A New Era in Autoimmune Disease Treatment: FDA Clears Trial for Lymphodepletion-Free sCAR-T Therapy
For millions grappling with the relentless challenges of autoimmune diseases, a potential turning point has arrived. The FDA has granted Investigational New Drug (IND) request clearance to Calibr-Skaggs Institute for Innovative Medicines, the drug discovery division of Scripps Research, to initiate a Phase 1 clinical trial (NCT06913608) evaluating a novel switchable chimeric antigen receptor T cell (sCAR-T) therapy – CLBR001 + SWI019 – for a range of debilitating autoimmune conditions. This breakthrough offers a promising choice to current treatments, potentially revolutionizing how we approach these chronic illnesses.
The Burden of autoimmune Disease & The Promise of CAR-T Therapy
Autoimmune diseases represent a significant global health concern, affecting an estimated 15 million individuals in the United States alone, adn as many as 12% of the world’s population. These conditions, ranging from rheumatoid arthritis and lupus to systemic sclerosis and myositis, arise when the immune system mistakenly attacks the body’s own tissues. Current treatments often rely on long-term immunosuppression, wich, while managing symptoms, carries significant side effects and doesn’t address the underlying cause of the disease.
Recent advancements in CAR-T cell therapy have ignited hope for a potential cure. CAR-T therapy works by genetically modifying a patient’s own T cells to recognize and destroy specific cells, effectively “resetting” the immune system. This approach has shown remarkable success in certain cancers and, increasingly, in select autoimmune diseases, offering the possibility of lasting remission and a substantially improved quality of life.
The Challenge of Lymphodepletion & The Innovation of sCAR-T
However,customary CAR-T cell therapies have a significant hurdle: the requirement for lymphodepletion. This pre-conditioning chemotherapy regimen aims to eliminate existing immune cells, creating space for the engineered CAR-T cells to expand and function effectively. While necesary for conventional CAR-T, lymphodepletion carries considerable risks, including increased susceptibility to infection, severe side effects, and limitations on which patients can safely undergo the treatment.
Calibr-Skaggs’ CLBR001 + SWI019 sCAR-T therapy represents a paradigm shift. This innovative approach is specifically engineered to eliminate the need for lymphodepletion, dramatically reducing the toxicity associated with CAR-T therapy and potentially expanding access to a wider patient population. This is a critical advancement, particularly for rheumatologists seeking safer and more effective treatment options for their patients.
how CLBR001 + SWI019 Works: A Two-Component System
The CLBR001 + SWI019 system utilizes a unique two-component design:
CLBR001 (sCAR-T cell): This is the genetically modified T cell engineered to target CD19-positive B cells, a key player in the autoimmune response in many conditions. The “switchable” aspect is crucial, allowing for controlled activation and deactivation of the CAR-T cells.
SWI019 (Protein-Based Biologic Switch): This protein acts as the activating agent,binding to the CLBR001 cells and triggering their anti-B cell activity. This switch allows for precise control over the therapy’s duration and intensity.
Preclinical and early clinical data demonstrate that CLBR001 + SWI019 not only functions effectively without lymphodepletion but also exhibits several advantages over conventional CAR-T therapies. Notably, it has shown the ability to shorten the duration of potentially life-threatening side effects like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover,early trials indicate robust expansion and persistence of CLBR001 cells in patients,exceeding levels observed with currently approved CAR-T products.Phase 1 Trial: Targeting Multiple Autoimmune Diseases
The upcoming Phase 1 clinical trial will initially focus on evaluating the safety and efficacy of CLBR001 + SWI019 in patients with:
Myositis
Systemic Sclerosis
Lupus
Rheumatoid Arthritis
The trial’s design allows for potential expansion to include other autoimmune indications in the future, highlighting the broad therapeutic potential of this innovative approach. Patient recruitment is expected to begin shortly.
“Patients with chronic autoimmune diseases need curative options that do not require life-long immunosuppressive therapy to manage their condition,” explains Travis Young, Vice President of Biologics at Calibr-Skaggs. “Our CLBR001 +
