Lite Strategy, Inc. · NASDAQ:LITS
Lite Strategy — MEI Pharma — Investor Presentation (May 2024)
41 slides from Lite Strategy's investor presentation, May 21, 2024
Slide 1: Corporate Overview
NASDAQ: MEIP Corporate Overview Novel drug candidates to address known resistance mechanisms to standard-of-care cancer therapies May 21, 2024
Slide 2: Forward Looking Statements
Forward Looking Statements Certain information contained in this communication that are not historical in nature are "forward-looking statements" within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 including, without limitation, statements regar
Slide 3: Clinical-stage Oncology Company Evaluating Novel Drug Candidates
Clinical-stage Oncology Company Evaluating Novel Drug Candidates to Address Known Resistance Mechanisms to Standard-of-care Cancer Therapies Significant Addressable Markets Near-term Value Drivers Clinical Data Support Combinations Cash sufficient to fund operations for at least the next 12 months T
Slide 4: Two Novel Oncology Drug Candidates
Two Novel Oncology Drug Candidates Investigational Agents Therapeutic Area Combination Pre-IND Phase 1/1b Phase 1/2 Voruciclib Oral CDK9 Inhibitor Acute Myeloid Leukemia Relapsed/refractory (2L+) Single-agent VENCLEXTA® (venetoclax) Solid Tumors* Single-agent & Vemurafenib ME-344 OXPHOS Inhibition H
Slide 5: Voruciclib: A Selective Oral CDK9 Inhibitor Drug Candidate
Voruciclib: A Selective Oral CDK9 Inhibitor Drug Candidate
Slide 6: Voruciclib: A Selective Oral CDK9 Inhibitor with Potential to Address Hematologic Malignancies and Solid Tumors
Voruciclib: A Selective Oral CDK9 Inhibitor with Potential to Address Hematologic Malignancies and Solid Tumors Dey, et al. Sci Reports (2017) 7(1):8007. Luedtke, et al. Signal Transduct Ther (2020) 5(1):17. Wiley, et al. Cancer Research (2021) 81(13 supp):1962 6 Myeloid leukemia 1 (MCL-1): An antia
Slide 7: Mcl-1 and Myc Proteins Represent Important Therapeutic Targets
MCL-1: Increase associated with poor prognosis in AML and several B-cell malignancies Upregulation is an established venetoclax resistance mechanism Venetoclax inhibits BCL2 but can lead to stabilization of Mcl-1 MYC: Over expressed in many cancers, including those with KRAS mutations CDK9 inhibitio
Slide 8: Voruciclib Program Overview
Voruciclib Program Overview Significant clinical experience: Over 150 patients treated to date, 82 with hematological malignancies and 77 with solid tumors Current focus on combination with venetoclax in R/R AML: Addresses established venetoclax resistance mechanism High Need: Poor outcomes with cur
Slide 9: Poor Outcomes Post Venetoclax Failure in Patients with No Actionable Mutations
Poor Outcomes Post Venetoclax Failure in Patients with No Actionable Mutations Maiti, A., et. al., Haematologica 2021: 106(3. Maiti, A., et. al., Blood 2023: 142 (Supplement 1): 4289. Zainaldin, C., et. al., Leuk Lymphoma 2022: 63(13):3245-3248. Daver, N., Blood (2022) 140 (Supplement 1): 141–144: 9
Slide 10: High Unmet Need Remains for ≥50% of AML Population With No Actionable Mutations
