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Share Name | Share Symbol | Market | Type |
---|---|---|---|
Ionis Pharmaceuticals Inc | NASDAQ:IONS | NASDAQ | Common Stock |
Price Change | % Change | Share Price | Bid Price | Offer Price | High Price | Low Price | Open Price | Shares Traded | Last Trade | |
---|---|---|---|---|---|---|---|---|---|---|
-1.12 | -2.60% | 41.97 | 40.00 | 44.31 | 43.76 | 41.93 | 43.54 | 1,375,102 | 05:00:12 |
☒ |
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
|
☐ |
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
|
Delaware
|
33-0336973
|
|
(State or other jurisdiction of incorporation or organization)
|
(IRS Employer Identification No.)
|
2855 Gazelle Court, Carlsbad, CA
|
92010
|
|
(Address of Principal Executive Offices)
|
(Zip Code)
|
Title of each class
|
Trading symbol
|
Name of each exchange on which registered
|
||
Common Stock, $.001 Par Value
|
“IONS”
|
The Nasdaq Stock Market LLC
|
Large Accelerated Filer ☒
|
Accelerated Filer ☐
|
|
Non-accelerated Filer ☐
|
Smaller Reporting Company ☐
|
|
Emerging Growth Company ☐
|
* |
Excludes 23,819,152 shares of common stock held by directors and officers and by stockholders whose beneficial ownership is known by the Registrant to
exceed 10 percent of the common stock outstanding at June 30, 2021. Exclusion of shares held by any person should not be construed to
indicate that such person possesses the power, direct or indirect, to direct or cause the direction of the management or policies of the Registrant, or that such person is controlled by or under common control with the Registrant.
|
● |
the impact on our operations and financial condition from the effects of the current COVID-19 pandemic;
|
● |
our ability to generate substantial revenue from the sale of our medicines;
|
● |
our and our partners’ ability to compete effectively;
|
● |
the availability of adequate coverage and payment rates for our medicines;
|
● |
our ability to successfully manufacture our medicines;
|
● |
our ability to successfully develop and obtain marketing approvals for our medicines;
|
● |
our ability to secure and maintain effective corporate partnerships;
|
● |
our ability to sustain cash flows and achieve consistent profitability;
|
● |
our ability to protect our intellectual property; and
|
● |
our ability to maintain the effectiveness of our personnel.
|
PART I
|
||
Page
|
||
Item 1.
|
Business
|
4
|
Item 1A.
|
Risk Factors
|
49
|
Item 1B.
|
Unresolved Staff Comments
|
66
|
Item 2.
|
Properties
|
66
|
Item 3.
|
Legal Proceedings
|
66
|
Item 4.
|
Mine Safety Disclosures
|
66
|
PART II
|
||
Item 5.
|
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
|
67
|
Item 6.
|
Selected Financial Data
|
68
|
Item 7.
|
Management’s Discussion and Analysis of Financial Condition and Results of Operations
|
68
|
Item 7A.
|
Quantitative and Qualitative Disclosures About Market Risk
|
79
|
Item 8.
|
Financial Statements and Supplementary Data
|
79
|
Item 9.
|
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure
|
79
|
Item 9A.
|
Controls and Procedures
|
79
|
Item 9B.
|
Other Information
|
82
|
Item 9C.
|
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
|
82
|
PART III
|
||
Item 10.
|
Directors, Executive Officers and Corporate Governance
|
82
|
Item 11.
|
Executive Compensation
|
82
|
Item 12.
|
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
|
83
|
Item 13.
|
Certain Relationships and Related Transactions, and Director Independence
|
83
|
Item 14.
|
Principal Accountant Fees and Services
|
83
|
PART IV
|
||
Item 15.
|
Exhibits, Financial Statement Schedules
|
83
|
Signatures
|
92
|
● |
Eplontersen: In July 2021, we achieved full enrollment in the NEURO-TTRansform Phase 3 study with data expected mid-2022. Enrollment is ongoing in the CARDIO-TTRansform
Phase 3 study
|
o |
In November 2021, we entered into an agreement with AstraZeneca for eplontersen, under which we will jointly develop and commercialize eplontersen in the U.S. AstraZeneca
has exclusive rights to commercialize eplontersen in the rest of the world
|
● |
Olezarsen: We initiated the Phase 3 CORE study in patients with severe hypertriglyceridemia, or SHTG, in October 2021. Enrollment is ongoing in the BALANCE Phase 3 study
in patients with FCS
|
o |
Data from the Phase 2 study of olezarsen in patients with moderate hypertriglyceridemia and at high risk for or with established cardiovascular disease were published in
the European Heart Journal
|
● |
Donidalorsen: Based on positive topline data from a Phase 2 study of donidalorsen in patients with hereditary angioedema which we reported in April 2021, we initiated the
Phase 3 OASIS-HAE study in November 2021
|
o
|
We reported additional positive results from the Phase 2 study of donidalorsen at the ACAAI annual scientific meeting in November 2021, demonstrating
rapid and sustained reductions in HAE attacks with favorable safety and tolerability
|
● |
ION363: In April 2021, we initiated a Phase 3 study in patients with amyotrophic
lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or FUS, or FUS-ALS, the most common cause of juvenile-onset ALS
|
● |
Pelacarsen: In August 2021, Novartis achieved 50 percent enrollment in Novartis’ Lp(a) HORIZON Phase 3 cardiovascular outcome study in patients with established
cardiovascular disease and elevated lipoprotein(a), or Lp(a)
|
● |
Tofersen: In October 2021, Biogen reported that tofersen did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring tofersen were
seen across multiple secondary and exploratory measures of disease activity and clinical function
|
o |
Biogen is actively engaging with regulators, the medical community, patient advocacy groups and other key stakeholders around the world to determine potential next
steps
|
o |
Given the high unmet medical need, Biogen expanded its ongoing early access program, or EAP, to the broader SOD1-ALS population
|
o |
The Phase 3 ATLAS study in patients with presymptomatic SOD1-ALS is ongoing
|
● |
Direct intervention in the disease process at the genetic level by targeting RNA: antisense technology represents a direct route from gene to drug. The
explosion in genomic information and RNA biology has led to the discovery of many new disease-causing proteins and RNAs and has created new opportunities that are uniquely accessible by antisense technology.
|
● |
Precise specificity: we design antisense medicines to target a single RNA, minimizing the possibility of binding to unintended targets, which can cause
unwanted side effects.
|
● |
Good drug properties: antisense medicines distribute well throughout the body. They also have a long half-life, in the range of weeks to months, which
means patients and/or healthcare providers can dose our medicines weekly, monthly or even less frequently depending on the medicine and target tissue.
|
● |
Ability to combine with other medicines: because antisense medicines do not interact with the enzymes that metabolize or break down other medicines,
physicians can use our medicines in combination with other medicines.
|
● |
Broad applications to multiple disease targets, multiple tissues and multiple mechanisms: there are virtually no “undruggable” targets with antisense
technology.
|
● |
Efficient discovery and early development: because of the efficiency of our antisense technology, our drug discovery and early development costs and
success rates compare favorably to small molecule or antibody drug discovery and development.
|
Type of Patent Claim
(Broadly Applicable to Specific)
|
||
● Chemically Modified Nucleosides and Oligonucleotides (target and sequence independent)
● Antisense Drug Design Motifs (target and sequence independent)
● Therapeutic Methods (sequence and chemistry independent)
● Antisense Sequence (chemistry independent)
● Drug Composition
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
7,101,993
|
OLIGONUCLEOTIDES CONTAINING 2’-O-MODIFIED PURINES
|
2023
|
Certain MOE nucleosides and oligonucleotides containing these nucleotides
|
||||
United States
|
7,399,845
|
6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
cEt nucleosides and oligonucleotides containing these nucleoside analogs
|
||||
United States
|
7,741,457
|
6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
cEt nucleosides and oligonucleotides containing these nucleoside analogs
|
||||
United States
|
8,022,193
|
6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
Oligonucleotides containing cEt nucleoside analogs
|
||||
Europe
|
1984381
|
6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
cEt nucleosides and oligonucleotides containing these nucleoside analogs
|
||||
Europe
|
2314594
|
6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
Oligonucleotides containing cEt nucleoside analogs and methods of use
|
||||
Japan
|
5342881
|
6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
cEt nucleosides and oligonucleotides containing these nucleoside analogs
|
||||
United States
|
7,569,686
|
COMPOUNDS AND METHODS FOR SYNTHESIS OF BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
Methods of synthesizing cEt nucleosides
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
7,015,315
|
GAPPED OLIGONUCLEOTIDES
|
2023
|
Gapmer oligonucleotides having 2’-O-alkyl-O-alkyl nucleosides
|
||||
United States
|
7,750,131
|
5’-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
|
2027
|
Oligonucleotides having 5’-methyl BNA nucleosides
|
||||
Europe
|
2092065
|
ANTISENSE COMPOUNDS
|
2027
|
Gapmer oligonucleotides having 2’-modifed and LNA nucleosides
|
||||
Europe
|
2410053
|
ANTISENSE COMPOUNDS
|
2027
|
Gapmer oligonucleotides having wings comprised of 2’-MOE and bicyclic nucleosides
|
||||
Europe
|
2410054
|
ANTISENSE COMPOUNDS
|
2027
|
Gapmer oligonucleotides having a 2’-modifed nucleoside in the 5’-wing and a bicyclic nucleoside in the 3’-wing
|
||||
Japan
|
5665317
|
ANTISENSE COMPOUNDS
|
2027
|
Gapmer oligonucleotides having wings comprised of 2’-MOE and bicyclic nucleosides
|
||||
United States
|
9,550,988
|
ANTISENSE COMPOUNDS
|
2028
|
Gapmer oligonucleotides having BNA nucleosides and 2’-MOE nucleosides
|
||||
United States
|
10,493,092
|
ANTISENSE COMPOUNDS
|
2028
|
Gapmer oligonucleotides having BNA nucleosides and 2’-MOE nucleosides and/or 2’-OMe nucleosides
|
||||
Europe
|
3067421
|
OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC NUCLEOTIDES AND USES THEREOF
|
2032
|
Gapmer oligonucleotides having at least one bicyclic, one 2’-modified nucleoside and one 2’-deoxynucleoside
|
Jurisdiction
|
Patent
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
9,127,276
|
CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE
|
2034
|
Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified
oligonucleotides
|
||||
United States
|
9,181,549
|
CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE
|
2034
|
Preferred THA conjugate having our preferred linker and cleavable moiety conjugated to any oligomeric compound or any nucleoside having
a 2’-MOE modification or a cEt modification
|
||||
Europe
|
2991661
|
CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE
|
2034
|
Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified
oligonucleotides
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
10,266,822
|
SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES
|
2025
|
Methods of increasing exon-7 containing SMN2 mRNA in a cell using an oligonucleotide having the sequence of SPINRAZA
|
||||
United States
|
8,110,560
|
SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES
|
2025
|
Methods of using antisense oligonucleotides having sequence of SPINRAZA to alter splicing of SMN2 and/or to treat SMA
|
||||
Europe
|
1910395
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING
|
2026
|
Sequence and chemistry (full 2’-MOE) of SPINRAZA
|
||||
Europe
|
3308788
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING
|
2026
|
Pharmaceutical compositions that include SPINRAZA
|
||||
United States
|
7,838,657
|
SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES
|
2027
|
Oligonucleotides having sequence of SPINRAZA
|
||||
United States
|
8,361,977
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING
|
2030
|
Sequence and chemistry (full 2’-MOE) of SPINRAZA
|
||||
United States
|
8,980,853
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT
|
2030
|
Methods of administering SPINRAZA
|
||||
United States
|
9,717,750
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT
|
2030
|
Methods of administering SPINRAZA to a patient
|
||||
Europe
|
3449926
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT
|
2030
|
Pharmaceutical compositions that include SPINRAZA for treating SMA
|
||||
Europe
|
3305302
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT
|
2030
|
Antisense compounds including SPINRAZA for treating SMA
|
||||
United States
|
9,926,559
|
COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT
|
2034
|
SPINRAZA doses for treating SMA
|
||||
United States
|
10,436,802
|
METHODS FOR TREATING SPINAL MUSCULAR ATROPHY
|
2035
|
SPINRAZA dosing regimen for treating SMA
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
8,101,743
|
MODULATION OF TRANSTHYRETIN EXPRESSION
|
2025
|
Antisense sequence and chemistry of TEGSEDI
|
||||
United States
|
8,697,860
|
DIAGNOSIS AND TREATMENT OF DISEASE
|
2031
|
Composition of TEGSEDI
|
||||
United States
|
9,061,044
|
MODULATION OF TRANSTHYRETIN EXPRESSION
|
2031
|
Sodium salt composition of TEGSEDI
|
||||
United States
|
9,399,774
|
MODULATION OF TRANSTHYRETIN EXPRESSION
|
2031
|
Methods of treating transthyretin amyloidosis by administering TEGSEDI
|
||||
Europe
|
2563920
|
MODULATION OF TRANSTHYRETIN EXPRESSION
|
2031
|
Composition of TEGSEDI
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
9,624,496
|
MODULATION OF APOLIPOPROTEIN C-III EXPRESSION
|
2023
|
Antisense compounds specifically hybridizable within the nucleotide region of ApoCIII targeted by WAYLIVRA
|
||||
United States
|
7,598,227
|
MODULATION OF APOLIPOPROTEIN C-III EXPRESSION
|
2023
|
Methods of treating hyperlipidemia, lowering cholesterol levels or lowering triglyceride levels with WAYLIVRA
|
||||
United States
|
7,750,141
|
MODULATION OF APOLIPOPROTEIN C-III EXPRESSION
|
2023
|
Antisense sequence and chemistry of WAYLIVRA
|
||||
Europe
|
1622597
|
MODULATION OF APOLIPOPROTEIN C-III EXPRESSION
|
2024
|
Antisense sequence and chemistry of WAYLIVRA
|
||||
Europe
|
2441449
|
MODULATION OF APOLIPOPROTEIN C-III EXPRESSION
|
2024
|
Antisense compounds specifically hybridizable within the nucleotide region of ApoCIII targeted by WAYLIVRA
|
||||
Europe
|
3002007
|
MODULATION OF APOLIPOPROTEIN C-III EXPRESSION
|
2024
|
Compounds complementary to an ApoCIII nucleic acid for use in therapy
|
||||
United States
|
9,157,082
|
MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION
|
2032
|
Methods of using ApoCIII antisense oligonucleotides for reducing pancreatitis and chylomicronemia and increasing HDL
|
||||
United States
|
9,593,333
|
MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS
|
2034
|
Methods of treating lipoprotein lipase deficiency with an ApoCIII specific inhibitor wherein triglyceride levels are reduced
|
||||
Europe
|
2956176
|
MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS
|
2034
|
ApoCIII specific inhibitors including WAYLIVRA for treating lipoprotein lipase deficiency or familial chylomicronemia syndrome
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
10,683,499
|
COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION
|
2034
|
Composition of eplontersen
|
||||
Europe
|
3524680
|
COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION
|
2034
|
Composition of eplontersen
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
9,163,239
|
COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION
|
2034
|
Composition of olezarsen
|
||||
Europe
|
2991656
|
COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION
|
2034
|
Composition of olezarsen
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
9,315,811
|
METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION
|
2032
|
Methods of treating HAE
|
||||
Europe
|
2717923
|
METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION
|
2032
|
Compounds for use in treating an inflammatory condition, including HAE
|
||||
United States
|
10,294,477
|
COMPOSITIONS AND METHODS FOR MODULATING PKK EXPRESSION
|
2035
|
Composition of donidalorsen
|
||||
Europe
|
3137091
|
COMPOSITIONS AND METHODS FOR MODULATING PKK EXPRESSION
|
2035
|
Composition of donidalorsen
|
Jurisdiction
|
Application No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
17/613,183
|
COMPOUNDS AND METHODS FOR REDUCING FUS EXPRESSION
|
2040
|
Composition of ION363
|
||||
Europe
|
20815459.1
|
COMPOUNDS AND METHODS FOR REDUCING FUS EXPRESSION
|
2040
|
Composition of ION363
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
9,574,193
|
METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION
|
2033
|
Methods of lowering Apo(a) and/or Lp(a) levels with an
oligonucleotide complementary within the nucleotide region of Apo(a) targeted by pelacarsen
|
||||
United States
|
10,478,448
|
METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION
|
2033
|
Methods of treating hyperlipidemia with an oligonucleotide
complementary within the nucleotide region of Apo(a) targeted by pelacarsen
|
||||
United States
|
9,884,072
|
METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION
|
2033
|
Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen
|
||||
Europe
|
2855500
|
METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION
|
2033
|
Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen for decreasing Apo(a) expression
|
||||
United States
|
9,181,550
|
COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION
|
2034
|
Composition of pelacarsen
|
||||
Europe
|
2992009
|
COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION
|
2034
|
Composition of pelacarsen
|
Jurisdiction
|
Patent No.
|
Title
|
Expiration
|
Description of Claims
|
||||
United States
|
10,385,341
|
COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION
|
2035
|
Composition of tofersen
|
||||
United States
|
10,669,546
|
COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION
|
2035
|
Methods of treating a SOD-1 associated neurodegenerative disorder by administering tofersen
|
||||
United States
|
10,968,453
|
COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION
|
2035
|
Methods of treating a SOD-1 associated neurodegenerative disorder by administering a pharmaceutical composition of tofersen
|
||||
Europe
|
3126499
|
COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION
|
2035
|
Composition of tofersen
|
● |
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and
Clinical Health Act, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information;
|
● |
Foreign and state laws governing the privacy and security of health information, such as the General Data Protection Regulation, or GDPR, in the EU; and
the California Consumer Privacy Act, or CCPA, in California, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect; and
|
● |
The Physician Payments Sunshine Act, which requires manufacturers of medicines, devices, biologics, and medical supplies to report annually to the U.S.
