Cabaletta's 2-patient CAR-T data hint at autoimmune remission, but investors want more

Cabaletta Bio’s shares tumbled 13% Friday morning as the biotech shared just a crumb of data from two patients in an autoimmune CAR-T trial that hinted at remission.

The data came from the first two patients who received Cabaletta’s CABA-201 in the phase 1/2 RESET-Myositis and RESET-SLE trials for idiopathic inflammatory myopathy (IMNM) and systemic lupus erythematosus (SLE), respectively. The biotech presented the tiny slice of data Friday at the EULAR European Congress of Rheumatology 2024 Industry Symposia.

Both patients experienced improvements in specific disease measurements, which Cabaletta said was “consistent with academic experience of a similar 4-1BB CD19-CAR-T.”

Long a target for oncology, CAR-T has moved into immunology on the strength of academic research last year that showed a patient with lupus achieving remission after treatment.

Cabaletta also reported that there were no cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), which are two key side effects of CAR-T. Patients received CABA-201 over a four-day hospital stay.

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The data also shows complete B cell depletion in both patients within 15 days of the infusion, while CAR-T cell expansion peaked at day 15.

“The magnitude of expansion was consistent with the academic experience with a similar 4-1BB CD19-CAR T construct,” Cabaletta said.

The patient with IMNM had a decline in creatinine kinase from 617 at infusion to 308 at week 12, which is again similar to the academic results. This biomarker is indicative of damage to the skeletal muscles. IMNM is a group of autoimmune diseases that cause inflammation in the muscles and other body systems.

Meanwhile, the patient with lupus had an improvement in disease activity at week four.

“Overall, the data were in line with our expectations and, while the follow-up is limited, we see the biomarker and clinical measurements as trending toward disease remission, and they appear consistent with what has been reported in academic studies,” William Blair analysts said in a Friday morning note.

Cabaletta's shares dropped after the presentation from a Thursday close of $12.56 to $10.85 Friday morning. 

The firm noted that this is the second IMNM and SLE patient without renal involvement to ever receive a CAR-T, which means comparing the data to any other company is challenging.

But William Blair was keen on the safety data, particularly the lack of CRS and ICANS: “We also continue to view the lack of CRS and ICANS favorably as a benign safety profile is critical, in our opinion, and although the patient numbers are small, this is the cleanest safety profile reported with a CAR-T in autoimmune diseases to date, in our opinion.”

Investors will now want to see enrollment accelerate ahead of a second-half readout that will hopefully have more details.

“We look forward to updated data, including more from more patients, in the second half of the year and expect biomarker and clinical responses to deepen further through six months of follow-up. That said, we appreciated the granularity of this data as the incremental data points provide increased insight into pharmacokinetics and dynamics of disease control with CAR-T,” William Blair said.