Supernus Pharmaceuticals said it has agreed to acquire Biscayne Neurotherapeutics for up to $185 million, in a deal that adds a Phase I epilepsy candidate to the buyer’s pipeline of treatments for central nervous system disorders.
The epilepsy candidate, which Supernus will rename SPN-817, uses a novel synthetic form of huperzine A, an acetyl cholinesterase inhibitor that according to the company has a novel mechanism of action and has shown anticonvulsant activity in preclinical models for partial seizures and Dravet Syndrome.
Supernus said it plans on studying SPN-817 initially in catastrophic pediatric epilepsy disorders, such as Dravet Syndrome, with an initial focus on the drug’s anticonvulsant activity.
A Phase I proof-of-concept trial (NCT03474770) launched by Biscayne has begun assessing the safety and pharmacokinetics profile of a new extended release formulation of the drug in adults with refractory complex partial seizures. The trial’s primary endpoint is reduction in average daily seizure count between baseline (pre-treatment) and evaluation (on treatment) video EEG monitoring periods.
“Huperzine A has a novel mechanism of action that represents a new approach for the treatment of epilepsy. We look forward to working with Supernus and progressing SPN-817 in the clinic, and eventually to its availability to patients,” Stephen Collins M.D., Ph.D., president and CEO of Biscayne, said yesterday in a statement.
Biscayne was spun out of Biscayne Pharmaceuticals in January 2017 with $3 million in Series B funding, to develop the antiepileptic candidate formerly known as BIS-001.
“Supernus, with its strong presence in epilepsy and its proven technologies and research and development capabilities, represents an ideal partner for us,” added Dr. Collins, a neurologist who has been involved over the past three decades with the development of several anti-epilepsy products.
Dr. Collins will be retained on a consulting basis to assist with the transition and potentially the future development of SPN-817, Supernus said.
According to Supernus, SPN-817 increases cortical acetylcholine and readily crosses the blood-brain barrier showing an increase in gamma-aminobutyric acid (GABA), a seizure inhibitor, in the cortical region of the brain.
In a predictive preclinical seizure model, huperzine A demonstrated 57 times more potency than levetiracetam, a leading anti-epilepsy drug. Supernus said it plans to focus on completing and optimizing the synthesis process of the drug and the development of a novel dosage form.
Given the potency of huperzine A, Supernus reasons, a novel extended-release oral dosage form will be critical to the success of SPN-817 because initial studies with immediate release formulations of non-synthetic huperzine A have shown dose-limiting serious side effects.
SPN-817 will join a Supernus portfolio that includes two Phase III candidates—SPN-810 (molindone hydrochloride), indicated for impulse aggression in attention-deficit/hyperactivity disorder (ADHD); and SPN-812, a novel non-stimulant for the treatment of ADHD.
SPN-810 is the subject of two Phase III trials, for which the company anticipates having data from one study by the first quarter of 2019, and from the other by mid-2019. SPN-812 is being assessed in four Phase III trials, with data from one anticipated during the fourth quarter, and data from the other three, in the first quarter of 2019.
Also in Supernus’ pipeline are new indications for one of its two marketed drugs—the epilepsy treatment Oxtellar XR® (extended-release oxcarbazepine), for which pivotal Phase III studies are set to be launched in bipolar disorder in the second half of 2019.
The company’s other marketed drug, Trokendi XR® (extended-release topiramate), is indicated for the prophylaxis of migraine and the treatment of epilepsy.
“We are excited to add SPN-817 to our portfolio as part of our long-term growth strategy. It represents a strong strategic fit with Oxtellar XR and Trokendi XR in neurology,” Supernus president and CEO Jack Khattar stated. “We are committed to epilepsy patients and to bringing to them novel alternative treatment options.”
SPN-817 has received the FDA’s Orphan Drug designation for the treatment of Dravet Syndrome, a severe form of childhood epilepsy, and will have a new chemical entity status (NCE) in the U.S. market.
Under the acquisition deal, Supernus will gain worldwide rights to SPN-817, except for some Asian markets where rights have been out-licensed. Supernus will also obtain rights to all the product candidate’s underlying and related intellectual property.
Supernus has agreed to pay $15 million upfront to Biscayne’s current security holders, $73 million tied to achieving development milestones, and up to $95 million tied to achieving sales milestones.
Supernus also agreed to pay a low single digit royalty on net sales to Biscayne and any applicable royalties to third parties for the use of in-licensed IP. The maximum combined royalty Supernus will pay to all parties is approximately 12%, depending on the IP covering the marketed product and the applicable tiered sales levels, the buyer said.
To reflect the Biscayne acquisition, Supernus has lowered its investor guidance on operating earnings and raised its guidance on R&D expenses for 2018. This year, the company now expects operating earnings that range from $115 million to $125 million, down from between $130 million and $145 million, and initially projected to range from $125 million to $135 million.
R&D expenses are now expected to be approximately $95 million, up from approximately $80 million, Supernus said.
Supernus has maintained its net product sales guidance for this year ranging from $385 million to $400 million—a guidance that the company raised after the first quarter from its initial forecast of between $375 million to $400 million.