Department of Health and Human Services information related to payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), other healthcare providers (such as
physician assistants and nurse practitioners), and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members.
|
Medicine
|
Company
|
Medicine Description (1)
|
Phase (1)
|
Route of Administration (1)
|
||||
Zolgensma
(Onasemnogene abeparvovec)
|
Novartis
|
Gene therapy targeting the genetic root cause of SMA by replacing the missing or nonworking SMN1 gene
|
Approved for pediatric SMA patients less than 2 years of age
|
Intravenous infusion
|
||||
Evrysdi
(Risdiplam)
|
Roche
|
A small molecule medicine that modulates splicing of the SMN2 gene
|
Approved for SMA patients of 2 months or older
|
Oral
|
(1) |
Taken from public documents including respective company press releases, company presentations, and scientific presentations.
|
Medicine
|
Company
|
Medicine Description (1)
|
Phase (1)
|
Route of Administration (1)
|
||||
Onpattro
(Patisiran)
|
Alnylam
|
An RNAi medicine formulated with lipid nanoparticles to inhibit TTR mRNA
|
Approved hATTR/
Phase 3 ATTR-CM
|
Intravenous infusion
|
||||
Vyndaqel/Vyndamax
(Tafamidis and tafamidis meglumine)
|
Pfizer
|
A small molecule medicine to stabilize TTR protein
|
Approved in U.S., EU, Japan and select other markets for hATTR-PN and/or ATTR-CM; indications vary by region
|
Oral
|
||||
Vutrisiran
|
Alnylam
|
An RNAi medicine conjugated with GalNAC to inhibit TTR mRNA
|
Submitted US/EU for ATTR-PN, Phase 3 for ATTR-CM
|
Subcutaneous Injection
|
||||
Acoramidis
|
Bridgebio
|
Small molecule that binds and stabilizes TTR in the blood
|
Phase 3 ATTR-CM
|
Oral
|
(1) |
Taken from public documents including respective company press releases, company presentations, and scientific presentations.
|
Medicine
|
Company
|
Medicine Description (1)
|
Phase (1)
|
Route of Administration (1)
|
||||
ARO-APOC3
|
Arrowhead Pharmaceuticals
|
Targets APOCIII by utilizing Targeted RNAi Molecule Platform
|
3 (FCS), 2 (SHTG)
|
Subcutaneous Injection
|
||||
Lomitapide
|
Amryt Pharma
|
Microsomal triglyceride transfer protein (MTP) inhibitor
|
2 (FCS) (investigator led)
|
Oral
|
||||
Evinacumab
|
Regenerion
|
ANGPTL3 mAb
|
2 (SHTG)
|
Intravenous Infusion
|
||||
BIO89-100
|
Bio 89
|
FGF21 analog
|
2 (SHTG)
|
Subcutaneous Injection
|
(1) |
Taken from public documents including respective company press releases, company presentations, and scientific presentations.
|
Medicine
|
Company
|
Medicine Description (1)
|
Phase (1)
|
Route of Administration (1)
|
||||
Takhzyro
(lanadelumab-flyo)
|
Takeda
|
A monoclonal antibody that inhibits plasma kallikrein activity
|
Approved for HAE patients 12 years and older
|
Subcutaneous
Infusion
|
||||
Cinryze
(C1-esterase inhibitor)
|
Takeda
|
A human plasma protein that mediates inflammation and coagulation
|
Approved for HAE patients 6 years and older
|
Intravenous
Infusion
|
||||
Orladeyo
(berotralstat)
|
BioCryst
|
Oral plasma kallikrein inhibitor
|
Approved for HAE patients 12 years and older
|
Oral
|
||||
Haegarda
(C1 esterase inhibitor)
|
CSL Behring
|
C1 esterase inhibitor
|
Approved for HAE patients 6 years and older
|
Subcutaneous
Infusion
|
||||
garadacimab
|
CSL Behring
|
An anti-factor XIIa monoclonal antibody
|
3
|
Subcutaneous
Infusion
|
||||
KVD824
|
KalVista
|
Oral plasma kallikrein inhibitor
|
2
|
Oral
|
||||
NTLA-2002
|
Intellia
|
CRISPR therapeutic candidate designed to inactivate the kallikrein B1 gene
|
1/2
|
Intravenous
Infusion
|
(1) |
Taken from public documents including respective company press releases, company presentations, and scientific presentations.
|
Medicine
|
Company
|
Medicine Description (1)
|
Phase (1)
|
Route of Administration (1)
|
||||
AMG 890
|
Amgen/ Arrowhead Pharmaceuticals
|
RNAi therapeutic designed to lower Lp(a)
|
2
|
Subcutaneous Injection
|
(1) |
Taken from public documents including respective company press releases, company presentations, and scientific presentations.
|
Medicine
|
Company
|
Medicine Description (1)
|
Phase (1)
|
Route of Administration (1)
|
||||
Arimoclomol
|
Orphazyme
|
Provides cellular protection from abnormal proteins by activating molecular “chaperone” proteins that can repair or degrade the damaged proteins
|
3
|
Oral
|
||||
NI-204
|
Neurimmune
|
A human derived antibody targeting misfolded SOD1
|
2
|
Intravenous
Infusion
|
(1) |
Taken from public documents including respective company press releases, company presentations, and scientific presentations.
|
● |
Safety of patients in clinical trials;
|
● |
Drug safety and supply chain management;
|
● |
Access to medicines and tackling devastating diseases;
|
● |
Human resources management;
|
● |
Diversity, equity and inclusion;
|
● |
Employee health and safety; and
|
● |
Governance and business ethics
|
● |
Comprehensive medical, dental and vision insurance;
|
● |
401(k) matching;
|
● |
Stock options, RSUs and Employee Stock Purchase Plan, or ESPP;
|
● |
Vacation, holiday, sick time and paid time off for volunteering;
|
● |
Wellness programs;
|
● |
Flexible spending accounts for health and dependent day care needs;
|
● |
Life, AD&D insurance and long-term disability insurance coverage options; and
|
● |
Employee Assistance Program, or EAP.
|
Name
|
Age
|
Position
|
||
Brett P. Monia, Ph.D.
|
60
|
Chief Executive Officer
|
||
Joseph T. Baroldi
|
44
|
Executive Vice President, Chief Business Officer
|
||
C. Frank Bennett, Ph.D.
|
65
|
Executive Vice President, Chief Scientific Officer
|
||
Onaiza Cadoret-Manier
|
57
|
Executive Vice President, Chief Product Strategy and Operations Officer
|
||
Richard S. Geary, Ph.D.
|
64
|
Executive Vice President, Chief Development Officer
|
||
Elizabeth L. Hougen
|
60
|
Executive Vice President, Finance and Chief Financial Officer
|
||
Patrick R. O’Neil, Esq.
|
48
|
Chief Legal Officer, General Counsel and Corporate Secretary
|
||
Eugene Schneider, M.D.
|
49
|
Executive Vice President, Chief Clinical Development Officer
|
||
Eric E. Swayze, Ph.D.
|
56
|
Executive Vice President, Research
|
● |
delays in clinical site initiation, site monitoring and patient enrollment due to restrictions imposed as a result of the COVID-19 Pandemic;
|
o |
For example, in March 2020, we instituted a temporary suspension of enrollment for new subjects in our Phase 3 studies of eplontersen based on advice from our trial
advisory committee; however, enrollment has resumed.
|
● |
some patients have not been able to meet protocol requirements, as quarantines have impeded patient movement and interrupted healthcare services;
|
● |
delays in site initiations due to principle investigators and site staff focusing on and prioritizing COVID-19 patient care; and
|
● |
delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced
furlough of government or contractor personnel.
|
● |
receipt and scope of marketing authorizations;
|
● |
establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines and their potential advantages over
competing products;
|
● |
cost and effectiveness of our medicines compared to other available therapies;
|
● |
patient convenience of the dosing regimen for our medicines; and
|
● |
reimbursement policies of government and third-party payers.
|
● |
priced lower than our medicines;
|
● |
reimbursed more favorably by government and other third-party payers than our medicines;
|
● |
safer than our medicines;
|
● |
more effective than our medicines; or
|
● |
more convenient to use than our medicines.
|
● |
Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;
|
● |
Patisiran, tafamidis, and tafamidis meglumine compete with TEGSEDI and could compete with eplontersen;
|
● |
Vutrisiran and acoramidis could compete with TEGSEDI and eplontersen;
|
● |
ARO-APOC3, lomitapide, evinacumab, BIO89-100, and gemcabene could compete with WAYLIVRA and olezarsen;
|
● |
AMG890 could compete with pelacarsen;
|
● |
Arimoclomol, ultomiris, mastinib and trehalose could compete with tofersen; and
|
● |
Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor
subcutaneous, garadacimab, KVD824, and NTLA-2002 could compete with donidalorsen.
|
● |
in the U.S., TEGSEDI’s label contains a boxed warning for thrombocytopenia and glomerulonephritis;
|
● |
TEGSEDI requires periodic blood and urine monitoring; and
|
● |
in the U.S., TEGSEDI is available only through a REMS program.
|
● |
fund our development activities for SPINRAZA;
|
● |
seek and obtain regulatory approvals for SPINRAZA; and
|
● |
successfully commercialize SPINRAZA.
|
● |
In April 2021, we entered into a distribution agreement with Sobi to commercialize TEGSEDI in the U.S. and Canada;
|
● |
In December 2020, we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe; and
|
● |
In August 2018, we granted PTC the exclusive right to commercialize TEGSEDI and WAYLIVRA in Latin America and
certain Caribbean countries.
|
● |
such authorities may disagree with the design or implementation of our clinical studies;
|
● |
we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for
any indication;
|
● |
such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in
countries where the standard of care is potentially different from that in the U.S.;
|
● |
we or our partners may be unable to demonstrate that our medicine’s clinical and other benefits outweigh its safety risks to support approval;
|
● |
such authorities may disagree with the interpretation of data from preclinical or clinical studies;
|
● |
such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial
supplies for our medicines, or may delay the inspection of such facilities due to restrictions related to the COVID-19 Pandemic; and
|
● |
the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly
change in a manner rendering our clinical data insufficient for approval.
|
● |
the clinical study may produce negative or inconclusive results;
|
● |
regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;
|
● |
we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a medicine on
subjects or lack of efficacy in the trial;
|
● |
we, or our partners, may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;
|
● |
enrollment in our clinical studies may be slower than we anticipate;
|
● |
we or our partners, including our independent clinical investigators, contract research organizations and other third-party service providers on which we
rely, may not identify, recruit and train suitable clinical investigators at a sufficient number of study sites or timely enroll a sufficient number of study subjects in the clinical study;
|
● |
the institutional review board for a prospective site might withhold or delay its approval for the study;
|
● |
people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the
clinical study process or personal issues;
|
● |
a clinical study site may deviate from the protocol for the study;
|
● |
the cost of our clinical studies may be greater than we anticipate;
|
● |
our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and
|
● |
the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.
|
● |
AstraZeneca for the joint development and funding of eplontersen;
|
● |
Novartis for development and funding of pelacarsen;
|
● |
Biogen for development and funding of tofersen; and
|
● |
Roche for development and funding of tominersen.
|
● |
conduct clinical studies;
|
● |
seek and obtain marketing authorizations; and
|
● |
manufacture, market and sell our medicines.
|
● |
pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;
|
● |
pursue higher-priority programs or change the focus of its own development programs; or
|
● |
choose to devote fewer resources to our medicines than it does for its own medicines.
|
● |
successful commercialization of SPINRAZA, TEGSEDI and WAYLIVRA;
|
● |
additional marketing approvals for WAYLIVRA and TEGSEDI;
|
● |
the profile and launch timing of our medicines, including eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen;
|
● |
changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;
|
● |
continued scientific progress in our research, drug discovery and development programs;
|
● |
the size of our programs and progress with preclinical and clinical studies;
|
● |
the time and costs involved in obtaining marketing authorizations;
|
● |
competing technological and market developments, including the introduction by others of new therapies that address our markets; and
|
● |
our manufacturing requirements and capacity to fulfill such requirements.
|
● |
interruption of our research, development and manufacturing efforts;
|
● |
injury to our employees and others;
|
● |
environmental damage resulting in costly clean up; and
|
● |
liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of
these materials and resultant waste products.
|
● |
compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;
|
● |
complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;
|
● |
difficulties in staffing and managing foreign operations;
|
● |
in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic
partners;
|
● |
foreign government taxes, regulations and permit requirements;
|
● |
U.S. and foreign government tariffs, trade restrictions, price and exchange controls and other regulatory requirements;
|
● |
anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;
|
● |
economic weakness, including inflation, natural disasters, war, events of terrorism, political instability or public health issues or pandemics, such as
the current COVID-19 Pandemic, in particular foreign countries or globally;
|
● |
fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing
business in another country;
|
● |
compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;
|
● |
workforce uncertainty in countries where labor unrest is more common than in the U.S.; and
|
● |
changes in diplomatic and trade relationships.
|
Property Description
|
Location
|
Square
Footage
|
Owned
or Leased
|
Initial Lease
Term End Date
|
Lease
Extension Options
|
|||||
Laboratory and office space facility
|
Carlsbad, CA
|
176,000
|
Owned
|
|||||||
Office and meeting space facility
|
Carlsbad, CA
|
74,000
|
Owned
|
|||||||
Manufacturing facility
|
Carlsbad, CA
|
26,800
|
Owned
|
|||||||
Manufacturing support facility
|
Carlsbad, CA
|
25,800
|
Leased
|
2026
|
One, five-year option to extend
|
|||||
Office and storage space facility
|
Carlsbad, CA
|
18,700
|
Leased
|
2023
|
One, five-year option to extend
|
|||||
Office space facility
|
Boston, MA
|
14,300
|
Leased
|
2029
|
One, five-year option to extend
|
|||||
Office space facility
|
Carlsbad, CA
|
5,800
|
Leased
|
2023
|
One, five-year option to extend
|
|||||
341,400
|
Dec-16
|
Dec-17
|
Dec-18
|
Dec-19
|
Dec-20
|
Dec-21
|
|||||||||||||||||||
Ionis Pharmaceuticals, Inc.
