Dianthus to develop experimental therapy DNTH212 for Sjögren’s
Other priority indications include systemic lupus erythematosus, dermatomyositis
Written by |
Dianthus Therapeutics has selected Sjögren’s disease as one of the first three priority indications for the clinical development of DNTH212, its experimental therapy for autoimmune conditions.
The treatment is currently being tested in healthy adult volunteers in a China-based Phase 1 clinical trial (NCT07323173), with top-line data expected in the second half of the year. The other two priority indications include systemic lupus erythematosus, the most common form of lupus, and dermatomyositis, which affects the skin and muscle tissue.
“We are … excited to announce the first three priority indications selected for DNTH212, our first-in-class bifunctional fusion protein and next potential best-in-disease pipeline therapeutic: Sjögren’s Disease, Systemic Lupus Erythematosus, and Dermatomyositis,” Marino Garcia, Dianthus’ CEO, said in a company press release.
DNTH212 targets a pair of immune proteins
Sjögren’s is caused by self-reactive antibodies that primarily target the glands that produce tears and saliva, leading to the hallmark symptoms of dry eyes and dry mouth. However, the disease can affect multiple parts of the body, leading to joint pain and fatigue.
DNTH212 is a bifunctional lab-made protein designed to simultaneously suppress B-cell function and reduce the production of type 1 interferons by plasmacytoid dendritic cells (pDCs). B-cells are the immune cells that produce antibodies, including those driving autoimmune diseases. Type 1 interferons are immune signaling proteins that are found at high levels in Sjogren’s and contribute to B-cell survival.
The experimental therapy specifically targets BAFF and APRIL, two immune proteins that promote B-cell survival, and the BDCA2 receptor protein, which is present at the surface of pDCs that produce type 1 interferons.
BAFF and APRIL are targets of telitacicept, an experimental therapy that has been shown to result in significant, clinically meaningful reductions in disease activity and patient-reported symptoms among adults with Sjögren’s participating in a China-based Phase 3 clinical trial (NCT05673993).
Dianthus believes that by targeting complementary immune mechanisms, DNTH212 has the potential to enhance efficacy in Sjögren’s and other autoimmune diseases.
“Compelling biological rationale and clinical data support the complementary potential of targeting both BDCA2 and BAFF/APRIL to drive differentiated efficacy compared with single-mechanism approaches,” Garcia said.
Treatment designed to remain in the bloodstream for longer
The treatment was developed using YTE half-life extension technology, an engineering strategy that extends the fusion protein’s time in the bloodstream. It is intended to be self-administered, through under-the-skin injections, as infrequently as once every four weeks.
Leads Biolabs originally developed DNTH212 in China. Dianthus holds DNTH212’s development, manufacturing, and commercialization rights outside Greater China.
Cellular studies have demonstrated that DNTH212 was superior to litifilimab, an experimental therapy that also targets cells that produce type 1 interferon, at reducing pro-inflammatory interferon molecules and pDCs counts. Litifilimab is being developed as a treatment for lupus.
In non-human primates, a single dose of DNTH212 was shown to reduce the levels of antibodies to a greater effect than povetacicept, a BAFF/APRIL suppressor under development for autoimmune diseases.
The Phase 1 trial is assessing DNTH212’s safety, pharmacological properties, and ability to elicit an immune response. Healthy participants are receiving a single injection of either one of seven escalating doses of the treatment (5 mg to 1,080 mg) or a placebo.
Based on safety and tolerability results in this population, the second part of the trial will test the optimal DNTH212 doses in people with SLE. Upon completion of the trial, the company will provide an update on the next steps for advancing DNTH212’s clinical development in priority indications.
