Looks like we have funding to take us deep into 2019. Negligible...

Looks like we have funding to take us deep into 2019. Negligible risk of a cap raise.


REVIEW OF OPERATIONS

The highlight of the past half-year period for Viralytics was the presentation of new and strongly positive data at major oncology conferences in the US and Europe from our two trials evaluating CAVATAK® in combination with leading checkpoint inhibitor1 drugs in late-stage melanoma patients. In October at the Annual Conference of the European Society of Medical Oncology (ESMO), we presented data on our Phase 1b MITCI trial of intralesional CAVATAK in combination with YERVOY®2 (ipilimumab). In November at the Annual Conference of the Society for Immunotherapy of Cancer (SITC), we reported on our Phase 1b CAPRA trial of CAVATAK in combination with KEYTRUDA®3 (pembrolizumab). These melanoma trial updates as well as data from our other trials were presented at various conferences in the second half of 2016 and are also detailed later in this report.

We are continuing to build and expand our clinical trial programme in order to establish an optimal path to product registration and to explore possible new indications for CAVATAK. We see this work as critical to strengthening partnering discussions and generating shareholder value. Strong news flow will continue in 2017 as we report on the clinical progress of CAVATAK as a potential new treatment in the fast-growing field of cancer immunotherapy.

CLINICAL TRIALS

Phase 1b MITCI Combination Clinical Trial

Viralytics presented clinical findings from the Phase 1b MITCI trial as part of the “Immunotherapy of Cancer” poster discussion session at ESMO in October. The MITCI (Melanoma Intra-Tumoral CAVATAK and Ipilimumab) study is designed to evaluate the tolerability and anti-cancer activity of the intralesional injection of CAVATAK in combination with the systemic administration of YERVOY, a top-selling immune checkpoint inhibitor, in patients with unresectable melanoma.

The data was well received, with demonstration of the potential for CAVATAK to drive enhanced activity of checkpoint inhibitors such as YERVOY with a low rate of adverse events. These data strengthen our confidence that CAVATAK has significant potential in combination with the checkpoint inhibitors across a range of cancer indications.


A disease control rate4 (DCR) of 82.4 percent was demonstrated in the first 17 evaluable patients, including nine patients with an objective tumour response and five patients with stable disease. Of these 17 patients, 66 percent had been previously treated with at least one line of systemic therapy.

In a subset analysis of patients who had been previously treated with checkpoint inhibitor therapies, overall tumour responses and stable disease were observed in 87.5 percent (7/8) of patients. A preliminary overall objective tumour response rate of 37.5 percent (3/8 patients) for the MITCI subset compares favourably with that of a 10 percent (4/40 patients) response rate among advanced melanoma patients undergoing YERVOY treatment following prior administration of anti-PD1 checkpoint therapies, according to recent clinical data reported in the British Journal of Cancer5. In the MITCI trial, responses were observed in injected lesions, non-injected non-visceral lesions, and in distant non-injected visceral lesions, including lung and liver metastases. This study continues at five sites in the United States.

Phase 1b CAPRA Combination Clinical Trial

Viralytics presented an update on the ongoing Phase 1b CAPRA clinical trial at the SITC annual meeting in November. The company-sponsored CAPRA (CAvatak and PembrRolizumab in Advanced Melanoma) study is designed to evaluate the tolerability of intratumourally administered CAVATAK in combination with the checkpoint inhibitor KEYTRUDA in 30 patients with advanced melanoma. Investigators are also assessing evidence of anti-cancer activity, including response rates and bio-markers of anti-tumour immunity.

According to preliminary data from the first 10 patients evaluable for best overall tumour response assessment, a disease control rate (DCR) of 100 percent (10/10 patients) was demonstrated, including seven patients (70 percent) with an objective tumour response and three patients (30 percent) with stable disease.

Phase 1 STORM Solid Tumour Cancer Clinical Trial

In the ongoing Phase 1 STORM (Systemic Treatment Of Resistant Malignancies) study, also known as the KEYNOTE 200 clinical trial, multiple intravenous doses of CAVATAK are being administered in combination with KEYTRUDA to patients with late-stage, non-small cell lung cancer and metastatic bladder cancer.


The trial, a collaboration with Merck (known as MSD outside the United States and Canada), has completed the first two cohorts with no demonstrated dose-limiting toxicities. The third and final expansion cohort commenced recruitment in January 2017. The trial is to be conducted in approximately 80 to 90 patients.

The intravenous delivery of CAVATAK, particularly in combination with checkpoint inhibitors such as KEYTRUDA, has the potential to significantly increase the commercial impact of CAVATAK while benefitting many more cancer patients. This study is the first clinical trial to explore the combination of an intravenously delivered oncolytic virus with a checkpoint inhibitor in these two very common cancer types.


Phase 2 CALM Extension Trial

The CALM extension trial, now complete, was conducted in a 13-patient cohort of the 70patient Phase 2 CALM clinical trial in patients with advanced melanoma. In the extension study, biopsies were taken from melanoma lesions prior to and after the administration of CAVATAK in order to develop a deeper understanding of the effect of CAVATAK on the tumour microenvironment.

Results from the tumour tissue analysis, presented in November, demonstrated that CAVATAK was able to facilitate notable changes within the tumour microenvironment, including increased immune cell infiltrates and greater expression of PD-L1 and other immune checkpoint inhibitory molecules, in particular within lesions displaying stable disease or response.

Phase 1 CANON Bladder Cancer Clinical Trial

The final results of the Phase 1 CANON trial in bladder cancer patients were presented at the “State-of-the-Art Immunotherapies” session at SITC in November. The 16-patient trial was designed to evaluate the tolerability and anti-cancer activity of CAVATAK delivered via catheter directly into the bladders of patients with non-muscle invasive bladder cancer (NMIBC) – both as a single agent and in combination with the standard chemotherapy, mitomycin C.

Clinical activity of CAVATAK was demonstrated by evidence of viral replication and notable signs of tumour inflammation following either single or multiple administrations of CAVATAK in multiple patients. While the study was not designed to assess efficacy, a complete response was observed in one of the three patients in the highest-dose cohort of the monotherapy.


Whether used alone or in combination with mitomycin C, CAVATAK facilitated notable changes within NMIBC tissue biopsies taken from treated patients by inducing increases in immune cell infiltrates and up-regulating immune checkpoint inhibitory genes such as PD-L1, compared to tissue samples taken from untreated patients. In addition, the intravesicular administration of CAVATAK, either as a single agent or in combination with standard chemotherapy, was generally well tolerated with no Grade 2 or higher product-related adverse events.

CLINICAL ADVISORY BOARD
In November the company formed a Clinical Advisory Board (CAB) to serve as a strategic resource to the company as it continues to broaden and advance the clinical development program for CAVATAK. The board will be chaired by Keith Flaherty, MD, Professor of Medicine at Harvard Medical School. Other members include Michael Boyer, MD, PhD, Professor of Medical Oncology at the Sydney Medical School and Chief Clinical Officer from the Chris O’Brien Lifehouse; J Randolph Hecht, MD Professor of Clinical Medicine at the David Geffen School of Medicine at UCLA; and Kurt Schalper, MD, PhD, Assistant Professor of Pathology at the Yale School of Medicine. The board will provide valuable strategic insight as Viralytics advances CAVATAK in multiple clinical trials in a variety of cancer types.

INTELLECTUAL PROPERTY
Viralytics continues to develop and strengthen its intellectual property portfolio while maintaining a focus on cost and relevance to its strategic goals. New intellectual property is being developed, including patents covering CAVATAK combination settings, and existing patent claims continue to be pursued through various international jurisdictions.