Avacta Group PLC · LSE:AVCT
Avacta — Avacta Therapeutics — Investor Presentation (January 2025)
34 slides from Avacta's investor presentation, January 2025
Slide 1: Avacta Therapeutics
Avacta Therapeutics Expanding the reach of highly potent cancer therapies January 2025
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s research, preclinical and clinical development activities, plans and projected timelines for AVA6000 and the Avacta pipeline, plans re
Slide 3: Avacta is a clinical stage biotech focused on the pre|CISION platform
Avacta is a clinical stage biotech focused on the pre|CISION platform • Allows for targeted delivery of payload in the TME, sparing healthy tissue pre|CISION Platform • Generation of multiple follow-on candidates with unique features and payloads • pre|CISION® platform with multiple advantages over
Slide 4: The Avacta Therapeutics Leadership Team
The Avacta Therapeutics Leadership Team Christina Coughlin, Brian Hahn, Simon Bennett, Karen Harrison Michelle Morrow, MD, PhD MBA DPhil PhD Chief Executive Officer Chief Financial Officer Chief Business Officer Chief Operating Officer Chief Scientific Officer and Head of R&D Chris is an oncologist
Slide 5: Potent cancer drugs kill indiscriminately, causing toxicity throughout the body
Potent cancer drugs kill indiscriminately, causing toxicity throughout the body 100% Therapeutic index challenge: Most oncology drugs Tumor control cause severe toxicity at the efficacious doses Treatment toxic Probability Expanding the therapeutic index of a drug requires a higher Therapeutic Thera
Slide 6: The pre|CISION peptide drug conjugates unleash powerful drugs selectively in the tumor
The pre|CISION peptide drug conjugates unleash powerful drugs selectively in the tumor through masking and release The goal of the pre|CISION peptide is to mask 1 3 The pre|CISION peptide binds to the active site of the toxic effects of an active payload in the 1 1 the FAP protease and is cleaved at
Slide 7: Avacta is redefining how oncology therapeutics are targeted specifically to the tumor
Avacta is redefining how oncology therapeutics are targeted specifically to the tumor Cytotoxic FAP-positive FAP-cleavable drug CAFs pre|CISION® medicines are a differentiated means of peptide targeting a drug specifically to the tumor by leveraging a specific enzyme (protease) activity in the TME F
Slide 8: The pre|CISION bystander effect
Tumor cell The pre|CISION® bystander effect intracellular space Released Released payload payload peptide Released (free) payload enters FAP- tumor or FAP+ CAF cells Peptide drug conjugate cannot enter cells Tumor: Stroma Interface FAP Expressed on cell surface of cancer associated fibroblasts (CAF)
Slide 9: pre|CISION PDCs have key advantages over conventional ADC approaches
pre|CISION PDCs have key advantages over conventional ADC approaches Avacta Conventional v. pre|CISION Peptide Drug Conjugate Antibody Drug Conjugate Extracellular warhead release in the TME Intracellular warhead release in the tumor with limited systemic exposure killing antigen-positive cells Byst
Slide 10: AVA6000: Avacta technology delivers cancer drugs directly to the tumor
AVA6000: Avacta technology delivers cancer drugs directly to the tumor while protecting healthy tissue Foundational pre|CISION® platform technology in the peptide drug conjugate format is the basis of our first clinical Doxorubicin asset, FAP-Dox (AVA6000) now completed its Phase 1 and I AVA6000 pay
Slide 11: FAP-enabled doxorubicin (AVA6000) demonstrates activity in a FAP-high model
FAP-enabled doxorubicin (AVA6000) demonstrates activity in a FAP-high model Human FAP model (HEK-hFAP) of Kidney Cancer with Significant Increase in MTD of AVA6000 versus doxorubicin • pre|CISION-enabled doxorubicin (FAP-Dox, 2000 AVA6000) results in a 6-fold increase in the MTD p< 0.05 versus conve
Slide 12: AVA6103: Building on a proven foundation with a novel payload
