-Data support VCN-01 acceptable safety profile with encouraging biological and clinical activity, and-Data support VCN-01 acceptable safety profile with encouraging biological and clinical activity, andidentify recommended Phase 2 dose (RP2D)-
-Publication further supports the development of Synthetic Biologics’ novel oncolytic adenovirus (OV)platform-
Rockville, MD, March 28, 2022 – Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinicalstageRockville, MD, March 28, 2022 – Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinicalstagecompany developing therapeutics designed to treat diseases in areas of high unmet need, todayannounced the peer-reviewed publication of a Phase 1, multicenter, open-label, dose-escalation studyinvestigating the therapeutic potential of intravenous VCN-01 oncolytic adenovirus with or withoutstandard-of-care (SoC) chemotherapy (gemcitabine/nab-paclitaxel) in patients with advanced solidtumors. The data, published in the Journal for ImmunoTherapy of Cancer, suggests that treatment withVCN-01 is feasible and has an acceptable safety profile, with encouraging biological and clinical activity.These findings provide valuable dose-finding context and inform the clinical development strategy forVCN-01.
“The results in this publication support VCN-01 administration intravenously at doses ≥3.3x1012vp/patient, resulting in viral exposure in the primary tumor and liver metastases, replication within thetumor, and the potential to remodel the tumor matrix to further promote tumor inflammation,” saidManel Cascallό, Ph.D., General Director of Synthetic Biologics’ European Subsidiary. “These clinical dataunderscore VCN-01’s differentiated mechanism of action and were used to inform our Phase 2 study inpatients with metastatic pancreatic adenocarcinoma, which is expected to initiate in the second half of2022. More broadly, these results will help guide our rapidly advancing clinical program for VCN-01 andfurther support the development of our novel OV platform.”
In the Phase 1, multicenter, open-label, dose-escalation study (NCT02045602), researchers evaluatedthe administration of a single dose of VCN-01 alone, in patients with solid tumors (Part I), or incombination with SoC chemotherapy (gemcitabine/nab-paclitaxel) in patients with locally advanced ormetastatic, unresectable, pancreatic adenocarcinoma (Parts II and III). In Part II, the VCN-01 wasadministered on the same day as the first dose of chemotherapy (Concomitant Regimen) and in Part IIIthe VCN-01 was administered 7-days prior to the first dose of chemotherapy (Sequential Regimen). Theobjective was to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01adenovirus.
Overall, systemic VCN-01 was well tolerated in the patient population. The most common treatmentrelatedadverse events (AEs) were pyrexia, flu-like symptoms and increases in liver transaminases. These AEs were dose-dependent, reversible and consistent with AEs previously described for other adenovirusbasedproducts. In Part II, transient increases in neutropenia and thrombocytopenia were observedwhen VCN-01 in combination with gemcitabine/nab-paclitaxel was administered using the ConcomitantRegimen, and one patient suffered a fatal episode of enterocolitis and thrombocytopenia. The AE profilewas significantly reduced in Part III when VCN-01 and gemcitabine/nab-paclitaxel was administeredusing the Sequential Regimen, and was similar to the observed AE profile when VCN-01 wasadministered alone. There were no dose limiting toxicities observed in patients administered VCN-01using the Sequential Regimen. The investigators determined the RP2D was 1x1013 viral particles(vp)/patient in Part I and Part III, and 3.3x1012 vp/patient in Part II.
The Phase 1 study provided encouraging clinical results and further confirmed the proposed VCN-01mechanism of action. In patients with pancreatic adenocarcinoma, overall response rates were 50%(Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies(primary pancreatic tumor and liver metastases) on day eight. A second peak of virus concentrations inplasma and increased serum hyaluronidase levels suggest replication after IV injection in all patients.Higher peaks of hyaluronidase serum levels were associated with maximum tumor shrinkage andincreased levels of immune biomarkers (IFNγ, sLAG3, IL-6, IL-10) were found in sera after VCN-01administration. Several markers of tumor inflammation (including CD8 infiltration and indoleamine 2, 3-dioxygenase [IDO] upregulation) were described in tumor biopsies indicating that VCN-01 promotes achange in the tumor immune environment.