High Unmet Need Remains for ≥50% of AML Population With No Actionable Mutations 10 1. Miyamoto, K., et. al., Int J Mol Sci. 2020;21(14):5114. 2. Malani, D., Cancer Discov. 2022;12(2):388-401 Diagram is for illustrative purposes. In comparison, approximately 30%, 30% and 20% of AML patients have NPM1
Slide 11: Large Potential Addressable Population with High Unmet Need for Mutation Agnostic Therapy
Large Potential Addressable Population with High Unmet Need for Mutation Agnostic Therapy Venclexta sales were ~$2.3B in 2023 WW across all indications; projected to grow to ~$3.3B by 2028 Sources: Evaluate, April 2024; Clarivate November 2023 Use of Venetoclax Based Therapy Increasing Across AML Tr
Slide 12: Preclinical Studies Demonstrate Voruciclib Suppresses Mcl-1 and Synergizes with Venetoclax
Preclinical Studies Demonstrate Voruciclib Suppresses Mcl-1 and Synergizes with Venetoclax in AML Murine Xenograft Model Luedtke, et al. Signal Transduct Ther (2020) Extends Survival in MV4-11 Tumor c. Suppresses Mcl-1 Level Increases Apoptosis VOR (nM) VEN (nM) 0 0 0 12.5 0 25 0 50 500 0 1000 0 200
Slide 13: Plan to Initiate a Phase 2 Study Arm in 2025
13 Plan to Initiate a Phase 2 Study Arm in 2025 After Determining Recommended Phase 2 Dose and Schedule (Phase 2 study arm subject to FDA advice) Ph 1/2 Study to Generate Data on ~106 Patients With R/R AML Administered Voruciclib Alone or with Venetoclax IS2w,2w: Intermittent dosing of voruciclib da
Slide 14: Single-Agent Voruciclib Well-Tolerated, Showed Clinical and Biomarker Activity in AML & CLL
Single-Agent Voruciclib Well-Tolerated, Showed Clinical and Biomarker Activity in AML & CLL AML CLL Davids et al, ASH 2023 14 Analysis of patient AML blasts showed a decrease in RNA Pol II phosphorylation after voruciclib treatment. CDK9 directly phosphorylates RNA Pol II. Longitudinal transcriptomi
Slide 15: Evidence of Activity and Tolerability in Dose Escalation Groups of Voruciclib Plus Venetoclax
Evidence of Activity and Tolerability in Dose Escalation Groups of Voruciclib Plus Venetoclax in R/R AML All V+V patients are heavily pretreated with a median of 2 prior therapies (range 1-7) including venetoclax in 28/29 patients 15 MEI Data on file 29 patients in dose escalation cohorts (IS2w,2w)
Slide 16: Combination Arm Characteristics: Patients Heavily Pretreated
Combination Arm Characteristics: Patients Typically Heavily Pretreated With a Median of 3 Prior Therapies and High Rate of Adverse Molecular and Cytogenetic Features 16 Total (N=29) 2017 ELN Risk Category Favorable Intermediate Adverse 3 (11%) 5 (17%) 21 (72%) Poor Cytogenetics Patients with adverse
Slide 17: Voruciclib Appeared Generally Well-Tolerated with No Apparent Dose Response to Adverse Events
Voruciclib Dosed up to 300 mg Appeared Generally Well-Tolerated with No Apparent Dose Response to Adverse Events Reported 17 (50 mg QOD) (N=6) (50 mg QD) (N=3) (100 mg QD) (N=4) (150 mg QD) (N=4) (200 mg QD) (N=4) (250 mg QD) (N=4) (300 mg QD) (N=4) Total (N=29) Nausea 0 0 2 (50.0) 3 (75.0) 2 (50.0)
Slide 18: Responses and Blast Count Reductions Demonstrate Anti-Leukemic Activity
Responses and Blast Count Reductions Demonstrate Evidence of Anti-Leukemic Activity in Heavily Pretreated Patients After Venetoclax Failure 18 ≥100 50% of Evaluable Patients with Pre/Post Bone Marrow Had a Decrease in Blast 85% (17/20) of patients administered voruciclib at ≥100 mg achieved response
