Rigel Pharmaceuticals : Earnings Presentation FY 2020

March 2021

Forward-Looking Statement

This presentation contains forward-looking statements relating to, among other things, the commercial success of TAVALISSE in the U.S. and TAVLESSE in Europe; Rigel's ability to achieve development, regulatory and commercial milestone payments; as well as tiered royalties; Rigel's expected operating results for the year ending and as of December 31, 2020, including net sales and cash, cash equivalents and short-term investments; expectations related to the market opportunity for fostamatinib as a COVID-19 therapeutic; Rigel's ability to further develop its clinical stage product candidates; and Rigel's partnering efforts and the safety, tolerability, design, timing and results of Rigel's products, product candidates and clinical trials.

Any statements contained in this presentation that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "potential," "may," intends," "expects." and similar expressions are intended to identify these forward-looking statements. These forward-looking statements are based on Rigel's current expectations and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of TAVALISSE; risks that the FDA, EMA or other regulatory authorities may make adverse decisions regarding fostamatinib; risks that TAVALISSE clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that TAVALISSE may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2020. In addition, the COVID-19 pandemic may result in further delays in Rigel's studies, trials and sales, or impact Rigel's ability to obtain supply of TAVALISSE. Rigel does not undertake any obligation to update forward-looking statements and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein.

Rigel Participants

Raul Rodriguez

President & Chief Executive Officer

Dolly Vance

Executive Vice President, Corporate Affairs & General Counsel

Dave Santos

Executive Vice President & Chief Commercial Officer

Wolfgang Dummer, M.D., Ph.D.

Executive Vice President & Chief Medical Officer

Esteban Masuda, Ph.D.

Executive Vice President, Research

Dean Schorno

Executive Vice President & Chief Financial Officer

Grew annual US sales of TAVALISSE to $61.7M in 2020, YoY increase of 41%

Generated analysis and data supporting early-line and long-term use

Expanded global access to TAVALISSE

~$2B2

Progressed Phase 3 enrollment to 66 of 90 patients

Advanced potential first to market therapeutic for wAIHA

Fast Track designation granted by FDA

Potential $1B US3

Started comprehensive clinical program for treatment of COVID-19

Awarded $16.5M from the DOD to support Rigel's Phase 3 trial

Published research supports exploration

>$2B4

MARKET OPPORTUNITY

Entered global collaboration with Lilly for RIP11 inhibitor program

Continued to advance development and assess opportunities for IRAK1/41 program

Substantial

1Investigational compound in this indication and has not been submitted for FDA review. 2Company's internal estimate based on 2018 sales of ITP therapies used for steroid-refractory patients. 3DelveInsight Research "Warm Autoimmune Hemolytic Anemia [wAIHA] - Market Insight, Epidemiology, and Market Forecast". 4Based on published 6.21 hospitalizations for each fatality and assumes at least 72K fatalities in the period from Oct '20 - Dec '21; assumes treatment duration of twelve days per hospitalized patient. Please see slides 39 & 40 for Important Safety Information. Please visitwww.TAVALISSE.com for full prescribing information.

Rigel RIP1 Inhibitor Program

Comprehensive RIP1 Inhibitor Program:

• ! R552, an oral systemic RIP1 inhibitor, which has completed a Phase 1 study

• ! RIP1 inhibitor candidates that cross the blood-brain barrier for CNS diseases

RIP1 inhibitors have broad potential in numerous large indications

Lilly is an ideal partner for Rigel's RIP1 inhibitor program

Global Collaboration with Lilly

• ! Lilly and Rigel to co-develop and commercialize Rigel's RIP1 inhibitor, R5521, for all indications including autoimmune and inflammatory diseases

• ! Lilly will lead the clinical development of brain-penetrating RIP1 inhibitors in CNS diseases

• ! Rigel will receive a $125M upfront cash payment and is eligible to receive up to $835 million in potential milestone payments, as well as tiered royalties

• ! Development costs for R552 will be shared between Lilly and Rigel subject to certain opt-out provisions for Rigel

Kinase inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (cITP) who have had an insufficient response to a previous treatment.

Select Important Safety Information

Adverse Reactions

! Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).

!

Common adverse reactions (!5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.

Please see slides 39 & 40 for Important Safety Information. Please visitwww.TAVALISSE.comfor full prescribing information.

*Bottles shipped to patients and clinics. Please see slides 39 & 40 for Important Safety Information. Please visitwww.TAVALISSE.com for full prescribing information.

