RegeneRx Biopharmaceuticals, Inc. (OTCQB: RGRX) ("the Company" or "RegeneRx"), a clinical-stage drug development company focused on tissue protection, repair and regeneration, today announced positive results from its second clinical trial evaluating RGN-259 for the treatment of dry eye sponsored by ReGenTree LLC, its U.S. joint venture with GtreeBNT in Korea. The 317-patient Phase 2/3 trial (ClinicalTrials.gov Identifier: NCT02597803) demonstrated statistically significant improvements in both signs and symptoms of dry eye with 0.05% and 0.1% RGN-259 compared to placebo in a dose dependent manner during a 28-day dosing period. While the primary outcome measures were not met, several key related pre-specified endpoints and subgroups of patients with more severe dry eye showed statistically significant treatment effects. These results confirm the findings from the previous Phase 2 trial providing clear direction for the clinical regulatory pathway and remaining registration trials for RGN-259.
RGN-259 was evaluated using the Controlled Adverse Environment (CAESM) Model developed by Ora, Inc., the product development firm managing the program. The CAESM was utilized to screen and enroll an enriched patient population and measure a patient's ability to withstand an acute adverse environmental challenge of the ocular surface.
On the final day of dosing (Day 28), patients receiving 0.1% RGN-259 had a statistically significant reduction in ocular discomfort during CAESM exposure when compared to placebo (Intent-to-Treat Population (ITT), p=0.043). Importantly, this result was also observed in the previous Phase 2 trial in patients treated with 0.1% RGN-259 (ITT, p=0.024), thereby demonstrating a symptom endpoint in two independent trials. A statistically significant ocular discomfort improvement after CAESM exposure on Day 28 was also observed in the 0.05% and 0.1% RGN-259 treatment arms when compared to placebo (ITT, p=0.0366 and p=0.0072, respectively) indicating a dose dependent response.
Efficacy in an environmental setting was also demonstrated in more symptomatic patients at baseline, with statistically significant improvements in ocular discomfort observed at day 28 prior to CAESM in patients receiving 0.05% and 0.1% RGN-259 compared to placebo (p=0.022 and p=0.006, respectively). These data suggest that RGN-259 has a fast-acting treatment effect on a dry eye symptom during exposure to an adverse environment as well as in the natural environment after 28 days of dosing.
RGN-259 also improved a common objective endpoint – ocular surface staining after 28 days of dosing in patients with compromised tear film break-up time at baseline. In this population, patients receiving 0.1% RGN-259 had a statistically significant reduction in corneal fluorescein staining prior to entering the CAESM on Day 28 when compared to placebo (p=0.034). The same result was observed in the previous Phase 2 trial for patients treated with 0.1% RGN-259, although it was not statistically significant in the smaller sample size of this previous Phase 2 trial. Additionally, a change from baseline analysis (Day 28 minus Day 0) demonstrated a statistically significant improvement in inferior corneal staining for the 0.1% RGN-259 treatment arm when compared to placebo (p=0.003). This finding was also observed at Day 14 compared to placebo (p=0.035). These data suggest that RGN-259 has a fast-acting treatment effect on a dry eye sign after 14 and 28 days of dosing.
There were no significant drug-related adverse or serious adverse events and RGN-259 was well-tolerated and comfortable for the patients with no irritation upon instillation.
"We are very pleased with the comprehensive efficacy findings in our clinical trial, especially with the reproducible nature of the data when compared to previous Phase 2 studies with RGN-259. ReGenTree is encouraged by the interest of industry in our dry eye technology and will continue to evaluate strategic opportunities in this area. Meanwhile, we are moving forward as rapidly as possible with our program to meet our target timeline for NDA approval in 2018," stated Won S. Yang, CEO of ReGenTree.
The global effect and rapid response of RGN-259 on ocular healing are similar to that reported in previous trials and reflect its known biological activities in promoting corneal epithelial cell migration to repair damaged areas, promoting laminin-5 production for increased migration and cell-cell and cell-matrix contacts, and its cytoprotective, anti-inflammatory, and anti-apoptotic properties. "A medication that can provide relief within a short period of time is much needed. These study results suggest that RGN-259 has the potential to help a wide variety of dry eye sufferers," commented Dr. Joseph B. Ciolino, a Cornea specialist at Mass Eye and Ear and Assistant Professor of Ophthalmology at Harvard Medical School.
