Neurocrine Biosciences will partner with Voyager Therapeutics to develop and commercialize its gene therapy programs for Parkinson’s disease and Friedreich’s ataxia, plus two other programs to be determined, through a collaboration that could generate more than $1.865 billion for Voyager, the companies said today.

“This is a transformational collaboration for Voyager that greatly enhances our efforts towards becoming the leading, fully-integrated gene therapy company focused on severe neurological diseases while allowing us to continue to invest in our additional pipeline programs and platform,” Voyager president and CEO Andre Turenne declared in a statement.

Neurocrine CEO Kevin Gorman, PhD, added, “The partnership with Voyager allows us to expand our clinical development pipeline addressing neurological disorders, leverage Voyager’s expertise in CNS-focused gene therapy, and develop potential treatments for diseases, such as Parkinson’s disease and Friedreich’s ataxia, which have significant unmet clinical needs.”

Neurocrine this week was included among GEN’s 10 Takeover Targets to Watch in 2019 based on it successfully commercializing its lead drug, the once-daily tardive dyskinesia treatment Ingrezza® (valbenazine), and more recently, the endometriosis treatment Orilissa® (elagolix), co-developed with AbbVie.

In its latest collaboration, Neurocrine plans to co-develop Voyager’s VY-AADC for Parkinson’s disease and VY-FXN01 for Friedreich’s ataxia.

VY-AADC is a gene therapy candidate designed to deliver the AADC gene directly into neurons of the putamen where dopamine receptors are located, bypassing the substantia nigra neurons and enabling the neurons of the putamen to produce the AADC enzyme to convert levodopa into dopamine.

Voyager reasons that through its method of action, VY-AADC has the potential to durably enhance the conversion of levodopa to dopamine and provide clinically meaningful improvements by restoring motor function in patients and improving symptoms following a single administration.

The FDA has granted its Regenerative Medicine Advanced Therapy (RMAT) designation for VY-AADC for the treatment of Parkinson’s disease in patients with motor fluctuations who are refractory to medical management, based on positive clinical data from a Phase Ib trial with VY-AADC in patients with Parkinson’s disease.

Last year, Voyager trumpeted results from the Phase Ib study (NCT01973543), in which one-time administrations of VY-AADC showed robust and durable improvements in patients’ motor function along with substantial reductions in the use of daily oral levodopa and other Parkinson’s disease medications. Infusions of VY-AADC were well-tolerated, with no vector-related serious adverse events reported at the time.

Phase II/III funding, then options

Neurocrine has agreed to fund the Phase II/III pivotal program for VY-AADC, which has advanced to the Phase II RESTORE-1 trial (NCT03562494). As of January 24, Voyager is recruiting patients for RESTORE-1, which has an estimated enrollment of 42 patients and is designed to assess the distribution, efficacy, and safety of VY-AADC02 in Parkinson’s patients with motor fluctuations. Voyager is seeking to recruit patients who have been diagnosed with Parkinson’s disease for at least four years, are not responding adequately to oral medications, and have at least three hours of OFF time during the day as measured by a validated self-reported patient diary.

Following data readout of the Phase II RESTORE-1 trial, Voyager will have two options. One calls for co-commercializing VY-AADC with Neurocrine Biosciences in the U.S. under a 50/50 cost- and profit-sharing arrangement, with Voyager receiving milestones and royalties based on ex-U.S. sales. The other option calls for Voyager to grant Neurocrine Biosciences full global commercial rights to VY-AADC, in exchange for milestone payments and royalties based on global sales.

Also covered by the collaboration is VY-FXN01, a gene therapy intended to restore FXN protein levels, with a one-time treatment, to at least 50% of normal in relevant neurons and cardiac myocytes, to slow the progression of disease. VY-FXN01 is designed to deliver a functional version of the FXN gene to the sensory pathways through intrathecal or intravenous injection.

“We believe this approach has the potential to improve the balance, ability to walk, sensory capability, coordination, strength, and functional capacity of Friedreich’s ataxia patients,” Voyager stated on its website.

The company noted that most Friedreich’s ataxia patients produce very low levels of the frataxin protein, which, though insufficient to prevent the disease, exposes the patient’s immune system to frataxin. That reduces the likelihood that the FXN protein expressed by AAV gene therapy would trigger a harmful immune response, according to Voyager.

Positive preclinical ataxia results

Voyager has cited positive results showing the company’s frataxin gene therapy vector durably improved ataxia and sensory function in a preclinical model of Friedreich ataxia, and rescued the disease phenotype based on multiple functional tests. In physiological and behavioral assays, Voyager said, its frataxin gene therapy vector showed dose-dependent and durable responses for more than 10 months after a single administration, preventing central and peripheral disease progression.

Additional preclinical studies are underway, according to Voyager, including steps to identify a lead clinical candidate for the treatment of Friedreich’s ataxia this year.

VY-FNX01 development will be funded by Neurocrine through a Phase I clinical trial. Following data readout of the trial, Voyager has the option to either co-commercialize VY-FXN01 with Neurocrine in the U.S. under a 60/40 cost- and profit-sharing arrangement, or grant Neurocrine full U.S. commercial rights in exchange for milestone payments and royalties based on U.S. sales.

Sanofi Genzyme retains its option for ex-U.S. rights to VY-FXN01.

Neurocrine will also fund development of the two yet-to-be-determined programs, with Voyager retaining the right to earn milestone payments and royalties based on global sales, the companies added.

Neurocrine agreed to pay Voyager $115 million upfront and make a $50 million equity investment in Voyager by purchasing 4,179,728 shares at $11.96 per Voyager share—a 49% premium over yesterday’s closing price of $8.04.

Since then, shares of Voyager surged 53% in early market trading, to $12.32 as of 9:42 a.m.

Neurocrine also agreed to fund Voyager for all development costs incurred on the four collaboration programs—and up to $1.7 billion in payments tied to achieving development, regulatory, and commercial milestone payments across the four programs, plus royalties.

According to Voyager’s regulatory filing disclosing the collaboration with Neurocrine, the milestone payments would include:

  • Up to $170 million for the Parkinson’s program
  • Up to $195 million for the Friedreich’s ataxia program
  • Up to $130 million for each of the two discovery programs
  • Up to $275 million in commercialization milestones for each program, with an aggregate cap for all four programs of $1.1 billion

The collaboration is subject to customary closing conditions that include the expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended.

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