Presentation to the Third Annual Dengue Endgame Summit
2025-08-14 · Island Pharmaceuticals · original irmau.com ↗
Island Pharmaceuticals Limited ACN 641 183 842 | Registered office: Suite 201, 697 Burke Rd, Camberwell VIC 3124, Australia 14 August 2025 ASX Announcement Presentation to the Third Annual Dengue Endgame Summit MELBOURNE Australia, 14 August 2025: Australian antiviral drug development company, Island Pharmaceuticals Ltd (ASX: ILA; Island or the Company) is pleased to provide the following presentation, which was presented by Dr Bert Slade, the Company’s Chief Medical Officer at the 2025 Dengue Endgame Summit on Wednesday, 13 August 2025 in Syracuse New York and hosted by SUNY Upstate’s Global Health Institute. The summit brings together global experts from academia, government, industry and public health to address the escalating burden of dengue worldwide. Over 12 to 14 August, the program explores the drivers of recent dengue surges, advances in vaccines and therapeutics, vector control strategies, immune responses, and human challenge models, while fostering collaboration to define and accelerate pathways toward long-term dengue control. Dr Slade presented the attached presentation to a large portion of the world’s leading dengue experts, all of which were in attendance by invitation. The attached presentation provides further data from the Company’s recently completed Phase 2a/b PROTECT trial using ISLA-101 (refer ASX announcement: 12 June 2025), supporting the ongoing development of the molecule as a dengue countermeasure. This additional data includes ongoing evidence of reduced viremia (viral load) across both the preventative and treatment cohorts, reduced dengue marker protein (NS1) in both arms in ISL A-101 treated subjects and improved white blood cell and platelet count, as well as a more favourable liver enzyme profile following infection, in ISLA-101 treated subjects when compared to controls. Management commentary: Island’s CEO and Managing Director, Dr David Foster said: “We are pleased to have been invited to present data from our recently completed Phase 2 trial at this very prestigious dengue summit . This will provide the Company with an opportunity to showcase additional data from the study and engage with leading dengue experts from around the globe.” ”The additional data which has come to light from ongoing review demonstrates that ISLA-101 treated subjects had a reduced viral load and improved markers of infection when compared to control, in both cohorts. This is very encouraging and makes up a larger data package that will help inform the planning for our next study using ISLA- 101.” - Ends - Island Pharmaceuticals Limited ACN 641 183 842 | Registered office: Suite 201, 697 Burke Rd, Camberwell VIC 3124, Australia Approved for release to the ASX by: David Foster (CEO and Managing Director) Island Pharmaceuticals Limited [email protected] Investors and media, for further information, please contact: Henry Jordan Six Degrees Investor Relations +61 (0) 431 271 538 [email protected] About Island Pharmaceuticals Island (ASX: ILA) is focused on areas of unmet need for drugs that can address urgent viral diseases, public health or biosecurity threats. The Company is executing a dual development strategy for its assets, ISLA-101 and Galidesivir. ISLA-101 has a well-established