8-K - TOVX - Equibles

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 eventreported): October 23, 2023

THERIVA BIOLOGICS, INC.

(Exact name of registrant as specified in its charter)

Nevada	001-12584	13-3808303
(State or other jurisdiction of<br><br> <br>incorporation)	(Commission File No.)	(IRS Employer Identification<br><br> <br>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)
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¨	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
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¨	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
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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 October 23, 2023, Theriva Biologics, Inc. (the “Company”) issued a press release announcing the presentation of new clinical data from the Phase 1 investigator-sponsored study with the Institut Catala d’Oncologia (ICO) evaluating VCN-01 in combination with durvalumab for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The poster titled “Survival Outcomes in Phase I Trial Combining VCN-01 and Durvalumab (MEDI4736) in Subjects with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Previous Immunotherapy Treatment” was presented at the European Society for Medical Oncology (ESMO) Congress, being held both virtually and in Madrid, Spain from October 20-24, 2023.

**Key Takeaways from the presentation include:**VCN-01 combined with durvalumab showed encouraging overall survival (OS) in patients who previously progressed on anti-PD(L)-1 therapy.

·	Survival:<br>VCN-01 induced upregulation of PD-L1, which correlated with enhanced patient survival.
·	In<br>the concomitant (CS) cohort at the 3.3×10^12^ viral particles (vp) dose, overall survival<br>(OS) was 10.4 months and progression free survival (PFS) was 1.7 months.
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·	In<br>the sequential (SS) cohort at the 3.3×10^12^vp dose OS was 15.5 months and PFS was<br>3.7, whereas in the SS cohort at the 1×10^13^ vp dose OS was 17.3 months and PFS was<br>2.1 months.
·	VCN-01induces changes in the immune status of tumors
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·	VCN-01<br>combined with durvalumab increased CD8 T cells, a marker of tumor inflammation and the expression of PD(L)-1 in tumors. An increase of<br>PD(L)-1 CPS (8/11 at day 8; 8/10 at day 28) and CD8 T cells (7/11 at day 8; 5/10 at day 28) from baseline were found in tumor biopsies.
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·	VCN-01<br>alone increased the CPS score of tumor biopsies at day 8 after administration by 62.5% in the sequential arm.
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·	VCN-01<br>induced PD(L)-1 upregulation with enhanced patient survival. A statistical correlation was observed between CPS on day 8 and patient<br>OS (p=0.005).
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·	Pharmacodynamicsand shedding of VCN-01
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·	PH20<br>expression from VCN-01 peaked on day 3-8 and remained elevated in some patients up to day 42. Quantification of VCN-01 genomes in stool<br>demonstrated viral shedding that peaked at day 8.
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A copy of the poster titled “Survival Outcomes in Phase I Trial Combining VCN-01 and Durvalumab (MEDI4736) in Subjects with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Previous Immunotherapy Treatment” is filed as Exhibit 99.2 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 October 23, 2023, the Company presented a poster at the European Society for Medical Oncology (ESMO) Congress, being held both virtually and in Madrid, Spain from October 20-24, 2023 with new clinical data from the Phase 1 investigator-sponsored study with the Institut Catala d’Oncologia (ICO) evaluating VCN-01 in combination with durvalumab for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC.

**Key Takeaways from the presentation include:**VCN-01 combined with durvalumab showed encouraging overall survival (OS) in patients who previously progressed on anti-PD(L)-1 therapy.

·	Survival:<br>VCN-01 induced upregulation of PD-L1, which correlated with enhanced patient survival.
·	In<br>the concomitant (CS) cohort at the 3.3×10^12^ viral particles (vp) dose, overall survival<br>(OS) was 10.4 months and progression free survival (PFS) was 1.7 months.
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·	In<br>the sequential (SS) cohort at the 3.3×10^12^vp dose OS was 15.5 months and PFS was<br>3.7, whereas in the SS cohort at the 1×10^13^ vp dose OS was 17.3 months and PFS was<br>2.1 months.
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·	VCN-01induces changes in the immune status of tumors
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·	VCN-01<br>combined with durvalumab increased CD8 T cells, a marker of tumor inflammation and the expression of PD(L)-1 in tumors. An increase of<br>PD(L)-1 CPS (8/11 at day 8; 8/10 at day 28) and CD8 T cells (7/11 at day 8; 5/10 at day 28) from baseline were found in tumor biopsies.
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·	VCN-01<br>alone increased the CPS score of tumor biopsies at day 8 after administration by 62.5% in the sequential arm.
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·	VCN-01<br>induced PD(L)-1 upregulation with enhanced patient survival. A statistical correlation was observed between CPS on day 8 and patient<br>OS (p=0.005).
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·	Pharmacodynamicsand shedding of VCN-01
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·	PH20<br>expression from VCN-01 peaked on day 3-8 and remained elevated in some patients up to day 42. Quantification of VCN-01 genomes in stool<br>demonstrated viral shedding that peaked at day 8.
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Item 9.01. Financial Statements and Exhibits.

