JP Morgan 2017: Axovant’s awe-inspiring ascendency faces year of reckoning in 2017, acknowledges CEO Vivek Ramaswamy

Axovant Sciences has attracted an outsized number of both backers and detractors since exploding onto the biotech scene with a massive IPO in mid-2015, and one thing becomes clear listening to CEO Vivek Ramaswamy tick off plans for the year ahead: vindication will be soon in coming for the bears or the bulls based on the litany of near-term readouts for the company’s programmes in Alzheimer’s disease (AD) and Lewy body dementia (LBD).

As of 12 months ago, 2016 had the potential to be a watershed moment for disease-modifying AD therapies. Not for the first time, however, things did not work out that way as Eli Lilly’s anti-beta-amyloid mAb solanezumab failed a third successive Phase III trial, touching off yet another round of soul-searching on the part of researchers and drug developers.

In contrast, if Ramaswamy’s plans for Axovant play out, 2017 is shaping up to be the year of incremental improvement for neurodegenerative diseases – which, to be fair, is nothing to scoff at considering the long list of clinical failures and lack of progress in treating conditions like AD and LBD.

Axovant’s single biggest inflection point is scheduled for 3Q17 when results are expected from the Phase III MINDSET trial of intepirdine to treat mild-to-moderate AD. The small molecule 5-HT6 receptor antagonist, which was in-licensed from GlaxoSmithKline for relative peanuts in late 2014, was after all the basis for the biotech’s eye-popping $360-million IPO in June 2015. (See ViewPoints: Axovant’s IPO goes gangbusters – why GlaxoSmithKline may be in a no-lose situation.)

Recent history has not been kind to 5-HT6 modulator class, as programmes from Pfizer and Lundbeck (partnered with Otsuka) fell by the wayside just last year, though Ramaswamy believes that Axovant’s compound and development plan will avoid the pitfalls that tripped up competing programmes.

“Lundbeck made significant changes between Phase II and Phase III after seeing some significant liver tox, which led to their decision to move forward with a lower total daily dose, and they also changed from mild to mild-to-moderate patients,” Ramaswamy told FirstWord this week. “By contrast, we preserved as much as we could from the Phase II trial of intepirdine, which showed a statistically significant improvement on cognition and function, including using the same dose and an analogous patient population,” he added.

The Street’s confidence in intepirdine has varied wildly, though given the current environment for biotech it is perhaps no surprise that the bears may have grabbed the upper hand lately, as Axovant is off more than 14 percent from its IPO price despite the fact the company has yet to reach any significant data readouts.

Intepirdine’s success or failure in the MINDSET study will be a massive inflection point for Axovant, with a win on the primary endpoint likely being sufficient for a 2018 approval (at which point the company will be committed to marketing the product itself), whereas disappointment would be a massive setback.

Rather than putting all its eggs in one basket, Ramaswamy has been working hard to ensure that Axovant has a diversified portfolio of programmes for neurodegenerative diseases such that it can use intepirdine’s success as a launch pad for becoming a fully integrated company or, if things don’t work out, be prepared to pivot to a readymade plan B (See ViewPoints: Axovant adds more eggs to its basket of symptomatic Alzheimer’s disease candidates.)

Beyond the MINDSET trial in AD, Axovant is also making a significant push into LBD and related disorders. Indeed, intepirdine is being evaluated in a potentially pivotal study to treat dementia with Lewy bodies (DLB) while a second candidate, nelotanserin, is in mid-stage testing for both visual hallucinations and REM behavior disorder in patients with LBD. Results from each of the studies are slated to readout later this year.

As if that wasn’t enough, Axovant also expects to report data from a proof-of-concept study of RVT-103, which combines the acetylcholinesterase donepezil and a peripherally acting muscarinic muscarinic receptor antagonist, to treat AD in 1H17. Ramaswamy believes the candidate's unique binding and penetration profiles gives it the potential to differentiate itself both from available therapies as well as a similar regimen being evaluated by Allergan. (See ViewPoints: Allergan buys a low-risk call option via Chase Pharma.)

Axovant’s programmes may not offer the sexy disease-modifying potential expected of more ballyhooed agents targeting the amyloid cascade, but that does not mean they wouldn’t offer important benefits to patients and produce significant returns for investors – only time will tell.

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