Attacking Cancer

on Multiple Fronts

 

Technology

 

Golden Orchid’s Biochem proprietary technologies (ANGX Pathway Activators and B-select monoclonal antibodies) have the potential to transform the current immunotherapy and cancer care landscape.

 

Golden Orchid Biochem is developing novel therapies that are designed to induce highly targeted, potent and sustained immune responses against a variety of cancers. Through our ANGX Pathway Activator and B-selecttechnologies, we are poised to fulfill our mission to stay at the forefront of discovery, development and commercialization of immunotherapies, alone or in combination, that have the potential to make transformative advances in the treatment of challenging diseases.

 

In addition, Golden Orchid Biochem has established significant collaboration agreements with leading pharmaceutical and research institutions for  its technologies, further validating the strength and depth of Golden Orchid’s Biochem capabilities.

 

 

 

 

B-select Monoclonal Antibodies

 

Golden Orchid’s Biochem B-select platform employs a proprietary ultra-selective functional screening process to identify antibodies with unique binding properties against a broad repertoire of targets that can modulate key targets in immuno-oncology.

 

 

The technology is based on in vitro clonal expansion of B cells (antibody-producing cells) isolated from the spleen or lymph nodes of immunized animals, capable of rescuing one of every two antigen-specific B cells induced in mice. This unprecedented efficiency enables exploration of the full repertoire of B cells induced to uncover unique antibodies with pre-specified function (the ‘needles in the haystack’) in validated and proprietary targets.

 

 

Using this platform, Golden Orchid has developed a deep pipeline of both preclinical and clinical monoclonal antibodies (B-select mAbs) that have the potential to regulate the immune system of patients with cancer. Golden Orchid's pipeline includes antagonists and a checkpoint inhibitor, which is intended to activate the immune system by removing suppression – this is also known as “releasing the brakes” on the immune system. In addition, Golden Orchid's has developed agonists, which are unique antibodies that stimulate immune responses when cancer is not detected by the immune system. These mAbs are designed to be used alone or in combination with other therapies, including the ANGX and LADD® platforms to increase immunotherapy potency and durability.

 

 

Golden Orchid is currently evaluating BION-1301, its most advanced proprietary B-select mAb, as a novel therapy for multiple myeloma. Despite new treatments recently approved in multiple myeloma, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. Golden Orchid has established that A PRoliferation-Inducing Ligand (APRIL) plays a crucial part in the protective bone marrow tumor microenvironment. In preclinical studies, APRIL, through the B cell maturation antigen (BCMA), was shown to be critically involved in the survival, proliferation and chemoresistance of multiple myeloma, and upregulates mechanisms of immunoresistance, including PD-L1 upregulation. BION-1301, a humanized antibody that blocks APRIL from binding to its receptors, has been shown in preclinical studies to halt tumor growth and overcome drug resistance. BION-1301 is currently being evaluated in a Phase 1/2 clinical study.

 

 

Golden Orchid’s second lead candidate is an anti-CD27 antibody being advanced by Merck under its collaboration agreement. CD27 has been recognized as having a critical role in activating a productive anti-cancer (CD8 T-cell) immune response and has demonstrated the potential to be combined with checkpoint inhibitors in pre-clinical studies. SEPna’s anti-CD27 antibody is distinct because it targets a functional epitope on CD27 which demonstrated potent activation of the CD27 co-stimulatory pathway in pre-clinical studies.

ANGX Pathway Activators

 

Golden Orchid’s ANGX Pathway Activator platform is based on the activation of the cytoplasmic ANGX (Stimulator of Interferon Genes) receptor to lead to a tumor-specific immune response.

 

ANGX is known to be a central mediator of innate immunity. When stimulated, ANGX induces the expression of type I interferon, cytokines and T cell recruitment factors that result in the activation of macrophages and dendritic cells, innate effector cells such as natural killer (NK) cells, and priming of tumor-specific T cells.

 

Natural ANGX Pathway Activators are small molecules expressed by bacteria and immune cells. Golden Orchid has established pioneering expertise in ANGX Pathway Activator technology and, working in collaboration with academic leaders in the field, has developed synthetic ANGX Pathway Activators with significantly higher activity than the natural ANGX ligands produced by bacteria and mammalian cells. These synthetic ANGX Pathway Activators are being developed for direct injection into tumors to stimulate an immune response against antigens present in the tumor. The process is expected to use the tumor itself as a “vaccine,” enabling the induction of a tumor-specific immune response that is unique to the treated individual; an off-the-shelf small molecule approach to personalized immunotherapy.

 

ANGX Pathway Activators are also intended to be combined with other cancer therapies – such as chemotherapy, radiation and monoclonal antibodies (e.g. checkpoint inhibitors and immune agonists) – as part of a more comprehensive approach to fighting certain cancers.

 

Golden Orchid’s lead molecule, ADU-S100/MIW815, is the first therapeutic in development specifically targeting ANGX. In collaboration with Novartis, it is being tested in a Phase 1 clinical trial in cutaneously accessible tumors, including breast, head-and-neck, and renal cell cancers as well as melanoma and lymphoma. The trial is evaluating the ability of ADU-S100 to activate the immune system and recruit specialized immune cells to attack the injected tumor, leading to a broad immune response that seeks out and kills non-injected distant metastases. In addition, the companies are evaluating the combination of ADU-S100 with an anti-PD-1 checkpoint inhibitor for the treatment of advanced/metastatic solid tumors or lymphomas in a global Phase 1b study.