National Cancer Centre of Singapore Pte Ltd.

MONDAY, April 24, 2023 -- A two-drug combination therapy can enhance survival odds for people with early-stage liver cancer through targeted attacks on tumor cells, a new clinical trial shows. The combo -- atezolizumab (Tecentriq) and bevacizumab (Avastin) -- reduced risk of cancer recurrence or death by 28% in patients who’d had surgery to remove their liver tumor, researchers report. This is the first time that any drugs have been shown to lower the risk of liver cancer returning in patients whose tumors were caught early enough to be removable, said researcher Dr. Pierce Chow , a senior consultant surgeon at the National Cancer Centre Singapore. “In that context, the results of this trial are historical, because for the first time patients with primary liver cancer, if they were to undergo surgical resection or ablation, there's an opportunity for them to receive therapy that can reduce recurrence,” Chow said. For this clinical trial , Chow and his colleagues tested the two-drug combination on patients with early-stage hepatocellular carcinoma, the most common form of liver cancer. The atezolizumab/bevacizumb combo already is being used to treat liver cancer that has either spread or can’t be treated with surgery. The U.S. Food and Drug Administration approved the combo for this use in 2020. Atezolizumab blocks the ability of cancer cells to hide from the immune system using a protein called programmed death-ligand 1 (PD-L1). PD-L1 can make a cancer cell appear healthy and thus avoid attack from immune cells. Meanwhile, bevacizumab blocks a protein called VEGF that makes blood vessels grow. Some cancer cells produce large amounts of VEGF, to encourage the development of new blood vessels that will bring oxygen and nutrition to a tumor. Given its effectiveness in treating advanced liver cancer, researchers thought the combination therapy might also be useful in preventing the recurrence of early liver cancers. The main treatments for early-stage liver cancer are surgery or thermal ablation, a treatment that destroys cancer cells with heat or cold, the researchers explained in background notes. Unfortunately, the risk of liver cancer recurring in these patients runs between 70% and 80%, Chow said. In the study, 334 patients were recruited; half were randomly assigned to receive the two-drug combo for one year following surgery. The rest were put on active surveillance to see if their cancer returned, which up to now has been the only other option available. After an average 17 months of follow-up, the combination therapy had reduced risk of recurrence or death by 28% in patients receiving the drugs. The findings were presented this week at the American Association of Cancer Research annual meeting, in Orlando, Fla. Such research is considered preliminary until published in a peer-reviewed journal. “This represents a major therapeutic development in the field of liver cancer,” said Dr. Edith Mitchell , a clinical professor of medical oncology with the Sidney Kimmel Cancer Center at Thomas Jefferson University Hospitals in Philadelphia. Mitchell was not involved in the trial. “The 12-month recurrence rate in the patients who did not receive this therapy was 34%, so this is a very significant and powerful study,” Mitchell said. Importantly, the combination therapy also did not produce more serious side effects in early-stage liver cancer patients than it does in those with advanced disease, even though these latest patients were on the drugs for longer, both Chow and Mitchell noted. Patients in the early-stage trial took the combo for about 11 months, on average, compared with about seven months for patients involved in the earlier trials aimed at advanced liver cancer, results showed. “They were on the therapy significantly longer in terms of the number of months compared to patients on the earlier trial for advanced cancer, but we don't see an increase in side effects in spite of the longer duration of treatment,” Chow said. “And the side effects that we see, most of them are very easily managed.” Chow expects that the sponsor of the clinical trial, drugmaker Genentech/Roche, will soon ask the FDA to approve this new use of the two-drug combo. In the meantime, researchers plan to continue tracking the health of the patients for around five years, “so further down the line, expect to see more data,” Chow added. The five-year relative survival rate of patients with early-stage, localized liver cancer is 36%, according to the American Cancer Society. Sources Pierce Chow, MBBS, MMed, FRCS(E), PhD, senior consultant surgeon, National Cancer Centre Singapore Edith Mitchell, MD, clinical professor, medical oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospitals, Philadelphia American Association for Cancer Research Annual Meeting and news release, April 16, 2023 Posted April 2023

