On November 3, 2021 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported financial results for the three and nine months ended September 30, 2021 and recent business achievements (Press release, Ionis Pharmaceuticals, NOV 3, 2021, View Source [SID1234594206]).

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"Among recent business highlights, we further expanded our broad late-stage pipeline to seven Phase 3 programs now that the olezarsen Phase 3 CORE study in patients with severe hypertriglyceridemia is underway. We were encouraged that while tofersen did not achieve the primary endpoint in the Phase 3 VALOR study, trends favoring tofersen were seen across multiple secondary and exploratory measures of disease progression in patients with SOD1-ALS. We also expanded our LICA platform capabilities by licensing technology from Bicycle Therapeutics," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We are looking forward to multiple near-term catalysts, beginning with the presentation of donidalorsen Phase 2 data in patients with hereditary angioedema at the ACAAI Annual Meeting this weekend. We anticipate initiating the donidalorsen Phase 3 study before year-end. We also expect multiple catalysts in 2022, including results from the eplontersen Phase 3 study in patients with TTR polyneuropathy mid-year 2022. Furthermore, at our virtual investor day on December 9th, we look forward to outlining commercial preparations for our lead programs ahead of our first potential launch with eplontersen in patients with TTR polyneuropathy in 2023. Based on our anticipated near- and mid-term catalysts, we remain on track to have 12 or more products on the market in 2026."

Third Quarter 2021 Financial Results

Third quarter results reflect Ionis’ focus on its strategic objectives
$133 million in total revenues
$185 million of operating expenses on a non-GAAP basis(1) and $219 million on a GAAP basis
Net loss of $48 million on a non-GAAP basis(1) and $82 million on a GAAP basis
Well capitalized with cash and investments of $2 billion as of September 30, 2021
"Since our last quarterly update, we further advanced our strategic objectives through investments in our expanding Phase 3 pipeline and technology. We also advanced our commercial readiness initiatives in anticipation of multiple product launches potentially beginning as early as 2023," said Elizabeth L. Hougen, chief financial officer of Ionis. "We remain on track to achieve our 2021 financial guidance driven by increased R&D revenue in the fourth quarter as several of our partner programs advance. We also project increased expenses in the fourth quarter as we continue to invest for growth. Importantly, with $2 billion in cash, we remain well-capitalized with the resources we need to achieve our strategic objectives."

(1)

All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards and 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.

Third Quarter 2021 Marketed Products Highlights

SPINRAZA: the global market leader for the treatment of spinal muscular atrophy (SMA) patients of all ages
$444 million in worldwide sales in the third quarter
More than 11,000 patients worldwide on therapy at the end of the third quarter across commercial, expanded access and clinical trial settings
Biogen plans to initiate the Phase 3b ASCEND study evaluating the potential benefit of an investigational higher dose of nusinersen in children, teens and adults with later-onset SMA previously treated with Evrysdi (risdiplam)
TEGSEDI and WAYLIVRA: important medicines approved for the treatment of patients with severe rare diseases
TEGSEDI achieved innovative drug pricing in Brazil reflecting the significant unmet medical need and prevalence of TTR polyneuropathy in Brazil
WAYLIVRA was approved in Brazil as the first and only treatment for patients with familial chylomicronemia syndrome
Third Quarter 2021 and Recent Events

