March 22, 2021 Update on ARISE-3 Statistical and Regulatory Plan

Summary of Answers to Statistical and Regulatory Questions at GtreeBNT Shareholder Meeting
March 18, 2021*

1.  Regarding topline data of ARISE-3 trial announced on March 18th

-     The topline data we received from a statistical analysis service company was around 15~20% of total data to be analyzed.

-      We’ll have a discussion with the statistical analysis service company and CRO using remaining prespecified parameters and post-hoc analysis to be available. All data analysis of ARISE-3 will be finished around the end of April.

-      Based on all the data of ARISE-3, one of future development scenarios would be to explore the prospects of a pre-BLA meeting as announced on the news release dated March 18th.

2.  The ground of the prospects of a pre-BLA meeting

①  Dry Eye: Developing Drugs for Treatment – Guidance for Industry (draft) announced by the FDA in December 2020

  • FDA recommends that the sponsor demonstrate one of the following:

-      A statistically significant difference between the investigational treatment and vehicle for at least one objective prespecified sign of dry eye (mean group score of test versus vehicle) and at least one subjective prespecified symptom of dry eye (mean group score, or

 (Source: FDA Dry Eye: Developing Drugs for Treatment Guidance for Industry, December 2020)

② The case of NDA approval from the FDA of Novartis’ Xiidra as the treatment of dry eye

-        Novartis submitted NDA with three clinical trials (Phase 2, two Phase 3 trials (OPUS-1 and -2), but FDA declined to approve it and requested an additional clinical study (2015).

-        Resubmission of NDA by including 4th clinical trial results (OPUS-3) (2016.1)

-        The FDA approved Xiidra based on evidence from four clinical trials (2016.7)

-        When Xiidra was approved, there was no FDA guidance to develop drugs for treatment of dry eye. FDA announced the draft guidance in December 2020 very first.

③ We have secured data shown statistical significance in secondary prespecified efficacy parameters in ARISE-1 and ARISE-2.

3.  A rough expected timeline to submit a meeting request of pre-BLA

-      To be finished all data analysis of ARISE-3 (End of April)

-      Advisory and strategic establishment of the prospect of pre-BLA meeting with regulatory experts (End of July)

-      Preparation and submission of Pre-BLA meeting request (End of August)

* Information provided by GtreeBNT to RegeneRx without editing