Six years after they began partnering to successfully develop the spinal muscular atrophy (SMA) treatment Spinraza® (nusinersen), Biogen and Ionis Pharmaceuticals said today they have launched a 10-year, $1 billion-plus expanded collaboration to develop more neurological drugs.

The companies said they plan to develop novel antisense drug candidates for a broad range of neurological diseases for which few treatments now exist. The indications include dementia, neuromuscular diseases, movement disorders, ophthalmology, diseases of the inner ear, and neuropsychiatry.

Biogen will retain the first choice of neurology targets on which to exclusively collaborate with Ionis. Ionis agreed to oversee the identification of antisense drug candidates based on selected targets, while Biogen will be responsible for and pay for nonclinical studies, clinical development, manufacturing, and commercialization, the companies said.

Biogen agreed to pay Ionis $1 billion in cash, to consist of $625 million toward the purchase of 11,501,153 shares of Ionis common stock at $54.34 per share, a price 18.5% above yesterday’s $45.85 closing price for Ionis shares—and $375 million upfront. The high up-front payment prompted the companies to trumpet their expanded partnership as “representing one of the most significant discovery stage collaborations in the industry.”

Under the companies’ new collaboration, Biogen will have the option to license therapies arising out of this collaboration and will be responsible for their development and commercialization. However, Biogen also agreed to pay milestone payments, license fees, and royalties on net sales.

“This new collaboration provides the potential opportunity to build an even stronger pipeline for Biogen and Ionis, with the expectation of bringing further benefit to patients in desperate need and value to Ionis’ shareholders,” Ionis CEO and chairman Stanley T. Crooke, M.D., Ph.D., said in a statement.

“This new collaboration’s financial terms, up-front payment, milestone payments, and royalties are substantially higher compared to our previous collaborations with Biogen, which demonstrates the value we have created in applying Ionis’ antisense technology platform to neurological disease,” Dr. Crooke added.

When Biogen exercised its option to license global rights to Spinraza in August 2016 following positive Phase III results, it agreed in return to pay Ionis $75 million upfront and up to $225 million overall.

Near-Blockbuster Sales, Looming Competition

Spinraza generated near-blockbuster global sales of $884 million last year, up from $5 million in 2016. Spinraza costs $750,000 for the first full year of treatment, a price tag that has generated controversy. But a bigger challenge to Spinraza looms in emerging competition from gene therapy candidates in development, most notably AveXis’ AVXS-101, which in November generated positive Phase I data in type 1 SMA, and has since advanced to a pivotal trial. AveXis is being acquired by Novartis for $8.7 billion.

“We believe that this new collaboration will allow us to meaningfully expand our neuroscience pipeline in a way that differentiates Biogen,” added Biogen CEO Michel Vounatsos. “With the large number of diseases that could benefit from Ionis’ antisense platform, we believe that the time is now to build upon our highly productive collaboration with Ionis as we aim to transform the treatment of neurological diseases around the world.”

The new collaboration builds on the partnership launched in 2012 by Biogen and Ionis, back when they were known as Biogen Idec and Isis Pharmaceuticals, respectively. That partnership advanced Spinraza through clinical phases to FDA approval in December 2016 and European Commission approval in June 2017.

Additionally, Biogen and Ionis have partnered to bring two antisense drug candidates into Phase I/IIa clinical studies:

  • BIIB080 (IONIS-MAPTRx), an antisense oligonucleotide designed to reduce production of the tau protein and its accumulation in brain cells, potentially slowing the progress of both in Alzheimer’s disease and frontotemporal dementia. A clinical study assessing the drug (NCT02623699) was recruiting patients as of April 13.
  • BIIB067 (IONIS-SOD-1Rx), an inhibitor of the mutated protein superoxide dismutase (SOD1) associated with the degeneration of motor neurons in a rare form of amyotrophic lateral sclerosis (ALS). The treatment is designed to slow the fatal progression of SOD1-ALS. A clinical study assessing the drug (NCT03186989) was recruiting patients as of February 21.

Biogen and Ionis said their existing collaboration has the potential to advance up to seven more drug candidates to the clinic within the next two years.

Ionis received $118 million from Biogen in milestone payments last year—including $90 million in milestone payments for Spinraza, $10 million for initiating the Phase I/II study of IONIS-MAPTRx and $15 million for validating two undisclosed neurological disease targets.

As for the new collaboration, Biogen and Ionis said they expect the deal to close in the second quarter, subject to customary closing conditions that include the expiration of the applicable waiting period under the Hart–Scott–Rodino Antitrust Improvements Act of 1976 in the U.S.

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