Metastatic Clear Cell Renal Cell Carcinoma

RMAT Designation Follows Positive Proof-of-Concept Data from the ALLO-316 TRAVERSE Trial in Adult Patients with Advanced or Metastatic CD70 Positive Renal Cell Carcinoma (RCC) Who Received Prior Immune Checkpoint Inhibitor and VEGF-Targeting Therapy ALLO-316 Advances Scientific Understanding and Applicability of the Dagger® Technology as the Next-Generation Allogeneic Platform to Maximize the Potential of a Single Infusion of an “Off-the-Shelf” CAR T Product Company to Present Updated Phase 1 Data from the TRAVERSE Trial at the Society for Immunotherapy of Cancer (SITC) Annual Meeting ALLO-316 was Previously Granted Fast Track Designation (FTD) in March 2022 by the U.S. Food and Drug Administration Oct. 29, 2024 -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer and autoimmune disease, today announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-316 for the treatment of adult patients with CD70 positive advanced or metastatic renal cell carcinoma (RCC). The RMAT designation was based on clinical data from the TRAVERSE trial indicating the potential of ALLO-316 to address the unmet need for patients with difficult-to-treat RCC who have failed multiple standard RCC therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy. The ongoing development of ALLO-316 continues to advance the scientific understanding and applicability of the Dagger® technology as the next-generation allogeneic platform to maximize the potential of a single infusion of “off-the-shelf” CAR T product in solid tumors. “The RMAT designation for ALLO-316 highlights the transformative potential of our AlloCAR T™ platform to offer new hope for heavily pretreated patients with renal cell carcinoma who have exhausted standard treatment options,” said Zachary Roberts, M.D., Ph.D., Executive Vice President of Research & Development and Chief Medical Officer. “This important milestone moves us closer to fulfilling the promise of “off-the-shelf” CAR T therapy—delivering faster, more reliable, and widely accessible treatments. We remain optimistic about the future of ALLO-316 and its potential to be an important advancement for patients.” The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic RCC. Initial results from the TRAVERSE trial were presented in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida, in 2023. The Company will present updated Phase 1 data from the TRAVERSE trial at the Society for Immunotherapy of Cancer (SITC) annual meeting. The RMAT designation is intended to accelerate the development and review of promising investigational products, including cell therapies. To qualify, a product must be designed to treat, modify, reverse, or cure a serious or life-threatening disease, with preliminary clinical evidence suggesting it can address unmet medical needs. The RMAT designation offers several key advantages, including early and frequent interactions with the FDA to discuss potential surrogate or intermediate endpoints, as well as strategies to meet post-approval requirements, potentially streamlining the path to market approval. ALLO-316, an AlloCAR T™ investigational product, targets CD70 which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. ALLO-316 utilizes the Dagger® technology to optimize CAR T cell expansion and persistence to maximize the potential efficacy in solid tumors with a one-time infusion. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In March 2022, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation (FTD) to ALLO-316, and in October 2024 the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-316 based on its potential to address the unmet need for adult patients with CD70 positive advanced or metastatic RCC who have failed standard RCC therapies. Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on X and LinkedIn. 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Objective response rate of 34% (2 responses pending confirmation) and 25% (confirmed) in the 100mg daily dose expansion cohort (n=32) of ARC-20, a Phase 1/1b study of casdatifan in metastatic clear cell renal cell carcinoma (ccRCC) Low rate of primary progression (19%) and high rate of disease control (81%) was observed in the 100mg expansion cohort with many of those patients still on treatment Arcus will host a conference call to discuss these results, including results from the 50mg expansion cohort, at 5:00 AM PT / 8:00 AM ET today HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, today presented the first clinical activity data for casdatifan, a HIF-2a inhibitor with best-in-class potential, in an oral plenary session by Dr. Toni K. Choueiri, Dana-Farber Cancer Institute at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. “Based on our experience in the ARC-20 study, we have seen casdatifan’s ability to quickly bring tumor growth under control and its high response and disease control rates,” said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber, the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School and lead investigator of ARC-20. “Based on these data, casdatifan has the potential to be a future treatment option for kidney cancer. I am particularly interested in planned research into novel combinations for casdatifan in both first- and second-line ccRCC.” “In the 100mg daily dose-expansion cohort of ARC-20, casdatifan showed encouraging results, particularly a low primary progressive disease rate and very durable responses. This was accomplished with a manageable safety profile,” said Dimitry Nuyten, M.D., Ph.D., chief medical officer of Arcus. “These data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC. We