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Building a Multi-Franchise Oncology Business 43RD ANNUAL J.P . MORGAN HEALTHCARE CONFERENCE JANUARY 13, 2025 Michael M. Morrissey, Ph.D. President and CEO
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Forward-Looking Statements 2 This presentation, including any oral presentation accompanying it, contains forward-looking statements, including, without limitation, statements related to: Exelixis’ plans to build a multi-product, multi-franchise oncology business and to be a market leader in both GU and GI oncology, including expectations for zanzalintinib to surpass cabozantinib in scope and scale; Exelixis’ overall strategy across all business components, including with respect to commercial and regulatory execution and continued growth for its cabozantinib franchise, expansion of the zanzalintinib development program and expectation for multiple data readouts, advancement of early-stage pipeline programs and plans to return value to shareholders through stock repurchase programs; the regulatory review process with respect to Exelixis’ sNDA for cabozantinib in previously treated advanced pNET and advanced epNET, including the Prescription Drug User Fee Act target action date assigned by the FDA; Exelixis’ 2025 financial guidance; potential new market opportunities for CABOMETYX in NET, should Exelixis obtain regulatory approvals for cabozantinib in those indications, including Exelixis’ goal to establish CABOMETYX as the small molecule market leader in NET; the potential of CABOMETYX to generate near-term growth and zanzalintinib’s potential to become Exelixis’ main revenue driver from 2030 onwards; Exelixis’ clinical development plans for, and beliefs regarding the therapeutic potential of, zanzalintinib; the therapeutic and commercial potential of XL309, XB010, XL495 and the rest of the Exelixis pipeline, and Exelixis’ belief that its pipeline could expand its patient impact and drive long- term growth; and Exelixis’ summary of key 2024 corporate objectives. 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 degree of market acceptance of CABOMETYX and other Exelixis products in the indications for which they are approved and in the territories where they are approved, and Exelixis’ and its partners’ ability to obtain or maintain coverage and reimbursement for these products; the effectiveness of CABOMETYX and other Exelixis products in comparison to competing products; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere, including the risk that the FDA may not approve cabozantinib as a treatment for pNET or epNET in a timely fashion, if at all; the level of costs associated with Exelixis’ commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; Exelixis’ ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; the availability of data at the referenced times; the potential failure of cabozantinib, zanzalintinib and other 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 pursuit of regulatory approvals for partnered compounds in new indications, their adherence to their obligations under relevant collaboration agreements and the level of their investment in the resources necessary to complete clinical trials or successfully commercialize partnered compounds in the territories where they are approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib, zanzalintinib and other Exelixis product candidates; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of its products and product candidates; Exelixis’ ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of Exelixis’ marketed products; changes in economic and business conditions; and other factors detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ other future filings with the Securities and Exchange Commission. 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. This presentation includes estimates and projections of Exelixis’ annual U.S. net revenues and its potential market and growth opportunities that relate to or are based on data obtained from third-party sources and Exelixis’ internal research. These data involve a number of assumptions and limitations, and investors are cautioned not to place undue reliance on this information. These and other factors could cause actual results to differ materially from those expressed in these estimates and projections.
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Notes Regarding Preliminary Financial Results 3 This presentation includes Exelixis’ preliminary financial results for the quarter and fiscal year ended January 3, 2025. Exelixis is currently in the process of finalizing its full financial results for the quarter and fiscal year ended January 3, 2025, and the preliminary financial results presented in this presentation are based only upon preliminary information available to Exelixis as of January 12, 2025. Exelixis’ preliminary financial results should not be viewed as a substitute for full audited financial statements prepared in accordance with U.S. GAAP , and undue reliance should not be placed on Exelixis’ preliminary financial results. Exelixis’ independent registered public accounting firm has not audited or reviewed the preliminary financial results included in this presentation or expressed any opinion or other form of assurance on such preliminary financial results. In addition, items or events may be identified or occur after the date of this presentation due to the completion of operational and financial closing procedures, final audit adjustments and other developments may arise that would require Exelixis to make material adjustments to the preliminary financial results included in this presentation. Therefore, the preliminary financial results included in this presentation may differ, perhaps materially, from the financial results that will be reflected in Exelixis’ audited consolidated financial statements for the fiscal year ended January 3, 2025.
