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Centrexion Therapeutics Announces New 6-Month Data Demonstrating Significant and Durable Pain Relief with CNTX-4975 for Treatment of Moderate to Severe Knee Osteoarthritis Pain

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Centrexion Therapeutics, a company focused on advancing the treatment
of chronic pain with one of the largest exclusively pain-focused
clinical pipeline of non-opioid therapies in active development, today
announced positive 6-month efficacy data from the Phase 2b TRIUMPH
clinical trial demonstrating durable response of CNTX-4975 for treatment
of chronic pain associated with knee osteoarthritis. The data are being
presented in an invited presentation at the European League Against
Rheumatism's Annual European Congress of Rheumatology (EULAR 2017) in
Madrid this week.

The new data show large and statistically significant pain relief
continuing through 24 weeks from a single 1 mg injection of CNTX-4975
(p=0.0002), as well as statistically and clinically significant improved
knee stiffness and physical function during the trial in patients with
moderate to severe knee osteoarthritis pain. Treatment with CNTX-4975
resulted in large levels of pain reduction compared to baseline and
statistical separation from placebo beginning at Week 1. These data
represent the largest reductions seen in knee osteoarthritis reported
for any drug treatment, marketed or in development. Additionally, safety
results continue to show that CNTX-4975 is well tolerated with a safety
profile similar to placebo.

"These impressive and robust 6-month data demonstrate the potential of
CNTX-4975 to be a long-lasting and efficacious treatment. Not only are
we seeing an onset of pain reduction in days, treatment with CNTX-4975
resulted in much larger pain reductions than has been seen with other
pain therapeutics in knee osteoarthritis and we are seeing this response
endure for six months," said Randall M. Stevens, M.D., chief medical
officer of Centrexion Therapeutics. "Importantly, in the context of
treating a chronic condition, we are seeing these exciting efficacy
responses with a safety profile that looks like placebo."

"Chronic pain, particularly knee osteoarthritis, is a growing problem,
not only creating a burden on our healthcare system but also having a
significant negative impact on lives of people living with pain," said
Philip Mease, M.D., clinical professor at the University of Washington
School of Medicine in Seattle, director of the Rheumatology Clinical
Research Division of Swedish Medical Center. "There is an urgent need
for new safe and effective treatments without running the risks of abuse
and addiction associated with opioid use or damaging side effects seen
with other pain treatments. CNTX-4975 has demonstrated remarkable
results in a difficult to treat population and shows promise as a new
approach for treating knee osteoarthritis pain."

TRIUMPH Phase 2b Clinical Trial Results and Design
The
dose-ranging 24 week Phase 2b study evaluated the safety and efficacy of
a single intra-articular injection (injected into the knee joint) of
CNTX-4975 in subjects aged 45-80 years with chronic knee osteoarthritis,
who had stable moderate to severe knee pain, radiographic damage from
moderate to severe, and had failed or were unable to tolerate existing
oral or intra-articular analgesics. The 175 patients were randomized to
receive either a single injection into the knee of CNTX-4975 0.5 mg
(n=34), CNTX-4975 1 mg (n=71) or placebo (n=70).

Primary and Secondary Endpoints Met at 12 Weeks
At 12 weeks,
the study showed that treatment with a single 1 mg dose of CNTX-4975
resulted in significant and clinically meaningful improvements in
primary and secondary outcome measures. The 12 week primary endpoint of
the study, pain with walking (WOMAC [Western Ontario and McMaster
Universities Arthritis Index] question A1), was met with high
statistical significance (p<0.0001). Significant improvements in pain
with walking were observed in subjects who were predominately obese
(BMI≥30kg/m2) and had K-L grades 2-4. Additional outcome
measures at week 12 were all statistically and clinically significant,
including knee joint stiffness and function (assessed by WOMAC B and
WOMAC C, respectively), patient global impression of change (PGIC), and
responder analysis (the proportion of patients improved by percent from
baseline pain).

Efficacy Endpoints Met At 24 Weeks
In order to determine the
duration of effect from a single injection of CNTX-4975, patients were
then followed under double blind, placebo control from the 12 week
timepoint out to 24 weeks. At 24 weeks post injection, patients treated
with the 1 mg dose continued to show a large and statistically
significant level of pain relief compared to placebo as well improved
knee stiffness and physical function.

