As biopharma companies have turned their attention to liver diseases like Nash and hepatitis B over the past few years, the annual EASL/ILC conference has increasingly come onto investors’ radars. Next month’s meeting in Vienna promises to deliver important updates from small and large companies, including Intercept, Alnylam and Assembly Biosciences.
The most consequential data are being held back for the conference, but abstracts released yesterday contained some notable updates from the likes of Viking Therapeutics, Altimmune and Spring Bank Pharmaceuticals. Viking in particular caused something of a stir with data on VK2809, a thyroid hormone receptor beta agonist that counts as one of the sector’s most closely watched Nash projects.
An abstract on a phase II trial contained the first data seen with a low 5mg dose of VK2809, suggesting that this could be as effective as 10mg, with obvious safety advantages. Leerink analysts wrote that should this be confirmed in larger studies, VK2809 could be a best-in-class compound.
An update from Spring Bank concerning its hepatitis B antiviral inarigivir also attracted attention; final results from the Achieve study of the Rig-1 agonist have been selected as a late breaker at the conference. A placeholder abstract was released yesterday, describing an ongoing dose-dependent response to therapy; results from the highest dose tested in Achieve, 200mg, have yet to be fully disclosed.
Preliminary data revealed that the 200mg dose of inarigivir produced a maximum HBV DNA reduction of 3.26 logs, although this could change. The company previously announced a 2.76 log reduction with a 100mg dose. This is considered impressive efficacy for an oral monotherapy, and these latest data will raise hopes for the impending clinical programme testing an even higher dose, 400mg.
Elsewhere, an abstract from Altimmune containing full data on its therapeutic hepatitis B vaccine HepTcell make for interesting reading; the company recently said it would push into phase II. An early look at the data from this study was not encouraging – immune responses were similar in the treated and placebo arms – but at the final analysis the company concluded that two adjuvanted HepTcell arms had markedly greater increases in T-cell immunity than placebo. The full data from the trial will be presented on Friday April 12.
NGM has a number of posters on its FGF19 analogue NGM282, which has largely disappointed, so most interest is likely to focus on NGM313, an antibody activator of βklotho/FGFR1c, over which Merck & Co recently exercised an option. The company will present encouraging early data from 25 NAFLD patients, appearing to show the insulin sensitiser reducing liver fat as well as inflammatory and fibrotic markers.
On April 12 Cirius Therapeutics will present data from a phase IIb trial called Emminence, testing its insulin sensitiser MSDC-0602K in Nash patients with fibrosis. The presentation is slated as a late breaker, and is presumably a closer look at the data released last October, though curiously the company did not highlight the presentation in a press release yesterday, only mentioning a couple of abstracts concerning preclinical findings. Earlier this year Cirius filed to raise $86m in an IPO on Nasdaq.
|EASL data to watch out for|
|Alnylam||Givosiran||AHP; Envision phase III||Plenary Sat April 13|
|Myr Pharma/Hepatera||Myrcludex B||HBV; phase II data||Plenary Sat April 13|
|Promathera Biosciences||HepaStem||Liver failure; phase I/II data||Plenary Sat April 13|
|Assembly Biosciences||ABI-H0731||HBV; phase IIa data||Late breaker Sat Apr 13|
|Conatus||Emricasan||Nash; phase II data||Late breaker Sat Apr 13|
|Genfit||Elafibranor||PBC trial; phase II||Late breaker Sat Apr 13|
|Intercept||Ocaliva||Nash; Regenerate phase III||Thu Apr 11|
|Viking||VK2809||Nash; phase II data||Thu Apr 11|
|Spring Bank||Inarigivir||HBV; Achieve phase II study||Fri Apr 12|
|Cirius Therapeutics||MSDC-0602K||Nash; phase IIb results||Fri Apr 12|
|Altimmune||HepTcell||HBV; phase Ib data||Fri Apr 12|
|NGM/Merck & Co||NGM313||NAFLD; phase I||Fri Apr 12|
|Takeda||Maralixibat/SHP627||Alagille Syndrome; phase II data||Sat Apr 13|
|Albireo||A4250||Alagille Syndrome; phase II data||Sat Apr 13|
|AHP=acute hepatic porphyrias; HBV=hepatitis B virus; NAFLD=non-alcoholic fatty liver disease; PBC=primary biliary cholangitis. Source: EASL programme.|
Much of the data that investors are waiting for, however, has not been released in advance.
On the first day full results from Intercept’s Regenerate study will be the big draw. The company released ostensibly positive topline data in early March, but many remain to be convinced by the product’s profile, particularly regarding safety (Intercept's Nash hopes rest on Ocaliva's borderline hit, February 19, 2019).
Most of the high-profile late breakers will emerge on the Saturday. The plenary session on Saturday morning will see Alnylam get its moment in the spotlight with the Envision study of givosiran, with all eyes once again on the toxicity profile (Alnylam touts givosiran win despite toxicity fears, March 6, 2019).
The private Russian company Hepatera has also bagged a plenary spot with its hepatitis B therapy Myrcludex B, a viral entry inhibitor, alongside Promathera Biosciences’ stem cell-based liver failure therapy HepaStem.
Other late breakers on Saturday will feature Conatus’s Encore-PH trial of emricasan, which is known to have failed, a study of Genfit’s elafibranor in PBC, and an update on a phase IIa trial of Assembly Biosciences’s hepatitis B project ABI-H0731. Assembly is expected to report six-month data in a couple of patients for the first time, and a strong reading could see investors gain appreciation for this largely overlooked project.
There is everything still to play for in both hepatitis B and Nash. Although much of the data at EASL this year is from early trials, investors will hope for some important glimpses into several of the most promising pipeline projects.