[Edaily Reporter KIM SAE-MI ] It has been revealed that another COVID-19 treatment (APRG64), led by Kyung Hee University Professor Kang Se-chan, took 4.2 times longer to receive approval for its Investigational New Drug (IND) application from the Ministry of Food and Drug Safety than Genencell’s “ES16001.” While ES16001 was approved just 33 days after the IND application was submitted, APR’s “APRG64” took 140 days. This directly contradicts the claims made by the camp of Kim Seung-won, the nominee for Minister of Justice, who has maintained that the rapid approval of ES16001 was a standard procedure resulting from the expedited review process applied to COVID-19 treatments at the time.

The Common Thread in Kang Se-chan’s COVID-19 Treatments… Natural Products, GenenCell, and Clinical Trials in India

APRG64 is a natural product drug candidate based on extracts of Yong-a-cho (Seonhakcho) and Obaeja, developed by a research team led by Professor Kang Se-chan of Kyung Hee University. Originally developed as a treatment for hepatitis C, its indication was expanded to include COVID-19. In August 2020, APR acquired the technology for APRG64 from Professor Kang’s research team, and Professor Kang served as a registered director and Chief Technology Officer (CTO) at APR at the time. In other words, APRG64 is another COVID-19 treatment candidate for which Professor Kang led the development and GenenCell participated in the clinical trial process.

APR is an unlisted biotech company founded in 2020 that has focused on the development of the natural product-based new drug candidate “APRG64” as its core business. In July 2020, the company secured investment by selling a 30% stake to Gold Pacific (now KBIO COMPANY(038530)), a KOSDAQ-listed company, for 500 million won. In August of the same year, it acquired the rights related to the development of the new drug APRG64, as well as exclusive domestic and international distribution rights, through a technology transfer from the research team led by Professor Kang Se-chan of Kyung Hee University. Subsequently, the company appointed Professor Kang as an in-house registered director and Chief Technology Officer (CTO) and formed a consortium with GenenCell,KOREA PHARMA Co., Ltd.(032300), the Korea Institute of Pharmaceutical Science, and Kyung Hee University to develop a COVID-19 treatment.

Beyond the fact that they are simply COVID-19 treatments, the two candidate compounds share many commonalities. Both are natural product-based candidates led by Professor Kang, and ENCell Co., Ltd. was involved in their development. Their development trajectories are also similar: clinical trials were first conducted in India, and based on that data, they advanced to higher-phase clinical trials involving patients in South Korea. The outcomes for the publicly traded companies that invested in these candidate compounds have also been unfavorable.

First, ES16001 and APRG64 both share the common characteristic of being natural product-based COVID-19 treatments led by Professor Kang Se-chan of Kyung Hee University. ES16001 is a candidate based on Dampalsu extract, while APRG64 is a candidate utilizing extracts of Yong-a-cho (Seonhakcho) and Obaeja. Since Professor Kang’s research team led the development of the core technology for both compounds and ENCell Co., Ltd. was involved in the clinical development process, they can be viewed as COVID-19 treatments originating from virtually the same development network.

They also share the fact that clinical trials for both candidates were first conducted in India, and based on those data, they received approval for upper-phase clinical INDs targeting patients in South Korea. ES16001 received approval for a Phase 2/3 IND in South Korea based on the results of its Phase 2 clinical trial in India, and APRG64 also received approval for a Phase 2a IND for COVID-19 in South Korea following a trial in healthy volunteers in India. However, concerns were raised even within the Ministry of Food and Drug Safety regarding the statistical significance and safety assessment of the subsequent clinical trial results for ES16001 in India, and no specific figures were disclosed in the Indian clinical data for APRG64.

Another commonality is that while large amounts of capital from publicly listed companies flowed into these two candidate drugs, the value of the investment assets was ultimately severely impaired. For ES16001, SEJONG MEDICAL Co.Ltd.,(258830)and KOREA PHARMA Co., Ltd. invested in Genencell’s shares and convertible bonds (CBs), but the book value of the related investment assets eventually fell to 0 won. Similarly, for APRG64, the book value of the APR stake acquired by Gold Pacific for 500 million won fell to 0 won, and there have been no commercialization achievements to date. While expectations for a COVID-19 treatment served as a strong catalyst for the stock prices of related publicly traded companies and for attracting investment, they failed to translate into actual business results.