AVA6103: Building on a proven foundation and advancing our platform technology with a novel payload The MTD of pre|CISION exatecan (AVA6103) versus To leverage additional payloads (exatecan) and optimize therapeutic conventional exatecan index, the properties of the FAP cleavable peptide have been 6
Slide 13: The addressable population with pre|CISION extends across multiple indications
The addressable population with pre|CISION extends across multiple indications 100 • FAP expression was analyzed Percent tumor samples across >160,000 tumor samples using RNAseq profiling (Tempus AI) 50 • Tumors were characterized as FAP negative, FAP weak expression and FAP high expression with cut
Slide 14: Avacta Therapeutics Pipeline
Avacta Therapeutics Pipeline PLATFORM/ POTENTIAL IND- PROGRAM WARHEAD INDICATIONS PRECLINICAL ENABLING PHASE 1 PHASE 2 MILESTONES Head and Neck Cancers (HNSCC, Salivary gland Ca Expansion cohorts pre|CISION subset) to enroll in 2025 AVA6000 Doxorubicin Dedifferentiated liposarcoma Ph la/lb data (FAP
Slide 15: FAP-Dox: pre|CISION-enabled doxorubicin
FAP-Dox: pre|CISION-enabled doxorubicin Phase 1 data readouts © AVACTA LIFE SCIENCES LIMITED 2024 15
Slide 16: AVA6000 Phase 1 Trial Design and Patient Population
AVA6000 Phase 1 Trial Design and Patient Population Doses analyzed for efficacy PHASE 1: ARM 1 EXPANSION COHORTS Q3W iv 80 [54] 120 [81] 160 [108] 200 [135] 250 [169] 310 [209] 385 [260] (PHASE 1B) [dox equivalent] N=4 N=6 N=8 N=7 N=9 N=6 N=4 (mg/m2) Conventional escalated dose Triple Negative Breas
Slide 17: AVA6000 has reduced hematologic and cardiac toxicities compared to conventional doxorubicin
AVA6000 has reduced hematologic and cardiac toxicities compared to conventional doxorubicin AVA6000 reduces CTCAE Grade 3 or 4 bone marrow toxicity AVA6000 reduces severe cardiac toxicity compared to conventional doxorubicin (compared to conventional doxorubicin Neutropenia Leukopenia Febrile Severe
Slide 18: AVA6000: Preliminary Data Demonstrate Meaningful Tumor Shrinkage in Salivary Gland Cancers
AVA6000: Preliminary Data Demonstrate Meaningful Tumor Shrinkage in Patients with Salivary Gland Cancers 80 60 sum of the longest diameters 40 Best percent change in the 20 disease progression 0 * * * * * * * * -20 partial response -40 -60 Salivary gland cancer * Pts with ongoing treatment * Pts rea
Slide 19: AVA6000: Deep prolonged PR in Salivary Gland Cancer
AVA6000: Deep prolonged PR in Salivary Gland Cancer Durable RECIST response in the setting of FAP-negative tumor cells • 79 yo male with SGC (ductal histology). Prior therapy: triptorelin/ bicalutamide followed by disease progression • Enrolled in the AVA6000 trial (Oct 2023) in the 385 mg/m2 Q3W co
Slide 20: AVA6000 Results in Complete Regression of Large Skin Metastasis
AVA6000 Results in Complete Regression of Large Skin Metastasis in a Patient with a Minor Response Left parotid mass Skin metastasis (upper chest) Initial minor RECIST response with dramatic regression of large skin metastasis: 74 –year-old male with SGC Despite mid level of FAP expression Prior the
Slide 21: Concentration of doxorubicin in the tumor regardless of FAP level opens multiple indications
Concentration of doxorubicin in the tumor regardless of FAP level opens multiple indications Released Doxorubicin Concentration 24 hr After the First Dose of AVA6000 Patient Populations Addressable by 10000 Patients with FAPhigh pre|CISION technology (with other payloads) Patients with FAPmid FAPhig
Slide 22: pre|CISION-enabled doxorubicin results in four fundamental PK changes
pre|CISION-enabled doxorubicin results in four fundamental PK changes pre|CISON Reduced plasma exposure with peptide 3 3 Significant reduction in the volume of 1 distribution of released doxorubicin released doxorubicin 1 Released doxorubicin from AVA6000 has a Released doxorubicin from AVA6000 lowe
Slide 23: AVA6000 Clinical Development: Rapid route to market in an orphan indication
