Development strategy of BCV of Shin Bio Pharmaceutical Co., Ltd. <4582>
2. Development pipeline
BCV is currently being developed in multiple areas such as academic research in hematopoietic stem cell transplantation after AdV infection, brain tumors, hematological tumors, and neurodegenerative diseases. In May 2023, the company announced the establishment of POC in humans for a phase 2 clinical trial targeting AdV infection after hematopoietic stem cell transplantation. By establishing POC, it is expected that the development risks and development period can be reduced in other disease areas, and smooth progress is expected in partner contract negotiations for maximizing business value through the platform deployment of BCV.
(1) AdV infection after hematopoietic stem cell transplantation
As the first development target for BCV (injection), an international joint phase 2a clinical trial for AdV infection after hematopoietic stem cell transplantation targeting children (including adults) was started in the United States from August 2021. AdV is a virus that exists naturally and causes infectious diseases such as pharyngitis, tonsillitis, conjunctivitis, gastroenteritis, and hemorrhagic cystitis by infecting respiratory, eye, intestinal, and urinary systems. It is rare for healthy people to become seriously ill even if they are infected, but there is a high risk of becoming severe in patient groups with reduced immunity after hematopoietic stem cell transplantation, and there are no effective treatment or preventive drugs yet. The number of hematopoietic stem cell transplants in the world is 35,000 per year, and the number of patients with AdV infection is about 2,000※.
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In the phase 2 clinical trial, safety, tolerability, and efficacy (changes in AdV concentration in the blood) are evaluated to determine the recommended dosage for the next trial. The trial was conducted by dividing the dosage (0.2mg/kg, 0.3mg/kg, 0.4mg/kg※1) and administering it twice a week in four groups, including the group that administered 0.4mg/kg once a week, as a result, in the group that received 0.4mg/kg twice a week (10 cases), all patients had disappeared AdV in the blood, of which 90% of patients were confirmed to have virus clearance within 4 weeks after treatment. In addition, the report※2 stated that there were no serious adverse events related to treatment, including gastrointestinal and hepatic toxicity, confirmed by BCV oral formulation in all 27 patients. It is considered that POC has been established in humans. There was a great response by the presentation at the academic congress, and there were 3 requests from the families of patients who developed AdV infection after hematopoietic stem cell transplantation and attending physicians who requested to use BCV, and the company provided it free of charge from a humanitarian standpoint. Regarding the US teenagers, it has been reported that symptoms improved after BCV administration.
※1 If the body weight is 50 kg or more, the dosage is 10mg, 15mg, 20mg.
※2 Treatment-related serious adverse events, including gastrointestinal and hepatic toxicity, observed with the administration of 0.4mg/kg twice a week were reported in 1 of the 27 patients and 6 of the entire 27 patients, respectively, but disappeared after the end of treatment.
Based on the results of this clinical trial, the company has filed a patent application for the use of BCV in Japan and has announced that it has been registered with a short period of 4 months in January 2024 through expedited approval procedures. Furthermore, the company plans to acquire usage patents in Europe and the United States and aims to expand the business value of BCV through a patent strategy. By establishing POC, the company believes that the development of other diseases can also be progressed with a dose of 0.4mg/kg administered twice a week as a guide. This means that the development risks and the development period can be significantly reduced, and the deployment of the BCV platform will have significant implications for the company.
※It is stipulated that a certain amount of liquid BCV is intravenously administered at a certain interval according to the patient's weight, and administration is continued for a predetermined period and is terminated according to the discontinuation criteria.
As for the future development plan for AdV infection, the company plans to hold consultations with regulatory authorities in the United States, EU, and the United Kingdom towards the start of an international joint phase 3 clinical trial and wants to start the phase 3 clinical trial as early as the fourth quarter of the fiscal year ending in December 2024 in the future. The actual FPI (first patient enrollment) is expected to be in the first quarter of the fiscal year ending in December 2025, and a milestone payment of USD 5 million will occur when FPI is confirmed (not included in the December 2024 plan). If development proceeds smoothly, it is possible to obtain approval in the late 2028.
(2) BKV infection after kidney transplantation
As a second pipeline, we were conducting an international phase 2 clinical trial targeting BKV infection after kidney transplantation in Australia and Japan from December 2022. However, considering that the case accumulation is delayed compared to the plan and the development status of other development pipelines, we have decided to downgrade the development priority in August 2023.
※BK virus belongs to the Polyomaviridae family of DNA virus. Almost 100% of healthy individuals are naturally infected in childhood, and if the immune system is lowered after organ or bone marrow transplantation, the virus can be activated, causing hemorrhagic cystitis and interstitial nephritis. In addition, in some cases, the transplanted kidney also becomes dysfunctional and lost when the symptoms worsen.
Kidney transplantation is the only definitive treatment for end-stage renal failure, and the number of patients requiring transplantation surgery is about 100,000 worldwide. After kidney transplantation, there is a risk of developing various viral infections due to decreased immunity, and the number of patients with BKV infection is estimated to be about 8,000 per year※. Currently, immunosuppressants and CMV infection treatments are prescribed as symptomatic therapies, but their effects are limited. Thus, development of an effective treatment for this high-unmet medical need disease is desired. Although we have downgraded the development priority, we intend to resume clinical trials if circumstances permit.
※Source: Business plan and growth potential
(Written by FISCO guest analyst, Jo Sato)