Erasca, Inc. · NASDAQ:ERAS
Erasca — Investor Presentation (December 2022)
81 slides from Erasca's investor presentation, Dec 9, 2022
Slide 1: On a Journey to Erase Cancer: Erasca Corporate Presentation
Exhibit 99.1 On a Journey to Erase Cancer Erasca Corporate Presentation December 2022
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 the anticipated naporafenib licensing transaction an
Slide 3: Accelerating leadership in RAS/MAPK through in-licensing of naporafenib
Erasca is accelerating its leadership in the RAS/MAPK pathway through 1 in-licensing of exclusive worldwide rights to naporafenib (LXH254; pan-RAFi) • Naporafenib is a Phase 2, pivotal-ready pan-RAF inhibitor with a potential first-in-class and Bolsters best-in-class profile in NRASm melanoma & othe
Slide 4: Our name is our mission: to erase cancer
Pro forma with naporafenib 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
Slide 5: ~5.5m lives at stake annually with RAS/MAPK pathway alterations
Relevant RASm’s recut for naporafenib ~5.5m lives at stake annually worldwide with RAS/MAPK pathway alterations Naporafenib’s broad development strategy significantly expands our addressable patient populations New cases estimated worldwide per annum (thousands; numbers may not add up due to roundin
Slide 6: SEACRAFT trials to address naporafenib's Blue Ocean opportunities
Erasca’s SEACRAFT trials to address naporafenib’s Blue Ocean opportunities In any nautical journey, seacraft are needed to traverse the vast blue ocean not just in their capacity as seagoing ships, but also for their important second meaning: skill in navigation. Erasca is navigating the ”blue ocean
Slide 7: Our singular focus is on the RAS/MAPK pathway
Pro forma with naporafenib Our singular focus is on the RAS/MAPK pathway Naporafenib targets BRAF/CRAF node critical to driving signaling in a broad range of RASm cancers EGFR/ FLT3 Other RTKs Our Strategy RAS-GDP 2 GEF Comprehensively shut down GRB2 GDP the RAS/MAPK pathway GAP P GTP 1 Target RAS d
Slide 8: Naporafenib complements Erasca's RAS/MAPK pathway-focused pipeline
Pro forma with naporafenib Naporafenib complements and significantly advances Erasca’s deep modality-agnostic RAS/MAPK pathway-focused pipeline Program/ Erase Cancer Worldwide Target Modality Indication Discovery IND-enabling Phase 1 Phase 2 Phase 3 Company Strategy Rights Pan-RAS Q61X tissue agnost
Slide 9: Naporafenib is synergistic with pipeline shutting down every node
Pro forma with naporafenib Naporafenib is synergistic with Erasca’s industry-leading pipeline shutting down every node of the RAS/MAPK pathway ERAS-801 EGFR/ FLT3 ERAS-12 Other RTKs RAS-GDP ERAS-3490 GEF GRB2 GDP GAP P GTP 1 SOS1 ERAS-9 NF1 SHP2 RAS-GTP ERAS-2/3/4 ERAS-601 MAPK PI3K ERAS-10 pathway
Slide 10: Naporafenib milestones and trial readouts complement existing portfolio
Pro forma with naporafenib Naporafenib milestones and clinical trial readouts complement 4 Erasca’s existing portfolio and potentially accelerate path to market Program Trial Name 2022 2023 2024 Mechanism Indication SEACRAFT-1 H2 2023 H2 2024 – H1 2025 3 Ph 2 FPD Ph 2 combo data RAS Q61 Solid Tumors
Slide 11: 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 World expert in RAS/MAPK pathway with World expert in ERK, having studied Wo
Slide 12: Leadership team has global experience and drive to make a difference
Leadership team has global experience and drive to make a difference Jonathan Lim, MD Mike Varney, PhD David Chacko, MD Ebun Garner, JD Wei Lin, MD Lisa Tesvich- Chairman, CEO, Chairman of R&D, SAB Member, Chief Financial Officer General Counsel Chief Medical Officer Bonora, PhD and Co-Founder and B