|
$
|
100.00
|
$
|
105.16
|
$
|
113.03
|
$
|
126.30
|
$
|
118.21
|
$
|
63.62
|
||||||||||||
Nasdaq Composite Index
|
$
|
100.00
|
$
|
129.64
|
$
|
125.96
|
$
|
172.17
|
$
|
249.51
|
$
|
304.85
|
||||||||||||
Nasdaq Biotechnology Index
|
$
|
100.00
|
$
|
121.63
|
$
|
110.85
|
$
|
138.69
|
$
|
175.33
|
$
|
175.37
|
(1) |
This section is not “soliciting material,” is not deemed “filed” with the SEC, is not subject to the liabilities of Section 18 of the Exchange Act and is
not to be incorporated by reference in any of our filings under the Securities Act or the Exchange Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
(as revised*)
|
||||||||
Total revenue
|
$
|
810.5
|
$
|
729.3
|
||||
Total operating expenses
|
$
|
840.6
|
$
|
901.3
|
||||
Loss from operations
|
$
|
(30.2
|
)
|
$
|
(172.1
|
)
|
||
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders
|
$
|
(28.6
|
)
|
$
|
(479.7
|
)
|
||
Cash, cash equivalents and short-term investments
|
$
|
2,115.0
|
$
|
1,892.4
|
* |
We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 1, Organization and Significant Accounting Policies, for further information.
|
● |
Assessing the propriety of revenue recognition and associated deferred revenue; and
|
● |
Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities
|
● |
Identifying the performance obligations contained in the agreement
|
● |
Determining the transaction price, including any variable consideration
|
● |
Allocating the transaction price to each of our performance obligations
|
● |
Whether the milestone payment is probable (discussed in detail above under “Determining the transaction price, including any variable consideration”); and
|
● |
Whether the milestone payment relates to services we are performing or if our partner is performing the services:
|
● |
If we are performing services, we recognize revenue over our estimated period of performance in a similar manner to the amortization of upfront payments (discussed above
under “Amortization of Upfront payments”).
|
● |
Conversely, we recognize in full those milestone payments that we earn based on our partners’ activities when our partner achieves the milestone event and we do not have
a performance obligation.
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Revenue:
|
||||||||
Commercial revenue:
|
||||||||
SPINRAZA royalties
|
$
|
267.8
|
$
|
286.6
|
||||
TEGSEDI and WAYLIVRA revenue, net
|
55.5
|
70.0
|
||||||
Licensing and other royalty revenue
|
19.1
|
8.1
|
||||||
Total commercial revenue
|
342.4
|
364.7
|
||||||
R&D revenue:
|
||||||||
Amortization from upfront payments
|
77.5
|
79.6
|
||||||
Milestone payments
|
88.3
|
182.6
|
||||||
License fees
|
291.3
|
86.0
|
||||||
Other services
|
11.0
|
16.4
|
||||||
Total R&D revenue
|
468.1
|
364.6
|
||||||
Total revenue
|
$
|
810.5
|
$
|
729.3
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Operating expenses, excluding non-cash compensation expense related to equity awards
|
$
|
696.0
|
$
|
640.9
|
||||
Restructuring expenses
|
23.9
|
30.3
|
||||||
Total operating expenses, excluding non-cash compensation expense related to equity awards
|
719.9
|
671.2
|
||||||
Non-cash compensation expense related to equity awards
|
120.7
|
170.8
|
||||||
Restructuring expenses related to acceleration of Akcea’s stock-based compensation expense due to
Akcea Merger
|
—
|
59.3
|
||||||
Total operating expenses
|
$
|
840.6
|
$
|
901.3
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Cost of sales, excluding non-cash compensation expense related to equity awards
|
$
|
10.4
|
$
|
10.0
|
||||
Non-cash compensation expense related to equity awards
|
0.4
|
1.9
|
||||||
Total cost of sales
|
$
|
10.8
|
$
|
11.9
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Research, development and patent expenses, excluding non-cash compensation expense related to
equity awards
|
$
|
547.4
|
$
|
411.3
|
||||
Restructuring expenses
|
8.5
|
8.2
|
||||||
Total research, development and patent expenses, excluding non-cash compensation expense related to
equity awards
|
555.9
|
419.5
|
||||||
Non-cash compensation expense related to equity awards
|
87.6
|
115.6
|
||||||
Total research, development and patent expenses
|
$
|
643.5
|
$
|
535.1
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Antisense drug discovery expenses, excluding non-cash compensation expense related to equity awards
|
$
|
136.6
|
$
|
89.2
|
||||
Non-cash compensation expense related to equity awards
|
21.4
|
24.2
|
||||||
Total antisense drug discovery expenses
|
$
|
158.0
|
$
|
113.4
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
TEGSEDI and WAYLIVRA
|
$
|
11.4
|
$
|
20.3
|
||||
Eplontersen
|
79.1
|
34.0
|
||||||
Olezarsen
|
22.0
|
5.6
|
||||||
Donidalorsen
|
6.7
|
6.4
|
||||||
ION363
|
7.7
|
2.6
|
||||||
Other antisense development projects
|
104.5
|
69.9
|
||||||
Development overhead expenses
|
83.7
|
85.9
|
||||||
Restructuring expenses
|
7.7
|
8.0
|
||||||
Total antisense drug development, excluding non-cash compensation expense related to equity awards
|
322.8
|
232.7
|
||||||
Non-cash compensation expense related to equity awards
|
39.2
|
63.7
|
||||||
Total antisense drug development expenses
|
$
|
362.0
|
$
|
296.4
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Manufacturing and development chemistry expenses, excluding non-cash compensation expense related
to equity awards
|
$
|
47.2
|
$
|
55.7
|
||||
Restructuring expenses
|
0.8
|
0.2
|
||||||
Total manufacturing and development chemistry expenses, excluding non-cash compensation expense
related to equity awards
|
48.0
|
55.9
|
||||||
Non-cash compensation expense related to equity awards
|
11.5
|
10.9
|
||||||
Total manufacturing and development chemistry expenses
|
$
|
59.5
|
$
|
66.8
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Personnel costs
|
$
|
17.7
|
$
|
14.7
|
||||
Occupancy
|
13.1
|
10.2
|
||||||
Patent expenses
|
5.3
|
4.1
|
||||||
Insurance
|
3.2
|
2.4
|
||||||
Computer software and licenses
|
1.8
|
2.9
|
||||||
Other
|
7.3
|
7.4
|
||||||
Restructuring expenses
|
0.1
|
—
|
||||||
Total R&D support expenses, excluding non-cash compensation expense related to equity awards
|
48.5
|
41.7
|
||||||
Non-cash compensation expense related to equity awards
|
15.5
|
16.8
|
||||||
Total R&D support expenses
|
$
|
64.0
|
$
|
58.5
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
Selling, general and administrative expenses, excluding non-cash compensation expense related to
equity awards
|
$
|
138.1
|
$
|
219.7
|
||||
Restructuring expenses
|
15.4
|
22.1
|
||||||
Total selling, general and administrative expenses, excluding non-cash compensation related to
equity awards
|
153.5
|
241.8
|
||||||
Non-cash compensation expense related to equity awards
|
32.8
|
112.5
|
||||||
Total selling, general and administrative expenses
|
$
|
186.3
|
$
|
354.3
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
(as revised*)
|
||||||||
Convertible senior notes:
|
||||||||
Non-cash amortization of the debt discounts and debt issuance costs
|
$
|
4.9
|
$
|
3.2
|
||||
Interest expense payable in cash
|
1.9
|
3.8
|
||||||
Interest on mortgage for primary R&D and manufacturing facilities
|
2.4
|
2.4
|
||||||
Other
|
0.1
|
0.1
|
||||||
Total interest expense
|
$
|
9.3
|
$
|
9.5
|
* |
We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 1, Organization and Significant Accounting Policies, for further information.
|
Contractual Obligations
|
Payments Due by Period
(in millions)
|
|||||||||||
(selected balances described below)
|
Total
|
Less than 1 year
|
More than 1 year
|
|||||||||
0% Notes (principal payable)
|
$
|
632.5
|
$
|
—
|
$
|
632.5
|
||||||
0.125% Notes (principal and interest payable)
|
550.9
|
0.7
|
550.2
|
|||||||||
Building mortgage payments (principal and interest payable)
|
73.4
|
2.7
|
70.7
|
|||||||||
Operating leases
|
27.5
|
4.1
|
23.4
|
|||||||||
Other obligations (principal and interest payable)
|
0.8
|
0.1
|
0.7
|
|||||||||
Total
|
$
|
1,285.1
|
$
|
7.6
|
$
|
1,277.5
|
(1)
|
Any information that is included on or linked to our website is not part of this Form 10-K.
|
Plan Category
|
Number of Shares to
be Issued Upon Exercise
of Outstanding Options
|
Weighted Average
Exercise Price of
Outstanding Options
|
Number of Shares
Remaining Available
for Future Issuance
|
|||||
Equity compensation plans approved by stockholders (a)
|
14,088,816
|
$
|
54.04
|
11,102,267
|
(b)
|
|||
Total
|
14,088,816
|
$
|
54.04
|
11,102,267
|
(a) |
Consists of five Ionis plans: 1989 Stock Option Plan, Amended and Restated 2002 Non-Employee Directors’ Stock Option Plan, 2011 Equity Incentive Plan,
2020 Equity Incentive Plan and Employee Stock Purchase Plan, or ESPP.
|
(b) |
Of these shares, 588,529 were available for purchase under the ESPP as of December 31, 2021.
|
Exhibit Number
|
Description of Document
|
|
2.1
|
Agreement and Plan of Merger, dated as of August 30, 2020, among Akcea Therapeutics, Inc., Ionis Pharmaceuticals, Inc. and Avalanche Merger Sub, Inc., filed as an exhibit to the Registrant’s Current Report on Form 8-K filed August 31, 2020 and incorporated herein by reference.
|
|
3.1
|
Amended and Restated Certificate of Incorporation filed June 19, 1991, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference.
|
|
3.2
|
Certificate of Amendment to Restated Certificate of Incorporation, filed as an exhibit to the Registrant’s Notice of Annual Meeting and Proxy Statement, for the 2014 Annual Meeting of
Stockholders, filed on April 25, 2014 and incorporated herein by reference.
|
|
3.3
|
Certificate of Amendment to Restated Certificate of Incorporation, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed December 18, 2015 and incorporated herein by reference.
|
|
3.4
|
Amended and Restated Bylaws, filed as an exhibit
to the Registrant’s Current Report on Form 8-K filed March 29, 2021 and incorporated herein by reference.
|
|
4.1
|
Certificate of Designation of the Series C Junior Participating Preferred Stock, filed as an exhibit to Registrant’s Current Report on Form 8-K filed December 13, 2000 and incorporated herein by reference.
|
|
4.2
|
Specimen Common Stock Certificate, filed as an exhibit to
the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference.
|
|
4.3
|
Indenture, dated as of November 17, 2014, between the Registrant and Wells Fargo Bank, National Association, as trustee, including Form of 1.00 percent
Convertible Senior Note due 2021, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed November 21, 2014 and incorporated
herein by reference.
|
|
4.4
|
Indenture, dated as of December 19, 2019, by and between the Registrant and U.S. Bank National Association, as trustee, including Form of 0.125 percent
Convertible Senior Note due 2024, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed December 23, 2019 and incorporated
herein by reference.
|
|
4.5
|
Indenture, dated as of April 12, 2021, by and between the Registrant and U.S. Bank National Association, as trustee, including Form of 0 percent
Convertible Senior Note due 2026, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed April 13, 2021 and incorporated herein
by reference.
|
|
4.6
|
Form of Exchange and/or Subscription Agreement for Convertible Senior Notes due 2024, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed December 12, 2019 and incorporated herein by reference.
|
|
4.7
|
Form of Convertible Note Hedge Transactions Confirmation
for Convertible Senior Notes due 2024, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed December 12, 2019 and
incorporated herein by reference.
|
|
4.8
|
Form of Convertible Note Hedge Confirmation for Convertible Senior Notes due 2026, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed April 13, 2021 and incorporated herein by reference.
|
|
4.9
|
Form of Warrant Transactions Confirmation for Convertible
Senior Notes due 2024, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed December 12, 2019 and incorporated
herein by reference.
|
|
4.10
|
Form of Warrant Confirmation for Convertible Senior Notes due 2026, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed April 13, 2021 and incorporated herein by reference.
|
|
Description of the Registrant’s Securities.
|
||
10.1
|
Amended Board Compensation Policy, filed as an exhibit to the
Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 and incorporated herein by reference.
|
|
10.2
|
Form of Indemnity Agreement entered into between the Registrant and its Directors and Officers with related schedule, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference.
|
|||
10.3*
|
Registrant’s 1989 Stock Option Plan, as amended,
filed as an exhibit to Registrant’s Notice of Annual Meeting and Proxy Statement for the 2012 Annual Meeting of Stockholders, filed on April 16, 2012 and incorporated herein by reference.
|
|||
10.4*
|
Registrant’s Amended and Restated 2000 Employee Stock Purchase Plan, filed as an exhibit to Registrant’s Current Report on Form 8-K filed on March 26, 2019 and incorporated herein by reference.
|
|||
10.5
|
Form of Employee Confidential Information and Inventions Agreement, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference.
|
|||
10.6
|
Amendment #1 to the Research, Development and License Agreement dated May 11, 2011 by and between the Registrant and Glaxo Group Limited, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2011 and incorporated herein by reference. Portions
of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|||
10.7
|
Amended and Restated Collaboration and License Agreement between the Registrant and Antisense Therapeutics Ltd dated February 8, 2008, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2008 and incorporated herein by reference. Portions
of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|||
10.8
|
Strategic Collaboration, Option and License Agreement by and among Akcea Therapeutics, Inc. and Novartis Pharma AG, dated January 5, 2017,
filed as an exhibit to Akcea Therapeutics, Inc.’s Form S-1 filed March 27, 2017 and incorporated herein by reference.
|
|||
10.9
|
Amendment No. 1 to the Strategic Collaboration, Option and License Agreement between Akcea Therapeutics, Inc. and Novartis Pharma AG dated February
22, 2019, filed as an exhibit to Akcea Therapeutics, Inc.’s Quarterly Report on Form 10-Q for the quarter ended March 30, 2019 and incorporated herein by reference.
|
|||
10.10
|
Stock Purchase Agreement among the Registrant, Akcea Therapeutics, Inc. and Novartis Pharma AG dated January 5, 2017, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and incorporated herein by reference.
|
|||
10.11
|
Amendment #1 between the Registrant and Bayer AG dated February 10, 2017, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a
request for confidential treatment.
|
|||
10.12
|
Registrant’s Amended and Restated 10b5-1 Trading Plan dated September 12, 2013, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013 and incorporated herein by reference.
|
|||
10.13*
|
Registrant’s Amended and Restated 2002 Non-Employee Directors’ Stock Option Plan, as amended, filed as an exhibit to the Registrant’s Notice of Annual Meeting and Proxy Statement for the 2020 Annual Meeting of Stockholders, filed on April 24, 2020 and incorporated herein by reference.
|
|||
10.14*
|
Form of Restricted Stock Unit Agreement for Restricted Stock Units granted under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002
Non-Employee Directors’ Stock Option Plan, filed as an exhibit to the Registrant’s Registration Statement on Form S-8 filed on August 7, 2020 and
incorporated herein by reference.
