CLYM116 and APRIL
CLYM116 is a novel anti-APRIL mAb with a novel mechanism designed to promote potent degradation of APRIL and extend half-life
APRIL (A PRoliferation Inducing Ligand) plays a key role in B cell regulation, making it an attractive target for multiple B cell-mediated diseases.
APRIL signaling, through (BCMA and TACI), impacts B cells in key ways:
- Promotes differentiation and survival of plasma cells, the source of many pathogenic autoantibodies
- Regulates Ig class switching, the process in which mature B cells acquire expression of IgA
Targeting of APRIL has been clinically validated in registrational studies in IgA nephropathy (IgAN), a progressive renal disease. In IgAN, APRIL inhibition is a potentially disease-modifying approach, preventing the production of pathogenic IgA and the consequent immune complex formation that leads to kidney damage.
CLYM116 is the only known 'sweeper' anti-APRIL antibody in development
CLYM116 is designed for strong efficacy, less frequent dosing, and favorable safety
Novel ‘Sweeper’ mechanism
What is a sweeper?
The sweeper mechanism is a pH dependent bind-and-release design to promote APRIL blockade and degradation, coupled with Fc-engineering to promote antibody recycling.
The CLYM116 Variable Region exhibits pH-dependent binding to APRIL, resulting in both potent blocking of APRIL to its receptors and promotion of lysosomal APRIL degradation.
The CLYM116 Fc Region is engineered to promote recycling and reduced clearance of CLYM116, resulting in longer half-life.
Our CLYM116 development strategy
CLYM116 is being developed for the treatment of IgAN and may also have broader utility across other B cell-mediated diseases where APRIL plays a critical role.
IgAN is an autoantibody-mediated progressive renal disease caused by the APRIL-mediated production of Gd-IgA1 and deposition of immune complexes in the glomeruli.
LEAD INDICATION
IgA Nephropathy (IgAN)Clinical Trial
We anticipate filing an IND or CTA in the second half of 2025, with plans to initiate a Phase 1 clinical trial following completion of IND-enabling studies and subject to regulatory clearance.