Synthetic Biologics, Inc. (Form: 8-K, Received: 05/16/2022 17:44:05)

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): May 16, 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 LLC

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 7.01 Regulation FD Disclosure.

As previously announced by Synthetic Biologics, Inc., (the “Company”), on May 16, 2022, at an oral presentation at the 25^th Annual Meeting of the American Society of Gene & Cell Therapy, Ramon Alemany, Ph.D., Head of the Immunotherapy and Virotherapy Group at the Translational Research Laboratory of the Institut Catala d’Oncologia (ICO) and Institut de Investigacio Biomedica de Bellvitage and a founding member of VCN Biosciences, S.L., presented preclinical results showcasing the potential of VCN-11 to balance safety, with no major toxicities observed, and effectively target tumors after intravenous re-administration, even in the presence of high level NAbs.

A copy of the presentation materials are attached as Exhibit 99.1 to this Report on Form 8-K.

Item 8.01 Other Information.

On May 16, 2022, Ramon Alemany, Ph.D., Head of the Immunotherapy and Virotherapy Group at the Translational Research Laboratory of the Institut Catala d’Oncologia (ICO) and Institut de Investigacio Biomedica de Bellvitage and a founding member of VCN Biosciences, presented at the 25th Annual Meeting of the American Society of Gene & Cell Therapy preclinical results showcasing the potential of VCN-11 to balance safety, with no major toxicities observed, and effectively target tumors after intravenous re-administration, even in the presence of high level NAbs.

Item 9.01. Financial Statements and Exhibits.

(d)

Exhibits.

Exhibit Number		Description
99.1		Presentation Materials presented at the 25^th Annual Meeting of the American Society of Gene & Cell Therapy
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 report to be signed on its behalf by the undersigned hereunto duly authorized.

Dated: May 16, 2022	SYNTHETIC BIOLOGICS, INC.

	By:	/s/ Steven A. Shallcross
		Name:	Steven A. Shallcross
		Title:	Chief Executive Officer and Chief Financial Officer

Exhibit 99.1

Oncolytic Adenovirus With Hyaluronidase Activity That Evades Neutralizing Antibodies And Allows Re - administration: VCN - 11 Ana Mato - Berciano , Maria V. Maliandi , Sara Morgado , Marti Farrera - Sal, Paz Moreno, Rafael Moreno, Luis A. Rojas, Gabriel Capellà , Miriam Bazan - Peregrino , Manel Cascallo , and Ramon Alemany Virotherapy Group

Disclosures R. Alemany is advisor and owns stock of VCN Biosciences / Synthetic Biologics

VCN - 01 and VCN - 11 oncolytic adenoviruses Fiber Shaft RGDK Hexon ABD VCN - 01 VCN - 11 Ad5 wild type | Reduces liver tropism Fiber Shaft KKTK Host albumin | Enables replication in normal cells | Facilitates liver sequestration | Replication restricted to tumor cells (Rb - E2F defective) Degrades tumor stroma | Binds host albumin to protect against neutralizing antibodies Amplified replication in tumor cells (high levels of E2F) | L5 L3 E1a - Δ 24 415p SA pA K PH20 LITR RITR L1 L2 L4 MLP L5 L3 E1a LITR RITR L1 L2 L4 MLP L5 L3 E1a - Δ 24 415p SA pA K PH20 LITR RITR L1 L2 L4 MLP Fiber Shaft RGDK Lower hepatic toxicity Allows fractionated dosing to improve half life and tumor targeting Induces less NAbs Shielding from NAbs allows readministration

In vivo: VCN - 11 Infection causes hyaluronan degradation Melanoma SKmel28 tumors IT administration VCN - 11 expresses hyaluronidase In vitro:

VCN - 11 binds albumin

Virus in liver at 48 h post admin. IV P B S V C N - 0 1 ( 1 X ) V C N - 1 1 ( 1 X ) 0 200 400 600 800 1000 1500 2000 2500 3000 VCN-01 vs VCN-11 single IV A L T ( I U / L ) *** P B S V C N - 1 1 ( 1 X ) V C N - 1 1 ( 3 X ) V C N - 1 1 ( 6 X ) 0 200 400 600 800 1000 1500 2000 2500 3000 VCN-11 single IV dose escalation A L T ( I U / L ) ** Athymic nude mice bearing tumors VCN - 11 reduced hepatic toxicity compared to VCN - 01 1X Dose = 4E10 vp / mouse i.v.

Reduced VCN - 11 toxicity allows dose fractionation Increased t 1/2 for the second VCN - 11 dose (mouse model) 3 X S i n g l e 3 X ( 1 X @ 0 h + 2 X @ 4 h ) 3 X ( D 1 , D 2 , D 3 ) 0 10 20 30 40 t 1 / 2 ( m i n ) * * Dose fractionation slightly increases hepatic toxicity 5min 16min 14min 3X Dose = 1.2E11 vp / mouse i.v.