81,300 US Adult cITP Patients1

~75% of post-steroid market

44,300 patients actively treated2 ! 24,300 patients are 2L or later

Patient switching creates new patient opportunities

• ! COVID-19 presented challenges to clinicians in starting and switching patients last year

• ! Clinicians anticipate a surge of patients as we return to normal

Sales team leveraging novel MOA, early line data analysis and safety profile in communications

Continuing to publish and collect differentiated evidence

1Symphony Health, PatientSource®, 10 years ending September 2019. 2Internal market research conducted in October 2020. Please see slides 39 & 40 for Important Safety Information. Please visitwww.TAVALISSE.com for full prescribing information

45,000 US Adult wAIHA Patients1

Patients cycle on and off treatment

(Similar to ITP)

No FDA-approved therapy creates a significant unmet medical need

Only product in a Phase 3 pivotal trial provides potential first mover advantage

Fast Track designation granted by FDA

Synergies with ITP to create a highly accretive opportunity

• ! Established commercial infrastructure

• ! Same targeted physicians and product profile

Encouraging response and favorable safety profile in Phase 2 clinical trial2

1 Rigel AIHA Market Assessment - Mar 20, 2018 2ASH 2019 Poster Presentation: Fostamatinib, a Spleen Tyrosine Kinase (SYK) Inhibitor, for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): Results of the Phase 2, Multicenter, Open-Label Study.

Phase 3 Clinical Trial Update

Seeking to Make a Difference in COVID-19

Therapeutic potential of fostamatinib in COVID-191 supported by sound scientific rationale and external research2

Three clinical studies currently enrolling

• ! Rigel-led Phase 3 clinical trial

• ! NIH/NHLBI sponsored Phase 2 clinical trial

• ! Imperial College London sponsored Phase 2 clinical trial

Awarded $16.5M from the DOD to support Rigel's Phase 3 trial

Commercial availability could enable quick access and adoption

Need for therapeutics will persist even with vaccines

Leverage COVID-19 studies to potentially expand development into non-COVID related ARDS

1Investigational compound in this indication and has not been submitted for FDA review 2Rigel internal data

8-POINT ORDINAL SCALE

COVID-19 Trials Address Broad Patient Population

RIGEL

NIH

12345678

NOT HOSPITALIZED

No limitations on activities

Limitation on activities and/or requiring home oxygen

NOT HOSPITALIZED

HOSPITALIZED

Not requiring supplemental oxygen-no longer requires ongoing medical care

Not requiring supplemental oxygen-requiring ongoing medical care (COVID-19 related or otherwise)

HOSPITALIZED

HOSPITALIZED

Requiring supplemental oxygen

HOSPITALIZED

On noninvasive ventilation or high-flow oxygen devices

HOSPITALIZED

On invasive mechanical ventilation or extracorporeal membrane oxygenation

DEATH

NIH/NHLBI1 Phase 2 Clinical Trial Design

18 1Conducted at NIH Clinical Center and Inova Fairfax Hospital. 2Standard of care includes any treatments currently in use to treat the underlying disease, or comorbidities associated with COVID-19 (eg, remdesivir).

Stage 1: 57 patients/armStage 2: 95 patients/arm

Primary Endpoints:

! Reduce proportion of hospitalizedpatients progressing from mild to severe COVID-19 pneumonia

Secondary Endpoints: ! Multiple secondary measures designed to assess resolution of respiratory failure within 14 days

Enrollment: ! 106 patients enrolled as of March 1

Fostamatinib (150mg 2x daily for 14 days) + Standard of Care1

Ruxolitinib (2x daily for 14 days) + Standard of Care1

Standard of Care1 (for 14 days)

19 1Standard of care includes any treatments currently in use to treat the underlying disease, or comorbidities associated with COVID-19 (eg, dexamethasone).

Rigel Phase 3 Clinical Trial Design

Primary Endpoints:

ARM 1

! Progression to severe/critical disease within 29 days of first dose of study treatment

Secondary Endpoints:

~154 patients/arm

! Multiple secondary measures designed to assess patient improvement from severe disease and duration of hospitalization

ARM 2

Study could expand label to include hospitalized COVID-19 patients

Fostamatinib (150 mg 2x daily for 14 days) + Standard of Care1

Placebo (Twice daily for 14 days) + Standard of Care1

1Standard of care includes any treatments currently in use to treat the underlying disease, or comorbidities associated with COVID-19 (eg, remdesivir).

Esteban Masuda, Ph.D.

Sound Scientific Rationale to Explore SYK-Inhibition

1Investigational compound in this indication and has not been submitted for FDA review 2Fu Y. et al. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virologica Sinica. March 3, 2020 3Nadeem A. et al. Inhibition of spleen tyrosine kinase signaling protects against acute lung injury through blockade of NADPH oxidase and IL-17A in neutrophils and !" T cells respectively in mice. International Immunopharmacology 68 (2019) 39-47.