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EXEL 2025: Building a Multi-product, Multi-franchise Oncology Business 4 Continued strong cabozantinib performance across all key commercial metrics, with recent milestones driving optimism for the franchise’s revenue outlook into 2030 Zanzalintinib opportunity expected to surpass cabozantinib in scope and scale, and represents important component of mid-/long-term revenue growth Plan to optimize development of early-stage pipeline by rapidly and efficiently profiling compounds and advancing only potential winners into full development Balanced capital allocation strategy: BD activities targeting late-stage clinical assets in GU/GI oncology with potential for clinical and commercial differentiation; execution of stock repurchase program Exelixis aims to be a market leader in both GU and GI oncology BD = business development GU = genitourinary GI = gastrointestinal
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Entering 2025 with Strong Momentum Across All Business Components 5 Commercial and regulatory execution of cabozantinib franchise • Strong financial and commercial performance in 2024 with growth anticipated in 2025 • CABOMETYX® maintained its status as the leading TKI for RCC in the U.S. • Successful defense of cabozantinib IP enabling U.S. franchise revenues into 2030 • Cabozantinib sNDA in NET under regulatory review - PDUFA date of April 3, 2025 Expansion of zanzalintinib development program • Six ongoing or planned pivotal studies across CRC, RCC, HNSCC and NET • Merck collaboration enables cost-sharing clinical development • Multiple clinical data readouts and additional pivotal study initiations anticipated in 2025 Advancement of early-stage pipeline programs • Initiated phase 1 studies for XL309 (USP1i), XB010 (5T4-targeting ADC) and XL495 (PKMYT1i) • Three potential new INDs expected in 2025 Balanced capital allocation strategy • Leveraging strong balance sheet for potential BD opportunities with focus in GU/GI oncology • Returning $1B+ to shareholders through 2023-25 SRPs funded by free cash flows TKI = tyrosine kinase inhibitor RCC = renal cell carcinoma IP = intellectual property sNDA = supplemental New Drug Application NET = neuroendocrine tumors PDUFA = Prescription Drug User Fee Act CRC = colorectal cancer HNSCC = head and neck squamous cell carcinoma USP1i = ubiquitin specific peptidase 1 inhibitor ADC = antibody-drug conjugate PKMYT1i = protein kinase membrane associated tyrosine/threonine 1 inhibitor IND = Investigational New Drug Application BD = business development GU/GI = genitourinary / gastrointestinal SRP = stock repurchase program
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Preliminary Unaudited 2024 Results and 2025 Financial Guidance Fiscal Year 2024 Preliminary Results(1) Fiscal Year 2025 Financial Guidance* (Provided January 12, 2025) Total Revenues $2.165B $2.15B - $2.25B Net Product Revenues $1.805B $1.95B - $2.05B(2) Cost of Goods Sold 4.2% 4% - 5% of net product revenues R&D Expenses $910M $925M - $975M Includes $40M of non-cash stock-based compensation expense SG&A Expenses $495M $475M - $525M Includes $60M of non-cash stock-based compensation expense Effective Tax Rate n/a(3) 21% - 23% Ending Cash and Marketable Securities(4) $1.75B n/p *The financial guidance above reflects U.S. GAAP amount. (1) The fiscal year 2024 preliminary results have not been audited and are subject to change. (2) Exelixis’ 2025 net product revenues guidance range includes impact of a U.S. wholesale acquisition cost increase of 2.8% for CABOMETYX effective January 1, 2025. (3) Preliminary results not yet available. (4) Cash and marketable securities are composed of cash, cash equivalents, and marketable securities. Fiscal year 2025 guidance not provided (n/p). Current 2025 net product and total revenues guidance do not reflect any revenues resulting from a potential U.S. regulatory approval and commercial launch of CABOMETYX (cabozantinib) for the treatment of patients with previously treated advanced neuroendocrine tumors 6
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2024-2025 Stock Repurchase Program Activity (in millions, except per share amounts) 7 Amount Repurchased Shares Repurchased Average Purchase Price per Share Q1 2024 $190.7 8.638 $22.08 Q2 2024 $259.3 11.662 $22.23 Q3 2024 $12.4 0.483 $25.61 Q4 2024 $193.3 5.634 $34.30 Total $655.6 26.417 $24.82 $450M stock repurchase program authorized in January 2024 was completed in Q2 2024 $500M stock repurchase program authorized in August 2024, with $294.4M remaining as of the end of 2024 ~$1.2 billion of stock repurchased since March 2023 at an average pps of $22.90 Amounts in the table may not sum due to rounding. pps = price per share
