8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): September 12, 2022

SYNTHETIC BIOLOGICS, INC.

(Exact name of registrant as specified in its charter)

Nevada	001-12584	13-3808303
(State or other jurisdiction of incorporation)	(Commission File No.)	(IRS Employer Identification No.)

9605 Medical Center Drive, Suite 270

Rockville, Maryland 20850

(Address of principal executive offices and zip code)

(301) 417-4364

Registrant’s telephone number, including area code

N/A

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common stock, par value $0.001 per share	SYN	NYSE American

Indicate by check mark whether the registrant is an emerging growth company as defined in in Rule 405 of the Securities Act of 1933 (17 CFR §230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2 of this chapter).

Emerging growth company ¨

If an emerging growth company, indicate by checkmark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

Item 8.01. Other Events. 

On September 12, 2022, a poster entitled “A Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of VCN-01 in Combination with Durvalumab (MEDI4736) in Subjects with Recurrent/ Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC)” was presented at the European Society for Medical Oncology (ESMO) Congress in Paris by Dr. Ricard Mesia, Head of the Medical Oncology Department at Institut Català d'Oncologia (Barcelona, Spain). A copy of the Poster Presentation is filed as Exhibit 99.1.

Key data and conclusions featured in the Poster Presentation include:

· Safety: Treatment with VCN-01 had an acceptable safety profile when administered with durvalumab in the sequential regimen (single dose of VCN-01 administered 14 days prior to the first dose of durvalumab; n=14).

o The most common treatment-related adverse events (TRAEs) were pyrexia, flu-like symptoms and increases in liver transaminases.

o TRAEs were dose-dependent, reversible and consistent with TRAEs previously described for other adenovirus-based products.

· Pharmacokinetics (PK) and pharmacodynamics (PD): Based on toxicology and PK/PD analysis the recommended Phase 2 dose is 1x10¹³ viral particles (vp)/patient.

· Biological activity: Sustained blood levels of VCN-01 viral genomes and increased serum hyaluronidase levels were maintained for over six weeks.

o Observed an increase in CD8 T cells, a marker of tumor inflammation and an upregulation of PD-L1 in tumors.

o Analysis of serial tumor biopsies revealed differential gene expression profiles and downregulation of matrix-related pathways after VCN-01 administration.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

Exhibit Number	Description
99.1	Poster entitled “A Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of VCN-01 in Combination with Durvalumab (MEDI4736) in Subjects with Recurrent/ Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC)”
104	Cover Page Interactive Data File (embedded within the XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this Current Report on Form 8-K to be signed on its behalf by the undersigned hereunto duly authorized.

Dated: September 12, 2022	SYNTHETIC BIOLOGICS, INC.
	By:	/s/ Steven A. Shallcross
		Name:	Steven A. Shallcross
		Title:	Chief Executive Officer and Chief Financial Officer

