Viralytics

Background

Around 1999 a team led by the virologist Professor Darren Shafren at the University of Newcastle in Australia established that a Coxsackievirus called Coxsackievirus A21 was an oncolytic virus, in addition to being a common-cold virus causing mild upper respiratory tract infections. Shafren filed for patent protection over the use of the virus in oncology and the University of Newcastle subsequently formed a spin-out company called ViroTarg Pty Ltd. An ASX-listed biotech company called Psiron began to fund development of the ViroTarg project in June 2004 and in December 2006 acquired the Virotarg intellectual property. Psiron changed its name in the process to Viralytics to reflect the fact that oncolytic viruses were now its core focus. Shafren's wild-type Coxsackievirus A21, which Viralytics called Cavatak, was trialled in a Phase I in melanoma between 2007 and 2010 and in 2012 the product entered a Phase II trial in advanced melanoma called 'CALM', short for 'CAvatak in Late Stage Melanoma'. This trial took place under an Investigational New Drug application. The trial completed in 2015 with favourable results and multiple trials are now underway to establish various indications for Cavatak.

Cavatak

Cavatak is the trade name for a preparation of wild-type Coxsackievirus A21, as manufactured by Viralytics. Within the Picornaviradae family of viruses, Coxsackievirus A21 is a member of the Human enterovirus C species. The virus consists of a single positive-stranded RNA genome within a capsid of approximately 28 nm in diameter. The virus is known to utilise the viral entry receptor ICAM-1 as its primary entry receptor, with DAF as a co-receptor to infect host cells.

Mechanism of action

The firm argues that Cavatak has a dual mechanism of action. As well as oncolysis through the preferential targeting of cells that over-express the molecules ICAM-1 and/or DAF compared to normal cells, there is also an immunological involvement in which the infection promotes tumour inflammation, which in turn prompts the patient's immune system to attack the infected cancer cells.

Pre-clinical evidence of efficacy

Shafren et al. first published data showing that Cavatak could destroy malignant melanoma cells in the journal Clinical Cancer Research in January 2004. A June 2005 paper in the International Journal of Oncology showed that this effect worked as well for melanoma exhibiting a highly vascular phenotype. In April 2007, in a paper in the British Journal of Haematology, the Shafren lab showed that Cavatak could work in multiple myeloma and over the next two years papers in The Prostate (May 2008) and Breast Cancer Research and Treatment (January 2009) suggested similar pre-clinical efficacy in prostate and breast cancer respectively. What these cancers have in common is that they all have high levels of ICAM-1 expression.

Early clinical work, 2007–2011

In January 2010 Viralytics reported favourable results from a nine patient Phase I trial of Cavatak in Stage IV melanoma patients (ClinicalTrials.gov identifier NCT00438009) where the virus was administered intratumourally. In this trial, which was initiated in May 2007 but was not completed until 2009, all patients were given two Cavatak doses of the same size 48 hours apart into a single cutaneous melanoma lesion. Three patients received a low dose, three a middle dose and three a high dose.

These results were presented at the May 2011 Annual Meeting of the American Society of Clinical Oncology, held that year in Chicago.

The CALM study, 2012–2015

The Phase II CALM study (ClinicalTrials.gov identifier NCT01227551) took a considerable period of time for Viralytics to initiate – the pre-IND meeting with the FDA was held in June 2010 and Viralytics lodged its IND in November 2010, however the trial wasn't cleared until June 2011. This meant that the study didn't dose its first patient until after January 2012. However this open-label trial was eventually able to evaluate 57 patients with stage IIIc or stage IV melanoma. Each evaluated patient received 10 intratumoural injections of Cavatak over 18 weeks. The dose level was 3x10⁸ TCID₅₀ virus with the investigators measuring response rates as well as Progression Free Survival at 6 months, and tracking the immune response of the patient. The trial was one of the first in the world to make use of the new Immune-Related Response Criteria.

Current clinical studies of Cavatak

Viralytics stock

Viralytics stock is publicly traded on the ASX under the code VLA. In the US its ADRs have traded OTC since October 2006 and on OTCQX under the code VRACY since August 2013. The ratio of ADRs to the ordinary shares is 30:1.

Main people

Viralytics' Non-Executive chairman is Paul Hopper, an Australian bioentrepreneur based in Sydney who has been a director since September 2008 and chairman since November 2008. The company's CEO is Dr Malcolm McColl, a former executive of the major Australian pharmaceutical company CSL and the biotech company Starpharma who joined the company in January 2013.

Locations

Viralytics' is headquartered in the City Mutual Building, an art deco icon in the Sydney CBD located at 66 Hunter Street. Darren Shafren has a laboratory in Newcastle.