Gennbio Co. Ltd. has signed an agreement with fellow Korean biotech Genexine Inc. to in-license two immunosuppressant drug candidates called GX-P1 (PD-L1 hyfc) and BSF-110 (PD-L1-hyFc-1L10m). Gennbio will accelerate R&D of those candidates, aimed at reducing the side effects of current immunosuppressants used in allotransplantation and xenotransplantation. The total deal amounts to $164 million.
Under the agreement, Gennbio will receive the exclusive right to develop and commercialize the drugs for use in the transplantation field. Gennbio, based in Seoul, has paid $6 million up front to Genexine, based in Seongnam. Starting with $8.6 million to be paid after the phase III trial, Gennbio will pay additional technical fees each time its net sales milestones are achieved once they reach the cumulative sales of $86 million. Also, Gennbio plans to pay additional royalties according to sales when commercialized.
The two companies signed a memorandum of understanding last July and have conducted joint nonclinical studies with GX-P1 and BSF-110. Under the agreement, Gennbio will develop a new immunosuppressant that can be taken for a long time with fewer side effects.
Immunosuppressants are one of the standard treatments for organ transplant to prevent immune rejection. Calcineurin inhibitor (CNI) is the most commonly used immunosuppressant; however, its long-term use can cause side effects such as nephrotoxicity, malignant tumors and increased insulin resistance, which may lead to damage to the transplanted organs or reduce long-term survival rates. Thus, combination therapies with immunosuppressants like PD-L1-targeting therapies are gaining attention as they lower the CNI dosage, Gennbio said.
The medical industry has mainly targeted PD-L1 for immune-oncology use. PD-L1 inhibitors are known to suppress the PD-1/PD-L1 signal pathways to induce better immune response to fight the cancer cells.
GX-P1 and BSF-110, meanwhile, reduce T-cell activity and suppress the immune response by strengthening the signal of PD-L1. GX-P1, in particular, strengthens the signal pathways of PD-1/PD-L1 to suppress the unnecessary immune reaction. Gennbio said it has confirmed that GX-P1 and BSF-110 have immunosuppressive effects in the nonclinical tests.
Genexine has completed the preclinical test of GX-P1 and filed an IND for phase I testing with the Korea Ministry of Food and Drug Safety at the end of last year. The company has finished in vivo testing of BSF-110.
“We have decided to conduct transfer technology with Gennbio as we believe the company can greatly develop our immunosuppressant candidates for transplantation in a short time.” Genexine CEO Youngchul Sung said.
“We are working on a master plan that covers the development of source pigs created using genetic engineering technology to be used for xenotransplantation, nonclinical studies to verify the efficacy and safety of xenografts, new drugs and technologies related with the transplantation, and foundation of the transplant-specialized hospital,” Sungjoo Kim, CEO of Gennbio, told BioWorld.
“So far, we have signed a joint research agreement with three companies, including Genexine, and six research organizations to build a xenotransplantation platform. We also strengthened our capabilities for xenotransplantation R&D through the scientific advisory board, which consists of 28 local researchers in the transplantation field.” Kim added.
Medication is the biggest challenge for organ transplantation. In transplant rejection, there is an immune response to the transplanted organ, and it often results in transplant failure and the need for immediate removal of the organ from the recipient. Thus, the use of immunosuppressant drugs can reduce transplant rejection.
According to market research firm Grand View Research, the global organ transplantation immunosuppressant market was estimated at $4.64 billion in 2018 and is expected to reach $5.88 billion by 2026 with a CAGR of 3.3% from 2019 to 2026.
The market growth is driven by a huge demand for organ transplants. A total of 36,528 transplants were performed in 2018 and more than 113,000 people needed transplants, according to the Health Resources & Services Administration and the U.S. Department of Health and Human Services.
CNI drugs are still expected to take the biggest share of the global organ transplant immunosuppressant drugs market through the forecast period, despite the side effects such as nephrotoxicity, malignant tumors and increased insulin resistance. The two main drugs in that class are Prograf (tacrolimus) and Neoral/Sandimmune (cyclosporine), both developed by Sandoz International GmbH.