EX-99.1

Exhibit 99.1

0 - 1 C o nc o m ita n t Se q u e nti al 1 2 p=0,022  Value K ep ↑ K ep marker T2 relaxation time (n=20)  No differences. The percentile 25% of T2, was close to be statistically significant, (p - value =0.06349) • DWI biomarkers (n=16) (D* & D, perfusion & diffusion components, respectively)  No differences between treatment arms • DCE biomarkers (n=11): • V transfer constant plasma  extravascular/extracellular space (EES) (K trans )  reduced dispersion on sequential vs. concomitant (p=0,014) • rate transfer constant extravascular space ļ blood (k ep )  increased value on sequential group vs. concomitant - treated patients (p=0,022) 1231 P : Phase I Study to Evaluate the Safety, Tolerability, and Efficacy of VCN - 01 in Combination With Durvalumab (MEDI 4736 ) in Subjects With Recurrent/ Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M HNSCC) VCN - 01 is an oncolytic adenovirus designed to replicate selectively in cancer cells . It expresses a matrix remodeling - enzyme hyaluronidase and increases immune check - point antibody uptake in preclinical models . It also induces a pro - inflammatory tumor environment after intravenous [i . v] administration in pancreatic cancer patients (pts) . VCN - 01 may help to overcome previous resistance to anti - PD(L) - 1 therapies in patients with R/M HNSCC . Conclusi o ns Hypothes i s Systemic administration of VCN - 01 will lead to intratumoral viral replication causing tumor inflammation, PD - 1 /PD - L 1 up - regulation and strong CD 8 - infiltration . These intratumor effects may help to overcome resistance to PD - (L) - 1 checkpoint inhibitors (alone or in combination) in patients who have progressed during or after treatment with immune - checkpoint inhibitors Objective Phase I dose - escalation study testing two dose levels of i . v . VCN - 01 ( 3 , 3 E 12 & 1 E 13 viral particles, [vp]) combined with a fixed dose of Durvalumab ( 1500 mg) using 3 + 3 design in R/M HNSCC pts previously treated with antiPD(L) - 1 agents . Two treatment schedules were explored : concomitant (single dose VCN - 01 and Durvalumab on day 1 , CS), and sequential (single dose of VCN - 01 on day - 14 and Durvalumab on day 1 ; SS), both followed by Durvalumab q 4 weeks until progression or intolerable toxicity . Fresh tumor biopsies were taken at baseline, post - VCN - 01 and post - Durvalumab Study Population : Patients with metastatic squamous cell carcinoma of the head & neck who have progressed during or after treatment with immune - checkpoint inhibitors . Eligibility Criteria included the selection of patients with levels of neutralizing antibodies against adenovirus < 1 / 350 dilution at the moment of inclusion in the study Treatment with VCN - 01 is feasible with an acceptable safety profile when administered with Durvalumab in a sequential schedule. Based on PK/PD and toxicity, VCN - 01 RP2D is 1E13vp. Encouraging biological activity is observed in R/M HNSCC pts. *Address correspondence to: Ricard Mesía (rmesia@iconcologia.net) Jové Maria 1 , Braña Irene 2 , Oliva Marc 1 , Hernando Alberto 2 , Erasun Carlos 1 , Assaf Juan David 2 , Bazan - Peregrino Miriam 3 , Mato - Berciano Ana 3 , Maliandi Maria Victoria 3 , Torres - Manjon Silvia 4 , 5 , Martínez de Villarreal Jaime 6 , Real Francisco X 6 , Nuciforo Paolo 7 , Alemany Ramon 4 , 5 , Capellà Gabriel 5 , Blasi Emma 3 , Blasco Carmen 3 , Cascallo Manel 3 , Mesia Ricard 8 ,* 1 Medical Oncology Department, Institut Catala d'Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain ; 2 Vall d 㼿 Hebron University Hospital & Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain ; 3 VCN Biosciences - Synthetic Biologics, Sant Cugat del Valles, Barcelona, Spain ; 4 ProCure Program, Institut Catala d'Oncologia, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain ; 5 Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Barcelona, Spain ; 6 Epithelial Carcinogenesis Group, Molecular