We caution you that this presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of ope

Erasca R&D Day September 2022

We caution you that this presentation

contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, research and

development plans, the anticipated timing, costs, design and conduct of our ongoing and planned preclinical studies and clinical trials for our product candidates, the potential benefits from our current or future arrangements with third parties,

the timing and likelihood of success of our plans and objectives, and future results of anticipated product development efforts, are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as

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regarded as a representation by us that any of our plans will be achieved. Actual results may differ from those set forth in this presentation due to the risks and uncertainties inherent in our business, including, without limitation: our approach

to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; we are early in our development efforts and have only three product candidates in early clinical

development and all of our other development efforts are in the preclinical or development stage; the retrospective analysis of pooled data covers multiple clinical trials with different designs, inclusion criteria, and dosing regimens, which cannot

be directly compared, and therefore may not be a reliable indicator of efficacy and safety data; interim results of clinical trials are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as

patient enrollment continues, following more comprehensive reviews of the data and more patient data become available; potential delays in the commencement, enrollment, and completion of clinical trials and preclinical studies; our dependence on

third parties in connection with manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or

commercialization, or may result in recalls or product liability claims; unfavorable results from preclinical studies or clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results;

the inability to realize any benefits from our current licenses and acquisitions and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; regulatory developments in the United

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financial condition and stock price; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our annual report on Form 10-K for the year ended

December 31, 2021, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to

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high degree of uncertainty and risk. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us. Disclaimer: Forward looking statements and market data

Company Overview Erasca pipeline and

drug development strategy Key scientific hypotheses and supportive preclinical data Dr. David Hong, MD Anderson Cancer Center Discussant Future directions Key milestones and clinical trial readouts Closing Remarks Q&A Session ERAS-007 / ERAS-601

Preliminary Results Retrospective pooled efficacy analysis Preliminary safety and pharmacokinetic assessment Clinical development plan for combinations Erasca R&D Day Agenda

* Post-Osimertinib resistant population

shown for EGFRm NSCLC except for SCLC transformation ** Co-occurring activating MAPK pathway alterations exclude EGFR overexpression Source: SEER database (2020), ECIS database (2020), GLOBOCAN database (2020), The AACR Project GENIE Consortium

version 8.1 (2020), TCGA Research Network: https://www.cancer.gov/tcga, Tyner JW et al. (2018) PMID: 30333627, Brenner CW et al (2013) PMID: 24120142, Chen J et al. (2020) PMID: 32015526, and Ostrom QT, et al. (2020) PMID: 33123732 New cases

estimated worldwide per annum (thousands; numbers may not add up due to rounding) Blue ocean opportunities Red ocean opportunities Alterations GBM HNSCC NSCLC CRC Melanoma PDAC Other solid tumors AML US EU ROW Global EGFR*/FLT3 125 513 184 338 - - -

61 82 222 917 1,220 NF1 25 58 98 35 33 1.9 434 3.2 75 159 453 687 KRAS G12C - 2.8 240 57 - 5.0 45 0.1 36 82 232 350 KRAS G12D 0.2 4.7 68 238 0.5 178 200 1.2 65 171 456 692 Other KRAS 0.4 9.4 183 465 1.2 242 326 3.5 114 299 817 1,230 NRAS 0.5 8.4

11.7 72 71 1.0 116 13.8 42 82 170 295 HRAS 0.2 45 7.8 0.4 3.0 0.2 57 - 11 24 80 114 BRAF V600E/K 2 1.9 23 180 93 1.4 158 0.4 63 127 271 461 BRAF Class 2 0.4 3.8 17.6 6.9 5.3 0.5 58 - 10.8 23.1 58 92 BRAF Class 3 0.1 0.9 11.7 16.8 2.5 - 29 0.2 6.1

14.8 40 61 Other BRAF - - 3.9 - 1.9 0.3 0.5 - 0.7 1.0 4.9 6.6 MEK 0.2 1.9 11.7 8.8 4.6 0.2 22 - 5 11 33 50 Co-occurring activating MAPK pathway alterations** 1.4 10.3 62 59 37 7.1 84 3.0 33 69 162 264 US 12 29 93 114 77 51 153 11 542 EU 34 76 194

