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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; our assumptions about
ERAS-0015 or ERAS-4001 development potential are based in large part on the preclinical data generated by the licensors and we may observe materially and adversely different results as we conduct our planned studies; we only have one product
candidate in clinical development and all of our other development efforts are in the preclinical or development stage; our assumptions around which programs may have a higher probability of success may not be accurate, and we may expend our limited
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Focus of today's update Our name is our mission: to erase cancer 1
Vision to one day erase cancer in at least 100,000 patients annually as a leading global oncology company Experienced leadership team and SAB with track record of serial successes Founded by Jonathan Lim, MD & Kevan Shokat, PhD around
disruptive idea to target RAS World class scientific advisory board of leading pioneers in RAS/MAPK pathway Team with deep experience in efficient planning and execution of global clinical trials Industry leading pipeline focused on
shutting down the RAS/MAPK pathway Naporafenib pan-RAFi with first-in-class (FIC) potential and Fast Track Designation for NRASm melanoma & FIC potential in RAS Q61X solid tumors + other RAS/MAPK targeting agents ERAS-0015
Pan-RAS molecular glue with BIC potential in RASm solid tumors ERAS-4001 Pan-KRASi with FIC potential in KRASm solid tumors Strong financial position with high quality investor base and industry visibility 2 $334M in cash, cash
equivalents, and marketable securities One of Fierce Biotech's 2021 "Fierce 15" most promising biotechnology companies CNS = central nervous system 1 Number of patients alive and free of cancer or free from cancer
progression 2 yrs after starting an Erasca regimen, as measured by disease-free survival (adjuvant setting) and progression-free survival (metastatic setting) 2 Unaudited, as of March 31, 2024 (includes $43.7m net proceeds from equity financing
announced on 3/27/2024) 3
Erasca Investor Update Agenda ERAS-0015: Pan-RAS molecular glue
RAS-Targeting Franchise ERAS-4001: Pan-KRAS inhibitor Pipeline and resource prioritization Corporate Update Key milestones and clinical trial readouts Q&A Session 4
RAS-Targeting Franchise
Our singular focus is on the RAS/MAPK pathway EGFR Other RTKs Our
Strategy RAS-GDP 2 GEF Comprehensively shut down GRB2 GDP the RAS/MAPK pathway GAP P GTP 1 Target RAS directly SOS1 2 NF1 with single agents and SHP2 combinations with upstream, RAS-GTP 2 downstream, and escape route PI3K MAPK targeted therapies
pathway pathway 1 RAF PI3K Target upstream and P P MEK AKT downstream RAS/MAPK nodes 1 3 Target escape routes with single agents and clamp P enabled by other proteins or oncogenic drivers (MAPKlamp) with ERK mTOR pathways to further disrupt
combinations RAS/MAPK pathway signaling MYC 3 Nodes targeted by Erasca 6
Pan-(K)RAS therapies: Expanding treatment options in (K)RAS-driven
tumors KRAS G12C INHIBITORS PAN-(K)RAS APPROACHES Compelling but challenges remain Designed to address current limitations Expands patient population KRAS KRAS G12X G13X No selective (K)RAS multi-allele targeting inhibitors for KRAS other mutations
Q61X Less likely to develop treatment resistance Susceptible to treatment resistance Prevents on-target Blocks WT RAS Emerging clinical data suggest tumors often RAS mutations or isoform activation 1,2 re-activation mount resistance to
mutant-specific inhibitors 1 Aw ad et al. NEJM 2021 2 Li et al. JCO 2022 7
RAS targeting landscape drives importance of identifying development
