Slide 1: On a Journey to Erase Cancer: Erasca Investor Update May 2024
Exhibit 99.1 On a Journey to Erase Cancer Erasca Investor Update May 2024
Slide 2: Disclaimer: Forward Looking Statements & Market Data
Disclaimer: Forward Looking Statements & Market Data 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 posit
Slide 3: Focus of today's update: Our name is our mission: to erase cancer
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 aro
Slide 4: Erasca Agenda
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
Slide 5: RAS-Targeting Franchise
ERASCA- RAS-Targeting Franchise
Slide 6: Our singular focus is on the RAS/MAPK pathway
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 targete
Slide 7: Pan-(K)RAS therapies: Expanding treatment options in (K)RAS-driven tumors
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
Slide 8: RAS targeting landscape drives importance of first-in-class or best-in-class potential
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 t
Slide 9: RAS targeting landscape drives importance of first-in-class or best-in-class potential
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 in
Slide 10: Ideal RAS targeting molecules integrate three key attributes
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
Slide 11: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
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:
Slide 12: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
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 me
Slide 13: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
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 me
Slide 14: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
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 me
Slide 15: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
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 provi
Slide 16: ERAS-0015's CYPA binding affinity may be a differentiator from RMC-6236
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
Slide 17: ERAS-0015 more potent inhibition of proliferation across KRAS mutant cell lines vs. RMC-6236
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
Slide 18: ERAS-0015 showed 10x higher potency than RMC-6236 in KRAS G12D PK-59 CDX model
ERAS-0015 showed 10x higher potency than RMC-6236, achieving tumor regression in doses as low as 0.1 mg/kg p.o. QD in the KRAS G12D PK-59 CDX model TGI in KRAS G12D CDX PK-59 % BWC in KRAS G12D CDX PK-59 th • ERAS-0015 achieved comparable tumor regression to RMC-6236 in this model at 1/10 of the dos
Slide 19: ERAS-0015 preferential distribution and long tumor residence time vs. RMC-6236 in PK-59
ERAS-0015 demonstrated preferential distribution and long tumor tissue residence time vs. RMC-6236 in PK-59, favorable attributes that support its enhanced antitumor activity Whole Blood and Tumor PK in the KRAS G12D CDX PK-59 ERAS-0015 Whole Blood PK RMC-6236 Whole Blood PK RMC-6236 1 mg/kg ERAS-00
Slide 20: ERAS-0015 showed 10x higher potency in KRAS G12V CDX model NCI-H727
ERAS-0015 showed 10x higher potency than RMC-6236, achieving tumor regression at 1 mg/kg p.o. QD in ongoing study in the insensitive KRAS G12V CDX model NCI-H727 TGI in NCI-H727 Body weight in NCI-H727 Preliminary TGI Summary Vehicle Vehicle Therapy Dose TGI on day 15 RMC-6236 10 mg/kg p.o. QD RMC-6