safety profile, being repurposed for the prevention and treatment of dengue fever and other mosquito (or vector) borne diseases. Galidesivir is a clinical-stage antiviral molecule with a broad spectrum of activity in over 20 RNA viruses, including high-priority threats such as Ebola, Marburg, MERS, Zika and Yellow fever – viruses with significant unmet medical needs and that may contribute to national security threats. Island encourages all current investors to go paperless by registering their details with the Company's share registry, Automic Registry Services, whose contact info is housed on the Shareholder Services page of the Company’s website. Visit www.islandpharmaceuticals.com for more on Island. Results of a Phase 2 Placebo-controlled Study of ISLA-101 using DENV-1-LVHC 45AZ5 Challenge Session 7. Advanced stage countermeasure update: therapeutics Third Annual Dengue Endgame Summit Conflicts of Interest • Bert Slade MD FAAAAI • Consultant, Chisholm Clinical Research Services • Medical Monitor for the study • No conflicts to declare Clinical Study Design ISLA-101 (fenretinide, 4-HPR) Interferes with NS5 transport to the nucleus NS5 is 70% conserved across serotypes Prophylactic [Cohort 1] 24 days of BID dosing, inoculation on Day 4 (after the 7th dose) Therapeutic [Cohort 2] 14 days of BID dosing, starting on Day 8 Study Design -90 -45 Week Week Week Week Week Week Week Week Week Week SCR1 SCR2 Wk1 Wk2 Wk3 Wk4 Wk5 Wk6 Wk13 Wk15 Wk18 Wk19 Innoculate x1 ¨d4 ISLA101 bid d1 d24 PK d1 d2 d24 Viremia d4 d7 d9 d11 d12 d14 d16 d18 d21 d23 d26 d28 d32 d36 d94 d124 Safety labs SCR d1 d4 d7 d14 d21 d28 Research labs SCR d1 d4 d7 d9 d11 d12 d14 d16 d18 d21 d23 d26 d28 d32 d36 d94 d124 Innoculate x1 ¨d1 ISLA101 bid d8 d21 PK d8 d9 d21 Viremia d1 d4 d6 d8 d9 d11 d13 d15 d18 d20 d22 d25 d29 d91 d121 Safety labs SCR d1 d4 d11 d18 d25 Research labs SCR d1 d4 d6 d8 d9 d10 d11 d12 d13 d14 d15 d16 d17 d18 d20 d22 d25 d29 d91 d121 COHORT 1COHORT 2 CONSORT Demographics Dosing EC50 EC90 Huh-7 cells PBMC THP-1 cells + ADE Vero DENV-1 2.6 µM 0.81 µM 0.78 µM DENV-2 2.1 µM 2.0 µM DENV-3 1.4 µM DENV-4 2.1 µM In Vitro inhibition Dosing PK modeling Drug Levels Levels achieved @ 300 mg/m2 q12h plus high fat, high calorie meal Cohort 2, Day 2 Dose 3 Time (hours) 0 1 2 3 4 5 6 Concentration (ng/mL) 0 200 400 600 800 1000 1200 1400 1600 1800 2000 mM concentration 0 1 2 3 4 5 Drug Levels Levels achieved @ 300 mg/m2 q12h plus high fat, high calorie meal Cohort 1, D24 Hour 0 2 4 6 8 Concentration (ng/mL) 0 200 400 600 800 1000 1200 1400 1600 1800 2000 2200 2400 Cohort 2 Day 21 Hour 0 2 4 6 8 Concentration (ng/mL) 0 200 400 600 800 1000 1200 1400 1600 1800 2000 2200 2400 Time to clear Effect on Virus RNA GE/mL, Virus PFU/mL Area Under the Curve Group Placebo Therapeutic Prophylaxis Exponent (common log) 8 9 20 30 40 50 60 70 80 90 10 100 Group vs PCR Group vs PFU Peak Group Placebo Therapeutic Prophylaxis 1e+3 1e+4 1e+5 1e+6 1e+7 1e+8 1e+9 1e+3 1e+4 1e+5 1e+6 1e+7 1e+8 1e+9 Group vs PCR Group vs PFU Effect on Virus Prophylactic group vs. all 3 controls Effect on Virus NS1 antigen Effect on Virus Clinical Observations Signs & symptoms of Dengue infection (solicited AEs) Grade 2 nausea and/or vomiting was seen only among controls. Clinical Lab Observations Hematology - WBC SID SCR2 V1 V4 V7 V11 V14 V18 V21 V25 V28 01-002 2.73 