|
|||
10.15
|
Research Collaboration, Option and License Agreement between the Registrant and Biogen MA Inc. dated December 19, 2017, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference. Portions of this exhibit have been
omitted and separately filed with the SEC with a request for confidential treatment.
|
|||
10.16*
|
Amended and Restated Ionis Pharmaceuticals, Inc. 2011 Equity Incentive Plan, filed as an exhibit to the Registrant’s Notice of 2021 Annual Meeting of Stockholders and Proxy Statement filed on April 23, 2021 and incorporated herein by reference.
|
10.17*
|
Form of Option Agreement under the 2011 Equity Incentive Plan,
filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference.
|
|
10.18*
|
Form of Time-Vested Restricted Stock Unit Agreement for Restricted Stock Units granted under the 2011 Equity Incentive Plan, filed as an exhibit to the Registrant’s Registration Statement on Form S-8 filed on August 8, 2011 and incorporated herein by reference.
|
|
Forms of Performance Based Restricted Stock Unit Grant
Notice and Performance Based Restricted Stock Unit Agreement for Performance Based Restricted Stock Units granted under the 2011 Equity Incentive Plan.
|
||
10.20*
|
Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, filed as an exhibit to the Registrant’s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.
|
|
10.21*
|
Form of Global Option Agreement for options granted under the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, filed as an exhibit to the Registrant’s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.
|
|
10.22*
|
Form of Global Restricted Stock Unit Agreement for restricted stock units granted under the Ionis Pharmaceuticals, Inc. 2020 Equity
Incentive Plan, filed as an exhibit to the Registrant’s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated
herein by reference.
|
|
10.23*
|
Forms of Restricted Stock Unit Grant Notice, Stock Option Grant Notice and Stock Option Exercise Notice for options granted under the Ionis
Pharmaceuticals, Inc. 2020 Equity Incentive Plan, filed as an exhibit to the Registrant’s Registration Statement on Form S-8 filed on December
31, 2020 and incorporated herein by reference.
|
|
10.24
|
Loan Agreement between Ionis Gazelle, LLC and UBS AG dated July 18, 2017, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed July 21, 2017 and incorporated herein by reference.
|
|
10.25*
|
Form of Option Agreement under the 1989 Stock Option Plan,
filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference.
|
|
10.26*
|
Form of Option Agreement for Options granted under the 2002 Non-Employee Director’s Stock Option Plan, filed as an exhibit to the Registrant’s Registration Statement on Form S-8 filed on August 7, 2020 and incorporated herein by reference.
|
|
10.27
|
Research, Development and License Agreement between the Registrant and Glaxo Group Limited dated March 30, 2010, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2010 and incorporated herein by reference. Portions of this exhibit have
been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.28
|
Loan Agreement between Ionis Faraday, LLC and UBS AG dated
July 18, 2017, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed July 21, 2017 and incorporated herein by reference.
|
|
10.29
|
Research Agreement dated August 10, 2011 between the Registrant and CHDI Foundation, Inc, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2011 and incorporated herein by reference. Portions of this exhibit have been omitted and
separately filed with the SEC with a request for confidential treatment.
|
|
10.30
|
Guaranty between the Registrant and UBS AG dated July 18,
2017, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed July 21, 2017 and incorporated herein by reference.
|
|
10.31
|
Development, Option and License Agreement between the Registrant and Biogen Idec International Holding Ltd. dated January 3, 2012, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2012 and incorporated herein by reference. Portions
of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.32
|
DMPK Research, Development, Option and License Agreement between the Registrant and Biogen Idec MA Inc. dated June 27, 2012, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2012 and incorporated herein by reference. Portions
of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
10.33
|
Amendment #2 to Research, Development and License Agreement between the Registrant and Glaxo Group Limited dated October 30, 2012, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference. Portions of
this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.34
|
Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated December 7, 2012, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference. Portions of this exhibit have been
omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.35
|
Amended and Restated Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc.
dated July 12, 2021, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and
incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
||
10.36
|
HTT Research, Development, Option and License Agreement among the Registrant, F. Hoffmann-La Roche Ltd and Hoffman-La Roche Inc. dated April 8,
2013, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2013 and incorporated herein by
reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.37
|
Letter Agreement between the Registrant and CHDI Foundation, Inc. dated April 8, 2013, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2013 and incorporated herein by reference. Portions of this exhibit have been omitted and separately
filed with the SEC with a request for confidential treatment.
|
||
10.38
|
Amendment #1 to Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated August 13, 2013, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013 and incorporated herein by reference.
Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.39
|
Amendment No. 3 to the Research, Development and License Agreement between the Registrant and Glaxo Group Limited dated July 10, 2013, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and incorporated herein by reference. Portions
of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.40
|
Amendment #4 to the Research, Development and License Agreement between the Registrant and Glaxo Group Limited dated April 10, 2014, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and incorporated herein by reference. Portions of this exhibit
have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.41
|
Amendment #5 to the Research, Development and License Agreement among the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property
Development Limited dated June 27, 2014, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30,
2014 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.42
|
Exclusive License Agreement between the Registrant and the University of Massachusetts dated January 14, 2010, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference. Portions of this exhibit have been
omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.43
|
Amended and Restated Collaboration and License Agreement between the Registrant and Cold Spring Harbor Laboratory dated October 26, 2011, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference.
Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.44
|
Amendment to Amended and Restated Collaboration and License Agreement between the Registrant and Cold Spring Harbor Laboratory dated March 14, 2014, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference.
Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.45
|
Research Collaboration, Option and License Agreement between the Registrant and Janssen Biotech Inc. dated December 22, 2014, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both
(i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.46
|
Amendment No.2 to the Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated October 15, 2014, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2014 and incorporated herein by reference. Portions of
this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.47
|
Strategic Collaboration Agreement between the Registrant and AstraZeneca AB dated July 31, 2015, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted and
separately filed with the SEC with a request for confidential treatment.
|
|
10.48
|
Amendment #6 to Research, Development and License Agreement between the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property Development
Limited dated September 2, 2015, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015
and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.49
|
Amendment Number One to the Second Amended and Restated Strategic Collaboration and License Agreement between the Registrant and Alnylam Pharmaceuticals, Inc.
dated July 13, 2015, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and
incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.50
|
License Agreement between the Registrant and Bayer Pharma AG dated May 1, 2015, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC
with a request for confidential treatment.
|
|
10.51
|
Second Amended and Restated Strategic Collaboration and License Agreement between the Registrant and Alnylam Pharmaceuticals, Inc. dated January 8, 2015, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and incorporated herein by reference. Portions
of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.52
|
Amendment #1 to HTT Research, Development, Option and License Agreement between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. dated
January 9, 2015, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and incorporated
herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.53
|
Amendment No.3 to the Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated January 18, 2016, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2016 and incorporated herein by reference. Portions
of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.54
|
Amendment #7 to the Research, Development and License Agreement among the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property
Development Limited dated March 4, 2016, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31,
2016 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
|
10.55
|
First Amendment to Research Collaboration, Option and License Agreement between the Registrant and Janssen Biotech Inc. dated December 21, 2016, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by reference. Portions of this exhibit have been
omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.56
|
Letter Agreement between the Registrant and Biogen MA Inc. dated October 28, 2016, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2016 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed
with the SEC with a request for confidential treatment.
|
|
10.57
|
Guaranty between the Registrant and UBS AG dated July 18, 2017,
filed as an exhibit to the Registrant’s Current Report on Form 8-K filed July 21, 2017 and incorporated herein by reference.
|
||
10.58
|
Environmental Indemnity Agreement among the Registrant, Ionis Gazelle, LLC and UBS AG dated July 18, 2017, filed as an exhibit to the Registrant’s Current Report on Form 8-K filed July 21, 2017 and incorporated herein by reference.
|
||
10.59*
|
Registrant’s Severance Benefit Plan and Summary Plan Description dated October 18, 2018, filed as an exhibit to the Registrant’s Current Report on form 8-K filed October 18, 2018 and incorporated herein by reference.
|
||
Fourth Amended and Restated Strategic Advisory Services Agreement by and between the Registrant and B. Lynne Parshall, dated February
22, 2022.
|
|||
10.61
|
Development, Commercialization, Collaboration, and License Agreement by and between the Registrant and Akcea Therapeutics, Inc., dated March 14, 2018, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2018 and incorporated herein by reference.
|
||
10.62
|
Amended and Restated Services Agreement by and between the Registrant and Akcea Therapeutics, Inc., dated March 14, 2018, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2018 and incorporated herein by reference.
|
||
10.63
|
New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc., dated April 19, 2018, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and incorporated herein
by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.64
|
Stock Purchase Agreement by and between the Registrant and Biogen MA Inc., dated April 19, 2018, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and incorporated herein by reference.
|
||
10.65
|
Second Amendment to Research, Collaboration, Option and License Agreement by and between the Registrant and Janssen Biotech Inc., dated August 7, 2018, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2018 and incorporated herein by reference.
Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.66
|
Factor B Development Collaboration, Option and License Agreement by and between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc.,
dated October 9, 2018, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated
herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.67
|
Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant
and Biogen MA Inc., dated October 17, 2018, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31,
2018 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.68
|
Amendment #1 to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB, dated October 18, 2018, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of
this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.69
|
Amendment #4 to the Collaboration, License and Development Agreement by and between the Registrant and AstraZeneca AB, dated October 18, 2018, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of
this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.
|
||
10.70
|
Amendment #1 to Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the
Registrant and Biogen MA Inc., dated May 2, 2019, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended
June 30, 2019 and incorporated herein by reference.
|
||
10.71
|
Amendment #1 to the New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement between the Registrant and Biogen MA
Inc., dated August 16, 2019, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 and
incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.72
|
Amendment #8 to the Research, Development and License Agreement between the Registrant, Glaxo Group Limited and Glaxosmithkline Intellectual Property
Development Limited, dated July 29, 2019, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September
30, 2019 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.73
|
Consent to Collateral Addition and Amendment to Loan Documents between the Registrant, Ionis Gazelle, LLC, Wells Fargo Bank, National Association, as Trustee
for the Benefit of the Registered Holders of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, dated August 1, 2019, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 and incorporated herein by reference.
|
|
10.74
|
License Agreement by and among Akcea Therapeutics, Inc. and Pfizer Inc. dated October 4, 2019, filed as an exhibit to Akcea Therapeutics, Inc.’s Annual Report on Form 10-K for the year ended December 31, 2019 and incorporated herein by reference.
|
|
10.75
|
Letter Agreement between the Registrant, Akcea Therapeutics, Inc., and Pfizer Inc., dated October 4, 2019, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2019 and incorporated herein by reference. Portions of this exhibit have been omitted
because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.76
|
Side Letter dated June 11, 2020 to the Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License
Agreement by and between the Registrant and Biogen MA Inc. dated October 17, 2018, filed as an exhibit to the Registrant’s Quarterly Report on
Form 10-Q for the quarter ended June 30, 2020 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.77
|
Amendment No. 2 dated April 30, 2020 to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB dated July 31, 2015, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and incorporated herein by reference. Portions
of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.78
|
Letter agreement dated October 21, 2020 to the License Agreement by and among Akcea Therapeutics, Inc. and Pfizer Inc. dated October 4, 2019, filed as an exhibit to the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 and incorporated herein by reference. Portions
of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.79
|
Amendment No. 3 dated December 17, 2020 to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB dated July 31, 2015, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by reference. Portions of
this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.80
|
Strategic Advisory Services Agreement by and between the Registrant and Stanley T. Crooke, dated December 17, 2020, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by reference.
|
|
10.81
|
Side Letter dated December 31, 2020 to the New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and
between the Registrant and Biogen MA Inc. dated April 19, 2018, filed as an exhibit to the Registrant’s Annual Report on Form 10-K for the year
ended December 31, 2020 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
|
10.82
|
Collaboration and License Agreement by and between the Registrant and BicycleTX Limited dated July 9, 2021, filed as an exhibit to the Registrant’s
Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly
disclosed.
|
|
Amendment No. 1 dated December 17, 2021 to the Collaboration and License Agreement by and between the Registrant and BicycleTX
Limited dated July 9, 2021. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
||
Collaboration and License Agreement by and between Akcea Therapeutics, Inc. and AstraZeneca AB dated December 6, 2021. Portions of
this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.
|
||
List of Subsidiaries for the Registrant.
|
||
Consent of Independent Registered Public Accounting Firm.
|
||
24.1
|
Power of Attorney – Included on the signature page of this Annual Report on Form 10-K.
|
|
Certification by Chief Executive Officer Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 302 of the Sarbanes-Oxley
Act of 2002.
|
||
Certification by Chief Financial Officer Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 302 of the Sarbanes-Oxley
Act of 2002.
|
||
32.1+
|
Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
|
|
101
|
The following financial statements from the Ionis Pharmaceuticals, Inc. Annual Report on Form 10-K for the year ended December 31, 2021, formatted in Extensive Business Reporting Language (XBRL): (i) consolidated balance sheets, (ii) consolidated statements of operations,
(iii) consolidated statements of comprehensive income (loss), (iv) consolidated statements of stockholders’ equity (v) consolidated statements of cash flows, and (vi) notes to consolidated financial statements (detail tagged).
|
|
104
|
Cover Page Interactive Data File (formatted in iXBRL and included in exhibit 101).
|
* |
Indicates management compensatory plans and arrangements as required to be filed as exhibits to this Report pursuant to Item 14(c).
|
+ |
This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that
section, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 133, as amended, or the Securities Exchange Act of 1934, as amended.
|
IONIS PHARMACEUTICALS, INC.
|
||
By:
|
/s/ BRETT P. MONIA
|
|
Brett P. Monia, Ph.D.
|
||
Chief Executive Officer (Principal executive officer)
|
Signatures
|
Title
|
Date
|
||
/s/ BRETT P. MONIA
|
Director and Chief Executive Officer
|
February 24, 2022
|
||
Brett P. Monia, Ph.D.
|
(Principal executive officer)
|
|||
/s/ ELIZABETH L. HOUGEN
|
Executive Vice President, Finance and Chief Financial Officer
|
February 24, 2022
|
||
Elizabeth L. Hougen
|
(Principal financial and accounting officer)
|
|||
/s/ JOSEPH LOSCALZO
|
Chairman of the Board
|
February 24, 2022
|
||
Joseph Loscalzo, M.D., Ph.D.
|
||||
/s/ SPENCER R. BERTHELSEN
|
Director
|
February 24, 2022
|
||
Spencer R. Berthelsen, M.D.
|
||||
/s/ ALLENE M. DIAZ
|
Director
|
February 24, 2022
|
||
Allene M. Diaz
|
||||
/s/ MICHAEL HAYDEN
|
Director
|
February 24, 2022
|
||
Michael Hayden, CM OBC MB ChB PhD FRCP(C) FRSC
|
||||
/s/ JOAN E. HERMAN
|
Director
|
February 24, 2022
|
||
Joan E. Herman
|
||||
/s/ JOSEPH KLEIN
|
Director
|
February 24, 2022
|
||
Joseph Klein, III
|
||||
/s/ FREDERICK T. MUTO
|
Director
|
February 24, 2022
|
||
Frederick T. Muto, Esq.
|
||||
/s/ B. LYNNE PARSHALL
|
Director and Senior Strategic Advisor
|
February 24, 2022
|
||
B. Lynne Parshall, J.D.
|
/s/ JOSEPH H. WENDER
|
Lead Independent Director
|
February 24, 2022
|
||
Joseph H. Wender
|
Page
|
|
Report of Independent Registered Public Accounting Firm
(PCAOB ID )
|
F-2
|
Consolidated Balance Sheets at December 31, 2021 and 2020
|
F-4
|
Consolidated Statements of Operations for the years ended
December 31, 2021, 2020
and 2019
|
F-5
|
Consolidated Statements of Comprehensive Income (Loss) for
the years ended December 31, 2021, 2020
and 2019
|
F-6
|
Consolidated Statements of Stockholders’ Equity for the
years ended December 31, 2021, 2020
and 2019
|
F-7
|
Consolidated Statements of Cash Flows for the years ended
December 31, 2021, 2020
and 2019
|
F-8
|
Notes to Consolidated Financial Statements
|
F-10
|
AstraZeneca – Eplontersen Collaboration
|
Description of the Matter
|
As discussed in Note 6 to the consolidated financial statements, the Company entered into a joint development and commercialization
agreement with AstraZeneca AB (“AstraZeneca”), referred to as the “AstraZeneca agreement”, which resulted in the recognition of $200 million in revenue for the year ended December 31, 2021. The Company determined that there were four material
components of the AstraZeneca agreement: (i) license granted to AstraZeneca to develop and commercialize eplontersen; (ii) the parties’ co-development activities for eplontersen; (iii) the parties’ co-commercialization activities for
eplontersen; and (iv) the parties’ co-medical affairs activities for eplontersen.
|
Auditing management’s initial application of the relevant US GAAP guidance under Accounting Standards Codification (ASC) 606, Revenue
from Contracts With Customers, and ASC 808, Collaborative Arrangements, related to the AstraZeneca Agreement was especially challenging due to the complex nature of its terms and conditions. In particular, determining the distinct performance
obligations with a customer was highly judgmental.
|
||
How We Addressed the Matter in Our Audit
|
We obtained an understanding, evaluated the design and tested the operating effectiveness of internal controls over management’s
review of the terms and conditions of the AstraZeneca Agreement, identification of performance obligations, and consideration of the appropriate accounting guidance in determining the appropriate conclusions.
