Strategic focus involves the proactive pursuit of First-in-Class and Best-in-Class small molecule therapeutics.
aGvHD, and Kidney Transplant Rejection
Developing
Difficult-to-Treat Cancers
BPC2001
BPC2003
BPC3001
BPC2001 A First-in-class liposomal drug that effectively regulates the immune system's balance for prophylaxis against acute Graft-versus-Host Disease (aGvHD).
What is GvHD?
Many blood disorders, such as leukemia, require allogeneic hematopoietic stem cell transplantation (AHSCT) as a vital treatment option. However, graft-versus-host disease (GvHD), where immune cells from the donor attack the recipient's organs, remains a major and potentially fatal complication of AHSCT1.
The action of balancing the immune system
BPC2001 (originally named RGI-2001) is a new chemical entity (NCE) formulated as a liposomal preparation encapsulating α-GalCer. Its primary mechanism involves inducing an increase in regulatory T cells (Treg), thereby initiating specific immune tolerance. This action serves to alleviate rejection-related immune responses while preserving the donor immune cells' anti-cancer effect (graft-versus-leukemia, GvL)2, ultimately achieving the prevention of acute Graft-versus-Host Disease (aGvHD).
BPC2001 has the potential to improve the success rate of bone marrow transplantation by preventing acute graft-versus-host disease (aGvHD), offering meaningful benefits to a broad population of patients with hematologic disorders.
BPC2003 is an innovative drug that employs a novel mechanism of immune modulation to reduce the rejection of kidney transplant.
What is kidney transplant rejection?
Kidney transplantation is the primary treatment for end-stage renal disease, offering effective restoration of kidney function and significant improvement in patients' quality of life. However, post-transplant rejection remains a common and serious complication that can lead to graft failure. Although immunosuppressive therapies are available, challenges such as side effects and inconsistent long-term efficacy persist. Effective and safer rejection control therefore remains a critical unmet medical need.
Immune Balance Regulation
BPC2003, a new indication of BPC2001, is designed to inhibit transplant rejection by inducing the proliferation of regulatory T cells (Tregs) and initiating antigen-specific immune tolerance.
BPC2003 is expected to enhance the anti-rejection response by modulating immune homeostasis, thereby preserving renal function and improving overall treatment outcomes in transplant patients.
Jordan SC, et al. Am J Transplant. 2020;20,42-56.
Rodriguez-Ramirez S, et al. Curr Opin Organ Transplant. 2022, 27,405–414.
New generation proteasome inhibitor for difficult-to-treat cancers
Mechanism of Action
BPC3001 is a novel anticancer molecule whose primary mechanism involves inhibition of the ubiquitin receptor RPN13 (ADRM1) within the 19S regulatory particle of the proteasome. It blocks substrate recognition and deubiquitinating processes within the 19S regulatory particle, leading to the accumulation of polyubiquitinated proteins, which induces endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and early apoptosis. Compared with traditional 20S proteasome inhibitors, BPC3001 acts through a distinctly different mechanism of action. Preliminary animal studies have demonstrated strong and effective suppression of solid tumors, along with favorable pharmacokinetic properties and an encouraging safety profile.
Target Indication
BPC3001 is being developed for multiple cancers, including ovarian cancer, triple-negative breast cancer, multiple myeloma, small-cell lung cancer, liver cancer and melanoma. In animal models, it has been shown to effectively inhibit tumor growth and enhance therapeutic efficacy synergistically when combined with platinum-based chemotherapy agents like cisplatin. This combination strategy holds promise for improving outcomes in hard-to-treat malignancies. In addition, its safety profile is superior to that of traditional proteasome inhibitors.
As a next-generation proteasome inhibitor, BPC3001 is expected to provide stronger efficacy with lower toxicity than first-generation agents, offering a better therapeutic option for patients with difficult-to-treat solid tumors.
Anchorri R.K., et al. Development and anticancer properties of Up284, a spirocyclic candidate ADRM1/RPN13 inhibitor. PLoS ONE. 2023, 18(6): e0285221.
Osei-Amponsa V. and Walters Kylie. Proteasome substrate receptors and their therapeutic potential. Trends in Biochemical Sciences. 2022, 47(11): 950-64.
Anchorri R.K., et al. A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. Cancer Cell. 2013, 24(6): 791-805.