Synthetic Biologics anticipates the initiation of multiple international studies, including a Phase 2 clinicaltrial of intravenous VCN-01 in combination with SoC chemotherapy using the Sequential Regimen as afirst-line therapy in newly diagnosed metastatic pancreatic adenocarcinoma patients in the fourthquarter of 2022, as well as a Phase 2/3 pivotal trial of intravitreal VCN-01 as either an adjunct tochemotherapy or a potential rescue therapy in pediatric patients with advanced retinoblastoma in early2023.
About Synthetic Biologics, Inc.
Synthetic Biologics, Inc. (NYSE American: SYN) is a diversified clinical-stage company developingtherapeutics designed to treat diseases in areas of high unmet need. The Company recentlyconsummated the acquisition of VCN Biosciences, S.L. (VCN), which is developing a new oncolyticadenovirus (OV) platform designed for intravenous (IV), intravitreal and antitumoral delivery to triggertumor cell death, improve access of co-administered cancer therapies to the tumor, and promote arobust and sustained anti-tumor response by the patient’s immune system. In addition, the Company'slead candidates are: (1) SYN-004 (ribaxamase) which is designed to degrade certain commonly used IVbeta-lactam antibiotics within the gastrointestinal (GI) tract to prevent (a) microbiome damage, (b)Clostridioides difficile infection (CDI), (c) overgrowth of pathogenic organisms, (d) the emergence ofantimicrobial resistance (AMR), and (e) acute graft-versus-host-disease (aGVHD) in allogeneichematopoietic cell transplant (HCT) recipients, and (2) SYN-020, a recombinant oral formulation of theenzyme intestinal alkaline phosphatase (IAP) produced under cGMP conditions and intended to treatboth local GI and systemic diseases. For more information, please visit Synthetic Biologics' website at www.syntheticbiologics.com.
Forward-Looking Statements
This release contains forward-looking statements within the meaning of the Private Securities LitigationReform Act of 1995. In some cases forward-looking statements can be identified by terminology such as"may," "should," "potential," "continue," "expects," "anticipates," "intends," "plans," "believes,""estimates," and similar expressions, and include statements regarding treatment with VCN-01 beingfeasible and having an acceptable safety profile, the administration of VCN-01 intravenously at doses≥3.3x1012 vp/patient resulting in viral exposure in the primary tumor, liver metastases and replicationwithin the tumor, as well as the potential to remodel the tumor matrix to further promote tumorinflammation, initiating a Phase 2 study of VCN-01 in patients with metastatic pancreatic adenocarcinomain the second half of 2022 and plans to initiate multiple international studies, including a Phase 2 clinicaltrial of intravenous VCN-01 in combination with SoC chemotherapy using the Sequential Regimen as a firstlinetherapy in newly diagnosed metastatic pancreatic adenocarcinoma patients in the fourth quarter of2022, as well as a Phase 2/3 pivotal trial of intravitreal VCN-01 as either an adjunct to chemotherapy or apotential rescue therapy in pediatric patients with advanced retinoblastoma in early 2023. These forwardlookingstatements are based on management's expectations and assumptions as of the date of this pressrelease and are subject to a number of risks and uncertainties, many of which are difficult to predict thatcould cause actual results to differ materially from current expectations and assumptions from those setforth or implied by any forward-looking statements. Important factors that could cause actual results todiffer materially from current expectations include, among others; the ability to complete clinical trials ontime and achieve the desired results and benefits; continuing clinical trial enrollment as expected; theability to obtain regulatory approval for commercialization of product candidates or to comply withongoing regulatory requirements, regulatory limitations relating to Synthetic Biologics' and VCN's abilityto promote or commercialize their product candidates for the specific indications; acceptance of productcandidates in the marketplace and the successful development, marketing or sale of Synthetic Biologics'and VCN's products; developments by competitors that render such products obsolete or non-competitive;Synthetic Biologics' and VCN's ability to maintain license agreements;, the continued maintenance andgrowth of Synthetic Biologics' and VCN's patent estate; the ability to continue to remain well financed;,and other factors described in Synthetic Biologics' Annual Report on Form 10-K for the year endedDecember 31, 2021 and its other filings with the SEC, including subsequent periodic reports on Forms 10-Q and 8-K. The information in this release is provided only as of the date of this release, and SyntheticBiologics undertakes no obligation to update any forward-looking statements contained in this release onaccount of new information, future events, or otherwise, except as required by law.
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