Lite Strategy, Inc. · NASDAQ:LITS
Lite Strategy — MEI Pharma — Investor Presentation (July 2024)
57 slides from Lite Strategy's investor presentation, Jul 30, 2024
Slide 1: Voruciclib: An Oral CDK9 Inhibitor for AML and Other Malignancies
Voruciclib: An Oral CDK9 Inhibitor for AML and Other Malignancies July 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: Voruciclib Presents a Strong Value Proposition as the Only Oral CDK9 Inhibitor
Voruciclib Presents a Strong Value Proposition as the Only Oral CDK9 Inhibitor in Clinical Development in Combination with Venetoclax in AML Estimated R&D costs Stage 1a: ~$1.2M 16 patients Evaluate 200 mg only Readout December 2024 Stage 1b: ~$1.1M 16 patients Evaluate 250 mg Readout March 2025 Sta
Slide 4: Program Overview: Voruciclib and Venetoclax Combination in R/R AML Patients
Program Overview: Voruciclib and Venetoclax Combination in R/R AML Patients July 2024
Slide 5: Limited Treatment Options and Poor Outcomes for AML Patients Post Venetoclax Exposure
Limited Treatment Options and Poor Outcomes for AML Patients Post Venetoclax Exposure 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
Slide 6: Majority of R/R AML Patients Do Not Have Actionable Mutations
6 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, FLT3 and IDH1/2 mutations, respectively1. In one study, approximately 80% of pa
Slide 7: Large Addressable R/R AML Population for Mutation Agnostic Therapy
Large Addressable R/R AML Population for Mutation Agnostic Therapy Sources: Clarivate November 2023 Addressable population in R/R AML will continue to grow as targeted agents shift to 1L with combination regimens ~7,500 Addressable Patient Population for Mutation Agnostic Therapy in Patients with R/
Slide 8: Voruciclib: An Oral CDK9 Inhibitor with Clinical Activity in R/R AML
161 patients enrolled to date in 4 Phase 1 studies 65 pts with AML: 21 single agent and 44 in combination with venetoclax (VORU+VEN) 19 pts with B-cell malignancies 77 pts with solid tumors Current focus on R/R AML, with substantial clinical, PK and PD datasets CRi/MLFS observed in patients with dis
Slide 9: Decrease in Mcl-1 Protein with VORU+VEN Demonstrates On-Target Biological Activity
Decrease in Mcl-1 Protein with VORU+VEN Demonstrates On-Target Biological Activity MEI Data on file Greater Decrease in Mcl-1 in Responders1 Mcl-1 Increases After Venetoclax then Decreases with Voruciclib1 Consistent Decreases in Mcl-1 Across Dose Levels 1. Mcl-1 protein expressed as mean fluorescen
Slide 10: On-Target Decreases in Mcl-1 and Phosphorylation of RNA Pol IISer2 Across Doses
Mcl-1 protein expression and phosphorylation of RNA Pol IISer2 values decreased from before first voruciclib dose to day 14 at the end of voruciclib dosing On-Target Decreases in Mcl-1 and Phosphorylation of RNA Pol IIser2 Across Doses 10 MEI Data on file
Slide 11: Patients with Clinical Responses Have Strongest Decreases in RNA Pol IISer2 Phosphorylation
Patients with Clinical Responses Have Strongest Decreases in RNA Pol IISer2 Phosphorylation Following VORU+VEN at 100-300 mg Clinical responders (MLFS/CRh/Cri) showed significant decreases in RNA Pol II phospho-Ser2 on Day 14 compared to pre VORU dosing on Day 3 Data normalized to each patient’s C1D
Slide 12: Anti-Leukemic Activity Observed After Venetoclax Failure
Anti-Leukemic Activity Observed After Venetoclax Failure 12 ~50% of Patients with Pre/Post Bone Marrow Biopsy Had a Decrease in Blast Counts 3 patients achieved a response 2 had a CRi 1 underwent HSCT transplant 1 had a CRi for 6 months then progressed 1 had a MLFS, ongoing at 9+ months 7 patients h
