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Exelixis, Inc. – ‘10-Q’ for 10/1/21 – ‘EX-101.DEF’

On:  Tuesday, 11/2/21, at 4:18pm ET   ·   For:  10/1/21   ·   Accession #:  939767-21-97   ·   File #:  0-30235

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  As Of               Filer                 Filing    For·On·As Docs:Size

11/02/21  Exelixis, Inc.                    10-Q       10/01/21   69:7.2M

Quarterly Report   —   Form 10-Q

Filing Table of Contents

Document/Exhibit                   Description                      Pages   Size 

 1: 10-Q        Quarterly Report                                    HTML    941K 
 2: EX-31.1     Certification -- §302 - SOA'02                      HTML     25K 
 3: EX-31.2     Certification -- §302 - SOA'02                      HTML     25K 
 4: EX-32.1     Certification -- §906 - SOA'02                      HTML     24K 
11: R1          Cover Page                                          HTML     74K 
12: R2          Condensed Consolidated Balance Sheets               HTML    135K 
13: R3          Condensed Consolidated Balance Sheets               HTML     39K 
                (Parenthetical)                                                  
14: R4          Condensed Consolidated Statements of Income (Loss)  HTML     93K 
15: R5          Condensed Consolidated Statements of Comprehensive  HTML     42K 
                Income (Loss)                                                    
16: R6          Condensed Consolidated Statements of Comprehensive  HTML     24K 
                Income (Loss) (Parenthetical)                                    
17: R7          Condensed Consolidated Statements of Stockholders'  HTML     73K 
                Equity                                                           
18: R8          Condensed Consolidated Statements of Cash Flows     HTML     97K 
19: R9          Organization and Summary of Significant Accounting  HTML     38K 
                Policies                                                         
20: R10         Revenues                                            HTML    122K 
21: R11         Collaboration Agreements, In-Licensing              HTML     67K 
                Arrangements And Business Development Activities                 
22: R12         Cash and Investments                                HTML     96K 
23: R13         Fair Value Measurements                             HTML     58K 
24: R14         Inventory                                           HTML     34K 
25: R15         Stock-Based Compensation                            HTML     56K 
26: R16         Provision For (Benefit From) Income Taxes           HTML     26K 
27: R17         Net Income (Loss) Per Share                         HTML     48K 
28: R18         Commitments and Contingencies                       HTML     31K 
29: R19         Organization and Summary of Significant Accounting  HTML     60K 
                Policies (Policies)                                              
30: R20         Revenues (Tables)                                   HTML    122K 
31: R21         Collaboration Agreements, In-Licensing              HTML     53K 
                Arrangements And Business Development Activities                 
                (Tables)                                                         
32: R22         Cash and Investments (Tables)                       HTML    108K 
33: R23         Fair Value Measurements (Tables)                    HTML     53K 
34: R24         Inventory (Tables)                                  HTML     35K 
35: R25         Stock-Based Compensation (Tables)                   HTML     54K 
36: R26         Net Income (Loss) Per Share (Tables)                HTML     49K 
37: R27         Organization and Summary of Significant Accounting  HTML     30K 
                Policies (Details)                                               
38: R28         Revenues - Revenues by Disaggregated Category       HTML     41K 
                (Details)                                                        
39: R29         Revenues - Revenues Disaggregated by Significant    HTML     50K 
                Customer (Details)                                               
40: R30         Revenues - Revenues Disaggregated by Geographic     HTML     34K 
                Region (Details)                                                 
41: R31         Revenues - Net Product Revenues Disaggregated by    HTML     34K 
                Product (Details)                                                
42: R32         Revenues - Activities and Ending Reserve Balances   HTML     43K 
                for Significant Categories of Discounts and                      
                Allowances (Details)                                             
43: R33         Revenues - Contract Assets and Liabilities          HTML     41K 
                (Details)                                                        
44: R34         Collaboration Agreements, In-Licensing              HTML     37K 
                Arrangements And Business Development Activities -               
                Collaboration Revenues under the Collaboration                   
                Agreement with Ipsen (Details)                                   
45: R35         Collaboration Agreements, In-Licensing              HTML     30K 
                Arrangements And Business Development Activities -               
