UCSF Benioff Children's Hospital Oakland

Extreme heat events were associated with increased asthma hospital visits, according to new research. For children seeking care at a California urban pediatric health center, extreme heat events were associated with increased asthma hospital visits, according to research published at the ATS 2024 International Conference. "We found that both daily high heat events and extreme temperatures that lasted several days increased the risk of asthma hospital visits," said corresponding author Morgan Ye, MPH, research data analyst, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco School of Medicine. "Understanding the impacts of climate-sensitive events such as extreme heat on a vulnerable population is the key to reducing the burden of disease due to climate change." Ms. Ye and colleagues looked at 2017-2020 electronic health records from the UCSF Benioff Children's Hospital Oakland, which included data on asthma hospital visits by patients of the hospital, some of whom are from Benioff Oakland's Federally Qualified Health Center, and demographics including patients' zip codes. They used data from the PRISM Climate Group of Oregon State University to determine the timing of daily maximum (daytime heat waves) and minimum (nighttime heat waves) for each zip code. The researchers restricted their analyses to the region's warm season (June to September). To evaluate the potential range of effects of different heat wave measurements, they used 18 different heat wave definitions, including the 99th, 97.5th and 95th percentile of the total distribution of the study period for one, two or three days. They designed the study in a way that allowed them to determine the association between each heat wave definition and a hospital visit. They repeated the analysis for Bay Area and Central California zip codes. The team discovered that daytime heat waves were significantly associated with 19 percent higher odds of children's asthma hospital visits, and longer duration of heat waves doubled the odds of hospital visits. They did not observe any associations for nighttime heat waves. According to Ye, "We continue to see global temperatures rise due to human-generated climate change, and we can expect a rise in health-related issues as we observe longer, more frequent and severe heat waves. Our research suggests that higher temperatures and increased duration of these high heat days are associated with increased risk of hospital visits due to asthma. Children and families with lower adaptation capacity will experience most of the burden. Therefore, it is important to obtain a better understanding of these heat-associated health risks and susceptible populations for future surveillance and targeted interventions." The authors note that past research has suggested positive associations between extreme heat and asthma, but findings regarding hospitalizations and emergency room visits have been conflicting. Additionally, many other studies have focused on respiratory hospitalizations and not hospitalizations for asthma, specifically, and have not included or had a focus on children. This study is also unique because it investigated the effect of daily high temperatures but also the effects of persistent extreme temperatures. The San Francisco Bay Area and California overall are unique areas of interest because the state is considered a coastal region with less prevalence of cooling units, such as air conditioners. While temperatures may not reach the extremes experienced in other parts of the country, this study demonstrates that even milder extreme heat temperatures may significantly impact health. These effects are more pronounced in climate-susceptible populations, including children and those who are medically vulnerable, such as those served by the urban pediatric health center in this study. The authors hope these study results will lead to more equitable health outcomes and reduce racial/ethnic disparities observed in climate-sensitive events. "These results can be used to inform targeted actions and resources for vulnerable children and alleviate health-related stress during heat waves," they conclude.

