Both as a monotherapy and also when used in combination with other anti-angiogenic agents.

Results from the trial are expected to be available in the second half of 2012.


VGX-100 background

VGX-100 is a human antibody that acts against the human VEGF-C protein. Treatment for cancers, particularly glioblastoma and metastatic colorectal cancers, are the first target indications for VGX-100.

Studies in animal model studies across a wide range of tumour types have shown that when combined with Avastin® and/or chemotherapy, VGX-100 can significantly reduce tumour growth and tumour spread as well as significantly improve tumour inhibition over and above that of Avastin® and/or chemotherapy alone.

Recent studies have also implicated VEGF-C as a key mediator of disease progression during Avastin® treatment, implying that combination therapy with VGX-100 and Avastin® could significantly improve treatment outcomes in cancer patients.

Circadian chairman, Ms Dominique Fisher, said “On behalf of the board and the shareholders of Circadian, I thank both Jonathan and Carlo for their valuable contributions and commercial insights over the years.

"While it is disappointing to lose them as Directors we are glad that we will maintain their expertise through their ongoing roles with Circadian’s Product Development Review Committee.”

Circadian is currently in a very interesting phase, and just last week announced that the company had taken a significant step forward, filing a new drug application to the U.S. Food and Drug Administration (FDA) to start clinical studies for its VGX-100 antibody to treat cancer. 

An Investigational New Drug Application (IND) is a request for authorisation from the U.S. Food and Drug Administration (FDA) to administer an investigational drug to humans.

The first trial or Phase I will involve the treatment of a variety of different cancer types in patients with late stage cancer.

Circadian is focussed on developing VGX-100 (a human antibody against VEGF-C) as a treatment for solid tumours - including glioblastoma and colorectal cancer - as the first target indications for VGX-100.

VGX-100 works by blocking the growth of lymphatics. Circadian has already invested considerably in the VGX-100 molecule in terms of manufacturing, toxicology studies and other pre-clinical activities.

With Circadian moving into the clinical development phase of its development in oncology and eye disease, Leitch will initially be based in the USA and will relocate to Australia in early 2012 with Circadian.

For the past 5 years he has been within the Medical Sciences group at Amgen Inc (Nasdaq: AMGN) in Thousand Oaks California, involved in the development of novel therapeutics in Amgen’s oncology pipeline.

In his role as Senior Manager in the Early Development Oncology Therapeutic Area he had responsibility for the oversight, design, management and execution of Phase 1-2 clinical studies in oncology.

Circadian’s chief executive officer, Robert Klupacs said “As we move into the clinical development phase of our development in oncology and eye disease it is critical that we have the best people managing this activity.

"We are extremely fortunate to be able to recruit someone of Ian’s experience and expertise to this key role. It is also extremely gratifying that we have been able to convince an expat Australian to return home. We believe this is a great endorsement for Circadian, our technology as well as the continuing growth and international recognition of the Australian biotechnology industry.”

Dr Leitch said “I am very excited to be returning to Australia and joining Circadian at such an important time in its evolution into a clinical stage drug development company. I believe its technology has enormous potential and that its management, advisory team and Board are world class. It is a great opportunity for me to come back to Australia and be part of the ongoing development of the Australian biotechnology industry.”

Circadian Technologies last traded at $0.55 per share.

Klupacs purchased 46,000 shares for a consideration of $25,740, which equates to an average entry price of $0.56.

Klupacs now holds almost 244,000 shares in the company, and also has three lines of around half a million unlisted employee options.

Circadian - the year ahead

In the Circadian preliminary report released last week, the company outlined the year ahead, with key events including:

- IND filing in respect of the VGX-100 with the US FDA and subsequent commencement of clinical trials;

- Generation of additional data in animal models on corneal diseases to support development of VGX-100 in corneal disease settings;

- Launch of CUP diagnostic test by Healthscope;

- Development of additional clinical diagnostic tests for the measurement of VEGF-C, VEGF-D and/or VEGFR-3 in patient tissue as diagnostic assays in oncology; and

- Continued expansion of the marketing of our VEGF-D based diagnostic test for LAM, outside of the USA.

This platform includes VEGF-C, VEGF-D and VEGFR-3 as therapeutic and diagnostic products in cancer and eye disease.