Dose fractionation increases VCN - 11 bioavailability and improves tumor targeting Fiber mRNA in tumor (accumulated dose) PH20 mRNA in tumor (availability of the post - dose) • Pre - dose with an oncolytic virus (ICOVIR15KABD) not expressing PH20 @ 1X = 4E+10vp/animal to block liver kupffer cells • Post - dose with VCN - 11 that expresses PH20

Single administration in Naïve models 20 40 80 160 320 640 1280 2560 5120 Hamster N A b T i t e r ( 1 / S e r u m D i l u t i o n ) Ad5 VCN-11 Vaccination PBS Ad5 Ad5 + Ad5 VCN-11 Ad5 + VCN-11 Ad5 VCN-11 20 40 80 160 320 640 1280 2560 5120 Mouse N A b T i t e r ( 1 / S e r u m D i l u t i o n ) * p=0.0002 Ad5 VCN-11 20 40 80 160 320 640 1280 2560 5120 Hamster N A b T i t e r ( 1 / S e r u m D i l u t i o n ) * p=0.003 Administration in Ad5 - primed model * Neutralizing antibodies are measured in a specific cell - based functional assay for Ad5 ( ● ) and for VCN - 11 ( ● ) VCN - 11 induces less NAbs compared to Ad5

Albumin shields VCN - 11 against anti - Ad5 NAbs (in vitro hexon flow cytometry ) VCN - 01 VCN - 11 VCN - 01 VCN - 11 No neutralizing antibody + anti - Ad5 neutralizing antibody No virus Count Count FITC - A FITC - A FITC - A FITC - A FITC - A Hexon + 6% Hexon + 22% Hexon + 83% Hexon + 7% Hexon + 0.3% Hexon + 0.03% Hexon + 97% Hexon + 95% Hexon + 97% Hexon + 96% No Albumin + Albumin

Tumor cells injection Immunization Ad5 (IP) Immunization (IV) Ad5 (IV) Day 1 Day 8 Day 15 Serum collection C57BL/6 mice immunocompetent Athymic nuce mice immunodeficient Passive immunization Second admin (IV) VCN - 01 or VCN - 11 Day - 1 Day 0 0.0001 0.001 0.01 0.1 1 10 F o l d C h a n g e V G w i t h N A b s / V G w i t h o u t N A b s 1 / 4 0 1 / 1 2 8 0 1 / 4 0 1 / 5 1 2 0 N o N A b s N o N A b s NAbs Titer 1 / 1 2 8 0 * * VCN-01 VCN-11 Albumin shields VCN - 11 against anti - Ad5 NAbs in vivo Viral genomes in tumors

0 10 20 30 40 50 60 70 80 90 0 250 500 750 1000 1250 1500 1750 Days T u m o u r g r o w t h ( % ) PBS VCN-01 * p<0.05 vs PBS VCN-11 * * * * SK-MEL-28 VCN - 11 shows antitumor activity in the presence of anti - Ad5 NAbs

10 0 10 1 10 2 10 3 10 4 10 5 V i r a l g e n o m e s / µ g D N A ( H P - 1 T u m o u r s ) PBS VCN-11 VCN-11 + VCN-11 Vaccination ns VCN-11 # VCN-11 administrations 1 2 3 VCN-11 tumour targeting 10 20 40 80 160 320 640 1280 2560 5120 N A b T i t e r ( 1 / S e r u m D i l u t i o n ) anti-VCN-11 NAbs * * p<0.05 vs PBS PBS VCN-11 VCN-11 + VCN-11 Vaccination NAbs after VCN-11 # VCN-11 administrations 0 1 2 Immunocompetent Syrian Hamster Sustained VCN - 11 tumor targeting despite high NAbs upon multiple i.v. doses

VCN - 11 antitumor activity in the presence of antiAd5+antiVCN - 11 NAbs Non - immunized animals 0 5 10 15 20 25 30 0 200 400 600 800 1000 Pre-immunized animals PBS VCN-01 (NAbs 1/320) VCN-11 (NAbs 1/320) Days T u m o u r v o l u m e ( m m 3 ) *p<0.05 vs PBS *

0 5 10 15 20 25 30 35 40 0 250 500 750 1000 1250 1500 Days % T u m o u r g r o w t h VCN-11 Nabs 1/320 VCN-11 Nabs 1/640 Ad5 Nabs 1/640 SW480 Tumours Naive Ad5 Nabs 1/640 + VCN-11 + PBS Passive immunity Treatment ^ * * * * * ^ * * * ^ * * * * * * * , p<0.05 vs PBS VCN - 11 antitumor activity in the presence of antiAd5+antiVCN - 11 NAbs

• VCN - 11 expresses functional hyaluronidase . • Reduced hepatic toxicity of the ABD - modified virus allows to “fractionate” VCN - 11 administration which improves circulating half - life and tumor targeting . • VCN - 11 administration results in lower levels of neutralizing antibodies . • VCN - 11 reaches tumors and is effective after systemic administration in the presence of NAbs • VCN - 11 ´ s albumin shield from NAbs allows effective readministration . Conclusions

This project has been funded by VCN Biosciences, a wholly owned subsidiary of Synthetic Biologics: Ana Mato Maria V. Maliandi Sheila Connelly Michael Kaleko Frank Tufaro Manel Cascalló Miriam Bazan - Peregrino Sara Morgado Martí Farrera - Sal Rafael Moreno Paz Moreno Luís Rojas Gabriel Capellà PID2020 - 119692RB - C21