ES16001: 33 days vs. APRG64: 140 days… 4.2-fold difference in IND approval speed

Nevertheless, there was a significant difference in the speed of IND approval for the two candidate compounds.

ES16001 filed for an IND for a domestic Phase 2/3 COVID-19 clinical trial on September 23, 2021, and received approval on October 26 of the same year. This means it took 33 days from application to approval. During this process, the Ministry of Food and Drug Safety (MFDS) requested supplementary information on 14 items on September 30, and on October 12—while the review was still underway—candidate Kim specifically requested expedited processing for Genencell Co., Ltd. from Kim Kang-rip, then head of the MFDS.

At the time, Nominee Kim sent a message to former Commissioner Kim stating, “Please ask the staff in charge to process this a bit more quickly. The company is GenenCell.” Subsequently, GenenCell submitted the supplemental materials, and the IND was approved 14 days after Nominee Kim’s request.

In contrast, APRG64 filed an IND application for a Phase 2a clinical trial involving 90 patients with mild to moderate COVID-19 on February 22, 2022, but approval was not granted until July 12 of the same year. It took 140 days from application to approval—107 days longer than for ES16001, or approximately 4.2 times as long.

APRG64 was also sponsored by Genencell and tested on 40 healthy adults in India. At the time, the company promoted this as an “Indian Phase 1 clinical trial,” stating that it had confirmed safety and tolerability. Subsequently, based on this data and other materials, the trial progressed to a Phase 2a clinical trial involving patients in South Korea.

Kim Seung-won Claims, “It Was Fast Because It Was a COVID-19 Treatment”… The APRG64 Case Directly Contradicts This Claim

This discrepancy becomes even more striking when considering the explanation provided by Nominee Kim’s camp. In the biotech industry, some have cautiously speculated that requests from Nominee Kim’s camp may have influenced the differing speeds of IND approval for the two new drug candidates.

Regarding recent allegations surrounding ES16001, Nominee Kim drew a clear line, stating that under the circumstances of the COVID-19 pandemic at the time, the development of treatments and vaccines was fast-tracked. He argued, “I called the head of the Ministry of Food and Drug Safety (MFDS) with the intention of asking them to expedite the delayed procedures,” adding, “I never made any improper requests to the MFDS, nor did the MFDS’s review fail to proceed fairly as a result.” The nominee’s camp has explained that the Ministry of Food and Drug Safety (MFDS) conducted expedited reviews for COVID-19 treatments with the goal of processing applications within 15 days of receiving supplemental data, and that ES16001 was also approved in accordance with this standard procedure.

However, APRG64—a drug in which Professor Kang was involved and which progressed from clinical trials in India to trials involving domestic patients around the same time—took 140 days to receive IND approval. This suggests the possibility that the MFDS made a significant number of requests for supplementary information during the review process. GeneOneLifeScience(011000) Considering that the COVID-19 treatment “GLS-1027” also took 222 days to receive IND approval, it was not the case that all COVID-19 treatments could obtain IND approval within a matter of tens of days.

Critics in the biotech industry point out that the explanation that “it was approved quickly because it was a COVID-19 treatment” is insufficient to fully account for the 33 days it took for ES16001. Some have even raised suspicions that Nominee Kim’s influence was that strong. This stems from doubts that Nominee Kim’s request for expedited processing played a major role in the difference in the speed of IND approval for the two candidate drugs.

A biotech industry official stated, “It is difficult to conclusively label the APRG64 case as preferential treatment based on that alone, but if one took 140 days and the other 33 days along a similar development path, it is true that the difference in time is significant,” adding “If Nominee Kim’s camp has argued that other COVID-19 treatments were also reviewed quickly at the time, then it is necessary to compare why APRG64 took 140 days using the same criteria,” the official added.