- Combination biologics with LD IL-2 as a backbone may represent
next-generation approaches that target complex immune pathways in
neurodegenerative diseases
- Expansion of COYA 302 into Alzheimer’s Disease leverages
synergistic mode of action and intellectual property position of
the biologic combination of the Company’s proprietary low-dose
interleukin-2 formulation (LD IL-2) with its proprietary CTLA4-Ig
that is intended to enhance the anti-inflammatory function of
regulatory T cells (Tregs), suppress pro-inflammatory cells, and
reduce oxidative stress
- Updated pipeline may be viewed here
Coya Therapeutics, Inc. (NASDAQ: COYA) (“Coya” or the
“Company”), a clinical-stage biotechnology company developing
multiple therapeutic programs intended to enhance regulatory T cell
(Treg) function, releases the following letter to stockholders from
its Chief Executive Officer and Chairman, Dr. Howard Berman.
Dear Fellow Stockholders,
Just over two months ago we announced our partnership with Dr.
Reddy’s Laboratories for COYA 302 in Amyotrophic Lateral Sclerosis
(ALS), our lead product candidate in our lead indication.
This pivotal collaboration is worth up to $733 million ($677.25
million in non-dilutive sales and milestone payments, $40 million
in development and regulatory milestones, and two tranche payments)
plus low-to-mid teens product royalties to us. We have already
received $7.5 million as an upfront payment tranche from that
transaction and expect to receive an additional $8.4 million
tranche in 2024 following the IND filing and first patient dosed in
the Ph. 2 ALS trial.
Our team continues to see strong value in COYA 302, as exhibited
by our announcement in January 2024 that we were expanding the
potential indications for that product candidate to include
Frontotemporal Dementia (FTD) and Parkinson’s disease (PD) as
additional indications. FTD and PD are two neurodegenerative
diseases that share common inflammatory disease pathways with ALS,
and we believe COYA 302 can target these multiple pathways by
restoring dysfunctional regulatory T cells (Tregs), reducing
oxidative stress, and inhibiting toxic neuroinflammation.
COYA 302 – “Pipeline in a Product” with Expansion into
Alzheimer’s Disease
Today, we announce that we are further expanding the pipeline
for COYA 302, adding Alzheimer’s disease (AD) to its growing list
of indications expected to be validated in the clinic. We recognize
the historical challenges faced by pharma companies looking to
address the massive problem that AD is posing to patients,
families, and the healthcare system. Yet, researchers have shown
that ALS, FTD, PD, and AD share common features, including
neuroinflammation and catastrophic neuronal loss that leads to
cognitive or motor dysfunction through the complex interplay of the
body’s immune system and dysfunctional anti-inflammatory Tregs. We
believe the traditional “one disease – one target - one drug”
approach might not be the most appropriate framework for
neurodegenerative disorders, and may be partly responsible for the
lack of available and truly effective treatments
Based on the results to date from our studies of COYA 302, which
is the combination of our proprietary low dose interleukin-2 (COYA
301, or LD IL-2) and the immunomodulatory drug CTLA4-Ig, we believe
this combination has the potential to provide a sustained and
durable effect on these devastating neurodegenerative disorders
through the targeting of multiple pathways. Our research and
clinical efforts lead us to believe that combination biologics
using our LD IL-2 as a backbone modality could be the best way to
treat neurodegenerative conditions that are inherently driven by a
complexity of pathways. We also believe that our growing
intellectual property portfolio across such combination therapies
positions us well to navigate this evolving landscape, with COYA
302 representing the most clinically advanced of what we hope will
be a family of combination therapies that all feature our
proprietary LD IL-2.
Moreover, given its growing list of indications, we can now
refer to COYA 302 as a “Pipeline in a Product.” It is not
just potentially viable in its lead indication of ALS. Rather, due
to its multi-modal mechanism of action, we believe it may be
efficacious across the spectrum of neurodegenerative diseases that
share a similar mechanistic cascade underlying pathophysiology,
such as FTD, PD, and AD, and therefore may have utility for more
patients beyond the ~20,000 patients suffering from ALS in the
U.S.
