Relay Therapeutics, Inc. · NASDAQ:RLAY
Relay Therapeutics — Corporate Update (October 2021)
51 slides from Relay Therapeutics's corporate update, Oct 8, 2021
Slide 1: Corporate Update Call: Data Presentations at AACR-NCI-EORTC Molecular Targets Conference
Corporate Update Call: Data Presentations at AACR-NCI-EORTC Molecular Targets Conference October 2021 Exhibit 99.3
Slide 2: Disclaimer
Disclaimer This presentation contains forward-looking statements and information about our current and future prospects and our operations and financial results, which are based on currently available information. All statements other than statements of historical facts contained in this presentatio
Slide 3: Relay Tx Has Delivered Against All Key Objectives
Relay Tx Has Delivered Against All Key Objectives Clear focus on execution Programs RLY-4008 (FGFR2) RLY-1971 (SHP2) RLY-2608 (PI3Kα) Goal Set at Time of July 2020 IPO Status Limit off-target toxicities / be highly selective for FGFR2 Show initial data to support promising tolerability Show initial
Slide 4: Highlights from Recent RLY-4008 Interim Clinical Data Disclosure
FGFR2 – Highlights from Recent RLY-4008 Interim Clinical Data Disclosure Robust inhibition of FGFR2 with promising initial tolerability data Safety and Tolerability Early evidence of tumor regressions across several tumor and alteration types (with 3 out of 6 fusion positive cholangiocarcinoma FGFR-
Slide 5: PI3Kα Opportunity Is Among the Largest Ever for Precision Oncology
PI3Kα Opportunity Is Among the Largest Ever for Precision Oncology Sources: FoundationInsights® database; SEER 1. Annual incidence of solid tumors with KRAS G12C, PI3K H1047R, PI3K H1047X, PI3K E542X + E545X alterations; 2. KRAS wild-type colorectal cancer; 3. Head & Neck Squamous Cell Carcinoma; 4.
Slide 6: PI3Kα – Highlights from Recent RLY-2608 Preclinical Data Disclosure
PI3Kα – Highlights from Recent RLY-2608 Preclinical Data Disclosure Mutant-selective binding to novel allosteric site discovered by Dynamo™ platform Novel Mechanism Inhibited not only H1047X, but also E542X and E545X, potentially doubling the addressable population, while sparing WT PI3Kα Pan-Mutant
Slide 7: Relay Tx – We Have Validated Our Approach
DISCOVERY DISCOVERY IND ENABLING CLINICAL Selection of Validated Target Motion-Based Hypothesis Supporting Preclinical Data Selection of DC Clinical Execution Supporting Early Clinical Data Innovators (Wholly owned programs) FGFR2 RLY-4008 RLY-4008 PI3Kα Franchise PI3KαPAN RLY-2608 Pan-mutant allost
Slide 8: Relay Tx – Our Vision
Relay Tx – Our Vision Current focus Future focus Additional therapeutic areas Additional modalities Franchise expansion Validated targets Small molecule inhibitors Oncology and genetic diseases The more we do, the better we get Motion-Based Drug Design™ Chemical biology insights Deep structural unde
Slide 9: Extensive Precision Medicines Pipeline
Innovators (Wholly-owned programs) FGFR2 RLY-4008 Mutant + WT 3-5K Fusion 5-15K Amp/Mut PI3Kα Franchise PI3KαPAN RLY-2608 Pan-mutant allosteric inhibitor RLY-2608 Pan-mutant allosteric inhibitor 25-110K H1047X, E542X, E545X 10-45K H1047R To be announced at DC or clinical start PI3KαSPECIFIC H1047R-s
Slide 10: Relay Tx Programs
Relay Tx Programs
Slide 11: Extensive Precision Medicines Pipeline – Innovators
Extensive Precision Medicines Pipeline – Innovators Note: Patient #’s refer to total annual number of US patients with late-line cancers compared to comprehensive annual incidence that may be amenable to treatment with our programs Innovators (Wholly-owned programs) FGFR2 RLY-4008 Mutant + WT 3-5K F
