PAX5

Clinical data demonstrated treatment with AGA2118 resulted in dose-dependent increases in bone mineral densityWOODLAND HILLS, Calif., Sept. 30, 2024 (GLOBE NEWSWIRE) -- Angitia Biopharmaceuticals, a clinical-stage biotechnology company focused on the discovery and development of innovative therapeutics for serious musculoskeletal diseases, today announced data from its ongoing program evaluating AGA2118 for the treatment of osteoporosis, as presented at the American Society for Bone and Mineral Research 2024 Annual Meeting (ASBMR) on September 27-30, 2024, in Toronto, ON, Canada. Treatment with AGA2118, a bispecific antibody targeting both sclerostin and DKK1, led to rapid and durable increases in bone formation, decreases in bone resorption, and improvements in bone mineral density (BMD) and bone strength in humans and in animal models, as highlighted in multiple abstracts presented at the conference. “AGA2118 is the first clinical stage bispecific antibody to target two key regulators of bone metabolism, and our first-in-human data demonstrate clinical proof-of-concept for AGA2118,” said David Ke, M.D., Chairman and Chief Executive Officer of Angitia. “AGA2118 is well-tolerated and possesses a pharmacokinetic profile that has translated well to the clinic. In men and otherwise healthy postmenopausal women, we observed rapid and robust bone mineral density gains. We look forward to engaging regulators and continuing development in a diseased population.” In the first-in-human (FIH) trial, 88 men and otherwise healthy postmenopausal women, received AGA2118 or placebo (randomized 6:2) either subcutaneously or intravenously. Subjects were either dosed with a single dose of AGA2118 up to 15 mg/kg or multiple doses of AGA2118 up to 12mg/kg every 4 weeks for a total of three doses and were followed for 85 days in the single ascending dose (SAD) cohort or 169 days in the multiple ascending dose (MAD) cohort. AGA2118 was safe and well-tolerated at all dose levels tested, with adverse events balanced between treatment and placebo. No treatment-related serious adverse events (SAEs) were reported. In addition to safety, the Company observed clinical activity, including dose-dependent increases in bone formation markers P1NP, BSAP, and osteocalcin, as well as dose-dependent decreases in the bone resorption marker CTX-1. In both SAD and MAD cohorts, BMD increased from baseline in the lumbar spine, total hip, and femoral neck in a dose- and exposure-dependent manner. “The rapidity and robustness of the BMD and biomarker responses with AGA2118 in this first-in-human trial demonstrate the potential of AGA2118 to become an important new treatment option for patients with skeletal disease,” said Matthew Drake, M.D., Ph.D., Associate Professor of Medicine at the Mayo Clinic, Divisions of Endocrinology and Hematology. “In addition, the pharmacokinetics and safety of AGA2118 support further development.” The abstract and oral presentation outlining the FIH trial is entitled, “AGA2118, a Bispecific Antibody Neutralizing both Sclerostin and DKK1, Increased Bone Formation, Decreased Bone Resorption, and Led to Rapid BMD Gains in a First in Human, Single- and Multiple-Dose, Placebo-Controlled Randomized Study." Angitia made three additional presentations at ASBMR, including a second oral presentation and two posters. Those presentations summarize data from AGA2118 in a non-human primate (NHP) model of osteoporosis, AGA2118 pharmacokinetics (PK) in NHPs and humans, and long-term follow-up in NHPs treated with AGA2118. Results translated well from preclinical models to humans, and the PK profile of AGA2118 is supportive of future development. About Osteoporosis Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis has become a global epidemic, especially for older women, due to an aging population and longer life expectancies. Estimates indicate that more than 200 million patients worldwide suffer from osteoporosis. Although there are a number of approved therapies for osteoporosis, limitations remain regarding the efficacy and/or safety of each of these options. Research also indicates that most severely osteoporotic individuals do not receive a bone-active agent. As a result, a large unmet medical need remains for the development of new osteoporosis therapies. About AGA2118 AGA2118 is a bispecific antibody that targets sclerostin and DKK1 and is in clinical development for the treatment of osteoporosis. Sclerostin and DKK1 are two critical, negative regulators of WNT signaling in osteoblasts and of bone metabolism. By targeting both proteins, AGA2118 is thought to prevent compensatory increase of either agent, aiming to improve the magnitude of bone mineral density gains in osteoporotic patients. Angitia wholly owns the bispecific antibody. About Angitia Biopharmaceuticals Angitia Biopharmaceuticals is a clinical-stage biotechnology company focused on the discovery and development of innovative therapeutics for serious musculoskeletal diseases. Angitia is currently studying 3 biologic product candidates in the clinic for the treatment of osteoporosis, osteogenesis imperfecta (OI), and spinal fusion. Leveraging the team's extensive experience and scientific acumen in novel drug development, Angitia is committed to providing groundbreaking therapies to satisfy key unmet medical needs. Learn more at www.angitiabio.com. Investor & Media Contact: William WindhamSolebury Strategic Communicationswwindham@soleburystrat.com646-378-2946 Forward-Looking Statements This press release is prepared by Angitia (the “Company”, “We”) for informational purposes only. Forward-looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “anticipate”, “expect”, “intend”, “plan”, “believe”, “continue”, “could”, “potential”, “may”, “will”, “goal” or similar expressions and the negatives of those terms. However, not all forward-looking statements contain these identifying words. These forward-looking statements involve substantial known and unknown risks, uncertainties, and other factors that are beyond the Company’s control and are difficult to predict and may cause our actual results, timing of results, or achievements to be materially different from the information expressed or implied by these forward-looking statements. We anticipate that subsequent events and developments may cause our expectations and assumptions to change, and we undertake no obligation to 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. Except as expressly required by law, the Company and/or its officers, directors, employees, and agents shall not assume responsibility for the accuracy and completeness of the forward-looking statements in the information provided.