Ongoing Double-Blind Trial for LD IL-2 in AD: A
Proof-of-Concept Study to Support COYA 302 in AD
A double-blind, placebo-controlled, proof-of-concept study with
LD IL-2 in patients with AD is ongoing (and still blinded) at the
Houston Methodist Hospital, with top-line results anticipated in
mid-2024. While the primary objectives in this study are the
customary safety endpoints, a secondary endpoint to be measured is
the change in Treg percentage out of the total number of CD4 cells.
This study is intended to serve as a proof-of-concept to support
the development of COYA 302 as a treatment for AD, including a
potential partner strategy.
Since COYA 302 targets both the adaptive and innate immune
systems with the addition of CTLA4-Ig to our LD IL-2, we expect a
more sustained and durable effect than from just LD IL-2 alone.
This synergistic combination effect has, in fact, been clinically
documented by sustaining Treg anti-inflammatory suppressive
function and increasing Treg count over a 1-year period when given
to ALS patients. Further, this combination enhanced suppression of
macrophage mediated oxidative stress and proinflammatory cytokine
biomarkers in this population, which is critical since inflammation
and oxidative stress are hallmarks of neurodegenerative diseases.
We believe that this synergistic mechanism leads to the
re-establishment of immune balance and amelioration of inflammation
in a sustained and durable manner that may not be achieved by
either low-dose IL-2 or CTLA4-Ig alone. In AD, there is an
additional complex interaction between inflammation and protein
aggregation, including amyloid plaques and tau, and both may serve
as triggers for the other. Therefore, focusing solely on protein
aggregation as some therapies do without addressing inflammation
may not be adequate. Our combination therapy from COYA 302 aims to
address both pathways.
Additional Clinical Development Updates for COYA 302:
- ALS: Following the encouraging results of an open-label
academic study in patients with ALS that was led by Dr. Appel and
Dr. Thonhoff, we are planning a controlled, statistically-powered
clinical study to demonstrate the safety and efficacy of COYA 302
for the treatment of ALS. The study is expected to commence upon
the filing of the IND in the first half of 2024. This study
represents our lead indication.
- FTD: We intend to file an IND for the treatment of FTD
by Q4 2024.
- PD: We are performing ongoing mechanistic validation
studies in animals and intend to present data by Q3 2024.
Expanding Combination Therapies Beyond COYA 302
Beyond COYA 302, our therapeutic platform includes additional
drug product combinations using COYA 301 (our proprietary LD IL-2)
as their backbone. These combination candidates may have
therapeutic effects in diseases driven by inflammation and immune
system dysfunction and could enable potential strategic
collaborations.
We recently announced a licensing agreement with University of
Nebraska Medical Center covering multiple LD IL-2 combinations,
including LD IL-2 + Granulocyte-Macrophage Colony Stimulating
Factor (GM-CSF) in inflammatory disorders. This license expands our
multi-pathway approach in identifying and combining COYA 301 with
immunomodulatory drugs that are synergistic in simultaneously
enhancing Treg function and lowering inflammation.
Conclusion
With our current cash balance at the end of 2023, along with the
initial $7.5 million upfront payment received from Dr. Reddy’s in
early January 2024, we believe we have at least a two-year cash
runway to support our operations. We anticipate milestones in 2024
that could deliver additional shareholder value, including, but are
not limited to, 1) the publication of additional data from the COYA
302 investigator initiated trial in ALS patients and biomarker data
that is positively correlated to survival and rate of decline in
ALS patients, 2) the filing of INDs for COYA 302 in ALS and FTD,
and 3) topline data from the Ph. 2 investigator-initiated trial
with COYA 301 in AD that we expect will support the development of
COYA 302 in that same indication.
We are committed to developing our “Pipeline in a Product” in
COYA 302 with the ultimate goal of delivering safe and effective
therapies for patients affected by devastating neurodegenerative
diseases that collectively affect millions and millions of patients
in the U.S. alone. Based on the unveiling of Tregs and the role of
multiple pro-inflammatory mechanisms in the immune system by Dr.
