Skin Cancer Immunotherapeutic
TG1042: A NOVEL SKIN CANCER TREATMENT
Background
The Company in February 2011 signed a worldwide exclusive License Agreement with leading French biopharmaceutical company Transgene (Eurolist Paris: FR0005175080) to develop TG1042, a clinical-stage skin cancer immunotherapy product. Transgenehas previously conducted Phase II trials with TG1042 in patients with cutaneous B-cell lymphoma, a rare form of skin cancer. Thesetrials showed TG1042 to be safe and well-tolerated and also showed verypromising biological activity against the tumours. The positive findingof biologic activity in this orphan indication is particularly encouraging, as Virax plans to conduct its clinical trials in the much-larger Basal Cell Carcinoma (BCC) market. Specifically, Virax will target in patients with nodular BCC in its trials. This program represents a major opportunity in the Australian and Global market. In Australia, non-melanoma skin cancers such as BCC occur three times more frequently than all other cancers combined. This already high incidence is expected to increase as the population ages further. Nodular BCC is a common form of BCC. Other regions with high incidence of BCC are USA, UK, Europe and Scandinavia.
Skin Cancer Facts and Figures:
· There are currently 2-3 Million skin cancers occurring annually worldwide (Skin Cancer Foundation)
· One in every five Americans will develop skin cancer during their lifetime (Skin Cancer Foundation)
· Two of every three Australians will be diagnosed with skin cancer by age 70 (www.cancer.org.au)
· Incidence of skin cancer in North America, Europe and Australia is increasing 3-6% annually
Market Opportunity for TG1042
The initial indication for TG1042 will be treatment of nBCC. Arecent study published in the British Journal of Dermatology reported that nBCC is the most common form of BCC, accounting for more than 62-70% of BCC diagnoses. Of these, up to 80% occur on the face, head and neck, areas where surgical excision may not be the ideal first choice of therapy due to cosmetic considerations. In these instances, intralesional treatment with TG1042 may be an attractive alternative for both the surgeon and patient.
Peak sales at maturity of greater than USD 500 million per annum have been estimated.
About TG1042
TG1042 is based on an antigen-independent immunotherapy platform utilising a replication deficient adenovirus type 5 (Ad5) carrying the human IFN-γ gene. TG1042 is designed for direct intra-tumoral injection. IFN-γbelongs to a family of proteins called interferons. Type 1 (IFN-α and IFN-β) and type 2 interferons (IFN-γ) are central coordinators of tumor-immune system interactions. In prior clinical studies in cutaneous lymphoma (see below) with TG1042, it was shown thatthe observed clinical response of the treated lesions upon intra-tumoral injection related to induction of both Type 1 and type 2 interferon responses. TG1042 induced this dual interferon response by Type I interferons being produced upon infection of the tumor cells by the adenovirus vector and direct expression of TG1042 of the Type II IFN-γ.
Basis for use of TG1042 in Basal Cell carcinoma
Interferons in the form of recombinant proteins have previously been used with good effect for the treatment of BCC. Forexample, long term follow up (minimum 10 years, average 13.5 years) of BCCs treated with perilesional IFN α2b showed a cure rate of 96% (Tucker, 2006). However, their use has been discontinued because it required multiple injections by the doctor into the tumor (upto 9 times over a three week period). This was not practical from both a patient and doctor perspective. The use of the viral vector delivery approach utilized by TG1042 circumvents this problem as expression of IFN-γ by the virus lasts 1-2 weeks.
Development Status of TG1042
TG1042has undergone extensive prior development by Transgene in the area of cutaneous lymphoma with successful phase I and II trials having been completed. In addition significant progress was made in the development of manufacturing processes as well as pre-clinical and toxicological testing in animal models. This will significantly enhance the rate of development of TG1042 in the basal cell carcinoma indication. The development status of TG1042 in the manufacturing, non-clinical and clinical areas is summarised below.
Manufacturing
Acommercially scalable manufacturing process with associated testing performed according to Good Manufacturing Practice (GMP) has been developed for TG1042. Underthe Agreement, Transgene will provide an appropriate amount of clinicalgrade TG1042 for the planned clinical trials to be conducted in Australia. This is an important feature of the License Agreement and will enable Virax to pursue an aggressively timed clinicaldevelopment plan for TG1042.
Pre-Clinical testing
Extensive pre-clinical pharmacological and toxicological studies of TG1042 have been completed demonstrating both the efficacy of the direct intratumoral injection of a replication deficient adenovirus type 5 (Ad5) carrying the human IFN-γ gene as well as the safety of the approach. Thepre-clinical package detailing these studies is extensive and has supported the prior approval for human clinical testing of TG1042 as adjudged by the US regulatory authorities as well as various European authorities. Availability of this package will also facilitate rapid clinical testing of TG1042 in Australia in the area of BCC.
Prior-Human Clinical testing
TG1042has been tested previously in humans in skin cancer indications for thetreatment of cutaneous lymphomas (via intratumoral injection), where ithas shown highly promising results in Phase I and Phase II Clinical Trials.
InPhase I Trials, patients with advanced cutaneous T-cell lymphoma (CTCL)and multi-lesional cutaneous B-cell lymphoma (CBCL), treatment with TG1042 induced a high overall response rate of local clinical responses.
InPhase II Clinical Trial of Intra-lesional administration of TG1042 (Adenovirus-interferon-gamma), patients with relapsing primary cutaneousB-cell lymphomas, the primary endpoint was met in the first step of thePhase II trial as measured by overall objective response rate of 83%. These studies suggest that local administration of Ad-IFN-γ is both safe and demonstrates anti-tumor activity with clinical benefit
Thistreatment was highly promising and on this basis was awarded Orphan Drug status by the European medical regulatory body, European Medicines Agency (EMA) for the treatment of Cutaneous T cell Lymphomas. This prior human testing of the product has significantly lowered the technical risk of the project in nodular BCC.
Future clinical development of TG1042 in Basal cell carcinoma (BCC)
Viraxplans to now move rapidly into Phase I/IIa Clinical Trials for TG1042 in 2011 (subject to receiving the necessary regulatory approvals). Thetrials will be conducted in Australia in order to take advantage of thecountry’s world-leading skin cancer trial resources. The initial focus will be in nodular basal cell carcinoma.