The 2023 American Association for Cancer Research (AACR) Annual Meeting kicked off over the weekend, featuring advances in the treatment of several cancer types. Here are some notable presentations. Roche’s Tecentriq-Avastin Combo in Adjuvant Liver Cancer Interim results from Roche subsidiary Genentech’s Phase III IMbrave050 study showed the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) significantly improved recurrence-free survival (RFS) in adjuvant hepatocellular carcinoma (HCC), as compared with active surveillance. IMbrave050 enrolled 668 patients who were deemed to be at a high risk of recurrence following surgery. After a median of 17.4 months, treatment with Genentech’s antibody combo reduced the risk of recurrence or death by 28%. Overall survival data and those for other secondary endpoints were not yet mature at the time of the interim analysis, Pierce Chow, lead study author and senior consultant surgeon at the National Cancer Centre Singapore, said in a press interview. There is a lack of proven and effective adjuvant treatments for HCC, Chow said, adding that patients who undergo resection or ablation typically have poor survival and often see their disease recur. Results from IMbrave050 help address this urgent need, he said. According to a story from Fierce Pharma, there were 27 deaths in the Tecentriq-Avastin arm, two of which were directly attributed to the study treatment. Twenty patients in the active surveillance group died. Serious adverse events occurred in 24.1% of patients treated with Tecentriq-Avastin, as opposed to 10.3% in active surveillance comparators. The Tecentriq-Avastin combo is approved for use in HCC patients with unresectable or metastatic disease who have not previously received systemic therapy. Moderna and Merck’s High-Risk Melanoma Combo In the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial, Moderna’s individualized mRNA vaccine combined with Merck’s Keytruda (pembrolizumab), a PD-1 blocker, boosted recurrence-free survival in patients with resected stage III/IV melanoma. The mRNA vaccine, an individualized neoantigen therapy, works by priming the patient’s immune system to launch a potent anti-tumor response specific to their cancer’s mutation signature. Compared with Keytruda alone, the combination led to a 44% drop in the risk of recurrence or death. Over 12 months of observation, the RFS rate was 83.4%, which dropped slightly to 78.6% by 18 months. In an exploratory subgroup analysis of patients with high and low tumor mutational burden, the use of the mRNA vaccine reduced the risk of recurrence or death by 35% and 41%, respectively. As for safety, the observed adverse events were largely consistent with what had been previously recorded. Common toxicities included fatigue, injection-site pain and chills. These data point to the potential of combining an individualized vaccine with PD-1 blockage in high-risk melanoma, Kyle Holen, senior vice president and head of development, therapeutics and oncology at Moderna, said in a statement. Moderna looks forward to beginning a Phase III trial soon, he said. Beyond melanoma, Moderna also plans to study this candidate in lung cancer, Holen said. AstraZeneca’s Imfinzi in Late-Stage NSCLC In a planned interim analysis of the Phase III AEGEAN study, AstraZeneca’s Imfinzi (durvalumab) plus neoadjuvant chemotherapy, followed by Imfinzi on its own, significantly improved event-free survival (EFS) in patients with early-stage non-small cell lung cancer (NSCLC), as compared with neoadjuvant chemotherapy alone. The Imfinzi-based regimen cut the risk of recurrence, progression or death by 32%. Pathologic complete response (pCR), defined as having no viable tumor after neoadjuvant treatment, was a key secondary endpoint of AEGEAN. The Imfinzi regimen led to a 17.2% pCR rate, as opposed to 4.3% after neoadjuvant chemotherapy alone. AEGEAN’s results underline the importance of diagnosing NSCLC and initiating treatment earlier, when patients are most likely to be cured, Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, said in a statement. AstraZeneca will discuss these data with the regulatory bodies, Galbraith said. The AEGEAN study consisted of 802 NSCLC patients who were given Imfinzi at a fixed dose of 1,500 mg. Those with tumor mutations in the EGFR and ALK genes were excluded from the study. AEGEAN found no new safety signals in either the neoadjuvant or adjuvant settings. Affimed’s Mid-Stage Lymphoma Study Final data from the Phase II REDIRECT study showed that Affimed’s AFM13 was effective for the treatment of heavily pretreated, advanced relapsed or refractory peripheral T Cell Lymphoma (PTCL). Affimed’s candidate induced a 32.4% objective response rate (ORR) and a 10.2% complete response rate (CRR) in the study’s intention-to-treat population. In the subgroup of patients with angioimmunoblastic T cell lymphoma, a common PTCL subtype, AFM13 elicited ORR and CRR values of 53.3% and 26.7%, respectively. AFM13’s effects endured for a median of 2.3 months, and treated patients showed a median progression-free survival of 3.5 months. Overall survival was 13.8 months. AFM13 is an investigational, first-in-class innate cell engager that works by activating innate immune players including natural killer cells and macrophages to attack CD30-positive hematologic cancer cells. It is Affimed’s most advanced innate cell engager. REDIRECT is a multicenter, registration-directed trial enrolling 108 patients who received 200-mg intravenous infusions of AFM13. Affimed reported an adverse event pro was consistent with what had previously been reported. Common treatment-emergent toxicities included infusion-related reactions, neutropenia and pyrexia. There were no side effects that led to death. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com