Sound Scientific Rationale to Explore SYK-Inhibition

NETosis is a form of cell death experienced by COVID-19 patients Fostamatinib is shown to counteract NETosis in plasma of COVID-19 patients4

1Investigational compound in this indication and has not been submitted for FDA review 2Fu Y. et al. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virologica Sinica. March 3, 2020 3Nadeem A. et al. Inhibition of spleen tyrosine kinase signaling protects against acute lung injury through blockade of NADPH oxidase and IL-17A in neutrophils and !" T cells respectively in mice. International Immunopharmacology 68 (2019) 39-47.

Immune Complexes (Fc!R-mediated) and DAMPs (CLR/ TLR-mediated) Induction of NETosis of Neutrophils1

NETosis is Postulated as a Key Pathologic Mechanism Behind Tissue Damage and Coagulopathy in COVID-191

Markers of NETosis are elevated in the circulation during severe COVID-192

1Meaghan E Colling and Yogendra Kanthi - COVID-19-associated coagulopathy: An exploration of mechanisms - Vascular Medicine 2020, Vol. 25(5) 471-478 2M. Leppkes et al- Vascular occlusion by neutrophil extracellular traps in COVID-19 / EBioMedicine 58 (2020) 102925

R406 Inhibits NETosis Induced by Plasma from Severely Ill COVID-191 Patients in Published NIH Study2

1Investigational compound in this indication and has not been submitted for FDA review 2Strich JR, et al. Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic - J Infect Dis. December 2020.

HIT-like Disease in Severe COVID-19 Patients is a Sign of Activated Platelets and Neutrophils 1, 2, 3, 4

Heparin-induced Thrombocytopenia

Fc!RIIA Syk

Fc!RIIA

Taisheng Li, Hongzhou Lu & Wenhong Zhang. (2020), 9:1, 687-690

Ling Lin et al. Emerg Microbes Infect. 2020 Mar 20:1-14.

Natalie S Evans et al. Vascular Medicine 2017, Vol. 22(4) 353- 355

Thrombosis

Thrombosis

Nakamura Y. et al. Case Rep Vasc Med. 2015; 2015: 383104

1 Li T, Lu H, Zhang W. Clinical observation and management of COVID-19 patients. Emerg Microbes Infect. 2020 Dec;9(1):687-690 2 Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020 Dec;9(1):727-732. 3 Evans NS, Gomes M. Heparin-induced thrombocytopenia (HIT). Vasc Med. 2017 Aug;22(4):353-355. 4 Nakamura Y, et al. Peripheral Thrombosis and Necrosis after Minimally Invasive Redo Mitral Valve Replacement due to Unknown Etiology: Difficult Diagnosis of Heparin Induced Thrombocytopenia. Case Rep Vasc Med. 2015;2015:383104.

Fostamatinib Potently Inhibits Platelet Aggregation1

Dose-response to R406 of washed platelets stimulated via Fc!RIIA clustering

ATP secretion and aggregation were assessed in parallel using lumi-aggregometry

1T. Lhermusier et al. J Thromb Haemost 2011; 9: 2067-76

Fostamatinib has the Potential to Inhibit Thrombosis Without Affecting Normal Hemostasis1

1N. Cooper, et al - Immune Thrombocytopenia Treatment with Fostamatinib, a Spleen Tyrosine Kinase Inhibitor: Reducing the Risk of Thrombosis - ISTH 2020 Virtual Congress- Abstract PB1356

SYK-mediated pro-inflammatory and pro-thrombotic pathway in the immune

system

Low Incidence of Thrombotic Events in Fostamatinib-Treated Patients vs TPO-RA1

• ! A decreased incidence of thrombosis was observed in the Phase 3 program, which includes up to 5 years of fostamatinib treatment

  • ! 1 event (0.7%) in 229 patient-years

  • ! Transient ischemic event which resolved

• ! Similar programs (ITP Phase 3 plus extension) of the 3 TPO-RAs showed thrombosis in:

  • ! 0 to 9.4% of patients in studies up to 7 months in duration

  • ! 2.6% to 8.9% in patients in studies of 2-8 years' duration

• ! Difference was not due to a selective difference in entry criteria (all studies excluded patients with history of coagulopathy or recent cardiovascular / thrombotic events)

1Ivy Altomare, MD, et al - Blood (2019) 134 (Supplement_1): 4889https://doi.org/10.1182/blood-2019-126558

Continue to Advance Development of IRAK1/4

Attractive opportunities in Heme/Onc and rare immunology diseases that align with Rigel's development strategy

R835 is a dual inhibitor of IRAK1 and IRAK4

!

