Biodexa Pharmaceuticals plc · NASDAQ:BDRX
Biodexa Pharmaceuticals — Investor Presentation (May 2023)
35 slides from Biodexa Pharmaceuticals's investor presentation, May 24, 2023
Slide 1: Corporate Presentation May 2023
Corporate Presentation NASDAQ:BDRX May 2023
Slide 2: Disclaimer & Cautionary Language Regarding Forward-Looking Statements
Disclaimer & Cautionary Language Regarding Forward - Looking Statements The following presentation, including a hard copy of these slides/the talks given by the presenters, the information communic ate d during any delivery of the presentation and any question and answer session and any document or
Slide 3: Risk Factors
Risk Factors Investing in our securities includes a high degree of risk . You should consider carefully the specific factors discussed below, together with all of the other information contained in our SEC filings, including the list of risk factors in the Risk Factors section of the Company's Form
Slide 4: Transaction Overview
Transaction Overview On May 18, 2023, Biodexa Pharmaceuticals PLC (NASDAQ:BDRX) and Varian Biopharmaceuticals Inc., a Delaware corporation (“VarianBio” or “VB”) entered a non - binding LOI for Biodexa to potentially acquire VarianBio, a targeted oncology therapies company. Building a portfolio of hi
Slide 5: Transaction Terms and Financing Requirements
Financing Requirements: • $7.0MM for IND - enabling and proof - of - concept study in VAR101 Consideration to VarianBio's debt holders and equity holders: 10MM ADS At closing of contemplated transaction: Contingent consideration: 3MM ADS Initiation of first pivotal study of VB product: 3MM ADS First
Slide 6: VarianBio: aPKCi inhibitors VAR-101 and VAR-102
Focused on getting VAR - 101 into first - in - man clinical trial in BCC Atypical Protein Kinase C iota ( aPKCi ) inhibitor VAR - 102 VAR - 101 Oral Agent Topical Application Solid Tumors / AML Basal Cell Carcinoma (“BCC”) Pre - Clinical Pre - Clinical Novel Protein Kinase Target • PKCi is required
Slide 7: BDRX + VarianBio Development Pipeline
Next Milestone Phase2 Phase 1 Preclinical Indication IND for DMG Phase II submission Q3 - 2023 Diffuse Midline Glioma MTX 110 ( panobinostat ) P hase I PFS data Q3 - 2023 Glioblastoma MTX 110 ( panobinostat ) Completion of final IND - enabling skin tox studies Q4 - 2023 Basal Cell Carcinoma VAR - 10
Slide 8: Anticipated Catalysts
Q2’ 23 Q3’ 23 Q4’ 23 Anticipated Catalysts 8 Q1’ 23 MTX110 DSMB clearance to escalate rGBM dose to 90 μ M VAR - 101 Delivery of GLP topical gel for IND - enabling tox studies H1’ 24 CONFIDENTIAL – NOT FOR PUBLIC DISTRIBUTION MTX110 Final patient in ‘203 Phase I study in DMG MTX110 IND for DMG Phase
Slide 9: MTX110
biodexa pharmaceuticals MTX110
Slide 10: MTX110 Rationale for Panobinostat
• In a screen of 83 drugs panobinostat was among the most effective agents 1 • Convection - enhanced delivery (CED) to directly infuse panobinostat into the pons of a DMG orthotopic xenograft model showed: • A marked effect on the rate of DMG xenograft growth 1 • Significantly prolonged survival com
Slide 11: MTX110 Product Concept
Delivered directly into tumor Drug bypasses blood brain barrier Re - fillable implanted pump Optimized Therapeutic Dose with Minimal Potential for Systemic Exposure MTX110 Product Concept 11
Slide 12: MTX110 Diffuse Midline Glioma (DMG) Opportunity