Slide 13: Product Development Team leadership with track record of approvals
Product Development Team leadership with deep collective experience and track record of successfully obtaining approvals Complex / Novel HA Negotiations, Global Marketing Commercialization, CDP and Study Implementation, Application ROW Submissions, Study Designs Overall Development Content & Strateg
Slide 14: Key license terms for naporafenib (LXH254)
Key license terms for naporafenib (LXH254) pan-RAFi: Potential first-to-market molecule for melanoma, tissue agnostic, and more Expected financial terms Amount ($M unless otherwise indicated) • License scope: Exclusive license to patent Total upfront $100 rights, know-how, and regulatory – Cash $20
Slide 15: Naporafenib Overview
ERASCA- Naporafenib Overview
Slide 16: BRAF/CRAF is a critical node of the RAS/MAPK pathway
BRAF/CRAF is a critical node of the RAS/MAPK pathway EGFR/ FLT3 Other RTKs RAS-GDP GEF • BRAF and CRAF drive downstream RAS/MAPK GRB2 GDP pathway signaling in RAS mutant cancers GAP P GTP 1 SOS1 NF1 SHP2 • NRASm melanoma and RAS Q61X solid tumors RAS-GTP Autophagy are exquisitely dependent on BRAF a
Slide 17: 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 Biochemical activity of naporafenib against RAF kinase family Biochemical kinome profiling of LXH254 in HCT116 cell lysates Assay Value (nM) Biochemical CRAF IC
Slide 18: Naporafenib clinical development to date
Naporafenib clinical development to date in more than 500 patients Wealth of early phase data has established safety, tolerability and preliminary POC EGFR Other RTKs • Trial LXH254X2101 (n=142): naporafenib FIH dose escalation study RAS-GDP GEF conducted in patients with RAS/MAPK-driven solid tumor
Slide 19: Focused development plan leveraging RAS/MAPK pipeline synergies
Erasca is well positioned to advance naporafenib through a focused development plan that leverages RAS/MAPK pipeline synergies Top priority to address unmet needs in ~395,000 patients WW Focus on securing regulatory approval for naporafenib + trametinib in RAS Q61X tissue agnostic solid tumors (SEAC
Slide 20: Prioritized plan potentially addresses ~3.5m patients
~5.5m lives at stake annually worldwide with RAS/MAPK pathway alterations Prioritized development plan for naporafenib potentially addresses ~3.5m (over 63%) of these New cases estimated worldwide per annum (thousands; numbers may not add up due to rounding) Other solid Alterations GBM HNSCC NSCLC C
Slide 21: Focused development plan in Q61X tissue agnostic solid tumors (SEACRAFT-1)
Focused development plan in Q61X tissue agnostic solid tumors (SEACRAFT-1) Focus on securing regulatory approval for naporafenib + trametinib in RAS Q61X tissue agnostic solid tumors (SEACRAFT-1) and/or NRASm melanoma (SEACRAFT-2) as soon as possible Top Priority 21
Slide 22: Cell line screening data across different RAS mutants
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 22 Source: Monaco K-A, Delach S, et al. LXH254, a P
Slide 23: Activity of naporafenib + trametinib in NRASm melanoma
Strong activity of naporafenib + trametinib observed in NRASm melanoma in LXH254X2102 Phase 1 may also be driven by natural enrichment of Q61X mutations • Strong antitumor activity observed, with ORR = 44% • 15 out of 16 patients had confirmed codon Q61X melanoma (1 patient had no data) Source: Nova
Slide 24: Activity of naporafenib + trametinib in KRASm NSCLC
Strong activity of naporafenib + trametinib also observed in KRASm NSCLC (N=49) in LXH254X2102 Phase 1, showing 34x higher ORR in Q61X/G13R mutated group • ORR in mutated group is 34x more than the ORR in the non-mutated group - ORR in mutated group (n=4): 75% (95% CI: 19.4% - 99.4%) (variability is
