Revenue minus cost of goods sold. Graham's ≥40% threshold identifies businesses with durable pricing power. Note: software and financial companies naturally exceed this; retailers and manufacturers rarely reach it due to their cost structures.
Operating Margin-47.7%
Profit after operating costs before interest and taxes. A consistent ≥15% operating margin signals a business with real competitive advantages. Capital-intensive industries (airlines, auto, commodities) rarely hit this threshold due to their structural cost base — compare within industry for context.
Net Income Margin-37.6%
Bottom-line profit as a percentage of revenue. The ≥20% target reflects Buffett's preference for highly profitable businesses. Financial engineering (buybacks, tax optimisation) can inflate this temporarily — look for consistency across multiple years rather than a single strong result.
Financial Health
C
Years to Pay Off Debt-22.1 yrs
Total Debt ÷ Net Income. Lower = stronger balance sheet. Important caveat: utilities, telecoms, REITs, and infrastructure companies carry large structural debt by design — their bond-like cash flows service it comfortably at ratios that would alarm Graham. Compare within sector.
Working Capital vs Long-Term Debt$871M
Working Capital minus Long-Term Debt. Negative results are common and expected in capital-return-focused businesses like Apple, Domino's, and McDonald's — where aggressive buybacks and dividends intentionally reduce book equity. This does not indicate financial distress in high-FCF businesses.
Working Capital$2.2B
Current Assets minus Current Liabilities. Negative working capital can be a deliberate efficiency strategy in businesses that collect cash before paying suppliers (retailers, fast food franchises, subscription businesses). Assess alongside free cash flow generation for full context.
Valuation
F
Price-to-Book24.93x
Market price vs book value per share. Rarely below 1.5x for quality businesses today. Intangible assets (brand, software, patents) don't appear on the balance sheet under accounting rules, making P/B artificially high for asset-light companies like software and consumer brands.
Cash Flow
F
Free Cash Flow-$816M
Operating cash flow minus capital expenditures. Buffett's most important metric — cash a business actually generates for its owners after maintaining and growing its asset base. Consistently positive FCF is one of the strongest indicators of a durable, well-run business regardless of accounting profits.
Owner Earnings-$62M
Net Income + Depreciation & Amortisation − Capital Expenditures. Buffett's preferred measure of a company's true annual earning power — what could theoretically be distributed to owners without impairing the business. More reliable than reported EPS because it accounts for the capital cost of maintaining the business.
About Ionis Pharmaceuticals, Inc.
Ionis Pharmaceuticals, Inc., a commercial-stage biotechnology company, provides RNA-targeted medicines in the United States. The company offers TRYNGOLZA reduces triglyceride levels in adults with familial chylomicronemia syndrome (FCS) and acute pancreatitis; DAWNZERA for prophylaxis to prevent attacks of hereditary angioedema in adults; WAINUA for the treatment of the polyneuropathy of hereditary transthyretin-medicated amyloidosis (ATTRv-PN) in adults; and SPINRAZA for pediatric and adult patients with spinal muscular atrophy (SMA). It also provides QALSODY for the treatment of Amyotrophic Lateral Sclerosis (ALS); TEGSEDI for the treatment of ATTRv-PN in adults; and WAYLIVRA for treatment for FCS and familial partial lipodystrophy. It also develops products under Phase 3 clinical trials, such as Olezarsen for patients with hypertriglyceridemia (SHTG) and cardiovascular disease (CVD); and Zilganerse, a potential treatment for people with genetically confirmed Alexander disease, as well as ION582 which is in Phase 3 clinical trial for the potential treatment of AS, a rare genetic neurological disease. In addition, the company develops Eplontersen to degrade mutant and wild-type TTR mRNA through binding to the TTR mRNA; Pelacarsen to inhibit the production of apolipoprotein(a) in the liver to offer a direct approach for reducing lipoprotein(a); Bepirovirsen to inhibit the production of viral proteins associated with hepatitis B virus; Sefaxersen to reduce the production of complement factor B and lower activation of the alternative complement pathway; and Ulefnersen to reduce the production of the fused in sarcoma, as well as other mid-stage pipeline investigational medicines. It has a strategic collaboration with Biogen for the treatment of neurological disorders; and collaboration and license agreement with GSK, AstraZeneca, Novartis, and Roche, as well as with Metagenomi. The company was incorporated in 1989 and is headquartered in Carlsbad, California.
