Erasca, Inc. · NASDAQ:ERAS
Erasca — Investor Presentation (June 2023)
35 slides from Erasca's investor presentation, Jun 5, 2023
Slide 1: On a Journey to Erase Cancer: Erasca Investor Presentation
On a Journey to Erase Cancer Erasca Investor Presentation June 5, 2023 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: Agenda
Erasca Investor Presentation Agenda Portfolio prioritization Portfolio Update Q&A Session Development Update ERAS-007 monotherapy results HERKULES-3: ERAS-007 master protocol in GI cancers HERKULES-2: ERAS-007 master protocol in NSCLC
Slide 4: ERK is a critical target as terminal node of RAS/MAPK pathway
P P P Autophagy MAPK pathway ULK PI3K pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK PI3K AKT mTOR RAS-GDP EGFR Other RTKS MYC GEF As the terminal node of the RAS/MAPK pathway, ERK is a critical target ERK ERK Inhibition of ERK is less susceptible to pathway reactivation compared to inhib
Slide 5: ERAS-007 monotherapy data support combinations across tumor types
1 Based on ERK inhibitors of which we are aware; 2 Comparator ERKi’s are ulixertinib and ravoxertinib; 3 Across ASN007-101 and HERKULES-1 studies at doses from 120-250mg QW and 125mg BID-QW Note: uPR = unconfirmed partial response; cPR = confirmed partial response; PK = pharmacokinetics ERAS-007 mon
Slide 6: ERAS-007 CDP enables efficient evaluation of three key biological hypotheses
ERAS-007 CDP enables efficient evaluation of three key biological hypotheses Targeting adjacent pathways Preventing in-pathway resistance Reversing in-pathway resistance Regimen ERAS-007 + EC Indication EC-naïve BRAF V600E-mutant CRC Regimen ERAS-007 + EC Indication EC-treated BRAF V600E-mutant CRC
Slide 7: ERAS-007 CDP enables efficient evaluation of three key biological hypotheses
ERAS-007 CDP enables efficient evaluation of three key biological hypotheses Targeting adjacent pathways Preventing in-pathway resistance Reversing in-pathway resistance Regimen ERAS-007 + EC Indication EC-naïve BRAF V600E-mutant CRC Regimen ERAS-007 + EC Indication EC-treated BRAF V600E-mutant CRC
Slide 8: Opportunity to improve SoC in patients with 2L+ BRAFm CRC
Opportunity to improve SoC in patients with 2L+ BRAFm CRC (10% of all CRC) Patient Population Benchmark Standard of Care 2/3L BRAFm CRC (EC-naïve) ORR 20% mDOR 6.1m mPFS 4.2m encorafenib + cetuximab 3L+ BRAFm CRC (EC-treated) ORR 6% mDOR N/A mPFS 5.6m TAS-102 + bevacizumab SoC: standard of care; ORR
Slide 9: Scientific rationale: Triple blockade of BRAF, EGFR, and ERK in BRAFm CRC
P P P Autophagy MAPK pathway ULK PI3K pathway RAS-GTP GRB2 GAP GDP GTP P1 NF1 SOS1 RAF MEK PI3K AKT mTOR RAS-GDP EGFR Other RTKS MYC GEF ERK Scientific rationale: Triple blockade of BRAF, EGFR, and ERK in BRAFm CRC SHP2 Combined blockade of ERK plus BRAF/EGFR via treatment with ERAS-007 + encorafeni
Slide 10: ERAS-007 blocked MAPK feedback reactivation in BRAF V600E CRC cell lines
BRAF V600E CRC Cell Lines MEKi combination ERKi combinations Binimetinib 1 µM + Encorafenib 0.1 µM ERAS-007 0.1 µM + Encorafenib 0.1 µM LY3214996 1 µM + Encorafenib 0.1 µM Ravoxertinib 1 µM + Encorafenib 0.1 µM RKO HT29 MAPK Feedback Reactivation No Reactivation Reactivation Reactivation Source: Unp
Slide 11: ERAS-007 + EC in BRAFm CRC: Robust in vivo combination activity
ERAS-007 + EC in BRAFm CRC: Robust in vivo combination activity in BRAF V600E CRC ERAS-007 60 mpk QD dose showed similar activity to 30 mpk BID, either as a mono or combo Tx with encor. +/- cetux. ERAS-007 combinations were generally well tolerated across the tested models as demonstrated by the min
Slide 12: HERKULES-3: Ph 1b/2 evaluating ERAS-007 + EC in BRAFm CRC
HERKULES-3: Ph 1b/2 evaluating ERAS-007 + EC in BRAFm CRC Preventing resistance Reversing resistance Signal-Seeking Expansion in Patients with EC-naïve BRAFm CRC Signal-Seeking Expansion in Patients with EC-treated BRAFm CRC ERAS-007 75 mg BID-QW + EC ERAS-007 100 mg BID-QW + EC ERAS-007 150 mg QW +
