Starpharma Holdings Limited · ASX:SPL
Starpharma — 6th Targeted Radiopharmaceuticals Summit Europe (December 2024)
30 slides from Starpharma's conference presentation, Dec 4, 2024
Slide 1: DEP Presentation at Radiopharmaceuticals Summit
ASX Announcement DEP® Presentation at Radiopharmaceuticals Summit Melbourne, Australia; 4 December 2024: Starpharma (ASX: SPL, US OTC: SPHRY) today announces a presentation that was delivered at the 6th Targeted Radiopharmaceuticals Summit Europe, in Amsterdam, Netherlands, showcasing the potential
Slide 2: About Starpharma
About Starpharma Starpharma ASX: SPL, OTCQX: SPHRY) is an innovative biotechnology company with two decades of experience in advancing dendrimer technology from the lab to the patient. Our mission is to help patients with significant illnesses, such as cancer, achieve improved health outcomes and qu
Slide 3: DEP Dendrimers – a Platform for Novel Targeting Moieties and Payloads
For personal use only DEP® Dendrimers – a Platform for Novel Targeting Moieties and Payloads for Enhanced Radioisotope Specificity, Efficacy and Safety Dr Jeremy Paull, PhD VP, Development and Regulatory Affairs Workshop B 3 December 2024 6th Targeted Radiopharmaceuticals Summit Europe
Slide 4: Disclaimer and Forward-Looking Statements
Disclaimer and Forward-Looking Statements For personal use only This presentation contains forward-looking statements that involve risks and uncertainties. Although we believe that the expectations reflected in the forward-looking statements are reasonable at this time, Starpharma can give no assura
Slide 5: Summary
Summary DEP® dendrimers provide a versatile, customisable platform for enhancing delivery of For personal use only radiotheranostic payloads to tumours using novel targeting moieties ❑ Proprietary DEP® platform – clinically validated via 4 clinical programs, multiple drug classes ❑ Starpharma’s are
Slide 6: Starpharma
Starpharma… An innovative, biopharmaceutical company and leader in For personal use only dendrimer technology Focus: Dendrimer Drug (DEP®) Delivery Technology Clinically validated technology Uniquely experienced team More than 350 patients treated with Expertise in dendrimer science and DEP® across
Slide 7: Starpharma's Validated DEP Platform
Starpharma’s Validated DEP® Platform DEP® dendrimers have a unique construction based G2 G3 G4 G5 For personal use only on concentric layers (generations) of lysine monomers • Synthetic, reproducible, scalable, precise • Customisable size, generation and surface Clinically validated • Phase II oncol
Slide 8: Dendrimers – Synthetic Molecules, With Precise Architecture
Dendrimers – Synthetic Molecules, With Precise Architecture, Customizable Size, Generation and Surface Functionality • Low polydispersity, near For personal use only monomodal MW distributions • Characterisation via standard methodologies, e.g., NMR, LCMS, HPLC, UPLC, SEC etc. • Standard synthetic c
Slide 9: Why Dendrimers? Opportunities to Solve Complex Challenges
Why Dendrimers? Opportunities to Solve Complex Challenges Facing Traditional Small or Large Molecule Drug Conjugates Large Molecules (e.g., mAb) Small Molecules (e.g., small molecules, peptides) For personal use only Efficacy Challenges Efficacy Challenges • Limited tumour penetration • Limited tumo
Slide 10: DEP Dendrimers – A Unique Solution to Payload/Target Delivery Challenges
DEP® Dendrimers – A Unique Solution to Solving Complex Payload/Target Delivery Challenges DEP® dendrimers bridge the gap between small and large molecule targeting and payload delivery For personal use only Potential for improved tumour penetration and retention Tuneable solubility, PK Tuneable plas
Slide 11: DEP Offers Highly Specialised Tuneable PK and Plasma Clearance Profile
DEP® Offers Highly Specialised Tuneable PK and Plasma Clearance Profile • Plasma clearance and half-life can be tailored with specific dendrimer For personal use only generation (size) and surface properties, including PEG Non-targeted Poly-L-Lysine dendrimers in rats (IV dose)1 A B E A DEP1 (PEG200
Slide 12: DEP Dendrimer Payload Release with Different Linkers
DEP® Dendrimer Payload Release with Different Linkers to Achieve Custom PK Profile • Tuneable drug release profile using different linker chemistry For personal use only Compounds with Compound A different drug linkers (pH 7.4, 37°C) 0.8 60 pH A Drug release (%) 0.6 4.0 B Dox (488nm) 5.0 40 0.4 C 6.