look forward to initiating our first Phase 3 study for casdatifan, PEAK-1, in the first half of 2025, and expanding our development program into the first-line setting with a novel combination, as well as into other ccRCC subpopulations.” ARC-20 is a Phase 1/1b dose-escalation and -expansion study. In the dose escalation (20mg to 200mg) portion of the study, the safety pro comparable across the doses; there were no dose-limiting toxicities, and the maximum tolerated dose was not reached at daily doses of up to 150 mg (200 mg portion of the study is currently ongoing). The 100 mg daily dose (50 mg BID [twice daily]) was selected for dose expansion, and casdatifan was evaluated in patients with metastatic ccRCC who had progressed on at least two prior lines of therapy, including both an anti-PD-1 and a tyrosine kinase inhibitor (TKI) therapy (n=33). The patient population was heavily pre-treated: 52% had received at least three prior lines of therapy; 26% had received at least four prior lines of therapy; and 61% had an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor of intermediate. At the time of data cut off (DCO, Aug. 30, 2024), median follow-up was 11 months. Casdatifan showed a rapid time to response, and only 19% of patients had primary progressive disease (progressed at or before their first disease assessment). The majority of patients (81%) experienced disease control with either a partial response or stable disease. At the time of the DCO, the median progression-free survival had not been reached. 34% of patients experienced an objective response, meaning their tumor shrank by at least 30%. A summary of initial results is below. Objective Response Rate (ORR) per RECIST v1.1 100mg Efficacy-Evaluable* Population (n=32) ORR [95% CI] 34% (11)** [16,50] Responses Pending Confirmation 2** Confirmed ORR [95% CI] 25% (8) [12,43] Progressive Disease 19% (6) Disease Control Rate [95% CI] 81% [64,93] Median Progression-Free Survival Not Reached CI=confidence interval *100mg daily dose is 50mg BID (twice daily); efficacy-evaluable population for this expansion cohort is defined as all eligible participants who have measurable disease at baseline, receive at least one dose of casdatifan, and have at least one post-baseline efficacy assessment, or who discontinue study treatment due to progressive disease or death. One participant was enrolled but deemed not eligible for the study and was not evaluated for efficacy. **One patient achieved a response after DCO and nearly a year on treatment, which increased the ORR from 31% (10) to 34%. In the 100mg dose-expansion cohort, no unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile. Grade 3 treatment-emergent adverse events (TEAEs) related to casdatifan were 42%, including anemia (36%) and hypoxia (9%). No patients discontinued treatment from anemia. No TEAEs were life-threatening or led to death. Arcus is pursuing a broad development program in both the first-line and post-anti-PD-1 settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. In addition to the monotherapy cohorts of ARC-20, the study is also enrolling a cohort to evaluate casdatifan in combination with cabozantinib, a VEGFR TKI which is intended to support the initiation of Arcus’s planned first Phase 3 study, PEAK-1, evaluating casdatifan in combination with cabozantinib versus cabozantinib monotherapy in patients with metastatic ccRCC who have previously received anti-PD-1 therapy. The primary endpoint will be progression-free survival with a key secondary endpoint of overall survival. Arcus also recently announced a clinical collaboration as part of its first-line strategy in advanced ccRCC to evaluate casdatifan in combination with volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody. Investors may dial in to the conference call at +1 (404) 975- 4839 (local) or +1 (833) 470-1428 (toll-free), using Conference ID: 595409 on Thursday, October 24, 2024 at 5:00 AM PT / 8:00 AM ET. Participants may also register for the call online using the following link: . In addition to the ARC-20 data, the conference call will address the development strategy and market potential for casdatifan. Arcus will also be joined by Dr. Rana McKay of the University of California San Diego. To access the live webcast and accompanying slide presentation, please visit the “Investors & Media” section of the Arcus Biosciences website at . A replay will be available following the live event. About Casdatifan (AB521) Casdatifan is a small-molecule inhibitor of HIF-2a, a tumorigenic transcription factor involved in oxygen sensing in multiple organs as well as in tumors. Clear cell RCC is almost universally associated with HIF-2a dysregulation as a result of genetic abnormalities in the VHL pathway. This creates a situation of pseudohypoxia and the abnormal increase in HIF-2a-mediated expression of a broad range of oncogenic proteins. By selectively inhibiting HIF-2a, casdatifan is designed to disable a wide array of pathways involved in tumor proliferation and survival, treatment resistance and angiogenesis, leading to cancer cell death. Casdatifan is being evaluated in ARC-20, a Phase 1/1b study in cancer patients, and STELLAR-009, a Phase 1b/2 study in combination with zanzalintinib in patients with advanced solid tumors, including ccRCC. Under the Gilead and Arcus collaboration agreement, Gilead has the right to opt-in to development and commercialization for casdatifan after Arcus’s delivery of a qualifying data package. Casdatifan is an investigational molecule. Approval from any regulatory authority for its use has not been received, and its safety and efficacy have not been established. About RCC According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 81,600 Americans will be diagnosed with kidney cancer in 2024. