Iterion Therapeutics Announces Initiation of Phase 1/2 Clinical Trial to Study Tegavivint in Pediatric Cancers

HOUSTON, Nov. 9, 2021 /PRNewswire/ -- Iterion Therapeutics, Inc., a venture-backed, clinical-stage biotechnology company developing novel cancer therapeutics, today announced the initiation of a Phase 1/2 clinical trial to investigate tegavivint as a potential treatment for pediatric cancers, including sarcomas, lymphomas and other solid tumors that are prevalent in pediatric populations. This Children's Oncology Group Pediatric Early Phase Clinical Trials Network (COG PEP-CTN)-sponsored trial, led by Sarah Whittle, M.D. Assistant Professor, Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine and pediatric oncologist at Texas Children's Cancer Center, started recruiting patients this month.

COG and PEP-CTN are National Cancer Institute (NCI)-supported clinical trials groups, comprising the world's largest organization devoted exclusively to childhood and adolescent cancer research including early-phase trials. The PEP-CTN is dedicated to conducting early phase clinical trials in children with cancer, building upon the success of the Children's Oncology Group (COG) Phase 1 & Pilot Consortium.

Tegavivint is a potent and selective first-in-class small molecule inhibitor of Transducin Beta-like Protein One (TBL1), a novel downstream target in the Wnt/beta-catenin signaling pathway.  Beta-catenin and TBL1 expression are associated with metastasis and poor prognosis in a broad range of tumor types that are predominantly found in pediatric populations. Tegavivint's targeting of TBL1 prevents the TBL1/beta-catenin complex from forming and specifically inhibits beta-catenin's oncogenic activity without disrupting key cell membrane functions that have been linked to toxicity common to other drugs in this pathway.

"We are very pleased to collaborate with COG-NCI to initiate this Phase 1/2 clinical trial of tegavivint as a potential targeted treatment for pediatric cancers," said Rahul Aras, Ph.D., CEO of Iterion. "Research involving tegavivint suggests that it could be ideally suited to addressing a range of pediatric cancers based on its ability to inhibit TBL1 and, in turn, disrupt the oncogenic activity of beta-catenin.  This unique mechanism of action, combined with tegavivint's demonstrated safety profile in desmoid tumor patients, formed the basis for COG PEP-CTN to initiate the Phase 1/2 trial as a first step in the potential development of tegavivint for both solid and hematologic pediatric tumors."

The Phase 1/2 clinical trial (COG Study PEPN2011; ClinicalTrials.gov Identifier: NCT04851119) of tegavivint in pediatric cancers is fully sponsored by COG PEP-CTN, with support from Iterion, and will be conducted at their 21 consortium clinical centers comprising the leading pediatric cancer centers in the United States. 

"We welcome the opportunity to lead this clinical trial of tegavivint, which targets TBL1, a novel therapeutic target in the Wnt-signaling pathway that has been implicated in multiple pediatric cancers," said Dr. Sarah Whittle, Principal Investigator for the study. "This trial gives us the ability to enrich our understanding of tegavivint's utility in multiple cancer types that specifically impact children and for which few treatments exist other than chemotherapy."

Each year more than 16,000 children in the US¹ and 400,000 worldwide² are diagnosed with cancer, making it the number one cause of death by illness in children³. Treatment options for children are limited and consist mostly of surgery, radiation and various chemotherapies.

Dr. Aras continued, "Cancer is a devastating disease, but particularly when it impacts children.  While current treatment options offer hope, they can be harsh on pediatric patients, leading to many unintended downstream consequences for survivors, such as heart and lung damage or secondary cancers including myelodysplastic syndrome, acute myeloid leukemia and solid tumors. The development of safer and potentially curative treaments that spare children from short-term and long-term treatment side effects remains a critical goal.  We believe tegavivint holds such promise."

The Phase 1/2 study of tegavivint in pediatric cancer patients follows compelling clinical data establishing the drug's safety and clinical activity in adults with progressive and nonresectable desmoid tumors. The Phase 1/2a desmoid study enrolled 24 patients who received tegavivint. The treatment was well-tolerated with no observed dose limiting toxicities with several patients having received treatment for more than a year.

