Toripalimab

– Casdozokitug, in combination with atezolizumab/bevacizumab, final data demonstrate durability of response and improvement in depth of response including a 17.2% complete response rate – – Antitumor activity was observed across both viral and non-viral etiologies – – Data support continued evaluation of casdozokitug with VEGF and PD-(L)1 blockade in HCC – – Randomized Phase 2 trial evaluating casdozokitug/bevacizumab/toripalimab now open for enrollment – REDWOOD CITY, CA, USA I January 22, 2025 I Coherus BioSciences, Inc. (Coherus, NASDAQ: CHRS), today announced final data from its Phase 2 open label clinical trial evaluating casdozokitug (casdozo), a selective and potent Interleukin (IL)-27-targeting antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC). These data are being presented at the 2025 ASCO Gastrointestinal Cancers Symposium taking place January 23-25, 2025, in San Francisco, California. These data showed an overall response rate of 38% compared to initially announced 27% 1 , and complete responses (CR) per RECIST v1.1 increased to 17.2% compared to previously announced 10.3% 2 and initial assessment of 0% 1 , demonstrating both an increase in ORR and a deepening of responses compared to previous datasets. Importantly, responses were seen in viral and nonviral disease, and toxicity was consistent with the known safety profiles of atezolizumab and bevacizumab, with no new safety signals identified. These data support continued evaluation of casdozo with other therapies, including a trial of casdozo/toripalimab (tori)/bev in HCC, which Coherus has now opened for enrollment. Casdozo is a first-in-class antibody, and the only clinical-stage immunomodulatory cytokine antagonist targeting IL-27, an immunoregulatory cytokine involved in suppressing anti-tumor immune responses and an important new target for cancer treatment. “The casdozo data in HCC demonstrate translation of the preclinical data in liver cancer to first-line HCC cancer patients with efficacy and a favorable safety profile. These data support the ongoing development of IL-27 as a promising novel target for advanced solid tumors,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “We recently opened enrollment for our randomized, controlled, multinational Phase 2 trial of casdozo in combination with toripalimab, our anti-PD-1 antibody, plus bev. The combination of tori plus bev has demonstrated promising Phase 3 results in HCC 3 , and we believe the addition of casdozo may further enhance anti-tumor effects and advance our next-generation immuno-oncology combinations focused on overcoming immune suppression in the tumor microenvironment.” “The treatment landscape for liver cancer, particularly for patients who are not eligible for surgery or who are metastatic, has improved in recent years thanks to immunotherapy combinations. However, there is still a clear unmet need for novel treatment options that can further improve survival without added toxicity,” said Daneng Li, M.D., Associate Professor in the Department of Medical Oncology & Therapeutics Research and Co-Director, Liver Cancer Collaborative Program, City of Hope Comprehensive Cancer Center. “These final casdozo data continue to be encouraging and compare very favorably in the current treatment landscape, and speak to the potential for its novel anti-IL-27 mechanism to address these substantial unmet needs.” Results from Phase 2 trial evaluating casdozo/atezo/bev combination in HCC This open-label Phase 2 clinical trial evaluated casdozo in combination with atezo and bev in 30 treatment-naïve patients with unresectable locally advanced or metastatic HCC. Patients received casdozokitug 10 mg/kg IV q3w in combination with atezolizumab (1200 mg) and bevacizumab (15 mg/kg). The primary endpoint was safety and tolerability. Key secondary endpoints included PFS and ORR based on investigator review per RECIST v1.1 (primary) and mRECIST (secondary), as well as disease control rate (DCR). As of the data cutoff date of September 4, 2024: Triplet blockade of the IL-27, PD-(L)1 and VEGF inhibitors with casdozo/atezo/bev demonstrated an acceptable safety profile with promising antitumor activity in immunotherapy naïve HCC. These results support continued evaluation of casdozo with VEGF and PD-(L)1 blockade in HCC. Recent Launch of New Phase 2 trial evaluating casdozo in combination with bev and toripalimab Coherus has initiated a new randomized Phase 2 study ( NCT06679985 ) evaluating casdozo, in combination with bev and tori, Coherus’ next-generation anti-PD-1 monoclonal antibody, in participants with unresectable locally advanced or metastatic HCC. This randomized, parallel, open-label Phase 2 study is designed to evaluate the safety, efficacy, and Project Optimus 4 dosing of the triplet combination. The study is expected to enroll up to 72 patients, who will be randomized to receive one of two biologically active doses of casdozo with tori plus bev or tori plus bev without casdozo. ASCO-GI 2025 Presentation Details Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC) Lead Author: Daneng Li, City of Hope National Comprehensive Cancer Center Abstract 605 : Poster Board #D6 Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract Date and Time: Friday, January 24, 2025; 11:30am – 1:00pm PT About Hepatocellular Carcinoma Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma; HCC), gall bladder, and bile ducts (collectively called biliary tract cancers). The most common type of primary liver cancer in adults is HCC (accounting for ~90%), which is the third leading cause of cancer-related deaths worldwide. According to the NCI Surveillance, Epidemiology and End Results Program (SEER), there will be an estimated 41,630 new cases and 29,840 deaths from liver and intrahepatic bile duct cancer in the US in 2024. 