IND-Enabling Studies to Repurpose CD19-TAC T Cells (TAC01-CD19) for Treatment of Systemic Lupus Erythematosus
Abstract
Systemic lupus erythematosus (SLE/lupus) is a severe condition of immune system attack against host tissues, causing widespread inflammation and tissue damage in various organs. It is estimated to affect 300,000 patients, or otherwise 1.5 million Americans per year. Currently, no cure exists and with most medicines causing harmful side effects, it is becoming hugely imperative to provide novel treatments. Cellular therapy is becoming of great interest in treating blood cancers and lupus diseases which involves modifying their immune cells (called T cells) to recognize and kill target disease cells. One common approach involves a specialized type of T cells called CAR-T cells, which has shown to effectively cure a type of cancer lymphoma affecting immune cells (called B cells) in pediatric and adult patients. B cells in this cancer and in lupus disease share a common marker on their surface, known as CD19. Thus, CD19-directed CAR-T cells have also shown early promising outcomes for relieving symptoms in lupus. However, the clinical development of CAR-based therapy in lupus is likely hampered by severely toxic side effects that have generally been well documented for the CAR approach. Triumvira is a clinical-stage biotechnology company developing novel T cell therapy approaches for cancer and autoimmune disease by genetically engineering T cells with the company s proprietary T-cell Antigen Coupler (TAC-T) technology. TAC-T cells have proven to elicit safe and highly efficacious responses in various preclinical models against various targets of cell surface, as well as ongoing phase 1/2 study in patients with HER2-positive solid tumors. TAC01-CD19 is an autologous CD19-directed TAC-T cell product originally developed for treating B cell cancers. Preclinical data demonstrated that low TAC T doses led to complete and specific eradication of B cell grafts without any signs of immune-related toxicities. An Investigational New Drug (IND) submission was cleared by the U.S. Federal Drug Administration previously, which also granted Fast Track Designation. Here, we propose preclinical studies to facilitate the rapid repurposing of TAC01-CD19 in patients with lupus. Since this program builds on work of the previous IND by effectively mirroring study designs and utilizing established criteria where applicable, it is expected that a lupus IND submission can be achieved within the 18-months time of this proposal and proceed to clinical testing shortly thereafter. Since an IND for this product has been cleared already, this application focuses on select lupus-focused studies and is expected to enable the rapid transition into clinical practice. Key study objectives are (i) demonstrating the manufacturability of TAC01-CD19 from SLE patient-derived T cells and (ii) evaluating the potency and safety of this product in vitro and in vivo models. This 1.5-year long program will anticipate discussing results with regulatory authorities in a pre-IND meeting followed by an IND submission. It addresses the FY22 LRP Focus areas of improving the quality of life for individuals living with lupus. Our TAC01-CD19 technology serves to not only avoid high-risk side effects common in other medicines and, thus, will improve likelihood of patient compliance, but also has the potential as a long term cure for a chronic disease. Lupus patients with an early onset of the disease as well as those that have failed a series of prior lines of therapy may benefit from TAC01-CD19 treatment. Specifically, the TAC therapy may be available to lupus patients that cannot receive other treatments due to drug-related toxicities and their dysfunctional immune systems that could help tolerate other regimens.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310925
Entities
People
- Andreas Bader
Organizations
- United States Army