Slide 13: DEP Dendrimers Achieve Tumour Targeting via Complementary Mechanisms
DEP® Dendrimers Achieve Tumour Targeting via Complementary Mechanisms Physical targeting based on size and EPR effect For personal use only → EPR: Enhanced permeability and retention → Allows dendrimers to accumulate in the tumour due to leaky vasculature and poor lymphatic drainage → DEP® dendrimer
Slide 14: Dendrimers Achieve Selective Tumour Accumulation by Size and EPR Effect
Dendrimers Achieve Selective Tumour Accumulation by Virtue of Size and EPR Effect, Leading to Improved Efficacy Tumour accumulation in human xenograft tumour models with Translates to enhanced efficacy in “physically” targeted DEP® agents… human xenograft tumour model For personal use only MDA-MB-23
Slide 15: Benefits of DEP Platform Demonstrated in the Clinic - Pipeline
Benefits of Starpharma’s DEP® Platform Technology Demonstrated in the Clinic - Pipeline For personal use only Starpharma Internal DEP® Pipeline Partnered DEP® Programs Target Pre- Product Research Phase I Phase II Phase III Strategy indication clinical License/co- Ovarian and DEP® SN38 colorectal Ph
Slide 16: Starpharma's Internal DEP Oncology Portfolio
Starpharma’s Internal DEP® Oncology Portfolio Multiple Clinical Stage Assets with Significant Commercial Potential to Address Unmet Need DEP® Cabazitaxel DEP® SN38 For personal use only • Dendrimer version of leading prostate cancer drug, cabazitaxel • Novel dendrimer-topoisomerase I (TOP1) conjugat
Slide 17: DEP Cabazitaxel Achieves Highly Encouraging Efficacy in Late-Stage Patients
DEP® Cabazitaxel Achieves Highly Encouraging Efficacy in Late-Stage Patients, Compared to Standard Therapies Results Presented at the 2024 ASCO Annual Meeting For personal use only DEP® Cabazitaxel in Advanced Prostate Cancer 41.80% Jevtana^ DEP® cabazitaxel 5 4.4 20 4 13.4 14.7 N=5801 N=251 2.9 15
Slide 18: DEP SN38 Phase II Study Shows Favourable Efficacy and Tolerability
DEP® SN38 Phase II Study Shows Favourable Efficacy and Tolerability Data in Late-Stage Patients Results Presented at the 2024 ASCO Annual Meeting For personal use only Advanced Colorectal Cancer Gastrointestinal Toxicity Profile Significantly Improved with DEP® SN38 Treatment, Compared to Published
Slide 19: Extend to Radiopharmaceuticals - Pipeline
Benefits of Starpharma’s DEP® Platform Technology Extend to Radiopharmaceuticals - Pipeline For personal use only Starpharma Internal DEP® Pipeline Partnered DEP® Programs Target Pre- Product Research Phase I Phase II Phase III Strategy indication clinical License/co- Ovarian and DEP® SN38 colorecta
Slide 20: HER2 Status, Imaging and Therapy
HER2 Status, Imaging and Therapy • Importance of understanding HER2 heterogeneity to drive appropriate treatment • HER2 status is diagnosed using HER2 IHC ± ISH on a tumour biopsy For personal use only • Results drive treatment decisions/planning (e.g., HER2-targeted therapy) • A biopsy may not be r
Slide 21: HER2 Status, Imaging and Therapy
HER2 Status, Imaging and Therapy • Decisions on HER2-targeted therapy may benefit from an accurate assessment of whole body HER2 status For personal use only • HER2-targeted therapies like Enhertu provide significant benefit to metastatic HER2+ patients • Now expanding to include HER2low and HER2ult