Slide 13: ERAS-007 + EC was generally well tolerated with primarily Grade 1 or 2 TRAEs
ERAS-007 + EC was generally well tolerated with primarily Grade 1 or 2 TRAEs observed Data cut 23MAR2023 / * Related to ERAS-007 aEC: encorafenib 300 mg oral daily + cetuximab 500 mg/m2 intravenous infusion once every 2 weeks bERAS-007 QW: ERAS-007 oral once a week. cERAS-007 BID-QW: ERAS-007 oral t
Slide 14: ERAS-007 exhibited predictable PK in combination with EC
ERAS-007 exhibited predictable PK when in combination with EC with no apparent drug-drug interactions Mean ERAS-007 Concentration-Time Profiles Following the First Dose Preventing resistance Reversing resistance Error bars = standard deviation EC = encorafenib 300 mg QD + cetuximab 500 mg/m2 Q2W ERA
Slide 15: Encouraging early efficacy results observed in BRAFm CRC patients
Encouraging early efficacy results observed in BRAFm CRC patients (EC-naïve and EC-treated) Data cut as of 21MAY2023 Response on the bar represents the best overall response based on investigator assessments. * Represents EC-naïve population 1 Per site communication, the patient with uPR was still i
Slide 16: Meaningful activity in EC-naïve BRAFm CRC supports dose expansion
Meaningful activity in EC-naïve BRAFm CRC supports initial focus on and dose expansion of this patient segment Preventing resistance Efficacy-Evaluable BRAFm CRC Patients Time on Treatment (Weeks) ERAS-007 150 mg QW + EC ERAS-007 75 mg BID-QW + EC ERAS-007 100 mg BID-QW + EC First response PD Death
Slide 17: ERAS-007 CDP enables efficient evaluation of three key biological hypotheses
ERAS-007 CDP enables efficient evaluation of three key biological hypotheses Targeting adjacent pathways Preventing in-pathway resistance Reversing in-pathway resistance Regimen ERAS-007 + EC Indication EC-naïve BRAF V600E-mutant CRC Regimen ERAS-007 + EC Indication EC-treated BRAF V600E-mutant CRC
Slide 18: HERKULES-2: ERAS-007 + osimertinib had acceptable and manageable AEs
HERKULES-2: ERAS-007 + osimertinib had acceptable and manageable AEs with no apparent DDI observed in patients with EGFRm NSCLC ERAS-007 150 mg QW + osimertinib 80mg QD identified as the MTD/RD Combination had acceptable and manageable AEs AEs similar to monotherapy ERAS-007 Most frequent (≥ 20%) TR
Slide 19: Efficacy data do not support continued evaluation of ERAS-007 + osimertinib
Efficacy data do not support continued evaluation of ERAS-007 + osimertinib Best response of ERAS-007 + osimertinib in limited sample size (N=16) was SD Data Cutoff 23SEP2022 PD: progressive disease; SD: stable disease; NE: not evaluable Reversing resistance 100 80 60 40 20 0 -20 -40 -60 -80 -100 0
Slide 20: ERAS-007 CDP enables efficient evaluation of three key biological hypotheses
ERAS-007 CDP enables efficient evaluation of three key biological hypotheses Targeting adjacent pathways Preventing in-pathway resistance Reversing in-pathway resistance Regimen ERAS-007 + EC Indication EC-naïve BRAF V600E-mutant CRC Regimen ERAS-007 + EC Indication EC-treated BRAF V600E-mutant CRC
Slide 21: ERAS-007 + palbociclib: acceptable safety and tolerability
ERAS-007 + palbociclib: acceptable safety and tolerability with reversible and manageable TRAEs ERAS-007 BID-QW Palbo QD n 75 mg 75 mg 7 75 mg 100 mg 2 100 mg 100 mg 7 75 mg 125 mg 14 100 mg 125 mg 15 125 mg 125 mg 1 All 46 Preferred Term Any Gr n (%) Gr ≥ 3 n (%) Any Gr n (%) Gr ≥ 3 n (%) Any Gr n
Slide 22: Efficacy data do not support continued evaluation of ERAS-007 + palbociclib
Efficacy data do not support continued evaluation of ERAS-007 + palbociclib Best response of ERAS-007 + palbociclib in limited sample size (N=34) was SD Targeting adj pathways Best Change in Sum of Measurable Target Lesion Diameters From Baseline (%) Efficacy-Evaluable KRASm/NRASm CRC or KRASm PDAC
Slide 23: Other ERAS-007 Clinical Update / Wrap-up