Sakaguchi and Dr. Appel, members of our scientific advisory board,
we believe our desire to treat ALS, FTD, PD, and AD with COYA 302
combination therapy can offer meaningfully sustainable benefits to
a large and growing patient base across numerous indications. The
traditional “one disease – one target - one drug” approach might
not be the most appropriate framework for neurodegenerative
disorders and may be partly responsible for the lack of available
and truly effective treatments in the indications we are pursuing.
At Coya, we aim to bridge this gap in the neurodegenerative world,
and given the success combination therapies are having in cancer,
we see our approach as a natural scientific progression.
I look forward to providing investors with additional periodic
updates on our research, clinical, corporate, and commercial
progress.
Sincerely, Howard Berman Chairman and CEO Coya Therapeutics
About COYA 302
COYA 302 is an investigational and proprietary biologic
combination therapy with a dual immunomodulatory mechanism of
action intended to enhance the anti-inflammatory function of
regulatory T cells (Tregs) and suppress the inflammation produced
by activated monocytes and macrophages. COYA 302 is comprised of
proprietary low-dose interleukin-2 (LD IL-2) and CTLA4-Ig and is
being developed for subcutaneous administration for the treatment
of patients with ALS. These mechanisms may have additive or
synergistic effects.
In February of 2023, Coya announced results from a
proof-of-concept, open-label clinical study evaluating LD IL-2 and
CTLA4-Ig in a small cohort of patients with ALS conducted at the
Houston Methodist Research Institute (Houston, Texas) by Stanley
Appel, M.D., Jason Thonhoff, M.D., Ph.D., and David Beers, Ph.D.
This study was the first-of-its-kind evaluating this dual-mechanism
immunotherapy for the treatment of ALS. Patients in the study
received investigational treatment for 48 consecutive weeks and
were evaluated for safety and tolerability, Treg function, serum
biomarkers of oxidative stress and inflammation, and clinical
functioning as measured by the ALSFRS-R scale.
During the 48-week treatment period, the therapy was well
tolerated. The most common adverse event was mild injection-site
reactions. No patient discontinued the study, and no deaths or
other serious adverse events were reported.
Patients' disease progression was measured using the ALSFRS-R
scale, a validated rating tool for monitoring the progression of
disability in patients with ALS. The mean (±SD) ALSFRS-R scores at
week 24 (33.75 ±3.3) and week 48 (32 ±7.8) after initiation of
treatment were not statistically different compared to the ALSFRS-R
score at baseline (33.5 ±5.9), suggesting significant amelioration
in the progression of the disease over the 48-week treatment
period.
Treg suppressive function, expressed as percentage of inhibition
of proinflammatory T cell proliferation, showed a statistically
significant increase over the course of the treatment period and
was significantly reduced at the end of the 8-week washout
post-treatment period. Treg suppressive function at 24 weeks (79.9
±9.6) and 48 weeks (89.5 ±4.1) were significantly higher compared
to baseline (62.1 ±8.1) (p<0.01), suggesting enhanced and
durable Treg suppressive function over the course of treatment. In
contrast, Treg suppressive function (mean ±SD) was significantly
decreased at the end of the 8-week washout period compared to
end-of-treatment at week 48 (70.3 ±8.1 vs. 89.5 ±4.1, p
<0.05).
The study also evaluated serum biomarkers of inflammation,
oxidative stress, and lipid peroxides. The available data up to 16
weeks after initiation of treatment suggest a decrease in these
biomarker levels, which is consistent with the observed enhancement
of Treg function. The evaluation of the full biomarker data is
ongoing.
COYA 302 is an investigational product not yet approved by the
FDA or any other regulatory agency.
About Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's
Disease, is a rare neurological disease that affects motor neurons,
the nerve cells in the brain and spinal cord that control voluntary
muscle movement. About 20,000 people live with ALS in the United
States and approximately 5,000 new cases are diagnosed every year.
The disease is progressive, meaning the symptoms get worse over
time. The functional status of ALS patients declines about 1 point
per month on average, as measured by the Revised ALS Function
Rating Scale1, or ALSFRS-R, a validated tool to monitor the
progression of the disease.
