Full Press Release Details
Eupraxia's DiffuSphere
Technology Demonstrates Targeted Drug Release while Minimizing Systemic Exposure for a Period of More Than Six Months
Victoria, B.C. - November 20, 2024 -
Eupraxia Pharmaceuticals Inc. ("Eupraxia" or the "Company") (NASDAQ: EPRX) (TSX: EPRX), a clinical-stage biotechnology
company, today unveiled new pharmacokinetic ("PK") data from its Phase 2a Eosinophilic Esophagitis ("EoE") program.
Management believes these data underscore the unique capabilities of Eupraxia's proprietary DiffuSphere platform technology,
which aims to provide precise, localized, safe, and effective long-lasting drug delivery.
Most conventional drugs release in a pattern
characterized by steep peaks and rapid declines in drug concentration, where peaks often lead to negative side effects, and troughs result
in reduced efficacy. In contrast, DiffuSphere is a unique microsphere that is designed to enable precise drug release into target
tissues with a flat, stable, and long-lasting profile, minimizing potential adverse events associated with high-dose systemic delivery.
What sets DiffuSphere apart is its composition:
a pure drug crystal encased in a microns-thick polymer shell. Eupraxia's proprietary technology uses this polymer to precisely control
a drug's release, ensuring high drug concentrations in the target tissues while minimizing exposure to the rest of the body. This
innovative approach has been observed in Eupraxia's clinical programs, demonstrating precision, tolerability, and extended duration
of delivering fluticasone propionate ("FP") directly to the intended tissues for EoE and knee osteoarthritis ("OA")
"Our DiffuSphere platform is designed
to enable us to deliver the right drug to the right place at the right time with a precise PK profile, aiming to ensure patients receive
safe, effective, and durable treatment," said Eupraxia's CEO, Dr. James Helliwell. "We are excited about the broad-based
potential of DiffuSphere . The clinical data from EoE and OA, combined with our extensive non-clinical data showing precise delivery
of numerous drugs in a broad array of target tissues, reinforces our optimism."
RESOLVE Trial Demonstrates Compelling
Pharmacokinetics in the Esophagus
DiffuSphere , when injected into
the esophageal wall (submucosa), shows a treatment duration exceeding six months from a single injection, with predictable dose control.
In Cohort 1 (4 mg FP), a steady level of 1.5 pg/ml was maintained for at least six months. In Cohort 5 (48 mg FP), 10pg/ml was observed
at three months. With this steady, localized, and long-lasting delivery, key EoE disease measures, including patient symptoms, esophageal
tissue health, and eosinophil counts, improved.
This impact of the DiffuSphere
technology was clearly demonstrated in a non-clinical study in pigs comparing local and systemic levels of FP after intraesophageal injection
of EP-104GI versus oral gavage. Presented at the American College of Gastroenterology meeting (poster), the study revealed that esophageal
tissue levels of fluticasone were more than 1000 times higher in the EP-104GI group compared to the oral gavage group, even at distances
of several centimeters from the injection sites. Moreover, despite significantly higher local concentrations, systemic levels of fluticasone
in the plasma were lower in the EP-104IAR group than in the oral gavage group. This underscores the targeted and precise delivery capabilities
of the DiffuSphere technology.
DiffuSphere in the Joint
DiffuSphere is the technology
behind Eupraxia's EP-104IAR for treating OA. In Eupraxia's Phase 2b clinical study, EP-104IAR was well tolerated and showed
significantly durable efficacy over placebo. The trial results were recently published in The Lancet, reinforcing the preclinical
work previously published in Cartilage. The Phase 2b data showed that EP-104IAR effectively controlled patients' pain for
up to 22 weeks (as measured by OARSI Strict Responders) and was well-tolerated. This includes no disruption to blood glucose metabolism
(a key factor for diabetics, who comprise almost 40% of the OA population) or adrenal function, which have been reported with other steroid
formulations used in this indication.
DiffuSphere in Other Applications
Eupraxia has successfully applied
DiffuSphere across multiple anatomic locations and drug classes. In preclinical studies, DiffuSphere has demonstrated its
precise, steady, and tunable delivery traits in intraarticular, intraesophageal, intravitreal, epidural, peritoneal, and subcutaneous
applications. Additionally, Eupraxia has demonstrated DiffuSphere's capability with local anesthetics such as ropivacaine
and various anti-infective agents.
