Lite Strategy, Inc. · NASDAQ:LITS
Lite Strategy — MEI Pharma — Merger or Acquisition (June 2023)
89 slides from Lite Strategy's merger presentation, Jun 20, 2023
Slide 1: MEI Pharma & Infinity Pharmaceuticals Merger and Clinical Program Update
JUNE 2023 MEI Pharma & Infinity Pharmaceuticals Merger and Clinical Program Update Exhibit 99.2
Slide 2: Today's Agenda
A Transaction with Potential to Create Significant Opportunities and Build Value TODAY’S AGENDA Welcome and Overview David Urso, President & CEO (MEIP and combined company) Eganelisib Dr. Robert Ilaria, Jr., Chief Medical Officer (INFI and combined company) Dr. Ezra Cohen Chief Medical Officer, Onco
Slide 3: Cautionary Statement Regarding Forward-Looking Statements
Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this presentation may be considered forward-looking statements within the meaning of the federal securities law. Such statements are based upon current plans, estimates and expectations of the management of MEI
Slide 4: Additional Information
Additional Information Important Information about the Merger and Where to Find It This communication relates to a proposed transaction between Infinity Pharmaceuticals, Inc. (“Infinity”) and MEI Pharma, Inc. (“MEI”). In connection with the proposed merger, MEI filed with the SEC a registration stat
Slide 5: Today's Agenda
A Transaction with Potential to Create Significant Opportunities and Build Value TODAY’S AGENDA Welcome and Overview David Urso, President & CEO (MEIP and combined company) Eganelisib Dr. Robert Ilaria, Jr., Chief Medical Officer (INFI and combined company) Dr. Ezra Cohen Chief Medical Officer, Onco
Slide 6: A Combined Company with Significant Opportunities for Value Creation
A Combined Company with Significant Opportunities for Value Creation Three differentiated, promising, clinical candidates based on solid science and data* Pipeline led by planned eganelisib Phase 2 Study in Squamous cell carcinoma of the head & neck (SCCHN) Voruciclib + Venclexta® P1 Study: Initial
Slide 7: Leadership with Extensive Industry and Oncology Drug Development Expertise
Leadership with Extensive Industry and Oncology Drug Development Expertise EXECUTIVE LEADERSHIP David Urso | Chief Executive Officer Robert Ilaria Jr., MD | Chief Medical Officer Stéphane Peluso PhD | Chief Scientific Officer BOARD David Urso Norman C. Selby (Chair) Charles V. Baltic III, JD Richard
Slide 8: Clinical-Stage Oncology Programs Expected to be Funded Through Mid-2025
3 Clinical-Stage Oncology Programs Expected to be Funded Through Mid-2025 INVESTIGATIONAL AGENTS THERAPEUTIC AREA COMBINATION PHASE 1/1B PHASE 2 PHASE 3 Initial Clinical Data* Eganelisib Oral PI3K Gamma Inhibitor Head & Neck Squamous Cell Carcinoma1 1L Recurrent KEYTRUDA® 2H 2024 Voruciclib Oral CDK
Slide 9: Transaction Summary
TRANSACTION STRUCTURE Stock-for-stock merger: Infinity stockholders will receive shares of MEI common stock Infinity will become a wholly owned subsidiary of MEI pharma Pro forma outstanding equity of the combined company post-closing: Approximately 58% MEI and approximately 42% Infinity Combined co
Slide 10: Clinical-Stage Oncology Programs Expected to be Funded Through Mid-2025
