eFFECTOR Therapeutics Inc · OTC:EFTR
eFFECTOR Therapeutics — Corporate Update (January 2023)
22 slides from eFFECTOR Therapeutics's corporate update, Jan 5, 2023
Slide 1: Zotatifin Clinical Data and Corporate Update
Exhibit 99.1 Zotatifin Clinical Data and Corporate Update January 5, 2023
Slide 2: Disclaimer: Forward-Looking Statements
Disclaimer FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding the future clinical development of eFFECTOR Therapeutics, Inc.’s (eFFECTOR or the Compa
Slide 3: Participants and Agenda
Zotatifin Clinical Data and Corporate Update Participants Agenda • Introductory Remarks • Steve Worland, Ph.D., President & CEO • Zotatifin Oncology Update • Doug Warner, M.D., Chief Medical Officer • Zotatifin COVID Update • Mike Byrnes, Chief Financial Officer • Tomivosertib Update • Business Upda
Slide 4: Oncogenic Signaling Selectively Activates Translation to Drive Tumor-Promoting Proteins
Oncogenic Signaling Selectively Activates Translation to Drive Production of Specific Tumor-Promoting Proteins • Multiple signaling pathways, including RAS and PI3K, activate mRNA translation to drive production of specific proteins • Tumors are dependent on upregulated protein production for growth
Slide 5: Selective Translation Regulator Inhibitor (STRI) Platform
Selective Translation Regulator Inhibitor (STRI) Platform: Controlling the Outputs of Tumor-driving Pathways • Focused on three targets that drive translation: o MNK: kinase phosphorylates RNA-binding proteins o eIF4A: helicase unwinds RNA secondary structures o eIF4E: binds 5’-cap of mRNA • Each ta
Slide 6: Preclinical Regulation of Translation by Zotatifin
Preclinical Regulation of Translation by Zotatifin Selectively Suppressed a Specific Set of Cancer Driving Proteins Zotatifin selectively bound specific sequences found in the 5’ non-coding region of mRNAs encoding certain cancer-driving proteins mRNA mRNA increasing NON-CODING SEQUENCE CODING SEQUE
Slide 7: Zotatifin Phase 1/2 Dose Escalation and Expansion Trial
Zotatifin Phase 1/2 Dose Escalation and Expansion Trial Expansion Cohorts in ER+ BC Part 1 Dose Escalation Combined with fulvestrant • Open label 3+3 design in mixed population +/- abemaciclib • Weekly dosing transitioned to two weeks on/one week off • Primary Objectives include • Safety, tolerabili
Slide 8: ECBF Cohort Zotatifin plus Fulvestrant
ECBF Cohort Zotatifin plus Fulvestrant 206-205 Genetics and Prior Treatments 211-201 201-208 + 209-201 * • 206-205 208-202 * o Confirmed PR continuing at Week 52 209-202 ^ 208-201 * amp mut o Cyclin D1 , ESR1 201-211 * 206-221 + o 7 lines of prior treatment including 206-224 * fulvestrant, palbocicl
Slide 9: Zotatifin Downregulation of Cyclin D1 and CDK4/6
Zotatifin Downregulation of Cyclin D1 and CDK4/6 Designed To Complement CDK4/6 Inhibitors That Target Kinase Subunit Zotatifin CDK4/6 kinase inhibitors 9
Slide 10: Zotatifin Downregulated Cyclin D1 and CDK4/6 in vitro; Combination Active in vivo
Zotatifin Downregulated Cyclin D1 and CDK4/6 in vitro Combination of Zotatifin with Palbociclib Was Highly Active in vivo Zotatifin Blocked Production of Zotatifin Was Active in Preclinical Models of ER+ BC Key Cell Cycle Targets in Cells and Showed Combination Benefit with Palbociclib Fulv Zotatifi
Slide 11: ECBF+A Cohort Zotatifin plus Fulvestrant and Abemaciclib
ECBF+A Cohort Zotatifin plus Fulvestrant and Abemaciclib ORR 29% (2/7) Genetics and Prior Treatments CBR 43% (3/7) • 201-210 o Stable Disease continuing at Week 33 amp amp o Cyclin D1 , FGFR1 o 7 lines of prior treatment including palbociclib • 206-210 On study Partial response o Confirmed PR, PFS o
