VICINIUM™

Our lead product candidate, Vicinium (VB4-845), is a next-generation ADC called a fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent cytotoxin, Pseudomonas Exotoxin A (ETA) directly to cancer cells. Unlike many ADC payloads, ETA can efficiently kill both replicating and non-replicating cancer cells and is not subject to the multidrug resistance pumps that can protect cancer cells from small molecule drug payloads.

Vicinium is constructed with a stable, genetically-engineered, peptide linker to ensure its potent protein payload remains attached until it is successfully delivered into the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. We believe this design will significantly reduce the potential for systemic toxicities and increase the probability of killing replicating and non-replicating cancer cells. Historically, separation of payload and the antibody has been a common issue with ADCs, which can cause off-target toxicities and decrease the amount of drug that ultimately reaches the target cancer cells.

Vicinium is currently being evaluated in the Phase 3 VISTA trial for the treatment of patients with non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG), which is the current standard of care for NMIBC. While BCG is effective in many patients, challenges with tolerability have been observed and many patients will experience recurrence of disease. If BCG is not effective or a patient can longer receive BCG, the recommended option for treatment is radical cystectomy, the complete removal of the bladder.

In a Phase 2 clinical trial, Vicinium demonstrated a complete response rate of 40 percent at three months, with no drug-related serious adverse events observed in the trial. In addition to its Phase 3 development for NMIBC, Vicinium is being evaluated in a Phase 1 trial in combination with durvalumab, AstraZeneca’s PD-L1 checkpoint inhibitor, in patients with NMIBC.

About the VISTA Trial for NMIBC
The VISTA trial is an open-label, multicenter, single-arm Phase 3 clinical trial evaluating the efficacy and tolerability of Vicinium in patients with high-risk NMIBC that is carcinoma in situ (CIS, cancer found on the inner lining of the bladder that has not spread into muscle or other tissue) or papillary (cancer that has grown from the bladder lining out into the lumen of the bladder but has not spread into muscle or other tissue), who have been previously treated with bacillus Calmette-Guérin (BCG). The primary endpoint of the trial is the complete response rate in patients with CIS with or without papillary disease. Patients in the study receive locally administered Vicinium twice a week for six weeks, followed by once-weekly treatment for another six weeks, then treatment every other week for up to two years. The trial was fully enrolled in March 2018 and topline data assessing responses and durability of responses at three-months on treatment are expected in mid-2018, with 12-month data anticipated in mid-2019.

Expanding Vicinium’s Benefit in Oncology
We also believe Vicinium may have potential treating additional cancers, including squamous cell carcinoma of the head and neck (SCCHN). We are developing an injectable form of Vicinium for the treatment of SCCHN, with Phase 1 trials completed in Russia and Brazil, that have demonstrated anti-tumor activity and safety. Data from these trials also demonstrated that certain patients who were injected with Vicinium in one tumor had responses in non-injected tumors as well, suggesting that Vicinium may promote an anti-tumor immune response and combine well with immunotherapies.

In addition to the Phase 1 trials, we completed a Phase 2 trial in the United States, which demonstrated a reduction in the bidirectional size of the principle targeted tumor observed in 71 percent (10/14) of patients evaluated in the study.

Vicinium's Mechanism of Action