AVA6000 Clinical Development: Rapid route to market in an orphan indication with TNBC to expand the label EA R LY SG C IN D I CA T IO N : T N B C : SE C O N D D E VE L O PME N T F IR ST A PPR O V A L A PPR O V A L Salivary gland cancer (SGC) Indication Phase I Phase II / III2 Phase Phase I I expansi
Slide 24: FAP-EXd: pre|CISION-enabled exatecan
FAP-EXd: pre|CISION-enabled exatecan Peptide Drug Conjugate © AVACTA LIFE SCIENCES LIMITED 2024 24
Slide 25: Exatecan is an ideal payload for the next evolution of the pre|CISION platform
Exatecan is an ideal payload for the next evolution of the pre|CISION platform Potency of Topo I 1 Exatecan (EXd) is the most potent topo I inhibitor with single agent inhibitor class activity in Ph 2 trials in several key FAP-positive indications (breast, gastric, small cell lung cancer) Exatecan (
Slide 26: Two key chemistry advances optimize exatecan delivery to create AVA6103
Two key chemistry advances optimize exatecan delivery to create AVA6103 pre|CISION-Doxorubicin in the FAP Docking Model pre|CISION-Exatecan in the FAP Docking Model Capping pre|CISION Self- pre|CISION group ® peptide immolative cleavage site linker pre|CISION peptide A B FAP FAP Active Site active s
Slide 27: Therapeutic Index: The MTD of AVA6103 Is 75-fold higher than conventional exatecan
Therapeutic Index: The MTD of AVA6103 Is 75-fold higher than that of conventional exatecan Maximum Tolerated Dose of AVA6103 • Frequent exatecan dosing in prior clinical trials was in a Multi-Dose Schedule designed to optimize inhibition of the topoisomerase I 60 enzyme MTD of Dosing Regimen (mg/kg/
Slide 28: FAP-EXd (AVA6103): Effective killing of FAP-negative tumor cells in the bystander assay
FAP-EXd (AVA6103): Effective killing of FAP-negative tumor cells in the bystander assay FAP-Exd (AVA6103) Kills FAP-ve Tumor Cells Only in the Presence of FAP+ve CAFs • In a bystander effect model, pancreatic cancer cells Soluble FAP present (PDAC, FAP-negative) were tested alone (monoculture), in s
Slide 29: AVA6103 drives long-term regression of tumors, whereas regrowth is observed with exatecan alone
AVA6103 drives long-term regression of tumors, whereas regrowth is observed with exatecan alone AVA6103 results in durable complete regressions 2.5 Vehicle Exatecan AVA6103 150 150 150 2.0 Tumour Volume (cm3) 100 100 100 1.5 Dosing starts Dosing 50 50 50 1.0 completed 0 0 0 0.5 -50 -50 -50 0.0 20 30
Slide 30: AVA6103: Leveraging AI to predict the most sensitive tumor types
AVA6103: Leveraging AI to predict the most sensitive tumor types will increase the probability of success in Phase 1 • Numerous studies have shown that higher expression of SLFN11 predicts sensitivity to the Topoisomerase I inhibitor mechanism of action • Among FAP high diseases, we looked for stron
Slide 31: AVA6103 Project Timelines
AVA6103 Project Timelines 2024 2025 2026 2027 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Candidate selection IND GMP DS GMP DP manufacture manufacture Dose range GLP toxicology Milestones finding studies finding studies and Key Activities Clinical protocol and start up Phase 1a Phase 1b © A VA CT A L I
Slide 32: Seizing the market opportunity: Payloads as a commercial success
Seizing the market opportunity: Payloads as a commercial success High Efficacy/ pre|CISION®-enabling results in a significant increase in Low Toxicity FAP-Dox (AVA6000) the therapeutic index for doxorubicin with three potential indications FAP-EXd (AVA6103) Exatecan has a very challenging therapeuti
Slide 33: Avacta: Data Outputs and Milestones
Avacta: Data Outputs and Milestones 2024 2025 2026 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 AVA6000 AVA6000 Pipeline AVA6000 AVA6000 AVA6000 AVA6000 Q3W Phase I assets Phase I Phase I Expansion Phase 2 AACR 2024 Q3W/Q2W preclinical update final data cohort data Initial Data AVA6103 Phase 1 data Data and Mil
Slide 34: Thank You
Thank You © AVACTA LIFE SCIENCES LIMITED 2024
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