Novartis closes the year with two head-scratchers

Cue quizzical eyebrow raising at two deals announced by Novartis yesterday. First was the acquisition of an eye disease researcher, adding a novel mechanism of action in a therapy area that many assume the pharma giant is looking to exit.

Then a second transaction saw Novartis pay $50m for an option over Conatus’s Nash candidate, emricasan. The trigger for a full licensing deal is the start of a phase IIb trial in decompensated cirrhotic patients which must happen by the end of October next year; with Conatus management insisting it knows no reason why this would not happen on time, the reason for delaying a full blown deal is far from clear.

On a conference call Steven Mento, chief executive of Conatus, shed little light on the matter, despite numerous questions from analysts. He pointed out that emricasan, a pan-caspase inhibitor, was one of only two candidates in clinical development for Nash cirrhosis, and as such the phase IIb study investigating this population, Encore-LF, was a “very important” trial.

The company now plans to use a composite clinical endpoint for the study rather than surrogate measures, and this has all been discussed with regulators, Mr Mento said, although he would disclose no further details. He did suggest, however, that should a trial of this design be successful it would raise the prospect of a faster route to full regulatory approval.

“This is why we want to maintain the time lines to initiate this trial and get data as soon as possible as it could effectively eliminate subsequent required studies to look at clinical outcomes associated with a surrogate endpoint. So it is an important study for us and Novartis,” he said.

Still, he also went on to say that Encore-LF was chosen as the trigger simply because it was the only trial of a four-study phase IIb programme yet to start. Should the full deal commence the San Diego company will continue to run the programme, with Novartis paying half the costs.

The Swiss company will take over the project from phase III, and Conatus stands to receive up to $650m in development, regulatory and commercial milestones. It will also be able to access a $15m loan note, bank another $7m should Novartis take a full license next year, and decide further down the line whether to co-commercialise in the US.

Emricasan phase IIb programme 
Trial name  Patient population Enrolment  Duration Key endpoints Trial ID
Encore-LF Decompensated Nash cirrhosis TBD 48 wks Undisclosed composite clinical endpoints TBD
Encore-PH Nash cirrhosis with portal hypertension 240 24 wks Hepatic Venous Pressure Gradient NCT02960204
Encore-NF Nash fibrosis 330 72 wks Nash Clinical Research Network histology NCT02686762
POLT-HCV-SVR Post transplant HCV-SVR with fibrosis or cirrhosis 60 Two yrs Ishak Fibrosis Score NCT02138253

Much emphasis on the call was placed on the potential to combine emricasan with Novartis’s FXR agonist, LJN452. Should this be pursued Novartis will lead and pay for the development. However with data unlikely to emerge until 2018 from the single-agent studies, the real potential in emricasan will take time to elucidate.

Indeed, underwhelming results to date have been responsible for supressing Conatus’s valuation, despite its activity in the red-hot Nash space. Before today the company was worth $49m, little more than its September 30 cash balance of $31m. This meagre sum could plausibly explain the hefty option fee – the company needed to bolster its cash balance quickly before starting the full phase IIb programme, avoiding the risk of not being able to fund it to completion.

Conatus shareholders will have to hope that Novartis was not moving to corner an asset in a competitive process while continuing to look around in the meantime. Or that the “other things” vaguely alluded to in the 8-K with regards to the trigger decision turn out to be more significant than just an issue of timeliness of the Encore-LF trial.

Looking for deals

The other deal Novartis announced, the acquisition of Encore Vision, is more of a strategic than a financial puzzle, as no terms were released.

The Texan company’s main asset is EV06, a mid-stage topical treatment for presbyopia – the age-related near-sightedness that affects more than 80% of adults over 45. Encouraging results were generated in a placebo-controlled phase I/II trial of 75 patients; the drug works by softening the gradual stiffening of the lens of the eye, a major cause of presbyopia.

Given that this condition can be solved by wearing glasses, this drug would seem to hold the potential to be hugely disruptive. That or a massive challenge for Alcon’s marketing department.

Clearly this approach still has far to travel. But it suggests the Novartis mothership has not totally given up on Alcon.  

To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com or follow @ByAmyBrown on Twitter

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