ALS has no cure, and the currently approved drug treatments
provide limited benefit to patients. ALS is a type of motor neuron
disease. As motor neurons degenerate and die, they stop sending
messages to the muscles, which causes the muscles to weaken, start
to twitch (fasciculations), and waste away (atrophy). Eventually,
the brain loses its ability to initiate and control voluntary
movements. Most people with ALS die from respiratory failure,
usually within three to five years from when the symptoms first
appear.2
About Frontotemporal Dementia
Frontotemporal dementia (FTD) is the result of damage to neurons
in the frontal and temporal lobes of the brain. Many possible
symptoms can result, including unusual behaviors, emotional
problems, trouble communicating, difficulty with work, or
difficulty with walking. FTD is rare and tends to occur at a
younger age than other forms of dementia. About 60% of people with
FTD are 45 to 64 years old. FTD is progressive, meaning symptoms
get worse over time. In the early stages, people may have just one
symptom. As the disease progresses, other symptoms appear as more
parts of the brain are affected. It is difficult to predict how
long someone with FTD will live. Some people live more than 10
years after diagnosis, while others live less than two years after
they are diagnosed. There is no cure for FTD, and no treatments
slow or stop the progression of the disease.3
About Parkinson’s Disease
Parkinson’s disease (PD) is a progressive brain disorder that
causes unintended or uncontrollable movements, such as shaking,
stiffness, and difficulty with balance and coordination. The most
prominent manifestations of PD occur when nerve cells in the basal
ganglia, an area of the brain that controls movement, become
impaired or die. As the disease progresses, people may have
difficulty walking and talking. They may also have mental and
behavioral changes, sleep problems, depression, memory
difficulties, and fatigue. Most people with PD first develop the
disease after age 60, but about 10% experience onset before the age
of 50. There is no cure for PD and currently available treatments
are intended to relieve some symptoms.4
About Alzheimer’s Disease
Alzheimer's disease is the most common cause of dementia, a
general term for memory loss and other cognitive abilities serious
enough to interfere with daily life. Alzheimer's disease accounts
for up to 80% of dementia cases, affecting an estimated 5.7 million
Americans. In more than 90% of people with Alzheimer’s, symptoms do
not appear until after age 60. The incidence of the disease
increases with age and doubles every 5 years beyond age 65.
Alzheimer's is a progressive disease, where dementia symptoms
gradually worsen over a number of years. In its early stages,
memory loss is mild, but with late-stage Alzheimer's, individuals
lose the ability to carry on a conversation and respond to their
environment. It is the sixth leading cause of death among all
adults and the fifth leading cause for those aged 65 or older. On
average, a person with Alzheimer's lives 4 to 8 years after
diagnosis but can live as long as 20 years, depending on other
factors. 5, 6
References
- Atassi N, et al. The PRO-ACT database: design, initial
analyses, and predictive features. Neurology, 2014;83:1719–1725.
doi: 10.1212/WNL.0000000000000951.
- National Institutes of Health (NIH) Website
(https://www.ninds.nih.gov), accessed on January 8, 2024.
- National Institutes of Health (NIH) Website
(https://www.nia.nih.gov), accessed on January 8, 2024.
- National Institutes of Health (NIH) Website
(https://www.nia.nih.gov), accessed on January 8, 2024.
- Alzheimer’s Association (www.alz.org).
- Centers for Disease Control and Prevention (www.cdc.gov).
About Coya Therapeutics, Inc.
Headquartered in Houston, TX, Coya Therapeutics, Inc. (Nasdaq:
COYA) is a clinical-stage biotechnology company developing
proprietary treatments focused on the biology and potential
therapeutic advantages of regulatory T cells (“Tregs”) to target
systemic inflammation and neuroinflammation. Dysfunctional Tregs
underlie numerous conditions, including neurodegenerative,
metabolic, and autoimmune diseases, and this cellular dysfunction
may lead to sustained inflammation and oxidative stress resulting
in lack of homeostasis of the immune system.
Coya’s investigational product candidate pipeline leverages
multiple therapeutic modalities aimed at restoring the
anti-inflammatory and immunomodulatory functions of Tregs. Coya’s
therapeutic platforms include Treg-enhancing biologics,
Treg-derived exosomes, and autologous Treg cell therapy.