2.89 2.77 2.28 0.88 2.26 2.98 1.2 - 4.0 = normal range, lymphocytes 01-004 1.09 1.16 1.58 1.26 0.82 0.83 0.82 CTCAE lymphocytes 01-019 2.81 2.57 2.63 2.14 1.15 2.00 2.54 GR1 GR2 GR3 GR4 01-008 1.35 1.06 1.07 0.26 0.31 US 0.52 0.85 <LLN-.8 .5-.8 .2-.5 <.2 01-012 1.32 1.49 1.24 0.68 0.97 1.56 01-030 1.92 1.84 1.93 0.98 1.51 1.96 01-036 1.38 1.34 1.46 0.45 0.66 0.99 01-037 0.77 1.68 1.50 0.57 1.28 1.59 01-038 1.64 1.48 1.59 0.78 0.6 US 1.14 1.30 01-044 1.46 1.46 1.72 0.77 1.29 1.17 01-046 2.64 2.21 2.23 1.66 1.51 2.21 01-022 1.89 1.65 1.94 1.61 2.39 0.58 0.99 01-043 1.41 1.56 1.48 0.82 1.38 1.54 01-045 1.94 1.72 0.19 2.00 0.60 2.39 SCR2 V1 V4 V7 V11 V14 V18 V21 V25 V28 01-002 4.32 5.56 5.35 4.78 3.37 2.14 4.41 1.8 - 7.0 Normal range, neutrophils 01-004 3.81 2.45 5.09 5.45 2.81 1.7 2.39 CTCAE neutrophils 01-019 5.92 5.86 7.07 10.46 3.77 3.28 6.54 GR1 GR2 GR3 GR4 01-008 2.83 2.82 2.99 3.35 2.38 2.36 <LLN - 1.5 <1.5 - 1.0 <1.0 - 0.5 <0.5 01-012 4.10 4.72 3.81 2.55 2.34 4.27 01-030 3.68 2.72 2.80 2.15 1.37 2.19 01-036 3.21 5.04 3.66 1.96 2.59 2.14 01-037 4.91 3.84 4.23 3.90 2.28 4.47 01-038 2.03 1.4 1.51 0.91 0.6 US 1.28 1.77 01-044 2.75 3.66 3.23 2.32 2.35 1.83 01-046 4.53 4.12 4.67 4.70 2.07 4.02 01-022 3.23 2.55 2.88 3.25 2.64 1.03 1.85 01-045 3.18 2.25 6.38 0.73 2.57 2.20 2.08 01-043 3.50 2.32 2.66 1.86 1.81 2.02 LYMPHOCYTESNEUTROPHILS Clinical Lab Observations Hematology - WBC SID SCR2 V1 V4 V7 V11 V14 V18 V21 V25 V28 01-002 2.73 2.89 2.77 2.28 0.88 2.26 2.98 1.2 - 4.0 = normal range, lymphocytes 01-004 1.09 1.16 1.58 1.26 0.82 0.83 0.82 CTCAE lymphocytes 01-019 2.81 2.57 2.63 2.14 1.15 2.00 2.54 GR1 GR2 GR3 GR4 01-008 1.35 1.06 1.07 0.26 0.31 US 0.52 0.85 <LLN-.8 .5-.8 .2-.5 <.2 01-012 1.32 1.49 1.24 0.68 0.97 1.56 01-030 1.92 1.84 1.93 0.98 1.51 1.96 01-036 1.38 1.34 1.46 0.45 0.66 0.99 01-037 0.77 1.68 1.50 0.57 1.28 1.59 01-038 1.64 1.48 1.59 0.78 0.6 US 1.14 1.30 01-044 1.46 1.46 1.72 0.77 1.29 1.17 01-046 2.64 2.21 2.23 1.66 1.51 2.21 01-022 1.89 1.65 1.94 1.61 2.39 0.58 0.99 01-043 1.41 1.56 1.48 0.82 1.38 1.54 01-045 1.94 1.72 0.19 2.00 0.60 2.39 SCR2 V1 V4 V7 V11 V14 V18 V21 V25 V28 01-002 4.32 5.56 5.35 4.78 3.37 2.14 4.41 1.8 - 7.0 Normal range, neutrophils 01-004 3.81 2.45 5.09 5.45 2.81 1.7 2.39 CTCAE neutrophils 01-019 5.92 5.86 7.07 10.46 3.77 3.28 6.54 GR1 GR2 GR3 GR4 01-008 2.83 2.82 2.99 3.35 2.38 2.36 <LLN - 1.5 <1.5 - 1.0 <1.0 - 0.5 <0.5 01-012 4.10 4.72 3.81 2.55 2.34 4.27 01-030 3.68 2.72 2.80 2.15 1.37 2.19 01-036 3.21 5.04 3.66 1.96 2.59 2.14 01-037 4.91 3.84 4.23 3.90 2.28 4.47 01-038 2.03 1.4 1.51 0.91 0.6 US 1.28 1.77 01-044 2.75 3.66 3.23 2.32 2.35 1.83 01-046 4.53 4.12 4.67 4.70 2.07 4.02 01-022 3.23 2.55 2.88 3.25 2.64 1.03 1.85 01-045 3.18 2.25 6.38 0.73 2.57 2.20 2.08 01-043 3.50 2.32 2.66 1.86 1.81 2.02 LYMPHOCYTESNEUTROPHILS Grade 1 Grade 1 Clinical Lab Observations Hematology - platelets SCR2 V1 V4 V7 V11 V14 V18 V21 V25 V28 01-002 346 386 367 336 299 230 370 150-400 Normal range, platelets 01-004 222 209 218 205 214 160 232 GR1 GR2 GR3 GR4 01-019 326 384 373 375 335 268 410 <LLN - 75 <75.0 - 50 <50.0 - 25 <25 01-008 278 322 323 303 181 380 01-012 258 286 273 236 180 311 01-030 285 305 269 241 177 329 01-036 244 390 421 --- 156 303 01-037 274 312 306 249 293 319 01-038 192 175 182 166 142 US 188 289 01-044 253 275 257 215 259 259 01-046 302 291 329 289 244 297 01-022 178 