Advancing Ionis’ leading cardiovascular and metabolic disease pipeline
Initiated the Phase 3 CORE study of olezarsen (IONIS-APOCIII-LRx) in patients with severe hypertriglyceridemia (sHTG)
Reached 50 percent enrollment in the Phase 3 Lp(a) HORIZON outcome study of pelacarsen for patients with established cardiovascular disease and elevated Lp(a), resulting in a $25 million payment from Novartis
Achieved full enrollment in the Bayer Phase 2b RE-THINc ESRD study of fesomersen (IONIS-FXI-LRx), with data expected in the first half of 2022
Achieved proof-of-mechanism, a strong indication of proof-of-concept and good safety and tolerability in a Phase 2 study and a preliminary assessment from an open-label extension study of cimdelirsen (IONIS-GHR-LRx) in acromegaly patients uncontrolled on standard of care therapy, supporting continued development. Data from the ongoing open-label extension study and monotherapy study are expected in 2022. The results from the Phase 2 study of cimdelirsen are posted to Ionis’ website and may be accessed here
Addressing substantial unmet medical need with Ionis’ broad neurological disease pipeline
The Biogen Phase 3 VALOR study of tofersen in patients with SOD1-ALS did not meet the primary endpoint of change from baseline to week 28 in the ALS Functional Rating Scale-Revised (ALSFRS-R); however, signs of reduced disease progression across multiple secondary and exploratory endpoints were observed
Achieved full enrollment in the Phase 3 NEURO-TTRansform study of eplontersen in patients with TTR polyneuropathy, with data expected in mid-2022
Reported data from the Biogen Phase 1/2 study of IONIS-MAPTRx in patients with Alzheimer’s disease, demonstrating durable, time and dose-dependent reductions in CSF tau protein; IONIS-MAPTRx was generally well tolerated
Investing in expanding the reach of Ionis’ technology
Entered a license agreement with Bicycle Therapeutics for exclusive rights to Bicycle’s peptide technology targeting transferrin receptor 1 to expand the capabilities of Ionis’ LICA technology
Entered a license agreement with Flamingo Therapeutics for the development and commercialization of programs from Ionis’ oncology pipeline
2021 Pipeline Milestones(2)

In the third quarter of 2021, the Company continued to advance its late-stage pipeline, including reaching 50 percent enrollment in the Phase 3 Lp(a) HORIZON study of pelacarsen for which it earned a $25 million milestone payment from Novartis. As its partnered programs advance, the Company expects R&D revenue to increase in the fourth quarter of 2021 compared with the third quarter of 2021.

In the second quarter of 2021, the Company successfully completed the transition of its TEGSEDI operations in North America to Sobi. As a result, the Company’s commercial revenue from product sales shifted to distribution fees based on net sales generated by Sobi. In the third quarter of 2021, the Company earned a $4 million milestone payment from PTC Therapeutics when WAYLIVRA was approved in Brazil.

Financial Impacts of Akcea Merger and Restructured Commercial Operations

In October 2020, Ionis completed a merger transaction with Akcea such that following the completion of the merger Akcea became a wholly owned subsidiary of Ionis. Additionally, in December 2020 and April 2021, Ionis restructured its European operations and its North American TEGSEDI operations, respectively, as a result of entering into distribution agreements with Sobi. For the three and nine months ended September 30, 2021, the Company incurred $3 million and $24 million of costs in conjunction with the Akcea merger and restructuring of the Company’s commercial operations, respectively. The Company excluded these costs from its non-GAAP amounts for those periods. Please refer to the detailed reconciliation of non-GAAP and GAAP measures that is provided later in this press release.

Operating Expenses

Ionis’ operating expenses for the three and nine months ended September 30, 2021 increased compared with the same periods last year driven by an increase in R&D expenses, partially offset by a decrease in SG&A expenses. Higher R&D expenses were primarily driven by the Company’s investments in advancing its late-stage wholly owned pipeline, including advancing the Phase 3 program for eplontersen and start-up costs associated with the Phase 3 study for a second indication for olezarsen. Additionally, the Company recognized $35 million in R&D expense in the third quarter of 2021 for licensing Bicycle’s technology. Lower SG&A expenses primarily reflect operating efficiencies achieved from integrating Akcea and restructuring the Company’s commercial operations. The Company projects its operating expenses to increase in the fourth quarter as it continues to invest for growth.

Net Loss Attributable to Ionis Common Stockholders

Net loss attributable to Ionis’ common stockholders for the three and nine months ended September 30, 2021 increased compared with the same periods in the prior year for the reasons discussed above.

Balance Sheet

As of September 30, 2021, Ionis had cash, cash equivalents and short-term investments of $2.0 billion, compared with $1.9 billion as of December 31, 2020. The Company intends to utilize $62 million of its cash to pay the remaining principal balance of its 1 percent convertible notes at maturity in November 2021.

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.