– Article Published in November 9th Issue of ASCO’s Journal of Clinical Oncology Precision Oncology (JCO PO) – – Results highlight PPMP as a tool for identifying most promising drug combinations for patients in high unmet medical needs, including JMML – FOSTER CITY, Calif., Nov. 09, 2023 (GLOBE NEWSWIRE) -- Notable Labs, Inc. (“Notable”) (Nasdaq: NTBL), a clinical stage therapeutic platform company developing predictive precision medicines for cancer patients, today announced the publication of data from an ex vivo study demonstrating the potential for its Predictive Precision Medicine Platform (PPMP) to identify more effective pre-hematopoietic stem cell transplantation (pre-HSCT) regimens for the treatment of juvenile myelomonocytic leukemia (JMML) in the November 9th Issue of the American Society of Clinical Oncology (ASCO) Journal JCO Precision Oncology. Part of this data was recently presented at the European Hematology Association (EHA) Hybrid Congress held in Frankfurt, Germany on June 8 – 15, 2023. Details of that presentation can be found on the Company’s website at https://notablelabs.com/. JMML is a rare, aggressive pediatric malignancy for which curative treatment is restricted to hematopoietic stem cell transplantation. Pre-HSCT therapies, i.e., therapies prior to transplantation, include moderately intensive chemotherapy (particularly fludarabine and cytarabine in combination (FLA)) and azacytidine (AZA) monotherapy. Unfortunately, in many cases, neither FLA nor AZA effectively eliminates the malignant cells and patients proceed to transplant with active disease. Applying its proprietary PPMP technology to blood or bone marrow samples from JMML patients, Notable screened 130 drug combinations and discovered that 27 of these combinations (26 dual-, 1 triple-combination) were more effective ex vivo than the components of these combinations tested individually. Of particular interest, investigators found that tretinoin (all-trans retinoic acid), a drug used as a standard-of-care agent in acute promyelocytic leukemia (APL), specifically enhanced the ex vivo effects of FLA and AZA. In addition to lowering the numbers of cells surviving FLA or AZA treatment, tretinoin, interestingly, also induced the cell surface expression of CD38, suggesting a potential rationale for use of CD38-targeting agents to further enhance the envisioned treatment effect. By identifying a superior combination effect with tretinoin, this research study identified potentially more effective pre-HCST regimens than those currently in use in JMML. “Publication in this prestigious, peer-reviewed journal not only highlights the profound need for better JMML treatment outcomes, but it further speaks to the powerful utility of Notable’s PPMP predicting treatment outcome, as demonstrated for other diseases,” said Thomas Bock, M.D., Chief Executive Officer of Notable. “In addition to identifying potentially more effective pre-HSCT drug combinations, these data may also serve as a valuable database for researchers and physicians by detailing the ex vivo effects of 130 drug combinations on JMML leukemic cells to prioritize therapeutic regimens for future clinical study and advance the standard of care.” The research article, titled “Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay” was first-authored by Dr. Elliot Stieglitz, M.D., Associate Professor at UCSF Benioff Children’s Hospital (UCSF, https://profiles.ucsf.edu/elliot.Stieglitz). “This publication marks the culmination of a multi-year collaboration between UCSF and Notable Labs,” remarked Dr. Stieglitz. “The ex vivo study described in the research article represents the largest high-throughput drug screen using primary samples conducted to date in this rare disease and will serve as a blueprint for researchers trying to bring novel combinations of medications to the clinic.” About Notable Labs, Inc. Notable Labs, Inc. is a clinical-stage platform therapeutics company developing predictive precision medicines for patients with cancer. Through its proprietary Predictive Precision Medicines Platform (“PPMP”), Notable bio- simulates a cancer treatment and predicts whether or not a patient is likely to respond to that specific therapeutic. Notable’s PPMP can identify and select clinically responsive patients prior to their treatment and thus fast-track clinical development in this patient population. By continually advancing and expanding the reach of the PPMP across diseases and predicted medical outcomes, Notable aims to be the leader in precision medicine and revolutionize the way in which patients seek and receive treatments that work best for them – patient by patient and cancer by cancer. Notable believes it has created a targeted and de-risked in-licensing strategy to deliver a product’s medical impact and commercial value faster, higher, and with a greater likelihood of success than traditional drug development. By transforming historical standards of care, Notable aims to create dramatic positive impact for patients and the healthcare community. Notable is headquartered in Foster City, California. Learn more at www.notablelabs.com and follow us @notablelabs. CONTACTS: Investor Relations: Daniel Ferry, LifeSci Advisors +1 (617) 430-7576, daniel@lifesciadvisors.com

