Ionis reports first quarter financial results and recent business achievements

On May 4, 2022 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported financial results for the first quarter of 2022 and recent business achievements (Press release, Ionis Pharmaceuticals, MAY 4, 2022, View Source [SID1234613507]).

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"We are off to a strong start this year highlighted by progress in our rich late- and mid-stage pipeline. We remain on track for data from the NEURO-TTRansform study of eplontersen in patients with hereditary ATTR polyneuropathy by mid-year. Assuming positive data, we plan to file for regulatory approval by the end of this year. We recently increased the size and duration of our CARDIO-TTRansform study of eplontersen in patients with ATTR cardiomyopathy. Our aim is to generate even more robust data and ensure a highly positive study outcome to successfully compete in this growing and dynamic market," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We also reported positive data from two potential best-in-class medicines. In the Phase 2b ETESIAN study, ION449, our investigational medicine targeting PCSK9, demonstrated robust LDL-C and PCSK9 reductions in statin-treated patients with hypercholesterolemia. ION449 was generally well tolerated in this study. Additional positive data from the Phase 2 study of donidalorsen demonstrated significant improvements in quality of life in people with hereditary angioedema. Looking ahead, we expect to provide additional key mid-stage data readouts and updates on our technology advancements. These upcoming catalysts, together with our recent achievements, position us well to continue to drive substantial growth and value for all stakeholders."

First Quarter 2022 Summary Financial Results

On track to achieve 2022 financial guidance, based on the following first quarter results:

$142 million in total revenues
$173 million of operating expenses on a non-GAAP basis(1) and $199 million on a GAAP basis
$39 million net loss on a non-GAAP basis(1) and $65 million on a GAAP basis
$2.1 billion of cash and short-term investments
"A key element of Ionis’ financial strength is our ability to generate substantial revenue from multiple diverse sources on a sustained basis. Our first quarter financial results in which revenues grew more than 25 percent year over year were an excellent example of this. We generated revenues from our marketed products, including SPINRAZA, and from numerous partnered medicines as they advanced. Our first quarter financial results also reflect our investments in our rich late-stage pipeline and in activities to prepare for our launches of eplontersen, olezarsen and donidalorsen," said Elizabeth L. Hougen, chief financial officer of Ionis. "We are on track to meet our 2022 financial guidance. With $2.1 billion of cash, we are well capitalized with the resources we need to continue investing in our large agenda 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

$473 million in worldwide SPINRAZA sales in the first quarter
Biogen provided updates from the ASCEND, RESPOND and NURTURE studies of SPINRAZA at the Muscular Dystrophy Association (MDA) Clinical and Scientific conference and the American Academy of Neurology (AAN) annual meeting
TEGSEDI and WAYLIVRA: important medicines approved for the treatment of patients with polyneuropathy caused by hereditary TTR amyloidosis and familial chylomicronemia syndrome, respectively

Continued to progress into new and existing markets in Europe and Latin America in the first quarter through Swedish Orphan Biovitrum AB (Sobi) and PTC Therapeutics, respectively
First Quarter 2022 and Recent Events

Advancing Ionis’ near-term commercial opportunities toward the market

Increased study size and duration in the Phase 3 CARDIO-TTRansform study of eplontersen in patients with ATTR cardiomyopathy with the aim to generate even more robust data and ensure a highly positive study outcome to successfully compete in this growing and dynamic market. Data from this study are expected in the first half of 2025
The U.S. FDA granted orphan drug designation to eplontersen for the treatment of patients with ATTR
Published positive data from the Phase 2 study of olezarsen in patients with hypertriglyceridemia and either at high risk for or with established cardiovascular disease in the European Heart Journal
Initiated a study of olezarsen in patients with hypertriglyceridemia to support the broad Phase 3 program
Published positive data from the Phase 2 study of donidalorsen in patients with hereditary angioedema (HAE) in the New England Journal of Medicine
Presented additional positive data from the Phase 2 study of donidalorsen in patients with HAE at the American Academy of Allergy, Asthma and Immunology (AAAAI) annual meeting
Advancing Ionis’ leading cardiovascular disease franchise

AstraZeneca presented positive data from the Phase 2b ETESIAN study of ION449 (AZD8233) targeting PCSK9 in statin treated patients with dyslipidemia at the American College of Cardiology (ACC) annual scientific session
Achieved full enrollment in the Phase 2b study of IONIS-AGT-LRx in patients with treatment-resistant hypertension, with data expected in the second half of 2022
Advancing Ionis’ leading neurological disease franchise

