AbbVie Acquires Capstan Therapeutics and its Novel CAR-T Therapy Candidate
Breakthrough Clinical Results
AbbVie has completed its acquisition of Capstan Therapeutics, gaining access to CPTX2309, a first-in-class in vivo targeted lipid nanoparticle (tLNP) anti-CD19 CAR-T therapy candidate. CPTX2309 is currently in Phase 1 trials for B cell-mediated autoimmune diseases. This acquisition strengthens AbbVie's immunology portfolio by adding a novel approach to CAR-T cell therapy that avoids the need for lymphodepleting chemotherapy and the challenges associated with conventional ex vivo CAR-T therapies. The acquisition also includes Capstan's proprietary tLNP platform for delivering RNA payloads.
Key Highlights
- AbbVie completed its acquisition of Capstan Therapeutics.
- Capstan's lead asset, CPTX2309, is a novel in vivo CAR-T therapy for B cell-mediated autoimmune diseases.
- CPTX2309 avoids lymphodepleting chemotherapy and challenges of conventional ex vivo CAR-T therapies.
- Acquisition includes Capstan's proprietary tLNP platform for RNA payload delivery.
Incidence and Prevalence
Global Estimates of B Cell-Mediated Autoimmune Diseases
According to available data, autoimmune diseases affect approximately 3-5% of the population globally. Based on a 1997 study, approximately 8,511,845 persons in the United States (about 1 in 31 Americans) were afflicted with one of 24 studied autoimmune diseases.
The diseases with the highest prevalence rates include: - Graves'/hyperthyroidism - Insulin-dependent diabetes mellitus (IDDM) - Pernicious anemia - Rheumatoid arthritis - Thyroiditis - Vitiligo
These six conditions comprise an estimated 7,939,280 people or 93% of the total number estimated in the United States.
Glomerulonephritis, multiple sclerosis (MS), and systemic lupus erythematosus (SLE) added an estimated 323,232 people. The prevalence of other autoimmune diseases reviewed were rare, with rates less than 5.14/100,000.
A significant gender disparity exists in autoimmune disease prevalence, with most being more common in women. Women are at 2.7 times greater risk than men to acquire an autoimmune disease. More recent data from 2005 indicates that nearly 80% of all people with autoimmune diseases are women.
From incidence data, an estimated 237,203 Americans would develop an autoimmune disease in 1996, with approximately 1,186,015 new cases occurring in the United States every 5 years.
Genetic factors play a significant role in susceptibility to autoimmune diseases. For example, HLA typing could be helpful in predicting autoimmune disease development. Specifically for rheumatoid arthritis, genetic susceptibility in females is linked to the HLA-DRB104 and 03 allelic groups, the DRB104/DRB104 and DRB103/DRB104 genotypes, and the DRB104-DRB4 or DRB103-DRB3 haplotypes. Conversely, the DRB101/DRB115 and DRB107/DRB116 genotypes and the HLA-DRB5 gene locus represent protective factors for RA.
It's worth noting that many autoimmune diseases are infrequently studied by epidemiologists, suggesting the total burden of disease may be an underestimate.
Mechanism of Action
Three Most Common Mechanisms of Action in Trials for Unapproved Drugs for B Cell-Mediated Autoimmune Diseases
T Cell Migration Inhibition
The first common mechanism involves blocking T cell migration from blood into organized lymphoid tissues and inflamed areas. A notable example is the monoclonal antibody L11, which targets murine CD43 and has demonstrated significant ability to inhibit T cell migration into inflamed islets and salivary glands. Studies have shown that this approach provides significant protection against diabetes development in nonobese diabetic mice. Importantly, this protection is long-lived, with decreased diabetes incidence persisting months after treatment ends. A key advantage of this approach is that it has no long-term effect on numbers or phenotypes of peripheral lymphocytes, suggesting a favorable safety profile.
Costimulation Pathway Modulation
The second mechanism focuses on targeting costimulatory molecules involved in T cell activation. Key molecules in this pathway include B7-1 (CD80), B7-2 (CD86), CD28, CTLA-4, ICOS, PD-1, OX 40, and CD40L. These molecules can be categorized into those that increase T cell activation (CD28, ICOS, OX 40, CD40L) and those that serve as inhibitory T cell costimulators (CTLA-4, PD-1). Most therapeutic approaches in this category work by blockade of their function with receptor specific immunoglobulin. A common strategy involves using soluble CTLA-4Ig to block B7 and disrupt the B7/CD28 pathway. Abatacept is an example that acts as a modulator of the CD80 or CD86-CD28 co-stimulatory signal. This approach has shown promise in various autoimmune disease models.
Endoplasmic Reticulum Stress Modulation
The third mechanism involves modulating endoplasmic reticulum stress. Tunicamycin exemplifies this approach, having been found to reduce the activation and pancreatic infiltration of CD8+ T cells. Research has demonstrated that this activity delayed the incidence of virus-induced diabetes and improved survival rates. The potential of tunicamycin to offer therapeutic opportunities for T cell-mediated autoimmune diseases such as diabetes makes this a promising avenue for drug development.
Other Emerging Approaches
Beyond these three primary mechanisms, several other approaches are being investigated, including histone deacetylase inhibitors (HDACi) like givinostat, anti-CD19 monoclonal antibodies, Rabeximod (a new chemical entity), PD-1/PD-L1 pathway inhibition, and plant-derived compounds like Platycodon grandiflorum. These emerging strategies represent additional promising directions for developing new treatments for B cell-mediated autoimmune diseases with potentially fewer side effects than current therapies.
These mechanisms collectively represent the cutting edge of research into novel therapeutic approaches for B cell-mediated autoimmune diseases, offering hope for patients who may not respond to currently approved treatments.
Drug used in other indications
CPTX2309 Clinical Trials Beyond B Cell-Mediated Autoimmune Diseases
Based on the available information, I cannot provide specific details about other indications for which CPTX2309 is being trialed beyond B cell-mediated autoimmune diseases, nor can I describe the intervention models for these trials.
The clinical development program for CPTX2309 may include various therapeutic areas, but without specific data on:
- Non-autoimmune indications that might be under investigation
- Intervention methodologies being employed in these trials
- Study designs for trials in alternative disease states
- Treatment protocols specific to non-autoimmune applications
- Dosing regimens that might differ from those used in autoimmune disease trials
Clinical trials typically follow several possible intervention models, including:
- Parallel assignment where different groups receive different interventions
- Crossover assignment where participants receive multiple interventions in sequence
- Factorial assignment testing multiple interventions simultaneously
- Single group assignment where all participants receive the same intervention
For a comprehensive understanding of CPTX2309's full clinical development program, one would need to consult:
- Clinical trial registries such as ClinicalTrials.gov
- Scientific publications detailing the compound's mechanism of action
- Investor presentations from the developing company
- Regulatory filings that might contain information about planned or ongoing studies
Without this specific information, I cannot provide details about CPTX2309 trials beyond B cell-mediated autoimmune diseases or their intervention models.
