eFFECTOR Therapeutics Inc · OTC:EFTR
eFFECTOR Therapeutics — Locust Walk Acquisition — SPAC Merger (June 2021)
48 slides from eFFECTOR Therapeutics's SPAC merger presentation, Jun 28, 2021
Slide 1: Research Analyst Teach In: Next Generation Targeted Therapy for Cancer
Research Analyst Teach In June 28, 2021 Next Generation Targeted Therapy for Cancer
Slide 2: Disclaimer
Disclaimer ABOUT THIS PRESENTATION This presentation is for informational purposes only to assist interested parties in making their own evaluation with respect to a proposed business combination (the Business Combination) between Locust Walk Acquisition Corp. (LWAC) and eFFECTOR Therapeutics, Inc.
Slide 3: Meeting Agenda
eFFECTOR Therapeutics Analyst Day June 28, 2021 Meeting Agenda Overview Team STRI platform Investment thesis Development pipeline Pipeline review Tomivosertib development Tomivosertib market opportunity Zotatifin development Manufacturing and Intellectual Property summary Financial overview and LWAC
Slide 4: Overview: Team, Pipeline, Platform
Overview Team, Pipeline, Platform Steve Worland, Ph.D., President and CEO
Slide 5: Executive Management Team
EXECUTIVE MANAGEMENT TEAM Steve Worland, Ph.D. Premal Patel, M.D., Ph.D. Alana McNulty Mike Byrnes President Chief Financ Officer
Slide 6: Experienced management team and scientific advisors
Steve Worland, Ph.D. Founder, President, CEO and Director Premal Patel, M.D., Ph.D. CMO Alana McNulty CBO Mike Byrnes CFO Experienced management team to lead EFTR Scientific Advisors Institution Expertise Kevan Shokat, PhD UCSF, eFFECTOR Co-founder Translation & KRAS Davide Ruggero, PhD UCSF, eFFECT
Slide 7: eFFECTOR meets demanding criteria of Locust Walk Acquisition Corp
eFFECTOR MEETS DEMANDING CRITERIA OF LOCUST WALK ACQUISITION CORP Locust Walk Acquisition Corp (LWAC) is a $175M SPAC focused on biotechnology with a comprehensive investment thesis that has been used to evaluate over 90 potential targets SUPERLATIVE CRITERIA Validating Partnership Novel Lead Asset
Slide 8: STRI Platform: Targeting key node in cancer
STRI Platform: Targeting key node in cancer Novel targets located at key node where two important cancer pathways converge and drive production of multiple disease-driving proteins Multiple potential advantages of inhibiting targets related to the eIF4F complex Simultaneously decrease production of
Slide 9: The next phase in cancer therapeutics
THE NEXT PHASE IN CANCER THERAPEUTICS Pioneering Selective Translation Regulator Inhibitors (STRIs) designed to: Simultaneously block production of multiple disease-driving proteins with a single drug Knock down oncoproteins, immune suppression and resistance to create better outcomes Strong IP posi
Slide 10: Major unmet need in oncology
Major UNMET NEED in ONCOLOGY: therapeutic strategies Designed to outsmart cancer Immuno-oncology and targeted therapies have improved outcomes, but only work for subsets of patients Most patients with metastatic cancer develop treatment resistance over time T cell exhaustion leads to disease progres
Slide 11: Imagine cancer medicines that are designed to
Imagine cancer medicines that are designed to: Be well tolerated and easier to take Shut down multiple drivers of cancer simultaneously Reactivate the immune system to eliminate tumors Make existing treatments work better and longer Delay need for toxic chemotherapy
Slide 12: Robust Pipeline: Multiple STRIs in development
ROBUST Pipeline: Multiple STRIs in development Program (Target) Discovery Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Global Rights Anticipated Milestones Tomivosertib (MNK 1/2i) Zotatifin (elF4Ai) eIF4Ei NSCLC – 1L Extension in combo with pembro Solid Tumors RTK BC and KRAS NSCLC Solid Tumors mBC