Roche plans to initiate a new Phase 2 study of tominersen in patients with Huntington’s disease based on findings from a post-hoc analysis of the GENERATION-HD1 study
Biogen initiated a Phase 1/2 study of ION260 (BIIB132) targeting ataxin-3 (ATXN3) in patients with spinocerebellar ataxia type 3 (SCA3), resulting in an $8 million milestone payment from Biogen
Biogen advanced the Phase 1/2 study of ION859 (BIIB094) targeting LRRK2 in patients with Parkinson’s disease, resulting in a $10 million milestone payment from Biogen
Announced the discontinuation of IONIS-C9Rx (BIIB078) due to lack of patient benefit demonstrated in the Phase 1/2 study in patients with C9orf72-ALS
2022 Pipeline Milestones(2)

Anticipated 2022 Regulatory Updates

Program

Anticipated Indication

Regulatory Action

H1

H2

Eplontersen

ATTRv polyneuropathy

NDA filing

Anticipated Key 2022 Data Readouts

Program

Data Readout

Anticipated Indication

H1

H2

Tominersen

Phase 3 post hoc

Huntington’s disease

ION449 (PCSK9)

Phase 2b (ETESIAN)

Cardiovascular disease

Donidalorsen

Phase 2

HAE

IONIS-C9Rx (BIIB078)

Phase 1/2

C9-ALS

Tofersen

Phase 3 OLE

SOD1-ALS

Eplontersen

Phase 3

ATTRv polyneuropathy

IONIS-AGT-LRx

Phase 2b

Treatment-resistant hypertension

Fesomersen (FXI)

Phase 2b

Thrombosis

Bepirovirsen (HBV)

Phase 2b

Hepatitis B virus infection

Donidalorsen

Phase 2 OLE

HAE

Cimdelirsen (GHR)

Phase 2 (monotherapy)

Acromegaly

Anticipated Key 2022 Study Initiations

Program

Phase

Anticipated Indication

H1

H2

Sapablursen

2

Polycythemia vera

IONIS-MAPTRx (BIIB080)

2

Alzheimer’s disease

ION904 (AGT)

2

Uncontrolled hypertension

ION717 (PRNP)

1/2

Prion disease

Anticipated Key 2022 Technology Advancements

Program

Anticipated Advancement

H1

H2

SMA

Advance follow-on program

Muscle LICA

Advance into preclinical development (IND-supporting)

MsPA Backbone

Advance into preclinical development (IND-supporting)

✓ = achieved • = planned

All non-GAAP amounts referred to in this press release exclude non-cash compensation
expense related to equity awards. In 2021 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 detailed reconciliation of non-GAAP and GAAP measures, which is
provided later in this press release.

The Company’s revenue in the first quarter of 2022 increased more than 25 percent compared to the same period last year. The increase was driven by significant partner payments across multiple partnered programs, including $20 million from AstraZeneca for its share of the global Phase 3 program costs for eplontersen. Since Ionis is conducting the ongoing Phase 3 program for eplontersen, Ionis recognizes revenue for the reimbursements it receives from AstraZeneca for development expenses in the same period Ionis recognizes the related development expenses. Refer to the detailed table of costs and reimbursements for the eplontersen collaboration provided later in this release. The Company also earned $40 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 the first quarter of 2022 compared to the same period last year 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 in 2021 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 the first quarter of 2022 compared to the same period in 2021. Higher R&D expenses were driven by the expanded number of Phase 3 studies the Company is conducting, which doubled over the course of 2021 from three to six studies. Lower SG&A expenses were largely due to the substantial savings Ionis achieved from integrating Akcea and restructuring its commercial operations. These savings were offset in part by the investments Ionis made in advancing its go-to-market activities for its near-term commercial opportunities.

Net Loss

Ionis’ net loss in the first quarter of 2022 decreased compared to the same period in 2021 primarily related to the changes in revenue and operating expenses, as discussed above.

Balance Sheet

As of March 31, 2022 and December 31, 2021, Ionis had cash, cash equivalents and short-term investments of $2.1 billion. Ionis’ debt obligations and working capital did not change significantly from December 31, 2021 to March 31, 2022.

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.