INVESTIGATIONAL AGENTS THERAPEUTIC AREA COMBINATION PHASE 1/1B PHASE 2 PHASE 3 Initial Clinical Data* Eganelisib Oral PI3K Gamma Inhibitor Head & Neck Squamous Cell Carcinoma1 1L Recurrent KEYTRUDA® 2H 2024 Voruciclib Oral CDK9 Inhibitor Acute Myeloid Leukemia Relapsed/refractory (2L+) VENCLEXTA® ~Y
Slide 11: Eganelisib: First-in-Class PI3K-gamma Inhibitor
Eganelisib: First-in-Class PI3K-�� Inhibitor for Next Generation Macrophage Reprogramming Cancer Immunotherapy
Slide 12: Eganelisib is a First-in-Class, Potent and Selective PI3K-γ Inhibitor
Cellular IC50 pAKT IC50 (nM) Eganelisib / IPI-549 Eganelisib is a First-in-Class, Potent and Selective PI3K-g Inhibitor with a Strong Scientific Foundation as Next Generation Cancer Immunotherapy Kaneda et al. Nature 2016 539 437 De Henau et al. Nature, 2016 539 443 Evans et al ACS Med Chem Let 2016
Slide 13: Reprogramming Tumor Associated Macrophages for Cancer Immunotherapy
Suppressed T cells M2-like Macrophages Growing Tumor Cells M1-like Macrophages Activated T Cells Dying Tumor Cells Immunosuppressive M2-like Macrophages Correlate with poor prognosis across most cancers Support tumor immune evasion, metastasis, angiogenesis Key contributors to resistance to immunoth
Slide 14: PI3K-γ is Uniquely Differentiated from Other PI3K Isoforms
PI3K-�� PI3K-δ PI3K-�� is Uniquely Differentiated from Other PI3K Isoforms vs PI3K-β PI3K-α Myeloid cells B cells and T-cells Ubiquitous Ubiquitous Immune cell trafficking Macrophage polarization B-cell and T-cell activation and function Platelet activation Insulin signaling Insulin signaling KO via
Slide 15: MARIO Clinical Program Demonstrates Eganelisib Activity and Safety
PHASE 1 PHASE 1B PHASE 2 Key Study Data ITT mOS of 15.4 mos vs 7.9 mos on Control Arm with HR of 0.621 MARIO Clinical Program Demonstrates Eganelisib Clinical Activity and Safety Across Multiple Combinations and Tumor Types MARIO-275 2nd Line Urothelial Cancer in combination with Opdivo ARC-2 TNBC a
Slide 16: MARIO Clinical Program Demonstrates Eganelisib Activity and Safety
PHASE 1 PHASE 1B PHASE 2 Key Study Data ITT mOS of 15.4 mos vs 7.9 mos on Control Arm with HR of 0.621 MARIO Clinical Program Demonstrates Eganelisib Clinical Activity and Safety Across Multiple Combinations and Tumor Types MARIO-275 2nd Line Urothelial Cancer in combination with Opdivo ARC-2 TNBC a
Slide 17: SCCHN Background
SCCHN Background Key risk factors include tobacco and alcohol use, as well as HPV infection Incidence of HPV-caused SCCHN is increasing over time Men are over twice as likely to be diagnosed with SCCHN as women Squamous cell carcinoma accounts for ~90% of all head and neck cancers, with an annual in
Slide 18: Current Landscape in R/M HNSCC
Current Landscape in R/M HNSCC Ezra Cohen, MD FIRST LINE SECOND LINE THIRD LINE + R/M= Recurrent/Metastatic
Slide 19: Current Landscape in R/M HNSCC
Current Landscape in R/M HNSCC Ezra Cohen, MD Anti-PD1 Monotherapy PDL1+ Lesser tumor burden FIRST LINE SECOND LINE THIRD LINE + R/M= Recurrent/Metastatic
Slide 20: Current Landscape in R/M HNSCC
Current Landscape in R/M HNSCC Ezra Cohen, MD Anti-PD1 Monotherapy PDL1+ Lesser tumor burden Anti-PD1 + chemotherapy PDL1 nil or unknown Greater tumor burden FIRST LINE SECOND LINE THIRD LINE + R/M= Recurrent/Metastatic
