Cabaletta Bio Announces Publication of Comprehensive Preclinical Study Results for DSG3-CAART in Pemphigus Vulgaris
- DSG3-CAART achieved autoantibody elimination and resolution of blisters in active immune mouse model of pemphigus vulgaris
- Soluble autoantibodies demonstrated potential to enhance DSG3-CAART efficacy and did not demonstrate off-target toxicity
- DesCAARTes™ Phase 1 clinical trial actively recruiting patients
The preclinical studies, conducted at the
In vivo studies included use of an active immune PV model, characterized by a PV clinical phenotype, including skin blistering and physiologic anti-DSG3 IgG levels. In these mice, DSG3-CAART reduced serum levels of pathogenic anti-DSG3 antibodies, as well as tissue bound antibodies in the epithelium, a hallmark of PV disease. Clinical and histologic resolution of blisters was observed in DSG3-CAART treated animals.
The potential impact of anti-DSG3 antibodies on DSG3-CAART toxicity and target engagement was also evaluated. The researchers studied whether anti-DSG3 antibodies could serve as a “cytotoxic bridge” enabling DSG3-CAART to kill cells which express antibody receptors on their surface, and no such cross reactivity was detected. Building on prior evidence that DSG3-CAART function is not meaningfully inhibited by anti-DSG3 antibodies, and that proliferation of DSG3-CAART in response to polyclonal PV serum IgG is observed (as previously reported in the 2016 publication in Science), the recently published studies demonstrated functional activation of DSG3 CAAR T cells in response to anti-DSG3 antibodies. This may improve the potential efficacy of DSG3-CAART in targeting rare B cells. The potential risk for CRS or other inflammatory responses resulting from DSG3-CAART interaction with soluble anti-DSG3 autoantibodies post-infusion is being mitigated in the DesCAARTesTM Phase 1 trial design through a conservative fractionated-dose approach where increasing fractions of the target dose are infused, enabling for safety monitoring between infusions while preserving the opportunity for the patient to receive a full dose.
“We believe these comprehensive preclinical data for DSG3-CAART, published in
The safety and tolerability of DSG3-CAART in targeting pathogenic B cells in patients with mPV is currently being evaluated in the DesCAARTes™ clinical trial, which recently started recruiting. The FDA granted Fast Track Designation to DSG3-CAART in
About Pemphigus Vulgaris
PV is a rare autoimmune blistering disease that is characterized by the loss of adhesion between cells of the skin or mucous membranes. PV is caused by the production of autoantibodies that disrupt structural proteins within the skin and/or mucosa that connect with other proteins to enable the skin and/or mucosal cells to connect with each other. The autoantibodies can target DSG3 and/or desmoglein 1 (DSG1), which are primarily expressed in the mucosal membranes and skin, respectively. mPV is characterized by autoantibodies against DSG3 only whereas mucocutaneous PV is characterized by autoantibodies against DSG3 and DSG1.
About CAAR T Cell Therapy
Chimeric AutoAntibody Receptor (CAAR) T cells are designed to selectively bind and eliminate only disease-causing B cells, while sparing the normal B cells that are essential for human health. CAAR T cells are based on the chimeric antigen receptor (CAR) T cell technology. While CAR T cells typically contain a CD19-targeting molecule, CAAR T cells express an autoantibody-targeted antigen on their surface. The co-stimulatory domain and the signaling domain of both a CAR T cell and a CAAR T cell carry out the same activation and cytotoxic functions. Thus, Cabaletta Bio’s CAARs are designed to direct the patient’s T cells to kill only the pathogenic cells that express disease-causing autoantibodies on their surface, potentially leading to complete and durable remission of disease while sparing all other B cell populations that provide beneficial immunity from infection.
This press release contains “forward-looking statements” of
Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: Cabaletta Bio’s ability to demonstrate sufficient evidence of safety, efficacy and tolerability in its preclinical and clinical trials of DSG3-CAART; risks related to the impact of public health epidemics affecting countries or regions in which we have operations or do business, such as COVID-19; Cabaletta’s ability to retain and recognize the intended incentives conferred by Fast Track Designation for DSG3-CAART for the treatment of PV; risks related to Cabaletta’s ability to protect and maintain its intellectual property position; uncertainties related to the initiation and conduct of studies and other development requirements for its product candidates; and the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Cabaletta’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Cabaletta’s most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Cabaletta’s other filings with the
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Source: Cabaletta Bio