Slide 12: Highlights from Recent RLY-4008 Interim Clinical Data Disclosure
FGFR2 – Highlights from Recent RLY-4008 Interim Clinical Data Disclosure Robust inhibition of FGFR2 with promising initial tolerability data Safety and Tolerability Early evidence of tumor regressions across several tumor and alteration types (with 3 out of 6 fusion positive cholangiocarcinoma FGFR-
Slide 13: Validated Target Present in Several Tumor Types
FGFR2 – Validated Target Present in Several Tumor Types FGFR2 Annual Cases (US, comprehensive) FGFR2-altered cancers remain a high unmet medical need Pancreatic Breast Endometrial Skin Melanoma Stomach Lung Bladder CUP Ovarian ~5K-15K patients in the US per year1 ~3K-5K patients in the US per year1
Slide 14: Selective Inhibitor Required to Address Large Unmet Medical Need
FGFR2 – Selective Inhibitor Required to Address Large Unmet Medical Need A selective inhibitor of FGFR2 with broad activity against acquired resistance mutations is necessary to address significant unmet need in patients with FGFR2-altered tumors Compound Company Stage FGFR2 Selective Response Rate
Slide 15: Standard Approach to Discovery Has Had Limited Success
FGFR2 – Standard Approach to Discovery Has Had Limited Success Standard Approach FGFR1 FGFR2
Slide 16: Increasing Experimental Resolution Reveals New Opportunities
FGFR2 – Increasing Experimental Resolution Reveals New Opportunities FGFR1 FGFR2 Down Up Down Up Down Up Down Up Down Up Up Up Down Down Down Up Exploiting the dynamic difference between FGFR1 and FGFR2 enabled Relay Tx to design a selective FGFR2 inhibitor We predicted that a segment of FGFR1 would
Slide 17: RLY-4008 Is Potentially the First Highly Selective Irreversible FGFR2 Inhibitor
FGFR2 – RLY-4008 Is Potentially the First Highly Selective Irreversible FGFR2 Inhibitor Pan-FGFR Inhibitors RLY-4008 AZD4547 Erdafitinib Pemigatinib Futibatinib FGFR2 Note: Single experiment that tested each compound run at 500nM against 468 targets in the absence of ATP and without preincubation So
Slide 18: RLY-4008 Designed to be Active Against Resistance Mechanisms
FGFR2 – RLY-4008 Designed to be Active Against Resistance Mechanisms Note: Left figure adapted from: Goyal L et al. 32nd EORTC/AACR/NCI Virtual Symposium. Abstract 49 and Varghese AM et al. JCO Precision Oncology. 2021;5: 44-50. Heat map displaying fold‑change in potency (IC50) for the indicated inh
Slide 19: RLY-4008 Has Potent In Vivo Antitumor Activity Against Primary FGFR2 Alterations and Resistance Mutations
FGFR2 – RLY-4008 Has Potent In Vivo Antitumor Activity Against Primary FGFR2 Alterations and Common Resistance Mutations Note: End-of-treatment waterfall plots (change in tumor volume) for tumor models treated with 30 mg/kg RLY-4008 or the indicated pan-FGFRi used at doses equivalent to their recomm
Slide 20: RLY-4008 First-in-Human (FIH) Study Design
FGFR2 – RLY-4008 First-in-Human (FIH) Study Design Orally dosed; BID and QD schedules explored using the Bayesian Optimal Interval Escalation (BOIN) design; Starting dose was 50 mg BID Key Objectives: MTD/RP2D, safety, pharmacokinetics, biomarkers (ctDNA, tumor markers), preliminary anti-tumor activ
Slide 21: RLY-4008 FIH Study: Baseline Characteristics
FGFR2 – RLY-4008 FIH Study: Baseline Characteristics Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference ECOG, Eastern Cooperative Oncology Group; PS, performance status; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1. *Soft tissue sarcoma pa