To test management’s initial application of the accounting guidance to the AstraZeneca Agreement, we performed audit procedures that
included, among others, reading the contractual agreement and assessing management’s application of the appropriate accounting guidance in their evaluation. Our procedures included evaluating management’s identification of distinct performance
obligations with a customer. We also evaluated alternative views and any contrary or corroborative evidence associated with management’s evaluation, and discussed with management the underlying business objectives of the AstraZeneca Agreement.
|
|
Estimated Liability for Clinical Development Costs
|
||
Description of the Matter
|
As of December 31, 2021, the Company accrued $65.7 million for accrued clinical development costs. As discussed in Note 2 to the
consolidated financial statements, the Company records costs for clinical trial activities based upon estimates of costs incurred through the balance sheet date that have yet to be invoiced related to clinical management costs, laboratory and
analysis costs, toxicology studies and investigator grants.
Auditing the Company’s accruals for clinical development costs is especially complex as the information necessary to estimate the
accruals is accumulated from multiple sources. In addition, in certain circumstances, the determination of the nature and level of services that have been received during the reporting period requires judgment because the timing and pattern of
vendor invoicing does not correspond to the level of services provided and there may be delays in invoicing from vendors.
|
|
How We Addressed the Matter in Our Audit
|
We obtained an understanding and evaluated the design and tested the operating effectiveness of controls over the accounting for
accrued clinical development costs. This included controls over management’s assessment of the assumptions and accuracy of data underlying the accrued clinical development expenses estimate.
To test the accuracy of the Company’s accrued clinical development costs, we performed audit procedures that included, among other
procedures, obtaining supporting evidence of the research and development activities performed for significant clinical trials. We corroborated the status of significant clinical development costs through meetings with accounting and clinical
project managers. We compared the costs for a sample of transactions against the related invoices and contracts, and examined a sample of subsequent payments to evaluate the accuracy of the accrued clinical development costs and compared the
results to the current year accrual.
|
December 31,
|
||||||||
2021
|
2020
|
|||||||
(as revised*)
|
||||||||
ASSETS
|
||||||||
Current assets:
|
||||||||
Cash and cash equivalents
|
$
|
869,191
|
$
|
397,664
|
||||
Short-term investments
|
1,245,782
|
1,494,711
|
||||||
Contracts receivable
|
61,896
|
76,204
|
||||||
Inventories
|
24,806
|
21,965
|
||||||
Other current assets
|
143,374
|
140,163
|
||||||
Total current assets
|
2,345,049
|
2,130,707
|
||||||
Property, plant and equipment, net
|
178,069
|
181,077
|
||||||
Patents, net
|
29,005
|
27,937
|
||||||
Deposits and other assets
|
59,567
|
50,034
|
||||||
Total assets
|
$
|
2,611,690
|
$
|
2,389,755
|
||||
LIABILITIES
AND STOCKHOLDERS’ EQUITY
|
||||||||
Current liabilities:
|
||||||||
Accounts payable
|
$
|
11,904
|
$
|
17,199
|
||||
Accrued compensation
|
38,810
|
65,728
|
||||||
Accrued liabilities
|
88,560
|
90,161
|
||||||
Income taxes payable
|
36
|
1,324
|
||||||
1 percent convertible senior notes, net
|
—
|
308,809
|
||||||
Current portion of long-term obligations
|
3,526
|
7,301
|
||||||
Current portion of deferred contract revenue
|
97,714
|
108,376
|
||||||
Total current liabilities
|
240,550
|
598,898
|
||||||
Long-term deferred contract revenue
|
351,879
|
424,046
|
||||||
0 percent convertible senior notes, net
|
619,119
|
—
|
||||||
0.125 percent convertible senior notes, net
|
542,314
|
540,136
|
||||||
Long-term obligations, less current portion
|
26,378
|
23,409
|
||||||
Long-term mortgage debt
|
59,713
|
59,984
|
||||||
Total liabilities
|
1,839,953
|
1,646,473
|
||||||
Stockholders’ equity:
|
||||||||
Common stock, $0.001 par value; 300,000,000 shares authorized, 141,210,015 and 140,365,594
shares issued and outstanding at December 31, 2021 and December 31, 2020, respectively
|
141
|
140
|
||||||
Additional paid-in capital
|
1,964,167
|
1,895,519
|
||||||
Accumulated other comprehensive loss
|
(32,668
|
)
|
(21,071
|
)
|
||||
Accumulated deficit
|
(1,159,903
|
)
|
(1,131,306
|
)
|
||||
Total stockholders’ equity
|
771,737
|
743,282
|
||||||
Total liabilities and stockholders’ equity
|
$
|
2,611,690
|
$
|
2,389,755
|
* |
We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 1, Organization and Significant Accounting Policies, for further information.
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
(as revised*)
|
(as revised*)
|
|||||||||||
Revenue:
|
||||||||||||
Commercial revenue:
|
||||||||||||
SPINRAZA royalties
|
$
|
267,776
|
$
|
286,583
|
$
|
292,992
|
||||||
TEGSEDI and WAYLIVRA revenue, net
|
55,500
|
69,999
|
42,253
|
|||||||||
Licensing and other royalty revenue
|
19,119
|
8,117
|
17,205
|
|||||||||
Total commercial revenue
|
342,395
|
364,699
|
352,450
|
|||||||||
Research and development revenue under collaborative agreements
|
468,061
|
364,565
|
770,149
|
|||||||||
Total revenue
|
810,456
|
729,264
|
1,122,599
|
|||||||||
Expenses:
|
||||||||||||
Cost of sales
|
10,842
|
11,947
|
4,384
|
|||||||||
Research, development and patent
|
643,453
|
535,077
|
465,688
|
|||||||||
Selling, general and administrative
|
186,347
|
354,322
|
286,644
|
|||||||||
Total operating expenses
|
840,642
|
901,346
|
756,716
|
|||||||||
Income (loss) from operations
|
(30,186
|
)
|
(172,082
|
)
|
365,883
|
|||||||
Other income (expense):
|
||||||||||||
Investment income
|
10,044
|
30,562
|
52,013
|
|||||||||
Interest expense
|
(9,349
|
)
|
(9,510
|
)
|
(12,440
|
)
|
||||||
Gain on investments
|
10,103
|
16,540
|
192
|
|||||||||
Loss on early retirement of debt
|
(8,627
|
)
|
—
|
(66,196
|
)
|
|||||||
Other expenses
|
(1,133
|
)
|
(62
|
)
|
(686
|
)
|
||||||
Income (loss) before income tax benefit (expense)
|
(29,148
|
)
|
(134,552
|
)
|
338,766
|
|||||||
Income tax benefit (expense)
|
551
|
(345,191
|
)
|
(51,507
|
)
|
|||||||
Net income (loss)
|
(28,597
|
)
|
(479,743
|
)
|
287,259
|
|||||||
Net (income) loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.
|
—
|
35,480
|
(9,116
|
)
|
||||||||
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders
|
$
|
(28,597
|
)
|
$
|
(444,263
|
)
|
$
|
278,143
|
||||
Basic net income (loss) per share
|
$
|
(0.20
|
)
|
$
|
(3.18
|
)
|
$
|
2.00
|
||||
Shares used in computing basic net income (loss) per share
|
141,021
|
139,612
|
139,998
|
|||||||||
Diluted net income (loss) per share
|
$
|
(0.20
|
)
|
$
|
(3.18
|
)
|
$
|
1.90
|
||||
Shares used in computing diluted net income (loss) per share
|
141,021
|
139,612
|
153,164
|
* |
We revised our 2020 and 2019 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to
Note 1, Organization and Significant Accounting Policies, for further information.
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
(as revised*)
|
(as revised*)
|
|||||||||||
Net income (loss)
|
$
|
(28,597
|
)
|
$
|
(479,743
|
)
|
$
|
287,259
|
||||
Unrealized gains (losses) on investments, net of tax
|
(11,486
|
)
|
3,729
|
6,633
|
||||||||
Currency translation adjustment
|
(111
|
)
|
617
|
93
|
||||||||
Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea
Therapeutics, Inc.
|
—
|
(127
|
)
|
—
|
||||||||
Comprehensive income (loss)
|
(40,194
|
)
|
(475,524
|
)
|
293,985
|
|||||||
Comprehensive income (loss) attributable to noncontrolling interest in Akcea Therapeutics, Inc.
|
—
|
(35,480
|
)
|
9,116
|
||||||||
Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders
|
$
|
(40,194
|
)
|
$
|
(440,044
|
)
|
$
|
284,869
|
* |
We revised our 2020 and 2019 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to
Note 1, Organization and Significant Accounting Policies, for further information.
|
Common Stock
|
Additional
|
Accumulated Other
|
Accumulated
|
Total Ionis
Stockholders’
|
Noncontrolling
Interest in Akcea
|
Total
Stockholders’
|
||||||||||||||||||||||||||
Description
|
Shares
|
Amount
|
Paid in Capital
|
Comprehensive Loss
|
Deficit
|
Equity
|
Therapeutics, Inc.
|
Equity
|
||||||||||||||||||||||||
Balance at December 31, 2018 (as revised*)
|
137,929
|
$
|
138
|
$
|
1,833,668
|
$
|
(32,016
|
)
|
$
|
(840,251
|
)
|
$
|
961,539
|
$
|
139,084
|
$
|
1,100,623
|
|||||||||||||||
Net income
|
—
|
—
|
—
|
—
|
278,143
|
278,143
|
—
|
278,143
|
||||||||||||||||||||||||
Change in unrealized losses, net of tax
|
—
|
—
|
—
|
6,633
|
—
|
6,633
|
—
|
6,633
|
||||||||||||||||||||||||
Foreign currency translation
|
—
|
—
|
—
|
93
|
—
|
93
|
—
|
93
|
||||||||||||||||||||||||
Issuance of common stock in connection with employee stock plans
|
3,100
|
3
|
119,654
|
—
|
—
|
119,657
|
—
|
119,657
|
||||||||||||||||||||||||
Issuance of warrants
|
—
|
—
|
56,110
|
—
|
—
|
56,110
|
—
|
56,110
|
||||||||||||||||||||||||
Purchase of note hedges, net of tax
|
—
|
—
|
(85,860
|
)
|
—
|
—
|
(85,860
|
)
|
—
|
(85,860
|
)
|
|||||||||||||||||||||
Repurchases and retirements of common stock
|
(535
|
)
|
(1
|
)
|
—
|
—
|
(34,387
|
)
|
(34,388
|
)
|
—
|
(34,388
|
)
|
|||||||||||||||||||
Stock-based compensation expense
|
—
|
—
|
146,574
|
—
|
—
|
146,574
|
—
|
146,574
|
||||||||||||||||||||||||
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee
stock options
|
(154
|
)
|
—
|
(19,242
|
)
|
—
|
—
|
(19,242
|
)
|
—
|
(19,242
|
)
|
||||||||||||||||||||
Noncontrolling interest in Akcea Therapeutics, Inc.
|
—
|
—
|
(65,254
|
)
|
—
|
—
|
(65,254
|
)
|
74,370
|
9,116
|
||||||||||||||||||||||
Balance at December 31, 2019 (as revised*)
|
140,340
|
$
|
140
|
$
|
1,985,650
|
$
|
(25,290
|
)
|
$
|
(596,495
|
)
|
$
|
1,364,005
|
$
|
213,454
|
$
|
1,577,459
|
|||||||||||||||
Net loss
|
—
|
—
|
—
|
—
|
(444,263
|
)
|
(444,263
|
)
|
—
|
(444,263
|
)
|
|||||||||||||||||||||
Change in unrealized gain, net of tax
|
—
|
—
|
—
|
3,729
|
—
|
3,729
|
—
|
3,729
|
||||||||||||||||||||||||
Foreign currency translation
|
—
|
—
|
—
|
617
|
—
|
617
|
—
|
617
|
||||||||||||||||||||||||
Issuance of common stock in connection with employee stock plans
|
1,721
|
1
|
52,033
|
—
|
—
|
52,034
|
—
|
52,034
|
||||||||||||||||||||||||
Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for
cancellation of Akcea Therapeutics, Inc. equity awards
|
—
|
—
|
(324,022
|
)
|
301
|
—
|
(323,721
|
)
|
(220,965
|
)
|
(544,686
|
)
|
||||||||||||||||||||
Repurchases and retirements of common stock
|
(1,478
|
)
|
(1
|
)
|
—
|
—
|
(90,548
|
)
|
(90,549
|
)
|
—
|
(90,549
|
)
|
|||||||||||||||||||
Stock-based compensation expense
|
—
|
—
|
230,117
|
—
|
—
|
230,117
|
—
|
230,117
|
||||||||||||||||||||||||
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee
stock options
|
(217
|
)
|
—
|
(13,410
|
)
|
—
|
—
|
(13,410
|
)
|
—
|
(13,410
|
)
|
||||||||||||||||||||
Deferred tax liability adjustment due to purchase of noncontrolling interest of Akcea Therapeutics,
Inc.
|
—
|
—
|
7,714
|
—
|
—
|
7,714
|
—
|
7,714
|
||||||||||||||||||||||||
Noncontrolling interest in Akcea Therapeutics, Inc.
|
—
|
—
|
(42,563
|
)
|
(428
|
)
|
—
|
(42,991
|
)
|
7,511
|
(35,480
|
)
|
||||||||||||||||||||
Balance at December 31, 2020 (as revised*)
|
140,366
|
$
|
140
|
$
|
1,895,519
|
$
|
(21,071
|
)
|
$
|
(1,131,306
|
)
|
$
|
743,282
|
$
|
—
|
$
|
743,282
|
|||||||||||||||
Net loss
|
—
|
—
|
—
|
—
|
(28,597
|
)
|
(28,597
|
)
|
—
|
(28,597
|
)
|
|||||||||||||||||||||
Change in unrealized gains, net of tax
|
—
|
—
|
—
|
(11,486
|
)
|
—
|
(11,486
|
)
|
—
|
(11,486
|
)
|
|||||||||||||||||||||
Foreign currency translation
|
—
|
—
|
—
|
(111
|
)
|
—
|
(111
|
)
|
—
|
(111
|
)
|
|||||||||||||||||||||
Issuance of common stock in connection with employee stock plans
|
1,132
|
1
|
11,563
|
—
|
—
|
11,564
|
—
|
11,564
|
||||||||||||||||||||||||
Issuance of warrants
|
—
|
—
|
89,752
|
—
|
—
|
89,752
|
—
|
89,752
|
||||||||||||||||||||||||
Purchases of note hedges
|
—
|
—
|
(136,620
|
)
|
—
|
—
|
(136,620
|
)
|
—
|
(136,620
|
)
|
|||||||||||||||||||||
Stock-based compensation expense
|
—
|
—
|
120,678
|
—
|
—
|
120,678
|
—
|
120,678
|
||||||||||||||||||||||||
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee
stock options
|
(288
|
)
|
—
|
(16,725
|
)
|
—
|
—
|
(16,725
|
)
|
—
|
(16,725
|
)
|
||||||||||||||||||||
Balance at December 31, 2021
|
141,210
|
$
|
141
|
$
|
1,964,167
|
$
|
(32,668
|
)
|
$
|
(1,159,903
|
)
|
$
|
771,737
|
$
|
—
|
$
|
771,737
|
* |
We revised our 2018, 2019 and 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer
to Note 1, Organization and Significant Accounting Policies, for further information.
