Erasca, Inc. · NASDAQ:ERAS
Erasca — Investor Presentation (January 2024)
41 slides from Erasca's investor presentation, Jan 9, 2024
Slide 1: On a Journey to Erase Cancer: Erasca Corporate Presentation
On a Journey to Erase Cancer Erasca Corporate Presentation January 2024 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 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 Una
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) World expert in ERK, having studied nearly every ERK inhibitor that has been or is being devel
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 TCR T cell therapy investment Deep modality-agnostic RAS/MAPK pathway-focused pipeline Program/ Company Target Modality Indication Discovery IND-enabling Phase 1 Phase 2 Phase 3 Worldwide Rights Naporafenib BRAF/CRAF Pan-RAS Q61X tissue agnostic NRASm melanoma ERAS-007
Slide 7: Clinical development plan generates multiple ways to win for patients
Erasca’s clinical development plan generates multiple ways to win for patients Indication Benchmark Regimen tested Erasca trial(s) CTCSA: clinical trial collaboration and supply agreement ORR: overall response rate; DOR: duration of response; GBM: glioblastoma HERKULES-32 BRAFm CRC EC-naïve ERAS-007
Slide 8: Naporafenib pan-RAFi could address unmet needs in over 200k patients
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 over 200k patients in the US and Europe ERK BRAF CRAF naporafenib Addressable Patient Pop. Tumor Type RAS Q61X So
Slide 9: 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 IC50 (IC50) 0.1 Biochemical BRAF IC50 (IC50) 0.2 Biochemical ARAF Inhibition (IC50) 6.4 Biochemical activity of naporafenib aga
Slide 10: In vivo efficacy of naporafenib and trametinib across NRASm melanoma PDX models
In vivo efficacy of naporafenib and trametinib administered across 10 NRASm melanoma PDX models shows strong synergy of combination vs. either monotherapy Untreated Naporafenib 50 mg/kg BID Trametinib 0.3 mg/kg QD Naporafenib 50 mg/kg BID + Trametinib 0.075 mg/kg QD PDX = patient derived xenograft;
Slide 11: Naporafenib dosed in more than 500 patients to date
Naporafenib has been dosed in more than 500 patients to date, establishing its safety, tolerability, and preliminary PoC in multiple indications Source: Novartis Non-Confidential Materials; PoC = proof-of concept P P P MAPK pathway PI3K pathway RAS-GTP GRB2 SHP2 GAP GDP GTP P1 NF1 SOS1 RAF MEK PI3K
Slide 12: Naporafenib: potential for rapid market entry
Naporafenib: potential for rapid market entry and multiple ways to benefit patients with RAS/MAPK-driven tumors patients diagnosed annually in the US and EU 157,000 patients diagnosed annually in the US and EU 54,000 NRASm Melanoma RAS Q61X Solid Tumors Potential for full approval based on high unme
Slide 13: SEACRAFT-1: naporafenib + trametinib in RAS Q61X solid tumors
SEACRAFT-1: Naporafenib + trametinib has the potential to provide therapeutic benefit to ~157k patients in the US + EU with RAS Q61X solid tumors Naporafenib (pan-RAFi) Dosed in >500 pts establishing safety and tolerability in a range of doses for combination partners Encouraging anti-tumor activity
Slide 14: Differences across RAS mutants in cell line screening data
Structural and cell line screening data suggest that differences exist across different RAS mutants in vitro; e.g., Q61X mutant tumors likely to be CRAF addicted Cellular activity of naporafenib across 265 cell lines, separated by RAS mutation type Source: Monaco K-A, Delach S, et al. LXH254, a Pote
Slide 15: Preliminary clinical PoC in NRAS Q61X melanoma and KRAS Q61X NSCLC
Preliminary clinical PoC in NRAS Q61X melanoma and KRAS Q61X NSCLC supports development in RAS Q61X tissue agnostic solid tumors (SEACRAFT-1) Strong antitumor activity, with confirmed ORR = 44% 15 out of 16 patients had confirmed codon Q61X melanoma (1 patient had no data) Source: LXH254X2102 Ph 1b
Slide 16: SEACRAFT-2: first-in-class targeted treatment 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 EOP2 process for Phase 3 design Napo + tram demonstrated compelling efficacy across Phase 1 and 2 studies (mPFS ~5 months) FDA Fast Tr
Slide 17: NRASm melanoma case study: partial response
NRASm melanoma case study: partial response with naporafenib + trametinib Source: Novartis Non-Confidential Materials On treatment Pre-treatment
Slide 18: Compelling, reproducible clinical efficacy across studies and doses
Compelling, reproducible clinical efficacy across studies and doses 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=32 ORR n (%) 41 (15%) 5 (15%) 9 (7%) 12 (31%) 7 (22%) DCR n
Slide 19: Naporafenib + trametinib favorable, manageable safety profile
Naporafenib + trametinib demonstrated a favorable, manageable safety 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 do
Slide 20: Dose optimization 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 21: SEACRAFT-2 and SEACRAFT-1 trial designs
SEACRAFT-2: NRASm Melanoma (Two-stage Phase 3) Pivotal Phase 3 and Phase 1b trial designs capitalize on promising efficacy signals and support potential successful registration in multiple indications Solid Tumors Post-available therapy RAS Q61X (NRAS, HRAS, KRAS) naporafenib + trametinib (200mg + 1