Slide 13: Poised for significant value inflection events
Foundation Platform – mRNA translation biology from UCSF Chemistry – world class SBDD expertise Culture – rigorous science and capital efficiency Next 12-24 months Tomi – definitive PoC for pembro combination Zota – ORR data from expansion cohorts Zota COVID – human antiviral PoC data eIF4E – in cli
Slide 14: Tomivosertib (eFT508)
Tomivosertib (eFT508) Designed to stimulate activation, prevent exhaustion and prolong memory of T cells MNK 1/2 Inhibitor Premal Patel M.D., Ph.D., CMO
Slide 15: Tomivosertib: potential to delay and reverse resistance to CPI therapy
Checkpoint inhibitors (CPIs) have advanced oncology treatment but: Most patients don’t respond The majority of responders develop resistance and must progress to more toxic chemotherapeutics agents In combination with CPIs, tomi may help overcome resistance to prolong the utility of checkpoint inhib
Slide 16: Tomivosertib designed to delay T cell exhaustion
T Cells Tomivosertib (tomi) designed to delay T cell exhaustion and reinvigorate anti-tumor activity to achieve: Increased target cell killing Simultaneous downregulation of several key checkpoint proteins associated with T cell exhaustion/dysfunction Decreased production of immunosuppressive IL-10
Slide 17: Tomivosertib is a highly selective MNK inhibitor
Tomivosertib is a highly selective mnk inhibitor Tomivosertib was tested against >400 protein and lipid kinases at 1 mM concentration Reich et al. J. Med. Chem. 2018 61, 3516-3540. Kinome Selectivity Map
Slide 18: Tomivosertib reprograms T cells to increase central memory pool
Target cell killing Tomivosertib Reprograms t cells from within to increase central memory pool and enhance cytotoxic function Central memory T cells Mouse Human
Slide 19: Tomivosertib triggered anti-tumor activity and enhanced PD-1 blockade in vivo
Tomivosertib triggered anti-tumor activity and enhanced the activity of PD-1 checkpoint blockade in vivo Immuno- suppressive proteins Tomivosertib Triggered Immune Memory Both as a Single Agent and In Combination with PD-1i Day 8 tumor volume measurement of second tumor implants with no further drug
Slide 20: Tomivosertib increased CD8+ T cell/Treg ratio
Tomivosertib increased ratio of CD8+ T cells/Tregs and decreased M2 macrophage population In CT-26 syngeneic model (efficacy data on slide 11), treatment with tomivosertib increased ratio of CD8+/FOXP3+ cells and decreased M2 macrophages in tumor biopsies Collaborators from McGill University* indepe
Slide 21: Generally well tolerated with single-agent activity
Tomivosertib: Generally Well Tolerated with Single-Agent Activity* Tomivosertib was generally well tolerated at the recommended Phase 2 dose (RP2D) as single agent and in combination with anti-PD-(L)1 agents The most common drug-related side effects have included low grade nausea, vomiting, fatigue
Slide 22: Phase 2a: Prolonged PFS with anti-PD-(L)1 agents
Phase 2a: Prolonged PFS when TOMIvosertib combined with anti-PD-(L)1 agents 39 patient Phase 2a study showed encouraging activity in multiple tumor types* Tomivosertib added on to patients not responding to anti-PD-(L)1 therapy with no change or break in anti-PD-(L)1 regimen Subset including all 17
Slide 23: Patient with checkpoint-refractory NSCLC showed durable tumor regression
Phase 2A: Patient with checkpoint-refractory NSCLC showed immediate and durable tumor regression Patient was PD-(L)1>50% Patient on Tomi/Pembro Combo Experienced Confirmed Complete Response after ~2 Years on Combo Therapy
Slide 24: Phase 2A: Extended PFS in NSCLC patients