MTX110 Diffuse Midline Glioma (DMG) Opportunity • Significant unmet medical need • About 300 children diagnosed in the US pa 1 , over 1,100 worldwide 2 • Median survival of approximately 10 months [ref] • Resection not possible, no effective treatment 3 • Phase I programme: • ‘201 study (UCSF) n=7 s
Slide 13: MTX110 Diffuse Midline Glioma (DMG) – Clinical Data
MTX110 Diffuse Midline Glioma (DMG) – Clinical Data 13 CONFIDENTIAL – NOT FOR PUBLIC DISTRIBUTION 1. Jansen et al, 2015. Neuro - Oncology 17(1):160 - 166 The median overall survival (OS) for cohort was 26.1 months (95% CI) Median survival based on a cohort of 316 cases was 10.0 months 1
Slide 14: MTX110 Glioblastoma (GBM) Opportunity
MTX110 Glioblastoma (GBM) Opportunity • Most common and aggressive form of brain cancer in adults • Survival with standard of care treatment ranges from approximately 13 to 30 months depending on MGMT methylation. • Standard of care: resection, radiation, limited drug options • Near 100% recurrence
Slide 15: MTX110 Glioblastoma (GBM) Pre-clinical Data
MTX110 Glioblastoma (GBM) Pre - clinical Data 15 • Problem: • Many drug failures due to poor BBB penetration • Potential Solution: • MTX110 is delivered intra - tumorally at high doses via CED, by - passing BBB • Compelling mechanism and preclinical evidence of efficacy in GBM models • Encouraging d
Slide 16: VarianBio VAR-101 & VAR-102
Dada VarianBio VAR-101 & VAR-102
Slide 17: aPKCi and the Hedgehog/GLI-1 pathway rationale
• Target canonical Hedgehog ( Hh ) pathway downstream of SMO inhibitors. aPKCi activation of transcription factor GLI - 1 regulates BCC growth, in vitro 1 . • Elevated levels of GLI - 1 in cancer are driven by non - canonical pathways, including RAS - RAF - MEK, TGFb and PI3K - AKT - mTOR. 2 • Sever
Slide 18: VAR-101 Basal Cell Carcinoma: Opportunity
VAR - 101 Basal Cell Carcinoma: Opportunity • Skin cancer that arises from basal cells, small round cells found in the epidermis. • Most common cancer in humans in the US, Europe, and Australia. – ~80% of all skin cancers are BCC – 4.3 million cases of BCC are diagnosed in the U.S. each year, result
Slide 19: VAR-101 Pre-clinical Data
VAR - 101 Pre - clinical Data VAR - 101: Evidence of Dose - dependent Modulation of BCC Cell Viability and Gli - 1 mRNA, in vitro Gli - 1 mRNA 6 - hour treatment 24 - hour treatment VAR - 101 BSC1 Viability • Relatively consistent profile in panel of murine and human BCC cell lines • All BCCs expres
Slide 20: VAR-102 Rationale for Solid Tumors / AML
VAR - 102 Rationale for Solid Tumors / AML • Plan to pursue systemic tumor indications in a “basket” solid tumor Phase 1 trial • Biomarker - driven approach targeting aPKCi / Gli - 1 / K - RAS positive tumors • BCC appears to help form clinical ”biomarker” training data set for solid tumors • Target
Slide 21: VAR-102 Pre-clinical Data in NSCLC Models
VAR - 102 Pre - clinical Data in NSCLC Models Dose - related Anti - Tumor Activity Observed in H1703 - ISO NSCL (SCC) Xenografts in Nude Mice 21
Slide 22: VAR-102 Pre-clinical Data in Small Animal Models
VAR - 102 Pre - clinical Data in Small Animal Models Species Dose (iv/po, mg/kg) CL (mL/min/kg) Vd (L/kg) Iv t1/2 (h) Cmax at top dose (ng/mL) F (%) Mouse 1/10 205 11.2 0.6 62 37 Rat 5/55 12 ± 5 4.7 ± 2.9 3.7 ± 0.9 699 ± 76 13 ± 2 Dog 1/3 & 10 4.33 8.51 ± 3.1 23.0 ± 4.12 730 ± 172 92 ± 10.4 Monkey 1
Slide 23: Pro-Forma Cap Table
biodexa pharmaceuticals PRO-FORMA CAP TABLE
Slide 24: Pro-Forma Cap Table as of May 19, 2023
