On January 10, 2022 Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) and Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences", HKEX: 1877; SSE: 688180) reported that Coherus has initiated the process to exercise its option to license JS006, Junshi Biosciences’ TIGIT-targeted antibody, in the United States and Canada, expanding the companies’ 2021 immuno-oncology collaboration agreement (Press release, Coherus Biosciences, JAN 10, 2022, View Source [SID1234598512]). Coherus will pay Junshi Biosciences $35 million upfront, up to $255 million in development regulatory and sales milestones, and an 18% royalty on net product revenue, subject to terms and conditions agreed between the parties. Closing of the transaction is expected to follow receipt of any applicable regulatory clearances. Antibodies blocking TIGIT (T cell immunoglobulin and ITIM domain) have shown potential for synergistic anti-tumor activity in combination with PD-1/PD-L1 inhibitors. In pre-clinical studies, JS006 has demonstrated excellent binding affinity and strong inhibition of the TIGIT pathway. Investigational new drug (IND) applications allowing clinical development of JS006 have been approved in Chinese Mainland and in the United States. A dose escalation, dose expansion clinical trial (NCT05061628) evaluating the safety, tolerability and pharmacokinetic properties of JS006 as monotherapy and in combination with PD-1 inhibitor toripalimab in patients with advanced solid tumors is ongoing.
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"TIGIT is a leading-edge immuno-oncology target with significant therapeutic potential across multiple major tumor types. The exercise of the option for JS006 marks the emergence of Coherus as an immuno-oncology development company with a rich clinical and preclinical pipeline of product candidates to drive long-term growth," said Denny Lanfear, CEO of Coherus. "We are making rapid progress on our objective to become a leading immuno-oncology company, and the development of toripalimab combinations with therapeutics addressing novel targets such as TIGIT will allow us to access future growing markets. While toripalimab + JS006 is the first novel combination in our pipeline, our internal analytic, protein science and bioinformatics capabilities have generated additional toripalimab combination candidates. The first of these proprietary product candidates is expected to enter human clinical trials in 2023."
"Blockade of the TIGIT pathway may be a crucial underlying mechanism for overcoming resistance to checkpoint inhibition. We believe the dual immuno-therapy approach of TIGIT with PD-1 could enhance PD-1 efficacy and create a new standard-of-care for multiple tumor types," said Theresa LaVallee, Ph.D., Chief Development Officer at Coherus. "We recently reported that our PD-1 inhibitor, toripalimab, in combination with chemotherapy, extends both progression free survival and overall survival in patients with advanced non-small cell lung cancer. We look forward to working with our Junshi Biosciences colleagues to build upon this efficacy signal and to evaluate the potential of the JS006 and toripalimab combination to bring new, more efficacious immuno-oncology treatments forward for patients."
"We are excited to extend our productive immuno-oncology collaboration with Coherus to include our anti-TIGIT monoclonal antibody JS006, after achieving several key milestones on toripalimab," said Dr. Ning Li, CEO of Junshi Biosciences. "Following our ‘In China, For Global’ corporate strategy, we are actively conducting global clinical R&D programs in China, the U.S., Southeast Asia and European countries. We are grateful for the joint effort from our pre-clinical as well as clinical teams at the company’s innovation centers in China and the U.S. We believe the collaboration with Coherus will strengthen the development and commercialization of our products in the U.S. and Canada."
"Since 2012, Junshi Biosciences has built a rich pipeline with complementary products in the area of immuno-oncology, which enable us to explore combination therapy of I-O drugs and combination of immunotherapy with other modalities, including traditional chemotherapy, radiotherapy, angiogenesis inhibitors and cytokine drugs, to provide patients with better treatment options," said Dr. Sheng Yao, Senior Vice President of Junshi Biosciences. "The combination of anti-TIGIT and anti-PD-1 is quite promising with a potential to not only increase patients’ response to I-O therapy, but also expand the beneficial patient population. We look forward to working together with Coherus to quickly advance the combination therapy of JS006 with toripalimab across multiple tumor types."
About JS006
JS006 is a recombinant humanized IgG4κ monoclonal antibody specifically against human TIGIT, developed independently by Junshi Biosciences. Including back-up candidates, the JS006 program encompasses molecules with silent and active Fc functions. According to the results of preclinical studies, JS006 can specifically block the TIGIT-PVR pathway. Expressed by T cells and NK cells, TIGIT can be engaged and activated by PVR family ligands highly expressed on tumor cells and suppressive immune cells to directly inhibit the killing effect of T cells and NK cells directed at tumor cells. A number of pre-clinical and clinical studies have showed that activation of the TIGIT pathway could be a crucial underlying mechanism for the resistance to PD-1 blockade therapy. Combination of TIGIT and PD-1/PD-L1 antibodies showed a synergistic potential to enhance antitumor response to overcome anti-PD-1 resistance and broaden the cancer patient population that can benefit from immunotherapy.
In early 2021, JS006 was approved for clinical trials in both China and the United States. In the same year, Junshi Biosciences commenced a phase I trial to evaluate the safety and tolerability of JS006 as monotherapy and in combination with toripalimab in patients with advanced tumors who have failed standard therapies. Coherus and Junshi Biosciences are planning late-stage clinical development of JS006 in combination with toripalimab in North America.
About toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promote the immune system’s ability to attack and kill tumor cells.
More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.
In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are 4 approved indications for toripalimab in China:
unresectable or metastatic melanoma after failure of standard systemic therapy;
recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy;
locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC.
The first three indications have been included in the National Reimbursement Drug List (NRDL) (2021 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for melanoma and NPC.
In addition, two supplemental New Drug Applications (NDAs) for toripalimab are currently under review by the National Medical Products Administration (NMPA) in China:
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC).
in combination with chemotherapy as the first-line treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) with no EGFR or ALK sensitizing mutations.
In the United States, the FDA has granted priority review for the toripalimab biologics license application (BLA) for the treatment of recurrent or metastatic NPC, an aggressive head and neck tumor which has no FDA-approved immuno-oncology treatment options. The FDA has assigned a Prescription Drug User Fee Act target action date for April 2022 for the toripalimab BLA. The FDA granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC in 2021 as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC in 2020. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and orphan drug designation for the treatment of esophageal cancer, NPC, mucosal melanoma and soft tissue sarcoma. In 2021, Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple other cancer types.