Erasca, Inc. · NASDAQ:ERAS
Erasca — Investor Presentation (January 2025)
51 slides from Erasca's investor presentation, Jan 13, 2025
Slide 1: On a Journey to Erase Cancer
On a Journey to Erase Cancer Erasca Corporate Presentation January 2025 Eric N., naporafenib clinical trial participant and cancer survivor, and his wife Margaret Exhibit 99.1
Slide 2: Forward-looking statements
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 plan
Slide 3: Our name is our mission: to erase cancer
Our name is our mission: to erase cancer 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 September 30, 2
Slide 4: SAB includes world's leading experts in the RAS/MAPK pathway
SAB includes world’s leading experts in the RAS/MAPK pathway Erasca co-founder. World expert in RAS who pioneered development of approaches to inhibit KRAS G12C (RAS-GDP) and active states of RAS (RAS-GTP) Kevan Shokat, PhD Erasca Chair of R&D. World expert in structure-based drug design; former hea
Slide 5: Our singular focus is on the RAS/MAPK pathway
Our singular focus is on the RAS/MAPK pathway P P P MAPK pathway PI3K pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK PI3K AKT mTOR ERK RAS-GDP EGFR Other RTKs MYC GEF Nodes targeted by Erasca Target upstream and downstream RAS/MAPK nodes with single agents and clamp oncogenic drivers (MAP
Slide 6: Deep modality-agnostic RAS/MAPK pathway-focused pipeline
large molecule small molecule Deep modality-agnostic RAS/MAPK pathway-focused pipeline Note: Pipeline also includes ERAS-801 brain-penetrant EGFR inhibitor for EGFR-altered GBM (for which we are concluding a Phase 1 trial and exploring advancement, including via partnership and/or investigator-spons
Slide 7: Ideal RAS targeting molecules integrate three key attributes
Ideal RAS targeting molecules integrate three key attributes Proprietary Chemical Matter Oral Bioavailability (OBA) Preclinical Potency RAS Targeting Molecule Bolsters ability to maximize clinical and commercial value in highly competitive market May enable lower clinically active dose which could t
Slide 8: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP Preclinical Potency1 OBA2 IP3 TPP: target product profile; OBA: oral bioavailability; IP: intellectual property; FIC: first-in-class; BIC: best-in-class; WT: wildtype; SMi: small molecule inhibitor; MG: molecular glue; 1 in vit
Slide 9: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP Potential best-in-class Pan-RAS molecular glue ~5x – 10x greater potency vs. pan-RAS MG in development Favorable ADME properties and PK performance in animals vs. pan-RAS MG in development Designed to address RASwt activation t
Slide 10: ERAS-0015's higher CYPA binding affinity may be a differentiator from RMC-6236
ERAS-0015’s higher CYPA binding affinity may be a differentiator from RMC-6236, demonstrating potential best-in-class profile SPR: surface plasmon resonance; KD: equilibrium dissociation constant; ITC: isothermal titration calorimetry 8-21x higher binding affinity to cyclophilin A (CYPA) may enable
Slide 11: ERAS-0015 vs RMC-6236 cell growth inhibition by mutation
Mutation Tumor type Cell line ERAS-0015 cell growth inhibition (nM) RMC-6236 cell growth inhibition (nM) ERAS-0015:RMC-6236 Fold Potency KRAS G12C NSCLC H358 (adagrasib-resistant) 0.8 3.6 4.5x NSCLC LU99 1.4 5.4 3.9x KRAS G12D NSCLC A-427 13.3 59.2 4.5x CRC SW620 0.2 1.3 6.5x CRC GP2d 0.9 4.6 5.1x P
Slide 12: ERAS-0015: 10x higher potency than RMC-6236 in KRAS G12D PDAC CDX model
ERAS-0015: Showed 10x higher potency than RMC-6236, achieving tumor regression in a KRAS G12D PDAC CDX model ERAS-0015 achieved comparable tumor regression to RMC-6236 in this model at 1/10th of the dose at 0.3 mg/kg p.o. QD No dose reductions or holidays and no body weight loss for all doses of ERA
Slide 13: ERAS-0015: tumor regression in insensitive KRAS G12V NSCLC CDX model
ERAS-0015: Showed 10x higher potency than RMC-6236, achieving tumor regression in an insensitive KRAS G12V NSCLC CDX model ERAS-0015 achieved comparable tumor regression to RMC-6236 in this model at 1/10th the dose at 1 mg/kg p.o. QD ERAS-0015 was well tolerated at all doses Therapy Dose TGI on Day
Slide 14: ERAS-0015: ~8x higher potency in KRAS G12V CRC CDX model
