CTLA4

2024 Harrington Prize for Innovation in Medicine Recognizes Pioneering Work in Immunology CLEVELAND, March 19, 2024 /PRNewswire/ -- The eleventh annual Harrington Prize for Innovation in Medicine has been awarded to Arlene H. Sharpe, MD, PhD, Kolokotrones University Professor and Chair of the Department of Immunology at Harvard Medical School. The award recognizes her breakthrough discoveries in immune regulation, which have established foundational principles in immunology and led to new cancer therapies that act by boosting the immune response to cancer. The Harrington Prize for Innovation in Medicine, established in 2014 by the Harrington Discovery Institute at University Hospitals and the American Society for Clinical Investigation (ASCI), honors physician-scientists who have moved science forward with achievements notable for innovation, creativity and potential for clinical application. Dr. Sharpe's research in immunology has led to significant advances in medical treatments. Her work helped identify key pathways that restrain the activity of T lymphocytes (immune cells) to fight cancer. Her work defined the PD-1 pathway and its immunoinhibitory functions as well as the inhibitory functions of CTLA-4 to restrain the activity of the immune system. Dr. Sharpe's research thus laid the foundation for the development of 'immune checkpoint inhibitors', drugs that target PD-1 and related pathways. These therapies, including pembrolizumab and nivolumab, have been approved by the FDA for treating numerous types of cancer. They work by preventing inhibition of T cell function, thereby unleashing the body's immune system to fight cancer cells more effectively. This approach has become a cornerstone in cancer treatment strategies. "Dr. Sharpe's body of work has shaped our understanding of the role of the T cell in regulating the immune response. Her innovative scientific discoveries are among the best examples of bench-to-bedside work in the past three decades," said Benjamin D. Humphreys, MD, PhD, Joseph Friedman Professor of Renal Diseases in Medicine and Chief, Division of Nephrology, Washington University in St. Louis and 2023-2024 President of the ASCI. "Immune checkpoint inhibitors are drugs that allow for dramatic remission, and even cures, of cancers that had previously been considered untreatable. Dr. Sharpe's foundational insights have thus been harnessed to transform cancer therapy. Her work provides a beautiful example of physician impact through creative science," said Jonathan S. Stamler, MD, President, Harrington Discovery Institute, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation and Professor of Medicine and of Biochemistry at University Hospitals and Case Western Reserve University. A committee composed of members of the ASCI Council and the Harrington Discovery Institute Scientific Advisory Board reviewed nominations from leading academic medical centers globally before selecting the 2024 Harrington Prize recipient. In addition to sharing the Prize's $20,000 honorarium, Dr. Sharpe will deliver the Harrington Prize Lecture at the 2024 AAP/ASCI/APSA Joint Meeting on April 5, will be a featured speaker at the 2024 Harrington Scientific Symposium May 22-23, and will publish an essay in the Journal of Clinical Investigation. The Harrington Prize has recognized outstanding and diverse innovations in medicine: 2014: Harry Dietz, MD, Johns Hopkins University, for his contributions to the understanding of the biology and treatment of Marfan syndrome, a disorder leading to deadly aneurysms in children and adults. 2015: Douglas R. Lowy, MD, The National Cancer Institute, in recognition of his discoveries that led to the development of the Human Papillomavirus vaccine to prevent cervical cancer. 2016: Jeffrey M. Friedman, MD, PhD, The Rockefeller University, for his discovery of leptin, which controls feeding behavior and is used to treat related clinical disorders. 2017: Jointly awarded to Daniel J. Drucker, MD, Mount Sinai Hospital, Canada, Joel F. Habener, MD, Massachusetts General Hospital, and Jens J. Holst, MD, DMSc, University of Copenhagen, Denmark, for their discovery of incretin hormones and for the translation of these findings into transformative therapies for major metabolic diseases such as diabetes. 2018: Helen H. Hobbs, MD, UT Southwestern Medical Center, for the discovery of the link between a gene mutation (PCSK9) and lower levels of LDL, which has improved the treatment of high cholesterol. 2019: Carl H. June, MD, University of Pennsylvania, for advancing the clinical application of CAR T therapy for cancer treatment, and for his sustained contributions to the field of cellular immunology. 2020: Stuart H. Orkin, MD, Harvard University, for breakthrough discoveries on red blood cells that offer new treatments for patients with sickle cell disease and beta-thalassemia, which are among the most common genetic disorders. 2021: Warren J. Leonard, MD, and John J. O'Shea, MD, NIH, for their respective contributions to the field of immunology, from fundamental discovery to therapeutic impact. 2022: James E. Crowe Jr., MD, and Michel C. Nussenzweig, MD, PhD, for their groundbreaking work, which has elucidated fundamental principles of the human immune response and enabled the use of human antibodies to treat COVID-19. 2023: Jean Bennett, MD, PhD, and Albert M. Maguire, MD, for their groundbreaking translational research to restore sight in inherited genetic diseases. SOURCE Harrington Discovery Institute