(d)	Exhibits.
ExhibitNumber	Description
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99.1	Press Release issued by Theriva Biologics, Inc., dated October 23, 2023
99.2	Poster titled “Survival Outcomes in Phase I Trial Combining VCN-01 and Durvalumab (MEDI4736) in Subjects with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Previous Immunotherapy Treatment”
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.

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 Presents Survival OutcomesData from Phase 1 Study Evaluating VCN-01 in Combination with Durvalumab in Patients with Recurrent/Metastatic Squamous Cell Carcinomaof the Head and Neck at ESMO Congress 2023

-Results show enhanced patient survival, correlatingwith VCN-01 mediated increases in the CPS score, a key determinant of outcomes with anti-PD-(L)1 checkpoint inhibitor therapies-

-Key Opinion Leader (KOL) webinar featuringexpert oncologist Ricard Mesia M.D., Ph.D., to be held today, Monday, October 23, 2023 at 8:00 a.m. ET-

Rockville, MD, October 23, 2023 – Theriva™ Biologics (NYSE American: TOVX), (“Theriva” or the “Company”), a clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, today announced new clinical data from the Phase 1 investigator-sponsored study with the Institut Catala d’Oncologia (ICO) evaluating VCN-01 in combination with durvalumab for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). These data were presented at the European Society for Medical Oncology (ESMO) Congress, held both virtually and in Madrid, Spain from October 20-24, 2023.

“Results presented at ESMO further validate VCN-01’s unique mechanism of action for devastating cancers with high unmet need,” said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. “We are encouraged by the data generated to date, highlighted by the enhanced patient survival, correlating with VCN-01 mediated increases in the CPS score, a key determinant of outcomes with anti-PD-(L)1 checkpoint inhibitor therapies. These results build on the previously reported acceptable safety profile seen with sequential dosing of VCN-01 and durvalumab. Taken together, we believe VCN-01 based combinations may address the need for improved treatments with the potential to overcome previous resistance to anti-PD-(L)1 therapies in patients with R/M HNSCC.”

The poster (#937P) titled “Survival Outcomes in Phase I Trial Combining VCN-01 and Durvalumab (MEDI4736) in Subjects with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Previous Immunotherapy Treatment,” was presented by Maria Jové (Hospitalet de Llobregat, Spain).

Presentation Highlights:

Key Takeaway: VCN-01 combined with durvalumab showed encouraging overall survival (OS) in patients who previously progressed on anti-PD(L)-1 therapy.

·	Survival:<br>VCN-01 induced upregulation of PD-L1, which correlated with enhanced patient survival.
·	In<br>the concomitant (CS) cohort at the 3.3×10^12^ viral particles (vp) dose, overall survival<br>(OS) was 10.4 months and progression free survival (PFS) was 1.7 months.
---	---
·	In the sequential (SS) cohort at the 3.3×10^12^vp dose<br>OS was 15.5 months and PFS was 3.7, whereas in the SS cohort at the 1×10^13^ vp dose<br>OS was 17.3 months and PFS was 2.1 months.
---	---
·	VCN-01induces changes in the immune status of tumors
---	---
·	VCN-01<br>combined with durvalumab increased CD8 T cells, a marker of tumor inflammation and the expression of PD(L)-1 in tumors. An increase of<br>PD(L)-1 CPS (8/11 at day 8; 8/10 at day 28) and CD8 T cells (7/11 at day 8; 5/10 at day 28) from baseline were found in tumor biopsies.
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·	VCN-01<br>alone increased the CPS score of tumor biopsies at day 8 after administration by 62.5% in the sequential arm.
·	VCN-01<br>induced PD(L)-1 upregulation with enhanced patient survival. A statistical correlation was observed between CPS on day 8 and patient<br>OS (p=0.005).
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·	Pharmacodynamicsand shedding of VCN-01
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·	PH20<br>expression from VCN-01 peaked on day 3-8 and remained elevated in some patients up to day 42. Quantification of VCN-01 genomes in stool<br>demonstrated viral shedding that peaked at day 8.
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KOL Webinar on Monday, October 23, 2023 at 8:00 a.m. ET (2:00 p.m.CEST)

