Ionis' Ups and Downs: Partnership with Progenity, 70% Job Cuts at Akcea and More

Ionis Building Exterior

Photo courtesy of Ionis.

Ionis Pharmaceuticals unleashed a string of news releases about activities at the company, including a partnership with Progenity and the launch of a Phase III trial for amyotrophic lateral sclerosis (ALS). It also announced that it was laying off almost 70% of the staff at Akcea Therapeutics as part of a reorganization. Let’s take a look at the company’s news.

In 2014, Ionis, based in Carlsbad, California, spun off Akcea Therapeutics to market a portfolio of drugs that were then facing regulatory decisions, primarily a family of drugs for rare lipid disorders.

Akcea raised $144 million via an initial public offering (IPO) in 2017, and within two years, had approvals for Waylivra, for familial chylomicronaemia syndrome (FCS), a rare lipid disease leading to high levels of triglycerides in the blood; and Tegsedi, for transthyretin amyloidosis. However, both drugs’ sales have been disappointing, with combined sales in 2019 of $42 million and $70 million in 2020. Then in 2020, Ionis re-acquired Akcea.

The SEC filing indicated they are reorganizing the company and cutting the Akcea workforce by almost 70%. The company expects to report restructuring charges ranging from $11 to $14 million in the quarter ending June 30, 2021.

On a financial note, Ionis announced it is planning to offer a $500 million aggregate principal amount of Convertible Senior Notes due 2026 in a private placement to qualified institutional buyers. It plans to use some of the proceeds to repurchase for cash some of its 1% Convertible Senior Notes due 2021 in private deals. It also plans to use some of the net proceeds to pay the cost of several convertible note hedge transactions.

On the clinical front, Ionis inked an agreement with San Diego-based Progenity to study the safety, tolerability and performance of Progenity’s Oral Biotherapeutics Delivery System (OBDS) for oral dosing of Ionis’ antisense oligonucleotides. Ionis’ antisense drugs work by targeting mRNA, so the amount of disease-causing protein is decreased; they can also treat diseases caused by too little protein by increasing protein production.

OBDS is an ingestible capsule based on Progenity’s needle-free technology. It allows a drug to be formulated in a way that it can be delivered directly into the tissues of the small intestine, where it will be systemically absorbed.

“We’re excited to work with Ionis, a leader in nucleic-acid-based biotherapeutics, to collectively evaluate the ODBS platform for the oral delivery of antisense therapies,” said Harry Stylli, chief executive officer, chairman and co-founder of Progenity. “We believe the OBDS platform shows promise to transform the systemic delivery of diverse biotherapeutics via oral administration.”

Ionis also announced it had initiated a Phase III clinical trial of its antisense drug ION363 in amyotrophic lateral sclerosis (ALS) patients with mutations in the fused in sarcoma gene (FUS). ION363 targets the FUS RNA to decrease the production of the FUS protein. The trial will enroll up to 64 FUS-ALS patients to receive the drug intrathecally.

In part one of the study, patients will be randomized 2:1 to receive a multi-dose regimen of ION363 or placebo for 29 weeks, followed by a part two open-label component, where all patients will receive ION363 for 73 weeks.

ALS is a rare, fast-moving and fatal neurodegenerative disease marked by muscle weakness, loss of movement, and difficulty in breathing and swallowing.

“Advancement of ION363 to a pivotal trial is the latest example of the power of Ionis’ antisense technology to potentially target the root causes of neurological diseases,” said Frank Bennett, Ionis’ chief scientific officer, and neurological program franchise leader. “Driven by our experience in developing medicines for motor neuron diseases such as ALS and spinal muscular atrophy and our intimate connection to the ALS patient community, Ionis decided to advance ION363 to the clinic and, ultimately, to the market because we believe we are uniquely positioned to make it available to patients living with FUS-ALS.”

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