candidates with first-in-class or best-in-class potential Comments on Class Preclinical Pre-IND/IND Phase I Encouraging preliminary clinical data Complementary combination of GTP + GDP Pan-RAS GF-547 RMC-6236 state inhibition to
address pERK rebound YL-17321 (G12X) Tolerability, combinability may be challenging Opportunity for greater therapeutic window by specifically targeting KRAS More straightforward mechanism via KRAS Pan-KRAS Switch II pocket
binding mode QTX3034 Translation to clinical efficacy TBD LY4066434 (G12D-preferring) (G12X) Potential for greater potency against MRTX1133 (G12D) RMC-9805 (G12D) specific mutation of interest and wt-sparing Mutant LY-3962673 (G12D)
Oral bioavailability has proven challenging 1 BI 3706674 Selective for G12Di (wt amp, G12V) RMC-G12V ASP3082 Susceptible to resistance mediated by INCB161734 (G12D degrader) wildtype RAS of the same isoform (G12D) Note: Select
coopetitors show n; list is not intended to be exhaustive 1 Mutant selective beyond KRAS G12C inhibitors 8
RAS targeting landscape drives importance of identifying development
candidates with first-in-class or best-in-class potential Comments on Class Preclinical Pre-IND/IND Phase I Encouraging preliminary clinical data Complementary combination of GTP + GDP ERAS-0015 Pan-RAS GF-547 RMC-6236 state
inhibition to address pERK rebound YL-17321 (G12X) Tolerability, combinability may be challenging Opportunity for greater therapeutic window by specifically targeting KRAS 2 ERAS-4 ERAS-4001 More straightforward mechanism via
KRAS Pan-KRAS Switch II pocket binding mode QTX3034 Translation to clinical efficacy TBD LY4066434 (G12D-preferring) (G12X) Potential for greater potency against MRTX1133 (G12D) RMC-9805 (G12D) specific mutation of interest and
wt-sparing Mutant LY-3962673 (G12D) Oral bioavailability has proven challenging 1 BI 3706674 Selective for G12Di (wt amp, G12V) RMC-G12V ASP3082 Susceptible to resistance mediated by INCB161734 (G12D degrader) wildtype RAS of the
same isoform (G12D) Note: Select coopetitors show n; list is not intended to be exhaustive 1 Mutant selective beyond KRAS G12C inhibitors 2 Select molecules from internal ERAS-4 program identified as backup for ERAS-4001 9
Ideal RAS targeting molecules integrate three key attributes
May enable lower clinically active dose which could translate to: - Lower risk of solubility-limited absorption and exposure plateau observed with another pan-RAS MG Preclinical in development Potency - Better GI tolerability profile due to lower
drug load - Improved therapeutic window for any potential off-target toxicities KRAS G12Ci class has demonstrated how RAS higher potency can translate into improved Targeting Molecule clinical activity Bolsters ability to Oral
Proprietary maximize clinical Bioavailability and commercial Chemical value in highly (OBA) Matter competitive market MG = molecular glue 10
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our
TPP 1 2 OBA IP Preclinical (in vitro and in vivo) Potency TPP: target product profile; OBA: oral bioavailability; IP: intellectual property; FIC: first-in-class; BIC: best-in-class; WT: w ildtype; SMi: small molecule inhibitor; MG: molecular glue;
DC: development candidate 1 2 3 4 in vitro potency assessed by CTG 2D and 3D-cell proliferation assay IC s; OBA or oral bioavailability assessed by %F; Predicted based on molecular profile; absent any patent term adjustments or extensions 50
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our
TPP 1 2 OBA IP Preclinical (in vitro and in vivo) Potency KRAS G12D: 0.2 - 13.3 nM KRAS G12D: Tumor regression in PK-59 CDX Mouse: 48% IP (composition of matter, methods KRAS G12V: 0.4 - 2.5 nM model at 0.3 mpk PO QD of use, and methods
