AVA-6103 / Avacta - LARVOL DELTA

Outlook (The Manila Times) - "The design of the FOCUS-1 trial of AVA6013 and preclinical updates will be presented in Trials in Progress presentations at both the American Association of Cancer Research (AACR) Conference on Pancreatic Cancer, being held on September 25-28, 2026, and the European Society for Medical Oncology (ESMO) Congress, being held on October 23-27, 2026; First efficacy data from the FOCUS-01 trial with AVA6103 is anticipated to be presented in H1 2027 - including data from clinical tumor biopsies which are anticipated to confirm AVA6103 is being retained in a 'drug reservoir' in the tumor, based on the preliminary Phase 1 data; The selection of the payloads and data to support clinical candidate selection for the Dual Payload Next Gen Program (AVA6207) will be presented in Q4 2026; Clinical data from the First Gen faridoxorubicin (AVA6000) program will also be presented in Q4 2026 at the ESMO Congress."

Clinical protocol • P1 data • Trial status • Cervical Adenocarcinoma • Cervical Adenosquamous Carcinoma • Colorectal Cancer • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma • Hormone Receptor Positive Breast Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Urothelial Cancer • Vulvar Adenocarcinoma

A phase I trial of FAP-Exd (AVA6103), a Fibroblast Activation Protein (FAP)-enabled pre|CISION® peptide-drug conjugate delivering sustained tumor microenvironment (TME) release of exatecan in patients with FAP-positive solid tumors (ESMO 2026) - No abstract available

Biomarker • Clinical • P1 data • Tumor microenvironment • Oncology • Solid Tumor • FAP

Avacta Achieves Clinical Proof of Mechanism for the Next Generation of pre|CISION Medicines with AVA6103 (FAP-Exd) in the Phase 1 FOCUS-01 Trial (The Manila Times) - "AVA6103 pre|CISION controlled-release exatecan demonstrates a clean safety profile through the first three dose levels, including a payload dose level 50% higher than the maximum tolerated dose (MTD) of conventional exatecan, and; The comparison of the preclinical modeled pharmacokinetic (PK) data and clinical trial PK data demonstrates an exceptional alignment through the first 3 dose levels with controlled release of exatecan evident in patients for days after dosing...Given the very short half-life of the released peptide (2-3 hours) that was demonstrated in the AVA6000 program, and the detection of low levels of the released peptide from AVA6103 in the plasma up to 48 hours after dosing indicates that the PDC is being retained in the tumor in a 'drug reservoir' that is slowly being cleaved to release the peptide and exatecan, as this mechanism was designed to do."

P1 data • PK/PD data • Cervical Adenocarcinoma • Cervical Adenosquamous Carcinoma • Colorectal Cancer • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma • Hormone Receptor Positive Breast Cancer • Pancreatic Ductal Adenocarcinoma • Small Cell Lung Cancer • Vulvar Adenocarcinoma

Preclinical efficacy comparison with Enhertu (The Manila Times) - "The comparative efficacy of Enhertu and AVA6103 was tested in a head-to-head format using a gastric cancer patient-derived xenograft model that is HER2+ and FAP+ (by IHC); When tumors had grown to 100-200 mm3 in size, animals were randomized to receive either AVA6103 or Enhertu at the preclinical dose with evidence of activity (Enhertu x 1 or AVA6103 QWx3 dose dense regimen); Enhertu treatment resulted in a slowed growth compared to vehicle control, with two animals demonstrating small tumor reductions and 1/6 with progression as best response. In comparison, AVA6103 treatment resulted in deep and prolonged partial responses in 6/6 animals treated."

Preclinical • Solid Tumor • HER-2

The new data analyses in the AVA6103 program comparing pre|CISION FAP-cleavable exatecan delivery with those of leading marketed ADCs have been extended to Datroway, an ADC targeting the TROP2 antigen, as well as Enhertu an ADC targeting the HER2 antigen. (GlobeNewswire) - "All three of these drugs (AVA6103, Enhertu and Datroway) feature tumor-targeted delivery of topoisomase I inhibitors (exatecan or deruxtecan) and these comparisons are designed to address the differences in the payload delivery and control for the differences in cancer models; The delivery kinetics of exatecan (derived from AVA6103) and deruxtecan (derived from Enhertu or Datroway) demonstrate more rapid tumor penetration of released exatecan from AVA6103 (Tmax of minutes, AVA6103 versus Tmax >24 hours, Enhertu or Datroway) and higher maximal concentration (Cmax) of released payload in the tumor with differences observed of over 1-log."