SAN DIEGO, March 19, 2024 (GLOBE NEWSWIRE) -- BioAtla, Inc. (Nasdaq: BCAB), a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics for the treatment of solid tumors, today announced that it plans to host a conference call and webcast on Tuesday, March 26, 2024 at 4:30 p.m. ET to discuss its financial results for the fourth quarter and full-year ended December 31, 2023 and provide business highlights. Conference Call and Webcast Information Date: Tuesday, March 26, 2024 Time: 4:30 p.m. ET Webcast Link: BioAtla Fourth Quarter and Full-Year 2023 Earnings Conference Call Dial-in Numbers: (877) 425-9470 (domestic), (201) 389-0878 (international) Conference ID: 13744024 The press release with the financial results will be accessible prior to the conference call through “News Releases” in the News & Events section of the company’s website. A replay of the call will also be available through “Events & Presentations” in the Investors section of the company’s website. About BioAtla, Inc. BioAtla is a global clinical-stage biotechnology company with operations in San Diego, California, and in Beijing, China through our contractual relationship with BioDuro-Sundia, a provider of preclinical development services. Utilizing its proprietary Conditionally Active Biologics (CAB) technology, BioAtla develops novel, reversibly active monoclonal and bispecific antibodies and other protein therapeutic product candidates. CAB product candidates are designed to have more selective targeting, greater efficacy with lower toxicity, and more cost-efficient and predictable manufacturing than traditional antibodies. BioAtla has extensive and worldwide patent coverage for its CAB technology and products with greater than 750 patents more than 475 of which have been issued. Broad patent coverage in all major markets include methods of making, screening and manufacturing CAB product candidates in a wide range of formats and composition of matter coverage for specific products. BioAtla has two first-in-class CAB programs currently in Phase 2 clinical testing, mecbotamab vedotin, BA3011, a novel conditionally active AXL-targeted antibody-drug conjugate (CAB-AXL-ADC), and ozuriftamab vedotin, BA3021, a novel conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC). The Phase 2 stage CAB-CTLA-4 antibody, BA3071, is a novel CTLA-4 inhibitor designed to reduce systemic toxicity and potentially enable safer combination therapies with checkpoint inhibitors such as anti-PD-1 antibody. The company’s first bispecific T-cell engager antibody, BA3182, is currently in Phase 1 development. BA3182 targets EpCAM which is highly and frequently expressed on many adenocarcinomas while engaging human CD3 expressing T cells. To learn more about BioAtla, Inc. visit . Internal Contact: Richard Waldron Chief Financial Officer BioAtla, Inc. rwaldron@bioatla.com 858.356.8945 External Contact: Bruce Mackle LifeSci Advisors, LLC bmackle@lifesciadvisors.com

JINAN, China, March 15, 2024 /PRNewswire/ -- On 8 March local time, during the 25th European Society of Gynecological Oncology (ESGO) Conference (ESGO 2024) in Spain, Qilu Pharmaceutical unveiled the Phase II clinical trial results for iparomlimab and tuvonralimab (QL1706) in an oral presentation. This trial, known as DUBHE-C-206, recruited patients with recurrent or metastatic cervical cancer who failed first-line standard treatments. The findings were presented by Professor Jihong Liu from the Sun Yat-sen University Cancer Center in China. Study Background and Design Cervical cancer is one of the most prevalent malignancies among women and a leading cause of cancer-related death. For those who have failed the first-line standard therapy, the currently available treatment options are inadequate. The objective response rate (ORR) for pembrolizumab was 12.2%, with an ORR of 0% in the PD-L1-negative population[1]. Additionally, the median progression-free survival (PFS) and median overall survival (OS) were reported to be 2.1 months and 9.4 months, respectively. Similarly, cemiplimab showed an ORR of 16.4%, with a median PFS of 2.8 months and a median OS of 12.0 months[2]. This highlights the unmet need for effective and safe clinical treatments for patients with cervical cancer who failed first-line therapy. By targeting and inhibiting two immune checkpoint pathways (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), Qilu Pharmaceutical's proprietary drug QL1706 has shown a favorable safety profile and preliminary efficacy in patients with cervical cancer in early studies. The DUBHE-C-206 study aimed to evaluate the efficacy and safety of QL1706 in patients with recurrent or metastatic cervical cancer. This study was a multi-center, single-arm, open-label phase II clinical trial which enrolled patients with recurrent or metastatic cervical cancer who failed first-line platinum-based chemotherapy (with or without bevacizumab) and without prior immunotherapy. Participants received QL1706 at a dose of 5.0 mg/kg once every three weeks (Q3W). The primary endpoint of the trial was the ORR as assessed by an Independent Evaluation Committee (IRC). Secondary endpoints included the ORR as evaluated by investigators, duration of response (DoR) and disease control rate (DCR) as assessed by both IRC and investigators, PFS, 6-month and 12-month PFS rates, OS, 12-month OS rate, as well as safety, pharmacokinetics, and immunogenicity. Study Results As of April 28, 2023, the study had enrolled 148 patients with a median age of 53.0 years, including 132 (89.2%) diagnosed with squamous cell carcinoma. Of these participants, 109 (73.6%) had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 1. Additionally, 105 (70.9%) patients had a combined positive score (CPS) of ≥1, while 43 (29.1%) had a CPS of <1. Notably, 39.9% of the participants had been treated with bevacizumab, and 37.2% had received second-line and subsequent therapy. The median follow-up duration of the study was 11.0 months. In terms of efficacy, the ORR as assessed by IRC was 33.8% (95% CI: 26.2%-42.0%), and the DCR reached 64.9% (95% CI: 56.6%-72.5%). The median PFS was 5.4 months (95% CI: 3.9-6.9), with 6-month and 12-month PFS rates of 45.0% and 16.1%, respectively. The median OS had not been reached, with 6-month and 12-month OS rates standing at 83.9% and 65.4%, respectively. In subgroup analyses, the ORR for patients with a CPS of ≥1 was 37.1%, compared to 25.6% for those with a CPS of <1. Furthermore, the ORR for patients who had previously received bevacizumab was 28.8%, whereas it was 37.1% for those who had not undergone such treatment. Regarding safety, among all the participants, 104 (70.3%) experienced treatment-related adverse events (TRAEs), with the most common being hypothyroidism (20.9%) and hyperthyroidism (18.9%). TRAEs of grade 3 or higher were observed in 36 individuals (24.3%), with anemia (4.1%), increased gamma-glutamyl transferase (GGT) (2.7%), and increased lipase level (2.7%) being the most frequently reported. Three patients (2.0%) discontinued treatment due to TRAEs. There were no reported deaths resulting from TRAEs. In the study, 65 participants (43.9%) experienced immune-related adverse events (irAEs), with grade 3 or higher irAEs reported in 21 (14.2%). In conclusion, QL1706 has shown promising efficacy and acceptable safety profile in patients with recurrent or metastatic cervical cancer who failed first-line standard therapy, regardless of their PD-L1 expression. This positions QL1706 as a more effective and safer therapeutic option for patients with cervical cancer whose disease progressed after first-line standard therapy. A phase III clinical trial is currently in progress, evaluating the use of QL1706 in combination with chemotherapy (with or without bevacizumab) as a first-line treatment option. Prof. Liu from the Sun Yat-sen University Cancer Center commented, "The findings from the DUBHE-C-206 study offer new evidence to support the use of dual immunotherapy in the second- and late-line treatment of recurrent or metastatic advanced cervical cancer (ACC). They also affirm QL1706's potential as a promising new treatment option for ACC patients. The study's results have shown the efficacy benefits of QL1706 across the whole ACC patient population while demonstrating its considerable safety advantages. These findings suggest that QL1706 has the potential to significantly enhance the quality of life for patients and provide superior clinical benefits. We eagerly anticipate the outcomes of the Phase 3 trial for QL1706, which is now in progress to assess the efficacy and safety of QL1706 in combination with chemotherapy, with or without bevacizumab, as a first-line treatment for recurrent or metastatic ACC." Professor Hanmei Lou from Zhejiang Cancer Hospital stated, "For ACC patients who have failed first-line therapy, the available treatment options are still limited and exhibit unsatisfactory efficacy, highlighting substantial unmet clinical needs. The efficacy and safety data from the DUBHE-C-206 study are promising. Compared with the previously reported combination therapy involving PD-1 and CTLA-4 inhibitors, QL1706 has demonstrated reduced toxicity and offers notable advantages in both safety and efficacy. This further supports the use of dual immunotherapy for the treatment of recurrent or metastatic ACC. Consequently, the data from the DUBHE-C-206 study holds significant clinical value and implications." Ms Xiaoyan Kang, Executive Deputy General Manager of Qilu Pharmaceutical's Clinical Research & Development Center and Chief Medical Officer (CMO) for Oncology, explained, "QL1706 represents the world's first dual-functional MabPair antibody targeting both PD-1 and CTLA-4 pathways. Data from several clinical studies of this novel drug have been released. The inclusion of the latest clinical trial results in the oral presentation at the ESGO conference underscores the international academic community's interest in and recognition of the clinical potential of this novel product. Currently, multiple Phase III clinical trials involving QL1706 are in progress, covering various disease indications. Going forward, we plan to further accelerate the clinical development of QL1706 to ensure that this treatment can reach and benefit patients as soon as possible." References: 1. J Clin Oncol. 2019;37(17):1470-1478. 2. N Engl J Med. 2022;386(6):544-555. SOURCE Qilu Pharmaceutical Co., Ltd.