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
(as revised*)
|
(as revised*)
|
|||||||||||
Operating activities:
|
||||||||||||
Net income (loss)
|
$
|
(28,597
|
)
|
$
|
(479,743
|
)
|
$
|
287,259
|
||||
Adjustments to reconcile net income (loss) to net cash provided by operating activities:
|
||||||||||||
Depreciation
|
15,487
|
13,365
|
12,540
|
|||||||||
Amortization of right-of-use operating lease assets
|
1,721
|
1,731
|
1,542
|
|||||||||
Amortization of patents
|
2,352
|
2,064
|
1,912
|
|||||||||
Amortization of premium (discount) on investments, net
|
17,776
|
11,521
|
(7,485
|
)
|
||||||||
Amortization of debt issuance costs
|
4,958
|
3,255
|
2,945
|
|||||||||
Stock-based compensation expense
|
120,678
|
230,117
|
146,574
|
|||||||||
Loss on early retirement of debt
|
8,627
|
—
|
66,196
|
|||||||||
Gain on investments
|
(1,092
|
)
|
(16,540
|
)
|
(192
|
)
|
||||||
Deferred income taxes, including changes in valuation allowance
|
—
|
341,729
|
911
|
|||||||||
Non-cash losses related to patents
|
2,707
|
1,948
|
2,226
|
|||||||||
Changes in operating assets and liabilities:
|
||||||||||||
Contracts receivable
|
14,308
|
(13,170
|
)
|
(47,674
|
)
|
|||||||
Inventories
|
(2,841
|
)
|
(1,261
|
)
|
(5,411
|
)
|
||||||
Other current and long-term assets
|
(877
|
)
|
(9,975
|
)
|
(44,659
|
)
|
||||||
Long-term income taxes receivable (payable)
|
1,008
|
(89
|
)
|
8,418
|
||||||||
Accounts payable
|
(6,000
|
)
|
(2,755
|
)
|
(16,343
|
)
|
||||||
Income taxes
|
(1,288
|
)
|
(31,190
|
)
|
31,656
|
|||||||
Accrued compensation
|
(26,918
|
)
|
28,371
|
8,089
|
||||||||
Accrued liabilities and other current liabilities
|
(8,381
|
)
|
32,424
|
16,406
|
||||||||
Deferred contract revenue
|
(82,829
|
)
|
(75,910
|
)
|
(119,283
|
)
|
||||||
Net cash provided by operating activities
|
30,799
|
35,892
|
345,627
|
|||||||||
Investing activities:
|
||||||||||||
Purchases of short-term investments
|
(1,124,193
|
)
|
(1,570,410
|
)
|
(1,946,726
|
)
|
||||||
Proceeds from the sale of short-term investments
|
1,344,185
|
1,885,935
|
1,951,734
|
|||||||||
Purchases of property, plant and equipment
|
(11,955
|
)
|
(35,120
|
)
|
(30,905
|
)
|
||||||
Acquisition of licenses and other assets, net
|
(5,946
|
)
|
(5,928
|
)
|
(5,377
|
)
|
||||||
Purchases of strategic investments
|
(7,185
|
)
|
—
|
(10,000
|
)
|
|||||||
Net cash provided by (used in) investing activities
|
194,906
|
274,477
|
(41,274
|
)
|
||||||||
Financing activities:
|
||||||||||||
Proceeds from equity, net
|
11,565
|
52,036
|
119,657
|
|||||||||
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee
stock options
|
(16,725
|
)
|
(13,411
|
)
|
(19,242
|
)
|
||||||
Proceeds from the issuance of 0 percent convertible senior notes
|
632,500
|
—
|
—
|
|||||||||
Proceeds from the issuance of 0.125 percent convertible senior notes
|
—
|
—
|
109,500
|
|||||||||
0 percent convertible senior notes issuance costs
|
(15,609
|
)
|
—
|
—
|
||||||||
0.125 percent convertible senior notes issuance costs
|
—
|
—
|
(10,428
|
)
|
||||||||
Repurchase of $247.9 million principal amount of 1 percent convertible senior notes
|
(256,963
|
)
|
—
|
—
|
||||||||
Repayment of remaining principal amount of 1 percent convertible senior notes at maturity
|
(61,967
|
)
|
—
|
—
|
||||||||
Proceeds from issuance of warrants
|
89,752
|
—
|
56,110
|
|||||||||
Purchase of note hedges
|
(136,620
|
)
|
—
|
(108,684
|
)
|
|||||||
Repurchases and retirements of common stock
|
—
|
(90,548
|
)
|
(34,392
|
)
|
|||||||
Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards
|
—
|
(544,686
|
)
|
—
|
||||||||
Principal payments on line of credit
|
—
|
—
|
(12,500
|
)
|
||||||||
Net cash provided by (used in) financing activities
|
245,933
|
(596,609
|
)
|
100,021
|
||||||||
Effects of exchange rates on cash
|
(111
|
)
|
617
|
93
|
||||||||
Net increase (decrease) in cash and cash equivalents
|
471,527
|
(285,623
|
)
|
404,467
|
||||||||
Cash and cash equivalents at beginning of year
|
397,664
|
683,287
|
278,820
|
|||||||||
Cash and cash equivalents at end of year
|
$
|
869,191
|
$
|
397,664
|
$
|
683,287
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
Supplemental disclosures of cash flow information:
|
||||||||||||
Interest paid
|
$
|
4,778
|
$
|
6,247
|
$
|
9,870
|
||||||
Income taxes paid
|
$
|
38
|
$
|
25,855
|
$
|
9,041
|
||||||
Supplemental disclosures of non-cash investing and financing activities:
|
||||||||||||
Right-of-use assets obtained in exchange for lease liabilities
|
$
|
6,641
|
$
|
2,149
|
$
|
14,178
|
||||||
Amounts accrued for capital and patent expenditures
|
$
|
705
|
$
|
4,059
|
$
|
3,126
|
||||||
0.125 percent convertible senior notes principal issued related to our December 2019 debt exchange/issuance
|
$
|
—
|
$
|
—
|
$
|
439,326
|
||||||
1 percent convertible senior notes principal extinguished related to our December 2019 debt exchange
|
$
|
—
|
$
|
—
|
$
|
375,590
|
* |
We revised our 2020 and 2019 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to
Note 1, Organization and Significant Accounting Policies, for further information.
|
Year Ended December 31, 2020
|
Weighted
Average Shares
Owned in Akcea
|
Akcea’s
Net Loss
Per Share
|
Basic Net Loss
Per Share
Calculation
|
|||||||||
Akcea’s net loss in the pre-merger period attributable to our ownership
|
77,095
|
$
|
(1.45
|
)
|
$
|
(111,775
|
)
|
|||||
Akcea’s net loss in the post-merger period attributable to our ownership
|
(85,987
|
)
|
||||||||||
Akcea’s total net loss attributable to our ownership
|
$
|
(197,762
|
)
|
|||||||||
Ionis’ stand-alone net loss
|
(246,702
|
)
|
||||||||||
Net loss available to Ionis common stockholders
|
$
|
(444,464
|
)
|
|||||||||
Weighted average shares outstanding
|
139,612
|
|||||||||||
Basic net loss per share
|
$
|
(3.18
|
)
|
Year Ended December 31, 2019
|
Weighted
Average Shares
Owned in Akcea
|
Akcea’s
Net Income
Per Share
|
Basic Net Income
Per Share
Calculation
|
|||||||||
Common shares
|
70,100
|
$
|
0.49
|
$
|
34,073
|
|||||||
Akcea’s net income attributable to our ownership
|
$
|
34,073
|
||||||||||
Ionis’ stand-alone net income
|
246,487
|
|||||||||||
Net income available to Ionis common stockholders
|
$
|
280,560
|
||||||||||
Weighted average shares outstanding
|
139,998
|
|||||||||||
Basic net income per share
|
$
|
2.00
|
● |
0.125 percent convertible senior notes, or 0.125% Notes;
|
● |
Note hedges related to the 0.125% Notes;
|
● |
1 percent convertible senior notes, or 1% Notes;
|
● |
Dilutive stock options;
|
● |
Unvested restricted stock units, or RSUs;
|
● |
Unvested performance restricted stock units, or PRSUs; and
|
● |
Employee Stock Purchase Plan, or ESPP.
|
● |
0 percent convertible senior notes, or 0% Notes; and
|
● |
Note hedges related to the 0% Notes.
|
Year Ended December 31, 2019
|
Net Income Available
to Ionis Common
Stockholders
(Numerator)
|
Shares
(Denominator)
|
Per-Share
Amount
|
|||||||||
Net income available to Ionis common stockholders
|
$
|
280,560
|
139,998
|
$
|
2.00
|
|||||||
Effect of dilutive securities:
|
||||||||||||
Shares issuable upon exercise of stock options
|
—
|
2,090
|
||||||||||
Shares issuable upon restricted stock award issuance
|
—
|
766
|
||||||||||
Shares issuable related to our ESPP
|
—
|
18
|
||||||||||
Shares issuable related to our 0.125 percent convertible notes
|
860
|
217
|
||||||||||
Shares issuable related to our 1 percent convertible notes
|
9,527
|
10,075
|
||||||||||
$
|
290,947
|
153,164
|
$
|
1.90
|
1. |
Identify the contract
|
● |
We and our partner approved the contract and we are both committed to perform our obligations;
|
● |
We have identified our rights, our partner’s rights and the payment terms;
|
● |
We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the
contract; and
|
● |
We believe collectability of the consideration is probable.
|
2. |
Identify the performance obligations
|
3. |
Determine the transaction price
|
4. |
Allocate the transaction price
|
● |
Estimated future product sales;
|
● |
Estimated royalties we may receive from future product sales;
|
● |
Estimated contractual milestone payments we may receive;
|
● |
Expenses we expect to incur;
|
● |
Estimated income taxes; and
|
● |
A discount rate.
|
● |
The number of internal hours we estimate we will spend performing these services;
|
● |
The estimated cost of work we will perform;
|
● |
The estimated cost of work that we will contract with third parties to perform; and
|
● |
The estimated cost of API we will use.
|
5. |
Recognize revenue
|
1) |
If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and
|
2) |
If the goods and/or services are at a stand-alone selling price.
|
● |
Whether the agreements were negotiated together with a single objective;
|
● |
Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or
|
● |
Whether the goods and/or services promised under the agreements are a single performance obligation.
|
Year Ending December 31,
|
Amortization
(in millions)
|
|||
2022
|
$
|
2.2
|
||
2023
|
$
|
2.1
|
||
2024
|
$
|
1.9
|
||
2025
|
$
|
1.8
|
||
2026
|
$
|
1.8
|
December 31,
|
||||||||
2021
|
2020
|
|||||||
Clinical expenses
|
$
|
65,730
|
$
|
39,477
|
||||
In-licensing expenses
|
8,044
|
8,264
|
||||||
Commercial expenses
|
2,471
|
11,559
|
||||||
Other miscellaneous expenses
|
12,315
|
30,861
|
||||||
Total accrued liabilities
|
$
|
88,560
|
$
|
90,161
|
December 31,
|
||||||||
2021
|
2020
|
|||||||
Raw materials:
|
||||||||
Raw materials- clinical
|
$
|
14,507
|
$
|
9,206
|
||||
Raw materials- commercial
|
4,139
|
7,502
|
||||||
Total raw materials
|
18,646
|
16,708
|
||||||
Work in process
|
5,770
|
2,252
|
||||||
Finished goods
|
390
|
3,005
|
||||||
Total inventory
|
$
|
24,806
|
$
|
21,965
|
Estimated Useful
|
December 31,
|
|||||||||||
Lives (in years)
|
2021
|
2020
|
||||||||||
Computer software, laboratory, manufacturing and other equipment
|
3 to 10
|
$
|
72,802
|
$
|
68,990
|
|||||||
Building, building improvements and building systems
|
15 to 40
|
144,046
|
137,879
|
|||||||||
Land improvements
|
20
|
10,077
|
8,391
|
|||||||||
Leasehold improvements
|
5 to 15
|
20,144
|
17,263
|
|||||||||
Furniture and fixtures
|
5 to 10
|
10,591
|
12,871
|
|||||||||
257,660
|
245,394
|
|||||||||||
Less accumulated depreciation
|
(102,653
|
)
|
(87,379
|
)
|
||||||||
155,007
|
158,015
|
|||||||||||
Land
|
23,062
|
23,062
|
||||||||||
Total
|
$
|
178,069
|
$
|
181,077
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
Beginning balance accumulated other comprehensive loss
|
$
|
(21,071
|
)
|
$
|
(25,290
|
)
|
$
|
(32,016
|
)
|
|||
Unrealized gains (losses) on securities, net of tax (1)
|
(11,486
|
)
|
3,729
|
6,633
|
||||||||
Currency translation adjustment
|
(111
|
)
|
617
|
93
|
||||||||
Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea
Therapeutics, Inc.
|
—
|
(127
|
)
|
—
|
||||||||
Net other comprehensive loss for the period
|
(11,597
|
)
|
4,219
|
6,726
|
||||||||
Ending balance accumulated other comprehensive loss
|
$
|
(32,668
|
)
|
$
|
(21,071
|
)
|
$
|
(25,290
|
)
|
(1)
|
We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2021 and 2020. For the year ended December 31,
2019, we had a tax benefit of $1.4
million included in other comprehensive loss.