Slide 22: RLY-4008 FIH Study: Pharmacokinetics and Predicted Receptor Occupancy Support QD Dosing
Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference; Pemigatinib – NDA Multi-Disciplinary Review Document, pg 70 BID, twice a day; QD, once a day; RO, receptor occupancy. Predicted receptor occupancy: projected level of engagement of oncogenic FGFR2 at given plasma
Slide 23: RLY-4008 FIH Study: Parallel Bayesian Dose Optimization Ongoing
FGFR2 – RLY-4008 FIH Study: Parallel Bayesian Dose Optimization Ongoing MTD not defined per protocol, RP2D selection is ongoing with the QD dosing schedule Preliminary data as of 09-Sept-2021 Dose reductions 2020 2021 SEP OCT NOV DEC JAN FEB MAR APR MAY JUN JUL AUG SEP Dose cohort enrollment periods
Slide 24: Tolerability Profile of Pan-FGFR Inhibitors for Relevant FGFR1 and FGFR4 AEs
Tolerability Profile of Pan-FGFR Inhibitors for Relevant FGFR1 and FGFR4 AEs Sources: Infigratinib (Truseltiq) Prescribing Information; Pemigatinib (Pemazyre) Prescribing Information; Futibatinib – AACR 2021 Presentation (Goyal et al) (diarrhea %s approximated from presentation) ~ ~ ~ Hyperphosphate
Slide 25: RLY-4008 FIH Study: Initial Evidence of RLY-4008's FGFR2 Selectivity
FGFR2 – RLY-4008 FIH Study: Initial Evidence of RLY-4008’s FGFR2 Selectivity Hyperphosphatemia Diarrhea Preliminary data as of 09-Sept-2021 Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference
Slide 26: RLY-4008 FIH Study: Initial Support for FGFR1- and FGFR4-Inhibition Sparing
FGFR2 – RLY-4008 FIH Study: Initial Support for FGFR1- and FGFR4-Inhibition Sparing in the Clinic Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference EOT, End of Treatment Normal range BID Schedule BID Schedule FGFR1 sparing: Hyperphosphatemia: n=9/49 (18%) patient
Slide 27: RLY-4008 FIH Study: Treatment-Emergent Adverse Events ≥ 20%
FGFR2 – RLY-4008 FIH Study: Treatment-Emergent Adverse Events (TEAEs) ≥ 20% No Grade 4-5 AE Most AEs are low-grade, including hyperphosphatemia and diarrhea TEAEs profile consistent with FGFR1- and FGFR4-sparing Retinopathy/Retinal Pigment Epithelial Detachment (RPED): 7 cases BID n=4/17 (24%) QD n=
Slide 28: Tolerability Profile of Pan-FGFR Inhibitors
Tolerability Profile of Pan-FGFR Inhibitors Sources: Infigratinib (Truseltiq) Prescribing Information; Pemigatinib (Pemazyre) Prescribing Information; Futibatinib – AACR 2021 Presentation (Goyal et al) (%s approximated from presentation for dry eye, alopecia, dry skin, diarrhea, fatigue, dry mouth,
Slide 29: RLY-4008 FIH Study: Promising Emerging Tolerability Profile of FGFR2 Selective Targeting
FGFR2 – RLY-4008 FIH Study: Promising Emerging Tolerability Profile of FGFR2 Selective Targeting Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference 1. Nail toxicities Includes onycholysis, nail disorder, nail discoloration, onychomadesis, paronychia; 2. PPE stands
Slide 30: RLY-4008 Induced Radiographic Tumor Regression in FGFR Inhibitor-Naïve FGFR2-Fusion+ Cholangiocarcinoma
FGFR2 – RLY-4008 FIH Study: RLY-4008 Induced Radiographic Tumor Regression in FGFR Inhibitor-Naïve FGFR2-Fusion+ Cholangiocarcinoma Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference *Confirmed PR; #Tumor resection after data cut off. FGFRi, fibroblast growth fact
Slide 31: RLY-4008 Resulted in Near Complete Regression in FGFR2-Fusion Cholangiocarcinoma