Slide 21: ERAS-0015 + docetaxel showed combination benefit in KRAS G12V NSCLC CDX
ERAS-0015 + docetaxel showed combination benefit and tolerability in the insensitive KRAS G12V NSCLC CDX NCI-H727 (ongoing study) Body weight in NCI-H727 Preliminary TGI Summary TGI in NCI-H727 Vehicle Vehicle ERAS-0015 0.3 mg/kg p.o. QD Therapy Dose TGI on day ERAS-0015 0.3 mg/kg p.o. QD Docetaxel
Slide 22: ERAS-0015 comparable tumor regression to RMC-6236 in KRAS G12V CDX SW620
ERAS-0015 achieved comparable tumor regression at 3 mg/kg p.o. QD to RMC-6236 at 10 – 25 mg/kg p.o. QD in the KRAS G12V CDX SW620 TGI Summary % BWC in KRAS G12V CDX SW620 TGI in KRAS G12V CDX SW620 Vehicle Vehicle RMC-6236 25 mg/kg p.o. QD RMC-6236 25 mg/kg p.o. QD RMC-6236 10 mg/kg p.o. QD Therapy
Slide 23: ERAS-0015 achieved tumor regression in KRAS G12R PSN-1 CDX model
ERAS-0015 achieved tumor regression at 5 mg/kg p.o. QD in the KRAS G12R PSN-1 CDX model TGI in KRAS G12R CDX PSN-1 % BWC in KRAS G12R CDX PSN-1 • No dose reductions or holidays and body weight loss < 1% for ERAS-0015 at 5 mg/kg p.o. QD Source: Joyo data p.o.: orally administered; QD: once daily; CDX
Slide 24: ERAS-0015 comparable TGI to RMC-6236 at 1/10 the dose in KRAS G12R CDX PSN-1
th ERAS-0015 achieved comparable TGI to RMC-6236 at 1/10 the dose in the KRAS G12R CDX PSN-1 TGI in KRAS G12R CDX PSN-1 TGI Summary % BWC in KRAS G12R CDX PSN-1 Vehicle Vehicle RMC-6236 25 mg/kg p.o. QD RMC-6236 25 mg/kg p.o. QD Therapy Dose TGI RMC-6236 10 mg/kg p.o. QD RMC-6236 10 mg/kg p.o. QD RM
Slide 25: ERAS-0015 preferential distribution and long tumor residence time vs. RMC-6236 in PSN-1
ERAS-0015 demonstrated preferential distribution and long tumor tissue residence time vs. RMC-6236 in PSN-1, favorable attributes that support its enhanced antitumor activity Whole Blood and Tumor PK in the KRAS G12R CDX PSN-1 ERAS-0015 Whole Blood PK RMC-6236 Whole Blood PK ERAS-0015 1 mg/kg RMC-62
Slide 26: ERAS-0015 combination benefit with anti-PD-1 in syngeneic KRAS G12D model KPC
ERAS-0015 showed compelling combination benefit with anti-PD-1 therapy in the syngeneic KRAS G12D model KPC TGI in syngeneic KRAS G12D CDX KPC % Body Weight Change TGI after rechallenge of KPC tumor cells Vehicle p.o. BID Vehicle p.o. BID Anti-PD-1 10 mg/kg i.p. BIW Vehicle Anti-PD-1 10 mg/kg i.p. B
Slide 27: ERAS-0015 showed promising IV and oral PK in mouse, rat, dog, and monkey
ERAS-0015 showed promising IV and oral PK in mouse, rat, dog, and monkey Mouse Rat Dog Monkey ERAS-0015 RMC-6236 ERAS-0015 RMC-6236 ERAS-0015 RMC-6236 ERAS-0015 RMC-6236 1 1 1 No Data Dose (mpk) 1 1 1 1 1.7 1.5 7.6 No Data T (h) 5.0 5.7 24.5 15.2 1/2 1.9 1.9 3.7 No Data IV Vd (L/kg) 5.3 1.9 3.8 1.8
Slide 28: ERAS-0015 demonstrated good overall ADME properties in vitro
ERAS-0015 demonstrated good overall ADME properties in vitro Assay Value Kinetic Solubility (FaSSIF, FeSSIF) (μg/mL) 127, 156 MDR1(A/B,B/A ER) 0.3, 1.7, 5.5 PPB (% Unbound) 0.4 (h), 2.1 (c), 0.4 (d), 0.2 (r), 0.6 (m) WBS T (min) >289 (h), >289 (d), >289 (r), >289 (m) 1/2 BPR, K 3.5 (h), 14.2 (c), 1.