|
December 31, 2020
|
||||||||||||
As Previously
Reported
|
ASU 2020-06
Adjustment
|
As Revised
|
||||||||||
1 percent convertible
senior notes
|
$
|
293,161
|
$
|
15,648
|
$
|
308,809
|
||||||
0.125 percent convertible
senior notes
|
$
|
455,719
|
$
|
84,417
|
$
|
540,136
|
||||||
Additional paid-in-capital
|
$
|
2,113,646
|
$
|
(218,127
|
)
|
$
|
1,895,519
|
|||||
Accumulated deficit
|
$
|
(1,249,368
|
)
|
$
|
118,062
|
$
|
(1,131,306
|
)
|
Year Ended December 31, 2020
|
||||||||||||
As Previously
Reported
|
ASU 2020-06
Adjustment
|
As Revised
|
||||||||||
Interest expense
|
$
|
(44,990
|
)
|
$
|
35,480
|
$
|
(9,510
|
)
|
||||
Loss before income tax expense
|
$
|
(170,032
|
)
|
$
|
35,480
|
$
|
(134,552
|
)
|
||||
Income tax expense
|
$
|
(316,734
|
)
|
$
|
(28,457
|
)
|
$
|
(345,191
|
)
|
|||
Net loss
|
$
|
(486,766
|
)
|
$
|
7,023
|
$
|
(479,743
|
)
|
||||
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders
|
$
|
(451,286
|
)
|
$
|
7,023
|
$
|
(444,263
|
)
|
||||
Basic and diluted net loss per share
|
$
|
(3.23
|
)
|
$
|
0.05
|
$
|
(3.18
|
)
|
Year Ended December 31, 2019
|
||||||||||||
As Previously
Reported
|
ASU 2020-06
Adjustment
|
As Revised
|
||||||||||
Interest expense
|
$
|
(48,768
|
)
|
$
|
36,328
|
$
|
(12,440
|
)
|
||||
Loss on early retirement of debt
|
(21,865
|
)
|
(44,331
|
)
|
(66,196
|
)
|
||||||
Income before income tax benefit (expense)
|
$
|
346,769
|
$
|
(8,003
|
)
|
$
|
338,766
|
|||||
Income tax expense
|
$
|
(43,507
|
)
|
$
|
(8,000
|
)
|
$
|
(51,507
|
)
|
|||
Net income
|
$
|
303,262
|
$
|
(16,003
|
)
|
$
|
287,259
|
|||||
Net income attributable to Ionis Pharmaceuticals, Inc. common stockholders
|
$
|
294,146
|
$
|
(16,003
|
)
|
$
|
278,143
|
|||||
Basic net income per share
|
2.12
|
(0.12
|
)
|
2.00
|
||||||||
Diluted net income per share
|
$
|
2.08
|
$
|
(0.18
|
)
|
$
|
1.90
|
December 31, 2020
|
||||||||||||
As Previously
Reported
|
ASU 2020-06
Adjustment
|
As Revised
|
||||||||||
Additional paid-in-capital
|
$
|
2,113,646
|
$
|
(218,127
|
)
|
$
|
1,895,519
|
|||||
Accumulated deficit
|
$
|
(1,249,368
|
)
|
$
|
118,062
|
$
|
(1,131,306
|
)
|
||||
Total stockholders’ equity
|
$
|
843,347
|
$
|
(100,065
|
)
|
$
|
743,282
|
December 31, 2019
|
||||||||||||
As Previously
Reported
|
ASU 2020-06
Adjustment
|
As Revised
|
||||||||||
Additional paid-in-capital
|
$
|
2,203,778
|
$
|
(218,128
|
)
|
$
|
1,985,650
|
|||||
Accumulated deficit
|
$
|
(707,534
|
)
|
$
|
111,039
|
$
|
(596,495
|
)
|
||||
Total stockholders’ equity
|
$
|
1,684,547
|
$
|
(107,088
|
)
|
$
|
1,577,459
|
At
December 31, 2021
|
Quoted Prices in
Active Markets
(Level 1)
|
Significant Other
Observable Inputs
(Level 2)
|
Significant
Unobservable Inputs
(Level 3)
|
|||||||||||||
Cash equivalents (1)
|
$
|
541,199
|
$
|
541,199
|
$
|
—
|
$
|
—
|
||||||||
Corporate debt securities (2)
|
764,059
|
—
|
764,059
|
—
|
||||||||||||
Debt securities issued by U.S. government agencies (2)
|
120,868
|
—
|
120,868
|
—
|
||||||||||||
Debt securities issued by the U.S. Treasury (2)
|
182,634
|
182,634
|
—
|
—
|
||||||||||||
Debt securities issued by states of the U.S. and political subdivisions of the states (3)
|
174,464
|
—
|
174,464
|
—
|
||||||||||||
Other municipal debt securities (2)
|
6,099
|
—
|
6,099
|
—
|
||||||||||||
Investment in Bicycle Therapeutics plc (4)
|
14,330
|
—
|
—
|
14,330
|
||||||||||||
Investment in ProQR Therapeutics N.V. (4)
|
3,875
|
3,875
|
—
|
—
|
||||||||||||
Total
|
$
|
1,807,528
|
$
|
727,708
|
$
|
1,065,490
|
$
|
14,330
|
At
December 31, 2020
|
Quoted Prices in
Active Markets
(Level 1)
|
Significant Other
Observable Inputs
(Level 2)
|
||||||||||
Cash equivalents (1)
|
$
|
221,125
|
$
|
221,125
|
$
|
—
|
||||||
Corporate debt securities (5)
|
846,315
|
—
|
846,315
|
|||||||||
Debt securities issued by U.S. government agencies (2)
|
174,861
|
—
|
174,861
|
|||||||||
Debt securities issued by the U.S. Treasury (6)
|
358,497
|
358,497
|
—
|
|||||||||
Debt securities issued by states of the U.S. and political subdivisions of the states (2)
|
136,309
|
—
|
136,309
|
|||||||||
Other municipal debt securities (2)
|
6,225
|
—
|
6,225
|
|||||||||
Investment in ProQR Therapeutics N.V. (4)
|
2,031
|
2,031
|
—
|
|||||||||
Total
|
$
|
1,745,363
|
$
|
581,653
|
$
|
1,163,710
|
(1) |
Included in cash and cash
equivalents on our consolidated balance sheet.
|
(2) |
Included in short-term
investments.
|
(3) |
$2.3 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our
consolidated balance sheet.
|
(4) |
Included in other current assets
on our consolidated balance sheet.
|
(5) |
$10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our
consolidated balance sheet.
|
(6) |
$17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our
consolidated balance sheet.
|
One year or less
|
51
|
%
|
||
After one year but within two years
|
34
|
%
|
||
After two years but within
|
15
|
%
|
||
Total
|
100
|
%
|
Amortized
|
Gross Unrealized
|
Estimated
|
||||||||||||||
December 31, 2021
|
Cost
|
Gains
|
Losses
|
Fair Value
|
||||||||||||
Available-for-sale securities:
|
||||||||||||||||
Corporate debt securities (1)
|
$
|
383,870
|
$
|
728
|
$
|
(226
|
)
|
$
|
384,372
|
|||||||
Debt securities issued by U.S. government agencies
|
48,493
|
19
|
(18
|
)
|
48,494
|
|||||||||||
Debt securities issued by the U.S. Treasury (1)
|
45,424
|
—
|
(64
|
)
|
45,360
|
|||||||||||
Debt securities issued by states of the U.S. and political subdivisions of the states
|
134,770
|
45
|
(37
|
)
|
134,778
|
|||||||||||
Total securities with a maturity of one year or less
|
612,557
|
792
|
(345
|
)
|
613,004
|
|||||||||||
Corporate debt securities
|
382,000
|
331
|
(2,644
|
)
|
379,687
|
|||||||||||
Debt securities issued by U.S. government agencies
|
72,935
|
—
|
(561
|
)
|
72,374
|
|||||||||||
Debt securities issued by the U.S. Treasury
|
137,635
|
139
|
(500
|
)
|
137,274
|
|||||||||||
Debt securities issued by states of the U.S. and political subdivisions of the states
|
39,909
|
1
|
(224
|
)
|
39,686
|
|||||||||||
Other municipal debt securities
|
6,136
|
—
|
(37
|
)
|
6,099
|
|||||||||||
Total securities with a maturity of more than one year
|
638,615
|
471
|
(3,966
|
)
|
635,120
|
|||||||||||
Total available-for-sale securities
|
$
|
1,251,172
|
$
|
1,263
|
$
|
(4,311
|
)
|
$
|
1,248,124
|
|||||||
Equity securities:
|
||||||||||||||||
Total equity securities included in other current assets (2)
|
$
|
11,897
|
$
|
7,145
|
$
|
(837
|
)
|
$
|
18,205
|
|||||||
Total equity securities included in deposits and other assets (3)
|
15,615
|
16,707
|
—
|
32,322
|
||||||||||||
Total equity securities
|
$
|
27,512
|
$
|
23,852
|
$
|
(837
|
)
|
$
|
50,527
|
|||||||
Total available-for-sale and equity securities
|
$
|
1,278,684
|
$
|
25,115
|
$
|
(5,148
|
)
|
$
|
1,298,651
|
Amortized
|
Gross Unrealized
|
Estimated
|
||||||||||||||
December 31, 2020
|
Cost
|
Gains
|
Losses
|
Fair Value
|
||||||||||||
Available-for-sale securities:
|
||||||||||||||||
Corporate debt securities (1)
|
$
|
514,182
|
$
|
2,194
|
$
|
(41
|
)
|
$
|
516,335
|
|||||||
Debt securities issued by U.S. government agencies
|
94,234
|
354
|
(2
|
)
|
94,586
|
|||||||||||
Debt securities issued by the U.S. Treasury (1)
|
307,576
|
233
|
(9
|
)
|
307,800
|
|||||||||||
Debt securities issued by states of the U.S. and political subdivisions of the states
|
104,271
|
196
|
(12
|
)
|
104,455
|
|||||||||||
Other municipal debt securities
|
5,191
|
—
|
(7
|
)
|
5,184
|
|||||||||||
Total securities with a maturity of one year or less
|
1,025,454
|
2,977
|
(71
|
)
|
1,028,360
|
|||||||||||
Corporate debt securities
|
325,079
|
4,941
|
(40
|
)
|
329,980
|
|||||||||||
Debt securities issued by U.S. government agencies
|
80,099
|
185
|
(9
|
)
|
80,275
|
|||||||||||
Debt securities issued by the U.S. Treasury
|
50,318
|
383
|
(4
|
)
|
50,697
|
|||||||||||
Debt securities issued by states of the U.S. and political subdivisions of the states
|
31,779
|
91
|
(16
|
)
|
31,854
|
|||||||||||
Other municipal debt securities
|
1,041
|
—
|
—
|
1,041
|
||||||||||||
Total securities with a maturity of more than one year
|
488,316
|
5,600
|
(69
|
)
|
493,847
|
|||||||||||
Total available-for-sale securities
|
$
|
1,513,770
|
$
|
8,577
|
$
|
(140
|
)
|
$
|
1,522,207
|
|||||||
Equity securities:
|
||||||||||||||||
Total equity securities included in other current assets (2)
|
$
|
4,712
|
$
|
—
|
$
|
(2,681
|
)
|
$
|
2,031
|
|||||||
Total equity securities included in deposits and other assets (3)
|
15,062
|
15,938
|
—
|
31,000
|
||||||||||||
Total equity securities
|
$
|
19,774
|
$
|
15,938
|
$
|
(2,681
|
)
|
$
|
33,031
|
|||||||
Total available-for-sale and equity securities
|
$
|
1,533,544
|
$
|
24,515
|
$
|
(2,821
|
)
|
$
|
1,555,238
|
(1) |
Includes investments classified
as cash equivalents on our consolidated balance sheet.
|
(2) |
Our equity securities included in other current
assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value.
|
(3) |
Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at cost minus
impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our consolidated balance sheet.
|
Number of
Investments
|
Estimated
Fair Value
|
Unrealized
Losses
|
||||||||||
Corporate debt securities
|
272
|
$
|
552,966
|
$
|
(2,870
|
)
|
||||||
Debt securities issued by U.S. government agencies
|
15
|
114,338
|
(579
|
)
|
||||||||
Debt securities issued by the U.S. Treasury
|
13
|
134,987
|
(564
|
)
|
||||||||
Debt securities issued by states of the U.S. and political subdivisions of the states
|
425
|
126,401
|
(261
|
)
|
||||||||
Other municipal debt securities
|
2
|
6,099
|
(37
|
)
|
||||||||
Total temporarily impaired securities
|
727
|
$
|
934,791
|
$
|
(4,311
|
)
|
December 31,
|
||||||||
2021
|
2020
|
|||||||
(as revised*)
|
||||||||
0.125 percent convertible senior notes
|
$
|
542,314
|
$
|
540,136
|
||||
1 percent convertible senior notes (1)
|
—
|
308,809
|
||||||
0 percent convertible senior notes
|
619,119
|
—
|
||||||
Long-term mortgage debt
|
59,713
|
59,984
|
||||||
Leases and other obligations
|
29,904
|
30,710
|
||||||
Total
|
$
|
1,251,050
|
$
|
939,639
|
||||
Less: current portion (1)
|
(3,526
|
)
|
(316,110
|
)
|
||||
Total Long-Term Obligations
|
$
|
1,247,524
|
$
|
623,529
|
(1) |
We classified the carrying value of
our 1% Notes as a current liability on our consolidated balance sheet at December 31, 2020 because it matured in November 2021.
|
* |
We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 1, Organization and Significant Accounting Policies, for further information.
|
0% Notes
|
||||
Outstanding principal balance
|
$
|
632.5
|
||
Unamortized debt issuance costs
|
$
|
13.4
|
||
Maturity date
|
|
|||
Interest rate
|
0 percent
|
|||
Effective interest rate
|
0.5 percent
|
|||
Conversion price per share
|
$
|
57.84
|
||
Effective conversion price per share with call spread
|
$
|
76.39
|
||
Total shares of common stock subject to conversion
|
10.9
|
0.125%
Notes
|
||||
Outstanding principal balance
|
$
|
548.8
|
||
Unamortized debt issuance costs
|
$
|
6.5
|
||
Maturity date
|
|
|||
Interest rate
|
0.125 percent
|
|||
Effective interest rate
|
0.5 percent
|
|||
Conversion price per share
|
$
|
83.28
|
||
Effective conversion price per share with call spread
|
$
|
123.38
|
||
Total shares of common stock subject to conversion
|
6.6
|
2022
|
$
|
3,498
|
||
2023
|
4,180
|
|||
2024
|
4,180
|
|||
2025
|
1,184,820
|
|||
2026
|
3,494
|
|||
Thereafter
|
57,439
|
|||
Subtotal
|
$
|
1,257,611
|
||
Less: current portion
|
(3,526
|
)
|
||
Less: fixed and determinable interest
|
(15,498
|
)
|
||
Less: debt issuance costs
|
(20,302
|
)
|
||
Plus: lease liabilities
|
22,058
|
|||
Plus: other liabilities
|
7,181
|
|||
Total long-term debt
|
$
|
1,247,524
|
At December 31, 2021
|
||||
Right-of-use operating lease assets (1)
|
$
|
18.0
|
||
Operating lease liabilities (2)
|
$
|
22.1
|
||
Weighted average remaining lease term
|
6.6 years
|
|||
Weighted average discount rate
|
6.0
|
%
|
(1) |
Included in
on our consolidated balance sheet. |
(2) |
Current portion of $2.6 million was included in
on our consolidated balance sheet, with the difference included in . |
Operating Leases
|
||||
Year ending December 31,
|
$ | |||
2022
|
4,075
|
|||
2023
|
4,314
|
|||
2024
|
4,223
|
|||
2025
|
4,062
|
|||
2026
|
3,778
|
|||
Thereafter
|
7,035
|
|||
Total minimum lease payments
|
27,487
|
|||
Less:
|
||||
Imputed interest
|
(5,429
|
)
|
||
Total operating lease liabilities
|
$
|
22,058
|
● |
arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);
|
● |
arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the
surviving or acquiring corporation (or its parent company);
|
● |
accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;
|
● |
arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;
|
● |
cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate
transaction, in exchange for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and
|
● |
arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award
would have received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise.
|
● |
An increase to the total number of shares reserved for issuance under the
plan from 2.0 million to 2.8 million shares;
|
● |
A reduction to the amount of the automatic awards under the plan;
|
● |
A revision to the vesting schedule of new awards granted; and
|
● |
An extension of the term of the plan.