Slide 13: Peripheral Blast Counts Decrease on VORU+VEN & Rebound on VEN Alone
18/24 pts (75%) had decreased peripheral blasts on Day 14 of Cycle 1, at the end of voruciclib and venetoclax combination dosing 8/18 pts (44%) had peripheral blasts rebound between Day 14 and 28, when voruciclib was stopped and patient received venetoclax alone Importance of Evaluating Voruciclib o
Slide 14: Voruciclib Plus Venetoclax is Well-Tolerated in Heavily Pre-Treated R/R AML Patients
MTD not reached on 14 days/cycle schedule evaluated to date Dose escalation stopped at 300 mg because plasma concentrations achieved exceed concentrations shown to be effective in nonclinical models Target dose for PD effect projected to be 150-250 mg No DLTs observed at doses evaluated No discontin
Slide 15: Dose Optimization Stage Timeline in H2-2024
2024 Jan Feb Mar Apr 2025 Remaining Cohorts (16-32 Patients) to Be Evaluated in the Dose Optimization Stage in H2-2024 Assumes Reactivation of Enrollment in September 2024 150 mg N=3 250 mg N=4-6 200 mg N=4-6 15 250 mg-EXP N=12 May June Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr 200 mg-EXP N=12 41 pts
Slide 16: Timeline for Stage 2 at RP2D with 24 Patients Enrolled
2024 2025 2022 Oct Nov Dec Jan Feb Mar Apr Sep Oct Nov Dec May Jun Jul Aug Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2026 Jan Feb Mar Apr Jun May Timeline for Stage 2 at RP2D with 24 Patients Enrolled Topline Results in Q4-2025 Voruciclib IS3w,1w (200 and 250 mg) plus venetoclax (N = 32 pts) 1
Slide 17: Phase 3 Ready Package for Voruciclib + Venetoclax in R/R AML in 2026
Phase 1/2 study enrolling up to 120 patients with R/R AML 100 patients in combination with venetoclax, with ~40 patients at RP2D Extensive PK data on > 150 patients Pharmacodynamics data for Mcl-1 and RNA Pol Phase 3 Ready Package for Voruciclib + Venetoclax in R/R AML in 2026 Pharmacology studies F
Slide 18: Registration Strategy in R/R AML
Phase 3 study design Randomized placebo-controlled vs SOC (HMA, LDAC, Venetoclax alone R/R AML, not to exceed 3 prior lines of therapy, exclude TP53 mutations Overall survival as primary endpoint for full approval Possible accelerated approval based on CR+CRh rate Sample size = 300 pts for survival
Slide 19: Voruciclib Intellectual Property and Exclusive Worldwide Rights
MEI Pharma has acquired exclusive worldwide rights to develop, manufacture and commercialize voruciclib from Presage Biosciences, Inc. 14 issued patents, 2 allowed and 7 pending U.S. non-provisional patent applications with the USPTO covering the composition of matter, pharmaceutical compositions, a
Slide 20: Voruciclib Mechanism of Action and Nonclinical Studies
Voruciclib Mechanism of Action and Nonclinical Studies
Slide 21: Voruciclib Modulates CDK9 Interactions and Transcription of MCL1 & MYC
Cytosol Nucleus DNA Pol II Cyc T CDK 9 P-TEFb DSIF P P Transcription of MCL1 & MYC Voruciclib Dey, et al. Sci Reports (2017) 7(1):8007. Li, et al. Transcription (2018) 9(2):88. Luedtke, et al. Signal Transduct Ther (2020) 5(1):17. Dollinger, et al. J Mol Biol (2021) 433(14):1666897. Wiley, et al. Ca
Slide 22: CDK9 Regulates Expression of MCL1 and MYC Genes
Dey, et al. Sci Reports (2017) 7(1):8007. Li, et al. Transcription (2018) 9(2):88. Luedtke, et al. Signal Transduct Ther (2020) 5(1):17. Dollinger, et al. J Mol Biol (2021) 433(14):1666897. Wiley, et al. Cancer Research (2021) 81(13 supp):1962. Huska, et al, Methods in Mol Biol (2019). MCL1 Cytochro