COYA 302 – the Company’s lead investigational product – is a
proprietary combination of COYA 301 (Coya’s proprietary LD IL-2)
and CTLA4-Ig for subcutaneous administration with a unique dual
mechanism of action that is now being developed for the treatment
of ALS, FTD, PD, and AD. Its multi-targeted approach enhances the
number and anti-inflammatory function of Tregs and simultaneously
lowers the expression of activated microglia and the secretion of
pro-inflammatory mediators. This synergistic mechanism may lead to
the re-establishment of immune balance and amelioration of
inflammation in a sustained and durable manner that may not be
achieved by either low-dose IL-2 or CTLA4-Ig alone.
For more information about Coya, please visit
www.coyatherapeutics.com
Forward-Looking Statements
This press release contains “forward-looking” statements that
are based on our management’s beliefs and assumptions and on
information currently available to management. Forward-looking
statements include all statements other than statements of
historical fact contained in this presentation, including
information concerning our current and future financial
performance, business plans and objectives, current and future
clinical and preclinical development activities, timing and success
of our ongoing and planned clinical trials and related data, the
timing of announcements, updates and results of our clinical trials
and related data, our ability to obtain and maintain regulatory
approval, the potential therapeutic benefits and economic value of
our product candidates, competitive position, industry environment
and potential market opportunities. The words “believe,” “may,”
“will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,”
and similar expressions are intended to identify forward-looking
statements.
Forward-looking statements are subject to known and unknown
risks, uncertainties, assumptions and other factors including, but
not limited to, those related to risks associated with the impact
of public health emergencies, including COVID-19; the success, cost
and timing of our product candidate development activities and
ongoing and planned clinical trials; our plans to develop and
commercialize targeted therapeutics; the progress of patient
enrollment and dosing in our preclinical or clinical trials; the
ability of our product candidates to achieve applicable endpoints
in the clinical trials; the safety profile of our product
candidates; the potential for data from our clinical trials to
support a marketing application, as well as the timing of these
events; our ability to obtain funding for our operations;
development and commercialization of our product candidates; the
timing of and our ability to obtain and maintain regulatory
approvals; the rate and degree of market acceptance and clinical
utility of our product candidates; the size and growth potential of
the markets for our product candidates, and our ability to serve
those markets; our commercialization, marketing and manufacturing
capabilities and strategy; future agreements with third parties in
connection with the commercialization of our product candidates;
our expectations regarding our ability to obtain and maintain
intellectual property protection; our dependence on third party
manufacturers; the success of competing therapies or products that
are or may become available; our ability to attract and retain key
scientific or management personnel; our ability to identify
additional product candidates with significant commercial potential
consistent with our commercial objectives; and our estimates
regarding expenses, future revenue, capital requirements and needs
for additional financing.
We have based these forward-looking statements largely on our
current expectations and projections about future events and trends
that we believe may affect our financial condition, results of
operations, business strategy, short-term and long-term business
operations and objectives, and financial needs. Moreover, we
operate in a very competitive and rapidly changing environment, and
new risks may emerge from time to time. It is not possible for our
management to predict all risks, nor can we assess the impact of
all factors on our business or the extent to which any factor, or
combination of factors, may cause actual results to differ
materially from those contained in any forward-looking statements
we may make. In light of these risks, uncertainties and
assumptions, the forward-looking events and circumstances discussed
herein may not occur and actual results could differ materially and
adversely from those anticipated or implied in the forward-looking
statements. Although our management believes that the expectations
reflected in our forward-looking statements are reasonable, we
cannot guarantee that the future results, levels of activity,
performance or events and circumstances described in the
forward-looking statements will be achieved or will occur. We
undertake no obligation to publicly update any forward-looking
statements, whether written or oral, that may be made from time to
time, whether as a result of new information, future developments
or otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20240221388488/en/
Investor Contact David Snyder
david@coyatherapeutics.com
CORE IR Bret Shapiro brets@coreir.com 561-479-8566
Media Contact Jessica Starman
jessica@elev8newmedia.com
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