Initial data from trial testing CLN-978 in Sjögren’s expected this year
Therapy aimed at helping to deplete B-cells to reduce disease severity
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Initial data from an early clinical trial testing CLN-978, Cullinan Therapeutics’ experimental therapy, in adults with moderate to severe Sjögren’s disease are expected in the final months of the year.
The announcement was part of a company press release providing the latest financial results and corporate updates.
The two-part Phase 1b OUTRACE study (NCT07041099), launch plans for which were announced last year, is enrolling up to 36 Sjögren’s patients at two sites in the U.S. and one in Germany.
Cullinan plans to share early results of the trial’s first, dose-escalation part between October and December. The data will focus on CLN-978’s safety and effects on target cells, disease biomarkers, and preliminary clinical activity.
CLN-978 can bind simultaneously to proteins on T-cells, B-cells
Sjögren’s disease is caused by the abnormal production of self-reactive antibodies that primarily target glands that produce tears and saliva, leading to symptoms such as dryness in the eyes and mouth, pain, and fatigue. The antibodies that drive the disease are produced by a type of immune cell called B-cells.
As a bispecific T-cell engager, CLN-978 can bind simultaneously to the CD3 protein complex on the surface of T-cells, immune cells that can kill other cells, and to the CD19 protein on the surface of B-cells. This brings T-cells closer to disease-causing B-cells, triggering T-cells to destroy them.
The therapy, administered via under-the-skin (subcutaneous) injections, is therefore expected to deplete B-cells and help reduce disease severity.
In studies of lab-grown cells from healthy donors and people with autoimmune diseases, including Sjögren’s, CLN-978 was found to deplete B-cells in a dose-dependent manner. In non-human primates, therapy doses ranging from 10 micrograms (mcg) to 100 mcg were well tolerated and led to B-cell depletion in the blood and organs where immune cells are produced and stored.
Additionally, in a first-in-human trial testing weekly subcutaneous injections of CLN-978 (30 mcg) in people with a type of blood cancer, B-cell counts dropped by over 93% within four days of the first dose in two patients.
This program has the potential to transform the treatment landscape in autoimmune diseases and deliver a compelling commercial opportunity.
In the first part of the Phase 1b OUTRACE study, researchers will test four dosing regimens of CLN-978. The first group will receive a single 10 mcg dose of the treatment, while the other three groups will receive the initial 10 mcg dose and a second dose of either 20 mcg, 30 mcg, or 45 mcg one week later.
Results from this part will help to determine the two best dosing regimens to be tested in a larger number of patients within the study’s second part. Each portion will last about one year.
The trial’s primary goal is to assess the treatment’s safety and tolerability. Secondary goals include assessing CLN-978’s pharmacological properties, including its effects on B-cell counts in the blood and its ability to trigger the production of antibodies against it. Exploratory goals include changes in measures of disease activity.
In addition to Sjögren’s, Cullinan is developing CLN-978 for systemic lupus erythematosus and rheumatoid arthritis, two diseases also thought to be driven by self-reactive antibodies produced by B-cells.
“CLN-978 is the ideal therapy for immune reset, with the optimal combination of target, CD19, and modality, T cell engager, together with the convenience of subcutaneous administration,” said Nadim Ahmed, Cullinan’s president and CEO. “This program has the potential to transform the treatment landscape in autoimmune diseases and deliver a compelling commercial opportunity.”