Slide 25: Opportunity to address unmet needs in Q61X tissue agnostic solid tumors
Naporafenib + trametinib combination has a compelling opportunity to address unmet needs in the Q61X tissue agnostic solid tumor indication • The targeted patient population has exhausted all treatment options • In these types of advanced patients without any SOC options, preventing Clinical progres
Slide 26: Focused development plan in NRASm melanoma (SEACRAFT-2)
Focused development plan in NRASm melanoma (SEACRAFT-2) Focus on securing regulatory approval for naporafenib + trametinib in RAS Q61X tissue agnostic solid tumors (SEACRAFT-1) and/or NRASm melanoma (SEACRAFT-2) as soon as possible Top Priority 26
Slide 27: NRAS mutant in vivo models sensitive to naporafenib
NRAS mutant in vivo models exhibited sensitivity to naporafenib both as a single agent and in anchored combinations NRASm model treated with NRASm melanoma PDX models treated with LXH254 single agent LXH254 anchored combinations Note: LEE011 or Rib. (ribociclib) is a CDK4/6 inhibitor; Tram (trametin
Slide 28: Current standard of care for NRAS mutant metastatic melanoma
Current Standard of Care for metastatic melanoma with NRAS mutation Poor SOC in post-IO setting highlights a high unmet need indication Frontline therapy is IO mono Post-IO therapy is predominantly chemo or combo Immunotherapy Chemotherapy MEKi (not approved) Nivolumab Dacarbazine Binimetinib Pembro
Slide 29: Clinical activity reproducible across Phase 1 and Phase 2 studies
The observed clinical activity of naporafenib + trametinib in NRASm melanoma was reproducible across Phase 1 and Phase 2 studies at two RDEs LXH254 (200 mg BID) + LXH254 (400 mg BID) + trametinib (1.0 mg QD) trametinib (0.5 mg QD) Data Study/Indication Cutoff ORR DCR DOR ORR DCR DOR Source LXH254X21
Slide 30: Naporafenib + trametinib anti-tumor activity in NRASm melanoma
Naporafenib + trametinib exhibited anti-tumor activity in NRASm melanoma Addition of naporafenib to MEKi improves the historical MEKi mono activity ORR 47% (21%-73%)* ORR 13% (1.7%-41%)* DCR 80% (n=15) DCR 67% (n=15) Regimen (n) Median Prior Therapy ^ ORR * DCR Napo + Trame (30 combined in both RDEs
Slide 31: Durable responses in NRASm melanoma
Naporafenib + trametinib exhibited durable responses in NRASm melanoma Duration of Exposure • Responses observed in patients with normal or high LDH • Median DOR was 3.75 months for both doses • Median PFS was 5.03 months (95% CI: 3.42–5.62)* BID, twice daily; CR, complete response; PD, progressive
Slide 32: Dual MAPK blockade effective in NRASm melanoma
Dual MAPK blockade with naporafenib regimens was effective in NRASm melanoma LXH254C12201 Ph 2 trial confirms encouraging activity of panRAFi + MEKi/ERKi combinations Best Overall Responses in NRASm Melanoma (n=70) Treatment Duration in NRASm Tumors + ERKi + MEKi + MEKi + CDK4/6i + ERKi ORR = 21% OR
Slide 33: Case Study: Partial response in a patient with NRASm melanoma
Case Study: Partial response with naporafenib 200 mg BID + trametinib 1 mg QD in a patient with NRASm melanoma Source: Novartis Non-Confidential Materials 33
Slide 34: Favorable safety and manageable AE profile
Naporafenib + trametinib has a favorable safety and manageable AE profile De Braud et al AACR 2022 34
Slide 35: Naporafenib demonstrates combinability with MAPK pathway inhibitors
Naporafenib demonstrates combinability with inhibitors of MAPK and other pathways No apparent drug-drug interactions noted Treatment-related AEs (in ≥5% of patients) 35 CONFIDENTIAL Source: Lebbe et al, ESMO 2022
Slide 36: Skin toxicities are the most common AEs