5 The U.S. 5-year relative survival rate for liver and intrahepatic bile duct cancer is 21.7%. 5 The liver cancer treatment pattern has changed in recent years with the emergence of immunotherapy combinations and will continue to evolve as more treatment options become available for these highly lethal cancers. About Casdozokitug Casdozokitug is a first-in-class human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Particular tumor types have been identified where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. Blocking IL-27 with casdozokitug in clinical trials has led to monotherapy tumor growth inhibition and partial responses in patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) (NCT04374877). An ongoing trial is studying combinations with PD-(L)1 pathway blockade in NSCLC, and a planned clinical trial will study the triplet combination of IL-27, PD-(L)1, and VEGF pathway blockade in HCC. Casdozokitug has been granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA. It is the first IL-27 antibody to enter the clinic. About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that is expected to be synergistic with its proven commercial capabilities in oncology. Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust antitumor immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel IL-27 antagonistic antibody currently being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors, including HNSCC. CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). An IND for CHS-1000 was allowed to proceed by the FDA in the second quarter of 2024 and proceeding to the first-in-human clinical study is subject to further evaluation in Coherus’ portfolio prioritization process. Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, and UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta. In December 2024, Coherus announced the planned divestiture of its UDENYCA franchise. The transaction is expected to close by the end of the first quarter of 2025. References 1 Coherus to Acquire Surface Oncology (2023, June 16) [ Press Release ] 2 Daneng Li et al., JCO 42, 470-470(2024). 3 Yinghong S, et al. Oral presentation at: CSCO 2024; September 27, 2024; Xiamen, China. 4 Project Optimus: Reforming the dose optimization and dose selection paradigm in oncology 5 National Cancer Institute Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer; retrieved December 17, 2024, from https://seer.cancer.gov/statfacts/html/livibd.html SOURCE: Coherus Biosciences

LEO Pharma will be gaining the rights to commercialise Junshi Biosciences’ toripalimab in Europe under a new distribution and marketing partnership. The collaboration is aimed at increasing the accessibility of the PD-1 inhibitor, which is designed to help the immune system fight cancer. The drug, sold under the brand name Loqtorz, was approved by the European Commission (EC) and Medicines and Healthcare Products Regulatory Agency (MHRA) last year as part of a first-line combination treatment for certain adults with recurrent or metastatic nasopharyngeal carcinoma. More than 120,434 new cases of the rare form of cancer, which affects the part of the throat connecting the back of the nose to the back of the mouth, were reported globally in 2022. Toripalimab was also approved by both regulators in 2024 as part of a first-line combination treatment for adults with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma. LEO will now be responsible for toripalimab’s distribution, promotion and sales in all EU and European Economic Area member states, as well the UK and Switzerland. TopAlliance Biosciences Europe will remain the marketing authorisation holder for toripalimab in Europe and will receive an upfront fee from LEO. The Junshi subsidiary will also be eligible for milestone payments if LEO wants to pursue any subsequently approved indications for the drug. Jean Monin, executive vice president of LEO’s thrombosis business unit at LEO, said: “The distribution and marketing partnership for [toripalimab] brings an important new treatment option to areas of high unmet medical need and focuses on a specialty hospital product that complement our existing heparin-based anti-coagulation treatments for cancer-associated thrombosis and other specialty patients.” Sheng YAO, senior vice president of Junshi Biosciences and chief executive officer of TopAlliance Biosciences, added: “By leveraging both parties’ strengths in research and development, manufacturing and commercialisation, we believe toripalimab will be efficiently integrated into the Europe markets benefitting local patients-in-need.” The agreement comes less than two weeks after LEO partnered with Gilead Sciences to advance its small molecule oral STAT6 programme for inflammatory diseases. The deal, worth $1.7bn, gave Gilead global rights to develop, manufacture and commercialise the oral STAT6 programme. Meanwhile, LEO will hold exclusive global rights to STAT6 topical formulations in dermatology, and will have the option to co-commercialise oral programmes for dermatology indications outside the US.