[K Bio Global Phase 3 | Plan 3] HLB Therapeutics challenges the US 2.3 trillion NK treatment market… Pay attention to the US phase 3 results for RGN-259 in November

Dompe ‘Oxservate’ US sales exceed $1.7 billion… Stored at room temperature, administered for 4 weeks RGN-259 Differentiation SEER-2 Topline scheduled for mid-November… If successful, expected to enter exclusive market for rare eye diseases

HLB Therapeutics (115450) is challenging the US market, which is virtually monopolized by Italy's Dompe's 'Oxervate', with its neurotrophic keratitis (NK) treatment candidate 'RGN-259'. The company is scheduled to announce the topline results of the US phase 3 clinical trial ‘SEER-2’ in November.

The core competitiveness of RGN-259 is its eye drop formulation that can be stored at room temperature and its short dosing period. It is evaluated that it can increase patient compliance with medication as it is more convenient to store and distribute than existing treatments and has a simpler dosing method.

According to Dompe Holdings' 2025 annual financial report, Oxervate's U.S. sales last year exceeded $1.724 billion before deducting discounts and rebates. This is an increase of approximately 53% compared to $1.127 billion in 2024. Considering the exchange rate, it is worth about 2.3 trillion won.

Oxervate is the only prescription eye drop approved by the U.S. Food and Drug Administration (FDA) for the treatment of NK. The distribution discounts and government rebates specified in the Dompe report amounted to approximately $38 million and $60 million, respectively, totaling approximately 5.7% of the presented U.S. sales. The amount simply deducted from the two items is approximately $1.626 billion, which means that approximately 94% of the sales amount is maintained based on the disclosed deduction items.

This suggests that Oxervate has high price maintenance power in the rare disease market where there are no approved eye drops to compete directly. It is interpreted as an indicator of the potential for commercialization of RGN-259 in the future along with sales growth.

[Description: Oxervate’s 2025 U.S. sales\Source: Dompe Holdings 2025 Annual Financial Report]

Frozen/refrigerated storage Oxervate vs room temperature eye drop RGN-259

Neurotrophic keratitis is a rare, incurable eye disease that reduces corneal sensation and the recovery ability of the corneal epithelium due to damage to the trigeminal nerve. Even if a wound occurs on the cornea, it is easy to miss the right time for treatment because pain or a foreign body sensation is not evident. As the disease progresses, corneal epithelial defects, ulcers, and perforations may occur, leading to decreased vision or the risk of blindness.

Oxervate, which was approved by the FDA in 2018, is based on cenegermin (cenegermin-bkbj), a recombinant human nerve growth factor (rhNGF). Patients should apply the drops 6 times a day for 8 weeks. Storage and use procedures are also relatively complicated. Pharmacies must keep the product frozen, and patients must keep unopened vials refrigerated after receipt. Dedicated adapters and pipettes must be used during the instillation process.

On the other hand, RGN-259 is an eye drop that is being developed based on thymosin beta 4. HLB Therapeutics differentiates itself by offering a disposable container that can be administered for 4 weeks and stored at room temperature. The administration method is similar to commonly used artificial tears.

The analysis is that if RGN-259 proves its effectiveness and safety in phase 3 clinical trials in the United States and receives FDA approval, it will be able to secure a competitive advantage differentiated from Oxervate in terms of convenience of storage and distribution and patient compliance.

SEER-2 topline in November is the gateway

The gateway to commercialization of RGN-259 is SEER-2, a global phase 3 clinical trial. A total of 50 medical institutions, including 41 hospitals in the U.S. and 9 hospitals in 3 European countries, participated in this trial, which was conducted through HLB Therapeutics' U.S. subsidiary ReGenTree.

Currently, all patient medications have been completed. The contract research organization (CRO) is conducting data verification, and the company announced in a notice on August 26 that it had received a topline data submission schedule from the CRO in mid-November. The company plans to officially announce the results as soon as they are secured.  

In the previous European phase 3 clinical trial SEER-3, the cure rate after 4 weeks of administration did not reach statistical significance compared to the placebo group. The company believed that the higher-than-expected cure rate in the placebo group affected the results, and analyzed the cause by reexamining individual patient data and reflecting the opinions of external experts.

HLB Therapeutics' position is that it has supplemented the test operation and evaluation process to prevent the same problem from recurring in SEER-2. However, whether these supplements have actually led to proof of effectiveness can be judged only after the top-line results are confirmed.

Possibility of expansion of dry eye disease off-label

The market is also paying attention to the possibility of expanding RGN-259 beyond the NK indication. A representative example is the area of ​​dry eye treatment.

Market research firm Grand View Research predicts that the global dry eye treatment market will grow to $6.7 billion in 2025 and $7.1 billion in 2026, and then expand to $11.1 billion in 2033 at an average annual growth rate of 6.6%. It is calculated that it can grow from about 9.6 trillion won in 2026 to about 15 trillion won in 2033.

In the United States, any FDA-approved drug can be used off-label, where medical staff prescribe it for diseases or usage other than those approved based on the patient's condition and medical grounds. Accordingly, if RGN-259 obtains FDA approval as an NK treatment, there is a possibility that it may be used for dry eye patients in the future depending on the judgment of medical staff.

However, the possibility of expanding off-label prescriptions is not automatically secured with NK approval alone. It must be supported by clinical evidence for dry eye syndrome, insurance coverage, prescribing practices, and the possibility of reflecting treatment guidelines.

RGN-259 has a history of clinical development in the past targeting dry eye patients. The developer explained that it observed potential improvement in symptoms and signs in some patient groups, but did not meet the pre-specified co-primary endpoint of the existing trial. The future use of dry eye disease is expected to vary depending on additional clinical evidence and the judgment of medical staff at actual treatment sites.

Interested in the possibility of technology transfer

First, the market's attention is focused on the SEER-2 results in November. If a significant treatment effect is proven compared to the placebo group, HLB Therapeutics can refine its FDA approval strategy and at the same time review the possibility of entering the U.S. NK treatment market centered on Oxervate.

The company previously announced that it had signed a non-disclosure agreement (NDA) to discuss technology transfer with multiple global pharmaceutical companies during the phase 3 clinical trial in Europe and was awaiting clinical results. Whether or not the actual technology transfer contract is concluded and its terms may vary depending on the results of SEER-2 and subsequent negotiations.

If RGN-259 presents positive efficacy and safety data at the top line in November, HLB Therapeutics will have a stepping stone to enter the trillion-won NK treatment market, which is monopolized by Oxervate in the United States. Conversely, if effectiveness is not proven, a review of the overall development, approval, and commercialization strategy is inevitable.