Slide 12: ECBF Cohort Summary of Treatment-Emergent Adverse Events
ECBF Cohort (Zotatifin plus Fulvestrant) Summary of Treatment-Emergent Adverse Events TEAE Listing for ECBF TEAEs (All Grades) N (%) Grade 3 or Higher N (%) n=18 n=18 0 (%) Nausea 7 (39%) Constipation 5 (27%) 0 (%) 0 (%) Abdominal pain 4 (22%) Anemia 4 (22%) 1 (6%) 1 (6%) Diarrhea 4 (22%) Vomiting 4
Slide 13: ECBF+A Cohort Summary of Treatment-Emergent Adverse Events
ECBF+A Cohort (Zotatifin plus Fulvestrant and Abemaciclib) Summary of Treatment-Emergent Adverse Events TEAE Listing for ECBF+A TEAEs (All Grades) N (%) Grade 3 or Higher N (%) n=7 n=7 Diarrhea 0 (%) 5 (71%) Nausea 4 (57%) 0 (%) Dry mouth 0 (%) 3 (43%) Fatigue 3 (43%) 0 (%) Vomiting 0 (%) 3 (43%) Co
Slide 14: ECBF+A Cohort Summary of Treatment-Emergent Adverse Events, cont'd
ECBF+A Cohort (Zotatifin plus Fulvestrant and Abemaciclib) Summary of Treatment-Emergent Adverse Events, cont’d TEAE Listing for ECBF+A All TEAEs (All Grades) (N %) Grade 3 or Higher N(%) n=7 n=7 Pain in extremity 0 (%) 1 (14%) Palpitations 1 (14%) 0 (%) Pleural effusion 0 (%) 1 (14%) Presyncope 1 (
Slide 15: eIF4A Target Engagement Assessed by RNA Stabilization in Whole Blood
eIF4A Target Engagement Was Assessed by Stabilization of Zotatifin-Sensitive RNA in Whole Blood Formation of ternary complex between zotatifin, eIF4A and RNA resulted in selective, dose-dependent stabilization of JUN RNA relative to housekeeping gene GAPDH 2.5 2.0 1.5 1.0 JUN 0.5 GAPDH 0.0 zotatfin
Slide 16: eIF4A Target Engagement Assessed by Changes in ctDNA Fraction
eIF4A Target Engagement Was Assessed by Changes in Fraction of Circulating Tumor DNA (ctDNA) Fraction of ctDNA decreased at higher doses of zotatifin 100 0.005 mg/kg/wk 50 0.01 mg/kg/wk 0.02 mg/kg/wk 0.035 mg/kg/wk 0 0.05 mg/kg/wk 0.07 mg/kg/wk -50 0.1 mg/kg/wk -100 Fraction of ctDNA relative to tot
Slide 17: Good Safety Results Motivate Additional Dose Escalation
Good Safety Results with Zotatifin To Date Motivate Additional Dose Escalation • Resumed dose escalation at 0.1 mg/kg dosed every other week (Q2W) o Preclinical in vivo data showed full retention of anti-tumor activity with extended-interval dosing • Also plan to resume testing weekly (QW) dosing, s
Slide 18: Zotatifin Well Positioned as Host-Directed Therapeutic for COVID-19
Zotatifin Well Positioned as Host-Directed Therapeutic for COVID-19 and Beyond Zotatifin observed to be more potent in vitro than remdesivir Phase 1b Double-Blind Trial Ongoing Future Development and nirmatrelvir* • Continued widespread • N=36, non hospitalized patients with mild to COVID-19 cases a
Slide 19: KICKSTART: Randomized Phase 2b Trial in Treatment-Naive NSCLC
KICKSTART: Randomized, Double-blind, Phase 2b Trial In Treatment-Naïve NSCLC Patients w/ PD-L1 ≥50% Tomivosertib + pembrolizumab PD-L1 ≥50% STRATIFICATION: 1L R 1:1 - PD-L1 50% to 69% vs. ≥70% Treatment naïve - Squamous vs. non- squamous N=60 Placebo + pembrolizumab • Tomi dosed 100 mg BID with food
Slide 20: Multiple Upcoming Clinical Milestones
Multiple Upcoming Clinical Milestones 2023 2024 Anticipated Milestones 1H 2H Top line data from P2b NSCLC frontline with pembro Tomivosertib Initiate P3 in NSCLC Initial ORR data from remaining 11 patients in ECBF+A P2a (n=18) expansion cohort Zotatifin Oncology Data from P1b dose escalation cohorts
Slide 21: eFFECTOR
eFFECTOR \
Slide 22: Zotatifin Clinical Data and Corporate Update
Zotatifin Clinical Data and Corporate Update January 5, 2023
eFFECTOR Therapeutics — Corporate Update (January 2023) on 6ix