Skin toxicities are the most common AEs in naporafenib combinations AEs are manageable and expected to improve with prophylactic skin care Treatment-related Skin AEs (in ≥5% of patients) Source: Lebbe et al, ESMO 2022 36 CONFIDENTIAL
Slide 37: Opportunity to address unmet needs in NRASm melanoma
Naporafenib + trametinib combination has a compelling opportunity to address unmet needs in NRASm melanoma • For patients with NRASm melanoma, the SOC therapies in the post-IO space are minimally active ⎼ Median PFS on chemotherapy is only 1.5 months Clinical ⎼ Median OS on chemotherapy is only 10.1
Slide 38: Proposed pivotal & Phase 2 trial designs
Preliminary plan subject to global Proposed pivotal & Phase 2 trial designs: Creative CDP strategy includes high health authority PTS randomized NRASm melanoma trial and potential for tissue agnostic indication feedback Initiate single-arm and randomized trials in quick succession. NRASm melanoma is
Slide 39: Patients on treatment show potential for PFS benefit in SEACRAFT-2
Analysis of pts with NRASm melanoma in Ph 2 who remain on treatment show potential for napo + tram to potentially demonstrate PFS benefit in SEACRAFT-2 Duration of Exposure (months) for naporafenib 200 mg BID + trametinib 1 mg QD SD >6 PR >5 SD >5 PR <6 PR >5 PR >5 SD >4 SD >4 PR >4 SD <4 SD <4 SD <
Slide 40: Patients continuing on naporafenib + trametinib
Ph 2 patients continuing on treatment on naporafenib + trametinib = potential for confirmation of Ph 1 DOR and potential PFS advantage in SEACRAFT-2 Naporafenib 200mg BID + trametinib 1mg QD 24 enrolled 15 off treatment 9 on treatment n=1 PR progression delayed < 6mo n=1 uPR progression delayed < 4m
Slide 41: Naporafenib broadens exploration into other defined indications
Naporafenib’s addition to Erasca’s pipeline can broaden our exploration into other well-defined indications Explore novel doublet, and possibly triplet, combination(s) in NF1 LOF, RAS G13R, KRAS G12C, and BRAF Class 2 and 3 altered solid tumors (SEACRAFT-3) Exploratory Combinations • These biomarker
Slide 42: Pipeline supports multiple pairwise combinations with naporafenib
Pro forma with naporafenib Our pipeline supports multiple pairwise combinations to expand the potential of naporafenib to patients with other RAS/MAPK-driven tumors and unmet clinical needs EGFR/ FLT3 Other RTKs RAS-GDP ERAS-3490 GEF GRB2 GDP GAP Potential Naporafenib combos with Erasca Pipeline P G
Slide 43: BRAF Class 2 and 3 mutations represent an unmet need
BRAF Class 2 and Class 3 mutations represent an unmet need Naporafenib provides us with an additional agent to target these Potential combinations within Erasca Pipeline that could target BRAF Class 2 and 3 mutations • naporafenib + ERAS-007 • naporafenib + ERAS-601 • ERAS-007 + ERAS-601 • ERAS-007
Slide 44: Pipeline can expand naporafenib into other RAS-driven tumors
Erasca’s pipeline can expand naporafenib into other RAS-driven tumors that lack direct targeted inhibitors • Confirmation of proof-of-concept in NRASm melanoma and RAS Q61X solid tumors, together with signals from exploration into RAS G13R, KRAS G12C, NF1 LOF, and BRAF Class 2 and 3 mutations, will
Slide 45: Clinical development plan generates multiple ways to win
Pro forma with naporafenib Erasca’s clinical development plan generates multiple ways to win for patients RAS/MAPK EGFRm NRASm KRASwt/ RAS Q61X melanoma altered solid NSCLC KRAS G12C BRAFm CRC BRAFm CRC KRASm/ NRASwt/ HPV-negative EGFR altered Indication tumors post-osi NSCLC EC-naïve EC-treated NRA
Slide 46: Compelling investment thesis
Pro forma with naporafenib 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 Leading pioneers in KRAS (Shokat, UCSF), SHP2 (B
Slide 47: Thank You!