Slide 22: HER2-Targeted Dendrimers Enable Enhanced Killing of HER2+ Cells
HER2-Targeted Dendrimers Enable Enhanced Killing of HER2+ Cells For personal use only HER2-targeted dendrimers with cytotoxic payload Cytotoxicity induced in range of HER2+ cell lines: induce HER2-specific cytotoxicity breast (SKBR3), oesophageal (OE19) and gastric (NCI-N87) 120 MDA-MB-231 HER2-targ
Slide 23: Higher Generation Targeted Dendrimers Achieve HER2+ Specific Tumour Accumulation
Higher Generation Targeted Dendrimers Achieve HER2+ Specific Tumour Accumulation, Which is Sustained via EPR Effect For personal use only HER2+ BT474 tumours 10.0 48h 89Zr HER2-targeted dendrimers 15.0 Non- HER2 16 targeted targeted 7.5 12.5 10.0 12 %ID/g %ID/g %ID/g 5.0 7.5 8 5.0 4 2.5 2.5 0.0 0 89
Slide 24: HER2-Targeted Larger Generation Dendrimers Accumulate in Tumours Like Trastuzumab
HER2-Targeted, Larger Generation Dendrimers (~50kDa) Accumulate in Tumours Similarly to HER2-mAb, Trastuzumab, with a Biodistribution Profile Showing More Rapid Clearance From Blood and Lungs For personal use only 48h PET/CT - HER2+ BT474 tumour model Tumour Blood Lungs 70 15 15 15 4h 89Zr 89Zr 60 1
Slide 25: HER2-targeted Dendrimer Biodistribution Indicates Higher Radiation Dose to Tumour
HER2-targeted Dendrimer Biodistribution Profile Indicates a Higher Radiation Dose can be Delivered to Tumour vs mAb Tumour : blood ratio Dosimetry: Absorbed doses For personal use only 0.932 50 ✱✱✱✱ ✱✱✱✱ 1.0 0.817 Trastuzumab 0.5 HER2-targeted DEP Dose (mGy/MBq) 40 Tumour:Blood ratio 0.25 30 (%ID/g)
Slide 26: Efficacy Observed With 177Lu-Radiolabeled Dendrimer Constructs
Efficacy Observed With Dendrimer Constructs Radiolabeled With 177Lu, Achieving Similar Efficacy to 177Lu-Trastuzumab in HER2+ BT474 Xenograft Tumour Model For personal use only Controls 1 x 9 MBq 1000 Tumour volume (mm3) Tumour volume (mm3) 1000 Vehicle Tumour Volume (mm3) 800 800 177Lu Trastuzumab
Slide 27: DEP Platform Technology: Versatile and Multifunctional
Starpharma’s DEP® Platform Technology: Versatile and Multifunctional for Delivery of Therapeutics & Diagnostics Multiple Opportunities; Multiple Partnerships For personal use only 6th Targeted Radiopharmaceuticals Summit Europe 25
Slide 28: Summary
Summary • DEP® dendrimers provide a versatile, customisable platform for enhancing delivery For personal use only of radiotheranostic payloads to tumours using novel targeting moieties ❑ Proprietary DEP® platform – clinically validated via 4 clinical programs, multiple drug classes ❑ Starpharma’s ar
Slide 29: Acknowledgements
Acknowledgements ▪ Starpharma For personal use only ▪ Graham Heery, Dana Piovesan, Alex Castellarnau, Brian Kelly, Stephanie Edmondson, Amanda Reese, Richard Hufton and colleagues in the Discovery, Development, and Commercial teams ▪ University of Queensland - Centre for Advanced Imaging / Australia
Slide 30: Thank you.
For personal use only Thank you. www.starpharma.com Jeremy Paull, PhD Amanda Reese, PhD VP Development and Regulatory Affairs Senior Director Business Development info@starpharma.com 6th Targeted Radiopharmaceuticals Summit Europe
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