Slide 21: Current Landscape in R/M HNSCC
Current Landscape in R/M HNSCC Ezra Cohen, MD Anti-PD1 Monotherapy PDL1+ Lesser tumor burden Anti-PD1 + chemotherapy PDL1 nil or unknown Greater tumor burden Chemotherapy +/- EGFRi aPD-1 unavailable or not preferred FIRST LINE SECOND LINE THIRD LINE + R/M= Recurrent/Metastatic
Slide 22: Current Landscape in R/M HNSCC
Current Landscape in R/M HNSCC Ezra Cohen, MD Anti-PD1 Monotherapy PDL1+ Lesser tumor burden Anti-PD1 + chemotherapy PDL1 nil or unknown Greater tumor burden Chemotherapy +/- EGFRi aPD-1 unavailable or not preferred FIRST LINE SECOND LINE THIRD LINE + Standard UNDEFINED Dependent on 1st line therapy
Slide 23: Current Landscape in R/M HNSCC
Current Landscape in R/M HNSCC Ezra Cohen, MD Anti-PD1 Monotherapy PDL1+ Lesser tumor burden Anti-PD1 + chemotherapy PDL1 nil or unknown Greater tumor burden Chemotherapy +/- EGFRi aPD-1 unavailable or not preferred FIRST LINE SECOND LINE THIRD LINE + Standard UNDEFINED Dependent on 1st line therapy
Slide 24: Current Landscape in R/M HNSCC
Current Landscape in R/M HNSCC Ezra Cohen, MD Anti-PD1 Monotherapy PDL1+ Lesser tumor burden Anti-PD1 + chemotherapy PDL1 nil or unknown Greater tumor burden Chemotherapy +/- EGFRi aPD-1 unavailable or not preferred FIRST LINE SECOND LINE THIRD LINE + Standard UNDEFINED Dependent on 1st line therapy
Slide 25: Pembrolizumab Monotherapy PFS and OS from Keynote-048 in Frontline SCCHN
Pembrolizumab Monotherapy PFS and OS from Keynote-048 in Frontline SCCHN patients with CPS1-19% and CPS >20% PFS, CPS≥201 OS, CPS≥202 OS, CPS 1-191 PFS, CPS 1-191 1. Burtness et al, J. Clin. Oncol. 2022; 2.Burtness et al, Lancet 2019
Slide 26: MARIO-8: Egan + Pembro Potential IO/IO Chemo Free Regimen
OS, CPS≥202 OS, CPS 1-191 PFS, CPS 1-191 MARIO-8: Egan + Pembro Potential IO/IO Chemo Free Regimen in Patients with CPS 1-19% and CPS>20%
Slide 27: MARIO-8 Randomized Phase 2 Study in SCCHN
MARIO-8 Randomized Phase 2 Study in SCCHN: Optimizing Eganelisib Dosing in Combination with Pembrolizumab Eganelisib Dosing Regimen 1 + Pembrolizumab Placebo + Pembrolizumab 2:2:1 Using an adaptive design in Part A, the eganelisib dosing regimen decision will be based on available efficacy and safet
Slide 28: MARIO-1: Phase 1/1b Clinical Study
MARIO-1: Phase 1 Clinical Study
Slide 29: MARIO-1: Phase 1/1b Study of Eganelisib Alone and With Nivolumab
MARIO-1: Phase 1/1b Study of Eganelisib Alone and in Combination With Nivolumab in Advanced Solid Tumors (N=224 Patients) Checkpoint inhibitor-naïve Immediate prior checkpoint inhibitor-resistant Checkpoint inhibitor-independent Checkpoint non-responsive tumors NSCLC Melanoma SCCHN TNBC Mesothelioma
Slide 30: Sustained inhibition above the PI3K-γ EC90 and below PI3K-δ EC50
Sustained inhibition above the PI3K-g EC90 and below PI3K-d EC50 at Eganelisib doses up to 40 mg Cycle 2 Day 1 EC90 PI3Kg EC50 PI3Kd Eganelisib concentration (mg/mL) Time (hr) Note: EC50/EC90 from ex-vivo whole blood PD assay PI3Kd:pAKT (S473) in CD19+ B cells PI3Kg:pAKT (T308) in CD14+ Monocytes Er
Slide 31: Eganelisib Monotherapy Leads to Immune Activation in Peripheral Blood