Phase 2A: Demonstrated extended PFS in NSCLC patients particularly enriched in PD-(L)1+ patients All patients: mPFS of 20 weeks compared to ~7 weeks in comparative data set in similar patients in the OAK study* PD-(L)1+ patients: mPFS of 53 weeks (in the OAK TBP cohort, PD-(L)1+ status did not impro
Slide 25: PD-(L)1 positive patients showed longer PFS
Pd-(L)1 positive patients in phase 2a trial showed longer pfs A post-hoc analysis showed that PD-(L)1 positive patients had three times lower risk of progression than PD-(L)1 negative patients in Phase 2a study In the OAK treatment beyond progression cohort, PD-(L)1 status was not correlated with be
Slide 26: KICKSTART randomized Phase 2b trial design
KEY ELIGIBILITY CRITERIA: Stage IV NSCLC No prior chemo PD-(L)1 50% Tomivosertib + pembrolizumab Placebo + pembrolizumab Aligned with FDA on novel indication, PFS as primary endpoint and control arm for 1L extension Trial design enriched for PD-(L)1+ patients who received the most benefit in the P2a
Slide 27: How do we define success in KICKSTART
How do we define success in kickstart Clinically meaningful results: PFS Hazard Ratio (HR) of0.65 (p 0.2) in either cohort Illustrative examples 1L extension: mPFS improvement from ~3 months in control arm to 4.5 months in tomivosertib arm OAK TBP cohort showed benefit of ~ 1.5 months vs. our Phase
Slide 28: Phase 2a vs Phase 2b KICKSTART comparison
PHASE 2A (completed) PHASE 2B KICKSTART (ongoing) Patient Population Patients were on any approved PD-(L)1 therapy and allowed prior chemo Pembrolizumab only, no prior chemo in the metastatic setting PD-(L)1 Status Any PD-(L)1 level eligible, including PD-(L)1 negative patients who had shorter PFS O
Slide 29: Tomivosertib Market Opportunity
Tomivosertib (eFT508) Market opportunity Alana McNulty, CBO
Slide 30: Potential market settings in NSCLC
Pembro Monotherapy Metastatic NSCLC ≥ 50% PD-(L)1 w/ No Actionable Mutations Chemotherapy regimens Novel Setting: Tomi + pembro – 1L Extension (reverse resistance) US addressable population ~9K Tomi + pembro – 1L (delay resistance) US addressable population ~27K Potential Market Settings – NSCLC PD-
Slide 31: Tomivosertib market opportunity estimate
Tomivosertib Market OPPORTUNITY Estimate US Markets $4.2B market for 1L $720M+ market for 1L extension Extensive market research conducted by Cello Health (formerly Defined Health) Refined patient populations using the KICKSTART protocol as the product concept Detailed analysis with multiple KOL/com
Slide 32: Drug price and patient number assumptions
Drug Price and patient number assumptions Annual drug price Comparable IO combo agents (~$155K) Avastin (VEGF Ab) $172K Alimta (chemo) $130K Inlyta (VEGF TKI) $205K Patients (PD-L1 > 50%) 1L Setting ~27K NSCLC patients >50% PD-L1 with no actionable mutations for which CPI monotherapy is SoC 1L Exten
Slide 33: Length of treatment assumptions
length of treatment assumptions 1L Setting ~1 year Based on anticipated increase over average time on tx in front line with ~7-10+ months (median PFS) for pembro alone 1L Extension Setting ~6 months (conservative) Based on average (mean) time on therapy of 6+ months in P2a study for all patients (ir
Slide 34: Zotatifin (eFT226) eIF4A Helicase Inhibitor
Zotatifin (eFT226) eIF4A Helicase Inhibitor Oncology: Designed to downregulate key oncoproteins and cell cycle proteins Premal Patel, M.D., Ph.D., CMO
Slide 35: Zotatifin designed to inhibit key oncoprotein production
4A- translationally regulated genes including RTKs, KRAS, Myc, ER, Cyclin D1, CDK4/6 Zotatifin DESIGNED TO inhibit production of key proteins driven by upstream oncogenes Zota Cancer signaling drives production of multiple tumor promoting proteins Zotatifin designed to block this multi-protein upreg
