Junshi Biosciences Announces Updated Clinical data from Phase I study of anti-BTLA antibody Tifcemalimab in Treatment of Relapsed/Refractory Lymphomas at 64th ASH Annual Meeting

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— Preliminary study results show that tifcemalimab is well-tolerated at all administered doses. Additional research is needed to confirm the clinical activity observed in patients with lymphoma refractory against checkpoint inhibitors using tifcemalimab and toripalimab. The expansion of the combination dose is underway.

— Among the 28 evaluable patients who received the combination regimen, while 85.7% of the patients progressed upon prior anti-PD-1, 39.3% achieved ORR, and median DoR has not yet been reached.

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SHANGHAI, China, Dec. 10, 2022 (GLOBE NEWSWIRE) — Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences”, HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to The discovery, development, and commercialization of novel therapies, announced today that the updated preliminary data from a Phase I study of tifcemalimab as a single agent or in combination with toripalimab in relapsed/refractory lymphomas in a poster at the 64^th Annual Meeting of the American Society of Hematology. Tifcemalimab is the world’s first-in-human anti-tumor anti-BTLA monoclonal antibody independently developed by the company.

“Nowadays, PD-1 inhibitors are widely used in the treatment of lymphomas, particularly relapsed or refractory classical Hodgkin’s lymphoma (R/R cHL),” said Dr. Yuqin Song of Peking University Cancer Hospital and Institute. “However, if PD-1 inhibitors fail, there is no standard treatment to resort to, thus new treatment methods are urgently needed in clinical practice. These patients will benefit again if they are treated with toripalimab and tifcemalimab. We’ve also observed a similar advantage in this treatment method as well as other immune checkpoint inhibitors—both may bring long-term survival benefits to patients. As the clinical trials continue, we look forward to observing tifcemalimab’s performance and the new treatment options it can bring to more lymphoma patients.”

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“The first of its kind in the entire world, tifcemalimab exhibits promising safety and efficacy in early clinical trials,” said Dr. Jianjun Zou, Global Research and Development President at Junshi Biosciences. “In particular, the updated research data released at the ASH Annual Meeting highlights that the tifcemalimab-toripalimab dual immunotherapy is promising for patients with relapsed/refractory lymphoma resistant to anti-PD-1 monoclonal antibodies, and is worth further evaluation. Apart from that, we’ve also seen its outstanding safety and efficacy in patients with solid tumors, and are eager for further verification in subsequent research.”

The single-arm, open label, multicenter dose-escalation phase 1 study (NCT0447772) evaluates safety and efficacy in treating relapsed/refractory lymphomas with tifcemalimab alone or in combination. This is the first time anti-BTLA antibodies have been evaluated for their safety and efficacy in treating lymphomas. Earlier this year, tifcemalimab was presented with preliminary data from clinical trials at ASCO’s annual meeting. This is a significant milestone for all BTLA targeting drugs in the cancer field. At the ASH annual meeting, the latest results from the lymphoma clinical trial have been presented. Dr. Jun Ma, Harbin Institute of Hematology and Oncology, and Dr. Jun Zhu, Peking University Cancer Hospital and Institute are the principal investigators of this study. Dr. Yuqin Song is the presenting author.

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By the cutoff date of October 26, 2022, a total of 63 patients with relapsed/refractory lymphoma were enrolled in the study, including 43 patients with Hodgkin’s lymphoma (HL) and 20 with non-Hodgkin’s lymphoma (NHL). The monotherapy treatment received by the 25 patients was monotherapy. 9 patients received monotherapy dose elevation and 16 received monotherapy expansion. Of the 38 patients who received combination therapy, 6 received combination dosage escalation while 32 received combination expansion. Patients received a median of 4 lines of therapy before they were referred to us. 46 patients (73.0%), received anti-PD-1L1 therapy prior to diagnosis.

Safety and tolerability were both good with combination dose escalation monotherapy. In addition, the combination had an immune related adverse event profile (irAE), which was consistent with monotherapy toripalimab. There were no new safety signs in combination cohorts.