About Iterion Therapeutics
Iterion Therapeutics is a venture-backed, clinical stage biotechnology company developing novel cancer therapeutics. The company's lead product, tegavivint, is a potent and selective small molecule that binds to TBL1 in the nucleus inhibiting nuclear beta-catenin signaling and oncogenic activity. Research demonstrating potent anti-tumor activity in a broad range of pre-clinical models indicate that tegavivint has the potential for clinical utility in multiple cancer types. Tegavivint is currently the subject of a Phase 1 clinical trial in patients with relapsed or refractory acute myeloid leukemia (AML) and a Phase 1/2 trial in pediatric patients with sarcomas, lymphomas and other solid tumors, excluding central nervous system (CNS) tumors. Iterion is also pursuing a clinical program in non-small cell lung cancer (NSCLC), in which nuclear beta-catenin signaling has been shown to play a role.  Data from a Phase 1/2a clinical trial of tegavivint in patients with progressive desmoid tumors demonstrated safety and preliminary clinical efficacy. Iterion is the recipient of an up to $15.9 million Product Development Award from the Cancer Prevention and Research Institute of Texas (CPRIT).  For more information on Iterion, please visit https://iteriontherapeutics.com.

About The Children's Oncology Group (COG) and Pediatric Early Phase Clinical Trials Network (PEP-CTN)
COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world's largest organization devoted exclusively to childhood and adolescent cancer research. COG unites over 10,000 experts in childhood cancer at more than 200 leading children's hospitals, universities, and cancer centers across North America, Australia, and New Zealand in the fight against childhood cancer. Today, more than 90% of the 16,000 children and adolescents diagnosed with cancer each year in the United States are cared for at COG member institutions. Research performed by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with a combined 5-year survival rate of 80%. COG's mission is to improve the cure rate and outcomes for all children with cancer.

COG PEP-CTN, funded by the NCI, is the largest early phase trial organization devoted to pediatric cancer, leveraging the expertise of 21 selected institutions within the COG based on their experience in new therapies for childhood cancer. The COG PEP-CTN designs and conducts pediatric early phase trials including phase 1 trials that often include phase 2 expansion cohorts. In addition, the PEP-CTN conducts pilot studies of novel agents/regimens to determine their tolerability so that promising agents/regimens can proceed to definitive testing in phase 3 clinical trials

About Texas Children's Hospital
Texas Children's Hospital, a not-for-profit health care organization, is committed to creating a healthier future for children and women throughout the global community by leading in patient care, education and research. Consistently ranked as the best children's hospital in Texas, and among the top in the nation, Texas Children's has garnered widespread recognition for its expertise and breakthroughs in pediatric and women's health. The hospital includes the Jan and Dan Duncan Neurological Research Institute; the Feigin Tower for Pediatric Research; Texas Children's Pavilion for Women, a comprehensive obstetrics/gynecology facility focusing on high-risk births; Texas Children's Hospital West Campus, a community hospital in suburban West Houston; and Texas Children's Hospital The Woodlands, the first hospital devoted to children's care for communities north of Houston. The organization also created Texas Children's Health Plan, the nation's first HMO for children; Texas Children's Pediatrics, the largest pediatric primary care network in the country; Texas Children's Urgent Care clinics that specialize in after-hours care tailored specifically for children; and a global health program that's channeling care to children and women all over the world. Texas Children's Hospital is affiliated with Baylor College of Medicine. For more information, go to www.texaschildrens.org. Get the latest news by visiting the online newsroom and Twitter at twitter.com/texaschildrens.

About Baylor College of Medicine
Baylor College of Medicine is a health sciences university that creates knowledge and applies science and discoveries to further education, healthcare and community service locally and globally.

It is the only private medical school in the greater southwest and is ranked 22^nd among medical schools for research and 17^th  for primary care by U.S. News & World Report. The Baylor pediatrics program is ranked 7^th  among all pediatric programs, reflecting the strong affiliation with Texas Children's Hospital where our faculty care for pediatric patients and our students and residents train. Located in the Texas Medical Center, Baylor has affiliations with seven teaching hospitals and jointly owns and operates Baylor St. Luke's Medical Center, part of CHI St. Luke's Health. More information on Baylor College of Medicine may be found on our website, https://www.bcm.edu/, on Facebook, http://facebook.com/BaylorCollegeOfMedicine, Twitter, http://twitter.com/bcmhouston, and LinkedIn, http://www.linkedin.com/company/baylor-college-of-medicine. 

¹ CA Cancer J Clin 2021; 71:7-33
² Steliarova-Foucher E, Colombet M, Ries LAG, et al. International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. 2017;18(6):719-731.
³ N Engl J Med 2018; 379:2468-2475 DOI: 10.1056/NEJMsr1804754

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SOURCE Iterion Therapeutics