The webinar will feature KOL, Ricard Mesia, M.D., Ph.D., head of Medical Oncology Department at Catalan Institut of Oncology in Barcelona. Dr. Mesia will discuss the unmet medical need in the head and neck cancer treatment landscape, the current limitations, and the need for new approaches, along with the key takeaways from Theriva’s ESMO poster presentation. A live Q&A session will follow the formal discussion. To register for the event, please click here. An archived webcast will also be accessible in the “Events” section of the company’s website at www.therivabio.com.

About VCN-01

VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to over 80 patients in Phase 1 and investigator-sponsored clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection).

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 wholly-owned Spanish 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. In addition to VCN-01, the Company’s clinical-stage candidates include: (1) 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 (2) 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 statementswithin the meaning of the Private Securities Litigation Reform Act of 1995. In some cases forward-looking statements can be identifiedby terminology such as “may,” “should,” “potential,” “continue,” “expects,” “anticipates,” “intends,” “plans,” “believes,” “estimates,” and similar expressions,and include statements regarding VCN-01 based combinations addressing the need for improved treatments with the potential to overcomeprevious resistance to anti-PD-(L)1 therapies in patients with R/M HNSCC. These forward-looking statements are based on management’sexpectations and assumptions as of the date of this press release and are subject to a number of risks and uncertainties, many of whichare difficult to predict that could 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 to differ materially from currentexpectations include, among others, the Company’s ability to complete enrollment in its trials when anticipated, the Company’sability to address the unmet medical needs for treatment of cancer and related diseases, the Company’s ability to take advantageof the potential benefits of orphan drug designation, the Company’s ability to reach clinical milestones when anticipated, the Company’sability to successfully operate the combined US and Spanish business entities , the Company’s product candidates demonstrating safetyand effectiveness, as well as results that are consistent with prior results; the ability to complete clinical trials on time and achievethe desired results and benefits, continuing clinical trial enrollment as expected; the ability to obtain regulatory approval for commercializationof product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to the Company’s abilityto promote or commercialize their product candidates for the specific indications, acceptance of product candidates in the marketplaceand the successful development, marketing or sale of the Company’s products, developments by competitors that render such productsobsolete or non-competitive, the Company’s ability to maintain license agreements, the continued maintenance and growth of the Company’spatent estate, the ability to continue to remain well financed and other factors described in the Company’s Annual Report on Form10-K for the year ended December 31, 2022 and its other filings with the SEC, including subsequent periodic reports on Forms 10-Q andcurrent reports on Form 8-K. The information in this release is provided only as of the date of this release, and Theriva Biologics undertakesno 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

