EVT801 / Evotec, Kazia - LARVOL DELTA

Exploratory biomarkers evaluation to enhance characterization and explore treatment response prediction in metastatic ovarian cancer patients undergoing therapy with EVT801, a highly selective VEGFR-3 inhibitor (ESMO 2025) - P1 | "Conclusions EVT801 showed encouraging signs of clinical activity in advanced ovarian cancer patients. These data support future biomarker-driven clinical development as monotherapy or in combination with established therapies for high-grade serous ovarian cancer."

Biomarker • Clinical • IO biomarker • Metastases • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8 • FLT4 • PD-1

Safety, Tolerability, and Pharmacokinetics of EVT801 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Kazia Therapeutics Limited | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Nov 2024 | Trial primary completion date: Apr 2025 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Renal Cell Carcinoma • Solid Tumor • FLT4

Safety, Tolerability, and Pharmacokinetics of EVT801 in Patients with Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Kazia Therapeutics Limited | Trial completion date: Oct 2024 ➔ Jun 2025 | Trial primary completion date: Oct 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Oncology • Renal Cell Carcinoma • Solid Tumor • FLT4

Kazia Therapeutics Announces Presentation of EVT801 Clinical Data at 15th Biennial Ovarian Cancer Research Symposium (PRNewswire) - P1 | N=32 | NCT05114668 | Sponsor: Kazia Therapeutics Limited | "Kazia Therapeutics Limited...is pleased to announce the presentation of data highlighting promising clinical activity of EVT801 in high grade serous (HGS) Ovarian Cancer at the 15th Biennial Ovarian Cancer Research Symposium, co-presented by American Association of Cancer Research (AACR) and the Rivkin Center for Ovarian Cancer Research on Saturday, September 21, 2024 in Seattle Washington....Biomarkers have shown strong VEGFR3 expression in multiple indications, including ovarian cancer; Encouraging clinical activity in High Grade Serous ovarian cancer patients with forty-six percent (46%) having stable disease or for at least three cycles, including two patients who received 9 cycles; One patient had a partial response (-39% decrease) after 2 cycles of EVT801 therapy."

Biomarker • P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Safety, Tolerability, and Pharmacokinetics of EVT801 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Kazia Therapeutics Limited | Recruiting ➔ Active, not recruiting | N=60 ➔ 32

Enrollment change • Enrollment closed • Metastases • Oncology • Renal Cell Carcinoma • Solid Tumor • FLT4

KAZIA REPORTS SUCCESSFUL STAGE 1 COMPLETION OF THE EVT801 PHASE 1 CLINICAL TRIAL IN ADVANCED CANCER PATIENTS (PRNewswire) - P1 | N=60 | NCT05114668 | Sponsor: Kazia Therapeutics Limited | "Kazia Therapeutics Limited...is pleased to announce that the Safety Review Team (SRT) of the EVT801 Phase 1 clinical trial has concluded that the primary and secondary objectives of stage 1 of the trial have successfully been met....In general, EVT801 was tolerated across all doses with the majority of toxicities being mild to moderate and transient in nature. Eleven different cancer types (ex. colon, renal cell, pancreatic) were enrolled in the study, with advanced ovarian cancer being the most prevalent (11 patients)....Forty-six percent (46%) of the ovarian cancer patients had stable disease or better for at least three cycles of EVT801 therapy....We look forward to sharing the final stage 1 data and next development steps at an upcoming scientific conference in the second half of 2024."

P1 data • Colon Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor

EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, is pursuing dose escalation stage of phase I first-in-human study (AACR 2024) - P1 | "Collection of safety data on these first enrolled patients showed no safety alert which allows further dose escalation and reinforces the good safety profile of EVT801 observed during the preclinical toxicology studies."

