nerve cells in the brain and spinal cord that control movement. The exact mechanisms leading to nerve cell damage in ALS are unclear, but an overly active immune system is believed to play a role.
COYA 302 contains a combination of low-dose interleukin-2 (IL-2), a signaling molecule that&#8217;s intended to increase the activity of anti-inflammatory immune cells called <a href="https://alsnewstoday.com/tregs/">regulatory T-cells</a> (Tregs), and a fusion protein known as CTLA4-Ig or abatacept. Abatacept is designed to decrease the activity of immune cells that promote inflammation and damage in ALS.
The combination therapy is given via a subcutaneous, or under-the-skin, injection.
[quote=&#8221;center&#8221;]We will benefit from and leverage Dr. Reddy’s manufacturing expertise and growing commercial infrastructure both in the USA and worldwide as we plan together for the future of COYA 302 in ALS.[/quote]
A small proof-of-concept trial tested the therapy in four people with ALS, who received treatment at the Houston Methodist Research Institute, in Texas, for 48 weeks, or about 11 months.
The results showed a marked slowing in disease progression, with patients experiencing less than a 2-point decline in ALS Functional Rating Scale (ALSFRS-R) scores over the 11 months. That was in comparison to a 1.1 monthly decline before entering the study.
COYA 302 also increased the activity of regulatory T-cells while leading to a reduction in markers of inflammation and oxidative stress — a type of cell damage caused by excessive inflammation. The treatment was well tolerated, with the most common side effect being mild reactions at the site of injection.
“Patients with ALS, commonly known as Lou Gehrig’s disease, have very few <a href="https://alsnewstoday.com/als-treatment/">treatment options</a>,” said Marc Kikuchi, CEO at Dr. Reddy’s North America.
&#8220;We are pleased to partner with Coya Therapeutics on this investigational therapy which may have a unique place in treating patients with this progressive neurodegenerative disease,&#8221; Kikuchi said.