Eganelisib Monotherapy Leads to Immune Activation in Peripheral Blood T Cell Reinvigoration Day 0 Day 28 Ki67+ of PD1+ memory CD8 (%) log2FC over baseline * N=35 all dose groups combined for monotherapy *p<.05 T-Test IFN-�� Responsive Cytokines CXCL10 Similar results for CXCL9 (not shown) IFN-�� Res
Slide 32: Treatment-related Adverse Events in Eganelisib Monotherapy Cohort
Treatment-related Adverse Events Occurring in at Least 5% of Patients or with Any Event of Grade 3 or Highera in the Eganelisib Monotherapy Cohort Eganelisib dose escalation (Part A) n (%) Eganelisib dose expansion (Part D: 60 mg) (n=20) n (%) 10–30 mg (n=12) 40 mg (n=4) 60 mg (n=3) Any grade G≥3 An
Slide 33: Treatment-related Adverse Events: Eganelisib plus Nivolumab
n (%) Eganelisib dose escalation + nivolumab (Part C) Eganelisib + nivolumab dose expansion (Parts E-H) 40 mg (n=149) 20 mg (n=7) 30 mg (n=12) 40 mg (n=12) Any grade G ≥ 3 Any grade G ≥ 3b Any grade G ≥ 3c Any grade G ≥ 3d Any treatment-related TEAE 4 (57) 1 (14) 9 (75) 4 (33) 9 (75) 5 (42) 110 (74)
Slide 34: MARIO-275: Eganelisib Added to Opdivo in Urothelial Cancer
MARIO-275 Addition of Eganelisib to Standard of Care Opdivo in I/O Naïve Urothelial Cancer Patients
Slide 35: MARIO-275 Study Design and FDA Fast-Track Designation
FDA Fast-Track Designation Eganelisib 40/30mg QD** + Nivolumab 480 mg Q4W Placebo + Nivolumab 480 mg Q4W Advanced Platinum Refractory 2nd Line Urothelial Cancer Patients MDSC all comers (pre-specified and stratified) PD-L1* status all comers (pre-specified) Primary objective: ORR in MDSC High Second
Slide 36: Increased Immune Activation with Eganelisib + Nivolumab vs Nivolumab Alone
log2FC from baseline Concentration (pg/mL) Eganelisib + Nivolumab Placebo + Nivolumab (n=28) (n=12) Day 0 Day 15 Day 0 Day 15 * Increased Immune Activation with Eganelisib + Nivolumab vs Nivolumab Alone in Peripheral Blood * NS *p<.05 Two-Way ANOVA Eganelisib + Nivolumab Placebo + Nivolumab (n=20) (
Slide 37: TEAEs Leading to Treatment Discontinuation
TEAEs Leading to Treatment Discontinuation of Eganelisib/Placebo and/or Nivolumab Hepatic TEAEs Non-Hepatic TEAEs Preferred Term (PT) Egan + Nivo N=33, n (%) Placebo + Nivo N=16 , n (%) Total N=49, n (%) Patients with >=1 non-hepatic TEAE 5 (15.2) 2 (12.5) 7 (14.3) Asthenia 2 (6.1) 0 2 (4.1) Amylase
Slide 38: ITT Two-Year Landmark Survival Analysis
ITT Two-Year Landmark Survival Analysis: 45% of Patients in the Eganelisib Plus Nivolumab Arm Alive vs 24% of Patients in the Nivolumab Control Arm Overall Survival Results: ITT HR of 0.58 (0.2737, 1.2394) Indicating 42% Reduction of Risk of Death Data Snapshot 29 July 2022 Eganelisib + Nivolumab Pl
Slide 39: PD-L1(-) Two-Year Landmark Survival Analysis
PD-L1(-) Two-Year Landmark Survival Analysis: 38% of Patients in the Eganelisib Plus Nivolumab Arm Are Alive vs 17% of Patients in the Nivolumab Control Arm Data Snapshot 29 July 2022 Eganelisib + Nivolumab Placebo + Nivolumab Overall Survival Results: PD-L1(-) HR of 0.59 (0.2081, 1.6796) Indicating
Slide 40: SCCHN Clinical Data (MARIO-1) and Planned MARIO-8 Trial
SCCHN Clinical Data (MARIO-1) and Key Elements of the Planned Randomized Trial of Eganelisib + Pembro vs Pembro as First line treatment for Relapsed/metastatic SCCHN (MARIO-8)