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CABOMETYX: Striving to Improve the Standard of Care for RCC Patients The #1 prescribed TKI+IO combination • CABOMETYX + nivolumab remains the most prescribed 1L RCC TKI+IO combination therapy for nine consecutive quarters • CABOMETYX market leader in 2L RCC Strong execution and momentum in Q4/FY 2024(1) • Q4’24 U.S. NPR = $509M (7% QoQ and 19% YoY) • FY24 U.S. NPR = $1.8B (11% YoY) • Strong TRx volume growth in Q4’24 of 4% QoQ and 13% YoY • Increasing demand and NPS driven by CABOMETYX + nivolumab in 1L RCC Potential for future CABOMETYX growth driven by NET opportunity • CABINET data, launch strategy and prescriber experience support rapid adoption • Goal to establish CABOMETYX as the small molecule market leader in NET 8 Sources: Internal Exelixis data; IQVIA National Prescription Audit and BrandImpact data through 12/27/2024 RCC = renal cell carcinoma TKI = tyrosine kinase inhibitor IO = immunotherapy 1L = first-line 2L = second-line NPR = net product revenue TRx = total prescriptions NPS = new patient starts NET = neuroendocrine tumors (1) Fiscal year 2024 preliminary results have not been audited and are subject to change. QoQ = Q4’24 vs Q3’24 YoY = compared to the corresponding period in 2023
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CABOMETYX Has Delivered Double Digit Annual Growth since 2020 9 $742 $1,077 $1,401 $1,629 $1,805 $2,000 2020 2021 2022 2023 2024* 2025** Cabozantinib Franchise NPR ($M) *Preliminary unaudited cabozantinib net product revenues **Mid-point of 2025 net product revenues guidance ~170% Growth ‘20A – ’25E CAGR: 22% Robust and continued growth since the 2021 approval of CABOMETYX + nivolumab in 1L RCC ~170% NPR growth from 2020 to 2025 ~11% NPR growth from 2024 to 2025 NPR = net product revenues CAGR = compound annual growth rate 1L = first-line RCC = renal cell carcinoma
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CABOMETYX: Changing the Paradigm of the RCC Treatment Landscape 10 *34 weeks since launch of CABOMETYX in the last week of April 2016 **2024 through 4Q24 (13 weeks) 1,512 1,556 2,013 134 562 1,183 1,646 2,117 3,196 Average Weekly RCC Market TRx 2016* 2020 2024** ~95% Growth in the RCC branded small molecule market since CABOMETYX launch in 2016 ~9x CABO Growth ~2x Market Growth Average Weekly CABOMETYX vs. RCC Market TRx CABOMETYX RCC Branded Small Molecule Competitors 2016* 2024** 31% CAGR ~785% Growth in CABOMETYX TRx since 2016, contributing ~65% of the RCC branded small molecule market growth 134 (8%) 1,183 (37%) Sources: IQVIA data through 12/27/2024 RCC Branded Small Molecule Market defined as Cabometyx, Inlyta, Sutent, Votrient, Lenvima, Fotivda, Welireg METEOR Launch CheckMate -9ER Launch RCC = renal cell carcinoma TRx = total prescriptions CAGR = compound annual growth rate
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Exelixis Aims to Be a Leader in NET Global NET Market Anticipated to Grow to >$4B in Global Revenues by 2030 11 Source: Evaluate Pharma Actual Sales and Consensus Forecast Estimates (August 2024); EXEL Commercial Estimates *Dependent on FDA approval and approved label language/indication. NET = neuroendocrine tumors RCC = renal cell carcinoma CAGR = compound annual growth rate ~$3.7B ~$10B 2016 2023 15% CAGR Global RCC Branded Therapy Market Size Novel, branded therapy launches (IO based regimens, CHECKMATE -9ER, CABOSUN, METEOR) Improved outcomes with longer treatment durations GROWTH DRIVERS ~$2.5B ~$4.6B 2023 2030 9% CAGR Estimated Global NET Branded Therapy Market Size Novel, branded therapy potential launches (novel PRRT, CABINET) Improved outcomes with longer treatment durations RCC provides potential blueprint for developing and growing a branded market Exelixis aspires to become a leader in NET market with CABOMETYX* in near-term and zanzalintinib in 2030+ Indolent nature of NET means more patients have the opportunity to receive more therapies Patients living longer and able to receive more therapies GROWTH DRIVERS IO = immunotherapy PRRT = peptide receptor radionuclide therapy