Coya, Dr. Reddy’s collaborate to advance COYA 302 for ALS

Treatment with <a href="https://alsnewstoday.com/tregs/">regulatory T-cells</a> (Tregs), a type of anti-inflammatory immune cell, reduced biomarker levels of inflammation and oxidative stress in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), a study shows.
The experimental approach may help curb these contributions to nerve cell damage in ALS, the findings suggest, and routinely measuring the biomarkers could aid in monitoring responses to Treg treatment.
&#8220;The simultaneously assessed levels of immunological and oxidative factors are candidates to monitor disease progression and to properly target clinical trial endpoints response to [Treg] therapy in ALS,&#8221; the researchers wrote in “<a href="https://ageneudisjournal.com/article/view/6047?utm_source=sendgrid.com&amp;utm_medium=email&amp;utm_campaign=website">Immunological, oxidative, and structural factors and their responses to regulatory t lymphocyte therapy in amyotrophic lateral sclerosis</a>,” which was published in <a href="https://ageneudisjournal.com/">Ageing and Neurodegenerative Diseases</a>.
In ALS, motor neurons, the nerve cells that control voluntary movements, become damaged and die. As a result, the brain progressively loses control of movement, triggering <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a> such as muscle weakness, atrophy (shrinking), and stiffness.
Biological hallmarks associated with motor neuron loss include an overactive inflammatory response and <a href="https://alsnewstoday.com/news/oxidative-stress-may-be-therapy-target-in-als-study-of-skin-cells-suggests/">oxidative stress</a>, a type of cell damage caused by highly reactive oxygen-containing molecules generated from normal metabolism. Oxidative stress is increased in ALS and likely contributes to disease progression.
“Our pre-clinical studies have suggested that oxidative stress results from and promotes neuroinflammation and neuronal injury in ALS,” Stanley Appel, MD, scientific advisory board chairman of <a href="https://coyatherapeutics.com/">Coya Therapeutics</a> said in a <a href="https://www.businesswire.com/news/home/20230831425850/en/Coya-Therapeutics-Announces-Publication-of-Potential-Novel-Blood-Biomarker-Data-in-Amyotrophic-Lateral-Sclerosis-ALS-Patients-That-Accurately-Reflect-Therapeutic-Responses-When-Treated-with-Regulatory-T-Cell-Treg-Enhancing-Therapies">company press release</a>. Coya is developing two investigational anti-inflammatory treatments for ALS that boost Treg function.
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<h3>Treg therapy&#8217;s effect on inflammation, oxidative stress</h3>
In the new study, Appel and his colleagues at Houston Methodist Hospital, Texas examined the levels of various blood-based biomarkers associated with inflammation, oxidative stress, and nerve cell structural integrity in 30 people with sporadic ALS (63.3% male). The samples were compared to those from 10 age-matched healthy people (controls).
Blood tests revealed significantly elevated levels of CCL2, an immune signaling molecule associated with inflammatory responses, compared with healthy people. CCL2 levels were particularly increased in patients with rapid ALS progression over those progressing more slowly, although this group&#8217;s levels were still significantly higher than the controls&#8217;.
Similarly, the pro-inflammatory signaling protein interleukin-18 (IL-18) was significantly elevated in patients versus controls and in patients whose disease was progressing rapidly compared with those progressing slowly.
4-HNE, an oxidative stress marker, was also significantly increased in ALS patients with rapidly progressive disease, but slower progressors had levels similar to controls. MDA, another oxidative stress marker, was elevated in both patient groups versus controls, indicating it didn&#8217;t correlate with disease progression.
Levels of NfL and pNfH, two markers of nerve cell damage were examined too. NfL was elevated in rapidly progressing patients compared with slow progressors, but the patient groups didn&#8217;t differ significantly from healthy people. pNfH was reduced in rapidly progressing patients compared with controls, but no other group differences were observed.
<h3>Biomarkers of treatment response</h3>
To validate the biomarkers as indicators of treatment response, the researchers tested samples from ALS patients who participated in one of two clinical trials.
A <a href="https://clinicaltrials.gov/ct2/show/NCT03241784">Phase 1 pilot trial (NCT03241784)</a> enrolled three people with ALS and treated them with a Treg therapy called COYA 101 (formerly ALS001). Tregs are white blood cells that suppress immune responses and prevent unnecessary inflammation.
The cells were isolated, grown to greater numbers in a laboratory, and then infused back into the same patient. The participants also received interleukin-2, an immune signaling protein that boosts Treg function. Data, published in 2018, showed it <a href="https://alsnewstoday.com/news-posts/2021/02/05/coya-therapeutics-als001-treg-off-shelf-therapy-als-progression-phase-2-trial/">slowed progression rates</a> during the early and later stages of the disease.
The Treg/IL-2 combination therapy also suppressed CCL2, IL-18, and 4-HNE, and stabilized clinical status, as assessed with the Appel ALS (AALS) scoring system. During a “washout” period without Treg therapy, the biomarker levels increased and clinical status deteriorated.
A <a href="https://clinicaltrials.gov/ct2/show/NCT04055623">Phase 2a study (NCT04055623)</a> investigated COYA 101 in ALS patients given monthly infusions for six months. A six-month, open-label extension followed.
In this trial, the combination therapy suppressed CCL2 levels in five of the eight patients and IL-18 levels in six. 4-HNE levels were elevated in two patients, but remained low in six. As <a href="https://alsnewstoday.com/news/coya-treg-therapy-als001-als-reduces-inflammation-early-trial/">previously reported</a>, COYA 101 reduced ox-LDL, another marker of oxidative stress, in both the Phase 1 and Phase 2a study patients.
“It is gratifying that biomarkers of oxidative stress — 4-HNE and ox-LDL — correlated with responsiveness to therapy in 2 ALS clinical trials of Treg-enhancing therapies, and may provide an objective confirmation of clinical benefit in forthcoming trials,” Appel said.
“Immunological and oxidative pathological factors accurately reflected therapeutic responses in these pathways and are candidates to target clinical trial endpoints,” the researchers said.
The biomarkers will help assess the effectiveness of COYA 302, a combination of IL-2 and a fusion protein known as CTLA4-Ig or abatacept, Coya maintains. This therapy is designed to further increase Treg activity, reduce inflammation, and slow disease progression.
So far, in a small proof-of-concept clinical trial, four ALS patients saw a <a href="https://alsnewstoday.com/news/mda-2023-coya-302-therapy-slows-als-progression-early-trial/">marked slowing in disease progression</a> with COYA 302. The company plans to <a href="https://alsnewstoday.com/news/coya-meet-fda-about-phase-2-trial-coya-302-als/">file a request</a> with U.S. regulators to continue testing COYA 302 in a Phase 2 clinical trial.

Tag: COYA THERAPEUTICS

Coya aligns with FDA on plans for developing COYA 302 for ALS

Coya, Dr. Reddy’s collaborate to advance COYA 302 for ALS

ALS biomarkers are lowered with Coya’s Treg therapy: Study