Pro - Forma Cap Table as of May 19, 2023 Excluding $7MM Financing Requirements 24 Combined company will have zero debt ADSs WAV Ex. Price BDRX VarianBio Pro Forma Outstanding 20,635,882 20,635,882 67% 56% Consideration 10,000,000 10,000,000 33% 27% ISSUED 20,635,882 10,000,000 30,635,882 100% 83% Wa
Slide 25: Investment Summary
Investment Summary • Clinical - stage company focused on therapeutics for rare and orphan / oncology • Main programs represent significant unmet need / commercial opportunities • Focused on a suite of delivery technologies • Multiple near - term catalysts • Funding to proof - of - concept • Plan for
Slide 26: Appendix
biodexa pharmaceuticals Appendix 26
Slide 27: MTX110 Inhibition of HDAC
MTX110 - V0024P Inhibition of HDAC by MTX110 IC 50 MTX110 - 10.9nM and panobinostat DMSO 2.61nM against HDAC Class I/II enzymes demonstrating that complexation of panobinostat to HPBCD did not alter its HDAC inhibition activity. Potency was highest against Class I (HDAC1, HDAC2, HDAC3, and HDAC8) an
Slide 28: MTX110 Cytotoxicity in DMG Cell Lines
MTX110 - V0287P Cytotoxicity in DMG Cell Lines • MTX110 was cytotoxic with IC 50 values in the low nM range, across a range of DIPG and GBM cell lines, with varying mutation status profiles Table shows major mutations across cell lines and respective IC 50 values for cytotoxicity in response to MTX1
Slide 29: MTX in vivo DIPG and GBM models
MTX - 110 in vivo DIPG and GBM models
Slide 30: MTX110 Efficacy in an Orthotopic DIPG Rat Model
MTX110 - R0288P Efficacy in an orthotopic DIPG Rat Model • Kaplan Meier survival plots from DIPG orthotopic rats demonstrating extended 50% survival to 64 days compared with 52 days in control group (p<0.037). • CED infusion of MTX110 @100µM twice weekly extended survival to 64 days compared with 52
Slide 31: MTX110 Efficacy in an Ectopic GBM Mouse Model
MTX110 - M0221P Efficacy in an ectopic GBM Mouse Model • Systemic administration of MTX110 resulted in non significant extensions in survival in an IDH1 Wild Type GBM tumour mouse model MTX110 resulted in a non - significant reduction in tumour growth compared to control (T - C 10.75 days p> 0.05) S
Slide 32: Distribution of MTX110 after single CED administration
MTX110 - R0250K Distribution of MTX110 after single CED administration Brain panobinostat was highest in the convected region of the brain. Concentrations declined after cessation of CED with a calculated half life of 2h. Tissue clearance of Panobinostat after CED delivery of MTX110 into the striatu
Slide 33: MTX110 Medulloblastoma Background
MTX110 Medulloblastoma Background • Cancerous brain tumour that starts in the cerebellum in the lower back part of the brain • Most common cancerous brain tumour in children • Accounts for 15 - 20% of childhood brain tumours 2 • 5 - year relative survival rate for children age 14 and younger of 72%
Slide 34: MTD217 Leptomeningeal Disease (LMD) Background
MTD217 Leptomeningeal Disease (LMD) Background • Cancer in the cerebrospinal fluid and leptomeninges caused by metastases • Most commonly arises from breast and lung cancers • Approximately 5% of people who have cancer develop 1 LMD • No effective treatments currently exist for LMD • With treatment,
Slide 35: aPKCi Rational Drug Design
aPKCi Rational Drug Design Key Attributes of Active Pharmaceutical Agent x Molecules designed through med chem, SAR, and in vitro and in vivo testing x Specific downstream targeting of aPKCi effects and evidence of resistance x Associated biomarkers: aPKCi, Gli - 1 mRNA, other phosphorylation compon
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