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Totality of CABINET Data Has Resulted in Favorable NCCN Guidelines Placement 12 Phase 3 CABINET BICR Analysis at ESMO’24 NCCN = National Comprehensive Cancer Network BICR = Blinded Independent Central Review ESMO = European Society for Medical Oncology NEJM = The New England Journal of Medicine KOL = key opinion leader PFS = progression-free survival pNET = pancreatic neuroendocrine tumors epNET = extra-pancreatic NET HR = hazard ratio *Sources: ESMO Congress 2024 data, EXEL Market Research, The New England Journal of Medicine, September 16, 2024 • KOLs find the tripled median PFS in pNET and doubled median PFS in epNET compelling • Subgroup analyses suggest benefits across all clinical subgroups, including primary tumor site, grade and prior anticancer therapy CABINET Data Published in NEJM
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Phase 3 CABINET Study Addresses an Unmet Medical Need with Its Broad Inclusion Criteria across pNET and epNET 13 CABINET was conducted in a contemporary setting and is the first and only phase 3 study to encompass the wide-ranging heterogeneity of NET NET = neuroendocrine tumors pNET = pancreatic NET epNET = extra-pancreatic NET GI = gastrointestinal G2 = intermediate grade NET G3 = high grade NET Pivotal Trial Sites of Origin > 40% G2/G3 Functional Disease >25% Previous LUTATHERAGI Lung Pancreas CABINET (CABOMETYX vs. placebo) Radiant 3 (everolimus vs. placebo) NA Radiant 4 (everolimus vs. placebo) SUN-1111 (sunitinib vs. placebo) Sources: ESMO Congress 2024 data, The New England Journal of Medicine September 16, 2024, Afinitor PI, Sutent PI, NEJM NEJM Feb 2011, Lancet March, 2016
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NET Prescriber Universe Significantly Overlaps with Exelixis’ Current Customers NET Physician Universe Sources: Exelixis Internal Market Research and Internal Field Sizing Data (2024) *Dependent on FDA approval and approved label language/indication ~3,500 Top NET Oncologists ~2.8K Current CABOMETYX Targets NET Oncologists Who Overlap with Current CABOMETYX Targets NET Only Oncologists Potential* Updated CABOMETYX Target Physician Universe Significant Overlap and Experience with Existing CABOMETYX Customers ~80% have prior CABOMETYX Experience ~700 • The target NET physician universe has significant overlap with existing CABOMETYX targets • ~80% of these ~3,500 physicians have prior experience using CABOMETYX in other approved indications • Of the ~700 non-overlapping physicians, ~550 are co-located with existing customers • Exelixis’ GI field force was recently expanded to ensure optimal coverage of these customers while not compromising focus of the GU field team and our core RCC business 14 NET = neuroendocrine tumors RCC = renal cell carcinoma GI = gastrointestinal GU = genitourinary
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NET Market Opportunity is Underappreciated 15 Potential Opportunity in NET** 7% 10% 20%8% 32% 24%26% 51% 52%58% 7% 4% 1L 2L 3L+ SSA Monotherapy Oral Small Molecule Therapies* +/- SSA PRRT +/- SSA Other* Current NET Treatment Landscape 100% 0% NET = neuroendocrine tumors 1L = first-line 2L = second-line 3L = third-line SSA = somatostatin analog SSTR = somatostatin receptor PRRT = peptide receptor radionuclide therapy Amounts in chart may not sum to 100% due to rounding. *Oral small molecule therapies include: sunitinib, everolimus and CAPTEM; Other includes: FOLFOX, clinical trials, etc. ~7,200 ~5,400 ~3,700 2025 Drug Treated Patients* Sources: *Exelixis Internal Market Research (2023 & 2024): Canadian Cancer Society; Cancer.net; Zihan et al. JAMA, 2021; Lung-NET are less likely to be SSTR+ (40-60%), overall NET patients are ~80% SSTR+; Zhang & Kunz, JCO 2021; Haq et al., Best Pract Res Clin Endocrinol Metab, 2023; Olmo-García et al., Al-Toubah et al., J Nucl Med. 2023; Kaemmerer et al., J Clin Endo & Meta, 2015; Assumes contemporary oral oncology pricing for branded drugs applied to small molecule class share; average drug duration estimates based on internal market research (2024) • Small molecule NET market valued ~$1B* in 2025 • Oncologists most commonly prescribe small molecule therapies in 2L and 3L+ settings with significant 1L utilization • Current options lack evidence broadly across key disease characteristics (e.g., site of origin, SSTR / functional status) • Lack of sequencing data across NET landscape • High level of unmet need and desire for treatment options relevant for a broad NET patient population provide compelling potential opportunity **Dependent on FDA approval and approved label language/indication.