- Phase 1b/2 trial to be conducted at the National University Cancer Institute, Singapore and the National Cancer Centre Singapore, in Collaboration with the Singapore Translational Cancer Consortium - - ADG106 now being evaluated in combinations with three leading anti-PD-1 therapies - SAN DIEGO and SUZHOU, China and SINGAPORE, Oct. 27, 2021 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), the National University Cancer Institute, Singapore (NCIS) at the National University Hospital in Singapore, National Cancer Centre Singapore (NCCS), and the Singapore Translational Cancer Consortium (STCC), today announced the initiation of a phase 1b/2 clinical trial of the anti-CD137 agonist antibody, ADG106, in combination with the anti-PD-1 antibody, Nivolumab. The trial will be led by Professor Goh Boon Cher, Senior Consultant, Department of Haematology-Oncology and Deputy Director (Research) at NCIS, and Associate Professor Daniel Tan, Head of the Division of Clinical Trials and Epidemiological Sciences and Senior Consultant, Division of Medical Oncology, NCCS. Both Professor Goh and Associate Professor Tan lead the STCC’s Cancer Clinical Trials & Investigational Medicine Unit that brings together centres in Singapore for scaled up capacity, efficiency and expertise in conducting cancer clinical trials. ADG106 is being developed by Adagene for the treatment of advanced solid tumours and non-Hodgkin’s lymphoma. The phase 1b/2 trial will evaluate this novel combination in advanced non-small cell lung cancer (NSCLC) patients who have progressed on prior therapies. Professor Goh commented, “NSCLC is the most prevalent type of lung cancer, which is the leading cause of cancer-related deaths worldwide. Despite recent progress, most patients will progress after receiving the newest generation of immunotherapy and immune checkpoint treatments. ADG106 has been shown to enhance the activity of T-cells based on pre-clinical data, including evidence of synergistic effect with anti-PD-1 agents in a refractory NSCLC tumour model. We look forward to evaluating the combination of ADG106 with Nivolumab and exploring the potential of this promising therapy in a patient population with unmet needs.” “Pre-clinical studies evaluating the use of ADG106 with anti-PD-1 antibodies have shown promising results and we believe that this novel combination therapy can potentially address resistance to immune checkpoint inhibitors in metastatic NSCLC,” said Associate Professor Tan. “Through this study, we plan to utilise a series of cutting-edge translational approaches to understand mediators of response and resistance to checkpoint inhibitors.” “We are excited to support this trial evaluating ADG106 in combination with Nivolumab, another leading anti-PD-1 therapy to be combined in clinical trials with ADG106 as a potential best-in-class treatment targeting CD137,” said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. “Building on the evidence of clinical efficacy demonstrated in our monotherapy trials, this trial will further explore the potential additive effect between ADG106 and anti-PD-1 agents. We are also delighted to partner with esteemed oncology research organisations that are leading cutting-edge care for patients in the region, as well as Bristol-Myers Squibb, a pioneer in research on anti-PD-1 therapy and anti-CD137 agonist antibodies.” The phase 1b/2 open label trial is designed to evaluate safety, tolerability, and anti-tumour activity of the combination in up to 53 patients with advanced NSCLC who have progressed after prior treatment. The trial will also include exploratory biomarker analyses, including immune cell profiling in response to treatment. The trial will involve work under the Lung Cancer programme that is supported by the RIE2020 Open Fund - Large Collaborative Grant (OF-LCG) programme, administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC) and supported by the National Research Foundation Singapore, where Associate Professor Tan is the Corresponding Principal Investigator. OF-LCG is composed of a multi-disciplinary team of clinician-scientists, clinicians, researchers, molecular biologists and computational biologists across various research institutes in Singapore. “This collaboration continues STCC’s goals to synergise cancer research capabilities across Singapore in a concerted approach, and promotes institutional-industry partnerships. We look forward to further collaborations with global biotech companies on innovations in screening, treatment and care for cancer patients,” said Professor Chng Wee Joo, Executive Director of STCC and Director of NCIS. About Non-Small Cell Lung Cancer There are two major types of lung cancers: small cell lung cancer and non-small cell lung cancer (NSCLC). About 85 percent to 90 percent of lung cancers are non-small cell lung cancers. The major differences between these two types of lung cancers are the size and shape of the cancer cell, forms of treatment and the speed at which the cancer spreads. NSCLC is the leading cause of cancer-related deaths worldwide, accounting for approximately 18 per cent of all cancer deaths. Despite the proven use of low-dose CT scan as a screening tool for lung cancer, most patients still present with stage 3 or 4 disease and only about 20 percent are operable, with a five-year survival overall of about 10 percent1. Metastatic disease is the primary cause of death from NSCLC. Until recently, chemotherapy has been the only available therapy for metastatic disease. However, much effort has been made to understand the molecular underpinning of NSCLC, and in non-squamous NSCLC, molecular drivers have been uncovered to direct the specific treatment of this subgroup of patients. About ADG106 ADG106, is a fully human ligand-blocking, agonistic anti-CD137 IgG4 mAb being developed for the treatment of advanced solid tumours and non-Hodgkin’s lymphoma. CD137 stimulates the immune system to attack cancer cells and is a key driver for long-lasting T-cell proliferation and survival. Clinical trials of ADG106 as monotherapy have been conducted in the U.S. and China. A trial in combination with toripalimab is underway in China, and one in combination with pembrolizumab is planned in