                         
            Week 12         Week 24  
  Assessment    

Decrease
from
Baseline

       

Difference
vs.
Placebo

        P value    

Decrease
from
Baseline

       

Difference
vs.
Placebo

        P value  
  Daily Pain with Walking (measured by AUC)     -3.9     -1.6     P<0.0001     -3.8     -1.3     P=0.0002  
  Daily Pain with Walking (measured by MMRM)         -4.4         -1.5         P=0.0003         -3.8         -0.9         P=0.067*  

* Statistical significance prespecified at 0.1
AUC: area
under curve; MMRM: mixed model for repeated measures

Safety results showed that the Day 1 injection of CNTX-4975 was
generally well tolerated. Adverse events were similar to those seen with
placebo and there were no drug-related serious adverse events.
Laboratory abnormalities were few and similar between placebo and
CNTX-4975.

"With these positive data and the successful End of Phase 2 meetings
with the FDA and the European authorities that we had earlier this year,
we look forward to advancing the development of CNTX-4975 with the
initiation of a Phase 3 trial for the treatment of chronic moderate to
severe knee osteoarthritis pain later this year," said Jeffrey B.
Kindler, chief executive officer of Centrexion Therapeutics.

Presentation Details
The data are being presented in an
invited presentation at the European League Against Rheumatism's Annual
European Congress of Rheumatology (EULAR 2017) in Madrid this week:

Title (OPO167): Efficacy And Safety Of CNTX-4975 in Subjects
with Moderate To Severe Osteoarthritis Knee Pain: 24-Week, Randomized,
Double-Blind, Placebo-Controlled, Dose-Ranging Study

Session:
Osteoarthritis: new horizons for treatment
Presentation Time:
10:50 a.m. CEST, June 15, 2017
Location: Room N117 / N118

About CNTX-4975
CNTX-4975 is based on Centrexion's
proprietary STRATI® technology (Synthetic TRans
cApsaicin ulTra-pure Injection), a highly potent,
ultrapure, synthetic form of trans-capsaicin (a medicine traditionally
derived from the chili plant). CNTX-4975 is designed to be injected
directly into the site of pain to provide rapid onset, large reduction
and long duration of relief from moderate to severe pain without
affecting touch sensibility or position sense.

CNTX-4975 works by targeting the capsaicin receptor (TRPV1) to
selectively and rapidly inactivate only the local pain fibers
transmitting signals to the brain. With a short half-life, CNTX-4975 is
cleared from the body within 24 hours. This approach provides pain
relief that can last for months until the ends of the local pain fibers
regenerate, while maintaining normal sensation, such as touch, pressure
and position, and without the risks of toxicities of NSAIDs and injected
corticosteroids or the side effects, including abuse and addiction,
associated with opioid treatments.

About Osteoarthritis
Osteoarthritis (OA) is the most
common form of arthritis, affecting approximately 14 million people in
the United States.1 It occurs when the protective cartilage
on the ends of the bones wears down over time, and the bone around the
joints harden and form edges. These changes cause pain, swelling and
problems moving the joint. OA also causes an inflammatory process to
occur in the affected joint, further damaging the cartilage. Although OA
can damage the majority of joints in the body, it most commonly affects
joints in the knees, hips, hands and spine. OA can cause pain severe
enough that patients experience difficulty walking, climbing stairs or
even rising from a chair. Despite currently available therapies, many
patients opt for total joint replacement to manage the painful condition.

About Centrexion Therapeutics
Centrexion
Therapeutics, Corp. is focused on advancing the treatment of chronic
moderate to severe pain with one of the largest exclusively pain-focused
pipelines of non-opioid, non-addictive therapies in active development.
Centrexion Therapeutics recognizes the needs of over a quarter of a
billion people living with chronic pain worldwide, and aims to develop
new, safer and more effective therapies that overcome the limitations
and challenges associated with current pain treatments. Founded by
world-renowned leaders in drug development and well-funded by key
investors, Centrexion Therapeutics is building a pain treatment
powerhouse to address the substantial and growing global chronic pain
epidemic. Centrexion Therapeutics has recently relocated from Baltimore,
Md. to Boston, Mass.

For more information about Centrexion, visit http://www.centrexion.com.

1. Deshpande, B., et al. Number of Persons With Symptomatic Knee
Osteoarthritis in the US: Impact of Race and Ethnicity, Age, Sex, and
Obesity. Arthritis Care & Research. Published online November 3, 2016

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