Ionis Pharmaceuticals, Inc., a commercial-stage biotechnology company, provides RNA-targeted medicines in the United States. The company offers TRYNGOLZA reduces triglyceride levels in adults with familial chylomicronemia syndrome (FCS) and acute pancreatitis; DAWNZERA for prophylaxis to prevent attacks of hereditary angioedema in adults; WAINUA for the treatment of the polyneuropathy of hereditary transthyretin-medicated amyloidosis (ATTRv-PN) in adults; and SPINRAZA for pediatric and adult patients with spinal muscular atrophy (SMA). It also provides QALSODY for the treatment of Amyotrophic Lateral Sclerosis (ALS); TEGSEDI for the treatment of ATTRv-PN in adults; and WAYLIVRA for treatment for FCS and familial partial lipodystrophy. It also develops products under Phase 3 clinical trials, such as Olezarsen for patients with hypertriglyceridemia (SHTG) and cardiovascular disease (CVD); and Zilganerse, a potential treatment for people with genetically confirmed Alexander disease, as well as ION582 which is in Phase 3 clinical trial for the potential treatment of AS, a rare genetic neurological disease. In addition, the company develops Eplontersen to degrade mutant and wild-type TTR mRNA through binding to the TTR mRNA; Pelacarsen to inhibit the production of apolipoprotein(a) in the liver to offer a direct approach for reducing lipoprotein(a); Bepirovirsen to inhibit the production of viral proteins associated with hepatitis B virus; Sefaxersen to reduce the production of complement factor B and lower activation of the alternative complement pathway; and Ulefnersen to reduce the production of the fused in sarcoma, as well as other mid-stage pipeline investigational medicines. It has a strategic collaboration with Biogen for the treatment of neurological disorders; and collaboration and license agreement with GSK, AstraZeneca, Novartis, and Roche, as well as with Metagenomi. The company was incorporated in 1989 and is headquartered in Carlsbad, California.
Metric Explanations
What each dimension measures and where the thresholds come from.
Gross Profit Margin
Revenue minus cost of goods sold. Graham's ≥40% threshold identifies businesses with durable pricing power. Note: software and financial companies naturally exceed this; retailers and manufacturers rarely reach it due to their cost structures.
Operating Margin
Profit after operating costs before interest and taxes. A consistent ≥15% operating margin signals a business with real competitive advantages. Capital-intensive industries (airlines, auto, commodities) rarely hit this threshold due to their structural cost base — compare within industry for context.
Net Income Margin
Bottom-line profit as a percentage of revenue. The ≥20% target reflects Buffett's preference for highly profitable businesses. Financial engineering (buybacks, tax optimisation) can inflate this temporarily — look for consistency across multiple years rather than a single strong result.
Years to Pay Off Debt
Total Debt ÷ Net Income. Lower = stronger balance sheet. Important caveat: utilities, telecoms, REITs, and infrastructure companies carry large structural debt by design — their bond-like cash flows service it comfortably at ratios that would alarm Graham. Compare within sector.
Working Capital vs Long-Term Debt
Working Capital minus Long-Term Debt. Negative results are common and expected in capital-return-focused businesses like Apple, Domino's, and McDonald's — where aggressive buybacks and dividends intentionally reduce book equity. This does not indicate financial distress in high-FCF businesses.
Working Capital
Current Assets minus Current Liabilities. Negative working capital can be a deliberate efficiency strategy in businesses that collect cash before paying suppliers (retailers, fast food franchises, subscription businesses). Assess alongside free cash flow generation for full context.
Price-to-Book
Market price vs book value per share. Rarely below 1.5x for quality businesses today. Intangible assets (brand, software, patents) don't appear on the balance sheet under accounting rules, making P/B artificially high for asset-light companies like software and consumer brands.
Free Cash Flow
Operating cash flow minus capital expenditures. Buffett's most important metric — cash a business actually generates for its owners after maintaining and growing its asset base. Consistently positive FCF is one of the strongest indicators of a durable, well-run business regardless of accounting profits.
