Market Overview

RegeneRx Releases Letter to Stockholders


ROCKVILLE, Md., May 17, 2016 /PRNewswire/ -- RegeneRx Biopharmaceuticals, Inc. (OTCQB: RGRX), a clinical-stage drug development company focused on tissue protection, repair and regeneration, today released the following letter to stockholders regarding its recent Phase 2/3 dry eye clinical trial:

Dear Stockholder:

We are very pleased to report to you in more detail on our recently completed Phase 2/3 dry eye clinical trial. Overall the results were very positive and accomplished much of what we and our partner, GtreeBNT, set out to accomplish. Results from clinical trials can be complicated for the layperson to fully understand so the purpose of this letter is to explain our achievements in a more stockholder-friendly manner. The key messages are that while we did not meet our specific primary outcome measures, (1) we did achieve numerous important and statistically significant efficacy endpoints, (2) we saw a dose response that enables us to identify the lowest and best dose, and (3) we demonstrated reproducibility in improving symptoms of dry eye that confirmed previous Phase 2 clinical results. These are all important to determining our next clinical steps.

The clinical trial was sponsored by ReGenTree, LLC, a U.S. joint venture between RegeneRx and GtreeBNT to develop RGN-259 eye drops for the treatment of dry eye in the U.S. and Canada. The Phase 2/3 trial was a double-masked, placebo-controlled trial in 317 patients with moderate to severe dry eye syndrome who were divided into three groups of patients: high dose (0.1% Tβ4), low dose (0.05% Tβ4), and placebo (no Tβ4). Each group had approximately 105 patients. The patients used RGN-259 four times daily for 28 days.

The clinical trial was managed by Ora Inc., the world's leading full-service ophthalmic contract research organization (CRO) and product development firm with offices in the United States, the United Kingdom and Japan. Ora supports a wide array of organizations, from start-ups to global pharmaceutical and device companies, to help bring their new products from concept to market.

The following are the key results from the trial, most of which represent important statistically significant benefits in favor of RGN-259 compared to placebo, as well as offer other insights into the performance of RGN-259, which we believe is of high interest to prospective pharma companies/partners:

We confirmed an important efficacy endpoint from our prior Phase 2a clinical trial.

We saw confirmation between our first Phase 2a trial and our Phase 2/3 trial at an important pre-specified endpoint at Day 29 (Visit 5), which was the day after the last day of dosing with RGN-259. The "symptom" endpoint was the patient's ocular discomfort at Time 0 in the controlled adverse environment (CAE) model compared to 75 minutes and 90 minutes in the CAE. Thus, we had two independent studies that saw statistically significant benefits of RGN-259 for ocular discomfort during CAE challenge when their dry eye symptoms were stressed. We believe that these two independent studies demonstrate reproducible results, an important factor as we move forward with clinical development. This endpoint is similar to the primary symptom endpoint designated in the protocol that was designed to assess ocular discomfort pre-CAE compared to discomfort post-CAE. 

We achieved a dose response in the trial.

A dose response assessment comparing 0.05% (low dose) to 0.1% (high dose) was an important component of the trial and was the purpose of having two active groups in addition to placebo. The 0.1% Tβ4 concentration showed a significantly stronger response in most cases than the 0.05% dose group and helps answer the question of the lowest and best active dose for regulatory and marketing purposes, which the FDA prefers for obvious reasons. 

We demonstrated quick relief of certain dry eye signs and symptoms and a statistically significant improvement in efficacy that increased with longer administration of RGN-259.

We saw improvement trends at 2 weeks, which we believe are faster than any product on the market or under development. These improvement trends continued and became statistically significant at 4 weeks. This indicates that RGN-259's effects on dry eye improve over time, even within a relatively short 28-day period of administration. We believe this activity is one of several advantages that will set us apart from other products on the market or under development and should be of significant interest to industry.

We also saw a statistically significant correlation between severity of dry eye and effect of RGN-259, i.e., the more severe the dry eye, the better RGN-259's effect.

Patients were assessed for their Tear Film Breakup Time (TFBUT).  TFBUT is an important marker that often correlates with the severity of corneal damage and dry eye. The longer the TFBUT the more stable the tear film.  Patients with short or poor TFBUT may have greater problems with corneal disruption and healing as evidenced by fluorescein staining. In patients having short TFBUT, we demonstrated significant improvement with RGN-259 that indicates it had an effect in more severe dry eye patients. This also correlates with what Dr. Gabriel Sosne reported with RGN-259 in his 9-patient trial in severe dry eye. (Cornea; Volume 34, Number 5, May 2015)

We observed a rapid increase in tear production in patients using RGN-259 that was statistically significant.