Slide 41: MARIO-1: Eganelisib + Nivolumab in Patients Progressed on Prior CPI Therapy
1st Line Chemo “X” 2nd Line Chemo “Y” 3rd Line Immediate Prior Checkpoint Inhibitor IPI-549 + Checkpoint Treatment Stable Disease Partial Response Progressive Disease Eganelisib Response MARIO-1 Study Start PD Progressive Disease PD PD PD Tumor Burden Study Concept: Design examines the activity of e
Slide 42: Overcoming Resistance to CPI in MARIO-1 SCCHN Patients
Patient A: stage IV disease at study entry Refractory to pembrolizumab after 15 months (best response PR) 63% tumor reduction PFS: 11 months Patient B: stage IV disease at study entry Refractory to pembrolizumab after 5 months (best response SD) 36% tumor reduction PFS: 7 months Start of MARIO-1 The
Slide 43: Manageable Safety Profile in SCCHN Cohort
Most Common TEAEs (All Grade) in ≥15% of Patients (N=21) Preferred Term / Grouped Term TEAE (All) Tx-Related TEAE (All) Fatigue 13 (61.9) 9 (42.9) Skin * 11 (52.4) 9 (42.9) Pyrexia 9 (42.9) 3 (14.3) Decreased Appetite 9 (42.9) 3 (14.3) Hepatic ** 6 (28.6) 5 (23.8) Weight Decreased 6 (28.6) 0 Nausea
Slide 44: Encouraging PFS in Heavily Pretreated SCCHN Patients
Total N = 21 ≤ 2 Prior Lines N = 11 ≥ 3 Prior Lines N = 10 Best Overall Response Partial Response (PR), n Stable Disease (SD), n Progressive Disease (PD), n Not evaluable, n 2 7 10 2 2 2 5 2 0 5 5 0 Overall Response Rate (ORR) (PR), n (%) 2 (9.5) 2 (18.2) 0 (0) Disease Control Rate (DCR) (PR + SD),
Slide 45: MARIO-8 Randomized Phase 2 Study in SCCHN
MARIO-8 Randomized Phase 2 Study in SCCHN: Optimizing Eganelisib Dosing in Combination with Pembrolizumab Eganelisib Dosing Regimen 1 + Pembrolizumab Placebo + Pembrolizumab 2:2:1 Estimated study start Q3 2023 Using an adaptive design in Part A, the eganelisib dosing regimen decision will be based o
Slide 46: Summary
Summary Encouraging data from heavily pretreated patients with advanced/metastatic head & neck squamous cell cancer, whose tumors had progressed on immediate prior ICI treatment, supports further development of eganelisib in this tumor type Data supports potentially greater activity in earlier lines
Slide 47: Q&A Participants
Q&A Participants Ezra Cohen, MD, FRCPSC, FASCO Chief Medical Officer, Oncology, Tempus Most recently, Chief, Division of Hematology-Oncology, and Associate Director of Clinical Science at UC San Diego Moores Cancer Center Robert Ilaria, Jr, MD Chief Medical Officer, Infinity Pharmaceuticals Previous
Slide 48: Q&A
Qé&A
Slide 49: Voruciclib: Oral CDK9 Inhibitor
Voruciclib: Oral CDK9 Inhibitor
Slide 50: Scientific Rationale & Mechanism of Action
Scientific Rationale & Mechanism of Action
Slide 51: Voruciclib is an Orally Administered CDK9 Inhibitor
Voruciclib is an Orally Administered CDK9 Inhibitor: Targeting Cell Proliferation Regulation Increased Mcl-1 is associated with poor prognosis in AML and CLL and is an established venetoclax resistance mechanism Venetoclax inhibits BCL2 but can lead to stabilization of Mcl-1 Voruciclib inhibits Mcl-
Slide 52: Voruciclib is an Oral, Selective and Specific CDK9 Inhibitor
Voruciclib is an Oral, Selective and Specific CDK9 Inhibitor Cyclin dependent kinases (CDK) bind with cyclins to regulate the cell cycle and transcription Voruciclib inhibits CDK9 Higher specificity and longer residence time on target vs CDK 4, 6 &1 Greater selectivity against CDKs relative to other
