Emphasis placed on patient convenience; focus on improvements in patient demographics and data quality for SEER-2
Top-line results targeted for mid-November; FDA consultations on follow-up confirmatory trials and discussions with global pharmaceutical firms underway
An Ki-hong, CEO of HLB Therapeutics (115450), has identified the convenience of patient administration as the primary competitive advantage of RGN-259, a candidate for the treatment of neurotrophic keratitis (NK). He explained that the company focused on reducing the burden of storage and medication preparation to ensure patient adherence to prescribed treatment regimens.
In a written interview with Market Times, CEO An noted that the patient inclusion criteria for the global Phase 3 “SEER-2” trial were applied more strictly than in previous European studies. He further explained that the company strengthened site training and verification processes to enhance the quality of corneal imaging. The company aims to report top-line results by mid-November, after which it plans to consult with the U.S. Food and Drug Administration (FDA) regarding subsequent development strategies.
The following is the Q&A with CEO An.
Q. What is the most significant differentiator of RGN-259 compared to existing treatments?
A. The fundamental differentiator of RGN-259 is that it is a drug that patients can easily use in their daily lives according to their prescription.
Unlike Oxervate, the RGN-259 eye drops can be stored and used at room temperature, and the single-dose, throw-away format will be highly noticeable to patients. It is surprisingly difficult for patients to maintain refrigerated storage conditions while traveling or moving. Furthermore, Oxervate requires multiple steps to assemble a multi-dose kit before application. Given that most NK patients are elderly, such packaging forms can be a burden in terms of convenience. Maintaining hygiene during assembly is also difficult to manage daily unless the patient is extremely meticulous, which leads to significant patient discomfort. RGN-259 can be stored at room temperature during the four-week treatment period, eliminating this burden as patients simply open a single-use container when needed.
For medical institutions, the prescription process is much smoother, as there is no need to complete complex insurance paperwork for orders or provide lengthy instructions on storage and hygiene as required for Oxervate. Additionally, the excellent safety profile confirmed in clinical trials is expected to be a strong incentive for medical staff to prescribe RGN-259. Inventory management is also simplified, as standard refrigeration—rather than a freezer—is sufficient.
When medication is administered as prescribed, the efficacy observed in clinical trials can be fully realized in real-world clinical settings, reducing instances of treatment abandonment or premature discontinuation. Since drugs that are easy for staff to explain, convenient for patients to use, and carry fewer safety concerns tend to see rapid growth in prescriptions, we expect RGN-259 to establish itself as a first-line treatment option within the market currently dominated by Oxervate. While Oxervate requires storage at -20°C in pharmacies, RGN-259 is expected to only require standard refrigeration (2–8°C) during distribution. This makes securing distribution channels easier, which is an attractive factor for potential commercial partners.
Q. What improvements were made in SEER-2 based on the analysis of the previous European SEER-3 results?
A. We analyzed the reasons why the complete recovery rate in the placebo group was higher than expected in SEER-3, and we have reflected those results in the ongoing SEER-2 trial.
1. SEER-2 had a higher screening failure rate compared to SEER-3 during the recruitment phase. We analyzed that a wide range of patients with varying baseline conditions were enrolled in SEER-3. Conversely, we believe that the patient selection criteria for SEER-2 were applied more strictly. The proportion of severe patients, based on corneal sensitivity, is also higher in SEER-2.
2. The patient dropout rate for SEER-2 is lower than that of SEER-3. We believe this leads to higher data integrity and reliability, as the results will better reflect the true efficacy of the clinical drug.
3. Some participants in the trials also suffered from glaucoma. Those in SEER-3 used multi-dose glaucoma eye drops containing preservatives that could potentially interfere with the healing of the corneal epithelium. We suspect these preservatives may have influenced the manifestation of RGN-259's efficacy.
4. If corneal images are of poor quality, the patient is marked as “Cannot Grade.” To minimize this, our clinical team strengthened pre-trial training and verification for clinical sites for SEER-2. As a result, the proportion of “Cannot Grade” patients in SEER-2 is lower than in SEER-3.
When we announce the top-line results, we cannot disclose all clinical data, so the most important metric will be the statistically significant difference between the treatment and placebo groups—the p-value.
Q. What is the current status of SEER-2, and what data do you plan to release?
A. As of late September, data cleaning is in the final stages. We plan to proceed with database lock and statistical analysis in early November, and the schedule to derive top-line results by mid-November is currently proceeding as planned.
When announcing the top-line results, we plan to disclose the group-specific recovery rates as the primary endpoint, statistical significance, and a summary of safety, including the incidence of adverse events. More detailed data, such as subgroup analyses, will be released later through conference presentations and academic papers.
Q. How do you plan to proceed with FDA approval and collaboration with global pharmaceutical companies after obtaining the results?
A. We are closely monitoring the FDA's recent stance. Once the SEER-2 top-line results are confirmed, we plan to request a meeting with the FDA to discuss whether an additional confirmatory trial is necessary. While the final determination of requirements rests with the FDA, we will prepare a comprehensive development package—centered on the SEER-2 results, but including SEER-1 and SEER-3 results, non-clinical and mechanistic data, and accumulated safety data—to discuss with the agency. Specific schedules, such as the timing of the submission of the license application, will be determined based on the outcome of our discussions with the FDA.
Regarding discussions with global pharmaceutical firms, please understand that I cannot disclose specific counterparties or details due to non-disclosure agreements. However, these discussions are ongoing, and I believe they will become more concrete once the SEER-2 top-line results are confirmed. We will decide on a commercialization strategy that maximizes corporate value, taking into account the top-line results and the outcome of the FDA consultation.
Q. Is there anything you would like to say to shareholders and investors?
A. First, I would like to sincerely thank our shareholders and investors for their patience and trust. Following the SEER-3 results, many of you sent us both concern and unwavering support, and that faith has been our greatest driving force.
SEER-2 has been a long-term, intensive effort involving 50 medical institutions, including 41 in the U.S. and 9 across three European countries (Italy, Spain, and Poland). We believe there are meaningful differences compared to SEER-3 in terms of patient composition and data quality. We will do our absolute best until the very last moment leading up to the top-line announcement in November.
Furthermore, we will ensure that our discussions with global big pharma lead to tangible results based on the top-line outcomes. Our entire team is committed to working as one to reward your support with successful results. Thank you.
