Regulus Therapeutics (NASDAQ: RGLS) has announced positive topline results from the second cohort of patients in its Phase 1b MAD study of RGLS8429 for the treatment of ADPKD. 14 patients were randomized 3:1 to receive either 2 mg/kg of RGLS8429 (delivered by subcutaneous injection) or placebo every other week for three months. The company will now progress to to a 3 mg/kg dose cohort and plans to also add a fourth cohort for an open label fixed dose of 300mg.
RGLS8429 was well tolerated with no safety findings of concern.
Urinary measurements of PC1 and PC2 demonstrated greater biological activity of RGLS8429 at 2mg/kg compared to 1mg/kg and placebo, which was most evident after 3 months of dosing.
Exploratory results of imaging-based biomarkers showed that 3 patients with the highest increases in PC1 and PC2 had reductions in height adjusted total kidney volume (htTKV) >4%, with corresponding reductions in total kidney cyst volume (TKCV).
A recent meeting with the FDA confirmed the potential for Regulus to use an accelerated approval pathway based on a single Phase 2 study.
RGLS8429 is a short, naked oligo which inhibits the binding of miRNA-17 to the PKD1 and PKD2 genes through preferential kidney targeting. A key challenge to be overcome in using this approach is that inhibition of miR-17 has the potential to cause off-target CNS toxicities due to its involvement in other physiological and pathological processes.
PYC will pursue ADPKD using a more specific and targeted approach than Regulus. Its PPMO, PYC-003, works by entering into the target renal tubular cells to upregulate the expression of the PKD1 gene, subsequently increasing PC1 protein expression.
Wilsons’ Advisory Research is of the view that a meaningful benefit demonstrated in Regulus’ study serves to validate and de-risk PYC’s ADPKD program in so far as both programs are based on the same theory of the mechanism of cyst development in the disease. In addition, it is considered that PYC stands to benefit from Regulus laying down a development pathway which PYC can then follow.
RGLS stock rose 71% on the positive news and Regulus quickly seized the opportunity to secure US$100m from a private placement to advance its program.
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