"This study demonstrates the utility and reproducibility of Ora's clinical models and operational approach which reduce the variability seen in dry eye studies and has helped ReGenTree take a significant step forward in the development of RGN-259 for the treatment of dry eye," stated George W. Ousler, Vice President of Dry Eye at Ora, Inc.
ReGenTree intends to meet with the FDA this summer to provide full results of the trial and its plan to conduct a confirmatory Phase 3 study to start by the 4th quarter of 2016.
ReGenTree, LLC is a U.S. joint venture company owned by GtreeBNT Co., Ltd., a bio venture company in Korea and RegeneRx Biopharmaceuticals, Inc., a clinical stage drug development company in the U.S. ReGenTree is developing a novel therapeutic peptide, RGN-259 (designated GBT-201 in Korea), in the U.S. for ophthalmic indications. GtreeBNT holds a majority equity stake in ReGenTree and is responsible for conducting and funding all clinical trials and product development. RegeneRx also holds a significant equity stake in the joint venture and has contributed all of its related intellectual property and non-clinical and early clinical data. ReGenTree seeks to become a top-tier pharmaceutical company specializing in ophthalmology and it is currently sponsoring the two late stage clinical trials in the US for two different indications, Dry Eye Syndrome and Neurotrophic Keratopathy.
RegeneRx is focused on the development of a novel therapeutic peptide, Thymosin beta 4, for tissue and organ protection, repair and regeneration. RegeneRx currently has three drug candidates in clinical development for ophthalmic, cardiac and dermal indications, three active strategic licensing agreements in China, Pan Asia (Korea, Japan, and Australia, among others) and in the U.S. and Canada. RGN-259, the Company's Tβ4-based ophthalmic drug candidate is being developed for dry eye syndrome and for the treatment of neurotrophic keratopathy (NK), both of which are being developed in the U.S and Canada through its joint venture, ReGenTree. ReGenTree has reported results of its recently completed Phase 2/3 U.S. trial in patients with dry eye syndrome and is conducting a Phase 3 clinical trial for the treatment of patients with NK, for which it has been granted orphan status by the U.S. FDA. RGN-352, the Company's Tβ4-based injectable drug candidate, is a Phase 2-ready drug candidate designed to be administered systemically to prevent and restore tissue damage associated with acute events such as heart attacks, strokes, and other similar injuries. RGN-137, the Company's Tβ4-based dermal gel, is in phase 2 clinical development. For additional information about RegeneRx please visit www.regenerx.com.
Ora, Inc. is the world's leading full-service ophthalmic CRO and product development firm with offices in the United States, the United Kingdom and Japan. Over the past 30 years, it has helped its clients earn 41 product approvals. Ora supports a wide array of organizations, from start-ups to global pharmaceutical and device companies, to efficiently bring their new products from concept to market. Ora's pre-clinical and clinical models, unique methodologies and regulatory strategies have been refined and proven across thousands of projects. Ora brings together the world's most extensive and experienced team of ophthalmic experts and R&D professionals to maximize the value of new product initiatives. For more information about Ora, please follow @oraclinical on Twitter, like Ora on Facebook (/Ora-Inc), follow on LinkedIn (http://bit.ly/1TgHErs) or go to oraclinicstage.wpengine.com.
Any statements in this press release that are not historical facts are forward-looking statements made under the provisions of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. There can be no assurance that any clinical trial results, including results from this study, will be confirmed in any future clinical trials or will result in approved products or future value. Please view these and other risks described in the Company's filings with the Securities and Exchange Commission ("SEC"), including those identified in the "Risk Factors" section of the annual report on Form 10-K for the year ended December 31, 2015, and subsequent quarterly reports filed on Form 10-Q, as well as other filings it makes with the SEC. Any forward-looking statements in this press release represent the Company's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any obligation to update this information, as a result of future events or otherwise, except as required by applicable law.