P1 data • Oncology • Solid Tumor • FLT4

Biomarkers analysis on samples from patients in EVT801 clinical trial: Patient characterization and immunomonitoring (AACR 2024) - P1 | "Our first biomarkers analyses on a subpopulation of patients with High Grade Serous Ovarian Cancer (HGS-OC) enrolled in the first stage of the study showed that levels of VEGFR3 expression had a negative correlation with CD8 positive T-cells infiltration in the tumor microenvironment and a tendency to positive correlation with a PD1 mAb resistance signature. VEGFR3 expression also tends to be correlated with higher levels of hypoxia (CAIX labelling). Our working hypothesis is that patients with hypoxic HGS-OC tumors with high VEGFR3 expression may benefit from EVT801 treatment; this will need to be reinforced by inclusion of additional patients in dedicated PD biomarkers cohorts during stage 2 of the clinical trial."

Biomarker • Clinical • IO biomarker • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • CA9 • CD8 • FLT4 • PD-1

Kazia announces presentation of new data at AACR Annual Meeting (PRNewswire) - "Kazia Therapeutics Limited...is pleased to announce the presentation of new data for both its pipeline molecules, paxalisib and EVT801, at the upcoming Annual Meeting of the American Association of Cancer Research (AACR) in San Diego, California, from 5-10 April 2024....There will be three presentations in total at AACR, including data from the phase 1 study of EVT801 in advanced solid cancers....In addition, data will be presented on the results of the combination therapy of paxalisib and gemcitabine for patients with relapsed/recurrent atypical teratoid/rhabdoid tumors AT/RT."

Clinical data • P1 data • Oncology • Solid Tumor

VEGFR-3 expression profiling by histology and mRNA signature to classify patient population for the selective VEGFR-3 inhibitor EVT801 (ESMO 2023) - P1 | "This enables us to select indications that might benefit from EVT801 as a monotherapy (e.g., clear cell renal cell carcinoma and soft tissue sarcomas) or in combination with standard of care. Accordingly, VEGFR-3 expression is retrospectively quantified during the EVT801 phase 1 clinical trial and may be used to stratify patients in the future."

Clinical • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD34 • FLT4

KAZIA THERAPEUTICS ANNOUNCES CLINICAL DATA AT ESMO 2023 FROM ONGOING PHASE 1 EVT801 STUDY (PRNewswire) - P1 | N=60 | NCT05114668 | Sponsor: Kazia Therapeutics Limited | "Kazia Therapeutics Limited...announces that selected clinical data from the company's ongoing Phase 1 clinical trial evaluating EVT801 in patients with advanced solid tumours was presented at the European Society of Medical Oncology Congress 2023 (ESMO 2023) on Saturday, 21 October 2023....The hypothesis for EVT801's mechanism of action involves three (3) sequential anti-cancer mechanisms, all of which are thought to contribute to the potential inhibition of tumour growth and metastasis: Preventing tumour growth by impairing both tumour angiogenesis and (lymph)angiogenesis, thereby stabilizing the tumour vasculature, reducing metastasis, and reducing hypoxia in the tumour microenvironment....'We look forward to completing dose escalation in stage 1 of the ongoing study and progressing to stage 2 of the Phase 1 Study'."

P1 data • Trial status • Gynecologic Cancers • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

KAZIA THERAPEUTICS ANNOUNCES PRESENTATIONS AT UPCOMING SCIENTIFIC MEETINGS (PRNewswire) - "Kazia Therapeutics Limited...is pleased to provide an update regarding upcoming data presentations at two international scientific meetings, European Society for Medical Oncology (ESMO) Congress 2023 and Society for Neuro-Oncology (SNO) Annual Meeting. The presentations will highlight data for both investigational clinical drugs, EVT801 and Paxalisib."

Clinical data • Preclinical • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Kazia Presents New Data for Paxalisib and EVT801 at AACR Annual Meeting (PRNewswire) - "Kazia Therapeutics Limited...is pleased to announce the presentation of new data for both of its pipeline molecules, paxalisib and EVT801, at the upcoming Annual Meeting of the American Association for Cancer Research (AACR), held in Orlando, FL, from 14 -19 April 2023....Abstract 427/22 - Newer generation mTOR inhibition represents effective therapeutic strategy for BRAF-mutant melanoma...Robert Andtbacka..."