Slide 53: Preclinical Studies Show Synergy with Venetoclax
Preclinical Studies Show Synergy with Venetoclax
Slide 54: Initial Development Focus: Address Upregulation of MCL1 Associated with Venetoclax
Initial Development Focus: Address Upregulation of MCL1 Associated with Venetoclax Increased Mcl-1 is an established venetoclax resistance mechanism and is associated with poor outcomes in AML and CLL Hypothesis ? Venetoclax inhibits BCL2 but can lead to stabilization of Mcl-1 Voruciclib inhibits MC
Slide 55: Voruciclib Synergizes with Venetoclax in AML Murine Xenograft Model
Voruciclib Synergizes with Venetoclax in AML Murine Xenograft Model Luedtke, et al. Signal Transduct Ther (2020) Suppresses Mcl-1 Level Extends Survival in MV4-11 Tumor Increases Apoptosis VOR (nM) VEN (nM) 0 0 0 12.5 0 25 0 50 500 0 1000 0 2000 0 1000 12.5 1000 25 2000 12.5 2000 25 VEN VOR VOR + VE
Slide 56: Voruciclib Synergizes with Venetoclax in Multiple Models, Including DLBCL
Voruciclib Synergizes with Venetoclax in Multiple Models, Including High Risk DLBCL Murine Xenograft Models Dey et al. Nature Sci Rep 2017 Suppresses Mcl-1 Level Inhibits Tumor Growth a. b.
Slide 57: Clinical Studies in Solid Tumors
Clinical Studies in Solid Tumors
Slide 58: Key Findings in 2 Monotherapy Phase 1 Studies in Solid Tumors
68 PTS ENROLLED IN 2 DOSE ESCALATION/EXPANSION STUDIES EVALUATING 2 DOSING SCHEDULES SAFETY Maximum Tolerated Dose (MTD) 600 mg on intermittent dosing of 14 days on/7 days off 350 mg on continuous daily dosing Most common adverse events (AE) involved the gastrointestinal tract No neutropenia No pulm
Slide 59: Decreased c-MYC Expression Observed in Phase 1 Study in Solid Tumors
Decreased c-MYC Expression Observed in Phase 1 Study in Solid Tumors 10 gene biomarkers evaluated in blood in daily dosing study c-MYC expression decreased in ~60% patients tested (n=25)
Slide 60: Current Clinical Study in Hematologic Malignancies
Current Clinical Study in Hematologic Malignancies
Slide 61: Voruciclib Pivot to Hematologic Malignancies
Voruciclib Pivot to Hematologic Malignancies Based on Clear Scientific Evidence and Medical Need Rationale Recognition that voruciclib is primarily a CDK9 inhibitor Evidence of effect in CLL patient samples and synergy with venetoclax in preclinical models Goal is to overcome the most common mechani
Slide 62: Ongoing Phase 1 Study of Voruciclib Alone and With Venetoclax
Ongoing Phase 1 Study of Voruciclib Alone and in Combination with Venetoclax in AML and B-cell Malignancies Voruciclib monotherapy dose escalation in AML and B-cell Malignancies Completed (N = 40) Voruciclib + Venetoclax dose escalation in AML Enrolling V2 Study population Relapsed/Refractory B-cell
Slide 63: Monotherapy Safety Results Do Not Suggest Overlapping Toxicity with Venetoclax
Monotherapy Safety Results Do Not Suggest Overlapping Toxicity with Venetoclax in Patients with AML or B-cell Malignancies Group I (n=16) Group II (n=13) n (%) Gr 3 Gr 4 Gr 3 Gr 4 Acute respiratory failure 0 1 (6.3) 0 0 Dyspnea exertional 0 1 (6.3) 0 0 Respiratory failure 0 1 (6.3) 0 0 Hypoxia 1 (6.
