[Edaily Reporter Kim Seung-kwon ] “For osteoarthritis treatments, simply reducing pain is not enough. They must also restore damaged joint structures, reduce inflammation, and demonstrate that patients actually experience less pain and improved mobility.”

Kim Dae-won, CEO of ICM, explained the development goals for “ICM-203,” a gene therapy candidate for osteoarthritis, in this way. The key lies in disease-modifying osteoarthritis drugs (DMOADs). The concept goes beyond treatments that merely provide temporary pain relief; it aims to slow or reverse the deterioration of joint structures—such as cartilage and the synovial membrane—and ensure that these changes lead to reduced pain and restored function. PharmDaily met with CEO Kim Dae-won to discuss ICM’s future business plans based on its clinical data.

Signs of Simultaneous Improvement in Pain and MRI Findings After a Single 52-Week Dose

Although osteoarthritis affects a large number of patients, treatment options are limited. A significant treatment gap remains between pain relievers, anti-inflammatory drugs, intra-articular injections, and joint replacement surgery. In particular, no DMOAD has yet received approval from major regulatory agencies by demonstrating simultaneous improvements in joint structure, pain relief, and function.

ICM is targeting this gap with an AAV (adeno-associated virus)-based single-dose gene therapy. ICM-203 delivers the transcription factor “Nkx3.2-D2”—which is involved in the survival and differentiation of chondrocytes—via AAV through a single injection into the knee joint cavity. CEO Kim stated, “We confirmed that Nkx3.2, which is essential for cartilage health, is reduced in the joints of osteoarthritis patients,” adding, “ICM-203 is designed to compensate for this lost function, thereby inhibiting cartilage calcification and cell death, while also regulating synovial inflammation.”

ICM conducted a Phase 1/2a clinical trial of ICM-203 in Australia involving patients with moderate knee osteoarthritis. The drug was administered intra-articularly once to patients with Kellgren-Lawrence (KL) grades 2–3, and safety and efficacy were monitored for 52 weeks.

The key analysis released by the company included data from three patients in the placebo group, three in the low-dose group, and two in the medium-dose group. Due to the small sample size, it is not yet possible to determine statistical significance. However, it is noteworthy that pain and functional indicators moved in the same direction as MRI-based structural indicators.

At the 52-week mark, the WOMAC score—a measure of osteoarthritis—worsened by an average of 0.7 points from baseline in the placebo group. In contrast, the low-dose group improved by 13.3 points, and the medium-dose group improved by 17.5 points. A lower WOMAC score indicates an improvement in pain, stiffness, and physical function.

The Numerical Rating Scale (NRS), which measures pain intensity, and the Knee Outcome Score (KOOS) also showed similar trends. A tendency toward greater improvement with higher doses was also observed.

CEO Kim stated, “Since the number of patients is small, we are not yet at the stage where we can discuss p-values,” but added, “Nevertheless, a dose-dependent trend was consistently observed in the WOMAC, pain, and functional indicators. I consider this a very encouraging sign based on what we’ve seen in this early-stage clinical trial.”

Structural assessment is another distinguishing feature of ICM-203. ICM utilized the MRI Osteoarthritis Knee Score (MOAKS) rather than simple X-rays. MRI was used to track actual changes inside the joint, such as full-thickness cartilage loss, bone marrow lesions, joint effusion, and synovitis.

In the medium-dose group, both the full-thickness cartilage loss score and the synovitis score improved. The composite osteoarthritis burden score—which combines the changes in cartilage loss and synovitis—showed an average worsening of 0.3 points in the placebo group, an improvement of 0.3 points in the low-dose group, and an improvement of 3.5 points in the medium-dose group.

CEO Kim emphasized, “It is difficult to classify this as a DMOAD based solely on patient reports of improved pain and function,” adding, “What is most important is that both cartilage and synovitis improved on MRI, and that these changes aligned with the trends observed in pain and functional indicators.” He continued, “We have confirmed the possibility that the trends observed in animal studies—cartilage protection and regeneration, inflammation control, and improvements in pain and gait—may also hold true in humans,” adding, “We will continue our verification efforts to determine whether this can become the world’s first successful DMOAD case.”

Open-Label Trial

with 24 Participants in Korea… “Reducing the Time Needed to Persuade Big Pharma”

ICM’s next step is an expanded clinical trial in Korea. The company has submitted an Investigational New Drug (IND) application to the Ministry of Food and Drug Safety for a domestic clinical trial involving 24 participants, centered at Severance Hospital and Seoul St. Mary’s Hospital. If approved, the company aims to administer the first dose to a patient within the year.

The domestic clinical trial is planned as an open-label study, with eight participants assigned to each of the low-, medium-, and high-dose groups. Rather than including a placebo group as in the Australian trial, the strategy is to accumulate data from patients receiving the drug in real time.

CEO Kim stated, “Global pharmaceutical companies understand the potential based on the initial data from Australia, but they have responded that it is difficult to proceed with a large-scale technology transfer based solely on a small number of patients.” He added, “By adding data from 24 patients in Korea, we can more quickly demonstrate consistency in dose-response and improvements in structure and pain.”

He continued, “In a double-blind clinical trial, data can only be reviewed after all patients have completed treatment and follow-up.” He explained, “This time, we’ve designed the trial as an open-label study so that we can discuss the findings with global pharmaceutical companies as the data accumulates. This is a strategic choice to expedite the decision-making process for technology transfer.”

The development of osteoarthritis treatments has long faced the significant hurdle of the placebo effect. In fact, Kolon TissueGene’s TG-C showed a trend toward pain and functional improvement in the first U.S. Phase 3 clinical trial, but at the 12-month mark, it failed to achieve statistical significance compared to the placebo on the combined primary endpoints of VAS and WOMAC. The VAS score decreased by 38.7 points in the TG-C group and 39.2 points in the placebo group, while the WOMAC total score decreased by 27.61 points and 26.54 points, respectively. This case illustrates just how difficult it is to control large-scale placebo responses in the development of osteoarthritis treatments.

ICM is attempting to differentiate itself by presenting structural indicators alongside clinical data. CEO Kim stated, “If osteoarthritis is assessed based solely on symptoms, the results can be swayed by the placebo effect,” adding, “If we objectively document changes in cartilage and synovitis through MRI, we can more clearly demonstrate the treatment’s potential to control the disease.”

Pet medications are also a key driver of mid- to long-term growth. ICM has completed animal trials for “ICM-502,” a canine osteoarthritis treatment for which it licensed the technology to Z, a global animal healthcare company. The company is currently conducting post-hoc analyses, including histopathology. If the efficacy results are positive in the first quarter of next year, the company expects Z to exercise its options and pay additional milestone payments accordingly.

CEO Kim said, “ICM-502 represents a different business pillar from human therapeutics,” adding, “The development process for veterinary drugs is relatively shorter than that for human drugs. If the technology transfer and commercialization materialize, it could help generate a stable cash flow for the company.”

The company will reconsider an initial public offering (IPO) once domestic clinical data has been accumulated. CEO Kim said, “Rather than rushing an IPO, we will wait until the clinical value of ICM-203 becomes clearer,” adding, “If the domestic patient data replicates the trends seen in the Australian clinical trials, both the technology transfer and the company’s valuation could reach a new turning point.”