Cabaletta Bio (NASDAQ:CABA) Chief Executive Officer Steven Nichtberger said the company is trying to address what he described as the central limitations of autologous CAR T therapy in autoimmune disease: manufacturing scale, cost, logistics and the need for preconditioning chemotherapy.
Speaking in a discussion moderated by Douglas Tsao, senior analyst at H.C. Wainwright, Nichtberger said investor skepticism about autologous CAR T in large autoimmune indications is understandable if the model resembles the oncology CAR T infrastructure used in recent years.
Company Points to Automated Manufacturing Strategy
Nichtberger said Cabaletta’s lead program, rese-cel, was developed with those barriers in mind. He highlighted the company’s commercial agreement with Cellares, saying the automated manufacturing approach could produce “tens of thousands of products per year” for Cabaletta and others. He also said engineering runs showed comparability with manually produced product.
The CEO said Cabaletta recently reported at ASGCT that the first two patients dosed with Cellares-manufactured rese-cel showed the pharmacokinetic and pharmacodynamic responses the company wanted to see.
He also discussed the company’s manufacturing relationship with Lonza and said Cabaletta’s process can produce multiple doses from a single manufacturing run. Nichtberger said this could matter if patients need retreatment later, because an additional frozen dose could be stored and shipped without requiring a new manufacturing run.
Rese-cel Designed for Autoimmune Disease
Nichtberger said rese-cel was designed specifically for autoimmune patients rather than adapted from an oncology program. He described the product as a fully human CD19-directed autologous CAR T therapy and contrasted it with approaches that include murine components.
He said the fully human design could support redosing if needed. He also emphasized Cabaletta’s use of weight-based dosing, saying heavier patients receive more drug. According to Nichtberger, the company believes this dosing approach contributes to safety and could support use in pediatric patients.
The CEO said Cabaletta is studying rese-cel in conditions including myositis, scleroderma, lupus, myasthenia gravis and pemphigus. He said the company expects to present safety and efficacy data at EULAR, including follow-up extending more than a year and a half in some patients across myositis, scleroderma and lupus.
Focus on Removing Preconditioning
A major focus of the discussion was Cabaletta’s effort to deliver rese-cel without standard Flu-Cy preconditioning, which typically involves fludarabine and cyclophosphamide. Nichtberger said eliminating preconditioning would be one of the most important advances in the field.
He said Cabaletta’s hypothesis is that Flu-Cy is not necessary for autoimmune disease, even though it remains important in cancer. He pointed to an academic experience in which a myositis patient was retreated with Flu-Cy and cells but did not experience cell expansion or clinical improvement, arguing that the chemotherapy alone did not appear to drive benefit in that case.
Nichtberger said the company is particularly focused on the preconditioning-free opportunity in lupus, where he said Cabaletta already has FDA alignment on how it could conduct a pivotal trial. He said some patients enrolled in Cabaletta’s lupus program chose to move from a preconditioning arm into an arm testing rese-cel without preconditioning after learning the option existed.
Early Pemphigus Findings Surprised Company
Nichtberger said Cabaletta was “flat out surprised” by early results in pemphigus without preconditioning. He said two of four pemphigus patients treated at the starting dose had an elimination of symptoms through six months of follow-up and were on no medicines from the day they received a single dose of rese-cel.
“We didn’t expect there would be any treatment effect without Flu-Cy at the starting dose,” he said. Nichtberger added that the next cohort is fully enrolled and that Cabaletta has also started its lupus program without preconditioning.
He said the company hopes to have enough data before the end of June to discuss the first two lupus patients dosed without preconditioning, including pharmacokinetic and pharmacodynamic comparisons with lupus patients who received preconditioning.
On efficacy expectations, Nichtberger said Cabaletta has not assumed that all patients will achieve complete and durable responses. He said the company believes about 80% of patients across the autologous CAR T space may achieve durable outcomes off all medicines with a single dose. He added that even if a preconditioning-free regimen reached 60% and remaining patients could be redosed or treated with preconditioning, that would be a meaningful treatment approach.
CEO Addresses Competitive Modalities
Nichtberger also discussed in vivo CAR T and bispecific approaches, saying those modalities emerged partly because of the historical difficulty of scaling autologous CAR T. However, he argued that alternative modalities have not yet produced autoimmune data comparable to autologous CAR T.
He said in vivo approaches have not demonstrated the same efficacy in autoimmunity and suggested safety has been a greater issue. He also described bispecifics as “awesome drugs” but characterized them as annual therapy layered on top of existing treatments, rather than a single-dose curative approach.
Nichtberger said Cabaletta’s strategic focus remains on safely delivering an autologous CAR T product that can be manufactured at scale. He also said the company has added personnel with CAR T commercialization and supply-chain experience, including Chief Commercial Officer Steve Gavel, whom he said previously launched CARVYKTI at Legend.
About Cabaletta Bio (NASDAQ:CABA)
Cabaletta Bio is a clinical-stage biotechnology company pioneering chimeric autoantibody receptor T cell (CAAR-T) therapies for B cell–mediated autoimmune diseases. Its proprietary platform engineers patient-derived T cells to selectively target and eliminate pathogenic B cells that produce disease-driving autoantibodies, with the aim of preserving overall immune function and reducing off-target toxicity.
The company’s lead candidate, DSG3-CAART, is being evaluated in pemphigus vulgaris, a rare blistering disorder caused by autoantibodies against desmoglein 3.
