VBI-1901: AACR Data, Partial Response and Biomarker Strategy

Emerging data from the ongoing Phase 1/2a study suggest that patients with a normal baseline CD4+/CD8+ T cell ratio may be more likely to experience delayed progression or tumor reduction, reflected as a tumor response. Five out of the six tumor responses seen to-date, including a recently confirmed partial response (PR), defined as a tumor reduction of more than 50% per the Response Assessment in Neuro-Oncology (RANO) criteria, suggest that the biomarker may predict patients most likely to respond to, and derive clinical benefit from, treatment with VBI-1901. Based on the data seen to-date, VBI is exploring a randomized, controlled, registrational clinical study for the next phase of development, which, subject to approval from regulatory bodies, could begin in 2021. In parallel, enrollment in the Phase 1/2a Part B study arm of VBI-1901 in combination with GSK's AS01_B adjuvant systems continues, with immunologic and tumor data expected in Q4 2020.

'The identification of the CD4+/CD8+ T cell ratio as a potentially-predictive biomarker and a recently confirmed partial response are more promising developments in what has, to-date, been an encouraging Phase 1/2a clinical study of VBI-1901,' said David E. Anderson, Ph.D., VBI's Chief Scientific Officer. 'The CD4+/CD8+ ratio may reflect the immunologic fitness of CD4+ T cells in recurrent GBM patients and may be used in the next phase of clinical development to help identify patients most likely to respond to VBI-1901. Importantly, testing of the CD4+/CD8+ T cell ratio in this biomarker strategy would use a common assay that could be widely implemented throughout treatment settings. We are working diligently to advance an effective and accessible treatment for GBM patients, who currently have few options available.'

A webcast of Dr. Anderson discussing this data with Allen Waziri, M.D., CEO and Co-Founder, iCE Neurosystems, Former Director of the Brain Tumor Program at Inova Neuroscience Institute, and member of VBI's GBM/Immuno-Oncology Scientific and Clinical Advisory Board, can be found here: https://www.vbivaccines.com/wire/aacr-2020-video/

The e-poster is available on the 'Events/Presentations' page in the 'Investors' section of the VBI Vaccines website.

Highlights from the ongoing Phase 1/2a study of VBI-1901 in recurrent GBM patients

• Safety
  • VBI-1901 continues to be well-tolerated with no vaccine-related safety signals observed at any dose
• Immunogenicity
  • In Part A, 12-month overall survival (OS) rate of 83% in vaccine responders (n=6) vs. 33% in non-responders (n=9)
  • Vaccine responders saw a 6.25-month improvement in median OS (14.0 months) vs. non-responders (7.75 months)
  • In both Part A and B of the study, tumor responses have been observed in 6 patients: 5 stable disease (SD) and 1 recently confirmed PR, which was previously reported as SD in November 2019
• CD4+/CD8+ ratio biomarker
  • A normal CD4+/CD8+ T cell ratio present at baseline has been identified as a potentially predictive biomarker correlated with tumor response
  • CD4+ effector memory cells (T_em), a component of this baseline biomarker, are the dominant subset of T cells that are known to depart from the blood and traffic to the tumor microenvironment
  • Patients with tumor responses have shown dynamic loss and boosting of these T cells, which may indicate that the T cells are trafficking to the tumor tissue

About the Phase 1/2a Study Design

VBI's two-part Phase 1/2a study is a multi-center, open-label, dose-escalation study of VBI-1901 in up to 38 patients with recurrent GBM:

• Phase 1 (Part A)
  • Dose-escalation phase that defined the safety, tolerability, and optimal dose level of VBI-1901 adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF) in recurrent GBM patients with any number of prior recurrences.
  • This phase enrolled 18 recurrent GBM patients across three dose cohorts of VBI-1901: 0.4 µg, 2.0 µg, and 10.0 µg
  • Enrollment completed in December 2018.
• Phase 2a (Part B)
  • Subsequent extension of the optimal dose level, 10.0 µg, as defined in the Part A dose escalation phase.
  • This phase is a two-arm study, enrolling 10 first-recurrent GBM patients in each arm, assessing 10.0 µg of VBI-1901 in combination with either GM-CSF or GSK's proprietary AS01_Badjuvant system as immunomodulatory adjuvants.
  • Enrollment of the 10 patients in the GM-CSF arm is complete. Enrollment of the 10 patients in the AS01_B arm is ongoing.

VBI-1901 is administered intradermally when adjuvanted with GM-CSF and intramuscularly when adjuvanted with the AS01_B adjuvant system. Patients in both phases of the study receive the vaccine immunotherapeutic every four weeks until tumor progression.

Per the Response Assessment in Neuro-Oncology (RANO) criteria - an international working group that was created to benchmark brain tumor response - a partial response (PR) is defined as a greater than 50% reduction in the sum of products of perpendicular diameters of all measurable enhancing lesions compared with the baseline, sustained for at least four weeks, with no new lesions or clinical progression of disease.

About VBI-1901 and GBM

VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI's enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and is exceptionally lethal.