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Exelixis Intends to Play a Leadership Role in the Growing NET Market 16 Sources: **Exelixis Internal Market Research (2023 & 2024): Canadian Cancer Society; Cancer.net; Zihan et al. JAMA, 2021; Lung-NET are less likely to be SSTR+ (40-60%), overall NET patients are ~80% SSTR*+; Zhang & Kunz, JCO 2021; Haq et al., Best Pract Res Clin Endocrinol Metab, 2023; Olmo-García et al., Al-Toubah et al., J Nucl Med. 2023; Kaemmerer et al., J Clin Endo & Meta, 2015; Assumes $25K/month pricing for branded drugs with 70% GTN applied to small molecule class share; average drug duration estimates based on internal market research (2024) Significant Potential for Exelixis in NET* NET small molecule market size is estimated to be worth ~$1B** in 2025 • Physicians are excited about CABOMETYX relative to existing small molecule therapies • CABOMETYX would be only branded small molecule option in NET (sunitinib, everolimus, captem) • The opportunity for CABOMETYX will be further elaborated based on the label Zanzalintinib has potential to build on CABOMETYX’s anticipated success in this market • Differentiated trial design with an active comparator – goal to become SoC for NET oral therapies • Potential for earlier lines of therapy and longer treatment duration *Dependent on FDA approval and approved label language/indication NET = neuroendocrine tumors SoC = standard of care
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CABOMETYX Continues to Generate Near-term Growth, while Zanzalintinib Has Potential to Become Main Revenue Driver from 2030+ 17 2 Cabozantinib potential line extensions in NET and CRPC 1 Potential zanzalintinib launch planned per year, starting as early as 2026 (STELLAR-303) 6 Ongoing or 2025-planned zanzalintinib pivotal studies (including 2 Merck-sponsored trials) Building a Best-in-class GU and GI Oncology Company CABOMETYX projected total unadjusted U.S. net product revenues in 2030~$3B Zanzalintinib projected total unadjusted U.S. net product revenues in 2033~$5B NET = neuroendocrine tumors CRPC = castration-resistant prostate cancer GU = genitourinary GI = gastrointestinal
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Zanzalintinib Has the Potential to Significantly Advance Outcomes for Patients with GI, GU, and Other Cancers 18 *Estimated drug-treatable patients, eligible for zanzalintinib treatment Source: Decision Resources Group, EXEL Internal Assumptions (assumes market differentiating data from ongoing trials with label-enabling potential and planned pivotal trials that result in regulatory approvals) HNSCC = head and neck squamous cell carcinoma NET = neuroendocrine tumors RCC = renal cell carcinoma CRC HNSCC NET RCC Total Future Zanzalintinib Addressable Patients* Genitourinary Kidney Gastrointestinal Colorectal, NET Other Tumors Head & neck Approximate Number of Potentially Addressable U.S. Patients in 2033* (in thousands) 305 311 Phase 3 RCC Studies of Zanzalintinib + Belzutifan Ongoing/ Planned Pivotal Studies GI = gastrointestinal GU = genitourinary CRC = colorectal cancer
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Zanzalintinib Has Potential to Establish Exelixis Leadership in GU and GI across Multiple Tumors and Indications 19 *Assumes market differentiating data from ongoing trials with label-enabling potential and planned pivotal trials that result in regulatory approvals. ~45% ~45% ~10%~$5B in 2033 ~90% ~$1.8B in 2024~10% CABOMETYX Projected U.S. Net Product Revenues Zanzalintinib Projected U.S. Unadjusted Net Product Revenues* With investments in NET and CRC, GI tumors are expected to account for nearly half of 2033 zanzalintinib revenues Continued commitment to leadership in GU tumors, with multiple zanzalintinib trials ongoing and planned in RCC Genitourinary (GU) Gastrointestinal (GI) Head & Neck NET = neuroendocrine tumors CRC = colorectal cancer GU = genitourinary GI = gastrointestinal RCC = renal cell carcinoma