Slide 64: Key Findings From Monotherapy Phase 1 Study in Hematologic Malignancies
Key Findings From Monotherapy Ph 1 Study in Hematologic Malignancies (N = 40 pts) Safety/Tolerability Dose limiting toxicity (DLT) of respiratory failure at 100 mg daily in 2 pts with AML Confounded by prior allogeneic transplant and AML differentiation syndrome No DLTs on intermittent dosing at 100
Slide 65: Voruciclib + Venetoclax in R/R AML Shows Signs of Clinical Activity
Ongoing Evaluation of Voruciclib + Venetoclax in Relapsed/Refractor (R/R) AML Demonstrates Encouraging Signs of Clinical Activity at Low Dose Dose escalation began from a very low dose of 50 mg every-other-day Requested by FDA due to the introduction of a new formulation Encouraging results in 2 pat
Slide 66: Clinical Development Plan
Clinical Development Plan
Slide 67: Voruciclib Clinical Development Strategy
Acute Myeloid Leukemia Venetoclax in combination with a hypomethylating agent (e.g. azacitidine) or low-dose cytarabine is standard of care in unfit patients with previously untreated AML Median overall survival of 15 months with venetoclax-azacitidine1 indicates further improvement is needed Voruci
Slide 68: Voruciclib Summary
Voruciclib Summary Oral CDK9 inhibitor: Pre-clinical data demonstrate down regulation of Mcl-1 and synergy with venetoclax in multiple hematologic malignancy models Increased Mcl-1 is clinically established as a venetoclax resistance mechanism Early clinical data demonstrates encouraging initial tol
Slide 69: ME-344: Mitochondrial Inhibitor
ME-344: Mitochondrial Inhibitor
Slide 70: Scientific Rationale & Mechanism of Action
Scientific Rationale & Mechanism of Action
Slide 71: ME-344: A Potential Novel Mechanism of Action
ME-344: A Potential Novel Mechanism of Action to Address Multiple Cancers in Combination with Anti-angiogenic Therapies Like Avastin® ME-344 blocks the production of adenosine triphosphate (ATP), a source of cellular energy, by inhibiting the OXPHOS pathway. Anti-angiogenic therapies, like Avastin,
Slide 72: Non-Clinical Studies
Non-Clinical Studies
Slide 73: ME-344 as a Single Agent is an Inhibitor of Cancer Cell Proliferation
Log10 IC50 (uM) IC50 Rank (of 240 cancer cell lines) Inhibits cancer cell lines proliferation Inhibits ovarian cancer stem cell proliferation ME-344 as a Single Agent is an Inhibitor of Cancer Cell Proliferation in Pre-Clinical Models Color by Sensitive/Resistant Resistant Sensitive Data on file ME-
Slide 74: ME-344 Synergizes with Anti-angiogenic TKI in Colorectal Cancer Xenograft Model
Decreases Tumor Volume Data on file ME-344 + REGORAFENIB DECREASES MEAN TUMOR VOLUMES AND EXTENDS SURVIVAL Improves Survival ME-344 Synergizes with Anti-angiogenic TKI to Enhance Antitumor Effect in Colorectal Cancer Xenograft Model
Slide 75: Clinical Studies in Solid Tumors
Clinical Studies in Solid Tumors
Slide 76: ME-344 Initial Studies in Solid Tumors
ME-344 Initial Studies in Solid Tumors
Slide 77: ME-344 Monotherapy Phase 1 Key Safety Findings