Owner Earnings
Net Income + Depreciation & Amortisation − Capital Expenditures. Buffett's preferred measure of a company's true annual earning power — what could theoretically be distributed to owners without impairing the business. More reliable than reported EPS because it accounts for the capital cost of maintaining the business.
Net Income From Continuing Operation Net Minority Interest
-92,528
-229,394
Reconciled Depreciation
7,447
7,341
Reconciled Cost Of Revenue
3,000
7,957
EBITDA
-64,526
-199,515
EBIT
-71,973
-206,856
Net Interest Income
-22,537
-22,760
Interest Expense
20,337
21,060
Normalized Income
-121,368
-249,553
Net Income From Continuing And Discontinued Operation
-92,528
-229,394
Total Expenses
363,573
417,803
Total Operating Income As Reported
-117,424
-214,459
Diluted Average Shares
165,000
162,000
Basic Average Shares
165,000
162,000
Diluted EPS
0
0
Basic EPS
0
0
Diluted NI Availto Com Stockholders
-92,528
-229,394
Net Income Common Stockholders
-92,528
-229,394
Net Income
-92,528
-229,394
Net Income Including Noncontrolling Interests
-92,528
-229,394
Net Income Continuous Operations
-92,528
-229,394
Tax Provision
218
1,478
Pretax Income
-92,310
-227,916
Other Income Expense
47,611
9,231
Other Non Operating Income Expenses
-456
-16,287
Gain On Sale Of Security
48,067
25,518
Net Non Operating Interest Income Expense
-22,537
-22,760
Total Other Finance Cost
2,200
1,700
Interest Expense Non Operating
20,337
21,060
Operating Income
-117,482
-214,473
Operating Expense
360,573
409,846
Research And Development
210,173
279,646
Selling General And Administration
150,400
130,200
General And Administrative Expense
150,400
130,200
Other Gand A
132,000
117,400
Salaries And Wages
18,400
12,800
Gross Profit
243,091
195,373
Cost Of Revenue
3,000
7,957
Total Revenue
246,091
203,330
Operating Revenue
246,091
203,330
Balance Sheet
2026
2025
2024
Ordinary Shares Number
165,902
163,305
Share Issued
165,902
163,305
Net Debt
1,608,358
1,429,869
Total Debt
2,040,954
2,064,512
Tangible Book Value
491,414
489,089
Invested Capital
2,273,153
2,291,218
Working Capital
2,220,354
2,209,068
Net Tangible Assets
491,414
489,089
Capital Lease Obligations
259,215
262,383
Common Stock Equity
491,414
489,089
Total Capitalization
1,840,653
1,836,532
Total Equity Gross Minority Interest
491,414
489,089
Stockholders Equity
491,414
489,089
Gains Losses Not Affecting Retained Earnings
-31,023
-25,281
Other Equity Adjustments
-31,023
-25,281
Retained Earnings
-2,723,723
-2,631,195
Additional Paid In Capital
3,245,994
3,145,402
Capital Stock
166
163
Common Stock
166
163
Total Liabilities Net Minority Interest
2,958,555
3,034,747
Total Non Current Liabilities Net Minority Interest
2,241,964
2,253,180
Other Non Current Liabilities
557,765
551,353
Non Current Deferred Liabilities
75,745
92,001
Non Current Deferred Revenue
75,745
92,001
Long Term Debt And Capital Lease Obligation
1,608,454
1,609,826
Long Term Capital Lease Obligation
259,215
262,383
Long Term Debt
1,349,239
1,347,443
Current Liabilities
716,591
781,567
Other Current Liabilities
23,390
Current Deferred Liabilities
69,199
73,761
Current Deferred Revenue
69,199
73,761
Current Debt And Capital Lease Obligation
432,500
454,686
9,279
Current Debt
432,500
454,686
9,279
Other Current Borrowings
432,500
454,686
9,279
Pensionand Other Post Retirement Benefit Plans Current
36,049
116,236
Payables And Accrued Expenses
155,453
136,884
Current Accrued Expenses
126,549
