DELIVERING A NEW CLASS OF ONCOLYTIC VIRUS THERAPEUTICS
Theriva Biologics is a clinical-stage immuno-oncology company developing oncolytic viruses intended to overcome the protective barrier surrounding solid tumors and selectively kill tumor cells. Our therapies are designed to enable systemic delivery and have the potential to enhance current standard-of-care therapies, offering patients with difficult-to-treat cancers the chance of a longer life.
Led by a team of experienced leaders with a vision for clinical innovation, we are committed to offering new therapeutic modalities that improve the way cancer is treated.
The Theriva Difference
Theriva is developing highly differentiated oncolytic adenoviruses that are designed to overcome the challenges of accessibility, availability, and administration and can potentially enable multiple dosing to improve efficacy. The unique therapeutic properties of Theriva’s oncolytic viruses represent a new class of cancer therapies that are designed to selectively destroy tumor cells and enhance the effects of current standard-of-care therapies. Engineered for systemic delivery, Theriva’s oncolytic viruses can be administered intravenously or as a direct injection into the tumor or tumor compartment (intravitreal, intratumoral).
To improve efficiency, Theriva’s oncolytic viruses are designed for:
- Systemic delivery, which eliminates the need for invasive surgeries and permits the oncolytic virus to reach both the target tumor and metastases throughout the body
- Selective replication in tumor cells, which minimizes toxicity and destroys the tumor while avoiding damage to healthy tissues
- Stroma-Degrading, intended to break down the tumor’s protective barrier, improve tumor access by the oncolytic virus and other cancer therapies, and expose the tumor to robust and persistent attack by the patient’s immune system
This unique combination of features means that Theriva’s oncolytic viruses are particularly well-positioned to work alongside other cancer therapies (chemotherapy, immunotherapy, etc.) and may enhance the efficacy of both standard-of-care and developmental cancer therapies.
Theriva’s leading systemic, selective, and stroma-degrading oncolytic virus clinical candidate is VCN-01, which will be evaluated in the VIRAGE trial, an upcoming phase 2 clinical trial in patients with pancreatic ductal adenocarcinoma (PDAC) and in a planned Company Sponsored multicenter trial in patients with retinoblastoma.
VCN-01 is characterized by four interconnected advancements in oncolytic virus design that enable intravenous delivery at higher doses than have been feasible for other oncolytic viruses:
- High replication rate, which increases manufacturing yields and is expected to enable an antitumor effect even if low levels of the oncolytic virus are delivered to the tumor
- Tumor-selective replication, which is intended to maximize antitumor effects, minimize potential off-target effects, and limit damage to healthy tissues
- Liver detargeting, which is intended to reduce the loss of VCN-01 through hepatic clearance and avoid potential liver toxicities
- Expression of hyaluronidase (PH20), which will degrade tumor stromal hyaluronic acid, a substance that has been strongly associated with reduced tumor immunogenicity and poor prognosis in patients with PDAC and ovarian cancer
VCN-01 has been uniquely engineered to ensure that PH20 expression occurs only after VCN-01 has entered the tumor and undergone a viral replication cycle. This feature ensures a tumor-focused release of PH20 and provides a powerful biomarker for measuring VCN-01 tumor delivery and activity.
Clinical Evidence To Date
To date, more than 76 subjects have been dosed with VCN-01 in Phase 1 clinical trials in patients with a broad range of cancers, including PDAC, retinoblastoma, colorectal cancer, and head and neck squamous cell carcinoma (HNSCC). Additional investigator-sponsored studies are ongoing in patients with brain cancers and ovarian cancers.
VCN-01 has demonstrated an acceptable safety profile at the doses used, and accumulated data support the proposed VCN-01 mode of action and Phase 2 dosing regimen. Although these were not randomized controlled trials, there were encouraging observations in VCN-01-treated patients with respect to tumor response and patient survival.
A Pipeline With Expansive Potential
Theriva’s oncolytic viruses have the potential to treat a broad range of difficult-to-treat tumor types and may be combined with a variety of cancer therapies.
In an upcoming VIRAGE Phase 2 clinical trial in patients with PDAC, VCN-01 will be tested in combination with standard-of-care chemotherapy gemcitabine/nab-paclitaxel. VCN-01 was also administered with the checkpoint inhibitor durvalumab in a Phase 1 study in patients with HNSCC and is currently being evaluated in combination with huCART-meso cells in an investigator-sponsored study in patients with either pancreatic cancer or ovarian cancer.
The diversity of tumor types and coadministered cancer treatments highlight the broad anticipated utility of Theriva’s systemic, selective, and stroma-degrading oncolytic viruses.
Building on the clinical advancement of VCN-01, Theriva developed the Albumin Shield™ technology to protect oncolytic viruses from circulating anti-oncolytic virus antibodies after systemic administration. We anticipate that this technology will enable multiple oncolytic virus doses to be administered in therapeutic cycles to treat particularly refractory tumors. Preclinical proof of concept for the Albumin Shield™ technology has been demonstrated with the archetype VCN-11, and a range of Albumin Shield™ oncolytic viruses with different therapeutic payloads are currently under consideration. Other technologies in earlier stages of development are also being explored by our experienced scientific team.