ERASCA- Thank You!
Slide 48: Naporafenib (LXH254): Phase 2, pivotal-ready pan-RAF inhibitor
Naporafenib (LXH254): a Phase 2, pivotal-ready pan-RAF inhibitor with potential first-in-class and best-in-class profile in RAS/MAPK-altered tumors Naporafenib • Potent (sub-nanomolar IC50 against BRAF and CRAF), • 500+ patients treated with naporafenib selective, orally bioavailable pan-RAF inhibit
Slide 49: Naporafenib inhibits RAS/MAPK signaling in RAS mutant cells
Naporafenib inhibits RAS/MAPK pathway signaling in RAS mutant cells pMEK MEK Cellular Assay IC50 (nM) pERK pMEK (Calu-6, KRAS Q61K) 14 ERK Cellular proliferation 470 BRAF inhibition (Calu-6) CRAF GAPDH HCT116 MEL-JUSO MIA PaCa-2 KRAS G13D KRAS Q61L KRAS G12C NRAS G13D Source: Monaco K-A, Delach S, e
Slide 50: ERK is a critical terminal node of the RAS/MAPK pathway
As the terminal node of the RAS/MAPK pathway, ERK is a critical target EGFR/ FLT3 Other RTKs RAS-GDP GEF GRB2 GDP GAP P GTP 1 SOS1 • ERK is less susceptible to pathway reactivation NF1 SHP2 compared to MEK RAS-GTP Autophagy MAPK PI3K • ERK is implicated in acquired resistance to pathway pathway RAFi
Slide 51: ERAS-007 is the most potent ERK inhibitor in development
We believe ERAS-007 is the most potent ERK inhibitor in development Assay Type Assay ERAS-007 IC50 (nM) ERAS-007 ERK1 2 Biochemical designed to be a potent, selective, ERK2 2 reversible, oral inhibitor of ERK1/2 Cell-based mechanistic (HT-29) pRSK 7 ERAS-007 exhibited potent anti-proliferative activ
Slide 52: ERAS-007's long target residence time may enable dosing flexibility
ERAS-007’s uniquely long target residence time may enable dosing flexibility In multiple assays, ERAS-007 had longer target residence time vs. other ERKi’s, which may allow for longer intervals between doses in patients -1 Compound k (s ) Residence Time (min) off -4 ERAS-007 0.30 x 10 550 -4 Ulixert
Slide 53: HERKULES and SU2C clinical trial series
HERKULES and SU2C clinical trial series – ERAS-007 master protocols HERKULES-1 HERKULES-2 HERKULES-3 Stand Up To Cancer Tissue Agnostic Lung Cancer GI Cancer Lung and GI Cancer Agent(s) Indication Regimen Indication Regimen Indication Regimen Indication Regimen Indication Exploring safety ERAS-007 +
Slide 54: ERAS-007 in vivo combination activity in BRAF V600E CRC
ERAS-007 showed strong in vivo combination activity in BRAF V600E CRC TGI in RKO (BRAF V600E CRC) TGI in WiDr (BRAF V600E CRC) EC-resistant CDX Model EC-sensitive CDX Model Treatment group Treatment group ERAS-007 30 mpk BID ERAS-007 30 mpk BID 1,500 2,000 Cetux. 30 mpk Q3D Cetux. 30 mpk Q3D Encor.
