Perelman School of Medicine

Study offers hope for treating a potentially deadly childhood cancer PHILADELPHIA, Oct. 24, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) announced significant findings in the treatment of neuroblastoma, a cancer of the peripheral nervous system that usually occurs as a solid tumor in a child's chest or abdomen. The study offers insights that could lead to new, personalized medicine approaches in immunotherapy treatment. The findings were published today in the journal Cancer Cell. Neuroblastoma is the most common cancer in infants, accounting for a disproportionate share of pediatric cancer deaths. Currently, monoclonal antibody-based immunotherapy is the only Food and Drug Administration (FDA) approved treatment for neuroblastoma. However, this type of immunotherapy can cause painful side effects, and patients often relapse. All these factors led researchers to seek new and innovative approaches to treating this disease and safely improve cure rates. In this study, researchers used a multi-omics approach to analyze and identify potential new targets for immunotherapy, integrating proteomic, transcriptomic, and epigenomic data to pinpoint biologically relevant proteins on the surfaces of cancer cells that are visible to the immune system. Reviewing comprehensive data helps scientists understand how cells function and what goes wrong in diseases like cancer. Based on their findings, the researchers prioritized the protein, Delta-like canonical notch ligand 1 (DLK1). They showed that high expression of DLK1 in cancer cells promotes tumor growth and discovered how neuroblastoma cells increase DLK1 levels. They also found that DLK1 is produced at a higher rate in many childhood and adult cancers. "Our study demonstrates the power of an integrative multi-omics approach to identify immunotherapeutic targets," said senior author, Sharon J. Diskin, PhD, a member of the Center for Childhood Cancer Research and Department of Biomedical and Health Informatics at CHOP and an Associate Professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. The researchers subsequently studied a novel treatment called ADCT-701, an antibody-drug conjugate (ADC) that delivers a potent therapy targeting DLK1-expressing cancer cells, as part of the National Cancer Institute's (NCI) Pediatric Preclinical in Vivo Testing (PIVOT) Program. They demonstrated that ADCT-701 was highly effective in eradicating highly resistant patient-derived tumors. The NCI is currently conducting a phase 1 clinical trial for treatment of neuroendocrine neoplasms with ADCT-701 in adults 18 and older. "Our findings provided important validation and preclinical data to support an ongoing first-in-human DLK1-directed immunotherapy clinical trial for adult patients diagnosed with neuroendocrine neoplasms, including neuroblastoma," said the study's primary author, Amber Hamilton, PhD, a post-doctoral fellow at CHOP. "This research brings hope to families, offering the potential for more effective treatments." The research was supported by a grant from the W.W. Smith Charitable Trust, an Innovation Award from Alex's Lemonade Stand Foundation, and a Stand Up 2 Cancer-St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113 ). This work was also supported by National Institutes of Health (NIH) grants U54-CA232568, R01-CA204974, R01-CA237562, R03-CA230366, U01-CA199287, R35-CA220500, U01-CA263957, U01-CA199222, F31-CA225069 and T32-CA009140. The work was delivered in part by the NexTGen Cancer Grand Challenges partnership funded by Cancer Research UK (CGCATF-2021/100002), the National Cancer Institute (CA278687-01) and The Mark Foundation for Cancer Research. Hamilton et al. "A proteogenomic sufaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma." Cancer Cell. Online October 24, 2024. DOI:10.1016/j.ccell.2024.10.003. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Jennifer Lee Children's Hospital of Philadelphia (267) 426-6084 [email protected] SOURCE Children's Hospital of Philadelphia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

iStock, Aleksandra Zhilenkova Despite substantial variability in the presented data and no well-controlled trial, the FDA advisory committee voted in favor of Stealth BioTherapeutics’ Barth syndrome therapy elamipretide, citing the urgent unmet need. The FDA’s Cardiovascular and Renal Drugs Advisory Committee on Thursday threw its support behind Stealth BioTherapeutics’ peptide drug elamipretide for the treatment of the ultrare genetic disease Barth syndrome. In a 10–6 vote, the panel of external experts found that elamipretide is an effective treatment for Barth syndrome—though this verdict was hardly unequivocal. Many of the committee members, even those who voted affirmatively, flagged the flawed nature of Stealth’s data supporting elamipretide and uncertainties regarding the drug’s clinical efficacy. Still, most of the panelists recognized the practical difficulties of conducting trials in rare diseases and noted the urgent and major need for a treatment in Barth syndrome. “This was just impossible,” Gerard Berry, professor of Pediatrics at Harvard Medical School, said during the meeting. “As a pediatrician and metabolic specialist who’s cared for these patients, to deprive somebody of being able to get the medicine that might help is just untenable for me.” Berry voted in favor of elamipretide. “I don’t know if the case was made for me that there was an [adequate and well-controlled trial],” said Carole Tucker, chair of the Department of Physical Therapy and Rehabilitation Sciences at the University of Texas Medical Branch. “I don’t think the sponsor has necessarily provided that level of evidence.” However, the data available showed a “trend toward the positive,” she continued. Combined with anecdotal evidence from patients who spoke at the committee meeting, this strengthened elampiretide’s case for her. Tucker voted yes. “I felt like the most compelling thing that we heard was from the people who spoke in the open public hearing and it’s hard to know what to do with that,” Susan Ellenberg, professor emerita of Biostatistics, Medical Ethics and Health Policy at the Perelman School of Medicine in Pennsylvania. Ellenberg, who voted no, explained that in many cases, patients who receive experimental treatments experience improvements but still the therapies fail to delivery significant results in randomized trials. “I don’t know how much regulatory flexibility the FDA is prepared to implement here,” Ellenberg added. The FDA, for its part, has expressed strong skepticism regarding elamipretide and Stealth’s supporting data. In a briefing document released earlier this week, internal reviewers cast doubt on the approvability of the drug candidate, pointing out that it fell short of its primary endpoint in the Phase II TAZPOWER trial. The regulator’s staffers also noted that elamipretide is unlikely to qualify for accelerated approval based on the proposed surrogate biomarker of left ventricle stroke volume, which according to the FDA cannot reliably predict clinical outcomes in Barth syndrome patients. The FDA is currently reviewing Stealth’s application with a target action date of January 29, 2025 .