Treatment-Related Adverse Events in ≥10% of Patients (N= 30) Toxicitya Grade 1 Grade 2 Grade 3 Total Neuropathyb 1 (3%) 1 (3%) 4 (14%) 6 (20%) Nausea 4 (13%) 2 (7%) 0 6 (20%) Dizziness 3 (10%) 1 (3%) 2 (7%) 6 (20%) Fatigue 2 (7%) 3 (10%) 0 5 (17%) Vomiting 2 (7%) 2 (7%) 0 4 (13%) Diarrhea 1 (3%) 2 (
Slide 78: ME-344 Monotherapy Phase 1 Key Efficacy Findings
Duration of ME-344 therapy vs immediate prior therapy in patients achieving a partial response or stable disease Bendel et al. Cancer 2015 1 PR in SCLC lasting 52 weeks 10 SD DCR = 37% (11/30 pts) Proprietary & Confidential ME-344 Monotherapy Ph 1 Dose Escalation Study – Key Efficacy Findings
Slide 79: Clinical Study Objectives: ME-344 + Bevacizumab in Breast Cancer
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 Arm B Bevacizumab 15 mg/kg day 1 ME-344 10mg/kg days 8, 15, 21 Bevacizuma
Slide 80: ME-344 + Bevacizumab Demonstrated Anti-tumor Activity in Breast Cancer
ME-344 in combination with bevacizumab in Her2-negative breast cancer patients demonstrated anti-tumor activity as evidenced by decreased Ki67 ME-344: A Novel Mitochondrial Inhibitor with the Potential to Prevent Anti-Angiogenic Escape in Combination with Bevacizumab Qunitela-Fandino, Clin Cancer Re
Slide 81: Current Clinical Study in Colorectal Cancer
Current Clinical Study in Colorectal Cancer
Slide 82: Phase 1b Study of ME-344 + Bevacizumab in Colorectal Cancer
Cohort 1 ME-344 + Bevacizumab 28-day cycle N = 20 (Open expansion cohort if 4-mo PFS of > 20%) Cohort 1 Expansion ME-344 + Bevacizumab 28-day cycle N = 20 TREATMENT UNTIL DISEASE PROGRESSION OR UNACCEPTABLE TOXICITY RELAPSED/REFRACTORY COLORECTAL CANCER Patients with progressive disease after failed
Slide 83: Clinical Development Plan
Clinical Development Plan
Slide 84: ME-344 Clinical Development Strategy
Colorectal Cancer Oral TKI VGEF inhibitors and trifluridine-tipiracilare ± bevacizumab are standard treatment options for patients with colorectal cancer after failures of standard therapies Median overall survival of 6-12 months indicates a significant medical need ME-344 in combination with bevaci
Slide 85: ME-344 Summary
ME-344 Summary ME-344 demonstrated Ki67 decrease in combination with Avastin compared to placebo in HER2-negative breast cancer study, indicative of antitumor activity Pharmacodynamics supports on-target effect Normalized tumor vasculature and hypoxia correction correlate with enhanced antitumor act
Slide 86: Q&A Participants
Q&A Participants Nick Abbott, PhD Principal, Abbott Biotech Consultancy Most recently, Senior Analyst Equity Research, Wells Fargo Corporate and Investment Banking Richard Ghalie, MD Chief Medical Officer, MEI Pharma Formerly Ligand, Favrille and others, and practicing oncologist
Slide 87: Q&A
Qé&A
Slide 88: A Combined Company with Significant Opportunities for Value Creation
A Combined Company with Significant Opportunities for Value Creation Three differentiated, promising, clinical candidates based on solid science and data* Pipeline led by planned eganelisib Phase 2 Study in Squamous cell carcinoma of the head & neck (SCCHN) Voruciclib + Venclexta® P1 Study: Initial
Slide 89: @MEI & CA] Infinity”
@MEI & CA] Infinity” PHARMACEUTICALS harma