Preclinical • Oncology

AVA6103 is a FAP-enabled pre|CISION®peptide-drug conjugate delivering sustained release of exatecan in the tumor microenvironment with potent antitumor activity (AACR 2026) - "Additional mechanistic studies demonstrated on-target activity and supported utility of AVA6103 in specific cancer indications to exploit genetic vulnerabilities.This preclinical data package highlights the potential for AVA6103 to selectively target exatecan to the tumor microenvironment in a wide range of cancers. A Phase 1 dose escalation study designed to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of AVA6103 in gastric, pancreatic, cervical and small cell lung cancers is anticipated to start in 1H 2026."

Biomarker • Tumor microenvironment • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CAFs • FAP • SLFN11 • TOP1

Characterization and translational development of novel pre|CISION® technology compounds delivering complementary dual payloads to the tumor microenvironment following FAP cleavage (AACR 2026) - "AVA6103 is a pre|CISION®-enabled exatecan candidate in clinical development...We show the potential of the technology to deliver a therapeutically relevant combination of payloads specifically to the TME while reducing systemic dose-limiting toxicities. This broadens the utility of the pre|CISION® platform in the delivery of novel medicines."

Biomarker • Tumor microenvironment • Oncology • Solid Tumor • CAFs • TOP1

AVA6103 (FAP-EXd) Preclinical and Clinical Trial in Progress Highlights (Rink, C. et al.) (Avacta Press Release) - "The data demonstrate that AVA6103 has robust activity in multiple patient-derived xenograft (PDX) models with FAP levels ranging from very low to high, suggesting excellent antitumor effects even at the lowest levels of FAP expression in stromal cells only....AVA6103 has recently entered the clinic, with the first patient receiving treatment in the FOCUS-01 study in March. FOCUS-01 (NCT07454642) is a multicenter, open‑label Phase 1 clinical trial of AVA6103 in adults with selected advanced cancers, and the initial clinical data readout from the study is anticipated later this year. Based on favorable preclinical activity and biomarker readouts from the strategic collaboration with Tempus, two indications have been added to the trial: colorectal cancer (CRC) and hormone receptor-positive breast cancer (HR+ BC)."

P1 data • Preclinical • Trial status • Cervical Adenocarcinoma • Cervical Adenosquamous Carcinoma • Colorectal Cancer • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma • Hormone Receptor Positive Breast Cancer • Pancreatic Ductal Adenocarcinoma • Small Cell Lung Cancer • Vulvar Adenocarcinoma

Comparative pharmacokinetics and tumor activation of fibroblast activation protein (FAP)-enabled pre|CISION® peptide drug conjugates (AACR 2025) - "Two payloads are described using this platform: AVA6000 (doxorubicin [dox]; pre-clinical and clinical) and AVA6103 (exatecan, pre-clinical). In the Phase 1 trial, AVA6000 exhibits promising tumor-targeting characteristics with encouraging clinical activity and reduced systemic toxicities validating the tumor-specific FAP cleavage mode of action. These AVA6000 data along with the preclinical PK data with AVA6103 have informed the predictive modeling to support the clinical development of AVA6103 by optimizing the delivery of the exatecan payload."

First-in-human • PK/PD data • Oncology • Salivary Gland Cancer • Solid Tumor

Avacta announces first patient treated in Phase 1 FOCUS-01 trial of FAP-Exd (AVA6103) - a sustained-release pre|CISION exatecan peptide drug conjugate (The Manila Times) - "The trial is expected to enroll approximately 144 patients and is designed to identify a dose and regimen for further clinical development using a Bayesian statistical method."

Trial status • Cervical Adenocarcinoma • Cervical Adenosquamous Carcinoma • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma • Neuroendocrine Carcinoma • Pancreatic Ductal Adenocarcinoma • Small Cell Lung Cancer • Vulvar Adenocarcinoma

The novel peptide drug conjugate AVA6103 is a FAP-enabled pre|CISION® medicine which targets exatecan, a topoisomerase I inhibitor, to the tumor microenvironment following FAP cleavage (AACR 2025) - "Tolerability profiles of AVA6103, allied with tumor growth inhibition efficacy, shows a greatly increased therapeutic window compared to conventional exatecan, with pharmacodynamic biomarkers demonstrating on-target activity of the warhead. The enhanced therapeutic index and efficacy data shown here supports the rationale to progress AVA6103 towards clinical development and supports wider utility of the pre|CISION® platform to target warheads to the tumor while reducing systemic dose-limiting toxicities."