                Ipsen Collaboration Narrative (Details)                          
46: R36         Collaboration Agreements, In-Licensing              HTML     37K 
                Arrangements And Business Development Activities -               
                Collaboration Revenues under the Collaboration                   
                Agreement with Takeda (Details)                                  
47: R37         Collaboration Agreements, In-Licensing              HTML     30K 
                Arrangements And Business Development Activities -               
                Takeda Collaboration Narrative (Details)                         
48: R38         Collaboration Agreements, In-Licensing              HTML     29K 
                Arrangements And Business Development Activities -               
                GSK (Details)                                                    
49: R39         Collaboration Agreements, In-Licensing              HTML     33K 
                Arrangements And Business Development Activities -               
                Royalty Revenues under the Collaboration Agreement               
                with Genentech (Details)                                         
50: R40         Collaboration Agreements, In-Licensing              HTML     54K 
                Arrangements And Business Development Activities -               
                In-Licensing Collaborations (Details)                            
51: R41         Cash and Investments - Reconciliation of Cash,      HTML     32K 
                Cash Equivalents, and Restricted Cash (Details)                  
52: R42         Cash and Investments - Narrative (Details)          HTML     33K 
53: R43         Cash and Investments - Investments by Security      HTML     71K 
                Type (Details)                                                   
54: R44         Cash and Investments - Fair Value and Gross         HTML     35K 
                Unrealized Losses of Investments                                 
                Available-for-Sale in an Unrealized Loss Position                
                (Details)                                                        
55: R45         Cash and Investments - Fair Value of Cash           HTML     30K 
                Equivalents and Investments by Contractual                       
                Maturity (Details)                                               
56: R46         Fair Value Measurements (Details)                   HTML     69K 
57: R47         Fair Value Measurements - Narratives (Details)      HTML     31K 
58: R48         Inventory (Details)                                 HTML     34K 
59: R49         Stock-Based Compensation - Allocated Employee       HTML     30K 
                Stock-Based Compensation Expense (Details)                       
60: R50         Stock-Based Compensation - Based Compensation       HTML     34K 
                Expense (Details)                                                
61: R51         Stock-Based Compensation - Narrative (Details)      HTML     81K 
62: R52         Stock-Based Compensation - Estimate Grant-Date      HTML     34K 
                Fair Value (Details)                                             
63: R53         Provision For (Benefit From) Income Taxes           HTML     23K 
                (Details)                                                        
64: R54         Net Income (Loss) Per Share - Computation of Basic  HTML     56K 
                and Diluted Net Income Per Share (Details)                       
65: R55         Net Income (Loss) Per Share - Potential Shares of   HTML     26K 
                Common Stock Not Included in the Computation of                  
                Diluted Net Income (Loss) Per Share (Details)                    
67: XML         IDEA XML File -- Filing Summary                      XML    128K 
10: XML         XBRL Instance -- exel-20211001_htm                   XML   1.86M 
66: EXCEL       IDEA Workbook of Financial Reports                  XLSX     83K 
 6: EX-101.CAL  XBRL Calculations -- exel-20211001_cal               XML    157K 
 7: EX-101.DEF  XBRL Definitions -- exel-20211001_def                XML    463K 
 8: EX-101.LAB  XBRL Labels -- exel-20211001_lab                     XML   1.22M 
 9: EX-101.PRE  XBRL Presentations -- exel-20211001_pre              XML    746K 
 5: EX-101.SCH  XBRL Schema -- exel-20211001                         XSD    143K 
68: JSON        XBRL Instance as JSON Data -- MetaLinks              309±   458K 
69: ZIP         XBRL Zipped Folder -- 0000939767-21-000097-xbrl      Zip    344K 


‘EX-101.DEF’   —   XBRL Definitions — exel-20211001_def


This Exhibit is an XBRL XML File.


                                                                                                                                                                                
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2 Previous Filings that this Filing References

  As Of               Filer                 Filing    For·On·As Docs:Size             Issuer                      Filing Agent

 8/05/21  Exelixis, Inc.                    10-Q        7/02/21   71:7.7M
 3/03/21  Exelixis, Inc.                    8-K:3,5,9   2/25/21   13:651K
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Filing Submission 0000939767-21-000097   –   Alternative Formats (Word / Rich Text, HTML, Plain Text, et al.)

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