of making Rat: 38% ERAS-0015 KRAS G12C: 0.8 - 1.4 nM KRAS G12V: Tumor regression in NCI-H727 licensed compounds, incl. the Pan-RAS KRAS G12X: 4.1 - 7.4 nM CDX model at 1 mpk PO QD Dog: 22% current DC) has potential coverage Molecular 4
KRAS G13D: 2.8 - 5.5 nM KRAS G12R: Tumor regression in PSN1 CDX through 2043 Monkey: 17% Glue KRAS WT: 4.1 - 13.8 nM model at 5 mpk PO QD 3 H/NRAS WT: Active Potential BIC Pan-RAS MG for RASm solid tumors with ~5x - 10x greater
potency as well as favorable ADME properties and PK performance in animal species (vs. current Pan-RAS MG in development) TPP: target product profile; OBA: oral bioavailability; IP: intellectual property; FIC: first-in-class; BIC: best-in-class; WT:
w ildtype; SMi: small molecule inhibitor; MG: molecular glue; DC: development candidate 1 2 3 4 in vitro potency assessed by CTG 2D and 3D-cell proliferation assay IC s; OBA or oral bioavailability assessed by %F; Predicted based on molecular
profile; absent any patent term adjustments or extensions 50 12
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our
TPP 1 2 OBA IP Preclinical (in vitro and in vivo) Potency KRAS G12D: 0.2 - 13.3 nM KRAS G12D: Tumor regression in PK-59 CDX Mouse: 48% IP (composition of matter, methods KRAS G12V: 0.4 - 2.5 nM model at 0.3 mpk PO QD of use, and methods
of making Rat: 38% ERAS-0015 KRAS G12C: 0.8 - 1.4 nM KRAS G12V: Tumor regression in NCI-H727 licensed compounds, incl. the Pan-RAS KRAS G12X: 4.1 - 7.4 nM CDX model at 1 mpk PO QD Dog: 22% current DC) has potential coverage Molecular 4
KRAS G13D: 2.8 - 5.5 nM KRAS G12R: Tumor regression in PSN1 CDX through 2043 Monkey: 17% Glue KRAS WT: 4.1 - 13.8 nM model at 5 mpk PO QD 3 H/NRAS WT: Active KRAS G12D: 1.0 - 2.6 nM KRAS G12D: Tumor regression in Panc04.03, Mouse:
27% IP (composition of matter, methods KRAS G12V: 0.7 - 9.1 nM PK-59, and LU-01-1381 CDX/PDX models at 30 of use, and methods of making Rat: 5 - 27% KRAS G12C: 1.1 - 4.5 nM - 100 mpk PO BID; combo with anti-PD-1 licensed
compounds, incl. the ERAS-4001 (variable KRAS G12X: 6.5 - 37.7 nM achieved complete disappearance of tumors in current DC) has potential coverage Pan-KRAS PK in rat) 4 KRAS G13D: 5.8 - 56.0 nM all mice (7/7) on D31 at 100 mpk PO BID
through 2043 Inhibitor KRAS WT: 3.6 - 10.8 nM KRAS G12V: Tumor regression in RKN and Dog: 16% H/NRAS WT: No activity NCI-H727 CDX models at 30 - 300 mpk PO BID Potential BIC Pan-RAS MG for RASm solid tumors with Potential FIC/BIC
Pan-KRAS or "KRAS-selective" SMi that spares ~5x - 10x greater potency as well as favorable ADME H/NRAS WT, predicted to provide greater therapeutic window (vs. properties and PK performance in animal species Pan-RAS MG) for KRASm
solid tumors and address KRASwt (vs. current Pan-RAS MG in development) activation to prevent resistance (vs. mutant-selective inhibitors) TPP: target product profile; OBA: oral bioavailability; IP: intellectual property; FIC: first-in-class; BIC:
best-in-class; WT: w ildtype; SMi: small molecule inhibitor; MG: molecular glue; DC: development candidate 1 2 3 4 in vitro potency assessed by CTG 2D and 3D-cell proliferation assay IC s; OBA or oral bioavailability assessed by %F; Predicted based
on molecular profile; absent any patent term adjustments or extensions 50 13
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our
TPP 1 2 OBA IP Preclinical (in vitro and in vivo) Potency KRAS G12D: 0.2 - 13.3 nM KRAS G12D: Tumor regression in PK-59 CDX Mouse: 48% IP (composition of matter, methods KRAS G12V: 0.4 - 2.5 nM model at 0.3 mpk PO QD of use, and methods
of making Rat: 38% ERAS-0015 KRAS G12C: 0.8 - 1.4 nM KRAS G12V: Tumor regression in NCI-H727 licensed compounds, incl. the Pan-RAS KRAS G12X: 4.1 - 7.4 nM CDX model at 1 mpk PO QD Dog: 22% current DC) has potential coverage Molecular 4