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Six Ongoing and 2025-Planned Pivotal Studies Position Zanzalintinib to Drive Revenue in Several High-Unmet Need Tumors 20 Six Ongoing or Planned Zanzalintinib Pivotal Studies in 2025 311 Merck RCC Studies 3L+ = third-line and later 1L = first-line RCC = renal cell carcinoma NET = neuroendocrine tumors pNET = pancreatic NET epNET = extra-pancreatic NET Pivotal Study Arms Setting Gastrointestinal Cancers Genitourinary Cancers Head & Neck Zanza + Atezo Regorafenib 1:1 3L+, non-MSI high, non-dMMR mCRC Advanced NET (pNET & epNET) Zanza + Nivo Sunitinib 2:1 1L, nccRCC: papillary, unclassified, and translocation-associated Zanza + Pembro Pembrolizumab 1:1 PD-L1+ 1L metastatic HNSCC Zanzalintinib + Belzutifan Phase 3 in RCC Study #1 Details TBA Zanzalintinib Everolimus 1:1 TBA = to be announcednccRCC = non-clear cell RCC PD-L1+ = programmed death-ligand 1 positive HNSCC = head and neck squamous cell carcinoma Zanzalintinib + Belzutifan Phase 3 in RCC Study #2 Details TBA 303 304 305 Zanzalintinib clinical development plans build on expertise and data generated from CABOMETYX MSI = microsatellite instability dMMR = mismatch repair deficient mCRC = metastatic colorectal cancer
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STELLAR-303: Potential New Standard of Care in 3L+ mCRC NLM Patients 21 • 3L+ market is fragmented and there is an emerging segmentation of liver metastasis vs. non-liver metastasis (NLM) without clear standard of care • NLM patients represent ~30% of mCRC • High unmet need remains: Current options in NLM offer limited efficacy (mPFS ~3.7 months, mOS ~12 months1) while conferring added toxicity Zanzalintinib Opportunities in 3L+ mCRC • Estimated addressable U.S. patients in 2033 in 3L+ CRC2 • NLM represents approximately ~11,000 addressable U.S. patients 37 thousand LEAP-017 negative for OS endpoint • Pembro + len benefit was limited to patients with NLM in subgroup analysis 2023 2024 2025+ Increasing number of trials reporting data in NLM vs. LM (e.g., Bot/Bal, SUNLIGHT, FRESCO) STELLAR-303: Earliest launch in 2026 • Potential 1st IO + TKI combo in CRC • Potential 1st therapy targeting NLM patients Sources: (1) ARCAD = Aide et Recherche en Cancérologie Digestive; data reflects 2,137 3L+ mCRC patients selected from 4 placebo-controlled randomized trials (CORRECT, RECOURSE, CONCUR, TERRA); (2) DRG drug treatable patients in 2033 3L+ = third-line and later mCRC = metastatic colorectal cancer NLM = non-liver metastasis MSI = microsatellite instability PFS = progression-free survival mPFS = median PFS OS = overall survival mOS = median OS 303 Zanza + Atezo Regorafenib 1:1 3L+, non-MSI high, non-dMMR mCRC 1° EP: OS in NLM patients 2° EP: OS (full ITT), PFS, ORR dMMR = mismatch repair deficient EP = clinical endpoint ITT = intent-to-treat population ORR = objective response rate LM = liver metastasis Bot/Bal = botensilimab and balstilimab IO = immunotherapy TKI = tyrosine kinase inhibitor
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STELLAR-304: First & Only Randomized Phase 3 Study in nccRCC 22 • Non-clear cell renal cell carcinoma (nccRCC) consists of heterogenous histological subtypes, where patient outcomes are generally worse than clear cell RCC (ccRCC) • No clear standard of care given lack of randomized controlled clinical trials to date • Limited data and lack of approved treatments specific to nccRCC: STELLAR-304 first pivotal trial focusing on nccRCC Zanzalintinib Opportunities in 1L nccRCC Ph2 PAPMET shows significant PFS improvement for cabozantinib vs. sunitinib in pRCC • NCCN guidelines recommend cabo +/- nivo as preferred regimen for nccRCC histology Ph2 cabo + nivo demonstrates promising efficacy in most non-clear cell histologies2 • ORR = 48% • mPFS = 13 months • mOS = 28 months STELLAR-304: Primary endpoint PFS is expected to be available in 2H 2025 • Reinforces our leadership in and commitment to RCC 2:1 1L, nccRCC: papillary, unclassified, and translocation-associated Zanza + Nivo Sunitinib 304 2021 2022 2025+ Estimated addressable U.S. patients in 203317 thousand 1) DRG Drug treatable patients in 2033 2) Fitzgerald et al European Urology 2024 1L = first-line nccRCC = non-clear cell renal cell carcinoma pRCC = papillary renal cell carcinoma Dual 1° EP: PFS, ORR EP = clinical endpoint PFS = progression-free survival ORR = objective response rate NCCN = National Comprehensive Cancer Network mPFS = median PFS mOS = median overall survival