Scientists have completed the largest study of families affected by Hodgkin lymphoma and identified novel variants linked to cancer predisposition. Why did my child get cancer? Clinicians have longed for a way to help answer this question. Doctors knew Hodgkin lymphoma sometimes occurs in families, but why this happens has been a mystery. Scientists at St. Jude Children's Research Hospital have now helped solve it. The researchers studied multiple families affected by Hodgkin lymphoma and identified genetic variants linked to an increased risk of developing the disease. The findings appeared as a first edition in Blood. Hodgkin lymphoma is a cancer of the lymphatic system (part of the immune system) that affects lymph nodes but can spread to the spleen, liver, bone marrow and lungs. As many as 7,000 new cases of the disease are diagnosed in the United States each year. Hodgkin lymphoma is the most common type of cancer in adolescents and has a five-year survival rate of 90-95%. "We've never been able to tell these families anything other than its just bad luck because nobody knew why more than one family member would develop Hodgkin lymphoma," said co-first and co-corresponding author Jamie Flerlage, M.D., St. Jude Department of Oncology. "We took on this study because understanding what is causing cancer in these families will help us to better counsel people about their chances of passing on genetic risk to their offspring, as well as help us identify novel targets that might potentially be used to create new treatments." Family pedigrees help reveal variants To study Hodgkin lymphoma occurrences in families, the researchers created pedigrees, a type of diagram that reveals familial connections while tracking the incidences of cancer. The selection criteria required two or more first-degree relatives with Hodgkin lymphoma, one of whom needed to be younger than 21 years of age when diagnosed. Scientists performed whole genome sequencing on 234 members of 36 families and identified 44 variants (33 coding and 11 noncoding) that increase the risk of developing Hodgkin lymphoma. The findings included novel gene variants that had not been previously linked to predisposition to the disease such as PAX5, GATA3, IRF7, EEF2KMT and POLR1E as well as known variants such as KDR and KLHDC8B. "Inherited variants can be an important missing piece of the puzzle when you're trying to understand why certain people are more likely to get a type of cancer," said co-corresponding author Jun J. Yang, Ph.D., St. Jude Comprehensive Cancer Center Hematologic Malignancies Program. "Whole genome sequencing that allows you to look beyond the main genetic variants to the non-coding or epigenetic variants is a powerful tool to help explain what puts a person at a higher risk of developing Hodgkin lymphoma." Bioinformatics behind the findings A powerful bioinformatics pipeline created at St. Jude was essential to analyzing and tracking the variants through the family pedigrees. The process included running algorithms to identify the variants in every individual, and then taking the pedigree and tracing the variants back through the family tree to figure out which ones were related to the cancer. More than 40 annotation databases and pieces of software powered the effort, which resulted in a fast, robust pipeline to analyze familial data. "We married several existing tools as well as customized approaches to make a pipeline that could process data from these families in a meaningful way," said co-first author Jason Myers, St. Jude Center for Applied Bioinformatics. "The work that went into making this pipeline is not specific to Hodgkin lymphoma; the pipeline can be used for any other disease where families are involved, including other types of cancer and neurological disorders such as epilepsy." The cohort of families included patients who were treated at St. Jude as well as many families who were part of a familial lifetime cohort study pioneered by the National Cancer Institute. The analysis revealed inherited variants likely to predispose individuals to the disease in most of the families, highlighting the important role of genetic predisposition in understanding Hodgkin lymphoma. "The family pedigrees and whole genome sequencing approach set this study apart because they allowed us to throw everything in our genomics toolkit at this question to tease apart what was happening in each family," said co-corresponding author Evadnie Rampersaund, Ph.D., St. Jude Center for Applied Bioinformatics. "We had the amazing opportunity to develop a highly comprehensive bioinformatic pipeline for interrogating coding, noncoding and copy-number variants in families. This project was a large-scale collaboration that shines brightly on the interconnective opportunities and talents within St. Jude." Authors and funding The study's other authors are Lynn Goldin, Neil Caporaso, Margaret Tucker, Mary McMaster and Melissa Rotunno, National Cancer Institute and National Institutes of Health; Aurelie Vogt, Kathleen Wyatt and Jia Liu, Leidos Biomedical Research Inc.; Deborah Flamish, Westat, Inc.; Jamie Maciaszek, Ninad Oak, Sara Rashkin, Yawei Hui, Yongdong Wang, Wenan Chen, Gang Wu, Ti-Cheng Chang, Kayla Hamilton, Saima Sultana Tithi, Charles Mullighan and Kim Nichols of St. Jude; and Monika Metzger, formerly of St. Jude. The study was supported by grants from the National Institutes of Health (R03HD104066, CA-21765), the Lymphoma Research Foundation, a Gabriella Miller Kids First X01 Grant and ALSAC, the fundraising and awareness organization of St. Jude.