VEGFR-3 expression profiling by histology to classify patient population for the selective VEGFR-3 inhbitor EVT801 (AACR 2023) - P1 | "This held true even in patients treated with sunitinib, positioning EVT801 as a potential treatment option after failure of such multi tyrosine kinase inhibitors. We were able to quantify VEGFR-3 expression in the kidney and soft tissue sarcoma cohorts plus several others, such as hepatocarcinoma and non-small cell lung cancer. This enables us selecting indications that might benefit from EVT801 as a monotherapy (e.g., clear cell renal cell carcinoma and soft tissue sarcomas) or in combination with standard of care. Accordingly, VEGFR-3 expression is retrospectively quantified during EVT801 clinical trial phase 1 trial and may be used to stratify patients in the future."

Clinical • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD34 • FLT4

KAZIA PRESENTS NEW DATA FOR PAXALISIB AND EVT801 AT AACR ANNUAL MEETING (PRNewswire) - "Kazia Therapeutics Limited...is pleased to announce the presentation of new data for both of its pipeline molecules, paxalisib and EVT801, at the upcoming Annual Meeting of the American Association for Cancer Research (AACR), held in Orlando, FL, from 14 – 19 April 2023. In total, there will be five presentations at AACR, four of which build on previous positive data for paxalisib in melanoma and childhood brain cancer. The new data being presented provide significant support and direction for the future development of paxalisib in these expansion indications. In addition, a presentation by scientists from Kazia's partner, Evotec, will outline the novel biomarker strategy employed in the phase I study of EVT801, and anticipates the potential initial clinical data from EVT801 in CY2023."

Clinical data • P1 data • Brain Cancer • CNS Tumor • Melanoma • Oncology • Skin Cancer • Solid Tumor

Targeting Tumor Angiogenesis with the Selective VEGFR-3 Inhibitor EVT801 in Combination with Cancer Immunotherapy. (PubMed, Cancer Res Commun) - "Here, we report the novel VEGFR-3 inhibitor EVT801 that presents a more selective and less toxic profile than two major inhibitors of VEGFRs (i.e., sorafenib and pazopanib). EVT801 showed potent antitumor effects in VEGFR-3-positive tumors, and tumors with VEGFR-3-positive microenvironments through blood vessel homogenization, and reduction of tumor hypoxia and limited immunosuppression. EVT801 increases immune checkpoint inhibitors' antitumor effects."

Combination therapy • Journal • Immune Modulation • Oncology • FLT4 • VEGFC

Kazia Therapeutics raises A$7 million to fund R&D pipeline (Proactiveinvestors) - "Kazia Therapeutics Ltd...has raised more than A$7 million from a round of equity financing. The raise was broken into a placement to sophisticated and institutional investors which resulted in $4.5 million and a share purchase plan (SPP), which brought in $2.606 million....KZA will use the money towards its R&D pipeline, which comprises two assets in nine clinical trials. The pipeline has several inflection points expected in CY2023, which the oncology-focused drug development company believes have the potential to substantially revalue its' paxalisib and EVT801 development candidates." "

Financing • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

COMPELLING PRECLINICAL DATA FOR KAZIA'S EVT801 PUBLISHED IN PEER-REVIEWED CANCER RESEARCH JOURNAL (PRNewswire) - "Kazia Therapeutics Limited...is pleased to announce the publication of positive preclinical data for EVT801, a clinical-stage drug candidate currently in a clinical trial for multiple forms of cancer....EVT801 was confirmed in preclinical studies to be a potent and selective inhibitor of VEGFR3, with activity in the low nanomolar range....EVT801 combined with immune checkpoint inhibitors in mouse models of several tumor types showed strongly synergistic activity, with the combination performing better than either drug alone....EVT801 is currently the subject of an ongoing phase I clinical trial as monotherapy in patients with advanced solid tumors (NCT05114668)....It is expected that initial data from this study will be available in 1H CY2023."

