Starpharma Holdings Limited · ASX:SPL
Starpharma — PepTalk 2025, Targeted Radioligand Therapies
28 slides from Starpharma's conference presentation, Jan 16, 2025
Slide 1: Starpharma showcases DEP dendrimer platform at PepTalk Targeted Radioligand Therapies Conference
ASX Announcement Starpharma showcases DEP® dendrimer platform at PepTalk Targeted Radioligand Therapies Conference Melbourne, Australia; 16 January 2025: Starpharma (ASX: SPL, US OTC: SPHRY), an innovative biotechnology company with two decades of experience in advancing dendrimer technology from th
Slide 2: Disclosure and Forward-Looking Statements
WE Communications Starpharma Holdings Limited Disclosure Hannah Howlett Cheryl Maley, Chief Executive Officer This ASX Announcement was +61 450 648 064 Justin Cahill, CFO and Company Secretary authorised for release by the Chair, WE-AUStarPharma@we- +61 3 8532 2704 Mr Rob Thomas. worldwide.com inves
Slide 3: Dendrimer Nanoparticles (DEP) Enable Targeted Precision Delivery for Cancer Radiotheranostics
For personal use only Dendrimer Nanoparticles (DEP®) Enable Targeted Precision Delivery and Customized Biodistribution for Cancer Radiotheranostics Dr Jeremy Paull, PhD VP, Development and Regulatory Affairs NOVEL TARGETING MECHANISMS AND EMERGING TARGETS Targeted Radioligand Therapies 15 January 20
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 are 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 th
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 and Radio Conjugates Large Molecules (e.g., mAb) Small Molecules (e.g., small molecules, peptides) For personal use only Efficacy Challenges Efficacy Challenges • Limited tumour penetration • Li
Slide 10: DEP Dendrimers – A Unique Solution to Complex 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 4.0 Drug release (%) 0.6 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 Biological targeting with wide range of targeting For personal use only → EPR: Enhanced permeability and retention moieties → Allows dendrimers to accumulate in tumour due to → Targe
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: 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 16: DEP Cabazitaxel Achieves 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 17: 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 18: 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 19: 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 • HER2low and HER2ultra low patient population
Slide 20: 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 21: Higher Generation Targeted Dendrimers Achieve HER2+ Specific Tumour Accumulation
Higher Generation Targeted Dendrimers Achieve HER2+ Specific Tumour Accumulation, Sustained via EPR Effect For personal use only HER2+ BT474 tumours 48h 89Zr HER2-targeted dendrimers 15.0 Non- HER2 16 targeted targeted 12.5 10.0 12 %ID/g %ID/g 7.5 8 5.0 4 2.5 0.0 0 891 Zr 891 Zr 891 Zr 89 1 Zr G2 G3
Slide 22: 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 4h 89Zr 89Zr 60 15 2
Slide 23: 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 with DEP® vs mAb Tumour : blood ratio Dosimetry: Absorbed doses For personal use only 0.932 50 ✱✱✱✱ ✱✱✱✱ 1.0 0.817 Trastuzumab 40 0.5 HER2-targeted DEP Dose (mGy/MBq) Tumour:Blood ratio 0.25
Slide 24: Efficacy With Dendrimer Constructs Radiolabeled With 177Lu
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 1000 Tumour volume (mm3) Vehicle Tumour volume (mm3) Tumour Volume (mm3) 800 800 177Lu Trastuzumab
Slide 25: Starpharma's 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 PepTalk 2025, Targeted Radioligand Therapies 23
Slide 26: Summary
Summary • DEP® dendrimers are 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 th
Slide 27: 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 28: 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 PepTalk 2025, Targeted Radioligand Therapies
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