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STELLAR-305: Advancing SoC in 1L PD-L1+ HNSCC with a Chemo-Free Option 23 • Majority of the 1L metastatic patients are PD-L1+ (~50-80%1,2) • Significant unmet medical need, despite recent improvements with pembrolizumab +/- chemo (mPFS ~6 mos, mOS ~13 mos1) • Due to the need for aggressive multimodal treatment in earlier stages of disease, metastatic HNSCC patients are typically more frail and susceptible to toxicities3,4, highlighting the need for better tolerated and chemo-free treatment options Zanzalintinib Opportunities in 1L PD-L1+ Metastatic HNSCC Clinical POC established with cabozantinib + pembrolizumab6 • ORR = 54% • mPFS = 14.6 months • mOS = 22.3 months 2022 2023-2024 2025+ LEAP-010 did not meet its OS endpoint7 • High discontinuation rate due to toxicity of lenvatinib reinforces the importance of tolerability Clinical development collaboration with Merck to supply KEYTRUDA for STELLAR-305 STELLAR-305: Ph2/3 gate expected in 2H’25 • Potential 1st immunotherapy + TKI combo and chemo-free option in 1L PD-L1+ HNSCC 1:1 305 PD-L1+ 1L metastatic HNSCC Zanza + Pembro Pembrolizumab 1) Burtness et al., LANCET 2019 2) Qiao et al. Front. Immunol 2020 3) Li, Sig Transduct Target Ther 2023 4) Mascarella, Head Neck 2022 Estimated addressable U.S. patients in 2033515 thousand 5) DRG Drug Treatable Patient 2033; 60% is used as internal assumption for PD-L1+ (CPS ≥ 1) 6) Saba, ASCO 2022 7) Licitra, ASTRO MHNCS 2024 Dual 1° EP: PFS, OS SoC = standard of care 1L = first-line PD-L1+ = programmed cell death ligand 1 positive HNSCC = head and neck squamous cell carcinoma EP = clinical endpoint PFS = progression-free survival mPFS = median PFS OS = overall survival mOS = median OS POC = proof of concept ORR = objective response rate TKI = tyrosine kinase inhibitor
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STELLAR-311: Zanzalintinib Has Potential to Build on CABOMETYX’s Anticipated Success and Become a Leader in NET 24 • High unmet need remains in NET, particularly for high disease burden and symptomatic patients • Potential to be used in earlier lines of therapy, resulting in a longer treatment duration • Addition of cabozantinib to NET NCCN guidelines as preferred/Category 1 regimen1 reinforces the role of TKIs as a mainstay of NET treatment Zanzalintinib Opportunities in NET Ph3 CABINET met its PFS endpoint • First/only phase 3 study to encompass the wide-ranging heterogeneity of NET 2023 2024 2025+ CABINET updated BICR results at ESMO’24 • >3x mPFS benefit in pNET and >2x mPFS benefit in epNET3 • Benefits observed across all clinical subgroups STELLAR-311: expected to initiate in 1H’25 • 1st small molecule in Phase 3 study randomized against active control arm • Establishes Exelixis’ leadership in NET, leveraging expertise & enthusiasm for CABO 311 Zanzalintinib Everolimus 1:1 Advanced NET (pNET & epNET) Estimated addressable U.S. patients in 2033223 thousand 1) NET NCCN Guidelines Version 3.2024; Category 1 recommendation dependent on prior treatment 2) DRG Drug treatable patients in 2033 3) Chan JA et al NEJM 2024 NET = neuroendocrine tumors pNET = pancreatic NET epNET = extra-pancreatic NET NCCN = National Comprehensive Cancer Network TKI = tyrosine kinase inhibitor PFS = progression-free survival BICR = Blinded Independent Central Review ESMO = European Society for Medical Oncology mPFS = median PFS
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Ongoing Expansion of Zanzalintinib Development to Additional Tumors and Settings Represents Significant Incremental Opportunity 25 Current Zanzalintinib Development Opportunities Anticipated to reach ~$5B in total U.S. NPR by 2033 Colorectal Cancer Head & Neck Cancer Renal Cell Carcinoma Future Zanzalintinib Opportunities Expected to Provide Additional Revenues in GU, GI and Other Indications Earlier Lines of Therapy Earlier Stage Disease New Combinations (Internal and External Partnerships) Prostate Cancer Endometrial Cancer Neuroendocrine Tumors Earlier Line/ Stage CRC Zanzalintinib has potential to improve SoC for solid tumor patients across multiple tumors and settings Renal Cell Carcinoma Lung Cancer Hepatocellular Carcinoma Bladder Cancer NPR = net product revenues GU = genitourinary GI = gastrointestinal CRC = colorectal cancer SoC = standards of care