106,089
Payables
28,904
30,795
Total Tax Payable
2,874
2,713
Income Tax Payable
2,874
2,713
Accounts Payable
26,030
28,082
Total Assets
3,449,969
3,523,836
Total Non Current Assets
513,024
533,201
Other Non Current Assets
135,559
171,604
Net PPE
377,465
361,597
Accumulated Depreciation
-109,080
-106,316
Gross PPE
377,465
470,677
Leases
89,153
54,375
Other Properties
377,465
238,549
Machinery Furniture Equipment
101,174
96,395
Buildings And Improvements
41,801
41,228
Land And Improvements
0
8,569
Current Assets
2,936,945
2,990,635
Other Current Assets
306,080
237,092
Restricted Cash
632,511
Inventory
5,557
10,048
Finished Goods
990
1,096
276
Work In Process
4,077
7,913
6,679
Raw Materials
490
1,039
5,557
Receivables
73,684
66,059
Other Receivables
73,684
66,059
Cash Cash Equivalents And Short Term Investments
1,919,113
2,677,436
Other Short Term Investments
1,745,732
2,305,176
Cash And Cash Equivalents
173,381
372,260
Cash Flow
2026
2025
2024
Free Cash Flow
-816,068
-160,366
Repayment Of Debt
-44
-267,692
Issuance Of Capital Stock
57,302
107,817
Capital Expenditure
-23,249
-22,657
Interest Paid Supplemental Data
90
5,383
Income Tax Paid Supplemental Data
End Cash Position
173,381
372,260
Beginning Cash Position
372,260
338,341
Effect Of Exchange Rate Changes
-138
-43
Changes In Cash
-198,741
33,962
Financing Cash Flow
57,258
591,176
Cash Flow From Continuing Financing Activities
57,258
591,176
Net Common Stock Issuance
57,302
107,817
Common Stock Issuance
57,302
107,817
Net Issuance Payments Of Debt
-44
502,308
Net Long Term Debt Issuance
-44
502,308
Long Term Debt Payments
-44
-267,692
Investing Cash Flow
536,820
-419,505
Cash Flow From Continuing Investing Activities
536,820
-419,505
Net Investment Purchase And Sale
560,069
-396,848
Sale Of Investment
752,824
395,119
Purchase Of Investment
-192,755
-791,967
Net Intangibles Purchase And Sale
-1,486
-1,365
Purchase Of Intangibles
-1,486
-1,365
Net PPE Purchase And Sale
-21,763
-21,292
Purchase Of PPE
-21,763
-21,292
Operating Cash Flow
-792,819
-137,709
Cash Flow From Continuing Operating Activities
-792,819
-137,709
Change In Working Capital
-730,124
23,856
Change In Other Working Capital
-653,168
-16,451
Change In Other Current Assets
-7,390
90,277
Change In Payables And Accrued Expense
-62,279
-9,445
Change In Accrued Expense
-59,184
-23,134
Change In Payable
-3,095
13,689
Change In Account Payable
-3,095
13,756
Change In Tax Payable
Change In Income Tax Payable
Change In Inventory
338
926
Change In Receivables
-7,625
-41,451
Other Non Cash Items
7,844
5,701
Stock Based Compensation
43,275
43,320
Amortization Of Securities
-6,190
-5,672
Depreciation Amortization Depletion
7,447
7,341
Depreciation And Amortization
7,447
7,341
Amortization Cash Flow
661
638
Amortization Of Intangibles
661
638
Depreciation
6,786
6,703
Operating Gains Losses
-22,543
17,139
Gain Loss On Investment Securities
-22,583
157
Gain Loss On Sale Of PPE
7,290
Net Income From Continuing Operations
-92,528
-229,394
📊Quarterly mode — Graham Fair Value & 7 Criteria require annual data. Switch to Annual for full analysis.
Quarter vs Same Quarter Last Year
YoY strips seasonality
Revenue Growth (YoY)
Prior year: $132M▲ $246M+87.0%
Revenue growth vs same quarter last year strips seasonality. Consistent double-digit growth is a Buffett hallmark.
Gross Margin
Prior year: 98.9%▲ 98.8%-0.1pp
Buffett: consistent gross margin above 40% signals durable pricing power and competitive moat.