Slide 55: ERAS-007 + palbociclib enhanced tumor growth inhibition
ERAS-007 + palbociclib enhanced tumor growth inhibition (TGI) in KRASm CRC and PDAC models TGI in KRAS G13D CRC CDX LoVo TGI in KRAS G12D PDAC PDX PAN026 • Combination was tolerated in mice (e.g., no dose holidays, deaths, or euthanizations) • ERAS-007 and palbociclib were dosed orally and continuou
Slide 56: ERAS-007 + ERAS-601 MAPKlamp activity in BRAF class 3 and NF1 LoF models
ERAS-007 + ERAS-601 MAPKlamp showed consistent combination activity in BRAF class 3 and NF1 loss of function (LoF) models TGI in NF1 LoF NSCLC NCI-H1838 TGI in BRAF Class 3 NSCLC PDX LUN023 • MAPKlamp combination showed activity in both models and was tolerated in mice (e.g., no dose holidays, death
Slide 57: SHP2 is a critical on/off switch for GTP-bound KRAS signaling
SHP2 is a critical “on/off switch” that activates GTP-bound KRAS signaling EGFR/ FLT3 Other RTKs • SHP2 is a convergent node for upstream RAS-GDP GEF RTK signaling GRB2 GDP GAP P GTP 1 SOS1 NF1 SHP2 • A SHP2i can block dephosphorylation to SHP2 RAS-GTP Autophagy maintain GTP-bound KRAS in a “dark MA
Slide 58: ERAS-601 demonstrates high potency and selectivity against SHP2
ERAS-601 demonstrates high potency and selectivity against SHP2 IC (nM) 50 Cell Line Cancer Type Biochemical SHP2 1 Compound ERAS-601 RMC-4550 inhibition IC50 (nM) HCC44 NSCLC 48 95 ERAS-601 4.6 MIA PaCa-2 Pancreatic 6 17 NCI-H1373 NSCLC 64 474 NCI-H1792 NSCLC 40 27 KRAS G12C NCI-H2122 NSCLC 259 1,8
Slide 59: ERAS-601 physicochemical, ADME, and PK properties
ERAS-601: favorable physicochemical, ADME, and PK properties well suited for combination therapy ERAS-601 PK Route of Assay ERAS-601 Parameter Mouse Rat Dog Administration (Unit) (CD-1) (SD) (Beagle) cLogP/PSA <1/<130 Cl IV 13 9.9 9.8 (mL/min/kg) MW <600 PO %F 63 48-83 75-107 PBS solubility (µM) >30
Slide 60: ERAS-601 in FLAGSHP-1 and HERKULES master protocol
ERAS-601 in FLAGSHP-1 clinical trial and HERKULES master protocol HERKULES-2 FLAGSHP-1 Sub-Study B Part A, B, and C Part D ERAS-601 + sotorasib combination in Monotherapy ERAS-601 + NSCLC Dose Escalation 1 cetuximab Combination Dose Escalation Dose Expansion QD Dose Dose Escalation Cohorts Cohorts C
Slide 61: ERAS-601 + cetuximab tumor inhibition in triple wildtype CRC and HNSCC models
ERAS-601 + cetuximab demonstrated significantly greater tumor inhibition vs. cetuximab alone in triple wildtype CRC and HPV-negative HNSCC models TGI in Triple WT CRC PDX model CRC1021 TGI in HPV-negative HNSCC PDX HN3411 700 Vehicle 1,000 Vehicle Cetuximab 20 mg/kg BIW Cetuximab 30 mg/kg Q3D ERAS-6
Slide 62: SHP2 and ERK are critical nodes of the RAS/MAPK pathway
SHP2 and ERK are critical nodes of the RAS/MAPK pathway EGFR/ FLT3 • As the terminal node, ERK is Other • SHP2 is a convergent RTKs less susceptible to node for upstream RTK RAS-GDP GEF pathway reactivation signaling GRB2 GDP compared to MEK GAP P GTP 1 SOS1 • A SHP2i can block NF1 SHP2 SHP2 • ERK i
Slide 63: ERAS-601 and ERAS-007 target SHP2 and ERK
ERAS-601 and ERAS-007 target SHP2 and ERK, respectively EGFR/ FLT3 Other RTKS Potent, RAS-GDP GEF selective, orally GRB2 GDP bioavailable GAP P GTP 1 SOS1 SHP2 inhibitor NF1 SHP2 ERAS-601 in clinical SHP2 RAS-GTP Autophagy development in FLAGSHP-1 MAPK PI3K pathway pathway and HERKULES-2 RAF PI3K Po