Slide 19: Decreases in Mcl-1 Demonstrate On-target Biological Activity
Decreases in Mcl-1 Demonstrate On-target Biological Activity Relative Mcl-1 Protein By Response MEI Data on file Relative Mcl-1 Protein in PBMC Greater Decrease in Mcl-1 Protein in Responders Mcl-1 Increases After Venetoclax Then Decreases with Voruciclib More Consistent Decrease in Mcl-1 at Higher
Slide 20: Peripheral Blast Counts Decrease on Voruciclib + Venetoclax Combination
24 patients had serial blood tests for blasts with values >0 18/24 pts (75%) had decreased balsts on Day 14, at the end of voruciclib dosing 8/18 pts (44%) had increased blasts between Day 14 and 28, when off voruciclib but receiving venetoclax Peripheral Blast Counts Decrease on Voruciclib + Veneto
Slide 21: Near-term Data to Inform RP2D for Phase 2 Study Arm in R/R AML
Near-term Data to Inform RP2D for Phase 2 Study Arm in R/R AML Anticipated Total of ~40 Patients at RP2D & Schedule to Support Phase 3 Ready Program Potential H2 2024 Updates: IS2w,2w Dose Expansion (N=12) IS3w,1w Dose Escalation/Expansion (N=12/12) Phase 2 Study Arm* – Initiation and Data in 2025 R
Slide 22: Voruciclib Presents Novel Mechanism to Evaluate Treating Solid Tumors via MYC Inhibition
Voruciclib Presents Novel Mechanism to Evaluate Treating a Range of Solid Tumors via MYC Inhibition
Slide 23: Opportunities to Address both Hematologic Malignancies and Solid Tumors
Opportunities to Address both Hematologic Malignancies and Solid Tumors MCL-1: Increase associated with poor prognosis in AML and several B-cell malignancies Upregulation is an established venetoclax resistance mechanism Venetoclax inhibits BCL2 but can lead to stabilization of Mcl-1 MYC: Over expre
Slide 24: Single-Agent Phase 1 Studies in Solid Tumors Demonstrated Reduction in MYC
2 weeks on, 1 week off schedule (N = 29 pts) 75 to 850 mg MTD = 600 mg 41% disease control rate Daily continuously schedule (N = 39 pts) 75 to 500 mg MTD = 350 mg 31% disease control rate Safety data No evidence of myelosuppression Most common AEs involved GI tract Single-Agent Phase 1 Studies in So
Slide 25: CDK9 can influence MYC protein stability in KRAS mutant cancer cells
CDK9 can influence MYC protein stability in KRAS mutant cancer cells Cell Stimulatory Signals KRAS PI3K GSK3β CDK9 RAF MEK MYC MYC MYC protein degradation by proteasome SCF-Fbw7 Ubiquitin sotorasib adagrasib pT58 Pin1 Pin1 PP2A pS62 pS62 pT58 (unstable) Voruciclib (stable) Transcriptional activation
Slide 26: Voruciclib Inhibits KRAS Mutant Cell Lines In Vitro and In Vivo
VOR inhibited proliferation of KRAS mutant cell lines from multiple indications CRC Esophageal Multiple Myeloma NSCLC Ovarian PDAC VOR inhibited proliferation of cell lines with various KRAS mutations G12C, G12D, G12A, G12V G13C, G13D Q61H Wiley, SE. et al. AACR, 2021 & unpublished. Time (days) Ave
Slide 27: Combining Voruciclib with Sotorasib Results in Enhanced Cell Death
Combining Voruciclib with Sotorasib Results in Enhanced Cell Death in an in vivo MIA PaCa-2 Tumor Model Con VOR SOTO Combo DAPI 40X Cell death around each microinjection site measured by nuclear condensation and fragmentation 27 Wiley, SE. et al. AACR, 2021.
