PainReform Ltd. announced that it has commenced a Phase 3 clinical trial of PRF-110, the Company's lead drug candidate, targeting the post-operative extended pain relief market. The Phase 3 trial is a randomized, double-blind, placebo- and active- controlled, multicenter study to evaluate the analgesic efficacy and safety of intra-operative administration of PRF-110 following unilateral bunionectomy. PRF-110 is an oil-based, viscous, clear solution that is deposited directly into the surgical wound bed prior to closure to provide localized and extended post-operative analgesia.

The study will be conducted in two parts. In the first part, a total of 15 patients will be enrolled in an open-label safety pharmacokinetic (PK) study at two clinical sites in Texas (First Surgical Hospital in Bellaire Texas and Endeavor Clinical Trials in San Antonio Texas). PRF-110 will be administered intra-operatively to measure peak blood concentration in order to further validate safety of the lead formulation.

This study will also serve to train surgeons in best practices for administering PRF-110, optimally covering inner wound surfaces for most efficient analgesia. Following the confirmation of peak blood levels, the study will proceed to the second, larger, part of the Phase 3 clinical trial. The second part of the trial will be double-blinded, in which the Company plans to randomize approximately 400 patients at up to seven clinical sites in the U.S. PRF-110 will be administered intra-operatively and patients will be divided into three cohorts, PRF-110, ropivacaine, and placebo in a 2:2:1 ratio.

The primary efficacy endpoint is mean area under the curve (AUC) of the numerical rating scale (NRS) of pain intensity scores over 72 hours (AUC0-72) for PRF- 110 compared with placebo. Secondary efficacy endpoints include: mean AUC0-72 of the NRS of pain intensity scores for PRF-110 compared with plain ropivacaine; total post-surgery opioid consumption (in morphine equivalents) over 72 hours for PRF-110 compared with saline placebo; the proportion of subjects who are opioid-free through 72 hours for PRF-110 compared to that of plain ropivacaine; and the total postoperative opioid consumption through 72 hours for PRF-110 compared to that of plain ropivacaine. Safety endpoints include incidence of treatment emergent adverse events and serious adverse events, physical examination, vital signs and wound healing.

As previously reported, PRF-110 provided pain reduction for up to 72 hours post-operatively in the Company's prior Phase 2 proof-of-concept clinical study in herniorrhaphy (hernia repair). PRF-110 is a highly uniform solution, resulting in consistent sustained and extended release of the analgesic. Ropivacaine, the active drug used in PRF-110, is a safe, well-tolerated, and well-characterized local anesthetic.

The other components that make up the remainder of the PRF-110 formulation have been designated by the FDA as Generally Recognized as Safe (GRAS), by the FDA, mitigating many potential safety issues that are common in drug development. Key surgical benefits observed to date, include: PR110 d does not alter the integrity of common surgical devices, such as sutures and meshes ed to in a lararge variety of surgical procedures; PRF-110 does not interfere with normal macro and microscopic wound healing of surgical incisions in soft tissue and bone models; and PRF-110 does not alter the tensile strength of healed skin at the surgical sites in an animal study mimicking real surgical procedures.