Safe and Well Tolerated at all Dose Levels

Clinically Meaningful Reductions in Pain Lasting for a Week

SAN FRANCISCO, CA, USA I May 14, 2018 I Concentric Analgesics, Inc., a clinical-stage biopharmaceutical pain company, today announced topline results from its Phase 1b clinical trial for CA-008 in post-surgical pain. The primary objective of the clinical study was to demonstrate the safety and pharmacokinetics of CA-008, with secondary endpoints including efficacy. The study showed that CA-008, a novel, non-opioid therapeutic, was well tolerated at all dose levels compared to the control group following surgery in bunionectomy patients. Although the study was not powered for efficacy, the highest dose cohort of CA-008 showed statistically significant and clinically meaningful (greater than 50%) reductions in area under the curve (AUC) for pain intensity compared to the control group lasting up to 168 hours.

“The long-lasting duration of effect of a single intraoperative injection of CA-008, and the reductions in pain scores compared to control are remarkable, particularly as this Phase 1b trial was designed primarily for safety and not powered for efficacy,” said Neil Singla, MD, a board-certified anesthesiologist and chief scientific officer at Lotus Clinical Research, which conducted the Phase 1b study at Huntington Memorial Hospital in Pasadena, CA. “CA-008 showed a better pain response than the control group at nearly every time point in every dose group, a very convincing result.”

Study Design

The randomized, double-blind, placebo-controlled, dose-escalation study enrolled 40 patients undergoing bunionectomy with standard of care Mayo block (bupivacaine HCl 0.5%, up to 30 ml) and evaluated the safety of CA-008 compared to a saline control. The study was comprised of five cohorts of eight patients each, with six patients receiving CA-008 at ascending doses and two patients receiving control. Across the five cohorts, 30 patients received CA-008 across a nearly 10-fold dose range. CA-008, a prodrug to capsaicin in an aqueous solution, was administered via wide infiltration at the surgical site. The primary endpoints of this Phase 1b study were safety and pharmacokinetics, with various secondary endpoints including the effect on pain intensity out to two weeks post-surgery.

Safety Results

  • All doses of CA-008 were determined to be safe and well tolerated.
  • There was no dose-limiting toxicity, suggesting a large therapeutic window.
  • There were no serious or severe adverse events (AEs).
  • All AEs were mild to moderate, and most were deemed unrelated to study drug.
  • There was no observed effect on would healing.
  • There were no changes in local neurosensory exams.
  • There was no evidence of bone healing problems by exam or x-rays.
  • There were no significant ECG or laboratory changes.

Pharmacokinetic (PK) Results

Except for the highest dose, CA-008 could not be detected in plasma after 45 minutes, suggesting limited systemic exposure. The full PK profile for CA-008 and other analytes is pending.

Efficacy Results

Patients were evaluated for pain intensity and opioid consumption as part of a series of secondary analyses. This included using the standard Numerical Rating Scale (NRS), as measured by the area under the curve (AUC), as well as milestone reductions compared to the combined control group.

  • At the highest dose, CA-008 showed:
    • Statistically significant and clinically meaningful (greater than 50%) reduction of pain for AUC 0-168h (one week).
    • Statistically significant milestone reductions of pain at 48h, 72h, 96h and 120h.
    • Nearly a 50% reduction in opioid consumption.
  • Consistent and durable effect in reduction of pain with CA-008 showing a better pain response than the control group at nearly every time point for every dose group.
    • CA-008 reduced the mean pain score from moderate-to-severe (≥ 4/10) to mild (≤ 2 on average) by 48h which continued through 168h.

“In the surgical setting, the true unmet medical need is achieving sustained pain relief until pain has substantially subsided, typically around the fourth post-operative day,” said Steven Shafer, MD, Professor of Anesthesiology, Perioperative and Pain Medicine at Stanford University. “This study, to my knowledge, is the first demonstrating sustained analgesic efficacy at 72 hours and beyond following a single intra-operative injection. Concentric’s CA-008 is a potential game changer in perioperative pain management.”

“We are pleased our initial clinical study demonstrated that CA-008 can be administered safely to surgical patients and was well tolerated in this population. Additionally, the strong signal of efficacy is encouraging and supports CA-008’s unique and compelling therapeutic profile,” said John Donovan, MD, CEO of Concentric Analgesics. “We are now focused on advancing a broad-based development program to bring CA-008 to the millions of patients undergoing a wide range of surgeries who experience significant post-operative pain.”

Concentric Analgesics expects to present complete data, including pharmacokinetics and full 28-day follow-up results, from the Phase 1b clinical trial later this year.

The Company also plans to initiate a Phase 2b efficacy study with CA-008 in bunionectomy this summer with top-line data expected by the end of the year.

About Opioid Addiction & Post-Surgical Pain

Opioid addiction in the United States has reached epidemic proportions, destroying families, lives and communities throughout the country. New approaches for preventing this insidious disease are imperative, including in the post-surgical setting, which can be an unsuspecting gateway to prescription pain medicine abuse and beyond. A 2016 US News & World Report revealed that one in 10 patients report becoming addicted or dependent on opioids following surgery. With more than 100 million surgeries being performed in the US in 2017, 30 million of which require post-surgical pain management with non-over the counter (OTC) pain medications, the mandate to develop safe and effective non-opioid alternatives is clear.

About CA-008

Concentric Analgesic’s lead clinical candidate for post-surgical pain is CA-008. The compound is a proprietary water-soluble prodrug that converts into capsaicin – the naturally occurring molecule that gives chili peppers their heat. Capsaicin, a potent TRPV-1 agonist which has a long history of use as a topical analgesic, selectively and reversibly desensitizes pain conducting nerve fibers (C-fiber nociceptors). TRPV-1 agonism evokes an initial neuronal excitation that is followed by a durable refractory state to provide long lasting analgesia.

About Concentric Analgesics

Concentric Analgesics, Inc. is a privately-held, clinical-stage biopharmaceutical company focused on discovering and developing novel, non-opioid therapeutics for the management of acute and chronic pain. The Company’s core proprietary technology is the foundation of a broad portfolio of patented TRVP1-agonist prodrugs. In addition to its flagship post-surgical program with CA-008, the Company also has pre-clinical development programs in refractory cancer pain and osteoarthritis pain.

SOURCE: Concentric Analgesics