Slide 23: High Mcl-1 Levels Associated With Poor Prognosis and Resistance to Venetoclax in AML
23 High Mcl-1 Levels Associated With Poor Prognosis and Resistance to Venetoclax in AML 1. Glaser et al, Gene Dev 2012;26(2):120-125 2. Li et al, Onco Target Ther 2019;12:3295-3304 3. Carter et al, Haematologica 2022;107(1):58-76. High levels of Mcl-1 found consistently high in nearly all bone marro
Slide 24: Voruciclib Is a Selective and Potent Oral CDK9 Inhibitor
Voruciclib Is a Selective and Potent Oral CDK9 Inhibitor 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 24 Orally administered Patient convenience Half-life of 26-32 hours allows once a day dosing
Slide 25: Preclinical Studies Show Voruciclib Suppresses Mcl-1 and Synergizes with Venetoclax in AML
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 Suppresses Mcl-1 and MYC Protein Levels Increases Apoptosis VOR (nM) VEN (nM) 0 0 0 12.5 0 25 0 50 50
Slide 26: Voruciclib Results in R/R AML
Voruciclib Results in R/R AML
Slide 27: Completed Single-Agent Dose Escalation/Expansion in R/R AML & B-cell Malignancies
Completed Single-Agent Dose Escalation/Expansion in R/R AML & B-cell Malignancies (N = 40) Treatment Well Tolerated with Evidence of Anti-Leukemic Activity AML CLL Davids et al, Blood (2023) 142 (Supplement 1): 4286 27 Decreased RNA Pol II phosphorylation Reduced Mcl-1 mRNA Voruciclib up to 200 mg f
Slide 28: Completed Dose Escalation/Expansion of Voruciclib 2 Weeks/Cycle Plus Venetoclax
28 MEI Data on file Dosing schedule Voruciclib days 1-14 (day 3-14 in cycle 1) Venetoclax 200 mg on days 1-21 and 400 mg on days 22-28 41 patients enrolled 29 in dose escalation cohorts at 50-300 mg 12 in expansion cohort at 300 mg Clinical activity 2 CRh and 1 MLFS Improved blast counts Well tolera
Slide 29: Baseline Characteristics in Dose Escalation/Expansion Cohorts
Baseline Characteristics in Dose Escalation/Expansion Cohorts (N = 41) Patients Heavily Pretreated With High Rate of Adverse Cytogenetic and Molecular Features 29 Total (N=41) 2017 ELN Risk Category Favorable Intermediate Adverse 4 (10%) 7 (17%) 30 (73%) Poor Cytogenetics (n = 40) Patients with adve
Slide 30: Anti-Leukemic Activity Observed After Venetoclax Failure
Anti-Leukemic Activity Observed After Venetoclax Failure 30 ~50% of Patients with Pre/Post Bone Marrow Biopsy Had a Decrease in Blast Counts 3 patients achieved a response 2 had a CRi 1 underwent HSCT transplant 1 had a CRi for 6 months then progressed 1 had a MLFS, ongoing at 9+ months 7 patients h
Slide 31: AML Type Covariate Analysis
AML Type Poor risk AML had low disease control rate (<40%) vs favorable risk AML with higher disease control rate (≥50%) Covariate Analyses From All Cohorts on IS2W,2W (41 Patients) 31 AML Type No. Pts (N=41) CRi/MLFS SD ≥3 mo “Good Outcome” CRi/MLFS/SD “Poor Outcome” PD + SD <3 mo AML with MDS rela
Slide 32: ELN 2017 Risk Group Covariate Analysis
ELN 2017 Risk Group Patients with Adverse risk had low disease control rate (≤10%) vs patients with Intermediate/Favorable risk who had higher disease control rate (≥50%) Covariate Analyses From All Cohorts on IS2W,2W (41 Patients) 32 ELN 2017 Risk Group No. Pts (N=41) CR/MLFS SD ≥3 mo “Good Outcome
Slide 33: Molecular Mutations Covariate Analysis
Molecular Mutations Patients with adverse risk mutations (RUNX1, TP53, SRSF2) had low disease control rate, particularly for TP53 Patients with ASXL1, considered poor risk in general but reported by Sellas to be associated with better outcome when treated with GFH009, led to 2 CRi with VORU+VEN Cova
