DELIVERING A NEW CLASS OF ONCOLYTIC VIRUS THERAPEUTICS

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ABOUT SYNTHETIC

Synthetic 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.

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Our Science

The Synthetic Difference

Synthetic 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 Synthetic’s oncolytic viruses represent a new class of cancer therapies that are designed to destroy tumor cells more effectively than current standard-of-care therapies. Engineered for systemic delivery, Synthetic’s oncolytic viruses can be administered intravenously or as a direct injection into the tumor or tumor compartment (intravitreal, intratumoral).

To improve efficiency, Synthetic’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 Synthetic’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.

Synthetic MOA - VCN Viruses delivered intravenously
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Lead Candidate

Synthetic’s leading systemic, selective, and stroma-degrading oncolytic virus clinical candidate is VCN-01, which will be evaluated in an upcoming Phase 2 clinical trial in patients with pancreatic ductal adenocarcinoma (PDAC) and in a planned Phase 2/3 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.

 
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A Pipeline With Expansive Potential

Synthetic’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 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 Synthetic’s systemic, selective, and stroma-degrading oncolytic viruses.

Building on the clinical advancement of VCN-01, Synthetic 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.

Pre-IND
Phase 1
Phase 2
Collaborators
Status*
Oncolytic Virus Portfolio
Stroma Degrading Oncolytic Virus
VCN-01
Pancreatic Cancer (IV) ± Gem/nab-P
Pre-IND
Phase 1
Phase 2
Collaborators
Status*
Ph 2 Trial Initiation Expected Q4’22 (ODD EU)
Retinoblastoma (IVit)
Pre-IND
Phase 1
Phase 2
Collaborators
Status*
Ph 2/3 Trial Initiation Expected H2’23 (ODD US)
HNSCC (IV) + CPI
Pre-IND
Phase 1
Phase 2
Collaborators
Status*
Enrollment Complete, Initial Data H2’22
Solid Tumors – Brain, Ovarian, PDAC (IV)
Pre-IND
Phase 1
Phase 2
Collaborators
Status*
Ph 1 Investigator Sponsored Studies Initiated
Oncolytic Virus Albumin Shield
VCN-11
Solid Tumors (IV)
Pre-IND
Phase 1
Phase 2
Collaborators
Status*
IDI BELL and ICO - Collaborators
Preclinical studies are on-going
Antibiotic Degrading Enzyme Portfolio
Oral β-lactamase
SYN-004
Prevention of aGVHD in allo-HCT
Pre-IND
Phase 1
Phase 2
Collaborators
Status*
Washington University - Collaborator
Cohort 1 Phase 1b/2a Topline Data H2’22
Aligned with our oncology focus, our oral β-lactamase product SYN-004 (ribaxamase) continues clinical evaluation as a means of preventing critical adverse outcomes in patients who undergo allogeneic hematopoietic cell transplantation (HCT) to treat hematologic cancers. 80-90% of these patients will be treated with an IV β-lactam antibiotic and this antibiotic use has been strongly associated with increased incidence and severity of acute graft-versus-host disease (aGVHD), infection by vancomycin resistant enterococci (VRE), and Clostridioides difficile infection (CDI). Prevention of one or all of these outcomes by SYN-004 coadministration may significantly improve treatment outcomes and reduce patient mortality.
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LEADERSHIP

Our team is comprised of determined and experienced leaders who are committed to offering patients with difficult-to-treat cancers the chance of a longer life. We are fueled by our deep desire to change outcomes by working to enhance the current standard of care and transform the cancer therapy landscape.
Steven Shallcross
Chief Executive Officer,
Chief Financial Officer
Manel Cascallo
General Director,
EU Subsidiary
Frank Tufaro
Chief Operating Officer
Vince Wacher
Head of Corporate &
Product Development
Scientists in lab

WORK AT SYNTHETIC

As we grow, we continue to seek talented and driven scientists, marketers, analysts, and engineers who share in our mission. We are a collaborative, generous, and committed team devoted to leveraging the unique perspectives of every team member in our efforts to develop first-in-class cancer therapies.

Please reach out to info@syntheticbiologics.com to share your resume and hear about open positions.

Interested in learning more? We’d love to hear from you – info@sytheticbiologics.com