Slide 22: ERAS-007 ERKi could address unmet needs in ~45k patients
ERAS-007 ERKi could address unmet needs in ~45k patients annually in the US and Europe 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 ERAS-007 BRAF V600E CRC 45,000 Addressable Patient Pop. Tumor Type
Slide 23: ERAS-007 is the most potent ERK inhibitor in development
We believe ERAS-007 is the most potent ERK inhibitor in development, with a uniquely longer 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
Slide 24: HERKULES-3: ERAS-007 + EC for BRAF V600E CRC
HERKULES-3: ERAS-007 + EC is a potential best-in-class treatment for patients with BRAF V600E CRC ERAS-007 (ERKi) Inhibiting the terminal RAS/MAPK pathway node has potential to shut down oncogenic signaling and prevent reactivation Early signals of clinical efficacy in EC-naïve BRAFm CRC Clinical da
Slide 25: ERAS-007 + EC: in vivo combination activity in BRAF V600E CRC
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 26: Meaningful activity in EC-naïve BRAFm CRC
Meaningful activity in EC-naïve BRAFm CRC supports initial focus on and dose expansion of this patient segment 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 Treatment discontinuat
Slide 27: ERAS-007 + EC generally well tolerated
ERAS-007 + EC was generally well tolerated with primarily Grade 1 or 2 TRAEs observed Data cutoff 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 ora
Slide 28: ERAS-801 EGFRi could address high unmet need in 37k patients
ERAS-801 EGFRi could address high unmet need in 37k patients in US and EU 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 ERAS-801 Glioblastoma multiforme 37,000 Addressable Patient Pop. Tumor Type
Slide 29: Poor activity of legacy EGFRi in GBM
Poor activity of legacy EGFRi in GBM due to minimal activity against GBM-specific EGFR alterations and poor CNS penetration TCGA Cell, 2013 GBM: glioblastoma; CNS: central nervous system; PFS: progression free survival; OS: overall survival Therapy (brain penetration %) Clinical Trial Results*: NSCL
Slide 30: THUNDERBBOLT-1: ERAS-801 designed to overcome GBM treatment limitations
THUNDERBBOLT-1: ERAS-801 (CNS-penetrant EGFRi) designed to overcome the limitations of current GBM treatments Higher CNS penetration over legacy EGFR inhibitors Broad activity against oncogenic and wildtype EGFR Potential as a monotherapy treatment FDA Orphan Drug Designation and Fast Track Designat
Slide 31: ERAS-801 designed to inhibit EGFR in GBM with high brain penetration
ERAS-801, a potent EGFRvIII/wt inhibitor with a Kp,uu over 4-fold higher than approved EGFR inhibitors, was specifically designed to inhibit EGFR in GBM 1 Kp,uu is a measure of the ratio of unbound brain concentration to unbound plasma concentration Kim M, et al. Brain Distribution of a Panel of Epi
Slide 32: ERAS-801 significantly extends survival in GBM model
ERAS-801 significantly extends survival at clinically relevant exposures in an EGFR amplified and EGFRvIII model EGFR amplified and EGFRvIII patient-derived GBM model *** *** p-value < 0.005 Doses are estimated to reflect clinically relevant human exposures
Slide 33: THUNDERBBOLT-1: Dose escalation cohorts
THUNDERBBOLT-1: Dose escalation cohorts 20mg 280mg 320mg MTD 240mg 40mg 80mg MTD-1 160mg Safety Expansion EGFR amp mandatory Evaluate safety, tolerability, PK/PD, and preliminary efficacy including PET and CSF sampling Determine RP2D Clinicaltrials.gov: NCT05222802 Note: ERAS-801 dosed QD MTD: max
Slide 34: Anticipated key milestones and clinical trial readouts
Anticipated key milestones and clinical trial readouts 1 Data to include safety, pharmacokinetics (PK), and efficacy at relevant dose(s) in relevant population(s) of interest Program Mechanism Trial Name Indication (Combo partner if applicable) Anticipated Milestone Naporafenib Pan-RAF inhibitor SEA
Slide 35: 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: KRAS (Shokat, UCSF), SHP2 (Blacklow, HMS), ER
Slide 36: Thank You!
ERASCA- Thank You!
Slide 37: New cases estimated worldwide per annum by alteration
* 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 (20
Slide 38: Naporafenib: Potential first-in-class pan-RAF inhibitor
Naporafenib: Potential first-in-class pan-RAF inhibitor DCC-3084 IRICoR-Ipsen CUL-BRAF Degrader IND-enabling Licensed from IRICoR PRECLINICAL Most advanced pan-RAF inhibitor Dosed in more patients (500+) than any other pan-RAF inhibitor in development Potential to be first-to-market and raise SOC in
Slide 39: ERAS-007: Potential best-in-class ERK1/2 inhibitor
ERAS-007: Potential best-in-class ERK1/2 inhibitor in a field marked by attrition 51 Hit-and-run profile optimizing efficacy, tolerability Highest potency and longest target residence time of known ERKi’s enable ERAS-007 to be dosed intermittently instead of daily like other clinical ERKi’s Safety a
Slide 40: 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 41: Maximize time above IC90 while maintaining Cmin near IC50
Goal is to maximize the time above IC90 to improve cancer cell killing, while maintaining Cmin near or below IC50 to give normal cells a treatment break (i.e., extend time below IC50) Dosing Regimen Cmax, ng/mL Cmin, ng/mL T>IC90 T<IC50 250 mg QW 425 3 ~2/7 ~1/7 50 mg BID-QW 103 3 ~2/7 ~1/7 80 mg BI