Slide 34: Voruciclib Generally Well-Tolerated with No Apparent Dose Response to Adverse Events
Voruciclib Dosed up to 300 mg for 14 Days per Cycle Was Generally Well-Tolerated with No Apparent Dose Response to Adverse Events Reported 34 (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)
Slide 35: Decrease in Mcl-1 Protein with VORU+VEN Demonstrates On-Target Biological Activity
Decrease in Mcl-1 Protein with VORU+VEN Demonstrates On-Target Biological Activity MEI Data on file Greater Decrease in Mcl-1 in Responders1 Mcl-1 Increases After Venetoclax then Decreases with Voruciclib1 Consistent Decreases in Mcl-1 Across Dose Levels 1. Mcl-1 protein expressed as mean fluorescen
Slide 36: On-Target Decrease in Mcl-1 and RNA Pol IIser2 Phosphorylation
Mcl-1 and phosphorylation of RNA Pol IISer2 mean values decreased from before first voruciclib dose to day 14 on the last day of voruciclib dosing Change not as evident at 300 mg (compensatory pathways?) and 50 mg (dose too low) On-Target Decrease in Mcl-1 and RNA Pol IIser2 Phosphorylation 36 MEI D
Slide 37: Patients with Clinical Responses Have Strongest Decreases in RNA Pol IISer2 Phosphorylation
Patients with Clinical Responses Have Strongest Decreases in RNA Pol IISer2 Phosphorylation Following VORU+VEN at 100-300 mg Clinical responders (MLFS/CRh/Cri) showed significant decreases in RNA Pol II phospho-Ser2 on Day 14 compared to pre VORU dosing on Day 3 Data normalized to each patient’s C1D
Slide 38: % of Patients with Mcl-1 and p-Ser2 RNA Pol II Responses
Flow cytometry analysis of PBMC samples Changes in fluorescence signal for individual subjects analyzed for acute response (6 hr post-dose on day 3 or day 14 vs pre-dose on same day) or steady state response (day 14 pre-dose compared to day 3 pre-dose) Response defined as ≥20% decrease from baseline
Slide 39: Assessment of Voruciclib PD Responses by Raw Values
Assessment of Voruciclib PD Responses by Raw Values PD Assessment Cohort 12 (50 mg QOD) Cohort 14 (100 mg) Cohort 15 (150 mg) Cohort 16 (200 mg) Cohort 17 (250 mg) Cohort 18 + EXP1 (300 mg) PD day 3 and/or day 14, N 3 4 3 4 3 11 Pts with Mcl-1 decrease (≥ 20%) post VOR (acute or steady state) % (N)
Slide 40: Voruciclib PK Analysis 50-300 mg
Mean (%CV) single dose and multiple dose voruciclib Cmax and AUC24 Voruciclib multiple dose exposures on C1D14 was generally proportional to the dose in the range 50 mg to 300 mg. Voruciclib PK profiles are consistent with historical single agent data; it is inferred that venetoclax does not affect
Slide 41: Venetoclax PK at 50-250 mg
Mean (%CV) multiple dose venetoclax Cmax and AUC24 values Voruciclib once daily administration did not have an effect on venetoclax pharmacokinetics. Historical Venetoclax Data (Study M12-175) CLL/SLL NHL 200 mg QD 200 mg QD 7 3 1.44 (39%) 1.11 (27%) 24.28 (44%) 16.26 (28%) Venetoclax PK at 50-250 m
Slide 42: Peripheral Blast Counts Decrease on Voruciclib + Venetoclax and Rebound on Venetoclax Alone
18/24 pts (75%) had decreased blasts on Day 14, at the end of voruciclib and venetoclax combination dosing 8/18 pts (44%) had blasts rebound between Day 14 and 28, when voruciclib was stopped while continuing venetoclax Increasing duration of voruciclib exposure may prevent blast rebound and enhance
Slide 43: Patient Enrollment in VORU IS3w,1w + Venetoclax Cohorts Paused for Strategic Reasons
