HONG KONG Canadian company Pascal Biosciences Inc., headquartered in Vancouver, and South Korean biotech Y-biologics Inc., based in Daejeon, have signed a research collaboration agreement for the discovery and development of bispecific antibodies for the treatment of leukemia.
Under the agreement, Y-biologics will contribute its bispecific antibody platform technology called ALiCE (antibody-like cell engager) while Pascal will use its antibodies. Both companies will share responsibility for the discovery and validation of lead candidates and pursue optimal development processes. Further terms, including financial details, were not disclosed.
Y-biologics' ALiCE has a two-by-one structure to minimize the off-target toxicity. In contrast to mutation-based engineering platform technologies, ALiCE aims to harness the innate assembly mechanisms of cell lines to preserve natural domains from the original antibodies.
According to the company, the technology preserves the F(ab')2 structure of the parental antibody to maintain a high binding affinity to the cancer antigen. It also substitutes the Fc region with a monovalent Fv to induce an immune response.
"In our previous clinical studies, T-cell redirecting bispecific antibodies have shown effective redirection of T cells onto tumor cells and specifically kill the tumor cells," Wooshik Kim, senior manager of business development team at Y-biologics, told BioWorld. "Compared to one-by-one or two-by-two structure drugs, our two-by-one structure has better efficacy to treat cancers."
Taehee Kim, analyst at Mirae Asset Daewoo Co. Ltd., the largest investment banking and stock brokerage company in Korea, said that the two companies' collaboration has garnered attention.
"Investors will pay attention to the collaboration as it is [a] bispecific T-cell engager and the global investment in the technology is on the rise. Many of the global big pharmaceutical companies are also interested in introducing bispecific antibody-related technologies," Taehee Kim said.
Pascal was founded in 2013 to advance technology licensed from the University of British Columbia. The company is focused on cancer therapies, including targeted treatments for acute lymphoblastic leukemia, and cannabinoid-based therapeutics. It is developing three drug candidates, including lead drug PAS-403, a mitosis inhibitor that blocks cell division. PAS-403 was licensed from the University of Washington in Seattle. The cannabinoid-based product is under development for the treatment of glioblastoma and brain metastases originating from other cancers.
According to Pascal, several mitotic inhibitors approved for cancer treatment show substantial benefits in reducing solid tumors when combined with other chemotherapeutics. Those agents, however, do not cross the blood-brain barrier, unlike PAS-403, and have no activity on glioblastoma or other brain cancers. Another program in the pipeline, PAS-393, is an immunostimulatory cannabinoid to be used in combination with checkpoint inhibitor therapy. It is designed to restore the immunogenicity of tumor cells, thus rendering those cells once again susceptible to recognition and destruction by the immune system. The ability to reactivate the interaction between immune cells and cancer cells has potential in the immuno-oncology field, the company said.
In addition, Pascal develops antibodies against the pre-B-cell receptor (pre-BCR) for B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
The pre-BCR consists of a heavy chain paired with a surrogate light chain. VpreB and lamda 5, two components of the surrogate light chain, are expressed only on the leukemia cells and on pre-B cells. The expression on those cells represents an early stage in B-cell development. Thus, targeting those molecules aims to eliminate the tumor cells while sparing mature, activated and memory B cells that are essential for fighting infection. The pre-BCR antibody is designed to kill tumor cells in cell growth and exhibits properties amenable to engineering for effective cancer cell destruction.
Y-biologics has been focused on antibody therapeutics R&D since its foundation in 2007. The company develops antibodies using its human antibody library, Ymax-ABLTM, and platform technology, ALiCE.
The Korean biotech has five main programs: YBL-001, antibody-drug conjugate (ADC) targeting Delta-like homolog 1 (DLK-1), is in preclinical study; YBL-006, an antibody undergoing preclinical testing, targets PD-1 and PD-L1 interaction; and two antibodies and one bispecific antibody are undergoing cell line development for potential immuno-oncology indications.
The company also develops one bispecific antibody targeting autoimmune disease and has 10 aimed at immuno-oncology.
Y-biologics has partnered with other foreign biotechs to enhance bispecific cancer immunotherapies. The Korean firm signed a contract with Dualogics LLC, of Durham, N.C., in June, in which the two companies agreed to collaborate, with Y-biologics contributing monoclonal antibodies with activity against a variety of immuno-oncology targets and Dualogics using its Orthomab bispecific antibody generator technology to design novel bispecific antibodies from the Korean company's portfolio.