Ten young children born without functioning immune systems and lacking the ability to fight infections are on track for healthier lives thanks to a new gene therapy treatment. Ten young children born without functioning immune systems and lacking the ability to fight infections are on track for healthier lives thanks to a new gene therapy treatment pioneered at UC San Francisco, reports a Dec. 22 study in the New England Journal of Medicine. The children have Artemis-SCID, a very rare genetic disorder that is typically treated with a bone marrow transplant from a healthy donor, ideally a matched brother or sister. The new gene therapy allows researchers to treat newly diagnosed babies with their own cells -- adding a healthy copy of the Artemis gene to the baby's harvested marrow stem cells, then infusing the corrected stem cells back into their bodies -- in hopes of avoiding many of the short- and long-term complications of the standard treatment, including death. The children in the trial -- all under the age of 5 -- are living at home with their families, attending daycare and preschool, playing outside, and living normal lives, said Mort Cowan, MD, UCSF pediatrics professor and the trial's lead investigator. "Already, the course of their illness is so much better than with the typical treatment," said Cowan, who has treated more than 30 children with Artemis-SCID using standard bone marrow transplants. "I've never seen results like this in any of the other kids. It's amazing." Gene correction has been used before in patients with other genetic forms of SCID, but its use in Artemis-SCID is significant because these patients usually respond more poorly to standard bone marrow transplants. Complications can include rejecting the marrow graft, graft-vs.-host disease -- in which the donor T cells attack the recipient's tissues -- chronic infections leading to organ damage, stunted growth, and premature death. Signs of Stronger Immunity The first outcome of the Phase I/II trial involved the safe transfusion of gene-corrected cells that would differentiate into white blood cells by 42 days after infusion. Researchers theorized patients would need less chemotherapy to prepare their marrow for transfusion when their own cells were being used; thus only 25% of a full dose of busulfan was administered. The second outcome was T-cell reconstitution at 12 months, a measurement of the strength of the immune system. All 10 patients were safely transfused with their own gene-corrected stem cells that gave rise to corrected peripheral blood cells within 42 days. All 10 were growing their own T cells and B cells by 12 weeks, and four of nine (excluding a patient who received a second treatment) achieved full T-cell immune reconstitution by 12 months. Four of nine also achieved full B cell immunity by 24 months, allowing them to discontinue immunoglobulin replacement and receive standard childhood vaccinations. An additional three patients, who were followed for fewer than 24 months, had promising B cell development when compared to previous outcomes for donor-transplanted patients. One child required a second infusion of gene-corrected bone marrow due to a persistent infection with cytomegalovirus prior to gene therapy but is now infection free with good T- and B-cell immunity. "All of the results are better than those previously seen with Artemis-SCID patients who received donor bone marrow transplants," noted Jennifer Puck, MD, UCSF pediatrics professor and co-lead investigator in the study. "Having patients in the trial achieve full T-cell immunity is outstanding. B-cell recovery takes longer, but so far it looks as if the patients also have a far better chance for B-cell reconstitution than they would with a regular bone marrow transplant," Puck said. "Successfully using less chemotherapy is also a big win, minimizing the harmful side effects of full dose busulfan in small infants." Better B-cell immunity could help avoid issues such as chronic lung disease that often develop later in childhood for Artemis-SCID patients who receive a standard bone marrow transplant, Cowan added. The children in the trial are currently between the ages of 18 months and 4.5 years; nine were born in the U.S. and were diagnosed following newborn screening for SCID; one was born in Canada and diagnosed at five months of age with clinical illness. Four patients are of Navajo/Apache Native American descent, where the Artemis-SCID mutation is more common. Median follow-up was 31.2 months. At the time of study publication, six patients had been followed for at least 24 months. "We're pioneering gene therapy in this very rare disease right now, but we are using techniques that can be exported to other situations and can help many other conditions worldwide," said Puck. "Every new innovation happens one patient at a time." Co-authors: Also contributing to this research from UCSF were: Jason Yu, PhD; Carol Fraser-Browne, BA; Ukina Sanford, MS; Misako Kawahara, BA; Wendy Chan, BS; Shivali Chag, MS; and Robert Currier, PhD, of the UCSF Department of Pediatrics; Jess Oh, MS, of the UCSF Benioff Children's Hospital San Francisco; Jasmeen Dara, MD; Janelle Facchino, NP; Christopher Dvorak, MD, of the UCSF Department of Pediatrics and UCSF Benioff Children's Hospital San Francisco; Joan Hilton, DSc, MPH, of the UCSF Department of Epidemiology and Biostatistics; and Janel Long-Boyle, PharmD, PhD, of UCSF's Department of Pediatrics, School of Pharmacy and UCSF Benioff Children's Hospital San Francisco. Please refer to the paper for additional co-authors.