Lite Strategy, Inc. · NASDAQ:LITS
Lite Strategy — MEI Pharma — Corporate Update (April 2021)
28 slides from Lite Strategy's corporate update, Apr 13, 2021
Slide 1: Building a Leading Oncology Franchise
Building a Leading Oncology Franchise NASDAQ: MEIP April 13, 2021 Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains, and our officers and representatives may from time to time make, statements that are “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Examples of forward-
Slide 3: MEI Pharma: Who We Are
MEI Pharma: Who We Are Clinical Development Company Building a Leading Oncology Franchise with 4 Clinical-Stage Programs: Focus On HemOnc Zandelisib (f/k/a ME-401) Potential Best-in-Class PI3Kδ Inhibitor in Phase 2 Study Intended to Support Accelerated Approval Application with U.S. FDA Well Capital
Slide 4: Zandelisib Topline TIDAL Study Data on Track for Q4 CY2021
Zandelisib Topline TIDAL Study Data on Track to be Reported in the Fourth Quarter of CY2021 Announced Today: Enrollment Complete in Follicular Lymphoma Primary Efficacy Population of Global Phase 2 TIDAL The complete Phase 2 TIDAL study data are intended to be submitted to FDA to support accelerated
Slide 5: Voruciclib: Oral CDK Inhibitor with Potent CDK9 Activity Preclinical Data
Voruciclib: Oral CDK Inhibitor with Potent CDK9 Activity Preclinical Data
Slide 6: CDK9 Regulates MYC and MCL1 Transcription by RNA POL II
CDK9 Regulates MYC and MCL1 Transcription by RNA POL II DSIF HEXIM NELF Pol II DSIF Pol II Inhibitory Complex Productive elongation of RNA Pol II transcription of target genes (e.g., MYC, MCL1) Promoter proximal pausing relieved by PTEFb & CDK9 activity CDK9 P P PTEFb CDK9 PTEFb voruciclib Transcrip
Slide 7: Voruciclib Induces Rapid Down Regulation of RNA POL II Associated Proteins
Voruciclib Induces Rapid Down Regulation of RNA POL II Associated Proteins That Control MYC and MCL1 Transcription Summary of Phosphoproteomics Analysis Total Peptides 98,140 Total Proteins 5,753 Phosphoproteins (n) 4,806 Phosphosites (n) 21,384 Voruciclib (min) Downreg Phospho-peptides (n) Downreg
Slide 8: CDK9 Regulates MYC Protein Stability
CDK9 Regulates MYC Protein Stability 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 of MYC target genes MYC MYC ERK
Slide 9: Voruciclib Causes Rapid Inhibition of MYC pSer62 Phosphorylation
Voruciclib Causes Rapid Inhibition of MYC pSer62 Phosphorylation and Reduces MYC Protein Levels 0 min 5 min 15 min 30 min CON VOR AZD CON VOR AZD CON VOR AZD CON VOR AZD MYC β-actin p-MYC (S62) 1.0 0.9 1.1 1.0 0.4 0.4 1.0 0.8 0.9 1.0 1.1 1.0 1.0 0.3 0.3 1.0 0.3 0.3 1.0 1.0 1.1 1.0 0.9 1.1 β-actin MY
Slide 10: Voruciclib Inhibits KRAS Mutant Cell Growth In Vitro and In Vivo
Voruciclib Inhibits KRAS Mutant Cell Growth In Vitro and In Vivo in Xenograft Mice Cell Line Indication KRAS Mut IC50 (µM) Gp2D CRC G12D 0.8 HCT-116 CRC G13D 1.8 LS-513 CRC G12D 0.6 SW-480 CRC G12V 3.9 SW837 CRC G12C 2.1 KYSE-410 Esoph G12C 1.9 RPMI-8226 MM G12A 2.4 A-549 NSCLC G12S 1.5 Calu-1 NSCLC
Slide 11: Exploring Synergy with Direct KRAS Inhibitors
Leveraging CDK9 Regulation of MYC: Exploring Synergy with Direct KRAS Inhibitors Synergy Scores Cell Line KRAS mut Sensitivity to G12C Inhibitors Voruciclib + Sotorasib Voruciclib + Adagrasib NCI-H23 G12C High HCC1171 G12C High MIA Paca-2 G12C High SW837 G12C Moderate - High NCI-H2030 G12C High Calu
Slide 12: In Vivo Synergy with Sotorasib in MIA PaCa-2 Tumors
Leveraging CDK9 Regulation of MYC: In Vivo Synergy with Sotorasib in MIA PaCa-2 Tumors Con VOR SOTO Combo 40X Representative IHC images of DAPI and H&E staining in a Murine Xenograph Model CIVO GLO Fluorescent tracking microspheres Intratumoral injection of drugs & fluorescent microspheres with Pres
Slide 13: In Vivo Synergy with Sotorasib in MIA PaCa-2 Tumors
Leveraging CDK9 Regulation of MYC: In Vivo Synergy with Sotorasib in MIA PaCa-2 Tumors VOR Combo SOTO Con CC3 Radial Distance from Injection Center (μm) % of Cell Area Cleaved Caspase 3+ 24% 20% 16% 12% 8% 4% 0 500 1000 1500 22% 18% 14% 10% 6% 2% SOTO + VOR VOR SOTO Con Data represents 5 tumors with
