Trial Updates

CALM Extension (Biopsy) Study Results
Dr Robert Andtbacka reported preliminary results from the 13-advanced melanoma patient CALM
extension study, in which biopsies were taken from melanoma lesions prior to and after CAVATAK
administration, yielding the following preliminary results:

• 5/12 patients (41.7%) achieved irPFS at 6 months.

• An objective response rate of 30.8% (4/13) was observed, including tumour responses in patients
that had failed prior immunotherapies including the checkpoint inhibitors, ipilimumab and
pembrolizumab.

• CAVATAK treatment mediated positive changes within the tumor microenvironment by inducing
increases in immune response genes, immune cell infiltrates and expression of PD-L1.

“The observation of CAVATAK-induced immune cell infiltration within the tumour, combined with the
encouraging results seen in the CALM trial, point to CAVATAK as an investigational agent with real
promise in combination with checkpoint inhibitors such as anti-CTLA-4 (ipilimumab) and/or anti-PD-1
(pembrolizumab),” said Dr Andtbacka. “In addition, CAVATAK treatment may have potential
application in a rescue strategy to reconstitute the immune cells within the tumor microenvironment of lesions
resistant to immune checkpoint inhibitors. I look forward to further studies assessing CAVATAK by
both the intralesional and intravenous delivery route in the combination setting in late stage
melanoma patients.”

Phase 1 MITCI Trial update
As the next stage in the clinical development of CAVATAK, Viralytics is conducting the MITCI
(Melanoma Intra-Tumoral CAVATAK and Ipilimumab) study, which is designed to evaluate the activity
of intralesional injection of CAVATAK in combination with systemic administration of ipilimumab2 in
patients with unresectable melanoma. The study is underway at three sites in the United States.
Preliminary findings in the MITCI study indicate no serious adverse advents to the
CAVATAK/ipilimumab combination to date, with a case report of one of the patients in the study
showing early signs of anti-tumour activity in metastatic visceral and non-visceral lesions at 14
weeks post-treatment initiation.

Phase 2 CALM Trial update
Updated results from the Phase 2 CALM (CAVATAK in Late-stage Melanoma) clinical trial confirm
previously reported positive treatment response data in difficult-to-treat, late-stage melanoma
patients. In his oral and poster presentation, Dr Robert Andtbacka of the Huntsman Cancer
Institute, University of Utah, and Lead Study Investigator, reported the following results:

• The CALM study achieved its primary endpoint, with 22/57 patient (38.6%) achieving immune-related
Progression Free Survival (irPFS3) at 6 months.

• Responses were observed in injected lesions, non-injected non-visceral lesions, and in distant
non-injected visceral lesions, including lung and liver metastases.

• An objective response rate4 of 28% (16/57) was demonstrated, with eight patients achieving
complete response.
• A durable response5 persisting for at least 6 months was seen in 21% of patients.

• A one-year survival rate of 75.4% was achieved, with updated median overall survival6 of 26.7
months.

• Multi-dose intralesional therapy with CAVATAK was generally well tolerated, with no grade 3 or 4
treatment related adverse events.