Slide 28: ME-344: An OXPHOS Inhibitor Drug Candidate
ME-344: An OXPHOS Inhibitor Drug Candidate
Slide 29: ME-344: A Novel Inhibitor of OXPHOS with Dual Effect on OXPHOS and Purine Synthesis
ME-344: A Novel Inhibitor of OXPHOS with Dual Effect on OXPHOS and Purine Synthesis 1 MEI data on file, 2Lim et al, Am J Cancer Res. 2015, 3Manevich et al, J Pharm and Exper Ther. 2016, 4Hurrish et al, Biochem Pharmacol 2024 Potent Inhibitor of Proliferation nM potency against majority of 240 cell l
Slide 30: ME-344 Program Overview: Inducing Synthetic Lethality in Solid Tumors
Novel MOA with OXPHOS inhibition leading to ATP depletion in malignant cells Significant need in large addressable patient populations: anti-angiogenics like bevacizumab and TKIs used in multiple settings as SOC, including: Colorectal, ovarian, renal cell, glioblastoma and pancreatic cancers Clinica
Slide 31: ME-344: A Novel Combination Approach with Anti-angiogenic Therapies
ME-344 blocks the production of ATP by inhibiting the OXPHOS pathway Anti-angiogenic therapies reduce glycolysis Cancer cells switch between mitochondria and glycolytic metabolic pathways to escape the blocking of either energy source The potential to inhibit both mitochondrial energy production via
Slide 32: ME-344 Synergizes with Anti-angiogenics in Multiple Murine Solid Tumor Models
ME-344 + Regorafenib in CRC Model2 Survival ME-344 Synergizes with Anti-angiogenics in Multiple Murine Solid Tumor Models Resulting in Tumor Growth Delay and Improved Survival 32 1 Navarro et al, Cell Reports 2016, 2 MEI Data on file ME-344 + TKI in PyMT Breast Cancer Model1 Tumor Volume OXPHOS Redu
Slide 33: Establishing Proof of Concept: ME-344 with Bevacizumab Demonstrates Ki67 Decrease
Clinical Study Objectives Assess ability of bevacizumab to shift tumor reliance from glycolysis to mitochondrial metabolism Assess ability of ME-344 + Avastin to inhibit tumor proliferation compared to Avastin + placebo Arm A N = 21 Bevacizumab 15 mg/kg day 1 ME-344 10mg/kg days 8, 15, 21 Arm B N =
Slide 34: Clinical Support of Concept: Phase 1B ME-344 Plus Bevacizumab in Relapsed mCRC
Patients with mCRC disease after failure of standard therapies Primary objective: 16-week PFS Secondary objectives: ORR, OS, safety Continue therapy until disease progression or toxicity Cohort 2 (not enrolled) Option for second 20 patient Cohort 2 if PFS at 4-mo ≥20% in Cohort 34 Cohort 1 (N=23) ME
Slide 35: Phase 1b Further Supports ME-344 Novel Therapeutic Strategy
Phase 1b Further Supports ME-344 Novel Therapeutic Strategy to Induce Synthetic Lethality 5 of 20 (25%) evaluable patients completed 16 weeks of therapy without evidence of disease progression, exceeding the 20% predetermined threshold as set forth in the Clinical Study Protocol. No overlapping toxi
Slide 36: Phase 1b: Encouraging Progression Free Survival and Overall Survival
Phase 1b: Encouraging Progression Free Survival and Overall Survival No. (%) of patients (N = 23) Complete Response 0 Partial Response 0 Stable Disease 9 (39.1%) Progressive Disease 11 (47.8%) Not Evaluable for response 3 (13.0%) Median PFS = 1.9 m (95% CI: 1.6-5.2) 4 m PFS = 31.2% (95% CI: 13.5-50.
Slide 37: All Adverse Events in ≥3 Patients
All Adverse Events in ≥3 Patients All Subjects (N=23) N (%) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 All Grade Fatigue 4 (17.4) 2 (8.7) 3 (13.0) 0 0 9 (39.1) Abdominal pain 3 (13.0) 3 (13.0) 2 (8.7) 0 0 8 (34.8) Diarrhea 2 (8.7) 4 (17.4) 1 (4.3) 0 0 7 (30.4) Constipation 4 (17.4) 1 (4.3) 0 0 0 5 (21.
Slide 38: ME-344 to Continue Advancing via Development of a New Formulation
ME-344 to Continue Advancing via Development of a New Formulation ME-344 New Formulation with Potential to: Increase Biological Activity Improve Patient Convenience Enhance Commercial Opportunity New Formulation Update Expected H1 2025
Slide 39: Financial Overview
NASDAQ: MEIP Financial Overview
Slide 40: Financial Highlights
Financial Highlights As of December 31, 2023, MEI had $59.5 million in cash, cash equivalents, and short-term investments with no outstanding debt. The Company believes its cash balance is sufficient to fund operations for at least the next 12 months
Slide 41: Corporate Overview
NASDAQ: MEIP Corporate Overview Novel drug candidates to address known resistance mechanisms to standard-of-care cancer therapies May 21, 2024