Operating Margin
Prior year: -89.3%▲ -47.7%+41.5pp
Graham: operating margin reflects true business economics before financing. Trend matters as much as level.
Net Margin
Prior year: -111.6%▲ -37.6%+74.0pp
Net margin can be distorted by one-time items, tax timing, or interest costs — compare to operating margin for signal quality.
Quarterly Health Checks
3 Graham/Buffett criteria that are valid and reliable on quarterly data
❌ Adequate Size
Graham required scale for resilience. Quarterly revenue × 4 gives an annualised proxy.
$246M/qtr (≈$984M ann.)
vs > $1.5B annualised revenue
✅ Financial Condition
Current assets vs current liabilities — a real-time liquidity snapshot. Valid and reliable on quarterly data.
4.10x current ratio
vs ≥ 2.0x
❌ Free Cash Flow
Buffett's most important single metric. A positive FCF quarter means the business generated real cash for owners after maintaining its asset base.
-$816M
vs Positive
Operating Cash Flow
-$793M
Latest quarter · Buffett's cash reality check
ROIC
-3.4%
Based on latest annual operating income
Return on Invested Capital — Buffett's preferred measure for asset-light businesses. ROIC > 15% consistently signals a durable competitive advantage (moat). More meaningful than P/B for software, pharma, and consumer brand companies where most value is intangible and off-balance-sheet.
Market Cap / Net Assets
24.9x
Net Assets: $491M
Asset Context — Biotechnology
R&D costs are expensed immediately under GAAP rather than capitalised as assets, meaning a pharma/biotech company's most valuable assets (drug pipeline, patents) are largely invisible on the balance sheet. Net Assets significantly understates true economic value. Pipeline depth and revenue diversification matter more.
"The management of a business is its most important single factor — more important than market position, patents, or financial structure."
— Benjamin Graham
Capital Allocation & Alignment
Insider Ownership
0.61%
Low — management has little skin in the game
Return on Equity (ROE)
-18.8%
Weak — poor returns on equity
Return on Assets (ROA)
-2.7%
Poor — assets are not generating adequate returns
Debt Trend YoY
-1.1% YoY
Debt is declining — management is deleveraging
Leadership Team
Brett Monia Ph.
Founder, CEO & Director
Age 64
Pay: $3,467,834
Elizabeth Hougen , ,
Executive VP of Finance & CFO
Age 63
Pay: $1,604,674
Eric Swayze Ph.
Executive Vice President of Research
Age 59
Pay: $1,233,732
Brian Birchler
Executive Vice President of Corporate & Development Operations
Age 59
Pay: $1,240,447
Wade Walke Ph.
Senior Vice President of Investor Relations
Top Institutional Holders
Institution
% Owned
Shares
FMR, LLC
14.86%
24,556,637
Capital World Investors
12.82%
21,186,369
Blackrock Inc.
6.32%
10,442,476
Vanguard Portfolio Management LLC
4.73%
7,808,902
Vanguard Capital Management LLC
4.31%
7,118,330
Wellington Management Group, LLP
3.87%
6,391,816
T. Rowe Price Investment Management, Inc.
3.73%
6,159,027
Two Sigma Investments, LP
3.54%
5,857,629
⚠️Very high debt-to-equity — leverage risk
Risk Analysis
Beta (Market Risk)
0.37
Low volatility — more stable than the market
Short Interest
13.6% of float
Moderate short interest
Debt-to-Equity
5.31x
High leverage — significant financial risk
Current Ratio
4.10x
Strong liquidity — Graham approved
52-Week Price Range
Low: $36.45Current: $74.12High: $86.74
Currently at 75% of 52-week range
Ionis Pharmaceuticals, Inc. (IONS) fundamental analysis — Overall grade F based on profitability, financial health, valuation and cash flow. Graham's
Fair Value: N/A (negative EPS). Gross profit margin: 98.8%. Operating margin: -47.7%. Net margin: -37.6%. Market cap: $12.2B. Sector: Healthcare. Industry: Biotechnology. Analysis powered by 360investing — free fundamental stock analysis based on Benjamin Graham and Warren Buffett
principles.
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