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Exelixis Oncology Pipeline of Small Molecules and Biotherapeutics 26 Pre-IND Phase 1 Phase 1b/2 Pivotal XB628: PD-L1 + NKG2A XL309: USP1 Zanzalintinib: MET/VEGFR/AXL Multiple solid tumors Zanzalintinib: 3L+ CRC XB371: TF-TOPOi XB010: 5T4-MMAE Zanzalintinib: nccRCC XB064: ILT2 XL495: PKMYT1 Zanzalintinib: RCC Zanzalintinib: HNSCC XB033: IL13Rα2-TOPOi ADU-1805: SIRPα Zanzalintinib: NET XB773: DLL3-TOPOi Zanzalintinib: RCC Zanzalintinib: RCC Small Molecule Monoclonal Antibody Antibody-Drug Conjugate Bispecific Antibody Drug Modality Combination Partner PD-(L)1 Novel ICI (e.g., LAG-3) Other (HIF2⍺) MMAE = monomethyl auristatin E TF = tissue factor 3L+ = third-line and later CRC = colorectal cancer PD-(L)1 = programmed death ligand 1 or programmed cell death protein 1 NKG2A = natural killer cell receptor group 2A nccRCC = non-clear cell renal cell carcinoma SIRPα = signal-regulatory protein alpha IL13Rα2 = interleukin 13 receptor alpha 2 HNSCC = head and neck squamous cell carcinoma PKMYT1 = protein kinase membrane associated tyrosine/threonine 1 TOPOi = topoisomerase inhibitor ILT2 = Ig-like transcript 2 ICI = immune checkpoint inhibitor USP1 = ubiquitin specific peptidase 1 HIF2⍺ = hypoxia-inducible factor 2 alpha LAG-3 = lymphocyte-activation gene 3 DLL3 = delta-like ligand 3 NET = neuroendocrine tumors
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Diversified Pipeline of Potentially Best-in-class and/or First-in-class Molecules Could Expand Our Patient Impact and Drive Long-term Growth 27 Drug MOA Best-in- Class First-in- Class GU GI Other Clinical XL309 USP1i ✓ ✓ XB010 5T4-MMAE ADC ✓ ✓ XL495 PKMYT1i ✓ Preclinical XB628 NKG2A x PD-L1 bsAb ✓ ✓ XB064 ILT2 mAb ✓ XB371 TF-TOPOi ADC ✓ • 3 additional internal clinical programs with best- and/or first-in-class potential are in development • 3 preclinical programs bolster innovative biotherapeutics pipeline, including first bispecific program (XB628) • Pipeline offers multiple opportunities to continue to improve standards of care for patients with GU and GI cancers, while also expanding into other tumors • Opportunities to maximize pipeline value with internal combinations Select Exelixis Early-Stage Pipeline Programs MOA = mechanism of action GU = genitourinary GI = gastrointestinal MMAE = monomethyl auristatin E mAb = monoclonal antibody bsAb = bispecific antibody USP1i = ubiquitin-specific peptidase 1 inhibitor PD-L1 = programmed death-ligand 1 NKG2A = natural killer cell receptor group 2A TF = tissue factor TOPOi = topoisomerase inhibitor ILT2 = Ig-like transcript 2 PKMYT1i = protein kinase membrane associated tyrosine/threonine 1 inhibitor ADC = antibody-drug conjugate
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Key 2025 Corporate Objectives Execute on business goals and maintain strong financial performance • Exceeded revenue goals in 2024; guiding to additional growth in 2025, potential upside with NET • Continue prudent expense management • Complete ongoing $500M stock repurchase program Pursue label expansion opportunities for CABOMETYX • Advanced NET (CABINET): PDUFA date of April 3, 2025 • Evaluate timing and finalize plans for potential mCRPC (CONTACT-02) U.S. filing Progress and expand zanzalintinib development program • Multiple clinical data readouts anticipated in STELLAR-303 (CRC) and STELLAR 304 (nccRCC) in 2H’25 • Initiate phase 3 STELLAR-311 in NET in 1H’25 • STELLAR-305 phase 2 data in 2H’25 to inform potential expansion into phase 3 • Merck to initiate two pivotal RCC zanzalintinib + belzutifan studies in 2025 Accelerate the development of phase 1 clinical-stage assets toward full development • XL309 (USP1i): plan to present data from program at a scientific meeting; continue enrollment in phase 1 study • Advance XB010 (5T4-ADC) and XL495 (PKMYT1i) - dose escalation and potential expansion/combination cohorts 28 NET = neuroendocrine tumors CRC = colorectal cancer RCC = renal cell carcinoma PDUFA = Prescription Drug User Fee Act mCRPC = metastatic castration-resistant prostate cancer nccRCC = non-clear cell RCC USP1i = ubiquitin specific peptidase 1 inhibitor ADC = antibody-drug conjugate PKMYT1i = protein kinase membrane associated tyrosine/threonine 1 inhibitor
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Building a Multi-Franchise Oncology Business 43RD ANNUAL J.P . MORGAN HEALTHCARE CONFERENCE JANUARY 13, 2025 Michael M. Morrissey, Ph.D. President and CEO