Biomarker • Tumor microenvironment • Oncology • Solid Tumor • CAFs • FAP • TOP1

AVA6103 in Subjects With Locally Advanced or Metastatic Selected Solid Tumors (clinicaltrials.gov) - P1 | N=144 | Recruiting | Sponsor: Avacta Life Sciences Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • Cervical Adenocarcinoma • Cervical Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gynecologic Cancers • Lung Cancer • Neutropenia • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • Vulvar Cancer

AVA6103 in Subjects With Locally Advanced or Metastatic Selected Solid Tumors (clinicaltrials.gov) - P1 | N=144 | Not yet recruiting | Sponsor: Avacta Life Sciences Ltd

First-in-human • New P1 trial • Cervical Adenocarcinoma • Cervical Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gynecologic Cancers • Lung Cancer • Neutropenia • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • Vulvar Cancer

Avacta’s pre|CISION Mechanism for Payload Delivery Shows Key Advantages Compared to an Antibody Drug Conjugate in Innovative AI-Driven Analysis (Avacta Press Release) - "Avacta expects to initiate the Phase 1 clinical trial of its FAP-Exd (AVA6103) program in Q1 2026....The analysis demonstrates three key pharmacokinetic (PK) advantages in the kinetics of the release of payload, specifically: AVA6103 results in more rapid drug penetration into the tumor, with the maximal concentration (Cmax) in tumor tissue occurring within minutes of dosing compared with T-Dxd maximum concentration observed at 24 hours; The observed absolute maximum concentration (Cmax) observed with FAP-Exd in the tumor was more than a log higher than the Cmax observed with T-Dxd; and The Tumor Selectivity Index (TSI, ratio of the area under the curve (AUC) observed over 14 days in the tumor v. plasma) was nearly three-fold higher with pre|CISION delivery (FAP-Exd) versus ADC delivery (T-Dxd)."

New P1 trial • PK/PD data • Preclinical • Breast Cancer • Gastric Cancer

Avacta Announces Year-end Trading Update (GlobeNewswire) - "Beginning of the FAP-Exd (AVA6103) clinical testing expected in Q1 2026. A group of U.S. clinical trial specialty centers are expected to open imminently with key investigators of different specialties to enroll the four selected tumor types: pancreatic cancer, gastric cancer, small cell lung cancer and cervical cancer. Preliminary data from this trial is anticipated in the second half of 2026."

New P1 trial • Cervical Cancer • Gastric Cancer • Pancreatic Cancer • Small Cell Lung Cancer

Avacta Announces U.S. Food and Drug Administration Clearance of the Investigational New Drug (IND) Application for the Second pre|CISION Medicine, FAP-Exatecan (AVA6103) (Yahoo Finance) - "The Phase 1 clinical trial will evaluate the safety and potential efficacy of FAP-Exd and seek to identify a dose for further clinical development in patients with four solid tumors, pancreatic cancer, cervical cancer, gastric cancer and small cell lung cancer...Adult participants will be enrolled in the dose-escalation part of the trial with two parallel arms investigating two schedules of administration (every two weeks, Q2W and every three weeks, Q3W) with preliminary data from this trial anticipated in the second half of 2026."

IND • New P1 trial • P1 data • Cervical Cancer • Gastric Cancer • Pancreatic Cancer • Small Cell Lung Cancer

Discovery and characterization of novel pre|CISION® technology compounds delivering complementary dual warheads to the tumor microenvironment following FAP cleavage (AACR-NCI-EORTC 2025) - "Previously we have presented AVA6103, a pre|CISION® -enabled exatecan candidate in IND-enabling studies...We show the potential of the technology to deliver a therapeutically relevant combination of warheads specifically to the TME while reducing systemic dose-limiting toxicities. This broadens the utility of the pre|CISION® platform in the delivery of novel medicines."

Biomarker • Tumor microenvironment • Oncology • Solid Tumor • CAFs

Avacta Provides Q2 2025 Business Update Outlining Progress Against Strategic Objectives (Avacta Press Release) - "FAP-EXd (AVA6103), a pre|CISION-enabled PDC comprised of the pre|CISION peptide linked to exatecan, continues preclinical development. AVA6103 is currently in investigational new drug (IND)-enabling studies with a Phase 1 trial anticipated to begin in the first quarter of 2026."

