Exelixis : William Blair Biotech Focus Conference Presentation

Building a Differentiated

Next-Generation Pipeline

in Oncology

Peter Lamb, Ph.D.

EVP, Scientific Strategy and CSO

William Blair Biotech Focus Conference

July 15, 2021

Safe Harbor Statement

This presentation, including any oral presentation accompanying it, contains forward-looking statements, including, without limitation, statements related to: potential discovery, clinical and regulatory milestones for Exelixis in 2021, including potential regulatory pathways for cabozantinib based on COSMIC-312 and COSMIC-021 clinical data, potential pivotal trials for XL092 and moving small molecule and biologics discovery programs towards development candidate status; Exelixis' strategy to build a robust and diverse oncology pipeline through discovery and collaboration efforts, and targeting patient populations with significant unmet needs; Exelixis' potential future financial and other obligations under its various collaboration agreements; Exelixis' plans to utilize its various partnered programs to expand its small molecule capabilities and develop next-generation ADCs, including the opportunity to improve the therapeutic index of mAb-based therapeutics and broaden the list of potential mAb cell surface targets; Exelixis' development plans for XL102 and XB002; Exelixis' belief that XL102 has the potential to be a best-in-class therapeutic agent; Exelixis' belief that its pipeline may yield one additional IND in 2021, as well as multiple INDs and DCs in the coming years; and Exelixis' plans to augment its pipeline through BD efforts. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the continuing COVID-19 pandemic and its impact on Exelixis' clinical trial and drug discovery activities; the level of costs associated with Exelixis' commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; the potential failure of Exelixis' product candidates, both alone and in combination with other therapies, to demonstrate safety and/or efficacy in clinical testing; uncertainties inherent in the drug discovery and product development process; Exelixis' dependence on its relationships with its collaboration partners, including their adherence to their obligations under relevant collaboration agreements and the level of their assistance to Exelixis in completing clinical trials, pursuing regulatory approvals or successfully commercializing partnered compounds in the territories where they may be approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' and its partners' continuing compliance with applicable legal and regulatory requirements; Exelixis' dependence on third-party vendors for the development, manufacture and supply of its product candidates; Exelixis' and its partners' ability to protect their respective intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting Exelixis and its product pipeline discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 6, 2021, and in Exelixis' future filings with the SEC. All forward- looking statements in this presentation are based on information available to Exelixis as of the date of this presentation, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

1

Executing Towards Our Goal of Becoming a Multi-Product Oncology Company

Commercial success with CABOMETYX® franchise

• Currently the #1 TKI in both RCC and 2L HCC; only single agent with OS benefit in both indications
• >$1B in cabozantinib global net revenue (2019, 2020)*; approved in more than 50 countries
• Successful launch of CABOMETYX and OPDIVO® combination in 1L RCC in Jan. 2021

Robust clinical and regulatory activity

• COSMIC-311/DTCdata presented at ASCO'21; sNDA submitted to the FDA
• Clinical data readouts from COSMIC-312/1L HCC and COSMIC-021 Cohort 6/CRPC; plan to discuss next steps toward potential regulatory path with the FDA
• Rapid development of XL092 as a single agent and in combination regimens, with potential to initiate pivotal trials this year
• Phase 1 trials for XL102 (CDK7 inhibitor) and XB002 (TF-targeting ADC) underway

Broad and deep early pipeline across small molecules and biologics

• Proven history of drug discovery and expansive ~4.6M in-house compound library
• Small molecule collaborations with Aurigene and StemSynergy to in-license novel targets
• Seven biologics collaborations to complement small molecule discovery efforts

	1L	= first-line	OS = overall survival	CDK7 = cyclin-dependent kinase 7
	2L	= second-line	DTC = differentiated thyroid cancer	TF = tissue factor
2	TKI = tyrosine kinase inhibitor	sNDA = supplemental New Drug Application	ADC = antibody-drug conjugate	*Includes ex-U.S. revenues from partners Ipsen and Takeda
RCC = renal cell carcinoma	FDA = U.S. Food and Drug Administration	CRPC = castration-resistant prostate cancer

HCC = hepatocellular carcinoma

A Strong Network of Clinical and Pipeline Collaborations to Advance the Next Wave of Our Small Molecule and Biologic Therapeutics

	Commercial Partnerships				Clinical Collaborations				Pipeline Expansion

Cooperative Group

ISTs

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Building a Robust and Diverse Oncology Pipeline Through Discovery and Collaboration Efforts

Strategy	Key Activities
Investment to expand	Ongoing pivotal trials
CABOMETYX indications
Target novel / promising MOAs	XL092, XL102, XB002
with next generation approaches	and others
Broaden discovery capabilities	In-licensing biologics capabilities to
beyond small molecules	build next-generation ADC platform

	MOAs		Modalities
▪	Tyrosine kinases	▪	Small Molecules
▪	Tissue factor	▪	Bispecifics
▪	CDK7	▪	ADCs

• Others

	MOA = mechanisms of action
4	CDK7 = cyclin-dependent kinase 7
ADC = antibody-drug conjugate