The good times roll for Dice
The company raises hopes that its oral IL-17 inhibitor could rival Sotyktu, but there are reasons to be cautious.
Oral agents for autoimmune diseases are having a moment following the approval of Bristol Myers Squibb’s Sotyktu. And Dice Therapeutics signalled its intent here today, with intriguing topline phase 1 data on its lead oral IL-17 inhibitor, DC-806, in psoriasis.
The group made much of a cross-trial comparison that showed DC-806 in a favourable light versus Sotyktu. However, with small patient numbers Dice’s claim that it might have the best oral drug for psoriasis look a little premature.
The group’s stock opened 90% higher on the news, though this faded to a 50% rise in later morning trade, giving the group a chunky market cap of $1.5bn.
The excitement was spurred by data from seven patients receiving the highest dose, 800mg twice daily. In this cohort the mean percentage reduction in Pasi from baseline was 43.7% at four weeks versus 13.3% in the placebo group.
Dice execs noted that the study was not powered for statistical significance, but highlighted an exploratory p value of 0.0008.
This reduction is slightly ahead of what has been seen with Sotyktu, with the usual caveats about cross-trial comparisons – heightened in this case by the fact that Bristol’s data came from phase 3 trials in hundreds of patients.
In another reason for caution, the low dose of DC-806 tested, 200mg twice daily, failed to separate from placebo on Pasi. However, Dice execs still believe that this dose could be active, given biomarker data also presented today.
Perhaps on this point things will become clearer with phase 2 results, and a 12-week dose-ranging study is due to start in the first half of next year. This will enrol moderate-to-severe patients, versus the mild-to-moderate population in the phase 1. Dice hopes that this will bolster efficacy further, and today pointed to a greater Pasi effect in the moderate subgroup.
The upcoming trial will also look at once-daily as well as twice-daily regimens – the former would put DC-806 in line with Sotyktu in terms of convenience.
Reassuringly for Dice, DC-806’s safety profile looked clean, and there were no hints of any liver toxicity, the issue that scuppered Lilly’s oral IL-17 inhibitor LY3509754.
At present, Dice does not have much in the way of competition in the oral IL-17 inhibitor space, although it is hoping to outdo DC-806 with a next-gen asset, DC-853, that it reckons is more potent.
The psoriasis space is very crowded, however. If Dice wants to unseat Sotyktu – and indeed, injected therapies – it will need to replicate this benefit in much larger trials.
|Selected oral IL-17 inhibitors
|Ph1 UK trial showed 44% mean reduction in Pasi in 7 psoriasis pts treated with high dose (800mg BID)
|Ph1 data in psoriasis pts due Oct 2022; also in ph1 in prostate cancer
|Ph1 in healthy volunteers completes Nov 2022
|Preclinical; first clinical data due H2 2023
|Oral IL-17A inhibitor programme
|Preclinical (via €7m licensing deal)
|Abandoned in ph1 after undisclosed liver findings (NCT04152382 & NCT04586920)
|Source: Evaluate Pharma & clinicaltrials.gov.