- Primary endpoint met assessing safety and tolerability in the Phase 1b monotherapy portion of the study - - Preliminary results demonstrate an encouraging trend in C-peptide levels, a biomarker for T1D disease progression - - Preliminary data shows an increase in the frequency of islet-specific Tregs, a potential mechanistic indicator of therapeutic activity - [10-August-2020]
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GERMANTOWN, Md., Aug. 10, 2020 /PRNewswire/ -- Precigen ActoBio, an innovative clinical-stage biotechnology company focused on a new class of microbe-based therapeutic agents and a wholly-owned subsidiary of Precigen, Inc. (Nasdaq: PGEN), today announced it has met the primary endpoint assessing safety and tolerability in the Phase 1b monotherapy portion of the ongoing Phase 1b/2a clinical study investigating AG019 ActoBiotics™ for the treatment of early-onset type 1 diabetes (T1D) (clinical trial identifier: NCT03751007, EudraCT 2017-002871-24).
T1D is an autoimmune disease in which the immune system destroys insulin-producing beta cells in the pancreas, resulting in a blood glucose imbalance. There is no approved disease-modifying treatment for T1D, which is currently managed through lifestyle modification and diet combined with exogenous insulin. Replacement insulin therapy is associated with a variety of near- and long-term adverse events, as is failure to properly control glucose levels within a narrow range. AG019 is formulated as an oral capsule consisting of engineered Lactococcus lactis specifically modified to deliver autoantigen human proinsulin (hPINS) and the tolerance-enhancing cytokine human interleukin-10 (hIL-10) to the mucosal lining of the gastrointestinal tissues. Administration of AG019 is designed to induce specific regulatory T cells (Tregs) that could reduce or eliminate the destruction of insulin-producing cells, potentially stabilizing or improving insulin production. The Phase 1b open-label portion of the study evaluates the safety and tolerability of AG019 administered as a single dose and repeated daily doses as a monotherapy in adult and adolescent patients. The primary endpoint for assessing safety and tolerability is treatment-emerging adverse events (TEAEs) reported up to six months after treatment initiation. Nineteen patients were treated in the Phase 1b monotherapy portion of the study and 17 patients were evaluated at six months. The Phase 2a portion of the study is currently ongoing and investigates the safety and tolerability of AG019 in combination with teplizumab (PRV-031), which is currently under investigation in the PROTECT Phase 3 study for the treatment of newly diagnosed T1D. Key findings from the Phase 1b AG019 monotherapy portion study for patients six months after treatment initiation include: - The study met its primary endpoint demonstrating safety and tolerability. No serious or severe TEAEs were reported in any of the patients treated with AG019 monotherapy, and no patient discontinued treatment. - Eight-week treatment with AG019 monotherapy was safe and well-tolerated in daily dosages up to 6 x 1011 CFU (colony-forming units) in adult and adolescent patients with T1D. - There was no evidence for systemic exposure of bacteria and proteins (hPINS/hIL-10) in the circulation, confirming the safety profile of AG019. The analysis of fecal samples confirmed gastrointestinal exposure of AG019 in most treated patients. - C-peptide levels, a common biomarker used to measure pancreatic beta cell function, demonstrate slower decline in C-peptide levels in 67% of adult patients (6 out of 9) receiving AG019 monotherapy with 44% of these adult patients (4 out of 9) showing stabilization of mean four hours C-peptide area under the curve (AUC) levels at six months (within 9.7% of the baseline level).1 This was based on the comparison of the median percent decline in mean four hours C-peptide AUC from baseline between patients receiving AG019 monotherapy and patients who received placebo from previous studies.2 Furthermore, in a preliminary analysis performed by the Immune Tolerance Network, a leading independent research group, AG019 monotherapy shows an increase in the frequency of islet-specific Tregs expressing inhibitory receptors, a potential mechanistic indicator of therapeutic activity, for patients three months after treatment initiation. “Though preliminary, C-peptide data for the Phase 1b AG019 monotherapy is encouraging in this limited data set,” said Kevan Herold, MD, Professor of Immunobiology and of Medicine at Yale University and Principal Investigator for the AG019 Phase 1b/2a clinical study. “The positive topline data from the Phase 1b monotherapy portion of study provides compelling rationale for continued clinical development of this promising investigational therapeutic candidate.” “These preliminary data for the Phase 1b monotherapy portion of the study are very promising,” said Pieter Rottiers, PhD, CEO of Precigen ActoBio. “In particular, the encouraging trend we are seeing in C-peptide levels indicates potential treatment-related disease modification over time. We look forward to providing expanded data in the coming months for both the AG019 Phase 1b monotherapy and the Phase 2a combination with teplizumab.” About Type 1 Diabetes (T1D) About AG019 ActoBiotics™ About Precigen ActoBio™ Precigen: Advancing Medicine with Precision™ Trademarks Cautionary Statement Regarding Forward-Looking Statements For more information, contact:
References
SOURCE Precigen, Inc.; Precigen ActoBio | ||||
Company Codes: NASDAQ-NMS:PGEN |
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