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EYEG: IDEs Approved. Both OBG Clinical Studies Set to Kick-Off

07/26/2018
By Brian Marckx, CFA

NASDAQ:EYEG

READ THE FULL EYEG RESEARCH REPORT

FDA Approves IDEs for Both OBG Clinical Studies; i.e. the second PRK pilot study and initial PE pilot study
As we noted in our Q1 ’18 earnings update in late-May, Eyegate Pharmaceuticals' (NASDAQ:EYEG) diligence in rapidly responding to FDAs follow-on questions related to their IDE submission has been key to keeping their Ocular Bandage Gel (OBG) programs on-track with updated forecasted timelines. That resilience paid dividends and culminated with yesterday’s news, that FDA approved IDEs for both the OBG-PRK (second pilot) study and the OBG-PE (initial pilot) study – which allows the OBG clinical programs to progress.

Concurrent approval of the PE IDE was actually a surprise to us as we had anticipated that that (i.e. PE IDE submission and subsequent evaluation) would not happen until just after a decision on the PRK application. Obviously, the timely and concurrent approval of both IDEs is a pleasant surprise.

EYEG had previously been guiding for commencement of both studies during Q3 (i.e. current quarter) – and with IDE approval in-hand, those timelines are now much more definitive. In fact, the PRK study’s clinicaltrials.gov listing cites an “estimated start date” of August 5th (as of today, the PE study is not listed).

Initial study indicated PRK wounds heal faster with OBG versus standard-of-care…
Photorefractive keratectomy (“PRK”) is a type of vision-correction laser eye surgery - recovery from which includes regrowth of the epithelium (i.e. thin outer layer of the cornea). While we have included the results of the initial PRK study below (along with a refresher on the backgrounds of OBG), as a summarized reminder; results of that study indicated that OBG may be associated with faster corneal healing following eye surgery as compared to standard-of-care. More specifically, 83% patients treated with OBG-alone met the primary endpoint (of complete wound healing on Day 3), compared to 64% of OBG+BCL (bandage contact lens) patients and just 54% of artificial tears+BCL patients. Noteworthy is that the OBG+BCL arm is excluded in the 2nd PRK study design (below) and, instead, is replaced with another OBG-alone cohort but at a modified dosing regimen.

Study details…
These new pilot studies will hopefully further validate OBG’s effectiveness in speeding healing of corneal wounds and, in the case of PE, reducing symptoms such as dry eye. EYEG had previously disclosed the anticipated design of both PRK and PE pilot studies in their recent investor presentations – which we assume is consistent with the actual design of both.

PRK: designed largely similar to that of the initial PRK study, with some exceptions. The most significant difference is that (as noted) this new PRK study does not include an OBG+BCL cohort (as the initial study did) but instead incorporates two OBG-alone treatment arms, differentiated by treatment regimen and overall number of administrations. Clearly, the reason for this new PRK pilot study incorporating two OBG-alone cohorts (and not using an OBG+BCL) arm is because of the superior efficacy of the OBG-alone group in the initial study (see results below). One of the OBG-alone cohorts will be dosed at the same regimen as was used in the first study (i.e. QID for 2 weeks), while the other OBG-alone arm will use a slightly more front-end weighted (i.e. 8x/day for 3 days, then QID for 11 days) dosing schedule and include 21% more aggregate administrations (i.e. 68 vs 56). Presumably, the aim of this new pilot study is determine optimal dosing for later-stage studies (assuming success of this second pilot study).

Control, which consists of artificial tears (AT) 4x/day for two weeks, is similar to the initial study. Also similar to the initial study, will enroll up to 45 patients (initial study had data on n=39) which have undergone bilateral PRK. Primary endpoint (per clinicaltrials.org) which will be assessed via (a masked) designated reading center, is time to complete corneal re-epithelization (i.e. wound healing) as assessed on Day 3 (same as initial study). The following is from EYEG’s April 2018 investor presentation;

• Randomized, masked, controlled 2-weeek study in up to 45 subjects undergoing bilateral PRK

• Subjects randomized to one of three cohorts (n=15 per arm);
     ◦ Arm 1: OBG every 2 hrs (8x/day) for 3 days then QID (i.e. 4x/day) for additional 11 days
     ◦ Arm 2: OBG QID for 2 weeks
     ◦ Arm 3: BCL (Acuvue Oasys plano lens) + AT QID for 2 weeks

