Gregory Friedman, MD

University of Alabama at Birmingham

in collaboration with Avidea Technologies, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Harvard Medical School, Brigham and Women’s and Boston Children’s Hospital, University of Cambridge, Northwestern University, Lurie Children’s Hospital and Treovir, LLC

CureSearch Acceleration Initiative Award: 2022-2025

Focus: Pediatric High-Grade Glioma

Project title: Overcoming the Adverse Microenvironment of Pediatric High-Grade Gliomas

I am a board-certified pediatric hematologist/oncologist who specializes in pediatric neuro-oncology and conducting pediatric brain tumor research as a Scientist in the Neuro-Oncology Program of the UAB O’Neal Comprehensive Cancer Center. I am also the Director of Developmental Therapeutics for the Alabama Center for Childhood Cancer & Blood Disorders and the site PI for the COG Pediatric Early Phase-Clinical Trial Network (PEP-CTN). My overarching goal is to improve outcomes for children with brain tumors by developing and improving novel, targeted immunotherapies like oncolytic engineered herpes simplex virotherapy (oHSV) in the lab and then translating these therapies to clinical trials. To maximize the benefit of oHSV to treat chemo- and radio-resistant pediatric brain tumors, my lab is focused on determining mechanisms of therapeutic resistance to oHSV by exploring the role of the tumor microenvironment and cellular defense mechanisms so that newer viruses, unique routes of virus delivery, and novel combinations may be developed to circumvent resistance mechanisms.

My experience in managing pediatric neuro-oncology patients and in conducting clinical oncology research complements my oHSV laboratory experience, which has enabled us to translate innovative immunotherapies to clinical trial to benefit children in need. I was the PI for the first completed oncolytic virotherapy pediatric brain tumor trial (NCT02457845; published in NEJM), and I am PI for the first-in-human trial of oHSV G207 in recurrent cerebellar tumors (NCT03911388).

The overarching goal of this CureSearch application is to overcome the cold, unfavorable tumor microenvironment of pediatric high-grade gliomas and diffuse midline gliomas by combining G207 with Avidea’s SNAPvax (self-assembling nanoparticle TLR-7/8 peptide tumor vaccine). Our preliminary data indicates that the combination is superior to either therapy alone. We will develop this combination and translate the approach from bench-to-beside through our collaborations with leading investigators across the globe and our public-private partnerships with biotechnology companies Treovir and Avidea Technologies. We have the experience and expertise to accomplish the proposed aims, and we have demonstrated the required experience in bench-to-bedside translation of novel therapeutics. We are positioned to rapidly translate the approach to clinical trials to positively impact children who are in desperate need of novel, targeted therapies.

Collaborative Team

Sejong Bae – The University of Alabama at Birmingham
Andrew Ishizuka – Avidea Technologies
Mariella Filbin – Dana-Farber Cancer Institute
Oren Becher – Lurie Children’s Hospital
Luca Peruzzotti-Jametti – University of Cambridge
Joshua Bernstock – University of Cambridge
James Markert - The University of Alabama at Birmingham and Treovir
G. Yancey Gillespie - The University of Alabama at Birmingham and Treovir
Richard Whitley - The University of Alabama at Birmingham and Treovir

Outcomes for pediatric high-grade gliomas (pHGGs) range from less than 25% to essentially 0%, in the case of diffuse midline gliomas (DMGs), and these dismal survival rates have not improved in 30 years. Safe, effective immunotherapies for pediatric high-grade glioma (pHGG) including diffuse midline glioma (DMG) have eluded investigators and represent a significant unmet need.

Gregory Friedman, MD, is a CureSearch Acceleration Initiative Award recipient conducting research at the University of Alabama at Birmingham. He and his colleagues are currently conducting a phase I clinical trial in pediatric high-grade glioma and have demonstrated that their oncolytic virus, G207, is safe with very promising efficacy. An oncolytic virus is a virus that is specifically able to enter and destroy cancer cells. Based on the results of the phase I trial, G207 was awarded FDA Fast Track Designation, and Dr. Friedman is developing a multi-institutional Phase 2 trial. While he continues to advance G207 clinically, Dr. Friedman’s goal is to maximize G207’s therapeutic benefit for future clinical trials. In this project, Dr. Friedman will be assessing a combination immunotherapy that he and his colleagues hypothesize will result in a stronger and sustained response to G207 resulting in lasting anti-tumor response. Dr. Freidman will assess combination of G207 with a highly innovative vaccine platform developed by his public-private collaborating partner, Avidea Technologies. In initial proof-of-principle preclinical mouse studies, vaccination prior to G207 treatment significantly enhanced efficacy compared to either therapy alone. The goal of this AI award will be to develop a protocol and obtain regulatory approvals for a Phase 1 clinical trial of the Avidea vaccine (SNAPvax) and G207.

Thank you, Rally Foundation for Childhood Cancer Research for supporting this innovative project.

Project Update: The team has identified additional antigens to target and is developing those vaccines. Working with their industry partner Vaccitech, Dr. Friedman has developed a flowchart for advancing to a clinical trial, and they are beginning to formulate a clinical protocol.

"Outcomes for children with high-grade gliomas including diffuse midline gliomas are unacceptably poor, and our standard therapies are minimally effective and toxic. We are thrilled to partner with CureSearch to help achieve our overall goal of developing safe and effective immunotherapies for pediatric high-grade gliomas. We have had early success using cold-sore virus G207 that kills tumor cells directly and stimulates the child’s immune system to attack the tumor.

This critical grant support from CureSearch enables us to assemble a “dream team” of researchers from academia including UAB and Children’s of Alabama, Dana-Farber, Cambridge, and Mount Sinai as well as industry partners Treovir (G207) and Vaccitech to develop a combination immunotherapy that can produce long-term responses with the virus and Vaccitech’s highly innovative SNAPvax tumor vaccine technology.

We plan to quickly translate the combination therapy to pediatric clinical trials with the goal of improving outcomes and lessening side effects for these children in desperate need of improved, targeted therapies."

- Dr. Gregory Friedman

Gregory Friedman, MD – Acceleration Initiative – Pediatric High-Grade Gliomas