ERAS-0015: Showed ~8x higher potency than RMC-6236, achieving tumor regression in a KRAS G12V CRC CDX model ERAS-0015 achieved comparable tumor regression to RMC-6236 in this model at ~1/8th the dose at 3 mg/kg p.o. QD No dose reductions, holidays, or body weight loss Therapy Dose TGI on Day 26 ERAS
Slide 15: ERAS-0015: tumor regression in KRAS G12R PDAC CDX model
ERAS-0015: Achieved tumor regression in a KRAS G12R PDAC CDX model ERAS-0015 tumor regression observed at 5 mg/kg p.o. QD No dose reductions or holidays and body weight loss < 1% for ERAS-0015 at 5 mg/kg p.o. QD TGI assessed on last day where vehicle and ERAS-0015 tumors were both measured (i.e., da
Slide 16: ERAS-0015: 10x higher potency in KRAS G12R PDAC CDX model
TGI in KRAS G12R CDX PSN-1 % Body Weight Change ERAS-0015: Showed 10x higher potency than RMC-6236, achieving >95% TGI in a KRAS G12R PDAC CDX model ERAS-0015 achieved comparable TGI to RMC-6236 in this model at 1/10th the dose starting at 0.3 mg/kg p.o. QD No dose reductions or holidays and body we
Slide 17: ERAS-0015 + anti-PD-1: combination benefit in syngeneic KRAS G12D PDAC model
ERAS-0015 + anti-PD-1: Compelling combination benefit in a syngeneic KRAS G12D PDAC model ERAS-0015 in combination with anti-PD-1 therapy resulted in a sustained complete response in 7 out of 7 treated mice starting on day 31 ERAS-0015 as a monotherapy and in combination with an anti-PD-1 was well t
Slide 18: ERAS-0015 preferential tumor distribution and longer residence time vs RMC-6236
ERAS-0015 demonstrated preferential tumor distribution and longer residence time vs. RMC-6236 in vivo PDAC: pancreatic ductal adenocarcinoma; CDX: cell-line derived xenograft Tumor PK Distribution Assessment in the KRAS G12D PDAC CDX Model, PK-59 Tumor PK Distribution Assessment in the KRAS G12R PDA
Slide 19: ERAS-0015 showed promising IV and oral PK across species
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 IV Dose (mpk) 1 1 1 1 1 1 1 No Data T1/2 (h) 5.0 1.7 5.7 1.5 24.5 7.6 15.2 No Data Vdss (L/kg) 5.3 1.9 1.9 1.9 3.8 3.7 1.8 No Data
Slide 20: ERAS-0015 demonstrated good overall ADME and toxicology properties
ERAS-0015 demonstrated good overall ADME and toxicology properties 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 T1/2(min) >289 (h), >289 (d), >289 (r), >289 (m) BPR, KB/P 3.5 (h), 14.2
Slide 21: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP Potential best-in-class Pan-RAS molecular glue ~5x – 10x greater potency vs. pan-RAS MG in development Favorable ADME properties and PK performance in animals vs. pan-RAS MG in development Designed to address RASwt activation t
Slide 22: ERAS-4001 selectively bound KRAS with high affinities, long residence times
ERAS-4001 selectively bound KRAS with high affinities, long residence times Target KD (nM) t1/2 (s) 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 SPR-based kinetic biophysical binding characterization of ERAS-4001
Slide 23: ERAS-4001 potent activity against GTP- and GDP-bound KRAS
ERAS-4001 showed potent activity against both GTP- and GDP-bound KRAS Assay Class Assay Target ERAS-4001 IC50 (nM) Biochemical Functional RAS-RAF Binding Assay (RBD) RBD KRAS G12D GDP 1.6 RBD KRAS G12D GMPPNP* 6.8 * GMPPNP is a nonhydrolyzable GTP analogue intended to approximate GTP-bound KRAS
Slide 24: ERAS-4001 inhibited cell growth in KRAS G12X, G13D and WT cell lines
ERAS-4001 potently and selectively inhibited cell growth in KRAS G12X, G13D and WT cell lines KRAS Mutation Tumor type Cell line ERAS-4001 cell growth inhibition (nM) KRAS G12D Pancreatic AsPC-1 1.8 Pancreatic Panc 04.03 1.9 Pancreatic HPAC 1.0 Pancreatic PK-59 2.6 KRAS G12V Lung NCI-H727 3.5 Lung N
Slide 25: ERAS-4001: tumor regression in KRAS G12D PDAC CDX model
ERAS-4001: Achieved tumor regression in a KRAS G12D PDAC CDX model at doses at or above 100 mg/kg BID KRAS G12D CDX Panc 04.03 TGI curves from 28 day repeat dose study ERAS-4001 was well tolerated at doses up to 300 mg/kg BID for 28 days (i.e., no dose reductions or holidays; no body weight loss or
Slide 26: ERAS-4001: tumor regressions in KRAS G12D and G12V CDX models
ERAS-4001: Achieved tumor regressions in KRAS G12D and G12V CDX models at doses as low as 30 mg/kg BID 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 significant health observations) TGI in KRAS G12D PDAC CDX PK