Slide 29: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
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 provi
Slide 30: ERAS-4001 selectively bound KRAS with high affinities, long residence times
ERAS-4001 selectively bound KRAS with high affinities, long residence times SPR-based kinetic biophysical binding characterization of ERAS-4001 Target KD (nM) t (s) 1/2 KRAS G12D 0.0006 273,079 KRAS G12V 0.0069 30,159 KRAS G12C 0.016 7,724 KRAS WT 0.058 3,409 HRAS WT 117 18.1 NRAS WT 2,660 1.2 Sourc
Slide 31: ERAS-4001 potently and selectively inhibited cellular viability in KRAS mutant and WT cell lines
ERAS-4001 potently and selectivity inhibited cellular viability in KRAS G12X, G13D and WT cell lines ERAS-4001 cell growth KRAS Mutation Tumor type Cell line inhibition (nM) Pancreatic AsPC-1 1.8 Pancreatic Panc 04.03 1.9 KRAS G12D Pancreatic HPAC 1.0 Pancreatic PK-59 2.6 Lung NCI-H727 3.5 Lung NCI-
Slide 32: ERAS-4001 dose independent inhibition of pERK and TGI in KRAS G12D CDX Panc 04.03
ERAS-4001 showed dose independent inhibition of pERK and TGI in the KRAS G12D CDX model Panc 04.03 TGI curves from 28 day repeat dose study pERK inhibition after single dose (day 29) Mouse plasma PK, single dose (day 29) Vehicle p.o. BID Vehicle,p.o.BID Panc0403 xenograft model 2000 MRTX-EX5 100 mg/
Slide 33: ERAS-4001 tumor regressions in additional KRAS G12X CDX models
ERAS-4001 achieved tumor regressions in additional KRAS G12X CDX models at doses as low as 30 mg/kg BID TGI in KRAS G12D CDX PK-59 TGI in KRAS G12V CDX RKN • ERAS-4001 was well tolerated in both studies at doses up to 300 mg/kg BID (i.e., no dose reductions or holidays; no body weight loss or signif
Slide 34: ERAS-4001 tumor regression in pan-KRASi insensitive KRAS G12V CDX model NCI-H727
ERAS-4001 achieved tumor regression in a pan-KRASi insensitive KRAS G12V CDX model NCI-H727 TGI in KRAS G12V CDX NCI-H727 % BWC in KRAS G12V CDX NCI-H727 • ERAS-4001 was well tolerated at doses ranging from 10 mg/kg p.o. BID to 100 mg/kg p.o. BID (i.e., no dose holidays or mortality) • ERAS-4001 at
Slide 35: Under MTA, Erasca reproduced in vivo activity of ERAS-4001 in KRAS G12D CDX HPAC
Under MTA, Erasca reproduced the promising in vivo activity of ERAS-4001 in the KRAS G12D CDX HPAC % BWC in KRAS G12D CDX HPAC TGI in KRAS G12D CDX HPAC • ERAS-4001 achieved tumor regressions at 50 and 100 mg/kg p.o. BID doses, reproducing the in vivo activity previously observed in external studies
Slide 36: ERAS-4001 combination benefit with anti-PD-1 in syngeneic KRAS G12D model KPC
ERAS-4001 showed combination benefit with anti-PD-1 therapy in the syngeneic KRAS G12D model KPC TGI of ERAS-4001 +/- anti-PD-1 Treatment stopped at day 38. KPC rechallenge demonstrated immune memory effect by a contralateral inoculation of KPC cells in combination treatment groups that resulted in
Slide 37: ERAS-4001 showed promising PK and oral bioavailability in mouse, rat, and dog
ERAS-4001 showed promising PK and oral bioavailability in mouse, rat, and dog PK Parameter Mouse Rat Dog Dose (mpk) 1.7 2 2.1 C (nM) 1,722 1,083 1,669 0 T (h) 1.9 3 5.8 1/2 IV V (L/kg) 5.16 10.1 14.1 d Cl (mL/Kg/min) 45.5 70.9 53.1 AUC (nM·h) 938 615 827 0-last Dose (mpk) 30.3 30.9 15.3 C (nM) 2,090
Slide 38: ERAS-4001 demonstrated good overall ADME properties in vitro
ERAS-4001 demonstrated good overall ADME properties in vitro Assay Value CLogP / tPSA 3.7 / 111.6 pKa / Kinetic Solubility (pH@7.4) 9.0 / 113.0 µM PPB (Unbound %), Human/Dog/Rat/Mice 1.3 / 1.6 / 0.8 / 1.5 HMS CL (mL/min/kg), H / D / R / M 38.8 / 212.3 / 511.6 / 830 int IS9 CL (mL/min/kg), H / D / R