43 3 patients enrolled in VORU+VEN group at 150 mg on IS3w,1w No DLTs 1 patient had a 49% reduction in bone marrow blasts Enrollment halted for strategic reasons despite investigator support for evaluation of 3-week schedule Enrollment of dose escalation and expansion cohorts on 3-week schedule can
Slide 44: Estimated R&D Cost to Evaluate Dose Only
44 Estimated R&D Cost to Evaluate 200 mg Only
Slide 45: Estimated R&D Cost to Evaluate Two Doses
45 Estimated R&D Cost to Evaluate 200 mg and 250 mg
Slide 46: Estimated R&D Cost to Evaluate Patients at RP2D in Phase 2
46 Estimated R&D Cost to Evaluate 24 Patients at RP2D in Phase 2
Slide 47: Voruciclib is the Only Oral CDK9 Inhibitor in Clinical Development in Combination with Venetoclax
Voruciclib is the Only Oral CDK9 Inhibitor in Clinical Development in Combination with Venetoclax in AML Drug Company Target(s) CDK9 IC50 (nM) ROA Indications (ongoing studies) Stage Voruciclib MEI Pharma CDK 9 0.63 oral AML (+venetoclax) Ph 1 Fadraciclib Cyclacel Pharma CDK 2, 9 26.2 oral AML (sing
Slide 48: Scientific Rationale for Voruciclib Development in B-cell Malignancies & Solid Tumors
Scientific Rationale for Voruciclib Development in B-cell Malignancies & Solid Tumors
Slide 49: Life Cycle Opportunities for Voruciclib
Lymphoid malignancies with MCL1 amplification or increased expression PTCL CLL in combination with venetoclax MCL DLBCL Multiple myeloma Solid tumors with MCL1 amplification or increased expression Prostate cancer Small cell lung cancer (SCLC) Hepatocellular carcinoma (HCC) Life Cycle Opportunities
Slide 50: Voruciclib Shows Single Agent Efficacy and Synergizes with Venetoclax in CLL Cells
Voruciclib Shows Single Agent Efficacy and Synergizes with Venetoclax in CLL Cells 50 Voruciclib + Venetoclax shows synergy in all CLL patient samples tested: independent of treatment status and cytogenetic risk2 TN: treatment naïve. RR: Relapsed / refractory Low risk=IGHV mutated plus low risk FISH
Slide 51: Voruciclib Synergizes with Venetoclax in DLBCL Nonclinical Models
Dey, et al. Scientific Reports, 2017 Dey et al. Blood, 2016. ASH conference poster #4167. Presage Biosciences (Data on file) VOR reduces MCL1 & MYC in DLBCL cell lines Voruciclib induces dose-dependent reduction in MYC and MCL1 proteins in DLBCL cell lines Voruciclib synergizes with venetoclax to in
Slide 52: 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 53: 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 54: Voruciclib Inhibits KRAS Mutant Cell Lines In Vitro and In Vivo in Xenograft Mice
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 55: Synergy of CDK9 Inhibition with Direct KRAS Inhibitors
Synergy of CDK9 Inhibition with Direct KRAS Inhibitors Voruciclib Synergizes with Sotorasib in an In Vivo MIA Paca-2 Tumor Model Voruciclib Synergizes With Kras G12c Inhibitors In Vitro Cell death around each microinjection site measured by nuclear condensation and fragmentation Wiley, SE. et al. AA
Slide 56: Voruciclib Presents a Strong Value Proposition as the Only Oral CDK9 Inhibitor
Voruciclib Presents a Strong Value Proposition as the Only Oral CDK9 Inhibitor in Clinical Development in Combination with Venetoclax in AML Estimated R&D costs Stage 1a: ~$1.2M 16 patients Evaluate 200 mg only Readout December 2024 Stage 1b: ~$1.1M 16 patients Evaluate 250 mg Readout March 2025 Sta
Slide 57: Voruciclib: An Oral CDK9 Inhibitor for AML and Other Malignancies
Voruciclib: An Oral CDK9 Inhibitor for AML and Other Malignancies July 2024