Shire LogoShire and Parion Sciences have announced they have entered into an agreement granting Shire exclusive worldwide rights to develop and commercialise P-321.

Shire will lead development of P-321, an investigational epithelial sodium channel (ENaC) inhibitor for the potential treatment of dry eye disease in adults, with the opportunity for Parion to co-fund.

P-321 is a Phase II compound being developed to address tear volume deficiency and promote ocular surface healing.

Although further clinical trials are needed to fully evaluate its safety profile and efficacy, P-321 is a novel molecule that is believed to address dry eye disease by inhibiting ENaC, which is thought to block the absorption of tears, and help keep the ocular surface hydrated; current prescription treatments target the effects of ocular inflammation.

“Ophthalmics is a continued focus for Shire, and the programme for P-321 will benefit from our development and commercial infrastructure and expertise,” said Flemming Ornskov, MD, MPH, Chief Executive Officer, Shire.

“This is an opportunity to apply our knowledge and experience from ophthalmics and dry eye disease for further innovation in this space. If approved, P-321 would expand our eye care portfolio.”

“Advancing P-321 with Shire, an emerging global leader in ophthalmics, offers the expertise and resources to move this promising potential therapy for dry eye sufferers forward,” said Paul Boucher, President and Chief Executive Officer of Parion.

“This collaborative license agreement enables us the opportunity to contribute and participate in P-321’s success, while continuing our drive to progress Parion’s pipeline of novel therapies.”

While specific terms of the deal were not disclosed, Shire will make an initial $20 million upfront license payment with an additional $20 million payment based on the achievement of a near term development milestone.

Parion will be entitled to receive additional potential milestone payments, with a total potential deal value of up to $535 million. Parion has the option to co-fund through additional stages of development in exchange for enhanced tiered double-digit royalties.

In addition, Parion has the option to co-fund commercialiation activities and participate in the financial outcome from those activities.

P-321 and Clinical Development Programme
P-321 is a novel small molecule inhibitor of ENaC, which is thought to block the absorption of tears, and help keep the ocular surface hydrated.

A Phase I/IIa placebo-controlled, dose escalation clinical study in 53 patients has been completed, which evaluated the safety and tolerability of P-321 in patients with mild to moderate dry eye disease.

Although the study – P-321-101 – was not powered to assess efficacy signals, positive trends were observed in improvement of signs and symptoms of dry eye disease in subsets of patients, compared with a placebo.

At the highest strength studied (0.01%), no discomfort or instillation irritation was reported with P-321. The adverse events seen in the patients assigned to P-321 were generally similar to or fewer than those that occurred in the patients assigned to the placebo, and none of the adverse events were considered serious.

A Phase IIb study is expected to begin after consultation with health authorities.

Based on preclinical models of dry eye disease, ENaC inhibitors are believed to have the potential to restore or improve tear volume on the ocular surface.

Further clinical trials are needed to evaluate the safety profile, efficacy and mechanism of action of P-321.