the U.S. and Asia Pacific (APAC). About Nivolumab Nivolumab, marketed globally as Opdivo, is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumour immune response. By harnessing the body’s own immune system to fight cancer, Nivolumab has become an important treatment option across multiple cancers, including advanced NSCLC. About Adagene Adagene Inc. (Nasdaq: ADAG) is a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based cancer immunotherapies. Adagene combines computational biology and artificial intelligence to design novel antibodies that address unmet patient needs. Powered by its proprietary Dynamic Precision Library (DPL) platform, composed of NEObody™, SAFEbody™, and POWERbody™ technologies, Adagene’s highly differentiated pipeline features novel immunotherapy programmes. Adagene has forged strategic collaborations with reputable global partners that leverage its technology in multiple approaches at the vanguard of science. For more information, please visit: . About National University Cancer Institute, Singapore (NCIS) NCIS offers a broad spectrum of cancer care and management covering both paediatric and adult cancers, with expertise in prevention, screening, diagnosis, treatment, rehabilitation and palliative care. The Institute’s strength lies in the multi-disciplinary approach taken to develop a comprehensive and personalised plan for each cancer patient and his or her family. Our award-winning clinician-scientists and clinician-investigators conduct translational research and clinical trials, providing patients with access to evidence-based cancer diagnostics, technology and therapies. For more information about NCIS, please visit . About Singapore Translational Cancer Consortium STCC aims to strengthen the overall impact of cancer research and translation in Singapore by bringing together key basic, clinical and translational teams on joint platforms to actively establish and implement collaborative cancer programmes. STCC strives to establish Singapore as a global leader for oncology in research translation and its applications to health and economic value creation. STCC is a business unit under the Consortium for Clinical Research and Innovation, Singapore (CRIS), a subsidiary of Ministry of Health Holdings (MOHH), and is anchored by the cancer research programmes and commercialisation platforms of STCC’s research partners (NCCS, NCIS, National University of Singapore [NUS] Cancer Science Institute [CSI] and Agency for Science, Technology and Research [A*STAR]). STCC is supported with funding from the National Research Foundation, Singapore and administered by the Singapore Ministry of Health. For more information, please visit . About the National Cancer Centre Singapore The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre with specialists who are experts in treating cancer. NCCS attends to the majority of cancer cases in Singapore’s public healthcare sector. In addition to offering holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct robust, cutting-edge clinical and translational research. To achieve the vision of being a global leading cancer centre, NCCS offers world class care and shares its depth of experience and expertise by training local and overseas medical professionals. To meet growing needs, the new NCCS building will be completed in 2022 with increased capacity and expanded facilities dedicated to cancer care, rehabilitation, research and education. To give patients the best treatment outcomes, NCCS will offer access to advanced and innovative treatment such as proton therapy at the new Goh Cheng Liang Proton Therapy Centre. For more information, please visit: Safe Harbor Statement This press release contains forward-looking statements, including statements regarding the potential impact of combination trial of ADG106 and nivolumab, potential implications of clinical data for patients, clinical development programs and related clinical trial data, the potential benefits, safety and efficacy of our collaboration partners’ products and investigational therapies, and Adagene’s advancement of, and anticipated preclinical activities, clinical development, regulatory milestones, and commercialization of its product candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including but not limited to Adagene’s ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may not support further development or regulatory approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of Adagene’s drug candidates; Adagene’s ability to achieve commercial success for its drug candidates, if approved; Adagene’s ability to obtain and maintain protection of intellectual property for its technology and drugs; Adagene’s reliance on third parties to conduct drug development, manufacturing and other services; Adagene’s limited operating history and Adagene’s ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; Adagene’s ability to enter into additional collaboration agreements beyond its existing strategic partnerships or collaborations, and the impact of the COVID-19 pandemic on Adagene’s clinical development, commercial and other operations, as well as those risks more fully discussed in the “Risk Factors” section in Adagene’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Adagene, and Adagene undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. Media Contact: Bruce Mackle LifeSci Advisors 646-889-1200 bmackle@lifesciadvisors.com Adagene Investor Contact: Ami Knoefler Adagene 650-739-9952 ir@adagene.com 1 Howlader N, Forjaz G, Mooradian MJ, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. New England Journal of Medicine 2020;383:640-9