KRAS G13D: 2.8 - 5.5 nM KRAS G12R: Tumor regression in PSN1 CDX through 2043 Monkey: 17% Glue KRAS WT: 4.1 - 13.8 nM model at 5 mpk PO QD 3 H/NRAS WT: Active KRAS G12D: 1.0 - 2.6 nM KRAS G12D: Tumor regression in Panc04.03, Mouse:
27% IP (composition of matter, methods KRAS G12V: 0.7 - 9.1 nM PK-59, and LU-01-1381 CDX/PDX models at 30 of use, and methods of making Rat: 5 - 27% KRAS G12C: 1.1 - 4.5 nM - 100 mpk PO BID; combo with anti-PD-1 licensed
compounds, incl. the ERAS-4001 (variable KRAS G12X: 6.5 - 37.7 nM achieved complete disappearance of tumors in current DC) has potential coverage Pan-KRAS PK in rat) 4 KRAS G13D: 5.8 - 56.0 nM all mice (7/7) on D31 at 100 mpk PO BID
through 2043 Inhibitor KRAS WT: 3.6 - 10.8 nM KRAS G12V: Tumor regression in RKN and Dog: 16% H/NRAS WT: No activity NCI-H727 CDX models at 30 - 300 mpk PO BID Potential BIC Pan-RAS MG for RASm solid tumors with Potential FIC/BIC
Pan-KRAS or "KRAS-selective" SMi that spares KRAS-selective SM + Pan-RAS MG ~5x - 10x greater potency as well as favorable ADME H/NRAS WT, predicted to provide greater therapeutic window (vs. "RASKlamp" combo could
uniquely properties and PK performance in animal species Pan-RAS MG) for KRASm solid tumors and address KRASwt shut down MAPK signaling in (vs. current Pan-RAS MG in development) activation to prevent resistance (vs. mutant-selective inhibitors)
KRASm solid tumors TPP: target product profile; OBA: oral bioavailability; IP: intellectual property; FIC: first-in-class; BIC: best-in-class; WT: w ildtype; SMi: small molecule inhibitor; MG: molecular glue; DC: development candidate 1 2 3 4 in
vitro potency assessed by CTG 2D and 3D-cell proliferation assay IC s; OBA or oral bioavailability assessed by %F; Predicted based on molecular profile; absent any patent term adjustments or extensions 50 14
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our
TPP ~5x - 10x greater potency as well as favorable ERAS-0015: Potential BIC ADME properties and PK performance in animal Pan-RAS MG species (vs. current Pan-RAS MG in development) Designed to spare H/NRAS WT, predicted to
provide greater therapeutic window (vs. Pan-RAS MG) for ERAS-4001: Potential FIC KRASm solid tumors Pan-KRAS or "KRAS- selective" SM inhibitor Designed to address KRASwt activation to prevent resistance (vs. mutant-selective
inhibitors) TPP = target product profile; BIC: best-in-class; FIC: first-in-class; MG: molecular glue; SM: small molecule; ADME: absorption, distribution, metabolism, and excretion; PK: pharmacokinetic 15
ERAS-0015's CYPA binding affinity may be a differentiator from
RMC-6236 Compound ka (1/[S*M]) kd (1/s) KD(M) CYPA ERAS-0015 3.85E+05 0.017 4.52E-08 RMC-6236 1.19E+05 0.023 1.94E-07 Stronger binding to cyclophilin A (CYPA) enables more potent RAS inhibition Source: Joyo data 16
ERAS-0015 demonstrated significantly more potent inhibition of cellular
proliferation across KRAS mutant cell lines vs. RMC-6236 ERAS-0015 cell growth RMC-6236 cell growth Mutation Tumor type Cell line inhibition (nM) inhibition (nM) KRAS G12C NSCLC H358 (adagrasib-resistant) 0.8 3.6 NSCLC LU99 1.4 5.4 NSCLC A-427 13.3
59.2 CRC SW620 0.2 1.3 CRC GP2d 0.9 4.6 PDAC AsPc-1 2.0 26.7 KRAS G12D PDAC HPAC 4.8 15.5 PDAC PK-59 10.7 10.7 PDAC KP-4 5.0 19.7 Sub-nM to nM potency PDAC Panc 04.03 5.7 26.4 against multiple KRAS Lung Cancer NCI-H727 0.4 1.7 wildtype and mutant
cell Lung Cancer NCI-H441 1.4 16.7 KRAS G12V CRC SW480 0.8 6.8 lines and RTK altered PDAC CAPAN-1 2.5 7.1 cell lines Ovarian leiomyosarcoma RKN 0.7 1.6 KRAS G12R PDAC PSN-1 5.3 17.1 KRAS G12S NSCLC A-549 4.1 38.3 KRAS Q61R PDAC Panc 02.13 7.4 44.3