Slide 27: ERAS-4001: tumor regression in pan-KRASi insensitive KRAS G12V NSCLC model
ERAS-4001: Achieved tumor regression in a pan-KRASi insensitive KRAS G12V NSCLC CDX model 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 300 mg/kg p.o. BID showed borderline tolerability with 4 out of 6 mi
Slide 28: ERAS-4001: tumor regression in KRAS G12D PDAC CDX model
ERAS-4001: Achieved tumor regression in KRAS G12D PDAC CDX model p.o.: orally administered; BID: twice a day; CDX: cell line-derived xenograft; TGI: tumor growth inhibition TGI in KRAS G12D HPAC % Body Weight Change Therapy Dose TGI on Day 28 ERAS-4001 50 mg/kg 106% 100 mg/kg 109% ERAS-4001 achieved
Slide 29: ERAS-4001 + anti-PD-1: combination benefit in syngeneic model
ERAS-4001 + anti-PD-1: Combination benefit in a syngeneic KRAS G12D PDAC model Anti-PD-1 ERAS-4001 Anti-PD-1 + ERAS-4001 TGI at day 26 12.7% 95.3% 108.5% Complete response rate at day 50 0% (0/7) 29% (2/7) 100% (7/7) TGI of ERAS-4001 +/- anti-PD-1 in KRAS G12D PDX model All treatment stopped by day
Slide 30: ERAS-4001 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 IV Dose (mpk) 1.7 2 2.1 C0 (nM) 1,722 1,083 1,669 T1/2 (h) 1.9 3 5.8 Vd (L/kg) 5.16 10.1 14.1 Cl (mL/Kg/min) 45.5 70.9 53.1 AUC0-last (nM·h) 938 615 827 Oral Dose (mpk) 30.3 30.9 15.3 Cmax (nM) 2
Slide 31: ERAS-4001 good overall ADME and toxicology properties
ERAS-4001 demonstrated good overall ADME and toxicology properties Assay Value CLogP / tPSA 3.7 / 111.6 pKa / Kinetic Solubility (pH@7.4) 9.0 / 113.0 µM PPB (Unbound %) 1.3 (h) / 1.6 (d) / 0.8 (r) / 1.5 (m) HMS CLint (mL/min/kg) 38.8 (h) / 212.3 (d)/ 511.6 (r)/ 830 (m) IS9 CLint (mL/min/kg) <9.6 (h)
Slide 32: 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) Adapted from Lee J., Sivakumar S., Schrock A., et al. “Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tum
Slide 33: Clinical development strategy
Focus on tumor types with largest number of potential patients to allow efficient clinical trial enrollment and potential for maximum patient benefit Patients 01 Parallel pursuit of monotherapy proof-of-concept & combination dose finding to expedite development Early combo assessment 02 Efficiently
Slide 34: Naporafenib pan-RAFi could address unmet needs in NRASm melanoma
P P P MAPK pathway PI3K pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK PI3K AKT mTOR RAS-GDP EGFR Other RTKs MYC GEF Erasca’s naporafenib pan-RAFi could address unmet needs in patients with both NRASm melanoma solid tumors ERK BRAF CRAF Potently inhibits CRAF and BRAF and blocks downstrea
Slide 35: Naporafenib is a potent and selective inhibitor of BRAF and CRAF
Naporafenib is a potent and selective inhibitor of BRAF and CRAF with sub-nanomolar IC50 potency and most advanced pan-RAFi in development Assay Value (nM) Biochemical CRAF Inhibition (IC50) 0.1 Biochemical BRAF Inhibition (IC50) 0.2 Biochemical ARAF Inhibition (IC50) 6.4 Biochemical activity of nap
Slide 36: Naporafenib dosed in more than 600 patients to date
Naporafenib has been dosed in more than 600 patients to date, establishing its safety, tolerability, and proof of concept in NRASm melanoma * As of SEACRAFT-1 DCO 03Sep2024 P P P MAPK pathway PI3K pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK PI3K AKT mTOR ERK RAS-GDP EGFR Other RTKs MYC
Slide 37: SEACRAFT-2: first-in-class targeted treatment potential for NRASm melanoma
SEACRAFT-2: Naporafenib + trametinib has the potential to be first-in-class targeted treatment for NRASm melanoma Naporafenib (pan-RAFi) Successfully completed US, EU and UK EOP2 process for Phase 3 design Napo + tram demonstrated compelling efficacy across Phase 1 and 2 studies (mPFS ~5 months) FDA
Slide 38: Positive preliminary efficacy in SEACRAFT-1 melanoma cohort
Positive preliminary efficacy observed in SEACRAFT-1 melanoma cohort bolsters rationale for pursuing tissue-specific NRASm melanoma indication in SEACRAFT-2 Data cutoff (DCO) as of 05Sep2024 * Patient response was confirmed after DCO 1 naporafenib 200 mg BID + trametinib 1 mg QD (BID: twice a day; Q
Slide 39: Early but encouraging durability in SEACRAFT-1 melanoma cohort