Slide 36: Zotatifin selective regulation of translation
Preclinical regulation of translation by zotatifin was selective for proteins that drive tumor growth and resistance Zotatifin Target Sequence KRASmut protein all forms Cell proliferation/ cycle proteins RTK proteins Control protein unaffected Non-coding sequence coding sequence Experimental structu
Slide 37: Zotatifin single agent and combo activity in preclinical studies
Zotatifin demonstrated single agent and combo activity in Preclinical studies ER+ Breast Cancer Model* Zotatifin demonstrated comparable single agent activity to marketed inhibitor of CDK4/6 (palbociclib) Strong combination activity with palbociclib KRAS G12C NSCLC Model Zotatifin demonstrated compa
Slide 38: Exposures achieved in dose escalation match preclinical exposures
Exposures achieved in dose escalation match exposures that showed activity in preclinical models Phase 1 dose escalation ongoing, IV, currently two weeks on/one week off Long observed half-life of ~4 days has potential to maintain target suppression with intermittent dosing Zotatifin achieved target
Slide 39: Finance and Operations
Finance and Operations Manufacturing, IP, Financial Mike Byrnes, CFO
Slide 40: Manufacturing
Manufacturing Hybrid approach to capture best of both worlds Strategy is set and monitored by a close-knit project team with deep expertise in CMC, procurement, and regulatory aspects of manufacturing Execution of manufacturing and supply chain activities is externalized to provide greater flexibili
Slide 41: Intellectual property summary
Intellectual property summary MNK Inhibitors – Eight U.S. and sixteen foreign issued patents, as well as seven pending U.S. patent applications, four pending PCT applications and 66 pending foreign patent applications. Composition of matter out to 2035, not including any adjustments or extensions eI
Slide 42: Financial overview
financial OVERVIEW $150M raised from top tier investors through three private rounds Up to $507M achievable under Pfizer eIF4E license agreement $42M received to date $465M potential additional development and sales milestones Retained US co-promote/profit share option Merger with LWAC (Locust Walk
Slide 43: Transaction overview
TRANSACTION OVERVIEW Illustrative Post-Money Valuation at Close Illustrative Estimated Transaction Cash Sources and Uses Illustrative Post-Transaction Ownership Note: Assumes eFFECTOR cash balance of $17 million and debt balance of $20 million as of March 31, 2021, a $60 million PIPE issuance at $10
Slide 44: Summary and Outlook
Summary and Outlook Steve Worland, Ph.D., President and CEO
Slide 45: Additional program opportunities
Additional program opportunities Tomivosertib Expansion into NSCLC with PD-(L)1 status 1-49% where CPI+chemo is SOC as triplet (tomi+CPI+chemo) Other immuno-responsive tumors (renal, bladder, MSI-high) Zotatifin – COVID-19 $5M DARPA grant funding Phase 1b trial as antiviral Potent antiviral activity
Slide 46: Multiple upcoming clinical milestones
Multiple upcoming clinical milestones
Slide 47: Outlook
Outlook Leverage strong scientific foundation as leaders in development of STRIs as a new class of therapies for cancer Two product candidates in clinical development Tomivosertib demonstrated prolonged disease stabilization in Phase 2a trial Biomarker-driven randomized Phase 2b study with tomivoser
Slide 48: Additional Information and Where to Find It
Research Analyst Teach In June 28, 2021 Next Generation Targeted Therapy for Cancer Additional Information and Where to Find It On May 26, 2021, eFFECTOR entered into a definitive Agreement and Plan of Merger (the “Merger Agreement”) with LWAC, a special purpose acquisition company, and Locust Walk