Exceeded 2021 financial guidance with revenues of more than $800 million

Webcast today, February 24, 2022, at 11:30 a.m. Eastern Time

CARLSBAD, Calif., Feb. 24, 2022 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today reported financial results for the fourth quarter and full year ended December 31, 2021, and recent business achievements.

"During 2021, we made significant progress towards achieving our vision of becoming a leading fully-integrated biotechnology company. We advanced our commercial strategy and go-to-market plans for our near-term commercial opportunities, eplontersen, olezarsen and donidalorsen. Our collaboration with AstraZeneca to jointly develop and commercialize eplontersen enables us to potentially maximize benefit for patients, bolster our commercial organization and accelerate preparations for our near-term product launches. Most recently, we initiated Phase 3 studies with olezarsen in patients with severely high triglycerides and donidalorsen in patients with hereditary angioedema. This expands our Phase 3 pipeline to six medicines addressing eight indications. We also advanced our technology, positioning us to build on our leadership in RNA-targeted therapeutics and add value for our future medicines," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We look forward to a steady cadence of catalysts throughout this year, highlighted by eplontersen Phase 3 data in patients with hATTR polyneuropathy planned for mid-year. We expect to file for regulatory approval for eplontersen before year end, assuming positive data. We also expect to make continued advancements to expand and diversify our technology. Based on our anticipated near- and mid-term catalysts, we believe we are well positioned to drive increasing value for patients and shareholders."

2021 Summary Financial Results

• Exceeded 2021 financial guidance
• $810 million in total revenues
• $695 million of operating expenses on a non-GAAP basis(1) and $840 million on a GAAP basis
• Net income of $116 million on a non-GAAP basis(1) and a net loss of $29 million on a GAAP basis
• Well capitalized with cash and short-term investments of $2.1 billion at year-end, enabling accelerating investments in 2022 with the goal to drive substantial future growth

Recent Marketed Products Highlights

• SPINRAZA®: the global market leader for the treatment of spinal muscular atrophy (SMA) patients of all ages
• $1.9 billion in worldwide SPINRAZA sales in 2021
• More than 11,000 patients worldwide on therapy at the end of 2021 across commercial, expanded access and clinical trial settings
• Biogen continued to expand upon SPINRAZA's competitive profile through the ongoing ASCEND, RESPOND and DEVOTE studies
• TEGSEDI® and WAYLIVRA®: important medicines approved for the treatment of patients with hereditary TTR amyloidosis with polyneuropathy and familial chylomicronemia syndrome, respectively
• TEGSEDI and WAYLIVRA achieved innovative drug pricing in Brazil
• WAYLIVRA is under review in Brazil for the treatment of familial partial lipodystrophy (FPL). If approved, WAYLIVRA will be the first approved treatment for patients with FPL in Brazil

Fourth Quarter 2021 and Recent Events

• Advancing Ionis' near-term commercial opportunities toward the market
• Eplontersen: potential to change the standard-of-care for patients with TTR amyloidosis (ATTR)
• Initiated a collaboration with AstraZeneca to jointly develop and commercialize eplontersen valued at up to $3.6 billion in an upfront and potential milestone payments, plus cost-sharing and royalties
• The U.S. FDA granted orphan drug designation to eplontersen for the treatment of patients with ATTR
• Olezarsen: potential first-in-class treatment for patients with elevated triglycerides
• Initiated the Phase 3 CORE study of olezarsen in patients with severe hypertriglyceridemia (SHTG) with data expected in 2024
• Reported positive data from the Phase 2 study of olezarsen in patients with moderate hypertriglyceridemia and at high risk for or with established cardiovascular disease in the European Heart Journal
• Donidalorsen: potential best-in-class prophylactic treatment for patients with hereditary angioedema (HAE)
• Initiated the Phase 3 OASIS-HAE study of donidalorsen in patients with HAE with data expected in 2024
• Presented positive data from the Phase 2 study of donidalorsen in patients with HAE at the ACAAI annual scientific meeting
• Advancing Ionis' leading cardiovascular disease franchise
• AstraZeneca presented new data from the Phase 1 multiple ascending dose study of ION449 (AZD8233) targeting PCSK9 in statin treated subjects with dyslipidemia at the AHA scientific sessions
• Addressing substantial unmet medical needs with Ionis' broad neurological disease franchise
• Biogen licensed ION306 (BIIB115) for the treatment of SMA with the potential for extended dosing intervals, resulting in a $60 million payment from Biogen
• Biogen reported that while the Phase 3 VALOR study of tofersen in patients with SOD1-ALS did not meet the primary endpoint, signs of reduced disease progression across multiple secondary and exploratory endpoints were observed. Biogen continues to engage with regulators to discuss a path forward for tofersen
• Roche announced plans to initiate a new Phase 2 study of tominersen in patients with Huntington's disease based on new findings from a post-hoc analysis of the Phase 3 GENERATION-HD1 study
• Initiated the Phase 1/2 HALOS study of ION582 (BIIB121) in patients with Angelman syndrome, resulting in a $10 million payment from Biogen
• Advanced three neurological disease programs, resulting in $23 million in payments from Biogen
• Dynacure advanced IONIS-DNM2-2.5Rx, resulting in $7.5 million in payments from Dynacure
• Advancing additional programs in Ionis' clinical pipeline for diseases with unmet medical need
• Initiated a Phase 2 study of sapablursen (formerly known as IONIS-TMPRSS6-LRx) in patients with polycythemia vera, the second indication for sapablursen
• Reported topline results from the Phase 2 study of cimdelirsen (formerly known as IONIS-GHR-LRx) in patients with uncontrolled acromegaly, achieving proof of mechanism with a strong indication of proof of concept
• Advanced two metabolic disease programs, resulting in $40 million in payments from AstraZeneca

2022 Pipeline Milestones(2) 

✓ = achieved      • = planned

2021 Financial Results and 2022 Financial Guidance

"Over the last year, we achieved numerous pipeline and technology milestones, advanced multiple medicines towards the market and accelerated preparations for our near-term commercial launches. We also exceeded our 2021 financial guidance, driven by revenue from advancing multiple partnered programs and by strengthening and streamlining our business," said Elizabeth L. Hougen, chief financial officer of Ionis. "We have a long history of financial responsibility that provides us with a strong financial foundation. With more than $2 billion of cash and a substantial and sustainable base of commercial and R&D revenues, we are well positioned to accelerate our investments in 2022 to drive substantial future growth."

2022 Financial Guidance

Ionis' full year 2022 financial guidance consists of the following components (on a non-GAAP basis)(1):

Guidance
Revenue	>$575 million
Operating Expenses (1)	$825 million to $850 million
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