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 15%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination medicines for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has expedited the development of multiple investigational medicines into clinical studies, including new combination approaches that target TIGIT, PD-1, HIF-2a, CD73, dual A2a/A2b receptor, CD39, and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . Forward Looking Statements This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the statements in Dr. Nuyten’s and Dr. Choueiri’s quotes and statements regarding: the potency, efficacy or safety of casdatifan, including its potential for a best-in-class profile; casdatifan’s safety profile; ability for casdatifan to be used in first-line therapy; how data from ARC-20 will support or advance Arcus’s development program for casdatifan, including plans for future development; plans to initiate a new Phase 3 study with casdatifan, including timing for initiating any such study; and combinations that Arcus plans to explore in future studies. All forward-looking statements involve known and unknown risks and uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to risks associated with: interim data not being replicated in future studies evaluating the same investigational molecules or regimen; the unexpected emergence of adverse events or other undesirable side effects in Arcus’s investigational products; risks associated with manufacturing or supplying product for such clinical trials; uncertainties in timelines associated with the conduct of clinical studies and with respect to the regulatory application process; difficulties associated with the management of the collaboration activities with our strategic partners or expanded clinical programs; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. Risks and uncertainties facing Arcus are described more fully in the “Risk Factors” section of Arcus’s most recent periodic report filed with the U.S. Securities and Exchange Commission. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Arcus disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release except to the extent required by law. The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners. Contacts Investor Inquiries: Pia Eaves VP of Investor Relations & Strategy (617) 459-2006 peaves@arcusbio.com Media Inquiries: Holli Kolkey VP of Corporate Communications (650) 922-1269 hkolkey@arcusbio.com

SHANGHAI, Oct. 15, 2024 (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, and its wholly-owned subsidiary, TopAlliance Biosciences Inc. (TopAlliance Biosciences), announce that toripalimab (Indian trade name: ZYTORVI®, Hong Kong trade name: LOQTORZI®) has been approved for marketing in India and China’s Hong Kong Special Administrative Region (“SAR”), for treatment of recurrent or metastatic nasopharyngeal carcinoma (“NPC”). The approved indications are: 1) toripalimab in combination with cisplatin and gemcitabine, for first line treatment of adults with metastatic or with recurrent, locally advanced NPC; 2) toripalimab as a single agent, for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy. Zytorvi® shall be imported and commercialized in India by Dr. Reddy’s Laboratories Ltd. Dr. Jianjun ZOU, General Manager and CEO of Junshi Biosciences, said, “As of now, toripalimab has been approved for marketing in over 30 countries and regions across three continents worldwide. With its differentiated clinical layout and outstanding clinical performance, it has brought a new treatment that can change the therapeutic landscape to local doctors and patients, which we are very excited about. Moving forward, we will continue to implement the company's international strategy of ‘In China, For Global’ and work with partners to provide more overseas patients with high-quality innovative drugs from China.” NPC is a malignant tumor that occurs in the epithelium of the nasopharynx. According to GLOBOCAN 2022 statistics, the number of newly diagnosed NPC cases in 2022 exceeded 120,000 worldwide. Due to the location of the primary tumor, surgery is rarely an option. Toripalimab is the first and only treatment for NPC approved in India and China’s Hong Kong SAR. The marketing approvals are supported by results from JUPITER-02, a randomized, double-blind, placebo-controlled, multinational multi-center Phase 3 clinical study (NCT03581786) that examined toripalimab in combination with gemcitabine-cisplatin as the first-line treatment of NPC, as well as results from POLARIS-02, a multi-center, open-label, pivotal Phase 2 clinical study (NCT02915432) that evaluated toripalimab as the second-line or later treatment for recurrent or metastatic NPC. The JUPITER-02 study is the first international multi-center, double-blind, randomized Phase III clinical study in the field of immunotherapy for NPC with the largest sample size, and the world’s first Phase III clinical study with preset statistical verification (Type I error control) for Overall Survival (“OS”) for first-line immunotherapy combined with chemotherapy for NPC compared to chemotherapy alone and demonstrated a survival benefit. The study results were presented in an oral report during the Plenary Session of the 2021 annual meeting of the American Society of Clinical Oncology (ASCO) (#LBA2) and were subsequently featured on the cover of Nature Medicine. The results were also published in full in the Journal of