[Edaily Reporter NA EUN-KYUNG ] Aptabio Therapeutics Inc.(293780)has completed approximately 65% of patient enrollment for the domestic Phase 2b clinical trial of “Isuzinacxib” (APX-115), a treatment for diabetic nephropathy. As it has taken time to recruit high-risk patients with impaired kidney function, the expected completion date for enrollment has been pushed back from the end of this year to the first half of next year. However, the company maintains its goal of releasing key clinical results (topline) in the second half of next year.

Lee Soo-jin, CEO of Aptabio Therapeutics Inc., said in a recent interview with Pharm E-Daily, “We have enrolled about 65% of patients so far, and drug administration is underway,” adding, “We have increased the number of clinical sites to speed up patient enrollment and are employing various methods to accelerate recruitment.”

Time Needed to Recruit High-Risk Patients… Aiming to Release Results in the Second Half of Next Year

Isuzinacxib is a broad-spectrum NADPH oxidase (NOX) inhibitor developed in-house by Aptabio Therapeutics Inc. NOX is an enzyme involved in the production of reactive oxygen species in the body; when overactivated, it can induce oxidative stress, leading to damage and inflammation in kidney tissue. Isuzinacxib is being developed to reduce kidney damage by inhibiting NOX.

The ongoing Phase 2b clinical trial in South Korea targets patients whose kidney function has already significantly declined. The primary recruitment criteria are patients with an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m². eGFR indicates the kidneys’ ability to filter waste products from the blood; a lower value signifies reduced kidney function.

CEO Lee explained, “The Phase 2b trial already consists of a high-risk patient population. Since we are only recruiting severely ill patients with an eGFR of 60 or lower, it is taking longer than expected.”

Aptabio Therapeutics Inc. plans to complete patient enrollment in the first half of next year and secure topline data in the second half. The company expects to obtain the Clinical Study Report (CSR) in early 2028.

CEO Lee said, “Patient enrollment isn’t proceeding as quickly as we’d hoped, which is frustrating,” but added, “We’re receiving significant support from the Korea Drug Development Fund (KDDF), which is helping us conduct the clinical trial.”

This Phase 2b trial is significant because it will determine whether the therapeutic efficacy observed in certain patient subgroups during the previous European Phase 2a trial can be replicated in a larger-scale follow-up trial.

Aptabio Therapeutics Inc. completed a Phase 2a clinical trial of Isuzinacxib in Europe in 2022, involving 140 patients with diabetic nephropathy. At that time, after 12 weeks of treatment, the urinary albumin-to-creatinine ratio (UACR) decreased by 20.6% in the treatment group and 2.5% in the placebo group across the entire patient population; however, the difference between the two groups was not statistically significant (p=0.088).

UACR is a marker used to assess the extent of kidney damage based on the amount of albumin excreted in the urine. Along with eGFR, which evaluates kidney function, it is used to determine the efficacy of kidney disease treatments.

However, among the 21 severe patients with an eGFR below 45 at the time, UACR decreased significantly compared to the placebo group (p=0.0197). Based on these results, Aptabio Therapeutics Inc. proceeded with a follow-up clinical trial focused on patients with severely impaired renal function.

CEO Lee cited the clinical environment during the COVID-19 pandemic and low medication adherence as the reasons why statistical significance was not achieved in the overall patient population of the previous Phase 2a trial.

“At the time, Eastern Europe was under lockdown due to COVID-19, making it difficult for patients to visit hospitals and for medical staff to properly monitor medication adherence,” he explained. “When we drew blood at every visit to analyze drug concentrations, we found that as many as 30% of patients had not taken their medication.”

He continued, “When we reanalyzed the data after identifying the subgroup of patients who had taken the medication properly, we confirmed statistical significance.” According to the disclosure at the time, among the 44 patients in the compliance group—classified based on drug concentrations—UACR was significantly reduced compared to the placebo group (p=0.0165). However, since the finding that statistical significance was not achieved in the overall patient population remains unchanged, it is crucial to confirm the reproducibility of the drug’s efficacy in this Phase 2b trial.
Due Diligence

for Technology Export with Global Pharmaceutical Companies… Negotiations Take Shape Based on Clinical Results

While awaiting the results of the Phase 2b trial for diabetic nephropathy, Aptabio Therapeutics Inc. is pursuing global technology export by leveraging recently obtained Phase 2 clinical data on contrast-induced acute kidney injury (CI-AKI). This is a packaged technology transfer strategy that targets both acute and chronic kidney diseases with the same candidate compound.

CEO Lee stated, “We are engaged in in-depth discussions with several global pharmaceutical companies. Since the clinical results for acute kidney injury were expected to be released during the due diligence (DD) process, our partners have been awaiting them.” He added, “We have agreed to hold more concrete discussions at BIO-Europe based on these results. We expect technology transfer discussions to take shape more quickly even before the Phase 2b results for diabetic nephropathy are released.”

In the recently disclosed Phase 2 CI-AKI clinical trial, patients were administered 400 mg of Isuzinacxib for five days, and renal function was monitored for up to 12 weeks. The results showed that the rate of eGFR decline was 1.8% in the treatment group and 7.4% in the placebo group. The difference between the two groups was statistically significant (p=0.02). However, the incidence of acute kidney injury immediately following the procedure was 6.2% in the treatment group and 5.1% in the placebo group, indicating no significant preventive effect.

The company is focusing on the results showing suppression of subsequent renal function decline rather than the prevention of short-term acute kidney injury. CEO Lee emphasized that in both clinical trials, more positive results were observed in patients with more severely impaired renal function.

He explained, “The causes of these conditions are different. One is acute injury, while diabetic nephropathy is a disease characterized by chronic, progressive damage,” adding, “Our global partners asked us to verify once more why the drug’s efficacy is particularly evident in severe cases, and in this acute kidney injury clinical trial, we confirmed even better results in severe patients.”

Aptabio Therapeutics Inc. plans to secure the final results report for the CI-AKI clinical trial in the first half of next year and to apply for Fast Track designation from the U.S. Food and Drug Administration (FDA). The company explained that a technology transfer agreement is possible even before the final results report is secured.

CEO Lee stated, “It is significant that we were able to once again confirm the renal protective effect in severely ill patients in the acute kidney injury clinical trial before the Phase 2b results for diabetic nephropathy are released,” adding, “Based on this, discussions regarding technology transfer will materialize more quickly.”