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Regarding clinical anti-tumor activity, as of October 26, 2022, the median follow-up was 29.1 weeks, 1 case of partial remission (PR) and 7 cases of stable disease (SD) were observed among the 25 evaluable patients receiving monotherapy. 24 (85.7%) of 28 evaluable patient received the combination regimen. One complete response, 10 PR and 13 SD were all observed. The objective response rate (ORR), was 39.3%. The disease control rate (DCR), was 85.7%. All patients who received CR/PR responses in combination groups are still active at the cutoff date. The median duration of response (DoR), is not yet reached.

Tifcemalimab (JS004/TAB004)
Tifcemalimab is the world’s first-in-human recombinant humanized anti-BTLA (B- and T-lymphocyte attenuator) monoclonal antibody independently developed by Junshi Biosciences. Currently, tifcemalimab is in phase Ib/II. There are also ongoing trials in China of tifcemalimab combined with toripalimab in patients suffering from different types of cancers.

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2003 was the year that B and T lymphocyte antagonist (BTLA) was identified as the target for tifcemalimab. It belongs to the CD28 receptor family. It is composed of a single IgSF V extracellular region; it sequences similarly to other molecules within the CD28 family (such PD-1 and CTLA-4).

BTLA is found in subpopulations of T lymphocyte, B lymphocyte, and dendritic cells. 2005 was the year that BTLA and HVEM, its ligand (Herpes virus entry mediator), were discovered. HVEM, a TNF receptor that is abundantly expressed in the hematopoietic systems, has been confirmed to be the ligand for BTLA.

BTLA is an immunoglobulin associating membrane protein. Its protein structure is identical to those of the transmembrane regulators (CTLA-4, PD-1). Normal physiological conditions allow BTLA to bind with HVEM and inhibit the activation of lymphocytes in humans. This prevents autoimmune injuries.

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Tifcemalimab binds to BTLA and blocks HVEM-BTLA interactions, activating tumor specific lymphocytes and preventing the BTLA mediated inhibitory signal pathways.

Tifcemalimab blocks the HVEM/BTLA interaction by binding with BTLA. This inhibits the inhibitory signal pathway mediated through BTLA. It activates tumor-specific lymphocytes.

Junshi Biosciences
Junshi Biosciences was founded in December 2012. The company has established a diversified R&D pipeline comprising over 50 drug candidates, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences, a Chinese pharmaceutical company, was the first to obtain marketing approval in China for anti-PD-1 monoclonal antibodies. Its first-inhuman anti-BTLA monoclonal monoclonal antibody against various cancers was approved by the FDA and NMPA. Since then, it has entered Phase Ib/II trials both in China and the USA. Its anti-PCSK9 monoclonal antibody was the first in China to be approved for clinical trials by the NMPA.

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In the face of the pandemic, Junshi Biosciences’ response was strong and immediate, joining forces with Chinese and international scientific research institutions and enterprises to develop an arsenal of drug candidates to combat COVID-19, taking the initiative to shoulder the social responsibility of Chinese pharmaceutical companies by prioritizing and accelerating COVID-19 R&D. Among the many drug candidates is JS016 (etesevimab), China’s first neutralizing fully human monoclonal antibody against SARS-CoV-2 and the result of the combined efforts of Junshi Biosciences, the Institute of Microbiology of the Chinese Academy of Science and Lilly. JS016 containing bamlanivimab received Emergency Use Authorizations (“EUAs) in more than 15 countries. VV116, an oral nucleoside analog anti SARS-CoV-2 drug, is now in global Phase III clinical trials. The JS016 and VV116 programs are a part of the company’s continuous innovation for disease control and prevention of the global pandemic.

Junshi Biosciences employs over 3,100 people in the United States (San Francisco & Maryland) as well as China (Shanghai Suzhou Beijing Guangzhou). Visit: http://junshipharma.com.

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