Treadwell Therapeutics, a clinical-stage biotechnology company developing novel medicines for highly aggressive cancers, today announced a presentation for the Company's CFI-402411 program, an oral, first-in-class inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) a negative regulator of immune cell activation, at the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting being held virtually and in-person from November 10-14, 2021 at the Walter E. Washington Convention Center in Washington, D.C.  This presentation will describe preliminary dose escalation data from TWT-101, a Treadwell-sponsored, first in human study of CFI-402411 in advanced solid tumors.

"CFI-402411 is a potent, orally available small molecule inhibitor of HPK1 (Hematopoietic progenitor kinase 1, also known as mitogen activated protein kinase kinase kinase kinase 1, MAP4K1). HPK1 is a negative regulator of both T and B cell responses. We have seen preliminary indications of tolerability and clinical benefit in patients with multiple solid tumors, including post PD1 progression" said Dr. Omid Hamid, Chief of Research/ Immuno-Oncology at The Angeles Clinic & Research Institute, a Cedars-Sinai affiliate, Los Angeles, California.

"HPK1 inhibition with CFI-402411 represents a novel means to stimulate anti-tumor immunity, through an orally available therapy," said Dr. Michael Tusche, co-Chief Executive Officer at Treadwell Therapeutics. "As the first HPK1 inhibitor in the clinic, we are excited by the promise of CFI-402411 and look forward to sharing additional results from TWT-101, including pembrolizumab combination and biomarker focused cohorts, throughout 2022 and beyond."

2021 SITC Poster Presentations and Details:

TWT-101: A First In-human, Phase 1/2 Study Of CFI-402411, Hematopoietic Progenitor Kinase-1 (HPK1) Inhibitor, As A Single Agent And In Combination With Pembrolizumab In Subjects With Advanced Solid Malignancies

Publication Number: 489

Poster Hall

Date and Time: November 12, 2021, 7:00 am - 8:30 pm

In the presentation titled, "TWT-101: A First In-human, Phase 1/2 Study of CFI-402411, Hematopoietic Progenitor Kinase-1 (HPK1) Inhibitor, as a single agent and in combination with pembrolizumab in subjects with advanced solid malignancies," CFI-402411 demonstrated a tolerable safety profile at doses up to 400 mg qd, linear pharmacokinetics, and biologically effective concentrations in patients, as assessed by an exploratory in vitro SLP-76 assay.  In this heavily pre-treated, all-comer patient population (N=16), 5 patients achieved stable disease as best response for at least one tumor evaluation, with 2 of those patients (salivary gland and basal cell carcinoma) exhibiting stable disease through at least 3 tumor evaluations.  The basal cell carcinoma patient had been previously treated with anti-PD1 antibodies.  The most common drug related toxicities of any grade, which occurred in greater than 10% of patients, were diarrhea (62.5%), nausea (43.8%), decreased appetite (31.3%), dyspepsia (25%), blood creatinine increase (25%), and fatigue (25%).  

About CFI-402411

CFI-402411 is a highly potent inhibitor of HPK1, which in preclinical studies has been shown to have an immune-activating effect including the alleviation of inhibition of T cell receptors (TCR), disruption of abnormal cytokine expression, alteration of the tumor immunosuppressive environment through effector cells (i.e. Regulatory T cells or Treg), and potent anti-leukemic effects in several mouse models.

About TWT-101

TWT-101 is a Phase 1/2 clinical trial of CFI-402411 in advanced solid malignancies.  The study is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CFI-402411, as well as to determine optimal dosing as a monotherapy and in combination with the anti-PD1 antibody, pembrolizumab. The trial will enroll approximately 170 patients at up to 15 sites in North America and Asia. It will involve 5 arms including monotherapy and combination dose escalation and expansion in a variety of tumor types, as well as biomarker backfills

About Treadwell Therapeutics

Treadwell Therapeutics is a science driven, clinical-stage multi-modality oncology company, spun out of the University Health Network (UHN), in Toronto, Canada.  The company is developing first-in-class and best-in-class medicines to address unmet needs in patients with cancer.  Founded by a cadre of pre-eminent scientific luminaries, including Dr. Tak W. Mak, the Company's robust, internally developed pipeline includes a first-in-class PLK4 kinase inhibitor, CFI-400945 and a best-in-class TTK inhibitor, CFI-402257, and CFI-402411, an oral immunomodulatory kinase inhibitor with activity toward HPK1.  Treadwell also has a robust pre-clinical pipeline with multiple biologic and next generation TCR based autologous cell therapy programs.