|
Number
of Shares
|
Weighted
Average Exercise
Price Per Share
|
Average
Remaining
Contractual Term
(Years)
|
Aggregate
Intrinsic
Value
|
|||||||||||||
Outstanding at December 31, 2020
|
12,439
|
$
|
54.11
|
|||||||||||||
Granted
|
3,382
|
$
|
53.07
|
|||||||||||||
Exercised
|
(219
|
)
|
$
|
38.69
|
||||||||||||
Cancelled/forfeited/expired
|
(1,513
|
)
|
$
|
54.65
|
||||||||||||
Outstanding at December 31, 2021
|
14,089
|
$
|
54.04
|
3.89
|
$
|
1,131
|
||||||||||
Exercisable at December 31, 2021
|
9,175
|
$
|
53.65
|
2.94
|
$
|
1,067
|
Number
of Shares
|
Weighted Average
Grant Date Fair
Value Per Share
|
|||||||
Non-vested at December 31, 2020
|
2,374
|
$
|
58.81
|
|||||
Granted
|
1,548
|
$
|
57.69
|
|||||
Vested
|
(834
|
)
|
$
|
57.47
|
||||
Cancelled/forfeited
|
(411
|
)
|
$
|
59.24
|
||||
Non-vested at December 31, 2021
|
2,677
|
$
|
58.51
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
Cost of sales
|
$
|
456
|
$
|
1,991
|
$
|
438
|
||||||
Research, development and patent
|
87,522
|
115,584
|
95,348
|
|||||||||
Selling, general and administrative
|
32,700
|
112,542
|
50,788
|
|||||||||
Total
|
$
|
120,678
|
$
|
230,117
|
$
|
146,574
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
Risk-free interest rate
|
0.6
|
%
|
1.5
|
%
|
2.3
|
%
|
||||||
Dividend yield
|
0.0
|
%
|
0.0
|
%
|
0.0
|
%
|
||||||
Volatility
|
54.0
|
%
|
58.6
|
%
|
60.3
|
%
|
||||||
Expected life
|
4.9 years
|
4.7 years
|
4.8 years
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
Risk-free interest rate
|
1.2
|
%
|
0.5
|
%
|
1.9
|
%
|
||||||
Dividend yield
|
0.0
|
%
|
0.0
|
%
|
0.0
|
%
|
||||||
Volatility
|
55.9
|
%
|
57.6
|
%
|
60.7
|
%
|
||||||
Expected life
|
7.3 years
|
6.7 years
|
6.6 years
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
Risk-free interest rate
|
0.1
|
%
|
0.8
|
%
|
2.4
|
%
|
||||||
Dividend yield
|
0.0
|
%
|
0.0
|
%
|
0.0
|
%
|
||||||
Volatility
|
42.4
|
%
|
47.9
|
%
|
45.6
|
%
|
||||||
Expected life
|
6 months
|
6 months
|
6 months
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
(as revised*)
|
(as revised*)
|
|||||||||||
United States
|
$
|
(29,966
|
)
|
$
|
(137,222
|
)
|
$
|
336,277
|
||||
Foreign
|
818
|
2,670
|
2,489
|
|||||||||
Income (loss) before income taxes
|
$
|
(29,148
|
)
|
$
|
(134,552
|
)
|
$
|
338,766
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
(as revised*)
|
(as revised*)
|
|||||||||||
Current:
|
||||||||||||
Federal
|
$
|
(200
|
)
|
$
|
(837
|
)
|
$
|
35,861
|
||||
State
|
(690
|
)
|
3,782
|
14,329
|
||||||||
Foreign
|
339
|
518
|
413
|
|||||||||
Total current income tax expense (benefit)
|
(551
|
)
|
3,463
|
50,603
|
||||||||
Deferred:
|
||||||||||||
Federal
|
—
|
341,728
|
904
|
|||||||||
State
|
—
|
—
|
—
|
|||||||||
Total deferred income tax benefit
|
—
|
341,728
|
904
|
|||||||||
Total income tax expense (benefit)
|
$
|
(551
|
)
|
$
|
345,191
|
$
|
51,507
|
Year Ended December 31,
|
||||||||||||||||||||||||
2021
|
2020
|
2019
|
||||||||||||||||||||||
(as revised*)
|
(as revised*)
|
|||||||||||||||||||||||
Pre-tax income (loss)
|
$
|
(29,148
|
)
|
$
|
(134,552
|
)
|
$
|
338,766
|
||||||||||||||||
Statutory rate
|
(6,121
|
)
|
21.0
|
%
|
(28,256
|
)
|
21.0
|
%
|
71,141
|
21.0
|
%
|
|||||||||||||
State income tax net of federal benefit
|
4,278
|
(14.7
|
)%
|
(37,705
|
)
|
28.0
|
%
|
49,000
|
14.5
|
%
|
||||||||||||||
Foreign
|
143
|
(0.5
|
)%
|
49
|
0.0
|
%
|
340
|
0.1
|
%
|
|||||||||||||||
Net change in valuation allowance
|
2,885
|
(9.9
|
)%
|
460,898
|
(342.5
|
)%
|
(37,314
|
)
|
(11.0
|
)%
|
||||||||||||||
Loss on debt transactions
|
262
|
(0.9
|
)%
|
—
|
—
|
9,911
|
2.9
|
%
|
||||||||||||||||
Impact from outside basis differences
|
—
|
—
|
—
|
—
|
(16,344
|
)
|
(4.8
|
)%
|
||||||||||||||||
Tax credits
|
(23,198
|
)
|
79.6
|
%
|
(18,774
|
)
|
14.0
|
%
|
(22,296
|
)
|
(6.6
|
)%
|
||||||||||||
Deferred tax true-up
|
(24
|
)
|
0.1
|
%
|
(206
|
)
|
0.2
|
%
|
646
|
0.2
|
%
|
|||||||||||||
Tax rate change
|
12,838
|
(44.0
|
)%
|
(32,951
|
)
|
24.5
|
%
|
1,248
|
0.4
|
%
|
||||||||||||||
Non-deductible compensation
|
5,085
|
(17.4
|
)%
|
7,931
|
(5.9
|
)%
|
3,361
|
1.0
|
%
|
|||||||||||||||
Other non-deductible items
|
84
|
(0.3
|
)%
|
193
|
(0.1
|
)%
|
329
|
0.1
|
%
|
|||||||||||||||
Stock-based compensation
|
4,720
|
(16.2
|
)%
|
17,435
|
(13.0
|
)%
|
(4,837
|
)
|
(1.4
|
)%
|
||||||||||||||
Foreign-derived intangible income benefit
|
—
|
—
|
—
|
—
|
(2,071
|
)
|
(0.6
|
)%
|
||||||||||||||||
Impacts from Akcea Merger
|
—
|
—
|
(22,032
|
)
|
16.4
|
%
|
—
|
—
|
||||||||||||||||
Other
|
(1,503
|
)
|
5.1
|
%
|
(1,391
|
)
|
0.9
|
%
|
(1,607
|
)
|
(0.6
|
)%
|
||||||||||||
Effective rate
|
$
|
(551
|
)
|
1.9
|
%
|
$
|
345,191
|
(256.5
|
)%
|
$
|
51,507
|
15.2
|
%
|
Year Ended December 31,
|
||||||||
2021
|
2020
|
|||||||
(as revised*)
|
||||||||
Deferred Tax Assets:
|
||||||||
Net operating loss carryovers
|
$
|
85,600
|
$
|
83,681
|
||||
Tax credits
|
269,538
|
245,746
|
||||||
Deferred revenue
|
104,330
|
124,452
|
||||||
Stock-based compensation
|
86,611
|
80,055
|
||||||
Intangible and capital assets
|
92,542
|
98,443
|
||||||
Convertible debt
|
45,681
|
22,395
|
||||||
Interest expense limitation
|
6,996
|
—
|
||||||
Other
|
15,048
|
13,402
|
||||||
Total deferred tax assets
|
$
|
706,346
|
$
|
668,174
|
||||
Deferred Tax Liabilities:
|
||||||||
Fixed assets
|
(3,303
|
)
|
(3,611
|
)
|
||||
Other
|
(5,270
|
)
|
(5,808
|
)
|
||||
Net deferred tax asset
|
$
|
697,773
|
$
|
658,755
|
||||
Valuation allowance
|
(697,773
|
)
|
(658,755
|
)
|
||||
Total net deferred tax assets and liabilities
|
$
|
—
|
$
|
—
|
* |
We revised our 2020 and 2019 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to
Note 1, Organization and Significant Accounting Policies, for further information.
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
Beginning balance of unrecognized tax benefits
|
$
|
54,163
|
$
|
69,784
|
$
|
68,301
|
||||||
Decrease for prior period tax positions
|
(695
|
)
|
(24,154
|
)
|
(867
|
)
|
||||||
Increase for prior period tax positions
|
263
|
7,023
|
736
|
|||||||||
Increase for current period tax positions
|
1,354
|
1,510
|
1,614
|
|||||||||
Ending balance of unrecognized tax benefits
|
$
|
55,085
|
$
|
54,163
|
$
|
69,784
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
SPINRAZA royalties (commercial revenue)
|
$
|
267.8
|
$
|
286.6
|
$
|
293.0
|
||||||
R&D revenue
|
161.0
|
122.0
|
180.6
|
|||||||||
Total revenue from our relationship with Biogen
|
$
|
428.8
|
$
|
408.6
|
$
|
473.6
|
||||||
Percentage of total revenue
|
53
|
%
|
56
|
%
|
42
|
%
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
R&D revenue
|
$
|
254.6
|
$
|
88.0
|
$
|
28.1
|
||||||
Percentage of total revenue
|
31
|
%
|
12
|
%
|
3
|
%
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
R&D revenue
|
$
|
1.1
|
$
|
3.2
|
$
|
14.3
|
||||||
Percentage of total revenue
|
0
|
%
|
0
|
%
|
1
|
%
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
R&D revenue
|
$
|
—
|
$
|
0.2
|
$
|
25.4
|
||||||
Percentage of total revenue
|
—
|
0
|
%
|
2
|
%
|
● |
R&D services for pelacarsen;
|
● |
R&D services for olezarsen;
|
● |
API for pelacarsen; and
|
● |
API for olezarsen.
|
● |
$75 million from the upfront payment;
|
● |
$28.4 million for the premium paid by Novartis for its purchase
of our common stock at a premium in the first quarter of 2017; and
|
● |
$5.0 million for the potential premium Novartis would have paid
if they purchased our common stock in the future.
|
● |
$64.0 million for the R&D services for pelacarsen;
|
● |
$40.1 million for the R&D services for olezarsen;
|
● |
$1.5 million for the delivery of pelacarsen API; and
|
● |
$2.8 million for the delivery of olezarsen API.
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
R&D revenue
|
$
|
25.5
|
$
|
1.0
|
$
|
187.4
|
||||||
Percentage of total revenue
|
3
|
%
|
0
|
%
|
17
|
%
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
R&D revenue
|
$
|
17.2
|
$
|
5.9
|
$
|
57.0
|
||||||
Percentage of total revenue
|
2
|
%
|
1
|
%
|
5
|
%
|
Year Ended December 31,
|
||||||||||||
2021
|
2020
|
2019
|
||||||||||
R&D revenue
|
$
|
—
|
$
|
47.9
|
$
|
24.1
|
||||||
Percentage of total revenue
|
—
|
7
|
%
|
2
|
%
|
Year Ended
December 31, 2021
|
Year Ended
December 31, 2020
|
|||||||
R&D expenses
|
$
|
5.1
|
$
|
3.9
|
||||
SG&A expenses
|
6.6
|
11.4
|
||||||
Total
|
$
|
11.7
|
$
|
15.3
|
Year Ended
December 31, 2021
|
||||
Beginning balance as of January 1, 2021
|
$
|
14.7
|
||
Amount expensed during the year
|
13.5
|
|||
Reserve adjustments during the year
|
(1.8
|
)
|
||
Net amount expensed during the year
|
11.7
|
|||
Amounts paid during the year
|
(26.4
|
)
|
||
Ending balance as of December 31, 2021
|
$
|
—
|
Year Ended
December 31, 2021
|
Year Ended
December 31, 2020
|
|||||||
R&D expenses
|
$
|
0.6
|
$
|
4.2
|
||||
SG&A expenses
|
1.1
|
8.3
|
||||||
Total
|
$
|
1.7
|
$
|
12.5
|
Year Ended
December 31, 2021
|
||||
Beginning balance as of January 1, 2021
|
$
|
12.4
|
||
Amount expensed during the year
|
2.6
|
|||
Reserve adjustments during the year
|
(0.9
|
)
|
||
Net amount expensed during the year
|
1.7
|
|||
Amounts paid during the year
|
(14.1
|
)
|
||
Ending balance as of December 31, 2021
|
$
|
—
|
Year Ended
December 31, 2021
|
||||
R&D expenses
|
$
|
2.3
|
||
SG&A expenses
|
7.1
|
|||
Total
|
$
|
9.4
|
Year Ended
December 31, 2021
|
||||
Beginning balance as of January 1, 2021
|
$
|
—
|
||
Net amount expensed during the year
|
9.4
|
|||
Amounts paid during the year
|
(9.4
|
)
|
||
Ending balance as of December 31, 2021
|
$
|
—
|
Three Months Ended December 31,
|
2021
|
2020
|
||||||
Revenue
|
$
|
440,006
|
$
|
290,281
|
||||
Operating expenses
|
$
|
219,403
|
$
|
312,945
|
||||
Income (loss) from operations
|
$
|
220,603
|
$
|
(22,664
|
)
|
|||
Net income (loss)
|
$
|
224,613
|
$
|
(355,687
|
)
|
|||
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders
|
$
|
224,613
|
$
|
(354,532
|
)
|
|||
Basic net income (loss) per share (1) (2)
|
$
|
1.59
|
$
|
(2.54
|
)
|
|||
Diluted net income (loss) per share (1) (3)
|
$
|
1.41
|
$
|
(2.54
|
)
|
(1) |
We compute net income (loss) per share independently for each quarter during the year.
|
(2) |
As discussed in Note 1, Organization and Significant Accounting Policies, we compute basic net income (loss) per share by dividing the total net income (loss)
attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. Our basic net income per share for the fourth quarter of 2021 was $1.59.
|
Three Months Ended December 31, 2020
|
Weighted
Average Shares
Owned in Akcea
|
Akcea’s
Net Loss
Per Share
|
Basic Net Loss
Per Share
Calculation
|
|||||||||
Akcea’s net loss in the pre-merger period attributable to our ownership
|
77,095
|
$
|
(0.05
|
)
|
$
|
(3,603
|
)
|
|||||
Akcea’s net loss in the post-merger period attributable to our ownership
|
(85,987
|
)
|
||||||||||
Akcea’s total net loss attributable to our ownership
|
$
|
(89,590
|
)
|
|||||||||
Ionis’ stand-alone net loss
|
(266,418
|
)
|
||||||||||
Net loss available to Ionis common stockholders
|
$
|
(356,008
|
)
|
|||||||||
Weighted average shares outstanding
|
139,956
|
|||||||||||
Basic net loss per share
|
$
|
(2.54
|
)
|
(3) |
We had net income available
to Ionis common stockholders for the fourth quarter of 2021. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):
|
Three Months Ended December 31, 2021
|
Income
(Numerator)
|
Shares
(Denominator)
|
Per-Share
Amount
|
|||||||||
Net income available to Ionis common stockholders
|
$
|
224,612
|
141,205
|
$
|
1.59
|
|||||||
Effect of dilutive securities:
|
||||||||||||
Shares issuable upon exercise of stock options
|
—
|
46
|
||||||||||
Shares issuable upon restricted stock award issuance
|
—
|
1,065
|
||||||||||
Shares issuable related to our ESPP
|
—
|
34
|
||||||||||
Shares issuable related to our 0 percent convertible notes
|
777
|
10,936
|
||||||||||
Shares issuable related to our 0.125 percent convertible notes
|
716
|
6,590
|
||||||||||
Shares issuable related to our 1 percent convertible notes
|
105
|
464
|
||||||||||
Income available to Ionis common stockholders, plus assumed conversions
|
$
|
226,210
|
160,340
|
$
|
1.41
|
1 Year Ionis Pharmaceuticals Chart |
1 Month Ionis Pharmaceuticals Chart |
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