Shown preclinically to block inflammatory cytokine production in response to TLR and IL-1R family signaling

In an LPS Challenge Proof-of-Mechanism (PoM) study, with human healthy volunteers, R835 profoundly inhibited inflammatory cytokine production2

Placebo Group

IRAK 1/4 Inhibitor Proof-of-Mechanism Study in Humans2

• ! LPS administered i.v. to trigger a proinflammatory response (n=8/group)

• ! Subjects administered R835 showed profound inhibition of cytokine (e.g. TNF! & IL6) production

cytokineconcentration

Individual profileMean profile

Foldovernormallevel

Strong Rationale for Targeting IRAK signaling in MDS

HAI-QING YANG. EXPERIMENTAL AND THERAPEUTICGañán-Gómez et al Leukemia (2015) 1458 - 1469

MEDICINE 9 2396 : 2394-2400, 2015

Dean Schorno

Q4 & YE 2020 Financial Highlights

! Net product sales:

• ! $17.8M in Q4 '20

• ! $61.7M in FY '20

• ! $119.4M since launch

! Total Bottles shipped: ! 1,899 in Q4 '20

!

6,651 in FY '20

! Q4 '20 Bottles: ! 1,725 shipped to patients & clinics

!

174 bottles remained in distribution channels1

1984 total bottles remained in distribution channels as of December 31, 2020.

Q1 '19

Q2 '19

Q3 '19

Q4 '19

Q1 '20

Q2 '20

Q3 '20

Q4 '20

Q4 2020 Financial Results

(In thousands, except for per share amounts)

3 Months Ended December 31, 2020 2019

Revenues

Net Product Sales

Contract revenues from collaborations

Total revenuesYear Ended December 31, 2020 2019

$

17,753 697 18,450

$

• 13,829 $ 1,571 15,400

108,621

59,288

Costs and expenses:

Cost of product sales

321

178

895 906

Research and development

15,138

14,247

60,101 52,885

21,818

18,312

76,598 74,588

Selling, general and administrative Total costs and expenses

Loss from operations

Interest income!

Interest expense

19 ( 429 )

464 ( 327 )

582 ( 1,353 )

2,532

37,277 ( 18,827 )

32,737( 17,337 )

Net loss

( 19,237 ) $

$ $

( 17,200 )$

( 29,744 ) $

Net loss per share, basic and diluted

( 0.11 ) $

( 0.10 )$

( 0.18 ) $

( 0.40 )

Weighted average shares used in computing net loss per share, basic and diluted

169,039

167,619

168,754

167,400

Please see slides 39 & 40 for Important Safety Information. Please visitwww.TAVALISSE.com for full prescribing information.

61,696 $ 43,772

46,925 15,516

! Contract revenues of $697K, consisting of $500K from Grifols for commercialization in additional territories and $197K for performance of R&D services pursuant to collaboration with Grifols.

137,594 ( 28,973 )

128,379 ( 69,091 )

( 335 ) ( 66,894 )

! Cash & short-term investment balance totaled $57.3M as of December 31, 2020

Continue to educate on the benefits of early-line useAccelerate TAVALISSE sales with increased interactions as pandemic conditions normalize

Support existing collaborations to expand global access

Leverage 90 sites in 22 countries to complete Phase 3 enrollment

Advance potential first to market therapeutic for wAIHA

~$2B2

Potential $1B US3

Topline results from NIH Phase 2 expected in April '21

Complete enrollment and generate topline results from Rigel Phase 3 trial

Apply for Emergency Use Authorization, if supported by clinical data

>$2B4

MARKET OPPORTUNITY

Support RIP11 collaboration in immune and neurodegenerative diseases

Pursue IRAK1/41 in heme/onc and rare immune diseases

Substantial

1Investigational compound in this indication and has not been submitted for FDA review. 2Company's internal estimate based on 2018 sales of ITP therapies used for steroid-refractory patients. 3DelveInsight Research "Warm Autoimmune Hemolytic Anemia [wAIHA] - Market Insight, Epidemiology, and Market Forecast". 4Based on published 6.21 hospitalizations for each fatality and assumes at least 72K fatalities in the period from Oct '20 - Dec '21; assumes treatment duration of twelve days per hospitalized patient. Please see slides 39 & 40 for Important Safety Information. Please visitwww.TAVALISSE.com for full prescribing information.

Indication and Important Safety Information

Indication

TAVALISSE® (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information

Warnings and Precautions

• • Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.

• • Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.

• • Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (!Grade 3), interrupt, reduce dose or discontinue TAVALISSE.

• • Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.

• • TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.

Important Safety Information (cont.)

Drug Interactions

• • Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.

• • It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.

• • Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.

• • Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.

Adverse Reactions

• • Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).

• • Common adverse reactions (!5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.

Please seehttp://www.tavalisse.com/ for full Prescribing Information

To report side effects of prescription drugs to the FDA, visithttp://www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088)