Oncology Programme, Spanish National Cancer Research Centre - CNIO, Madrid, Spain . CIBERONC, Madrid, Spain ; 7 Molecular Oncology Group, VHIO, Barcelona, Spain ; 8 Medical Oncology Department, Institut Catala d'Oncologia, Badalona, B - ARGO group, IGTP, Badalona, Spain Background Results NCT 03799744 is a multi - center, open - label dose - escalation phase I study to investigate the safety and tolerability of intravenous VCN - 01 with Durvalumab in the two regimens of administration and to establish the recommended phase II dose . Trial Design & Methods Figure 3 : VCN - 01 quantification in tumor biopsies . VCN - 01 is detected in tumor after 7 and 28 days after VCN - 01 systemic administration, in both arms, sequential and concomitant when genomes/biopsy are quantified by qPCR Figure 2 : Quantification of viral genomes in blood . VCN - 01 viral genomes were detected in blood at different times after administration, suggestive of viral replication . VCN - 01 genomes were quantified by qPCR, in both arms, sequential and concomitant . 0 2 0 0 1 - 5 0 10 1 0 0 10 0 0 100 0 0 10 0 0 0 0 50 1 0 0 1 5 0 Days post VCN - 01 Dilution 1 - S - 0 1 1 - S - 0 2 1 - S - 0 3 1 - S - 0 4 2 - S - 0 8 1 - S - 1 8 1 - S - 0 5 2 - S - 0 9 2 0 0 1 - 5 0 10 10 0 0 1 0 0 100 0 0 10 0 0 0 0 0 50 1 0 0 1 5 0 Days post VCN - 01 Dilution 2 - S - 11 1 - S - 2 1 2 - S - 1 3 1 - S - 2 2 1 - S - 2 4 1 - S - 2 5 0 2 0 0 1 - 5 0 10 1 0 0 10 0 0 100 0 0 100000 1000000 1000000 50 1 0 0 1 5 0 Days post VCN - 01 D i l u ti o n 2 - C - 0 1 2 - C - 0 2 1 - C - 0 3 2 - C - 0 4 1 - C - 0 5 2 - C - 1 0 Concomitant Arm Dose: 3,3E12 vp Figure 5 : Anti - Ad 5 NAbs quantification after administration of VCN - 01 in serum . Anti - Ad 5 neutralizing antibody (Nabs) levels were analyzed in serum from patients treated with VCN - 01 at different time points . Nab titer for each sample was calculated as the inverse of the serum dilution to obtain a 50 % of virus neutralization . 0 3 8 2 8 4 2 7 0 9 8 1 2 6 0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 D a y s P H 2 0 in s e ru m ( p g /m l) CD8 /Treg axis PD - 1 / PD - L1 axis IFN  / IDO pathway CTLA4 pathway 55% ↓Tregs* (6/11) 55% ↑PD - 1 (6/11) 64% ↑IDO (7/11) 36% ↑CTLA - 4 (4/11) D8 64% ↑CD8 (7/11) 73% ↑PD - L1 (8/11) 63% ↓Tregs* (5/8) 56% ↑PD - 1 (5/9) 60% ↑IDO (6/10) 33% ↑CTLA - 4 (3/9) D28 50% ↑CD8 (5/10) 80% ↑PD - L1 (8/10) Table 3 : Summary of immune markers variations by IHC of all paired biopsies (Sequential & Concomitant Arm samples) . % of samples showing modulation (positive / total analyzed samples) *Including FoxP 3 & CD 25 staining Table 1: Patient demographics and clinical characteristics Table 2: VCN - 01 Related AEs (except Grade 1 - 2 observed in n=1 ) Figure 4 : Quantification of PH 20 expression in serum . PH 20 expresión was measured on serum by ELISA in serum from treated patients at different time points . PH 20 expression is expressed as pg/mL minus background levels detected for each sample at day 0 (pre - treatment) . Safety profile of VCN - 01 Pharmacokinetics and pharmacodynamics of VCN - 01 Mechanism of action of VCN - 01 induces changes in tumor microenvironment Figure 6 : IHC analysis of tumor biopsies . IHC of immune markers in tumor biopsies for immune markers at day 0 (pre - treatment) day 8 and day 28 after VCN - 01 intravenous administration . PD - L 1 samples : 1 - S - 01 , 2 - S - 09 , 2 - S - 21 ; IDO samples 2 - S - 08 ; CD 8 samples 2 - S - 21 . Scale bars, 50 µm . Immunohistochemistry Transcriptomic analysis Radiomics Figure 8 : Analysis of radiomics markers from MRIs . T 2 * sequences, Diffusion weighted imaging (DWI) and Dynamic contrast enhanced (DCE) were acquired from MRI images using 1 . 