The new data in EOE patients further
supports DiffuSphere's ability to deliver drugs with local precision: stable drug delivery without peaks and troughs, and
a customizable duration to fit the clinical indication. This reinforces Eupraxia's confidence in the platform's broad potential.
About Eosinophilic Esophagitis (EOE) and the RESOLVE
EoE is an inflammatory-mediated disease
in which white blood cells migrate into and become trapped in the esophagus, creating pain and difficulty with swallowing food. According
to market research from Clearview Healthcare Partners, EoE affects more than 450,000 people in the United States and has been identified
by the American Gastroenterological Association as rapidly increasing in both incidence and prevalence. Impacts from both symptoms and
interventions frequently lead to mental health issues, compounding the disease burden of EoE for both the healthcare system and the individual.
RESOLVE is a Phase 1b/2a, multicenter,
open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of EP-104GI in adults with histologically
confirmed, active EoE. EP-104GI is administered as a single dose via four to 20 injections into the esophageal wall. Dose escalations
increase the dose per site and/or number of sites. Participants in the first through the fourth cohorts will be assessed for up to 24
weeks, and cohorts five and above will be assessed for up to 52 weeks.
About Osteoarthritis (OA)
Eupraxia's OA product candidate, EP-104IAR,
is designed to meet the significant unmet medical need and market demand for long-lasting disease relief in multiple indications, benefitting
from highly localized and longer delivery of corticosteroids. The lead indication is for pain relief in knee OA. The U.S. Centers for
Disease Control and Prevention estimates knee OA affects more than 30 million people in the U.S. alone. This includes 14 million that
suffer from knee pain or some form of disability. Knee OA is also associated with depression and loss of sleep, which can significantly
affect quality of life.
With EP-104IAR, Eupraxia hopes to change
the way knee OA pain is treated. The Company believes current therapies are challenged by poor safety, inadequate efficacy and/or limited
duration of activity. Corticosteroids are one of only two drug classes strongly recommended by the American College of Rheumatology and
the Arthritis Foundation for treating knee OA pain. Currently approved corticosteroids are very effective at reducing pain for a short
duration late in the disease but can expose the body to unwanted local and systemic side effects.
EP-104IAR is designed to prolong the
duration of pain relief with fewer adverse events. It encapsulates a highly potent corticosteroid (fluticasone propionate) within a microns-thin
polymer membrane, part of Eupraxia's patented technology platform.
Injected into the knee, EP-104IAR is
designed to diffuse the corticosteroid slowly into the knee joint providing local therapeutic concentrations for up to six months. This
has the potential dual advantage of providing longer duration of pain relief with fewer systemic adverse events. A robust safety and tolerability
profile would also benefit the estimated 70% of knee OA patients that experience pain in both knees by allowing simultaneous treatment
of both affected joints. EP-104IAR has also been designed to incorporate additional advantages, such as physician convenience, targeting
a long shelf life, no refrigeration and easy integration into existing delivery techniques.
About Eupraxia Pharmaceuticals Inc.
Eupraxia is a clinical-stage biotechnology
company focused on developing locally delivered, extended-release products that have the potential to address therapeutic areas with high
unmet medical need. DiffuSphere , a proprietary, polymer-based micro-sphere technology, is designed to facilitate targeted drug
delivery of both existing and novel drugs. The technology is designed to support extended duration of effect and delivery of drugs in
a hyper-localized fashion, targeting only the tissues that physicians are wanting to treat. We believe the potential for fewer adverse
events may be achieved through the precision targeting and the stable and flat delivery of the active ingredient when using the DiffuSphere
technology, versus the peaks and troughs seen with more traditional drug delivery methods. The precision of Eupraxia's DiffuSphere
technology platform has the potential to augment and transform existing FDA-approved drugs to improve their safety, tolerability, efficacy
and duration of effect. The potential uses in therapeutic areas may go beyond pain and inflammatory gastrointestinal disease, where Eupraxia
currently is developing advanced treatments, to also be applicable in oncology, infectious disease and other critical disease areas.
Eupraxia's EP-104GI is currently in
a Phase 1b/2a trial, the RESOLVE trial, for the treatment of EoE. EP-104GI is administered as an injection into the esophageal wall, providing
local delivery of drug. This is a unique treatment approach for EoE. Eupraxia also recently completed a Phase 2b clinical trial (SPRINGBOARD)
of EP-104IAR for the treatment of pain due to knee osteoarthritis. The trial met its primary endpoint and three of the four secondary
endpoints. In addition, Eupraxia is developing a pipeline of later and earlier-stage long-acting formulations. Potential pipeline indications