Rare disease specialist Amicus Therapeutics Inc. is breaking into the gene therapy field with the acquisition of 10 new assets through its purchase of Ohio-based Celenex Inc. for $100 million up front. The deal also features up to $277 million in development and regulatory milestones, plus potential sales-based payments. Two clinical-stage programs in Batten disease lead the in-licensed portfolio, which also includes lysosomal storage disorder programs in Niemann-Pick type C, Wolman disease and Tay-Sachs.

Nationwide Children's Hospital, from which Celenex was born, will continue to offer scientific support.

News of the deal, greeted with measured enthusiasm by Leerink analyst Joseph Schwartz as complementing the company's in-house expertise in biologics, also yielded moderate reaction from investors, who pushed Amicus shares (NASDAQ:FOLD) 6.9 percent higher to $12.62 on Thursday.

Amicus Chairman and CEO John Crowley foreshadowed the move in August when his team won FDA approval for its oral Fabry disease therapy, Galafold (migalastat), at which point he spoke openly about his team's aspirations in gene therapy. On Thursday, he suggested there's more dealmaking to come, possibly in the company's core areas of expertise in Fabry and Pompe. "This is just the beginning of Amicus' work in gene therapy for rare diseases," he said. (See BioWorld, Aug. 14, 2018.)

The acquisition provides Amicus with worldwide development and commercial rights for all 10 gene therapy programs Celenex has in its current portfolio. Each was developed by Brian Kaspar and Kathrin Meyer at Nationwide Children's Hospital's Center for Gene Therapy, along with collaborator Arthur Burghes, a professor at Ohio State University, working with Celenex CEO Samit Varma and colleagues. All of the acquired programs leverage intrathecal delivery, using the same AAV vector approach utilized successfully in clinical trials run by Novartis AG-acquired Avexis Inc. across other rare CNS indications, such as spinal muscular atrophy. (See BioWorld, April 10, 2018.)

Given the targeted delivery of AAV9 directly to the cerebrospinal fluid of patients, the approach requires an order of magnitude less AAV than other therapies that rely on I.V. delivery, said Jeffrey Castelli, Amicus' chief portfolio officer. The need for less volume of the therapy could have potential advantages, both in terms of safety and manufacturing, he said.

Batten disease, also known as neuronal ceroid lipofuscinosis, is a family of rare, fatal, lysosomal storage disorders of the central nervous system affecting children. By developing new medicines for it, the company is moving toward fulfilling its five-year vision of treating more than 5,000 patients with Amicus medicines.

In CLN6 Batten disease, the most advanced program acquired, Crowley estimated that there are about 1,000 patients across Amicus' commercial landscape today. For CLN3 Batten, about 5,000 patients are thought to live in the geographies Crowley expects Amicus can address. CLN8 Batten is thought to affect more than 750 patients. The remainder of the gene therapy programs, which cover disorders such as Niemann-Pick C, Wolman disease, Tay-Sachs and four others, have more than 3,500 patients in Amicus' addressable markets.

Based on positive preclinical data, a phase I/II study in CLN6 Batten disease was initiated a little more than two years ago with the intention of testing the safety and efficacy of a single intrathecal administration of AAV9-CLN6 gene therapy in about 12 children with the condition. Ten children have been treated to date, and more are due to be treated soon. So far, the treatment has been generally well-tolerated, Castelli said. Amicus expects to present additional data from the study in 2019. But two-year data on a pair of sisters enrolled in the study has so far proved encouraging, Castelli said, with some stabilization in disease progression seen in one of the girls to date.

The second most advanced program Amicus acquired would address the most prevalent form of all the Batten diseases, CLN3. A phase I/II study has now been initiated at Nationwide Children's with expectations that the first patients will be treated in the coming months, Castelli said.

To support the up-front payment to Celenex and several years of development costs for the new programs, Amicus obtained a $150 million debt facility from Biopharma Credit plc, an investment fund managed by Pharmakon Advisors LP. Now, "with the $553 million of cash on hand at the end of June and the proceeds of this debt facility, we'll remain in a very strong financial position to fully invest in the rapid advancement of these new gene therapy programs," Amicus' president and chief operating officer, Bradley Campbell, said.

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