MiMedx Group, Inc. announced top-line results from two late-stage musculoskeletal clinical trials of the company’s micronized dehydrated Human Amnion Chorion Membrane (mdHACM): a Phase 2B clinical trial for the treatment of Knee Osteoarthritis (KOA) and a Phase 3 clinical trial for the treatment of Plantar Fasciitis (PF). Top-line results from an interim analysis of the six-month efficacy data for the Phase 2B clinical trial for KOA did not meet primary endpoints, but did reveal varied efficacy signals between patient cohorts evaluated pre- and post- a blinded interim analysis performed in mid-2019, prompting the Company to plan for confirmatory efficacy studies for the KOA indication. The Phase 3 PF study did not meet its primary endpoint, and the company will not pursue a BLA for this indication at this time. Throughout both studies, the mdHACM product was found safe and well-tolerated. The Phase 2B KOA trial formally ends in October 2021. An interim review of the 446 patients enrolled in the clinical trial showed that the study did not meet its two primary efficacy endpoints of a statistically significant change in the Visual Analog Scale (VAS) for Pain or in the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. The top-line data indicate a potential positive clinical efficacy signal, but did not indicate a statistical difference between patients in the product treatment group and the placebo group, with all scores improving for both groups. Significant differences were observed between patients enrolled prior to the study’s initial blinded interim analysis (the Pre-Interim Analysis Cohort), and those patients enrolled following the initial blinded interim analysis (the Post-Interim Analysis Cohort). Patients in the treatment group in the Pre-Interim Analysis Cohort demonstrated a greater improvement in WOMAC-Total, WOMAC-Pain and WOMAC-Function scores, with statistically significant separation between treatment and placebo-treated patients at both the three-month and six-month endpoints. The patients in the Post-Interim Analysis Cohort showed a positive response to both treatment and placebo. Additional analyses are planned to explore these differences. Results for VAS did not indicate statistically significant differences between treatment and placebo-treated patients, or between the Pre-Interim Analysis Cohort and the Post-Interim Analysis Cohort at either the three-month or six-month endpoint, with a strong improvement in VAS observed across both cohorts. The company plans to meet with the FDA to thoroughly review the findings and determine the appropriate path forward toward the initiation of Phase 3 clinical trials in KOA. Based on the current analysis of the interim results for the Phase 2B clinical trial, the company now believes that two Phase 3 studies in KOA will be required to file a BLA and intends to provide an update for the timing of the filing, previously tentatively planned for late-2024 or early-2025, following review and discussion with the FDA. The Phase 3 PF study did not meet its primary endpoints. The product and placebo groups both improved during the treatment period, and demonstrated reduced VAS Pain and improved Foot Function Index-Revised (FFI-R) scores, without statistically significant separation between treatment groups. The company plans on a complete review of the full study data, but does not intend to pursue a BLA filing for PF at this time, instead focusing resources on advancing confirmatory Phase 3 studies for KOA. Both the Phase 2B KOA clinical trial and the Phase 3 PF clinical trial demonstrate strong safety results with no significant Adverse Events or Serious Adverse Events. The Company plans to review the full study results from both trials with investors at a future R&D Day, planned for later this year. Intra-articular Micronized dHACM Versus Saline in the Treatment of Osteoarthritis of the KneeTrial This study was a Phase 2B prospective, double-blinded, randomized controlled trial of PURION® Processed micronized dehydrated Human Amnion/Chorion Membrane (mdHACM) Injection, as compared to saline placebo injection in the treatment of osteoarthritis of the knee. Trial enrollment included 466 patients between the ages of 21 to 80 years, with a diagnosis of osteoarthritis defined as grade 1 to 3 on the Kellgren Lawrence grading scale and a Visual Analog Scale (VAS) for Pain score greater than 45. Due to a lower-than-expected number of study participant dropouts (3% in both arms) and with an adequate number of patients meeting the required time in study to assess the primary endpoint, the final number randomized was 446 patients. Micronized dHACM Injectable for the Treatment of Plantar Fasciitis Trial This study was a Phase 3 prospective, double-blinded, randomized controlled trial of a single injection of 40 mg of PURION® Processed micronized dehydrated Human Amnion/Chorion Membrane (mdHACM) into the plantar fascia, as compared to saline placebo injection in the treatment of plantar fasciitis. The trial enrolled 277 patients between the ages of 21 and 79 years, with an investigator-confirmed diagnosis of plantar fasciitis for greater than or equal to one month (30 days) and less than or equal to 18 months. Patients were required to have a Visual Analog Scale (VAS) Pain score of greater than or equal to 45 mm at randomization and to have received conservative treatment for greater than or equal to 1 month (30 days), including any of the following modalities: Rest, Ice, Compression, Elevation (RICE); stretching exercises; NSAIDs; or orthotics. The primary endpoints were change in VAS for Pain at 90 days and incidence of related adverse events at 180 days, serious adverse events and unanticipated events during the first 12 months post-injection. Secondary endpoints included self-reported responses to the Foot Function Index – Revised (FFI-R) at 90 days.