New P1 trial • Oncology

Preliminary Results for the Year Ended December 31, 2024 - "FAP-Dox (AVA6000) – first pre|CISION program: Completed Phase 1a enrollment dose escalation portion of clinical trial; Opening of the Phase 1b expansion cohorts in salivary gland cancers, triple negative breast cancer and high-grade soft tissue sarcoma; Anticipate releasing the initial data in salivary gland cancer in late 2025 and in triple negative breast cancer in H1 2026. Phase 2 trials in these indications planned for H1 2026. FAP-EXd (AVA6103): Clinical candidate selection enables move toward clinical testing, by advancing to Investigational New Drug (IND)-enabling studies and Good Manufacturing Practices (GMP) manufacturing process development to support initiation of the Phase 1 clinical trial in Q1 2026."

New P1 trial • New P2 trial • P1 data • Salivary Gland Cancer • Soft Tissue Sarcoma • Triple Negative Breast Cancer

Preclinical pharmacokinetic results from its second pre|CISION candidate AVA6103 (GlobeNewswire) - "Avacta Therapeutics...today announced...that were presented alongside preclinical pharmacokinetic results from its second pre|CISION candidate AVA6103 (FAP-EXd) at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, IL."

Preclinical • Oncology

Avacta Provides Business Update for the First Quarter of 2025 Outlining Progress Against Strategic Objectives (GlobeNewswire) - "AVA6103 is currently in investigational new drug (IND)-enabling studies with a Phase 1 trial anticipated to begin in the first quarter of 2026."

New P1 trial • Oncology

Avacta Therapeutics Announces Presentations at 2025 AACR Annual Meeting (GlobeNewswire) - "The poster presentations will feature data from the Company’s proprietary pre|CISION platform and pipeline of next generation peptide drug conjugates (PDCs), including AVA6000, a PDC consisting of doxorubicin conjugated with a peptide moiety that is specifically cleaved by FAP in the tumor microenvironment via a pharmacokinetics and clinical presentation, and preclinical pharmacology highlights for AVA6103, a PDC comprised of the pre|CISION peptide linked to exatecan. The third presentation will describe detailed analysis of the target fibroblast activation protein-alpha (FAPα), the protease that forms the basis of the pre|CISION platform."

Preclinical • Oncology

Avacta Reports Pipeline Advances with Two Novel Programs at the EORTC-NCI-AACR Molecular Targets Symposium in Barcelona (GlobeNewswire) - "The therapeutic index of exatecan is significantly increased by pre|CISION enabling, specifically the maximum tolerated dose of pre|CISION exatecan (AVA6103) observed is 75 times that of conventional exatecan in a daily dosing regimen; AVA6103 optimizes the bystander effect where the conjugate is only cleaved by FAP-positive fibroblasts, and released exatecan can enter FAP-negative cancer cells; High intratumoral warhead concentrations are seen at 4hr and 24hr timepoints for several pre|CISION exatecan compounds, with up to 50-fold higher warhead concentrations in the tumor versus plasma in a patient-derived xenograft model, AVA6103 inhibits tumor growth, with complete responses noted in a preclinical treated model engineered with human FAP expression (HEK-FAP) tumors. Increased survival was also shown in this model treated with AVA6103 compared with other models with vehicle-treated tumors."

Preclinical • Oncology

The novel peptide drug conjugate AVA6103 is a FAP-enabled preCISION™ medicine which targets Topoisomerase I to the tumor microenvironment via FAP cleavage (EORTC-NCI-AACR 2024) - "Pharmacodynamic biomarkers have also been investigated with the aim to demonstrate on-target activity of the topoisomerase inhibitor in the tumor. The enhanced therapeutic index and data shown here informs future clinical strategy for AVA6103 and supports wider utility of the preCISION™ platform to target warheads to the tumor while reducing systemic dose-limiting toxicities."

Biomarker • Tumor microenvironment • Oncology • TOP1

Avacta Expands its Pipeline with Two Novel Assets Developed Using its pre|CISION Platform (GlobeNewswire) - "Avacta Group plc...today announces the addition of two novel preclinical oncology assets, AVA6103 and AVA7100, to its pipeline of pre|CISION-enabled drug conjugates...Further details of these programs will be released in conjunction with the Company’s two presentations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held in Barcelona from October 23-25, 2024. The platform and the pipeline will be presented at the investor and analyst R&D Spotlight Event: Focus on pre|CISION, in London on October 30, 2024."

Pipeline update • Oncology