[Edaily Reporter NA EUN-KYUNG ] “The most challenging stage in the development of microneedle-based pharmaceuticals is demonstrating clinical efficacy. Since Raphas Co., Ltd. has largely secured its production technology infrastructure, the next critical step is to prove actual therapeutic efficacy in large-scale clinical trials.”

Jeong Do-hyun, CEO of Raphas Co., Ltd.(214260), made these remarks in an interview with E-Daily on the 7th. He expressed confidence, stating, “The value of our platform technology has been sufficiently proven,” after noting that DF19001, an immunotherapy for allergic rhinitis, had completed a proof of concept (PoC) through a Phase 1 clinical trial, demonstrating that it can safely induce an immune response in humans. In particular, he assessed that the Phase 1 clinical trial results alone are sufficient to initiate discussions with global pharmaceutical companies regarding technology transfer (L/O) and joint development.

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“Production Technology Infrastructure in Place”… Remaining Challenge Is Clinical Efficacy

Raphas Co., Ltd. is developing DF19001, a microneedle-based immunotherapy for patients with house dust mite-induced allergic rhinitis. While subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the most common forms of allergy immunotherapy, low patient compliance during long-term treatment is cited as their biggest limitation.

CEO Jeong stated, “While SCIT is highly effective, it requires repeated hospital visits and medical supervision due to the risk of anaphylaxis.” He added, “With SLIT as well, a significant number of patients discontinue treatment prematurely due to side effects such as oral itching or swelling, as well as the inconvenience of having to take the medication daily for several years.”

Raphas Co., Ltd.’s strategy is to address this unmet need with a patch-type immunotherapy. The concept involves delivering antigens directly to Langerhans cells in the epidermal layer of the skin to induce an immune response, while allowing patients to administer the treatment themselves at home.

The company explained that in Phase 1 clinical trials, it confirmed the potential to induce a sufficient immune response with a smaller amount of antigen than existing injectable or sublingual treatments.

CEO Jeong said, “While it is difficult to disclose specific dosages, we have confirmed an immune response—including IgG4—equivalent to or greater than that of existing injectable or sublingual treatments, even with significantly smaller amounts of allergen,” adding, “Because we directly target immune cells in the epidermis, we were able to achieve high immune induction efficiency even with a small amount of antigen.”

He cited safety as a key advantage of the patch formulation. “With injectable formulations, the allergen is delivered to the subcutaneous tissue, where blood vessels are well-developed, requiring monitoring for systemic hypersensitivity reactions,” he explained. “In contrast, the microneedle patch is designed to deliver the allergen locally to immune cells in the epidermis and upper dermis. By minimizing the entry of the allergen into the systemic bloodstream, we can reduce the risk of systemic side effects.”

Regarding why microneedle-based pharmaceuticals have not yet reached global commercialization, he attributed it to the difficulty of simultaneously resolving issues related to manufacturing, quality control (CMC), and mass production.

CEO Jeong said, “Conventional manufacturing methods made it difficult to maintain the stability of biopharmaceuticals, such as proteins and vaccines, due to high heat or prolonged drying processes, and it was also challenging to mass-produce micro-needles with consistent quality,” adding, “Regulatory agencies have also imposed very strict requirements regarding this consistency in quality.”

He continued, “Raphas Co., Ltd. has established a process to manufacture needles at room temperature in a short amount of time using its proprietary DEN (Droplet Extension Needle) technology,” emphasizing, “Based on this, we are laying the groundwork for global-level mass production and CMC capabilities, and the company’s top priority right now is to demonstrate clinical efficacy.”

He also expressed confidence in the potential for technology transfer, stating, “What global pharmaceutical companies value most are safety data obtained from human trials and CMC competitiveness. Since we have completed proof of concept through this Phase 1 clinical trial, demonstrating that we can safely induce an immune response in humans, the value of our platform technology has been sufficiently proven. We believe we are now at a stage where partnering for technology transfer and joint development is feasible.”

Verifying Therapeutic Efficacy with CSMS… “The Goal Is to Reduce the Need for Existing Medications”

Last May, Raphas Co., Ltd. submitted an Investigational New Drug (IND) application for the “Seamless” Phase 2b/3 clinical trial of DF19001 to the Ministry of Food and Drug Safety. The plan is to shorten the development period by more than a year by conducting Phases 2 and 3 consecutively.

The most significant change in the subsequent clinical trials is the evaluation method. While Phase 1 was a stage to confirm safety and immune responses, the core objective of Phases 2b and 3 is to demonstrate the extent to which patients’ symptoms improve.

To this end, Raphas Co., Ltd. has adopted the Composite Symptom-Medication Use Score (CSMS) as its primary endpoint. The CSMS is a metric that evaluates not only rhinitis symptoms—such as sneezing, runny nose, and nasal congestion—but also the amount of rescue medication, such as antihistamines, that patients take.

For example, if symptoms are severe and a patient takes a lot of medication, the symptom score may temporarily improve. However, it is difficult to attribute this to the efficacy of the treatment itself. Conversely, if a patient using the treatment experiences symptom improvement while taking fewer of their usual rhinitis medications, the actual therapeutic effect can be assessed as greater. Reflecting these considerations, the CSMS is an indicator that simultaneously evaluates symptom improvement and reduced medication dependence; it is currently a global standard endpoint that the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) consider crucial in the approval review of allergy immunotherapy treatments.

Regarding the market’s view that certain symptom measures (TNSS) did not achieve statistical significance compared to the placebo in the Phase 1 clinical trial, CEO Jeong explained, “The objectives of each clinical phase differ.”

He said, “Since the purpose of a Phase 1 clinical trial is to confirm safety, tolerability, and immunogenicity, it is not designed with a patient sample size large enough to ensure statistical power,” adding, “The goal for subsequent clinical trials is to significantly expand the number of participants and statistically demonstrate the efficacy of symptom improvement in actual patients through multicenter trials.”

He continued, “The goal of the patch-type immunotherapy is not to take market share away from existing treatments,” and emphasized, “Our ultimate goal is to expand the allergy immunotherapy market itself by enabling patients who were unable to start treatment or discontinued it due to the inconvenience of injections or sublingual formulations to resume treatment.”