Impel raises $67.5M as it eyes filing for nasal migraine drug

Impel NeuroPharma’s championing of the nasal delivery route for drugs has been rewarded with a fourth-round financing that will help it advance three projects through the clinic.

Proceeds of $67.5 million from the series D will keep the company going through 2020, according to chief executive John Congleton, sufficient time for Impel to submit its lead drug INP104 for approval in acute migraine and start a phase 3 program for Parkinson’s disease therapy INP103.

Drug absorption via the nasal cavity is an underutilized route for systemic drug delivery, he tells us, primarily because of difficulty achieving significant and consistent absorption in the lower and upper nasal cavities.

"The key to our Precision Olfactory Delivery, or POD technology is the use of HFA propellant to deliver drug directly to the upper nasal cavity, which is richly vascularized and allows for improved bioavailability and more consistent absorption and potentially improved outcomes."

INP104 uses the POD technology to deliver dihydroergotamine (DHE), a drug whose use the treatment of migraine attacks extends back decades. It tends to be reserved for use only in the most severe and treatment-resistant cases of migraine however, because it has to be delivered intravenously to get the best response.

Nasal spray formulations such as Valeant’s Migranal are available, but don’t seem to work as quickly as other intranasal drugs such as triptans and shouldn’t be used in tandem with the latter, says the American Migraine Foundation. On the plus side, it can be used later in migraine attacks, to prevent recurrence, and to help a patient out of rebound or medication overuse headache.

"We are excited to be bringing an optimized DHE that can be easily administered on an out-patient basis to patients," says Congleton, adding that Impel believes physicians will "welcome a new version of a proven compound as a valuable treatment option."

Impel has phase 2 data in hand for INP104 that shows it is three time more effective than a traditional nasal spray at increasing DHE levels in the blood, achieving clinically meaningful blood levels at 10-20 minutes and matching IV levels from 30 minutes through 48 hours. It’s now in a phase 3 safety study that should readout in the third quarter of 2019, with a filing scheduled later that year or in early 2020. The trial is using an electronic diary tool to measure efficacy endpoints such as speed and duration of relief.

There have been other attempts to develop new DHE products for acute migraine, notably Allergan’s orally inhaled Semprana (formerly Levadex), which was rejected three times by the FDA before being abandoned.

As INP104 is a variation on a well-accepted route of administration for DHE, Impel is hoping for an easier ride through the regulatory review process, and Congleton also thinks that the big changes in the market, such as the approval of new CGRP inhibitors for migraine prevention, are a plus.

"We know from research that well over 70% of migraine patients are dissatisfied and willing to try a new therapy [and] we believe the enthusiasm for new therapies and the significant unmet need, will be a benefit for INP104 upon introduction."

Turning to the Parkinson’s disease program, which aims to use POD-delivered levodopa to tackle OFF episodes where the effects of drugs wear off, Congleton says new data from two dose cohorts (35mg and 70mg) should be available before the end of the year.

"We believe INP103 will provide a distinct advantage for patients and caregivers given the ease of administration and the potential for a rapid clinical response.  This profile will fit very well in the Parkinson’s disease treatment armamentarium as there is currently no alternative for rescue of an OFF episode."

The cash injection will also help Impel advance its third clinical program for agitation associated with diseases such as bipolar and schizophrenia. Single ascending dose data for INP105, which delivers widely-used antipsychotic olanzapine, will be available before the end of the year, and it is planning a further trial for 2019 that could be enough to support a regulatory filing in 2020.

Between now and then Impel "will be considering additional options for funding our ongoing development and eventual commercial support of our pipeline," says Congleton.

The latest investment round was co-led by KKR and Norwest Venture Partners, with participation from existing investors Vivo Capital, 5AM Ventures and venBio Partners. Norwest’s Robert Mittendorf and KKR’s Ali DSatvat have now joined Impel’s board.

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