Date: 2016-12-03
Type of
information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Society of Hematology (ASH) annual meeting
Company: True North Therapeutics (USA - CA)
Product: TNT009 - humanised IgG4 monoclonal antibody against total complement component 1, subcomponent s
Action
mechanism: monoclonal antibody. TNT009 is a first-in-class monoclonal antibody that selectively inhibits the Classical Complement pathway by targeting C1s, a serine protease within the C1-complex in the Complement pathway of the immune system. TNT009 thereby prevents downstream disease processes involving phagocytosis, inflammation, and cell lysis. With a unique mechanism of action and high target specificity, TNT009 selectively inhibits disease processes in the classical complement pathway while maintaining the important immune surveillance provided by the Alternative complement pathway and lectin complement pathway.
Disease: bullous pemphigoid (BP), cold agglutinin disease, warm autoimmune hemolytic anemia, end-stage renal disease (ESRD)
Therapeutic
area: Rare diseases - Autoimmune diseases - Hematological diseases
Country: Austria
Trial
details: This prospective, double-blind, randomized, placebo-controlled First-In-Human study has three sub-parts: Part A, a single ascending dose study (SAD) in normal human volunteers (NHVs), Part B, a multiple ascending dose study (MAD) in NHVs, Part C, a multiple dose (MD) study in patients with a complement-mediated disorder. (NCT02502903)
Latest
news: * On December 3, 2016, True North Therapeutics presented updated clinical data from an ongoing Phase 1b trial of TNT009 for the treatment of cold agglutinin disease (CAD), a rare form of autoimmune hemolytic anemia. These interim clinical results further support TNT009 as a promising treatment for CAD, given the normalization of hemoglobin levels seen in severely anemic CAD patients. The data are described in oral and poster presentations by True North researchers and collaborators at the American Society of Hematology (ASH) annual meeting on December 3 – 6, 2016 in San Diego. The additional data from the ongoing clinical study demonstrated robust activity of TNT009 in patients with CAD, as described in the oral presentation titled “TNT009 Prevents Erythrocyte C3 Fragment Opsonization and Rescues Reticulocytes from Destruction in Patients with Cold Agglutinin Disease” and the poster presentation titled “Chronic Inhibition of Complement C1s by TNT009 Produces Sustained, Complete Remission in Patients with Severe, Transfusion-Dependent Cold Agglutinin Disease (CAD).”
The clinical data were reported on six CAD patients. All patients were dosed with TNT009 in the Phase 1b trial, followed by treatment under a named patient provision for some patients. The named patient provision was requested by the treating physicians and allowed for continued access to TNT009, treating some patients for over 3 months. Among the six patients in the Phase 1b trial, one patient had an active malignancy, a lymphoma with 70% bone marrow infiltration. Highlights from the presentations at ASH include:
- All five CAD patients without an active malignancy had a sustained response with improvements in hemoglobin of approximately 4-5 g/dL, reaching hemoglobin levels of > 12g/dL.
- Patients that required transfusions immediately prior to dosing in the Phase 1b trial became transfusion-free during treatment with TNT009.
- TNT009 was safe and well-tolerated in the study, with no serious or severe drug-related adverse events.
- The clinical data support TNT009’s mechanism of inhibition of the Classical Complement pathway, by showing reductions of C3 opsonized red blood cells concurrent with improvement in hemoglobin levels.
* On June 11, 2016, True North Therapeutics announced new clinical data for TNT009, which showed encouraging initial results for the first CAD patients dosed in the ongoing Phase 1b study. These interim data demonstrated a concordant improvement of blood parameters with rapid onset of action in patients with CAD, a form of hemolytic anemia in which autoantibodies target and destroy red blood cells. The data are being presented in a late-breaking oral presentation at the 21st Congress of the European Hematology Association (EHA) in Copenhagen. In an oral presentation titled “The Anti C1S Complement Antibody TNT009 Induces Rapid Complete Remissions of Anaemia in Patients with Primary Cold Agglutinin Disease,” Prof. Ulrich Jäger described interim data from the ongoing Phase 1b clinical study demonstrating robust activity of TNT009 in patients with CAD. The data reported on the first five CAD patients dosed in the study, each receiving an initial dose of 10 mg/kg of TNT009 followed by a full dose of 60 mg/kg 1-4 days later, and three additional weekly doses of 60 mg/kg. Four of these five CAD patients in the study responded to TNT009 within the first 24 hours, and of the four responders, three patients achieved a Complete Response (hemoglobin > 12 g/dL) after the 4-week dosing period. In addition, TNT009 was observed to be well-tolerated without need for premedication, and no serious, drug-related adverse events occurred in these study subjects.
Is
general: Yes
