On February 24, 2022 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported financial results for the fourth quarter and full year ended December 31, 2021, and recent business achievements (Press release, Ionis Pharmaceuticals, FEB 24, 2022, View Source [SID1234608969]).

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"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)

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):

(1)All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards. In 2021 and 2020 all non-GAAP amounts also excluded expenses related to the Akcea Merger and restructured commercial operations and the related tax effects. Please refer to the section below titled "Financial Impacts of Akcea Merger and Restructured Commercial Operations" for a summary of the costs specific to these transactions. Additionally, please refer to the detailed reconciliation of non-GAAP and GAAP measures, which is provided later in this press release.

(2)Partnered program milestones are based on partners’ most recent publicly available disclosures.

Revenue

Ionis’ revenue was comprised of the following (amounts in millions):

The Company’s revenue increased by more than 10 percent compared to 2020 driven in large part by significant partner payments across multiple partnered programs. In 2021, the Company earned $200 million from its new collaboration with AstraZeneca to jointly develop and commercialize eplontersen. The Company also earned more than $160 million from Biogen for advancing several neurology disease programs.

The Company successfully completed the transition of its TEGSEDI and WAYLIVRA operations in the EU and North America to Sobi in the first and second quarters of 2021, respectively. The decrease in TEGSEDI and WAYLIVRA revenue in 2021 compared to 2020 was due to the shift from product sales to distribution fees based on net sales generated by Sobi. As part of the transition, Ionis restructured its commercial operations resulting in substantial cost savings.

Operating Expenses

Ionis is advancing a large late-stage pipeline and as a result, its non-GAAP operating expenses increased in 2021 compared to 2020. Higher R&D expenses were driven by the expanded number of Phase 3 studies the Company was conducting, which doubled over the course of 2021 from 3 to 6 studies. Additionally, the Company recognized $35 million in R&D expense in the third quarter of 2021 for licensing Bicycle Therapeutic’s technology. Lower SG&A expenses primarily reflected operating efficiencies achieved from integrating Akcea and restructuring the Company’s commercial operations.

Net Loss Attributable to Ionis Common Stockholders

Net loss attributable to Ionis’ common stockholders in 2021 decreased compared to 2020 for the reasons discussed above. Also contributing to the decrease in Ionis’ net loss in 2021 compared to 2020 was the non-cash adjustment of the valuation allowance Ionis recorded against its federal net deferred tax assets in 2020.

Balance Sheet

As of December 31, 2021, Ionis had cash, cash equivalents and short-term investments of $2.1 billion, compared with $1.9 billion as of December 31, 2020.

The Company revised its 2020 amounts to reflect the simplified convertible instruments guidance the Company adopted retrospectively on January 1, 2021.

Webcast

Ionis will conduct a webcast today at 11:30 a.m. Eastern time to discuss this announcement and related activities. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address.