• Primary efficacy endpoints based on fluorescein staining:
     ◦ Time to corneal re-epithelization and
     ◦ Proportion of subjects with complete corneal re-epithelization of epithelial defect on day 3
     ◦ Evaluated by a masked reading center (Tufts) using digital photography of fluorescein stained slit lamp photos and image analysis

PE: EYEG’s press release announcing the IDE approvals notes that the PE study include 30 patients, with 15 patients in each of two arms. Primary outcome is change in NEI corneal staining score from baseline (Day 0) to Day 28. Additional details (assuming they are consistent with the approved IDE) are in the April 2018 presentation and include;

• 42-Day trial: 2-week wash-out/run-in followed by 4 weeks of two arms
     ◦ Day-14 screening: all subjects stop all topicals and take Refresh PF artificial tears QID OU for 14 days
     ◦ Day-0 randomization: OBG QID for 28 days vs Refresh PF artificial tears QID OU for 28 days

Primary performance outcome: change in NEI corneal staining score from baseline to Day 28 between OBG arm and artificial tears arm for the study eye

Refresher on the OBG programs
As a reminder, OBG is the lead CMHA-S candidate which came from the Jade Therapeutics acquisition and is being developed for corneal repair indications. Given the strong safety profile of the compound and expected (relatively streamlined) de novo 510(k) FDA pathway (in November 2016 FDA confirmed de novo 510(k) is an appropriate pathway for OBG to pursue in seeking U.S. regulatory clearance), we think OBG may represent one of EYEG’s most near-term commercialization opportunities. (See our Appendix in our updated report for more background on the compound).

As we have noted in recent updates, while the delays to OBG clinical programs have been disappointing, we think the de-risked nature of OBG (based on the long history of HA being used in human eyes and its broad use and extensive successful testing for corneal repair in animals) means that the likelihood of eventual commercialization could be reasonably high if positive results of the first PRK pilot study (results of which were published in the Journal of Cataract & Refractive Surgery in March 2018) can be confirmed in this follow-on pilot study (although eventual FDA approval would still require a pivotal study). As such and coupled with the attractiveness and size of the OBG targeted markets (particularly that of PE), we continue to look forward to further updates from these OBG programs.

Initial PRK Pilot Study Results…
In January 2017 EyeGate announced encouraging top-line results of its first human OBG pilot study in patients that had undergone PRK surgery. While the study was small, results indicate that OBG may be associated with faster corneal healing following eye surgery as compared to standard of care. The pilot study compared OBG to artificial tears with bandage contact lens (BCL) in patients undergoing bilateral PRK.

Ocular Bandage Gel photoreactive keratectomy pilot study
• Objective: evaluate safety and performance of OBG eye drop administered 4x/day for 14 days with or
without a BCL as compared to artificial tears and a BCL in healing of corneal epithelial defects

• Primary efficacy endpoint: complete wound closure by Day 3

• Design: prospective, randomized, controlled study in up to 39 subjects undergoing bilateral PRK surgery.

Subjects randomized to one of three cohorts;
     ◦ Arm 1 (n=12): EyeGate Ocular Bandage Gel 4x/day for 2 weeks after surgery without a BCL
     ◦ Arm 2 (n=14): EyeGate Ocular Bandage Gel 4x/day for 2 weeks after surgery in combination with a BCL
     ◦ Arm 3 (n=13): Artificial tears 4x/day and BCL

Topline results of the pilot study, which was the first in-human study of OBG, showed a greater proportion of OBG-treated patients versus those treated with standard of care met the primary endpoint of complete wound closure by Day 3. Top-line results were initially announced in January 2017 but EYEG subsequently provided some additional data. The updated data showed that 10 of the 12 (83%) patients treated with OBG alone (i.e. no BCL) met the primary endpoint, compared to 9 of the 14 (64.3%) OBG+BCL patients and just 7 of the 13 (53.8%) artificial tears+BCL patients.

Remaining wound surface area on Days 1 (24 hours following surgery) and 3 were also assessed and similarly favored the OBG-alone cohort which had an average wound size of just 18.5mm on Day 1 and 0.02mm on Day 3. This compares to 39.5mm and 0.37mm in the SOC patients at Days 1 and 3, respectively.



View Exhibit I

While specifics were not provided relative to adverse events, EYEG did note in their PR that the study demonstrated safety and tolerability.

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