Slide 39: KRAS alterations found most commonly in CRC, PDAC and NSCLC
KRAS alterations found most commonly in CRC, PDAC and NSCLC Estimated number of patients affected by KRAS mutant tumors in the US (thousands) 74.3 G12C G12D G12V G12A G12R Other Multiple 55.0 50.1 16.1 12.7 9.9 8.2 4.5 0.4 CRC NSCLC PDAC Urinary Endometrial Other GI Unknown Other GU Other Primary Ad
Slide 40: Innovative CDP designed to maximize efficiency and minimize clinical and regulatory risk
Innovative CDP designed to maximize efficiency and minimize clinical and regulatory risk 01 02 03 04 Early combo Data-driven Portfolio Patients assessment • Efficiently use clinical data to • Capitalize on unique • Focus on tumor types with • Parallel pursuit of prioritize mono and combo portfolio o
Slide 41: Erasca key license terms for ERAS-0015 Pan-RAS molecular glue
Erasca key license terms for ERAS-0015 Pan-RAS molecular glue • Licensor: Joyo Pharmatech Co., Ltd. Financial terms Amount ($m, except royalties) • License scope: Exclusive license covering ERAS-0015 (pan- Total upfront 12.5 RAS) and any other pan-RAS molecule covered by the licensed patents Total d
Slide 42: Erasca key license terms for ERAS-4001 Pan-KRAS inhibitor
Erasca key license terms for ERAS-4001 Pan-KRAS inhibitor Financial terms Amount ($m, except royalties) • Licensor: Medshine Discovery, Inc. Total upfront 10 • License scope: Exclusive license covering ERAS-4001 (pan- Total development milestones Up to 10 KRAS) and any other pan-KRAS molecule covere
Slide 43: Pipeline and resource prioritization
ERASCA- Corporate Update
Slide 44: Deep modality-agnostic RAS/MAPK pathway-focused pipeline
Deep modality-agnostic RAS/MAPK pathway-focused pipeline Program/ Worldwide Target Modality Indication Discovery IND-enabling Phase 1 Phase 2 Phase 3 Company Rights Pan-RAS Q61X tissue agnostic SEACRAFT-1 Naporafenib BRAF/CRAF NRASm melanoma SEACRAFT-2 (planned) BRAF V600E CRC HERKULES-3 ERAS-007 ER
Slide 45: Data-driven prioritization refocuses efforts and resources on most significant unmet needs
Data-driven prioritization refocuses efforts and resources on opportunities targeting the most significant unmet needs, with highest POS for patients Refocusing Efforts Action Rationale Clinical efficacy data do not support continued evaluation of Deprioritized HERKULES-3: ERAS-007 + EC in EC-naïve
Slide 46: Erasca's AURORAS and BOREALIS trials to address RAS opportunities
Erasca’s AURORAS and BOREALIS trials to address RAS opportunities During any long seafaring journey, the endless sea can often disorient a person’s sense of time and place. The appearance of the dawn, or aurora, provides a definitive sense of direction and a welcome signal to start the new day. At E
Slide 47: Prioritized modality-agnostic RAS/MAPK pathway-focused pipeline
Prioritized modality-agnostic RAS/MAPK pathway-focused pipeline Program/ Worldwide Target Modality Indication Discovery IND-enabling Phase 1 Phase 2 Phase 3 Company Rights Pan-RAS Q61X tissue agnostic SEACRAFT-1 Naporafenib BRAF/CRAF NRASm melanoma SEACRAFT-2 (planned) ERAS-0015 RAS RASm solid tumor
Slide 48: Anticipated key milestones and clinical trial readouts
Anticipated key milestones and clinical trial readouts Program Trial Name Anticipated Milestone Mechanism Indication (Combo partner if applicable) SEACRAFT-1 1 RAS Q61X Solid Tumors • Q4 2024: Ph 1b combination data (+ trametinib) Naporafenib Pan-RAF inhibitor SEACRAFT-2 • Q2 2024: Ph 3 pivotal tria
Slide 49: Thank You!
ERASCA- Thank You!