MONTREAL, Oct. 09, 2024 (GLOBE NEWSWIRE) -- Theratechnologies Inc. (“Theratechnologies” or the “Company”) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on development and commercialization of innovative therapies, today announced three upcoming poster presentations at IDWeek 2024, taking place October 16-19 in Los Angeles, Calif. One poster presents data linking excess visceral abdominal fat (EVAF) to increased cardiovascular risk in people with HIV, while a second poster documents how use of tesamorelin, a growth hormone-releasing factor (GHRF) analog, to reduce EVAF can lower cardiovascular disease risk in persons with HIV. Another poster reports on the study design and baseline characteristics of the PROMISE-US trial, an observational, real-world study of ibalizumab, a CD4-directed post-attachment inhibitor of HIV, in heavily treatment-experienced patients with multidrug resistance. “The IDWeek poster presentations shed new light on important medical issues facing people with HIV,” said Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer of Theratechnologies. “As people live longer with HIV and with greater exposure to anti-retroviral medicines, they may experience higher amounts of excess visceral abdominal fat and risk multidrug resistance. We look forward to sharing our findings with HIV clinicians and researchers at this premier meeting on infectious disease.” Theratechnologies will present the following posters at IDWeek 2024: Title: Impact of Tesamorelin on Cardiovascular Disease Risk Prediction Scores in Phase 3 Studies Treatment Arms: Subanalysis Lead Author: Steven Grinspoon, MD, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.Date & Time: Thursday, October 17, 2024, 12:15 PM – 1:30 PM PTSession Title: HIV: Complications and CoinfectionsLocation: Halls JKPoster Board Number: P-433 Title: Cardiovascular Risk Scores and Insulin Resistance are Higher with Excess Visceral Abdominal Fat in People with HIV in the Modern Antiretroviral (ART) Era. Presenting Author: Karam Mounzer, MD, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.Date & Time: Thursday, October 17, 2024, 12:15 PM – 1:30 PM PTSession Title: HIV: Complications and CoinfectionsLocation: Halls JKPoster Board Number: P-453 Title: A Prospective and Retrospective Observational Study of Multidrug-Resistant Patient Outcomes with and without Ibalizumab in a Real-World Setting: United States (PROMISE-US) Study Design and Baseline Characteristics Presenting Author: Dr. Charlotte-Paige Rolle, M.D., Orlando Immunology Center and Emory Rollins School of Public Health, Orlando, Fla.Date & Time: Thursday October 17, 2024, 12:15 PM – 1:30 PM PTSession Title: HIV: TreatmentLocation: Halls JKPoster Board Number: P-565 IDWeek is the joint annual meeting of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, the Pediatric Infectious Diseases Society and the Society of Infectious Diseases Pharmacists. About Theratechnologies Theratechnologies (TSX: TH) (NASDAQ: THTX) is a biopharmaceutical company focused on the development and commercialization of innovative therapies addressing unmet medical needs. Further information about Theratechnologies is available on the Company's website at www.theratech.com, on SEDAR at www.sedarplus.ca and on EDGAR at www.sec.gov. Follow Theratechnologies on Linkedin and Twitter. Forward-Looking Information This press release contains forward-looking statements and forward-looking information (collectively, the “Forward-Looking Statements”), within the meaning of applicable securities laws, that are based on our management’s beliefs and assumptions and on information currently available to our management. You can identify Forward-Looking Statements by terms such as "may", "will", "should", "could", “promising”, “would”, "outlook", "believe", "plan", "envisage", "anticipate", "expect" and "estimate", or the negatives of these terms, or variations of them. The Forward-Looking Statements contained in this press release include, but are not limited to, statements regarding the longevity of people with HIV and its relationship with increased excess visceral abdominal fat and the risk of multi-drug resistance. Forward-looking statements involve a number of assumptions, risks and uncertainties. The Company refers current and potential investors to the “Risk Factors” section of the Company’s Form 20-F dated February 21, 2024 available on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov under Theratechnologies’ public filings. The reader is cautioned to consider these and other risks and uncertainties carefully and not to put undue reliance on forward-looking statements. Forward-Looking Statements reflect current expectations regarding future events and speak only as of the date of this press release and represent the Company’s expectations as of that date. The Company undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise, except as may be required by applicable law. Contacts: Media inquiries:Julie SchneidermanSenior Director, Communications & Corporate Affairscommunications@theratech.com1-514-336-7800 Investor Inquiries:Philippe DubucSenior Vice President and Chief Financial Officerpdubuc@theratech.com438-315-6608