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): February 16, 2023

THERIVA 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(b) 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	TOVX	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 7.01. Regulation FD Disclosure.

On February 16, 2023, Theriva Biologics, Inc. (the “Company”) issued a press release announcing that the presentation of blinded safety and pharmacokinetic (PK) data from the ongoing Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). These data will be featured in a poster presentation at 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, being held in Orlando, Florida from February 15-19, 2023.

Cohort 1 of the study enrolled 19 patients who received at least 1 dose of study drug (SYN-004 or Placebo randomized 2:1). Twelve of these patients completed two doses of IV MER to be evaluable towards the study endpoints. While the study is on-going and remains blinded, key findings showcased in the poster presentation (#LBA6) titled “Interim Analysis of SYN-004 Phase 1b/2a Trial in Hematopoietic Cell Transplant (HCT) Recipients” include:

	·	Adverse events (AEs) and serious adverse events (SAEs) observed in Cohort 1 were typical of those observed in allo-HCT patients and no AEs or SAEs were determined to be related to study drug treatment by the investigators.

	·	Consistent with previous studies of SYN-004 in healthy volunteers, SYN-004 was not observed in blood samples from the majority of the evaluable patients.

Meropenem pharmacokinetics were as expected for this patient population.

A copy of the poster titled “Interim Analysis of SYN-004 Phase 1b/2a Trial in Hematopoietic Cell Transplant (HCT) Recipients” is filed as an exhibit to this Current Report on Form 8-K.

The information in this Item 7.01 and in the press release furnished as Exhibit 99.1 to this Current Report on Form 8-K shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended and shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

The press release furnished as Exhibit 99.1 to this Current Report on Form 8-K includes “safe harbor” language pursuant to the Private Securities Litigation Reform Act of 1995, as amended, indicating that certain statements contained therein are “forward-looking” rather than historical.

Item 8.01. Other Events.

On February 16, 2023, the Company presented blinded safety and pharmacokinetic (PK) data from the ongoing Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). These data will be featured in a poster presentation at 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, being held in Orlando, Florida from February 15-19, 2023.

	·	Adverse events (AEs) and serious adverse events (SAEs) observed in Cohort 1 were typical of those observed in allo-HCT patients and no AEs or SAEs were determined to be related to study drug treatment by the investigators.

	·	Consistent with previous studies of SYN-004 in healthy volunteers, SYN-004 was not observed in blood samples from the majority of the evaluable patients.

Meropenem pharmacokinetics were as expected for this patient population.

Item 9.01. Financial Statements and Exhibits.

(d)

Exhibits.

Exhibit Number		Description
99.1		Press Release issued by Theriva Biologics, Inc., dated February 16, 2023
99.2		Poster titled “Interim Analysis of SYN-004 Phase 1b/2a Trial in Hematopoietic Cell Transplant (HCT) Recipients”
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: February 16, 2023	THERIVA BIOLOGICS, INC.

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

Exhibit 99.1

Theriva Biologics Announces Presentation of Safety and Pharmacokinetic Data from Cohort 1 of the Phase
1b/2a Clinical Trial of SYN-004 (ribaxamase) in Allogeneic Hematopoietic Cell Transplant Recipients

- Data presented at the 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR -

-Analysis of patients receiving meropenem suggest that SYN-004 is well-tolerated with HCT and was not
observed in blood samples from the majority of the evaluable patients -

Rockville, MD, February 16, 2023 – Theriva Biologics (NYSE American: TOVX), (“Theriva” or the “Company”), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, today announced the presentation of blinded safety and pharmacokinetic (PK) data from the ongoing Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). These data will be featured in a poster presentation at the 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, being held in Orlando, Florida from February 15-19, 2023.

“SYN-004 (ribaxamase) is intended to address key limitations of broad-spectrum IV beta-lactam antibiotics and potentially improve treatment outcomes with this important and widely used class of therapeutics. We are encouraged by the favorable safety/tolerability profile and growing evidence from our initial meropenem (MER) cohort that supports the clinical advancement of SYN-004,” said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. “With our collaborators at Washington University we plan to continue to explore the therapeutic potential of SYN-004 and its ability to reduce serious adverse events in patients with hematologic cancers undergoing allogeneic HCT. Dosing is now underway for Cohort 2, which is designed to evaluate SYN-004 in combination with piperacillin/tazobactam and we look forward to providing further updates on our progress.”

	·	Adverse events (AEs) and serious adverse events (SAEs) observed in Cohort 1 were typical of those observed in allo-HCT patients and no AEs or SAEs were determined to be related to study drug treatment by the investigators.

	·	Consistent with previous studies of SYN-004 in healthy volunteers, SYN-004 was not observed in blood samples from the majority of the evaluable patients.