Slide 64: Sept. 2022 R&D Day and ENA 2022 highlights
Sept. 2022 R&D Day and ENA 2022 highlights • ERAS-007 and ERAS-601 are active drugs – monotherapy responses • ERAS-007: uPR in KRAS G12V PDAC on new BID-QW dosing • ERAS-601: cPR in BRAF Class III endometrial cancer—only second company to show Efficacy monotherapy response with SHP2 inhibitor Future
Slide 65: Segmentation framework to identify more responsive subsets
Segmentation framework to identify more responsive subsets within the Blue Ocean for prioritized combination development “Blue Ocean indications” of solid tumors with RAS/MAPK alterations and no approved targeted therapies Less sensitive to Phase 1/1b monotherapy monotherapy inhibition due responses
Slide 66: Methodology for retrospective pooled efficacy analysis
Methodology for retrospective pooled efficacy analysis for ERAS-007 and ERAS-601 in solid tumors with RAS/MAPK pathway alterations* All trials assessing ERAS-007 or ERAS-601 as monotherapies: Retrospective Pooled Analysis ASN007-101, HERKULES-1, FLAGSHP-1 Biologically relevant regimens above the eff
Slide 67: Best overall response in RAS/MAPK-altered Blue Ocean Indications
Best overall response with ERAS-007 or ERAS-601 in 15 RAS/MAPK-altered Blue Ocean Indications across lines of therapy 23% (6 out of 26) of patients responded (confirmed and unconfirmed PR) to single agent ERAS-007 or ERAS-601 * * * * * Unconfirmed partial responses indicated with an asterisk. NOTE:
Slide 68: Duration of treatment in Blue Ocean Indications
Duration of treatment observed with ERAS-007 or ERAS-601 in 15 RAS/MAPK-altered Blue Ocean Indications across lines of therapy Thyroid, BRAF V600E Ovarian, KRAS G12C Saliv. Gland, HRAS Q61 Endometrial, BRAF D594G Pancreatic, KRAS G12V Melanoma, BRAF rearr. Ampullary, KRAS G12V NSCLC, BRAF K601E Pleo
Slide 69: HERKULES-1 Case Study: Single agent ERAS-007 response
HERKULES-1 Case Study: Single agent ERAS-007 response 70-year-old female (Patient 0033) with KRAS G12V metastatic pancreatic cancer Diagnosis Stage II pancreatic cancer, metastatic disease, KRAS G12V, initially diagnosed in January 2018 Sites of Metastases Lung, lymph nodes Surgery, adjuvant radiati
Slide 70: Targetable, more responsive subset of patients with RAS/MAPK alterations
Targetable, more responsive subset of patients with RAS/MAPK alterations “Blue Ocean indications” of solid tumors with RAS/MAPK alterations and no approved targeted therapies CRC Non-CRC BRAFm • N = 9 (subset of the N = 26) • Higher rate of single agent responses to either agent was observed 70
Slide 71: Best overall response in BRAF-driven Blue Ocean Indications
Best Overall Response Observed with ERAS-007 or ERAS-601 in BRAF-driven Blue Ocean Indications across lines of therapy 44% (4 out of 9) of patients responded (confirmed and unconfirmed PR) to single agent ERAS-007 or ERAS-601 * * * * Unconfirmed partial responses indicated with an asterisk NOTE: Blu
Slide 72: Duration of treatment in BRAF-driven Blue Ocean Indications
Duration of Treatment Observed with ERAS-007 or ERAS-601 in BRAF-driven Blue Ocean Indications Thyroid, BRAF V600E (Class 1) Endometrial, BRAF D594G (Class 3) Melanoma, BRAF rearr. (Class 2) NSCLC, BRAF K601E (Class 2) Squamous cell, BRAF rearr. (Class 2) Small bowel, BRAF K601E (Class 2) Lung, BRAF
