Iterion Therapeutics Announces Presentation of Three Posters Involving Research into Tegavivint at the AACR 2022 Annual Meeting

Results from Phase 1 Dose Escalation Study of Tegavivint in Patients with Desmoid Tumors to Be Featured as in a Poster Presentation on April 12, 2022

HOUSTON, April 8, 2022 /PRNewswire/ -- Iterion Therapeutics, Inc., a venture-backed, clinical-stage biotechnology company developing novel cancer therapeutics, today announced that three posters involving research into tegavivint will be presented at the 2022 American Association for Cancer Research (AACR) Annual Meeting, including initial results from a Phase 1 study of tegavivint in patients with desmoid sarcomas. AACR 2022 is being held April 8-13, 2022, in New Orleans.

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

The first poster, titled, "A phase I dose escalation study of a tegavivint (BC2059) a first-in-class TBL1 inhibitor for patients with progressive, unresectable desmoid tumors," will be presented on Tuesday, April 12, 2022, at 9:00 a.m., CDT, during the Phase I Clinical Trials 2 session (poster board number 10; abstract number CT185).  The poster details results from the dose-escalation portion of a Phase 1 trial of tegavivint in adult patients with progressive, unresectable desmoid sarcoma.  The primary objective of the study was to evaluate the safety and tolerability of tegavivint administered once weekly and to determine a recommended phase 2 dose (RP2D).  As described in the poster, tegavivint was well tolerated with grade 3 treatment related adverse events (TRAEs) reported in four patients for hypophosphatemia, stomatitis, headache, and elevated ALT; no grade 4 or 5 TRAEs were observed. No dose-limiting toxicities (DLT) were observed, and the maximum tolerated dose (MTD) was not declared. Objective responses (WHO and RECIST) were observed at multiple dose levels and the clinical benefit rate was 82% (n = 14). The RP2D was declared based on lack of DLTs, pharmacologically relevant plasma concentrations, and preliminary efficacy. In conclusion, tegavivint's preliminary efficacy and favorable safety profile supported continued development through a dose expansion arm of the study, data from which will be presented at a future conference.

"We are very excited to report research describing tegavivint's unique properties and therapeutic potential in multiple poster presentations at AACR 2022; particularly the results of our first-in-man Phase 1 clinical study," said Rahul Aras, PhD, CEO of Iterion. "Taken together, these results demonstrate inhibition of TBL1 as a clinically viable strategy to curtail nuclear beta-catenin oncogenic activity in multiple cancer indications."

Dr. Aras continued, "Importantly, results from the dose-escalation part of the Phase 1 study of tegavivint in patients with progressive desmoid sarcomas demonstrated the drug to be well-tolerated and indicated clinical activity in this difficult-to-treat disease. While regarded as a high value oncology target, nuclear beta-catenin has historically been considered undruggable through conventional drug development. Upstream approaches targeting the Wnt/beta-catenin pathway have not clinically advanced, typically because of toxicity in early phase clinical development. However, we believe tegavivint's ability to selectively disrupt the interaction of beta-catenin and TBL1 results in the specific degradation of nuclear beta-catenin without impacting key cell membrane functions that have been linked to previously reported toxicity.  The Phase 1 data presented at AACR 2022 demonstrate this capability, which we are now further investigating in three separate, ongoing clinical trials of tegavivint in AML, non-small cell lung cancer, and pediatric solid tumors."

The second poster, titled, "Targeting TBL1 inhibits nuclear β-catenin activity and enhances immune checkpoint inhibition efficacy in osteosarcoma," will be presented virtually by Kengo Nakahata, MD, PhD, Postdoctoral Associate, Texas Children's Hospital on Friday, April 8, 2022, at 12:00 p.m., CDT. The poster reports results from a pre-clinical study examining the influence of tegavivint on the osteosarcoma (OS) tumor immune microenvironment and potential combination with anti-PD1 antibody therapy. Data from the study indicated that tegavivint as a monotherapy significantly suppressed the growth of murine OS tumors (p<0.05), while anti-PD1 monotherapy did not show any significant anti-tumor activity. Combining anti-PD1 with tegavivint was able to further improve overall anti-tumor activity. Tegavivint treatment was also associated with an intratumoral increase in CD8-positive T-cells and NK cells compared with control tumors.

The third poster, titled, "Novel combination therapies against AML with 3q26 lesions and EVI1 overexpression," will be presented virtually by Christine Birdwell, Research Scientist, MD Anderson Cancer Center on Tuesday April 12, 2022, at 9:00 a.m., CDT. The poster describes a study examining the potential for tegavivint as a therapy against AML models harboring 3q26 lesions and EVI1 overexpression. EVI1 overexpression is known to confer poor response to therapy and, subsequently, inferior relapse-free and overall survival in AML.  As reported in the poster, in vitro treatment with tegavivint dose-dependently induced apoptosis in AML cell lines and patient-derived AML cells with 3q26.2 lesions with and without monosomy. Furthermore, in vivo studies demonstrated that tegavivint combined with BCL2 inhibitor, venetoclax, significantly reduced AML burden and improved overall survival in mouse models, without toxicity, compared to treatment with each drug alone.

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. Currently, tegavivint is the subject of three separate clinical trials: a Phase 1 clinical trial sponsored by MD Anderson Cancer Center in patients with relapsed or refractory acute myeloid leukemia (AML); a Phase 1/2 clinical trial sponsored by Children's Oncology Group Pediatric Early Phase Clinical Trials Network in pediatric patients with sarcomas, lymphomas and other solid tumors, and a Phase 1 clinical trial sponsored by Ohio State University Comprehensive Cancer Center in EGRF-positive non-small cell lung cancer (NSCLC). 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.

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SOURCE Iterion Therapeutics