398 116 124 324 18 1,285 Rest of World 109 555 635 964 60 264 1,053 57 3,696 Global 155 660 923 1,476 253 438 1,530 86 5,522 ~5.5m lives at stake annually worldwide with RAS/MAPK pathway alterations Over 70% of unmet needs are

"Blue Oceans" with no approved targeted therapies

Erasca's tissue specific and

tissue agnostic trials target multiple indications New cases estimated worldwide per annum (thousands; numbers may not add up due to rounding) Blue ocean opportunities Red ocean opportunities Alterations GBM HNSCC NSCLC CRC Melanoma PDAC Other solid

tumors AML US EU ROW Global EGFR*/FLT3 125 513 184 338 - - - 61 82 222 917 1,220 NF1 25 58 98 35 33 1.9 434 3.2 75 159 453 687 KRAS G12C - 2.8 240 57 - 5.0 45 0.1 36 82 232 350 KRAS G12D 0.2 4.7 68 238 0.5 178 200 1.2 65 171 456 692 Other KRAS 0.4

9.4 183 465 1.2 242 326 3.5 114 299 817 1,230 NRAS 0.5 8.4 11.7 72 71 1.0 116 13.8 42 82 170 295 HRAS 0.2 45 7.8 0.4 3.0 0.2 57 - 11 24 80 114 BRAF V600E/K 2 1.9 23 180 93 1.4 158 0.4 63 127 271 461 BRAF Class 2 0.4 3.8 17.6 6.9 5.3 0.5 58 - 10.8

23.1 58 92 BRAF Class 3 0.1 0.9 11.7 16.8 2.5 - 29 0.2 6.1 14.8 40 61 Other BRAF - - 3.9 - 1.9 0.3 0.5 - 0.7 1.0 4.9 6.6 MEK 0.2 1.9 11.7 8.8 4.6 0.2 22 - 5 11 33 50 Co-occurring activating MAPK pathway alterations** 1.4 10.3 62 59 37 7.1 84 3.0 33

69 162 264 US 12 29 93 114 77 51 153 11 542 EU 34 76 194 398 116 124 324 18 1,285 Rest of World 109 555 635 964 60 264 1,053 57 3,696 Global 155 660 923 1,476 253 438 1,530 86 5,522 * Post-Osimertinib resistant population shown for

EGFRm NSCLC except for SCLC transformation ** Co-occurring activating MAPK pathway alterations exclude EGFR overexpression 1 Triple wildtype CRC is KRASwt, NRASwt, and BRAFwt Source: SEER database (2020), ECIS database (2020), GLOBOCAN database

(2020), The AACR Project GENIE Consortium version 8.1 (2020), TCGA Research Network: https://www.cancer.gov/tcga, Tyner JW et al. (2018) PMID: 30333627, Brenner CW et al (2013) PMID: 24120142, Chen J et al. (2020) PMID: 32015526, and Ostrom QT, et

al. (2020) PMID: 33123732 184 240 72 180 465 125 238 242 178 HERKULES-3 007 + palbociclib HERKULES-3 007 + encorafenib & cetuximab (EC) HERKULES-1 & FLAGSHP-1 ERAS-007 + ERAS-601 (our first MAPKlamp); 601 + cetuximab (triple WT CRC1 and HPV-

HNSCC) HERKULES-2 007 + osimertinib THUNDERBBOLT-1 801 HERKULES-3 007 + palbociclib HERKULES-2 007 or 601 + sotorasib

Erasca's clinical development

plan generates multiple ways to win for patients 1 Currently approved standard of care Indication Benchmark1 Regimen tested Erasca trial(s) HERKULES-2 Sub-study 1 EGFRm NSCLC post-osi ERAS-007 + osimertinib ORR 29%, mDOR 4.2 mos. HERKULES-3

Sub-study 1 BRAFm CRC EC-na ve ERAS-007 + encorafenib + cetuximab ORR 20%, mDOR 6.1 mos. HERKULES-3 Sub-study 1 BRAFm CRC EC-treated ERAS-007 + encorafenib + cetuximab ORR ~2%, mDOR NA HERKULES-3 Sub-study 2 KRASm/ NRASm CRC ERAS-007 +

palbociclib ORR ~2%, mDOR NA FLAGSHP-1 KRASwt/ NRASwt/ BRAFwt 3L CRC ERAS-601 + cetuximab ORR 20%, mDOR 5.4 mos. THUND- ERBBOLT-1 EGFR altered rGBM ERAS-801 monotherapy ORR 26%, mDOR 4.2 mos. HERKULES-2 Sub-study 2 KRAS G12C NSCLC ERAS-007 or