5 T and 3 T equipment . Imaging biomarkers were obtained by a non - invasive imaging post - processing procedure . The delta (  ) radiomic features for the lesions treated sequentially were extracted between the screening and the 1 st follow - up (corresponding to week 8 ) 1 0 2 0 0 4 0 0 6 0 0 8 0 0 1 0 2 0 3 0 S e q u e n t ia l A r m D o s e : 3 , 3 E 1 2 v p 2 3 D a y s p o s t V C N - 0 1 IL 6 p g /m L 1 - S - 0 1 1 - S - 0 2 1 - S - 0 3 1 - S - 0 4 2 - S - 0 8 1 - S - 0 5 2 - S - 0 9 1 0 2 0 0 4 0 0 6 0 0 8 0 0 1 0 2 0 3 0 S e q u e n t ia l A r m D o s e : 1 E 1 3 v p 2 3 D a y s p o s t V C N - 0 1 IL 6 p g /m L 1 - S - 2 1 1 - S - 2 4 1 - S - 2 5 2 - S - 1 1 2 - S - 1 3 1 - S - 2 2 Figure 1 : IL 6 levels were analyzed in serum from patients treated with VCN - 01 at different time points . 1 0 2 0 0 4 0 0 6 0 0 8 0 0 1 0 2 0 3 0 C o n c o m ita n t A r m D o s e : 3 , 3 E 1 2 v p 2 3 D a y s p o s t V C N - 0 1 IL 6 p g /m L 2 - C - 0 1 2 - C - 0 2 1 - C - 0 3 2 - C - 0 4 1 - C - 0 5 2 - C - 1 0 0 1 2 1 0 1 0 1 0 9 1 0 8 1 0 7 1 0 6 1 0 5 1 0 4 1 0 3 1 0 2 1 0 1 1 0 0 1 9 2 3 6 0 5 2 8 6 9 6 1 3 4 4 C o n c o m ita n t A r m D o s e : 3 , 3 E 1 2 v p V ira l g e n o m e s in b lo o d ( v p / m L ) 2 C 0 1 2 C 0 2 1 C 0 3 2 C 0 4 1 C 0 5 2 C 1 0 4 8 D 8 D 1 5 D 2 2 C 2 D 1 C 3 D 1 T im e 2 4 3 6 H o u rs D a ys ( D 2 9 ) ( D 5 8 ) L o Q 0 1 2 1 0 1 0 1 0 9 1 0 8 1 0 7 1 0 6 1 0 5 1 0 4 1 0 3 1 0 2 1 0 1 1 0 0 1 9 2 3 6 0 5 21 7 0 4 S e q u e n t ia l A r m D o s e : 3 , 3 E 1 2 v p V ira l g e n o m e s in b lo o d ( v p / m L ) 1 S 0 1 1 S 0 2 1 S 0 3 2 S 0 4 2 S 0 8 2 S 0 9 80 3 2 1 C 3 D 1 2 3 7 6 T im e 2 4 3 6 H o u rs D a ys 4 8 D 8 D 1 5 D 2 2 C 2 D 1 C 3 D 1 C 4 D 1 ( D 4 3 ) ( D 7 1 ) ( D 9 9 ) L o Q 0 1 2 3 6 1 0 1 0 1 0 9 1 0 8 1 0 7 1 0 6 1 0 5 1 0 4 1 0 3 1 0 2 1 0 1 1 0 0 1 9 2 3 6 0 5 2 8 1 0 3 2 S e q u e n t ia l A r m D o s e : 1 E 1 3 v p V ira l g e n o m e s in b lo o d ( v p / m L ) 2 S 1 1 1 S 2 1 2 S 1 3 1 S 2 2 1 S 2 4 1 S 2 5 4 8 D 8 D 1 5 D 2 2 C 2 D 1 ( D 4 3 ) T im e 2 4 H o u rs D a ys L o Q Figure 7 : RNA seq analysis . A . Principal Component Analysis including all the Pre - and Post - treatment samples . B . Differentially up - regulated and down - regulated genes in the D 8 vs Pre - treat . comparison, paired analysis (corrected for multiple testing) . No significant genes were found in the D 28 vs Pre - treat . comparison . C . Most significant Reactome and KEGG pathways in GSEA analysis D 8 vs Pre - treat . D . Most significant Reactome and KEGG pathways in GSEA analysis D 28 vs Pre - treat . P re - tre atme n t Post - D8 Post - D28 Up D8 Down D8 VCN - 01 modulates tumor microenvironment inducing up - regulation of PD - L1, CD8 and IDO in tumor cells Sustained differential gene expression profiles associated with downregulation of matrix - related pathways Radiomic markers suggest VCN - 01 increases perfusion from the extravascular space to the intravascular space Sustained levels of viral genomes are observed in all patients VCN - 01 is detected in tumor biopsies at D8 and D28 after systemic delivery Sequential Arm Dose: 3,3E12 vp Dose: 1E13 vp PH20 expression from VCN - 01 peaks on D3 - D8 and remains elevated in some patients up to D42 Anti - Ad5 NAbs after VCN - 01 peak on D28, then start decreasing over time, reaching a ~1 - 2 log reduction by D150 22 - 25624 - 1 C1.2 P5

XML

Cover	Sep. 12, 2022
Cover [Abstract]
Document Type	8-K
Amendment Flag	false
Document Period End Date	Sep. 12, 2022
Entity File Number	001-12584
Entity Registrant Name	SYNTHETIC BIOLOGICS, INC.
Entity Central Index Key	0000894158
Entity Tax Identification Number	13-3808303
Entity Incorporation, State or Country Code	NV
Entity Address, Address Line One	9605 Medical Center Drive
Entity Address, Address Line Two	Suite 270
Entity Address, City or Town	Rockville
Entity Address, State or Province	MD
Entity Address, Postal Zip Code	20850
City Area Code	301
Local Phone Number	417-4364
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Title of 12(b) Security	Common stock, par value $0.001 per share
Trading Symbol	SYN
Security Exchange Name	NYSEAMER
Entity Emerging Growth Company	false