Meropenem pharmacokinetics were as expected for this patient population.

Details on the poster can be found below.

	·	Lead Author: Mark Schroeder, MD, Associate Professor of Medicine, Division of Oncology, Section of Bone Marrow Transplantation and Leukemia, Washington University School of Medicine in St. Louis

	·	Session: (1460 – FPS 07) Retinoblastoma and Germ Cell Tumors

	·	Date & Time: Available for digital viewing and in-person beginning Thursday, February 16 at 12:00 p.m. ET

Location: Virtually and in person at the Orlando World Center Marriott, Orlando, Florida

About the Phase 1b/2a Clinical Trial

The ongoing randomized, double-blinded, placebo-controlled Phase 1b/2a clinical trial is being conducted at Washington University School of Medicine in St. Louis. The trial is designed to evaluate the safety, tolerability, and potential absorption of oral SYN-004 (150 mg q.i.d. for a maximum of 28 days) into the systemic circulation of allogeneic HCT recipients who receive an IV antibiotic to treat fever. To mitigate risk, Cohort 1 of the study administered meropenem as the study-assigned antibiotic. Meropenem is a carbapenem antibiotic that is not metabolized by SYN-004. Patients in Cohorts 2 and 3 will be administered piperacillin/tazobactam and cefepime respectively, each of which can be metabolized by SYN-004. The trial is also designed to evaluate potential protective effects of SYN-004 on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allogeneic HCT recipients. The trial is expected to enroll up to 36 participants with three sequential cohorts, each evaluating a different study-assigned IV beta-lactam antibiotic. Safety and pharmacokinetic data for each cohort will be reviewed by an independent Data and Safety Monitoring Committee that will make a recommendation on whether to proceed to the next IV beta-lactam antibiotic. More information on the study is available here (NCT04692181).

About SYN-004 (ribaxamase)

SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of Clostridioides difficile infection (CDI), overgrowth of pathogenic organisms, the emergence of antimicrobial resistance (AMR) and acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients. Allogeneic HCT recipients routinely receive long courses of IV beta-lactam antibiotics to treat infection following conditioning therapy. Antibiotic-mediated damage of the gut microbiome in allogeneic HCT recipients may lead to adverse outcomes including CDI, VRE colonization and potentially fatal bacteremia and aGVHD. A previously completed placebo-controlled Phase 2b clinical trial of 412 patients demonstrated SYN-004 protected the gut microbiome from antibiotic-mediated dysbiosis. Patients who received SYN-004 also demonstrated significantly better maintenance and recovery of the gut microbiome as well as lower incidences of new colonization by opportunistic and potentially pathogenic microorganisms such as VRE.

About Theriva Biologics, Inc.

Theriva Biologics (NYSE American: TOVX), is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. The Company’s subsidiary Theriva Biologics, S.L. , has been developing a new oncolytic adenovirus platform designed for intravenous (IV), intravitreal and antitumoral delivery to trigger tumor cell death, improve access of co-administered cancer therapies to the tumor, and promote a robust and sustained anti-tumor response by the patient’s immune system. The Company’s lead clinical-stage candidates are: (1) VCN-01, an oncolytic adenovirus designed to replicate selectively and aggressively within tumor cells, and to degrade the tumor stroma barrier that serves as a significant physical and immunosuppressive barrier to cancer treatment; (2) SYN-004 (ribaxamase) which is designed to degrade certain commonly used IV beta-lactam antibiotics within the gastrointestinal (GI) tract to prevent microbiome damage, thereby limiting overgrowth of pathogenic organisms such as VRE (vancomycin resistant Enterococci) and reducing the incidence and severity of acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients); and (3) SYN-020, a recombinant oral formulation of the enzyme intestinal alkaline phosphatase (IAP) produced under cGMP conditions and intended to treat both local GI and systemic diseases. For more information, please visit Theriva Biologics’ website at www.therivabio.com.