Other ERAS-007 Clinical Update / Wrap-up
Slide 24: HERKULES-1: ERAS-601 + ERAS-007 combination safety data
HERKULES-1: ERAS-601 + ERAS-007 combination safety data do not support continued evaluation of regimen tested Dosing Regimen Tested: ERAS-601 40 mg BID (3 weeks on/1 week off) + ERAS-007 50 mg BID-QW Rationale: ERAS-601 was positioned at its MTD as backbone therapy with dose escalation of ERAS-007 2
Slide 25: Early clinical data reinforce combinability of ERAS-007 as a backbone
Early clinical data reinforce potential combinability of ERAS-007 as a backbone to treat patients with GI cancers including BRAFm CRC Note: PK = pharmacokinetics; DDI = drug-drug interaction; Approved agents evaluated in clinic are osimertinib, encorafenib, cetuximab, and palbociclib Adequate exposu
Slide 26: Portfolio Update
ERASCA- Portfolio Update
Slide 27: Research and development program prioritization actions and rationale
Research Programs Action Rationale ERAS-9 SOS1 Deprioritized Focusing on SHP2 as key upstream RAS/MAPK pathway node due to promise of ERAS-601 compound ERAS-11 MYC Deprioritized Preclinical characterization does not support continued work ERAS-2/3 RAS Switch-II Groove targeting Deprioritized Pursuin
Slide 28: Erasca's modality-agnostic RAS/MAPK pathway-focused pipeline
Program/ Company Target Modality Indication Discovery IND-enabling Phase 1 Phase 2 Phase 3 Erase Cancer Strategy Worldwide Rights Naporafenib BRAF/CRAF Pan-RAS Q61X tissue agnostic ❶ NRASm melanoma ❶ NF1 LOF, pan-RAS G13R, BRAF Class 2/3 solid tumors ❶ ERAS-007ǂ ERK1/2 BRAF V600E CRC ❶ ERAS-601 SHP2
Slide 29: Anticipated key milestones and clinical trial readouts
Anticipated key milestones and clinical trial readouts FPD = first patient dose; PK = pharmacokinetics Program Mechanism Trial Name Indication (Combo partner if applicable) Upcoming Milestone(s) Naporafenib Pan-RAF inhibitor SEACRAFT-1 RAS Q61X Solid Tumors (+ trametinib) H2 2023: Ph 1b FPD Q2 2024
Slide 30: Thank You!
ERASCA- Thank You!
Slide 31: ERAS-007 is the most potent ERK inhibitor in development with long residence time
We believe ERAS-007 is the most potent ERK inhibitor in development, with a uniquely long target residence time Assay Type Assay ERAS-007 IC50 (nM) Biochemical ERK1 2 ERK2 2 Cell-based mechanistic (HT-29) pRSK 7 ERAS-007 was designed to be a potent, selective, reversible, oral inhibitor of ERK1/2 Co
Slide 32: ERK inhibitors more robust than MEK inhibitors in shutting down MAPK reactivation
ATP-competitive ERK inhibitors were more robust than MEK inhibitors in shutting down MAPK pathway reactivation; ERAS-007 was most robust in vitro a ERK directly phosphorylates the p90 ribosomal S6 kinase protein (RSK) so RSK phosphorylation (P-RSK) serves as a biomarker of ERK and ultimately RAS/MAP
Slide 33: Likely recommended dose of ERAS-007 for combinations has been well tolerated
Likely recommended dose of ERAS-007 for combinations has been generally well tolerated *includes uniocular chorioretinopathy, papilloedema, retinal detachment, retinal oedema, retinopathy, serous retinal detachment, subretinal fluid, vision blurred, visual impairment, and vitreous floaters. Data ext
Slide 34: ERAS-007 BID-QW enhances time above IC90 while allowing normal cell recovery
ERAS-007 BID-QW (monotherapy) enhances time above IC90 to drive tumor cell killing while extending time below IC50 to allow normal cell recovery ERAS-007: 50-125mg BID-QW dosing provided high target coverage (C>IC90) for enhanced activity, followed by lower PK coverage (C<IC50) for MAPK pathway reco
Slide 35: ERAS-007 PK in combination comparable to monotherapy PK
ERAS-007 PK when administered in combination (+ EC, + palbociclib, and + osimertinib) was comparable to monotherapy PK, suggesting no apparent DDI Error bars = Standard deviation PK: pharmacokinetics; EC: encorafenib + cetuximab; DDI: drug-drug interaction ERAS-007 + encorafenib and cetuximab Mean E