In the operations report, Klupacs highlighted the significant milestones achieved by the company during financial year 2011, which included:

- Completion of IND enabling studies for VGX-100 in the oncology setting. We plan to commence Phase I studies before the end of 2011;

- Our first therapeutic product candidate (IMC-3C5, a human antibody to VEGFR-3) being developed by our licensee ImClone Systems Inc entered into Phase I clinical trials;

- Our first clinical diagnostic product, a VEGF-D diagnostic test to diagnose patients with the debilitating lung disease – lymphangioleiomyomatosis (LAM), was launched in the USA through our partner Cincinnati Children’s Hospital Medical Centre;

- We successfully resolved the arbitration proceedings with Ark Therapeutics Limited relating to that company’s ongoing development of VEGF-D gene therapy products and which will result in improved licencing terms to us in the future;

- We achieved the grant of very important patents in the USA and Europe covering the use of any of our lead therapeutic product candidates or similar products of third parties, to treat cancer or eye disease which extended patent coverage to September 2023, as well as additional patents in the USA covering VEGF-D diagnostics;

- We considerably strengthened our dominant IP position in respect of VEGF-D and VEGF-D antibodies through the receipt of a worldwide exclusive licence to VEGF-D IP owned by the largest biotechnology company in Japan - Chugai Pharmaceutical Co;

- In collaboration with the Schepens Eye Research Institute at Harvard University, identified that the VEGF-C/VEGFR-3 pathway is a major mediator of inflammatory disease in the cornea and that VGX-100 could become a major new therapeutic in the treatment of front-o f- the eye diseases;

- We outlined in detail our clinical development strategy and projected timelines to develop VGX-100 in combination with existing standard of care chemotherapy regimens in patients with glioblastoma (brain cancers) and colorectal cancers; and

- Announced our strategy to develop VGX-100 as an agent to treat various corneal (front of the eye) diseases.

Advancing the Circadian product pipeline

Klupacs added that the company's short term goal is to file an IND with the FDA and subsequently commence Phase I clinical trials in cancer patients in the December quarter of 2011.

Circadian is continuing to undertake additional studies to evaluate VGX-100 in a range of different tumour types in rodent cancer models.

In regards to front of the eye disease - the company have an ongoing collaboration with scientists at the Schepens Eye Research Institute at Harvard University evaluating VGX-100 in a range of corneal disease models.

The Schepens scientists have previously identified the key role of the VEGFC/D/VEGFR-3 axis in mediating corneal inflammation and avascularity.

The year ahead

Circadian are targeting the following key events for the next 12 months, including:

- IND filing in respect of the VGX-100 with the US FDA and subsequent commencement of clinical trials;

- Generation of additional data in animal models on corneal diseases to support development of VGX-100 in corneal disease settings;

- Launch of CUP diagnostic test by Healthscope;

- Development of additional clinical diagnostic tests for the measurement of VEGF-C, VEGF-D and/or VEGFR-3 in patient tissue as diagnostic assays in oncology; and

- Continued expansion of the marketing of our VEGF-D based diagnostic test for LAM, outside of the USA.

Klupacs now holds a direct interest of 197,519 shares in the Australian biotechnology company, with three lines of 500,000 or more unlisted employee options.

Circadian has entered a very interesting phase - and from last month can now service interest from U.S. based investors after launching a Level 1 American Depositary Receipts (ADR) program and OTCQX quotation.

The dual listing was due to the company receiving interest from U.S. retail orientated broking houses, and also institutions with mandates to invest only in U.S. traded stocks.

Quotation commenced today, with each ADR equivalent to five Circadian ordinary shares.

Robert Klupacs, CEO of Circadian, said the company had received particular interest from U.S. retail orientated broking houses, and also institutions with mandates to invest only in U.S. traded stocks.

"The establishment of a sponsored ADR Program allows them the opportunity to invest, creates a broader secondary market for the company's listed securities, and enables U.S. investors to trade in the company’s securities without the hazards of cross-currency transactions.”

Circadian’s ADR program is sponsored by BNY Mellon.

The company is partnering with the Children’s Hospital Medical Centre to offer the test, with tests expected to exceed 25,000 in the medium term.

LAM is a serious but often misunderstood or misdiagnosed disease, and mainly effects women of child bearing age.

Robert Klupacs, chief executive officer for Circadian, said “Circadian is very excited about the launch of this test.

"It is the first product to emerge from our extensive VEGF technology portfolio, and hopefully the first of many, to become available from the range of diagnostics in development by Circadian and our partners."

Diagnostics are an important part of Circadian’s business which are progressing in parallel with the drug discovery activity.

Most importantly, they provide the stong potential for an early source of revenue, and complement the product portfolio.

Trinam® is a potential agent for inhibiting stenosis of venous access grafts in renal dialysis patients.

Under the settlement, both parties have agreed to terminate the arbitration process and to bear their own costs incurred to date.

Circadian, through its 100% owned subsidiary Vegenics Limited, will now receive an increased annual licence payment and royalties on any commercialisation income generated from Trinam®, and in return, Vegenics has granted Lymphatix an exclusive worldwide licence under its VEGF-D patent portfolio for VEGF-D gene therapy products including Trinam®.

Ark has announced that as part of its ongoing strategy it will be seeking partners to fund ongoing clinical development of this molecule.