Slide 73: FLAGSHP-1 Case Study: Single agent ERAS-601 response
FLAGSHP-1 Case Study: Single agent ERAS-601 response 63-year-old female (Patient 0009) with BRAF Class 3 metastatic endometrial cancer Diagnosis Stage III/IV endometrial cancer, metastatic disease, BRAF Class 3, initially diagnosed in September 2018 Sites of Metastases Lung, lymph nodes Prior Therap
Slide 74: Breakdown of tumor types and molecular drivers by trial
Breakdown of tumor types and molecular drivers by trial Number of patients in ERAS-007 and ERAS-601 trials CRC Non-CRC, Non-BRAF-driven 1 ASN007-101 trial : Non-CRC, BRAF-driven 34 ‒ ~93% of patients had non-CRC tumors 1 ‒ Of these, ~62% were 5 BRAF-driven 8 ASN007-101 14 1 HERKULES-1 trial : 0 ‒ ~6
Slide 75: TRAEs of ERAS-601 and ERAS-007 largely non-overlapping
TRAEs of ERAS-601 and ERAS-007 have been largely non-overlapping ERAS-601 and ERAS-007 by common SHP2i TRAEs ERAS-601 and ERAS-007 by common ERKi TRAEs ERAS-601 ERAS-007 ERAS-601 ERAS-007 50-125mg BID-QW 50-125mg BID-QW Treatment-related AEs in 20 and 40 mg BID Treatment-related AEs in 20 and 40 mg
Slide 76: Likely recommended dose of ERAS-007 well tolerated
Likely recommended dose of ERAS-007 for combinations was well tolerated Treatment-related Adverse Events Occurring in ≥ 20% and ≥ 2 Patients at Any Dose (arranged by descending frequency in the 250mg QW any grade column) 50 mg BID-QW (n=4) 100 mg BID-QW (n=11) 125 mg BID-QW (n=8) 250 mg QW (n=29) Sy
Slide 77: ERAS-007 and ERAS-601 target coverage strategies
ERAS-007 and ERAS-601 use different target coverage strategies that seek to achieve optimal efficacy and safety ERAS-007 Mean Cycle 1 PK Profile ERAS-601 Mean Steady State PK Profile * IC * 50 IC 90 * IC 50 ERAS-007: 50-125mg BID-QW dosing provided high target coverage ERAS-601: 40mg BID dosing prov
Slide 78: Dr. Kevan Shokat turned KRAS from undruggable to druggable
Dr. Kevan Shokat at UCSF turned KRAS from undruggable to druggable EGFR/ FLT3 Other RTKS RAS-GDP RAS-GDP GEF GRB2 GDP GAP P • Shokat identified a G12C-specific inhibitor that locks GTP 1 SOS1 NF1 KRAS in inactive state, spurring multiple companies SHP2 RAS-GTP Autophagy to develop KRAS G12C inhibito
Slide 79: CNS-penetrant KRAS G12Ci pre-candidates
We have discovered promising CNS-penetrant KRAS G12Ci pre-candidates Reference 1 Parameter 3490 3691 3599 3537 3788 2 compounds Mouse AUC /D po (hr*kg*ng/mL/mg) 693 597 1,333 535 326 102 - 637 Rat brain / plasma (%) total total 52% 13% 66% 68% 11% 1 - 6% Rat brain concentration (ng / g) 156 32 176 2
Slide 80: Beyond G12C: Targeting KRAS G12D and other RAS-GTP mutations
Beyond G12C: Targeting KRAS G12D and other RAS-GTP mutations EGFR/ FLT3 Other RAS-GDP State RTKS RAS-GDP 2 GEF GRB2 GDP GAP P GTP 1 SOS1 NF1 SHP2 RAS-GTP Autophagy 2 RAS-GTP MAPK PI3K pathway pathway • Targeting KRAS G12D and other RAS-GTP mutations is more challenging, as they are more commonly fou
Slide 81: Our EGFR franchise programs are highly differentiated
Our EGFR franchise programs are highly differentiated ERAS-12: ERAS-801: EGFR CNS- D2/D3 penetrant bispecific for EGFRvIII/wt CRC and inhibitor other tumors • High BBB penetration and good oral bioavailability • Next generation EGFR bispecific antibody discovered by Drs. Dev Sidhu, Sekar Seshagiri &