35-year-old male with FGFR2-FLIP1 fusion ICC. Prior treatment: Gemcitabine/Cisplatin 70 mg QD dosing (no dose modification). Relevant AEs: Gr 1 dry eye, Gr 1 onycholysis, Gr 2 stomatitis Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference Courtesy: Dr. V. Sahai (U
Slide 32: RLY-4008 Exhibited Activity in Pan-FGFR Inhibitor Resistant FGFR2-Fusion Cholangiocarcinoma
FGFR2 – RLY-4008 FIH Study: RLY-4008 Exhibited Activity in Pan-FGFR Inhibitor Resistant FGFR2-Fusion Cholangiocarcinoma Regardless of FGFR2 Resistance Mutations Preliminary data as of 09-Sept-2021 Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference Note: (N550, N54
Slide 33: RLY-4008 Produced Tumor Regression in Patient Pretreated with Futibatinib
FGFR2 – RLY-4008 FIH Study: RLY-4008 Produced Tumor Regression in a Patient with FGFR2-Fusion+ Cholangiocarcinoma Pretreated with Futibatinib 51-year-old female with FGFR2-CIT fusion ICC. Prior treatments: Gemcitabine/Cisplatin, Futibatinib Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC M
Slide 34: RLY-4008 FIH Study: Yet to Be Confirmed PR in FGFR2-Fusion CCA Patient
65-year-old male with FGFR2-WAC fusion CCA and 3 FGFR2 resistance mutations: N550K, N550D, V565I. Prior FGFR treatment: Infigratinib. RLY-4008 treatment is ongoing at C3 (30 mg QD). Data as of 01OCT21- post data lock Note: (N550, N549), (V565, V564) are different terminology for the same mutated sit
Slide 35: RLY-4008 Showed Tumor Regression in FGFR2 Oncogenic Mutations and Amplifications
FGFR2 – RLY-4008 FIH Study: RLY-4008 Showed Radiographic Tumor Regression in FGFR2 Oncogenic Mutations and in FGFR2 Amplifications Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference *Confirmed PR with increased tumor reduction after data cut; ^PR pending confirmat
Slide 36: RLY-4008 Resulted in Confirmed PR in Heavily Pretreated FGFR2 N550K Mutant Breast Cancer
Confirmed PR at Cycle 5 - 41% by RECIST v1.1 Source: RLY-4008 data as presented at 2021 AACR-NCI-EORTC Molecular Targets Conference Note: N550 and N549 are different terminology for the same mutated site Courtesy: Dr. A. Schram (MSKCC) 60-year-old female with breast cancer ER+ HER2- ESR1 mut PIK3CA
Slide 37: RLY-4008 FIH Study: Time on Treatment and Response by FGFR2-Alteration
FGFR2 – RLY-4008 FIH Study: Time on Treatment and Response by FGFR2-Alteration N=48 patients 26/48 patients (54%) ongoing on treatment Most treatment discontinuations (73%) due to Progressive Disease Duration on treatment: range 4-45 weeks Preliminary data as of 09-Sept-2021 Source: RLY-4008 data as
Slide 38: RLY-4008 FIH Study: RLY-4008 Initial Observations
FGFR2 – RLY-4008 FIH Study: RLY-4008 Initial Observations RLY-4008 is potentially the first highly selective FGFR2 inhibitor in the clinic that targets driver alterations and FGFR inhibitor resistance mutations Robust FGFR2 inhibition observed with ≥ 85% receptor occupancy and minimal off-isoform to
Slide 39: PI3Kα – Highlights from Recent RLY-2608 Preclinical Data Disclosure
PI3Kα – Highlights from Recent RLY-2608 Preclinical Data Disclosure Mutant-selective binding to novel allosteric site discovered by Dynamo™ platform Novel Mechanism Inhibited not only H1047X, but also E542X and E545X, potentially doubling the addressable population, while sparing WT PI3Kα Pan-Mutant
Slide 40: PI3Kα – Existing Inhibitors Establish POC but Have Limited Therapeutic Window
PI3Kα – Existing Inhibitors Establish POC but Have Limited Therapeutic Window Data from PhI/Ib Inavolisib Combination Trial in HR+, HER2-, PIK3CAmut mBC presented at SABC 2020 Dose modifications: 36% Hyperglycemia: 61% (23% Grade 3/4) GI toxicity: 48% Rash: 19% Dose modifications: 64% Hyperglycemia:
Slide 41: PI3Kα – Relay Tx Has a Unique Understanding of PI3Kα
PI3Kα – Relay Tx Has a Unique Understanding of PI3Kα PI3Kα Franchise PI3KαPAN RLY-2608 Pan-mutant allosteric inhibitor PI3KαSPECIFIC H1047R-specific allosteric inhibitor PI3KαOTHER Other PI3Kα allosteric programs Relay Tx has a unique understanding of PI3Kα RLY-2608 (pan-mutant selective) is the fou
Slide 42: PI3Kα – Proprietary Insights Unlock Additional Approaches
PI3Kα – Proprietary Insights Unlock Additional Approaches A differentiated understanding of the structure of PI3Kα and its relationship to function equips Relay Tx to design optimal mutant-selective inhibitors of PI3Kα Designed mutant selective PI3Kα inhibitor Discovered novel allosteric pocket favo
Slide 43: PI3Kα – RLY-2608 Has Shown Mutant and Isoform Biochemical Selectivity
PI3Kα – RLY-2608 Has Shown Mutant and Isoform Biochemical Selectivity Potency (nM) H1047R E542K E545K WT Alpelisib GDC-0077 RLY-2608 RLY-2608 has shown biochemical selectivity for mutant over wild type PI3Kα α-mut Potency (nM) β δ Alpelisib RLY-2608 GDC-0077 RLY-2608 was inactive on other isoforms γ
Slide 44: PI3Kα – RLY-2608 Is Selective Across the Kinome
PI3Kα – RLY-2608 Is Selective Across the Kinome RLY-2608 inhibited only PI3Kα, with preferential inhibition of mutant
Slide 45: PI3Kα – RLY-2608 Inhibited Mutant PI3Kα More Potently in Cells
PI3Kα – RLY-2608 Inhibited Mutant PI3Kα More Potently in Cells RLY-2608 was more potent against mutant cells Orthosteric binders were equipotent between WT and mutant Alpelisib GDC-0077 RLY-2608
Slide 46: PI3Kα – RLY-2608 Potently Inhibited Signaling and Viability in PIK3CA Mutant Cancer Cell Lines
PI3Kα – RLY-2608 Potently Inhibited Signaling and Viability in PIK3CA Mutant Cancer Cell Lines Activity observed in both kinase and helical domain mutant cell lines Activity observed in both kinase and helical domain mutant cell lines pAKT Viability
Slide 47: PI3Kα – In Vivo Tumor Regressions Across Both Mutation Hotspots
PI3Kα – In Vivo Tumor Regressions Across Both Mutation Hotspots (Mouse Study) H1047R mutant (HCC1954) (mouse) 1. This model also carries a second mutation at K567R; 2. HSC2 model; 3. Consistent results observed at 1hr timepoint in MCF7 (E545K) model; 4. Subject to submission and acceptance of IND by
Slide 48: PI3Kα – RLY-2608 Had Reduced Impact on Glucose Homeostasis
In higher species, dosing of RLY-2608 for 28 days showed no histopathological or ophthalmic findings associated with hyperglycemia PI3Kα – RLY-2608 Had Reduced Impact on Glucose Homeostasis (28-Day Dog Study) Adapted from Hanker Cancer Disc 2019 Less uptake increases glucose in blood Pancreas Liver
Slide 49: Extensive Precision Medicines Pipeline – Challengers
Extensive Precision Medicines Pipeline – Challengers Note: Patient #’s refer to total annual number of US patients with late-line cancers compared to comprehensive annual incidence that may be amenable to treatment with our programs Innovators (Wholly-owned programs) FGFR2 RLY-4008 Mutant + WT 3-5K
Slide 50: What To Expect From Relay Tx
What To Expect From Relay Tx Nearer-term milestones Medium-term drivers $671M Cash, cash equivalents and investments as of the end of Q2 2021 Continued evolution of our Dynamo™️ platform 5 additional innovator programs Pursuit of challenger targets through partnerships Execution focus underpins valu
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