b'POWERING MICHELLE MONJE, MD, PHDMICHELLEMONJE,MD,PHDProfessorofNeurology&Neurologi i cal l Sciences Leo D. Wang, MD, Ph.D. Investigator,HowardHughesMedca Institute Departments of Pediatrics Department of Pediatrics and Immunooncology CURESDepartment of ImmunooncologyBeckman Research Institute Jeri Wilson, Executive Directorand City of Hope 1500 E. Duarte Road Pediatric Cancer Research FoundationDuarte CA 91010-3000 2151 Michelson Drive, Suite 180Resolute in our quest to fund research thatIrvine, CA 92612626.218.8173 .Phone drives momentum and discovers treatmentMay, 2023 Fax626.301.8817 May,2023 February 14, 2022Emailleo.wang@coh.orgleowanglab.org breakthroughs, PCRF invested $3,294,094 inDear Jeri, Dear Jeri: www.cityofhope.orgI am writing to thank you for PCRF support of our work and to provide you with an update.research programs in 2022. We are proud toDear Jeri, andto provide you with anupdate. vous forPCRF support of work, childsdevelopingI wanted to thank you personally for the suppOur eorts to understand how pediatric brain cancers grow and progress in the environment of a childs developing nersupport innovative scientists who represent I am writing to thank you in theenvironment of a , your assistance made it p RF have shown for our work during a tumultuous and uncertain time. As weve discussed in the past ort that you and PCsystem led to the discovery that brain cancers depend on the most powerful factor regulating brain development - the activity how pediatricbrain cancers growandprogress powerful factor regulating braina devast ossible for us to continue the future of pediatric cancer care treatment. most responsible ating pandemic and its tremendous economic and labor conse to do groundbreaking science in the midst of of the nervous system itself. We found that the activity of neurons - brain cells responsible for conveying information and that depend of the brain cells thanks to your help, we were able to get back to work quickly and eciently. obviously didnt stop because of COVID, and Oureortsto understand brain cancers thattheactivity of neurons-systemledto thediscovery that systemitself. We found promotestheinitiation, growth andquences. Cancer As these letters indicate, your funding of nervous nervous ediatric brain cancers called gliomas -theactivityof the system function - spinalcordand optic nerve. As you know, your generous supporunderpin nervous system function - promotes the initiation, growth and progression of p brain andthat occur in the brain, brainstem, spinal cord and optic nerve. is brain activity-regulated cancer growth can be explained by development andthatunderpin nervous thebrain,brainstem, brain that normally PCRF is making a much-needed difference. that occur in in the t enabled us to start treating peforconveying information called gliomas released brainan innovative new immune therapy called CAR T cell therapy. diatric brain tumor patients with growth factors released in the brain that normally contribute to brain development and growth, and also by electrical brain cancers by growth factorsprogression of pediatric explained connectionsbetween the normal ever ything was still lo aOur trial opened in September of 2020, when connections between the normal brain and brain cancer. ese connections, called synapses, are critically important for glioma -regulatedcancer growth can be also by electrical progression. e twop cked down, but your support was critic l in allowing us to move forisbrain activity and growth,and for gliomatumor growth and anddiuseintrinsic atients on our trial before the end of 2020, which pl ward. With your help, we were able to treat contribute y of these connections also helps explain why childhood gliomas - includingas w to fund our trial in April of 2021. Since then, we have moved full steam ahead to en alifornia Institute for Regenerative to brain development synapses,arecritically important -including glioblastoma Medicineayed a pivotal role in convincing the Cpontine glioma(DIPG)-haveseemedso intractable.ecancersactually integrate electrically into glioblastoma and diuse intrinsic pontine glioma (DIPG) - have seemed so intractable. e cancers actually integrate structurally eseconnections,called explain whychildhood gliomas structurallyandcancer. also helps ell as to expand the trial to Childr boration withroll and treat more patients on the trial, tumor growth and progression. e discoverdiscovery of theseconnections than we woul ens Hospital of Los Angeles in colla Dr. Tom Belle Davidsd have liked, mostly due to legal negotiations on. \x1eis has taken longer and electrically into the brain.childhoodbrain cancers,we havebeen working toLooking back , but we are optimistic that the trial will open there before summer.In light of this fundamental new understanding of these insidious childhood brain cancers, we have been working to thebrain. insidious brains own activity.is work has , we have many things to be grateful fotherapeutically target and block glioma cancer cells ability to take advantage of the brains own activity. is work has uncovered In light of this fundamental new understanding of these to takeadvantage of the theseconnections grateful for your partnership and advocacy on our b r, and funding from the PCRF is near the top of the list. I am, however, even more block gliomacancercells ability epilepsy,thattarget therapeutic plans; they help fo ehalf. I very much appreciate our convers, normally used for other brain diseases like epilepsy, that target these connections between