Tuesday, Regulus Therapeutics Inc ( RGLS ) released topline results from the second cohort of patients in its Phase 1b multiple-ascending dose (MAD) study of RGLS8429 for Autosomal Dominant Polycystic Kidney Disease (ADPKD).

The study evaluates RGLS8429 treatment across three different weight-based dose levels, including measuring changes in urinary polycystins 1 and 2 (PC1 and PC2), height-adjusted total kidney volume (htTKV), cyst architecture, and overall kidney function. 

PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and have been shown to correlate with disease severity inversely. 

RGLS8429 was well tolerated, with no safety findings of concern.

Clear evidence of a mechanistic dose response at a 2mg/kg dose level based on urinary PC1 and PC2 polycystin levels was observed.

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 three months of dosing.

Exploratory results of imaging-based biomarkers were encouraging, with three patients with the highest increases in PC1 and PC2 having reductions in htTKV >4%, with corresponding reductions in total kidney cyst volume (TKCV).

The third cohort is being dosed at 3mg/kg of RGLS8429 or placebo every other week for three months. Data readout is anticipated in mid-2024.

The company recently added a fourth cohort for an open-label fixed dose of 300mg of RGLS8429 dosed every other week for three months. Screening is expected to start in the second quarter of 2024.

Concurrently, Regulus Therapeutics ( RGLS ) announced an oversubscribed $100 million equity private placement. 

Under the securities purchase agreement, the investors have agreed to purchase shares at $1.60 per share. 

Certain investors have also agreed to purchase, in lieu of common shares, shares of newly designated, non-voting Class A-6 convertible preferred stock at a purchase price of $160.00 per share. 

Price Action: RGLS shares are up 52% at $2.11 during the premarket session on the last check Tuesday.