Forward-Looking Statement

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform 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 SYN-004 (ribaxamase) being intended to address key limitations of broad-spectrum IV beta-lactam antibiotics and potentially improve treatment outcomes with this important and widely used class of therapeutics, plans to continue to explore the therapeutic potential of SYN-004 and its ability to reduce serious adverse events in patients with hematologic cancers undergoing allogeneic HCT, providing further updates on the Company’s progress, and the study enrolling up to 36 participants with three sequential cohorts, each evaluating a different study-assigned IV beta-lactam antibiotic. These forward-looking statements are based on management’s expectations and assumptions as of the date of this press release and are subject to a number of risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the SYN-004’s ability to address key limitations of broad-spectrum IV beta-lactam antibiotics and potentially improve treatment outcomes with this important and widely used class of therapeutics, the Company’s and VCN’s ability to reach clinical milestones when anticipated including enrolling the expected number of patients in each trial, , the Company’s and VCN’s product candidates, including SYN-004, demonstrating safety and effectiveness, as well as results that are consistent with prior results; the ability to complete clinical trials on time and achieve the desired results and benefits, continuing clinical trial enrollment as expected; the ability to obtain regulatory approval for commercialization of product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to the Company’s and VCN’s ability to promote or commercialize their product candidates for the specific indications, acceptance of product candidates in the marketplace and the successful development, marketing or sale of the Company’s and VCN’s products, developments by competitors that render such products obsolete or non-competitive, the Company’s and VCN’s ability to maintain license agreements, the continued maintenance and growth of the Company’s and VCN’s patent estate, the ability to continue to remain well financed, and other factors described in the Company’s Annual Report on Form 10-K for the year ended December 31, 2021 and its other filings with the SEC, including subsequent periodic reports on Forms 10-Q and current reports on Form 8-K. The information in this release is provided only as of the date of this release, and Theriva Biologics undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law.

For further information, please contact:

Investor Relations:

Chris Calabrese

LifeSci Advisors, LLC

[email protected]