P1 data • Preclinical • Oncology

EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, started enrollment for its phase I first-in-human study (AACR 2022) - "A potential third stage, consisting of a multiple ascending dose evaluation of the combination of EVT801 with immuno-oncology drugs, may be added to the ongoing trial, pending further technical discussions with physicians and regulators. In addition to conventional measures of safety, tolerability, efficacy, and pharmacokinetics, the phase I study will employ a rich suite of histological, immunological, and radiological biomarkers to provide early insights into the activity of EVT801."

IO biomarker • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • FLT4

Cutting edge biomarkers strategy to provide early insights into activity of EVT-801, a novel selective VEGFR-3 inhibitor that targets tumor angiogenesis during the FIH clinical trial (AACR 2022) - "Lastly, target engagement and pharmacodynamics effects will be investigated by immuno-monitoring as well as assessment of a defined set of proteins as markers of inflammation and angiogenesis as identified in preclinical in vivo models. We expect that these analyses will help to better understand the effects of the drug in human subjects and may also help to select the most responsive patients and provide early signs of clinical efficacy."

Biomarker • Clinical • Oncology • FLT4

TWO ABSTRACTS AT AACR CONFERENCE PRESENT DETAILED STUDY DESIGN AND INNOVATIVE BIOMARKER STRATEGY FOR ONGOING PHASE I STUDY OF EVT801 IN ADVANCED CANCER (PRNewswire) - "Kazia Therapeutics Limited...is pleased to announce two presentations detailing the ongoing phase I study of the company's investigational novel drug, EVT801, a selective VEGFR3 inhibitor with potential application in a variety of cancers. The poster presentations describe the study design and a highly innovative biomarker strategy employed in the study and are being delivered at the Annual Meeting of the American Association for Cancer Research (AACR), held in New Orleans, LA from 8 – 13 April 2022...The phase I clinical trial of EVT801 is currently recruiting patients at two sites in France. Initial data is provisionally expected in 2H CY2022."

P1 data • Oncology

KAZIA TO PRESENT AT UPCOMING INVESTOR CONFERENCE AND AACR ANNUAL SCIENTIFIC MEETING (PRNewswire) - "Four abstracts relating to Kazia's pipeline have been accepted for presentation at the upcoming American Association of Cancer Research (AACR) Annual Scientific Meeting, held in New Orleans, LA from 8th – 13th April 2022. Two abstracts relate to the ongoing phase I study of EVT801, a selective VEGFR3 inhibitor in development for advanced cancer. The other two pertain to paxalisib, a brain-penetrant PI3K inhibitor, currently in an international phase III clinical trial for glioblastoma and in exploratory studies for several other forms of brain cancer. All four posters are expected to be presented on Tuesday 12th April."

P1 data • P3 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Safety, Tolerability, and Pharmacokinetics of EVT801 in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: Kazia Therapeutics Limited

Clinical • New P1 trial • Oncology • Renal Cell Carcinoma • Solid Tumor • FLT4 • MRI

Kazia Enrols First Patient to EVT801 Phase I Clinical Trial (PRNewswire-Asia) - "Kazia Therapeutics Limited...is pleased to announce that it has commenced enrolment to a phase I clinical trial of EVT801, an investigational cancer therapy that Kazia licensed from Evotec SE in April 2021....The phase I study is expected to recruit a maximum of 60 patients, with the actual number dependent on the emergent safety profile of the drug. Timelines to completion will depend on the number of dose levels tested, and Kazia expects to provide further guidance on this as the study progresses."

Trial status • Oncology

Kazia Therapeutics to Present at HC Wainwright 23rd Annual Global Investment Conference (PRNewswire) - "Dr Garner will provide an overview of Kazia's key developments during FY2021, including: (i) Commencement of the GBM AGILE pivotal study for paxalisib in January 2021; (ii) Out-licensing deal with Simcere Pharmaceutical for Greater China rights to paxalisib in March 2021, realizing an US$11 million upfront consideration; (iii) Transformative in-licensing of EVT801 from Evotec, providing the company with a highly attractive second oncology asset."

Licensing / partnership • Trial status • Brain Cancer • Glioblastoma • Glioma • Oncology