Early but encouraging durability observed in SEACRAFT-1 melanoma cohort Data cutoff (DCO) as of 05Sep2024 * Patient response was confirmed after DCO 1 naporafenib 200 mg BID + trametinib 1 mg QD (BID: twice a day; QD: once a day) 2 Defined as patients who received at least one dose of study drug, ha
Slide 40: Compelling, reproducible clinical efficacy across studies and doses
Compelling, reproducible clinical efficacy across studies and doses shows potential to win on both SEACRAFT-2 primary endpoints MEKi Published literature SOC Pooled Ph 1 and Ph 24 Binimetinib1 Trametinib2 Chemo3 Naporafenib + Trametinib 45mg 2mg 1g/m2 IV 200mg+1mg 400mg+0.5mg N=269 N=33 N=133 N=39 N
Slide 41: Mandatory primary rash prophylaxis decreased dermatologic toxicity
Mandatory primary rash prophylaxis in SEACRAFT-1 significantly decreased incidence/ severity of derm tox, reduced drug discontinuations due to AEs, and improved RDI 200/1 = 200mg naporafenib BID + trametinib 1mg QD; G=CTCAE grade; Pts=patients; RDI=relative dose intensity; TEAE=treatment emergent ad
Slide 42: SEACRAFT-2: NRASm Melanoma two-stage Phase 3 design
SEACRAFT-2: NRASm Melanoma (Two-stage Phase 3) Pivotal Phase 3 trial design capitalizes on promising efficacy signals and potentially support successful registration N~350 Positive PFS acceptable for potential initial approval * Dose selection informed by data on 400+0.5 and 100+1 from SEACRAFT-2 St
Slide 43: Anticipated key milestones and clinical trial readouts
Anticipated key milestones and clinical trial readouts 1 IND filed by Joyo Pharmatech; CDE = Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) 2 Data to include safety, pharmacokinetics (PK), and efficacy at relevant dose(s) in relevant population(s) of interest P
Slide 44: Compelling investment thesis
Compelling investment thesis Experienced team with track record of serial successes Seasoned drug developers who have advanced multiple programs from discovery to IND to global approvals World-class Scientific Advisory Board Includes leading pioneers in the RAS/MAPK pathway (Shokat, UCSF; Lito, MSKC
Slide 45: Thank you
ERASCA- eek ; SeBati=ay, “Mogg 3 THAN k YOU!
Slide 46: ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP
ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our TPP Preclinical (in vitro and in vivo) Potency1 OBA2 IP3 TPP: target product profile; OBA: oral bioavailability; IP: intellectual property; FIC: first-in-class; BIC: best-in-class; WT: wildtype; SMi: small molecule inhibitor; MG: m
Slide 47: RAS targeting landscape comments on class
Comments on Class Opportunity for a wider therapeutic window by specifically targeting KRAS More straightforward mechanism via KRAS Switch II pocket binding mode Translation to clinical efficacy TBD Potential for greater potency against specific mutation of interest and wt-sparing Oral bioavailabili
Slide 48: Naporafenib potential first-in-class targeted therapy in NRASm melanoma
Naporafenib has the potential to be a first-in-class targeted therapy to address unmet need in NRASm melanoma Most advanced pan-RAF inhibitor Dosed in more patients than any other pan-RAF inhibitor in development Potential to be first-to-market and raise SOC in prioritized indications PoC establishe
Slide 49: Naporafenib + trametinib favorable, manageable AE profile
Naporafenib + trametinib demonstrated a favorable, manageable AE profile AE: adverse event; BID: twice daily; QD: once daily; SC: SEACRAFT Phase 1 data in NRASm melanoma from De Braud et al AACR 2022 AE profile consistent with expected toxicities associated with RAF and MEK inhibition 400+0.5 dose s
Slide 50: Dose optimization designed to enhance combination benefit/risk profile
Dose optimization designed to enhance combination benefit/risk profile to increase probability of regulatory success in light of Project Optimus naporafenib range of potentially efficacious doses* 400mg BID 100mg BID 200mg BID 0.5mg QD 1mg QD Data from SEACRAFT-1 and SEACRAFT-2 complement each other
Slide 51: Napo + tram OS data showed high consistency across studies and doses
Napo + tram OS data showed high consistency across studies and doses mOS: median overall survival Differences exist between trial designs and subject characteristics and caution should be exercised when comparing data across trials. Reproducibility of these results across studies and doses increases