the cancer and the severalmedicines, normally used for otherbrain diseaseslike astrategy that cus our eorts s ations around needs, challenges, and therapeutically targetand laboratory. Ithasalso motivated isalreadyallyship, irrespe o that we can achieve as much as possible as eciently as puncovered and brain to slow tumor growth in the eutic strategies that leverage the immune system toctive of funding support. It is tremendously valued and appreciated. ossible. \x1eank you for continued several medicines the to seekanddestroy thesebrain cancer cells, Support from cancer y.It has also motivated therap theseeorts,particularly the Looking forward, we have many things strategies , a strategy that is already proving hopeful for patients in clinical trial.between the system supported take al standpoint, City of Hop to accomplish; building out CHLA as a second site is just the rst of them. From an operation-brain to slow tumor growth in the laboratorproving hopeful for patients ts, particularly the identication of medicines that block these thatleveragetheimmune SupportfromPCRF has childhoodbrain cancers brain in clinicaltrial. thebrain that aggressive particular thos e has made a strong commitment to serving patients throughout Southern Californiaseek and destroy these brain cancer cells these growth signals from immunotherapiesfor thesegrowth signals from the brain that childhood brain cancers take advantage of, medicines that may ted these eor theecacy of promising ancers. e patients who might not otherwise b , including and in identication of medicinesthatblock augment gressive brain c One of our strategic goals in the next e able to access the cuPCRF has suppor thatmay help receive CAve years is to cr tting-edge care that we can provide on our main campus. help augment the ecacy of promising immunotherapies for these agadvantage of,medicines R T cell therapies in their own communities eate an implementation network that allows patients to safely and eectively cancers. charged with making this happen, and, rather than forcing them to drive hours to see us. I will be leading the team wisdom. would welcome the opportunity to partner with you and your netwoSincerely, From a research science standpoint rk for your insight and patients is moving for , our mission to improve CAR T therapy for peward with astonishing speed.Now that we have started treating pati diatric brain tumor MichelleMonje,MD,PhD lSciences have Michelle Monje (Stanford), Nick Vitanza (S ents with CAR T cells, as &Neurologica Psychiatry all of these patients during therapy to identif eattle), and Bilal Omer (Texas Childrens), we can examine samples obtained from Professor ofNeurology and us y features that will help us understand why CProfessor,bycourtesy,of Pediatrics, Pathology, Neurosurgery and e that information to build better CAR T cells AR T cells workand why they dontInvestigator,HowardHughesMedicalInstitute cells receive when they encounter tumor cells . Additionally, work in our laboratory is focusing on specic signals that CAR T immune responses , and on how to amplify those signals to make better and moStanfordUniversity . A central challenge in the eld is that CAR T ce re robust antitumor but cancer cells can learn to get rid of that target lls generally only recognize one particular target on cancer cells, create CAR T cells th . \x1eis renders the CAR T cells unable to kill the cancer cellsat teach other immune cells to recognize and kill cancer cells, s . We are working to they can still be killed. o that even after they lose target expression Again, thank you for your enduring support. I very much look forLorryI.LokeyStemCellResearchBuilding,265Campus Drive,RoomG3077 Very best wishes, ward to continuing to work together.Stanford, CA94305 Leo D. Wang, MD, Ph.D. Super job Hope for Henry! T650.721-5750REALIZING FUTURES Emmonje@stanford.edu over their trauma andThanks for getting kids letting them rediscover At eight years of age, Kenny Thomas came down with a cough he couldnt shake. He their smiles. also had night sweats and was losing weight.Eventually, tests confirmed that Kenny had One of the hardest parts of my job is to Precursor T-Cell Lymphoblastic Lymphoma, a form of non-Hodgkin Lymphoma. Treated with the AALL 0434 therapy protocol for two years, Kennys cancer went into remissionhave to tell a young patient and their family after several months of intensive chemotherapy.that we have no treatment left to offer Today, this healthy 19-year-old cancer survivor is preparing for his sophomore year at Michigan State.Hed like to pursue a career as an attorney in sports management or as athem. PCRF is a game changer in that they defense attorney. After making the Deans List in his first semester, he was invited to applysupport bringing ideas to discovery in our to the Social Sciences Scholars Program. He was accepted and will study in Europe during the summer of 2024. In his spare time, Kenny is an avid speaker on behalf of pediatriclaboratories which in turn become Phase I cancer research.He believes increasing awareness about the need for more research funding is vital to finding new cures. He has appeared at our Dribble events for the pastand Phase II clinical trials for children. There nine years and has addressed members of Congress, pressing for more Federal funding to help put an end to childhood cancer. is no substitute to giving hope for a cure! Kenny was treated by Dr. Theodore Moore at UCLA. PCRF has funded Dr. Moore for the~ Dr. Theodore B. Moorepast 16 years.11'