[K Bio Global Phase 3 | [Plan 4] Ahn Ki-hong, CEO of HLB Therapeutics, “RGN-259 is expected to be the first option for early NK treatment.”

Emphasis on patient convenience... SEER-2 Pays attention to differences in patient composition and data quality

Topline target for mid-November… Discussing with FDA and global pharmaceutical companies on whether to conduct additional confirmatory clinical trials

Ahn Ki-hong, CEO of HLB Therapeutics (115450), cited ease of use for patients as the core competitiveness of ‘RGN-259’, a neurotrophic keratitis (NK) treatment candidate. The explanation is that the focus is on reducing the burden of storage and medication preparation so that patients can continue treatment as prescribed.

In a written interview with the Market Times, CEO Ahn evaluated that the patient selection criteria for the global phase 3 clinical trial ‘SEER-2’ were applied more strictly than those in the previous European clinical trial. He explained that training and verification at testing institutions have been strengthened to improve the quality of corneal photographs. The company aims to produce topline results in mid-November, and plans to discuss follow-up development directions with the U.S. Food and Drug Administration (FDA) after securing the results.

The following is a Q&A with CEO Ahn.

Q. What is the biggest difference between RGN-259 and existing treatments?

A. The most essential difference of RGN-259 is that it is a drug that patients can easily use as prescribed in their daily lives.

Unlike Oxervate, RGN-259 eye drops can be stored and used in the refrigerator or at room temperature while the patient is actually using the medicine, and the most noticeable feature is that it is disposable and is discarded after one use. It is surprisingly difficult for patients to maintain refrigerated storage conditions for medications while traveling or in transit. Additionally, Oxervate must be assembled into a multi-use administration kit through several steps before instillation. Considering that most NK patients are elderly, this packaging format will also pose a burden in terms of ease of use. Also, unless you are a very meticulous person, it is difficult to strictly maintain the hygiene of eye drops during assembly every day. Patients are bound to find this a significant inconvenience. RGN-259 can be stored at room temperature when going out or moving during the 4-week treatment period, so there is no such burden because you only need to open the disposable container and instill it when necessary.

For medical institutions, the prescribing process is much easier as there is no need to fill out complicated insurance documents for ordering or provide lengthy instructions to patients on storage and hygiene management tips like with Oxervate. In addition, we expect that the excellent safety profile confirmed in clinical trials so far will be a strong incentive for medical staff to prescribe RGN-259. In addition, in terms of inventory management, general refrigeration rather than freezer storage is sufficient, reducing the burden.

If the medication is properly administered as prescribed, the effects confirmed in clinical trials can be fully seen in actual clinical settings, and the number of cases of giving up or arbitrarily stopping treatment midway will also decrease. In addition, drugs that are easy for medical staff to explain, easy for patients to use, and have a low safety burden tend to have a rapid increase in prescriptions, so we expect that they will be able to establish themselves as the first choice for initial treatment in the market formed by Oxervate. While Oxervate requires frozen (-20°C) storage in pharmacies, RGN-259 is expected to require general refrigerated (2-8°C) storage at the distribution stage. As a result, it will be easier to secure a distribution network, which will be an attractive factor for commercialization partners.

Q. By analyzing the results of the previous European clinical trial, SEER-3, what improvements were made in SEER-2?

A. We analyzed several aspects of the reasons why the cure rate in the placebo group was higher than expected in SEER-3. The results have been reflected in the SEER-2 progress.

1. SEER-2 had a higher screening dropout rate during the patient recruitment stage compared to SEER-3. We are analyzing that patients with various underlying conditions were recruited during the SEER-3 trial recruitment. In other words, it can be said that patients with various factors that could affect the effectiveness of the drug were included. On the other hand, SEER-2 is believed to have applied more stringently the patient selection criteria. Additionally, the proportion of seriously ill patients based on corneal perception is higher in SEER-2.

2. SEER-2 has a lower patient dropout rate than SEER-3. It is expected that the completeness and reliability of the data will be higher in that it will be possible to obtain results that fully reflect the effectiveness of the actual clinical drug.

3. Among the patients participating in the clinical trial, some suffered from glaucoma. Patients with glaucoma who participated in SEER-3 used multiple-use glaucoma eye drops containing preservatives that could interfere with the treatment of the upper cornea. We believe that this preservative may have affected the efficacy of RGN-259.

4. If the quality of the corneal photo is poor, the patient will be judged as Cannot Grade. To minimize this, in SEER-2, the clinical team strengthened prior training and strengthened prior verification for test sites. As a result, the proportion of unevaluable patients in SEER-2 was lower than that in SEER-3.

Because we cannot disclose all clinical data when announcing topline results, the most important data is the statistically significant difference between the treatment group and the placebo group, or p value.

Q. At what stage is SEER-2 currently, and what data do you plan to disclose when the results are announced?

A. As of the end of September, data cleaning work is in its final stages. Afterwards, DB lock and statistical analysis will be performed in early November, and the schedule for deriving topline results in mid-November is currently progressing as planned.

When announcing the topline results, we plan to disclose a summary of safety, including group results of the primary endpoint, cure rate, statistical significance, and adverse reaction status. More detailed data, including subgroup analysis, will be released through future conference presentations and papers.

Q. After securing the results, how do you plan to pursue FDA approval and cooperation with global pharmaceutical companies?

A. We are also paying attention to the FDA's recent direction. Once the SEER-2 topline results are confirmed, we plan to hold future meetings with the FDA based on them. At this meeting, we will discuss whether additional confirmatory clinical trials are needed. It is ultimately up to the FDA to determine whether the requirements are met, but we will prepare a full development package centered on the SEER-2 results, including the existing SEER-1 and SEER-3 results, non-clinical and mechanistic data, and accumulated non-clinical and clinical safety data, and engage in discussions with the FDA. We will inform you of the specific schedule, including the timing of application for approval, as soon as it is confirmed based on the results of FDA consultations.

Please understand that discussions on cooperation with global pharmaceutical companies are subject to confidentiality agreements, so it is difficult to disclose specific parties or details of discussions. However, cooperation discussions are still ongoing and are expected to become more concrete once the SEER-2 topline results are confirmed. The commercialization method will be decided in a way that maximizes corporate value by combining the topline results and FDA consultation results.

Q. What would you like to say to shareholders and investors?

A. First, we would like to express our sincere gratitude to our shareholders and investors who have trusted and waited for us for a long time. After the SEER-3 results, many people expressed their concern and continued support, and that trust became our biggest driving force.

SEER-2 is a clinical trial that has been painstakingly conducted over a long period of time by a total of 50 medical institutions, including 41 institutions in the United States and 9 institutions in 3 European countries (Italy, Spain, and Poland). We believe that there is a meaningful difference compared to SEER-3 in terms of patient composition and data quality. We will do our best to take care of the remaining process until the last minute until the announcement of the top line results in November.

In addition, we will do our best to ensure that discussions on cooperation with global Big Pharma lead to practical results based on top-line results.

All of our executives and staff will work together as one to repay your support with good results. thank you