TEAM JACK FOUNDATION INC

This project studies the drug Tovorafenib/DAY 101 (formerly TAK 580) as a possible treatment of pLGG (pediatric low grade gliomas) that have not responded to other treatments. The Team Jack Foundation committed $300,000 to this study to study the safety of the drug and define the appropriate dosage (phase I). In 2017, Team Jack made an additional investment of $500,000 for both MEK 162 and TAK 580 to further investigate. Research in the laboratory has shown that DAY101 may have activity against cancer cells. DAY101 belongs to a group of drugs called type II BRAF inhibitors. BRAF abnormalities are found in cancer cells. There are no type II BRAF inhibitors approved by the FDA for humans at the time of this study's start. In 2020, Day One Biopharmaceuticals acquired the rights to develop and commercialize DAY101 wordwide. In January 2023, Day One announced topline data from FIREFLY-1 trial which demonstrated meaningful responses.

DIPG is the deadliest type of brain tumor in children with less than 1% survival rate. The Team Jack Foundation committed $150,000 to Dr. Phillips at the University of Pennsylvania to study a very promising new therapy for the disease. In collaboration with the Therapeutics Discovery Institute at Memorial Sloan Kettering Cancer Center, Dr. Phillips and his lab have developed novel EZH2 inhibitors that exhibit brain penetrance in mouse models in vivo. The overall goal of this project is to optimize and validate these novel brain-penetrant EZH2 inhibitors in vivo and characterize biomarkers of anti-tumor response to EZH2 inhibition in DIPG toward eventual use in human clinical trials. The goal of this study is to translate findings into clinical trials to develop new treatments for children with DIPG.

In 2020, the Team Jack Foundation committed $325,000 to Dr. Ashley Plant-Fox at Lurie Children's Hospital to study a Heat Shock Protein (HSP) Neo-Antigen Vaccine Plus Checkpoint Blockade for Diffuse Intrinsic Pontine Glioma (DIPG), the deadliest form of childhood brain cancer. This phase I clinical trial is evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB. rHSC-DIPGVax is an off-the-shelf neo-antigen heat shock protein containing 16 peptides reflecting neo-epitopes found in the majority of DIPG and DMG tumors. The clinical trial officially opened and began enrolling patients in January 2022. In April 2022, the first patient received two doses and is currently doing well. This study will improve therapies for children diagnosed with DIPG.

Together with the Nebraska legislature, Team Jack has committed $3 million to the development of a childhood brain tumor program at UNMC’s Fred & Pamela Buffett Cancer Center. With the passing of LB 110 in 2015, public and private resources are continuously being raised to attract brain tumor experts to Nebraska and build a comprehensive program. The specialized treatment of pediatric brain tumors requires diagnosis and treatment recommendations from physicians who have developed brain tumor treatment as an area of sub-specialty.

As a continuation of the funding to the Nebraska Childhood Brain Tumor Program, the Team Jack Foundation launched the Power5 Childhood Brain Tumor Initiative in 2018. The Team Jack Foundation will invest $5 million at UNMC and Children's Hospital Omaha over ten years, beginning in 2019. These dollars will fund key areas: 1. Laboratory & Clinical Research Funding laboratory research will allow experts to develop new treatments and offer them to patients through clinical trials. In addition, Omaha will be able to host other national clinical trials as well. 2. Pain Management in Cancer Investing in pain management will help develop a national protocol to help all children fighting cancer better manage pain, especially at end of life. 3. Education The education piece of the POWER5 program will help develop expertise here in Nebraska with existing medical professionals.

The Team Jack Foundation awarded $50,000 to Memorial Sloan Kettering Cancer Center to allow Dr. Maya Graham to research the gaps in insights into oncohistone-mediated gliomagenesis that currently pose a barrier to therapeutic development for patients with high-grade gliomas. The proposed project will further understanding of the mechanisms underlying oncohistone-mediated transformation in pHGG and allow for rational selection of targeted therapies for this devastating disease, with implications for the broader role of epigenomic reprogramming in pediatric cancer. By Team Jack funding the early stages of Dr. Graham's project, she was able to retrieve preliminary data for several additional grants.

Primary high-grade gliomas (pHGGs) in children are almost uniformly lethal. The Team Jack Foundation has committed $100,000 to Dr. Sayour at the University of Florida to start a first-in-human clinical trial to test a novel form of immunotherapy to treat pHGG (pediatric high grade gliomas). The treatment platform which leverages the use of nanoparticles (NPs) combined with messenger RNA (mRNA) taken from the patient’s tumor to make a product that functions as both a vaccine and an agent that is capable of increasing activity of the immune system. To facilitate translation of this promising technology into first-in-human studies for pHGG, Dr. Sayour and colleagues have partnered with the Pacific Pediatric Neuro-Oncology Consortium (PNOC), where their clinical trial concept was accepted for multi-institutional trial development.

The Team Jack Foundation has committed $240,000 at Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center to Dr. Pratiti (Mimi) Bandopadhayhay to apply a genomic approach to identify drivers of pediatric low-grade glioma (pLGG) growth. Understanding these “mystery drivers” is critical to treating and ultimately curing pLGGs.