917-680-5608

Exhibit 99.2

• SYN-004 is an orally administered, β-lactamase enzyme designed to preserve the intestinal microbiome in patients receiving IV β-lactam antibiotics. • A previous study among patients with lower respiratory tract infections receiving ceftriaxone plus SYN-004 vs. placebo found decreased risk of Clostridioides difficile infection (CDI) among the SYN-004 group.1 • Patients who received SYN-004 also had fewer alterations to the gut microbiome and resistome, including reductions in the frequency of β-lactamase and vancomycin resistance genes.2 • Published data suggest improved outcomes among HCT recipients with a healthier microbiome at engraftment, including less GVHD and improved survival • SYN-004 may improve outcomes after HCT through microbiome preservation during IV β-lactam antibiotic administration. • This study evaluates the safety, tolerability, and potential absorption of SYN-004 in HCT recipients. • Interim blinded analyses after the MER cohort suggest SYN-004 is well tolerated in HCT patients. • SYN-004 detection was uncommon by ECL. • Functional drug was not detected in blood; positive ECL may represent absorption of inactive SYN-004 fragments. • BSIs were common among HCT patients (47%); all but 1 BSI were the precipitating event for MER initiation. • The BSI that occurred after MER initiation was caused by a methicillin resistant S. epidermidis, resistant to MER. • This study is currently enrolling in the piperacillin-tazobactam cohort. • Adults undergoing allogeneic HCT with myeloablative conditioning • Preserved organ function and no known antibiotic allergy • Phase 1b/2a, triple-blinded, randomized controlled trial • Randomized 2 (SYN-004) : 1 (placebo) • 3 antibiotic cohorts: meropenem (MER), piperacillin-tazobactam, and cefepime • Cohort 1 MER was used for neutropenic fever coverage. • Study drug was started on HCT day +1 and continued until 72h after MER discontinuation. • Figure 1 provides an overview of study activities. • Schema will be the same for the PIP/TAZO and cefepime study arms. • Target enrollment per cohort = 12 participants completing at least two antibiotic PK blood draw periods. • Primary outcomes: assess potential SYN-004 systemic absorption via plasma levels; assess effects of SYN-004 on systemic antibiotic concentrations; assess incidence of BSIs and bacterial intestinal infections while receiving SYN-004; assess tolerability and grade 3 or 4 adverse events; and assess overall survival at 30 days after study drug dosing completed. Theriva Biologics, Inc. (formerly Synthetic Biologics, Inc.) • 19 patients started study drug; 12 had at least two MER PK blood draws and were considered evaluable (Table 1). • A total of 13 SAEs occurred among 10 patients (Table 2). • None were found to be related to study drug or study procedures. • 9/19 (47%) developed a BSI while on study drug (Table 3). • 8 BSIs were the precipitating event for MER initiation. • 1 patient developed methicillin-resistant Staphylococcus epidermidis BSI while receiving MER. BACKGROUND METHODS RESULTS CONCLUSIONS TABLE 3. Bloodstream infections among patients who received study drug or placebo (N=19) Variable N (%) BSIs before meropenem initiation 8 (42) a Staphylococcus epidermidis 4 (21) Escherichia coli 1 (5) Klebsiella pneumoniae 3 (15) Capnocytophaga sputigena 1 (5) Leptotrichia spp. 1 (5) Streptococcus bovis 1 (5) BSIs after meropenem initiation 1 (5) Staphylococcus epidermidis, methicillin resistant 1 (5) BSIs within 30 days after end of study drug/placebo and meropenem (n=14 patients enrolled) 2 (14) Escherichia coli 1 (7) Staphylococcus epidermidis, methicillin resistant b 1 (7) TABLE 2. Severe adverse events among study participants (N=19) Severe Adverse Event N Sepsisa 6 Acute kidney injury 2 Kidney infection (BK virus)a 1 GI bleed 1 Anorexia 1 Endocarditisa, b 1 Vomiting 1 Interim Safety Analysis of SYN-004 Phase 1b/2a Trial in Hematopoietic Cell Transplant (HCT) Recipients Mark A. Schroeder, MD1 , Hailey Sappington, MPH1 , Jeremy Eisele 1 , Elijah Martin 1 , Gabbie Lampen 1 , Kimberly A. Reske, MPH2 , Tiffany Hink, MT, ASCP 2 , Victoria Teuscher 2 , Matthew R. Keller, MS3 , Andrew Bristol, PhD4 , Charles Le, PhD4 , Sheila Connelly, PhD4 , Michael Moenk, PhD5 , Vince Wacher, PhD4 , Michael Kaleko, MD, PhD4 , Joseph L. Kuti, PharmD, FIDP, FCCP6 , Margaret A. Olsen, PhD, MPH2 and Erik R. Dubberke, MD, MSPH2 1Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO; 2Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO; 3 Institute for Informatics, Washington University School of Medicine, Saint Louis, MO; 4Theriva Biologics, Inc., Rockville, MD; 5Charles River Laboratories, Skokie, IL; 6Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT Abstract #LBA6 aThree BSIs were polymicrobial, so total organisms adds up to more than 9. Polymicrobial BSIs included: S. epidermidis / K. pneumoniae; K. pneumoniae / S. bovis; S. epidermidis / C. sputigena. One patient had two separate BSIs: S. epidermidis and then E. coli. bCase of endocarditis reported as SAE a Infectious SAE; 1 sepsis event resulted in death (not related to study drug). bS. epidermidis; occurred after completion of study drug/placebo and meropenem. REFERENCES 1. Kokai-Kun JF et al. Lancet Infect Dis. 2019; 19 (5):487-496. 2. Kokai-Kun JF et al. Infect Drug Resist. 2020; 13:2521-2535. Results of PK analyses: •SYN-004 was detected in 3/137 (2.2%) specimens by ECL. •Patient A: 2/10 specimens positive: •9.45 ng/ml on day 2-3 after MER start •0.98 ng/ml on MER day 7. •Patient B: 1/4 specimens positive: 1.15 ng/ml within 72h of study drug start. •All were functional assay negative and SYN-004 absorption was adjudicated as indeterminate. •Meropenem concentrations best fitted a two-compartment model with CrCL proportional to CL. •Mean (SD) area under the curve for MER = 257mg*hr/L(159) (Table 4). Erik Dubberke, MD, MSPH Washington University School of Medicine Box 8051; 4523 Clayton Ave [email protected] St. Louis, MO 63110 TABLE 1. Demographics of study population Variable N (%) or median (range) Total enrollment 19 Number evaluable (at least 2 MER PK blood draws) 12 (63) Female 6 (32) White race 19 (100) Underlying malignancy AML 7 (37) MDS 8 (42) Other: Lymphoma, lymphoproliferative disease, PCL, CMML 4 (21) Time since diagnosis of hematologic malignancy (months) 10 (5-16) Transplant characteristics Peripheral blood stem cell 19 (100) Matched sibling 6 (32) Matched unrelated 12 (63) Haploidentical 1 (5) Match grade not 10/10 2 (11) Myeloablative conditioning 19 (100) FUNDING TABLE 4. Summary of meropenem pharmacokinetic and pharmacodynamic exposure parameters for the 12 patients on Day 2 and Day 7 of meropenema Parameter Day 2 Day 7 Cmax (µg/mL) 54.67 (51.69) 44.20 (23.42) Cmin (µg/mL) 1.46 (3.76) 0.91 (1.97) AUC24 (µg*h/mL) b 256.79 (159.48) Same as Day 2 fT>MIC Enterobacterales (%) c 69% (20) Same as Day 2 fT>MIC P. aeruginosa (%) d 58% (19) Same as Day 2 a Results presented as mean (standard deviation) total drug concentrations (Cmax, Cmin, AUC24 ) or free drug exposures (fT>MIC), corrected for protein binding of 2% b AUC24 calculated as the total dose received on day of therapy divided by the individual CL c Simulated exposure at the Enterobacterales susceptibility breakpoint (1 µg/mL) based on individual posterior PK parameters and actual dosing regimen received d Simulated exposure at the P. aeruginosa susceptibility breakpoint (2 µg/mL) based on individual posterior PK parameters and actual dosing regimen received NOTE: Target T>MIC is 40%. 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