Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug 
development company, 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. 

Key Points

-EVT801 is a small molecule inhibitor of VEGFR3, and acts by inhibiting 
lymphangiogenesis, the formation of new lymphatic vessels around the tumour. It 
has shown compelling evidence of activity in a wide range of preclinical cancer 
models and appears broadly well-tolerated in animal toxicology studies. 
-Kazia licensed EVT801 from Evotec SE, an international drug discovery alliance 
and development partnership company, in April 2021. 
-The phase I study will focus primarily on understanding the safety, 
tolerability, and pharmacokinetics of EVT801 across a range of doses. It is 
also designed to explore preliminary signals of clinical efficacy, and to 
investigate the biological activity of the drug via a rich suite of 
sophisticated biomarker analyses. 
-The lead clinical site in the study is L'Institut Universitaire du Cancer de 
Toulouse Oncopole (IUCT-Oncopole) in Toulouse, France. The lead investigator is 
Dr Carlos Gomez-Roca, a medical oncologist with a strong background in drug 
development and early phase clinical trials. 
-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. 

Dr Carlos Gomez-Roca commented, "We are pleased to now be enrolling patients to 
this phase I study of EVT801. Despite great progress in the treatment of cancer 
over recent years, there remains a substantial need for new therapeutic options 
in a wide range of tumours. EVT801 has shown promising preclinical data, and we 
very much hope that it may now prove beneficial to our patients."

Kazia CEO, Dr James Garner, added, "in the six months since we licensed EVT801, 
the Kazia and Evotec teams have been working assiduously to execute a 
first-in-human study of this very promising drug candidate. It has been a 
privilege to work with the team at the IUCT-Oncopole site in Toulouse, which is 
one of the leading cancer centres in France, and we hope to add an additional 
centre in the new year. We are delighted that the study is now open to 
recruitment. All of us in Kazia firmly believe that EVT801 has enormous 
potential as a novel cancer therapy, and we look forward to working closely 
with the investigators to explore that potential."

Dr Cord Dohrmann, Chief Scientific Officer of Evotec SE, said, "We are very 
excited to see EVT801 proceed to the clinic. The Phase I clinical trial will be 
conducted by Evotec, under the sponsorship of Kazia, at the renowned 
IUCT-Oncopole in Toulouse. Evotec will support the management of the Phase I 
clinical trial with analyses and biomarker development, which we anticipate 
will yield important data for the validation of the approach and to further 
contribute to the development of robust patient stratification strategies for 
the further clinical evaluation of EVT801."

Phase I Study Design

The phase I study of EVT801 is designed in two stages. The first stage is a 
multiple ascending dose (MAD) study, which is designed to determine the maximum 
tolerated dose (MTD) and recommended phase II dose (RP2D) for EVT801. Patients 
in the study will receive EVT801 at low doses, and this will be progressively 
escalated in subsequent cohorts as the safety profile of the drug is 
determined. 

The second stage of the study will recruit twelve patients, of whom six will 
have been diagnosed with renal cell carcinoma and six with soft-tissue sarcoma. 
All twelve patients will receive EVT801 at the RP2D determined in the first 
stage. These patients will participate in intensive analyses to better 
understand the biochemical activity of the drug. 

In addition to conventional measures of safety, efficacy, and pharmacokinetics, 
the phase I study will employ cutting edge biomarker technologies to provide 
early insights into the activity of EVT801. A rich program of tissue and blood 
biomarker analyses has been developed by Evotec scientists, in collaboration 
with the team at Oncopole. It is expected that these analyses will help to 
better understand the effects of the drug in human subjects and may also help 
to identify the most responsive patients and provide early predictors of 
clinical efficacy.

Kazia is also collaborating with Radiomics, an imaging analysis organisation 
based in Belgium, to apply sophisticated AI-based analyses to the CT and MRI 
scans collected during the study. Proprietary machine-learning algorithms 
developed by Radiomics can provide exceptionally detailed insights into the 
behaviour of the tumour while on treatment, and this information may help to 
predict and understand clinical response. 

Clinical Sites

The lead site in the study is the Institut Universitaire du Cancer de Toulouse 
Oncopole (IUCT-Oncopole) in Toulouse, France. IUCT-Oncopole combines several 
leading clinical cancer treatment facilities with a world-class research 
infrastructure, on an integrated campus that brings together public and private 
stakeholders, including industry participants. The centre treats more than 
10,000 new patients each year, and more than one in eight patients are enrolled 
in clinical studies. 

The lead investigator for the study is Dr Carlos Gomez-Roca, medical oncologist 
and Chair of the Early Phase Unit at IUCT-Oncopole, Dr Gomez-Roca's clinical 
research is focused on development of targeted therapies and immuno-oncology 
drugs. He is a member of ESMO, ASCO, FITC and AACR, and has contributed to more 
than 60 peer-reviewed publications, including as first or second author, in 
journals such as the Journal of Clinical Oncology and Annals of Oncology.

Source Kazia Therapeutics Limited