168 183 172 185 124 160 01-043 199 181 209 188 181 226 01-045 238 269 222 259 293 329 PLATELETS Clinical Lab Observations Chemistry – Hepatic Enzymes SID SCR2 V1 V4 V7 V11 V14 V18 V21 V25 V28 01-002 37 37 45 50 49 55 56 <41 = normal range, alanine aminotransferase 01-004 --- 40 43 32 30 35 31 CTCAE ALT 01-019 53 20 5 17 27 27 26 GR1 01-008 34 46 39 35 126 124 91 US >ULN - 3.0 x ULN if baseline was normal; 1.5 - 3.0 x baseline if baseline was abnormal 01-012 30 32 31 24 29 51 20 US GR2 01-030 16 16 15 35 21 33 >3.0 - 5.0 x ULN if baseline was normal; >3.0 - 5.0 x baseline if baseline was abnormal 01-036 29 19 22 43 29 29 GR3 01-037 20 16 14 17 19 12 >5.0 - 20.0 x ULN if baseline was normal; >5.0 - 20.0 x baseline if baseline was abnormal 01-038 24 23 22 31 24 19 GR4 01-044 22 23 22 38 24 42 >20.0 x ULN if baseline was normal; >20.0 x baseline if baseline was abnormal 01-046 19 14 16 21 25 29 01-022 --- 36 40 45 55 136 60 01-043 83 70 67 97 94 107 01-045 11 16 21 21 57 37 SCR2 V1 V4 V7 V11 V14 V18 V21 V25 V28 01-002 22 24 28 27 30 41 26 <40 = normal range, aspartate transferase 01-004 25 25 26 22 25 24 23 CTCAE AST 01-019 33 22 5 17 24 33 28 GR1 01-008 --- 35 31 25 112 58 47 US >ULN - 3.0 x ULN if baseline was normal; 1.5 - 3.0 x baseline if baseline was abnormal 01-012 18 15 20 17 21 24 GR2 01-030 24 20 21 32 21 30 >3.0 - 5.0 x ULN if baseline was normal; >3.0 - 5.0 x baseline if baseline was abnormal 01-036 26 15 18 29 22 22 GR3 01-037 27 17 22 16 20 19 >5.0 - 20.0 x ULN if baseline was normal; >5.0 - 20.0 x baseline if baseline was abnormal 01-038 27 23 21 42 28 21 GR4 01-044 23 23 25 37 23 39 >20.0 x ULN if baseline was normal; >20.0 x baseline if baseline was abnormal 01-046 21 16 19 22 23 26 01-022 --- 27 22 30 34 84 32 01-043 65 53 52 82 72 77 01-045 13 14 22 16 32 24 ALTAST Adverse Events (unsolicited) Prophylactic subjects • GI disorders (3/4, 75%) • Nervous system disorders (2/4, 50%) • Skin and subcutaneous tissue disorders (2/4, 50%) • Grade 2 drug rash led to discontinuation of 1 subject Treatment subjects • Eye disorders (2/8, 25%) • GI disorders (1/8, 12.5%) Regardless of treatment, all subjects had clinical AEs assessed as Grade 1 or 2 (mild or moderate) severity. Conclusions • Drug levels were in the targeted zone for 50% inhibition • Drug effect on virus was seen with both prophylactic and therapeutic use • Prophylactic use showed more profound effects • 48 doses vs 28 • Drug on board at inoculation • ISLA-101 was associated with rash, night vision disturbance and gastrointestinal complaints Discussion • The chosen dose was at the low end of doses found to be safe in Ph1 single ascending dose (300, 600, 900 mg/m2 tested); higher doses are possible • Reported EC50 were in vitro, with constant drug level • No subject dropped out due to drug effects • Impact on virus was evident • Evaluating avoidance of warning signs / severe Dengue will require field trials • Household contacts is a consideration for trial design Acknowledgments Kris Paolino MD Stephen Thomas MD Adam Waickman PhD SUNY Study Team Michelle Klick BreAnn Burnette Lisa Ware Island Study Team David Foster PhD JD Nick McCoy (McCoy Clinical Consulting) Mari Heghinian PhD (Seran LLC) H.B.Slade MD (Chisholm Clinical Research Services) Bobbi Drais (Drais Regulatory Consulting)
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