Improvement of tear production tends to occur only with longer dosing. To date, the only FDA-approved drug for dry eye does not induce tear production as quickly at 2-4 weeks as RGN-259 does. Rapid increase in tear production is not typically or randomly seen in dry eye trials, therefore, we believe the statistically significant results in the Schirmer's Test for tear production was a real effect. The big jump in the Schirmer's Test with RGN-259 may be explained by RGN-259's anti-inflammatory properties leading to reduction of inflammation in the lacrimal glands that produce tears, therefore improving tear production.

Patients reported more comfort with our product than has been reported with other products either on the market or under development.

RGN-259 eye drops were very comfortable to use. Below is a chart that compares patient responses to various products for dry eye:


Comfort level     
1 = best





Currently approved product


Burning and stinging

Current product under


Burning, stinging, dysgeusia
(foul taste in mouth)


The analyses from the trial were in the Intent To Treat (ITT) population, which is typically the highest threshold in which to show statistically significant results.

There are two ways to evaluate patients in the study per the clinical protocol:  Intent To Treat (ITT) and Per Protocol (PP). ITT includes all randomized patients in the trial and PP includes all patients except those having significant protocol deviations, i.e., didn't finish taking the drug or dropped out of the trial. We showed statistical significance in most cases when looking at the ITT population, which is typically the tougher threshold.

RGN-259 is safe and well-tolerated.

A critical issue for all pharmaceutical products is their safety profile. This has a bearing on regulatory pathway, patient compliance and, ultimately, market share. RGN-259 eye drops have been administered to over 400 dry eye patients and our product candidate has been well-tolerated, there have been no safety issues, and patients have reported a high comfort level.

Next Steps

We believe the results of our dry eye trial are very encouraging as numerous sign and symptom efficacy endpoints showed statistical significance. The data support RGN-259's mechanisms of action as we have reported over the years, i.e., RGN-259 has broad activities by promoting corneal wound healing, preventing apoptosis (cell death), and reducing inflammation, all of which are believed to have a role in dry eye syndrome.

ReGenTree is preparing the final clinical study report and will be submitting it to the FDA. Our team also intends to meet with the FDA this summer prior to initiating our next clinical trial or trials planned for this fall. Assuming we can replicate the results of this current trial, we believe ReGenTree will be in a good position to achieve its goal of submitting an NDA for RGN-259 in the U.S. in the 2017-2018 timeframe.

We want to personally thank our partners at GtreeBNT who, through our ReGenTree joint venture, have worked very hard to sponsor this clinical trial and conducted the numerous ancillary activities that are required for late stage clinical trials. In particular, their rapid and successful development of a CMC (chemistry, manufacturing, and controls) package, which will be utilized for continued registration trials and commercial manufacturing and marketing, has been a big effort requiring a significant allocation of human and financial resources and constant travel around the globe. Such activities going forward will be crucial for our continued success.

To our stockholders, thank you for patiently standing by and supporting us as we move RGN-259 forward. Clinical development of new pharmaceutical products is not for the faint-hearted as it is complicated and requires significant outlays of human and financial capital, patience, and a belief in the product and those moving it forward.

We look forward to updating you as ReGenTree continues to implement its development plans for RGN-259.


J.J. Finkelstein 

Allan L. Goldstein, Ph.D.

President & CEO

Chairman and Chief Scientific Advisor


Forward-Looking Statements

Any statements in this shareholder letter 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.  Forward-looking statements in this shareholder letter include, but are not limited to, statements regarding our strategic and research partnerships, future royalty and milestone payments, regulatory applications and approvals, the development of our drug candidates, the use of our drug candidates to treat various conditions, our growth strategy, and our financial needs. The proposed clinical trials and costs and resources to support such trials, as well as the other forward-looking statements, are expectations and estimates based upon information obtained and calculated by the Company at this time and are subject to change. Moreover, there is no guarantee any of these trials will be successful or confirm previous clinical results. 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 shareholder letter 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.


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SOURCE RegeneRx Biopharmaceuticals, Inc.

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