Slide 14: Conclusions
CONCLUSIONS MYC is implicated in KRAS mutant tumors. CDK9 is a known regulator of MYC transcription and a modulator of MYC protein phosphorylation at Ser62 Treatment of KRAS G12C mutant MIA PaCa-2 pancreatic cancer cells with voruciclib resulted in a rapid decrease in both phosphorylation of protein
Slide 15: Voruciclib: Oral CDK Inhibitor with Potent CDK9 Activity Clinical Experience
Voruciclib: Oral CDK Inhibitor with Potent CDK9 Activity Clinical Experience
Slide 16: Piramal Monotherapy Phase Studies in Solid Tumors
Piramal Monotherapy Phase 1 Studies in Solid Tumors 2 weeks on, 1 week off schedule 75 to 850 mg 29 pts in dose escalation / expansion at 600 mg cohorts 41% disease control rate 1 PR and 8 SD lasting 2 to 6 months Daily continuously schedule 75 to 500 mg 39 pts in dose escalation / expansion at 350
Slide 17: Decreased c-MYC Expression in Solid Tumors
Decreased c-MYC Expression in Solid Tumors 10 gene biomarkers evaluated in Phase 1 daily dosing study c-MYC expression decreased in 17/25 patients (68%) tested Data on file.
Slide 18: Piramal Study of Voruciclib + Vemurafenib in Melanoma
Piramal Study of Voruciclib + Vemurafenib in BRAF-mut Advanced/Inoperable Malignant Melanoma Voruciclib 150 mg daily plus vemurafenib 720 mg or 960 mg BID in 28-day cycles 9 pts treated before study termination for business reasons 8 patients evaluable for efficacy 5 patients were BRAFi refractory B
Slide 19: CR in a Patient with Pulmonary Metastases
CR in a Patient with Pulmonary Metastases Data on file.
Slide 20: Phase Study in R/R B-Cell Malignancies and AML
Leveraging CDK9 Regulation of MCL1: Phase 1 Study in R/R B-Cell Malignancies and AML Study population Relapsed/Refractory B-cell malignancies Relapsed/Refractory AML Dose escalation with standard 3+3 design Endpoints Safety and tolerability Pharmacokinetics Biologic correlative studies BH3 profiling
Slide 21: Phase Study in Hematologic Malignancies
Phase 1 Study in Hematologic Malignancies 24 pts treated in 3 dose levels 10 AML and 14 B-cell malignancies No drug related GI toxicity or neutropenia at doses studied Favorable PK profile across all voruciclib studies Half life 24-28 hours supports once-a-day dosing Dose proportional Cmax and AUC H
Slide 22: Voruciclib Shows Preferential Tumor Accumulation in Preclinical Model
HCT-116 CRC cell xenograft in SCID mice. 8 mice per time point (2 control, 6 orally dosed with voruciclib at 100 mpk). Voruciclib fold increase in tumors relative to plasma are indicated. Voruciclib Shows Preferential Tumor Accumulation in Preclinical Model Data on file.
Slide 23: Evidence of Biologic Activity in AML
Evidence of Biologic Activity in AML Suspected Differentiation syndrome seen in 5 pts (50%) Increased WBC without increased in blasts, bone pain, and/or pulmonary symptoms Response to corticosteroids Differentiation syndrome reported with ATRA, IDHi, and other AML targeted therapies Data on file.
Slide 24: Voruciclib Synergizes with Venetoclax in Cell Lines
Voruciclib Synergizes with Venetoclax in Venetoclax Sensitive and Resistant Cell Lines Ven Sensitive Ven Resistant Luedtke, et al. Nat Sign Trans and Targ Ther. 2020
Slide 25: Phase Study of Voruciclib + Venetoclax in AML Planned Amendment
Phase 1 Study of Voruciclib + Venetoclax in AML Planned Amendment Study population Relapsed/Refractory B-cell malignancies Relapsed/Refractory AML Dose escalation with standard 3+3 design Endpoints Safety and tolerability Pharmacokinetics Biologic correlative studies BH3 profiling, MCL-1 expression
Slide 26: Key Upcoming Milestones Across Portfolio
Key Upcoming 12 Month Milestones Across Portfolio Zandelisib TIDAL, study intended to support accelerated approval application for R/R follicular lymphoma: Announce top-line data fourth quarter CY2021 New clinical studies to expand development, including: COASTAL, intended confirmatory Phase 3 study
Slide 27: Q&A
MEL Q&A NASDAQ: MEIP
Slide 28: Building a Leading Oncology Franchise
Building a Leading Oncology Franchise NASDAQ: MEIP April 13, 2021