ERAS-601 + sotorasib ORR 36%, mDOR 10 mos. ERAS-3490 AURORAS-1 (planned) HERKULES-1 RAS/MAPK altered solid tumors ERAS-007 + ERAS-601 (our first MAPKlamp) SOC is largely chemo ERAS-007 (alternative schedules) ERAS-601 (alternative schedules)

FLAGSHP-1 100% of CRC FLAGSHP-1 HPV-negative HNSCC ERAS-601 + cetuximab ORR 13%, mDOR 5.8 mos.

Are there more responsive subsets

within the Blue Ocean where promising combination approaches can be particularly effective? ? Key scientific hypotheses and supportive preclinical data

Reminder: ERAS-007 & ERAS-601

target key downstream and upstream RAS/MAPK nodes P P MAPK pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK ERK RAS-GDP EGFR/ FLT3 Other RTKS MYC GEF ERAS-601 ERAS-007 SU2C = Stand Up To Cancer Potent, selective, orally bioavailable SHP2

inhibitor in clinical development in FLAGSHP-1 and HERKULES-2 Potent, selective, orally bioavailable ERK inhibitor in clinical development in HERKULES-1, -2, -3 and SU2C

ERK inhibition with CDK4/6 or SHP2

inhibition offers two compelling approaches to target solid tumors with MAPK pathway alterations P P MAPK pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK ERK RAS-GDP EGFR/ FLT3 Other RTKS MYC GEF Scientific Hypothesis #1: Dual inhibition

of RAS/MAPK and the cell cycle pathways in KRASm/NRASm CRC and KRASm PDAC Enhance tumor cell killing due to deeper inhibition of cell cycle progression and cell growth Overcome compensatory reactivation of the RAS/MAPK pathway ERAS-601 ERAS-007

CDK4/6 CDK4/6 inhibitor ERAS-007 + ERAS-601 "MAPKlamp" Scientific Hypothesis #2: Simultaneous inhibition of upstream and downstream RAS/MAPK pathway nodes Induce stronger pathway suppression and tumor cell killing than either agent alone

Overcome compensatory reactivation of the RAS/MAPK pathway ERAS-007 ERAS-007 + palbociclib

Dual inhibition of cell cycle and

MAPK pathways enhanced tumor shrinkage in PDX models of KRAS/NRAS mutant CRC Modified from AACR 2021; Courtesy of Scott Kopetz, MD, PhD (MD Anderson Cancer Center) Regimen: Vehicle Palbociclib100 mpk QD Trametinib0.25 mpk QD Combo100/0.25 mpk QD

C1047 KRas G12V B8093 NRas Q61K C1035 KRas G12V C1012 KRas A146V B1008 KRas G12D C0997 NRas Q61K F3008 KRas G12C C1151 KRas A146T C1138 KRas G13D B1011 KRas A146D Tumor volume change (%) Treatment time (days) Inhibition of MEK and CDK4/6 represented

highly active combination regimen in vivo

ERK directly phosphorylates the p90

ribosomal S6 kinase protein (RSK) so RSK phosphorylation (P-RSK) serves as a biomarker of ERK and ultimately RAS/MAPK pathway activity Source: Unpublished data ATP-competitive ERK inhibitors were more robust in shutting down RAS/MAPK pathway

reactivation than allosteric MEK inhibitors; ERAS-007 was most robust SW1463 (KRAS G12C CRC) Selumetinib (1 M) Binimetinib (1 M) SW1463 (KRAS G12C CRC) Trametinib (30 nM) Ulixertinib (1 M) ERAS-007 (1 M) a a P MEK P ERK RSK P

ERAS-007 + palbociclib enhanced

tumor growth inhibition (TGI) in KRASm CRC and PDAC models Combination was tolerated in mice (e.g., no dose holidays, deaths, or euthanizations) ERAS-007 and palbociclib were dosed orally and continuously TGI in KRAS G13D CRC CDX LoVo TGI in KRAS

G12D PDAC PDX PAN026

Scientific Hypothesis #2:

"MAPKlamp" inhibition of upstream and downstream RAS/MAPK pathway nodes has potential for deeper, more durable responses P P MAPK pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK ERK RAS-GDP EGFR/ FLT3 Other RTKS MYC GEF

ERAS-601 ERAS-007 + ERAS-601 "MAPKlamp" Scientific Hypothesis #2: Simultaneous inhibition of upstream and downstream RAS/MAPK pathway nodes Induce stronger pathway suppression and tumor cell killing than either agent alone Overcome

compensatory reactivation of the RAS/MAPK pathway ERAS-007

ERAS-007 + ERAS-601 MAPKlamp showed

increased in vivo tumor growth inhibition in two KRAS mutant NSCLC CDX models MAPKlamp combination showed activity in both models and was tolerated in mice (e.g., no dose holidays, deaths, or euthanizations) ERAS-007 and ERAS-601 were dosed orally

and continuously TGI in KRAS G12A NSCLC CDX NCI-H2009 TGI in KRAS G12V NSCLC CDX NCI-H441

ERAS-007 + ERAS-601 MAPKlamp showed

increased in vivo tumor growth inhibition in two KRAS mutant PDAC PDX models MAPKlamp combination showed activity in both models and was tolerated in mice (e.g., no dose holidays, deaths, or euthanizations) ERAS-007 and ERAS-601 were dosed orally

and continuously TGI in KRAS G12D PDAC PDX PAN031 TGI in KRAS G12D PDAC PDX PAN092

ERAS-007 + ERAS-601 MAPKlamp showed

consistent combination activity in BRAF class 3 models that had differing sensitivities to single agents MAPKlamp combination showed activity in both models and was tolerated in mice (e.g., no dose holidays, deaths, or euthanizations) ERAS-601

showed regression as a monotherapy in NCI-H508 while ERAS-007 showed regression as a monotherapy in LUN023 ERAS-007 and ERAS-601 were dosed orally and continuously TGI in BRAF Class 3 NSCLC CDX NCI-H508 TGI in BRAF Class 3 NSCLC PDX

ERAS-007 + ERAS-601 MAPKlamp showed

promising combination activity in two NF1 loss of function (LoF) models MAPKlamp combination showed activity in both models and was tolerated in mice (e.g., no dose holidays, deaths, or euthanizations) ERAS-007 and ERAS-601 were dosed orally and

continuously TGI in NF1 LoF melanoma CDX MeWo TGI in NF1 LoF NSCLC NCI-H1838

Are there more responsive subsets

within the Blue Ocean where ERK + cell cycle or ERK + SHP2 inhibition can be particularly effective? ? Preliminary clinical data

CRC Segmentation framework to

identify more responsive subsets within the Blue Ocean for prioritized combination development Non-CRC Evaluation of combinations addressing these mechanisms is ongoing in HERKULES-3 (and combination addressing triple wildtype CRC is ongoing in

FLAGSHP-1) Phase 1/1b monotherapy responses used to inform prioritized combination development "Blue Ocean indications" of solid tumors with RAS/MAPK alterations and no approved targeted therapies Less sensitive to monotherapy inhibition

due to more RAS/MAPK reactivation and bypass pathway activation

CRC Segmentation framework to

identify more responsive subsets within the Blue Ocean for prioritized combination development Non-CRC Evaluation of combinations addressing these mechanisms is ongoing in HERKULES-3 (and combination addressing triple wildtype CRC is ongoing in

FLAGSHP-1) Targetable, more responsive subset of patients prioritized for combination development "Blue Ocean indications" of solid tumors with RAS/MAPK alterations and no approved targeted therapies Less sensitive to monotherapy

inhibition due to more RAS/MAPK reactivation and bypass pathway activation Phase 1/1b monotherapy responses used to inform prioritized combination development

Retrospective Pooled Analysis All

trials assessing ERAS-007 or ERAS-601 as monotherapies: ASN007-101, HERKULES-1, FLAGSHP-1 Methodology for retrospective pooled efficacy analysis for ERAS-007 and ERAS-601 in solid tumors with RAS/MAPK pathway alterations* * The clinical data

presented in the following slides are based on a retrospective analysis of pooled data across multiple clinical trials with different designs, inclusion criteria, and dosing regimens. Results across such clinical trials cannot be directly compared.