the American Medical Association (JAMA). The results showed that, compared to chemotherapy alone, toripalimab in combination with chemotherapy reduced the risk of disease progression by 48% and the risk of death by 37%. The median progression-free survival (“PFS”) in the toripalimab plus chemotherapy group was prolonged by 13.2 months compared to chemotherapy alone, from 8.2 months to 21.4 months. In addition, patients treated with this combined therapy achieved a higher objective response rate (ORR), longer duration of response (DoR), and no new safety signal was identified. Long-term survival follow-up data, presented at ASCO 2024, reported a 5-year survival rate of 52.0% in the toripalimab treated arm. The POLARIS-02 results were published online in January 2021 in the Journal of Clinical Oncology. The results showed that toripalimab demonstrated durable antitumor activity in patients with recurrent or metastatic NPC who failed previous chemotherapy, with an ORR of 20.5%, a DoR of 12.8 months, and a median OS of 17.4 months while maintaining a manageable safety profile. So far, toripalimab has been approved for marketing in over 30 countries and regions, including the Chinese mainland, Hong Kong SAR, the US, European Union, and India. Several marketing applications are currently under regulatory review or submitted for review in UK, Australia, Singapore, Malaysia, South Africa, Chile, Jordan, Brazil, Columbia, Philippines, Thailand and Indonesia. 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 promotes the immune system’s ability to attack and kill tumor cells. More than forty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and Europe. 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 the Chinese mainland, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI®). Currently, there are ten approved indications for toripalimab in the Chinese mainland: 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;in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (“ESCC”);in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (“NSCLC”);in combination with chemotherapy as perioperative treatment and subsequently with monotherapy as adjuvant therapy for the treatment of adult patients with resectable stage IIIA-IIIB NSCLC;in combination with axitinib for the first-line treatment of patients with medium to high risk unresectable or metastatic renal cell carcinoma (RCC);in combination with etoposide plus platinum for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC);in combination with paclitaxel for injection (albumin-bound) for the first-line treatment of recurrent or metastatic triple-negative breast cancer (TNBC). The first six indications have been included in the National Reimbursement Drug List (NRDL) (2023 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for the treatment of melanoma. In the United States, the US FDA has approved the Biologics License Application for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy in October 2023. The FDA has granted toripalimab 2 Breakthrough Therapy designations for the treatment of NPC, 1 Fast Track designation for the treatment of mucosal melanoma, and 5 Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer (SCLC). In Europe, the European Committee approved marketing authorization applications (MAA) for toripalimab 1) combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC and 2) combined with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC in September 2024. The UK Medicines and Healthcare products Regulatory Agency (MHRA) accepted the MAA in February 2023. In Australia, the new chemical entity (NCE) application was accepted by the Australia Therapeutic Goods Administration (TGA) in November 2023. The TGA has also granted toripalimab an Orphan Drug designation for the treatment of NPC. In Asia, toripalimab obtained import license from the National Regulatory Authority (NRA) of India in September 2024, and marketing approval from Pharmacy and Poisons Board of China’s Hong Kong SAR in October 2024, for the treatment of recurrent or metastatic NPC. In Singapore, the new drug application (“NDA”) application was accepted by the Singapore Health Sciences Authority (HSA) in January 2024. The HSA has also granted priority review designation for the NDA. About Junshi Biosciences Founded in December 2012, Junshi Biosciences (HKEX: 1877; SSE: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapeutics. 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. Four of the company’s innovations have already reached the Chinese or international markets, one of which is toripalimab, China’s first domestically produced and independently developed anti-PD-1 monoclonal antibody, approved in over 30 countries and regions including China, the US, the European Union, etc. Additionally, more than 30 drugs are currently in clinical development. During the COVID-19 pandemic, Junshi Biosciences actively shouldered the social responsibilities of a Chinese pharmaceutical company through its involvement in developing etesevimab, MINDEWEI®, and other novel therapies for the prevention and treatment of COVID-19. With a mission of “providing patients with world-class, trustworthy, affordable, and innovative drugs,” Junshi Biosciences is “In China, For Global.” At present, the company boasts approximately 2,500 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing, Guangzhou, etc.). For more information, please visit: http://junshipharma.com. Junshi Biosciences Contact InformationIR Team:Junshi Biosciencesinfo@junshipharma.com+ 86 021-6105 8800 PR Team:Junshi BiosciencesZhi Lizhi_li@junshipharma.com+ 86 021-6105 8800