BEIJING – Yisheng Biopharma Co. Ltd., of Beijing, said it has inked a pact with U.S. biotech Tavotek Biotherapeutics, of Ambler, Pa., to co-develop a combination therapy with Yisheng’s YS-ON-001/002 and Tavotek’s Tavo-301/303, which the companies hope could prove a more efficacious cancer treatment than the popular anti-PD-1/PD-L1 monotherapies.
YS-ON-001 and YS-ON-002 are potent agonists of TLR3, MDA5 and RIG-I pathways. Meanwhile, Tavo-301/303 is a series of novel multispecific antibody-based immuno-oncology assets.
“Our approach allows us to develop a combination therapy that can activate the immune system differently from PD-1/PD-L1-based molecules,” Yisheng’s CEO David Shao told BioWorld.
He added that current immune-oncology approaches such as PD-1/PD-L1 antibodies as a single agent achieve only around 20% to 30% response rates in clinical settings.
By combining YS-ON-001/002 with multispecific antibodies like Tavo-301/303 directed against tumors, the two companies hope they can develop a first-in-class immunotherapy with potentially higher response rates.
“We may find a very good application of this combination for different types of solid tumor, such as lung cancer, breast cancer and liver cancer,” he said, adding that the two drug candidates can create synergy.
Shao also revealed to BioWorld that both companies aim to move this combination approach into clinical development in 2021, potentially in multiple countries, including China and the U.S.
Chinese biotechs have started to look beyond PD-1/PD-L1 antibodies as monotherapies, as the country has approved six of them so far and the craze for them has cooled down.
“PD-1/PD-L1 antibodies as monotherapy is the first-generation approach. Right now, people are working on the second generation, such as bispecific antibodies, in order to improve the response rate for different tumor types,” he added.
According to Yisheng, YS-ON-001 and YS-ON-002 have demonstrated promising effects in activating the innate and adaptive immune systems and modulating the tumor microenvironment. They can reduce the immunosuppressive effects of tumor microenvironments and enhance antitumor immune responses.
Currently in a phase I trial in China and Singapore, YS-ON-001 has shown a good safety profile to date. It also received orphan drug designations from the FDA for the treatment of pancreatic and liver cancers. The drug candidate can be delivered via intramuscular, subcutaneous or intratumoral injection.
In preclinical studies, YS-ON-001 was found to significantly increase the proportion of natural killer and natural killer T cells in addition to increasing CD4+ and CD8+ T-cell responses. The drug candidate also reduced the number of T regulatory cells and myeloid-derived suppressor cells in some tumor models.
Meanwhile, YS-ON-002 is in the IND-ready stage. It was found to significantly enhance the expression levels of PD-L1 in tumor cells, proving the rationale for combination therapy with PD-1 antibodies.
Yisheng has said it believes that YS-ON-001/002 could prove to be integral immunotherapy components of standard oncology care, joining other therapies such as chemotherapies, targeted therapies and checkpoint inhibitors or emerging immunotherapies for additive or synergistic treatment benefits.
Both compounds were developed using the company’s PIKA immunomodulating technology, which augments both innate and adaptive immune responses through the TLR3, RIG-I and MDA5 pathways. Through TLR3, RIG-I and MDA-5 signaling, PIKA technology can enable the prompt production of interferon, cytokines, chemokines and co-stimulatory factors. Producing type I interferon using PIKA administration can facilitate antigen cross-presentation by dendritic cells, while augmenting CD4+ T-cell, CD8+ T-cell and natural killer cell responses. That makes PIKA-based therapeutics suitable for both antiviral and antitumor applications.
“Our PIKA technology platform has achieved proof-of-concept results in phase I and phase II trials. It has demonstrated a good result in activating human immune system in clinical trials,” Shao said.
He revealed to BioWorld that in the company’s immune-oncology pipeline, a third drug candidate is being developed to target human papillomavirus-induced cancer.
What is intriguing is that Yisheng is better known as a vaccine maker, with four known assets in its vaccine pipeline.
Using the same PIKA technology platform, Yisheng has developed hepatitis B vaccine YS-HBV-001 and the PIKA rabies vaccine for accelerated protection against rabies infection.
Its most advanced asset is the YSJA rabies vaccine, which has been marketed already. It is also developing YS-HBV-002 for chronic hepatitis B treatment.
Its new U.S. partner, Tavotek, however, has kept a lower profile, with an undisclosed pipeline. It is known for extensive work on multispecific antibodies and advanced technology platforms with a focus on cancers, autoimmune conditions and infectious diseases.
Its Tavoselect platform, which the company used to develop Tavo-301/303, is designed to offer highly diversified human antibody sequences that can be utilized in different formats, such as multispecific antibodies. It is said to be able to capture and optimize the best candidates rapidly with NGS analyses and AI.
Tavotek also has three technology platforms for biologics, namely the Targeted Biologics Engineering Platform to develop monoclonal and multispecific antibodies against unique targets; the Tavo-Immune Modulator Platform to enable novel synthetic biologic design for auto-immune diseases and chronic viral infections; and the Multicyclic Intracellular Peptide Platform to develop unique multicyclic peptides with great potency targeting intracellular protein-protein interactions.
The partnership with Yisheng is the first that the U.S. biotech has unveiled, and the collaboration could go beyond oncology.