ccalabrese@lifesciadvisors.com

917-680-5608

Exhibit 99.2

937P Survival outcomes in Phase I trial combining VCN-01 and Durvalumab (MEDI4736) in Subjects With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma refractory to previous immunotherapy treatment. Background Jove Maria1 , Braña Irene2 , Oliva Marc1 , Hernando Alberto 2 , Erasun Carlos 1 , Assaf Juan David 2 , Mato-Berciano Ana 3 , Maliandi Maria Victoria 3 , Torres-Manjon Silvia 4,5 , Moreno Rafael 4,5 , Le Charles3 , Nuciforo Paolo7 , Alemany Ramon4,5 , Capellà Gabriel 5 , Blasco Carmen 3 , Cascallo Manel 3 , Mesia Ricard 7* 1 Medical Oncology Department, Institut Catala d'Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain; 2 Vall d´Hebron University Hospital & Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 3 Theriva Biologics, Parets 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 Molecular Oncology Group, VHIO, Barcelona, Spain; 7 Medical Oncology Department, Institut Catala d'Oncologia, Badalona, B-ARGO group, IGTP, Badalona, Spain This research was conducted with support from AstraZeneca Farmacéutica Spain, S.A. 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. • Encouraging survival was observed in patients treated with systemic VCN-01 with durvalumab after progressing on anti-PD(L)-1 agents. • VCN-01-induced upregulation of PD-L1, which correlated with enhanced patient survival. Conclusions Hypothesis Systemically administered VCN-01 will undergo intratumoral viral replication and cause tumor inflammation, PD-1/PD-L1 up-regulation and strong CD8-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 (3,3E12 & 1E13 viral particles, [vp]) combined with a fixed dose of Durvalumab (1500 mg) using 3+3 design in patients with metastatic squamous cell carcinoma of the head & neck previously treated with antiPD(L)-1 agents (R/M HNSCC). 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 q4 weeks until progression or intolerable toxicity. Fresh tumor biopsies were taken at baseline, post-VCN-01 and post-Durvalumab. Study Population: R/M HNSCC patients 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. Results NCT03799744 is a multi-center, open-label dose-escalation phase I study to investigate the safety and tolerability of i.v. VCN-01 with Durvalumab in the two regimens of administration and to establish the recommended phase II dose. *Address correspondence to: Ricard Mesía (rmesia@iconcologia.net) Trial Design & Methods Demographics Figure 1: Patient demographics and clinical characteristics Survival Figure 2: Kaplan-Meier Curves of PFS (upper graph) and OS (lower graph) in the different arms of the trial NCT03799744 trial. 0 5 10 15 20 25 30 10 0 10 1 10 2 10 3 10 4 10 5 10 6 50 100 150 VCN-01 genomes in Stool Days post VCN-01 Viral genomes/200mg Stool LOQ 2x10 4 vg/200mg Sequential Low dose (3.3E12vp) Sequential High dose (1E13vp) Concomitant Low dose (3.3E12vp) ARM ICI Treatment (Pre-trial) Current Trial 1st Line after Current Trial 2nd Line after Current Trial Median OS post-1st ICI ORR Median PFS Median OS ORR Median PFS Median OS ORR Median PFS Median OS Concomitant Low (3.3E12vp) 21.6 (19.2-NE) 0/6 1.7 (1.6-NE) 10.4 (8.9-NE) 3/5 3.7 (0.4-NE) 7.4 (5.7-NE) 1/2 2.0 (0.6-NE) 3.3 (2.3-NE) Sequential Low (3.3E12vp) 23.9 (16.6-NE) 1/6 3.7 (2.2-NE) 15.5 (15.1-NE) 3/6 5.7 (2.9-NE) 12.1 (9.5-NE) 1/6 0.7 (0.7-NE) 6.2 (4.8-NE) Sequential High (1E13vp) 21.8 (12.9-NE) 0/6 2.1 (1.4-NE) 17.3 (11.3-NE) 2*/5 2.2 (1.9-NE) 12.6 (8.4-NE) 1/4 3.7 (2.4-NE) 10.6 (5.0- NE) Pharmacodynamics and Shedding of VCN-01 0 3 8 28 42 70 98 126 0 100 200 300 400 500 600 700 PH20 in serum (pg/ml) PH20 in serum Days post-VCN-01 PH20 expression from VCN-01 peaks on D3-D8 and remains elevated in some patients up to D42. Viral shedding in stool peak at D8 VCN-01 induces changes in the immune status of tumors Figure 4: Clinical Outcomes for each line of treatment before and after clinical trial participation Median values (95% CI) per KM; *Complete response SCR Peak -50 0 50 100 150 Intratumoral CPS (CPS peak D8 or D28) CPS score ✱ P value 0.0137 1 8 0 20 40 60 80 100 CPS Dynamic change (Peak D8 or D28) CPS score SCR Peak 1-C-05 2-C-04 1-C-03 1-S-25 2-S-13 1-S-21 2-S-11 2-S-09 1-S-18 2-S-08 2-S-04 1-S-03 1-S-02 1-S-01 SCR Peak -500 0 500 1000 1500 2000 2500 Intratumoral CD8 (Peak: D8 or D28) CD8 (cells/mm2) ✱✱ P value 0.0067 1 8 0 500 1000 1500 2000 CD8 Dynamic change (Peak: D8 or D28) CD8 (cells/mm2) 1-S-01 1-S-02 1-S-03 2-S-04 2-S-08 1-S-18 2-S-09 2-S-11 1-S-21 2-S-13 1-S-25 1-C-03 2-C-04 1-C-05 SCR Peak Figure 6: Expression analysis of PDL1 (CPS score) and CD8 in tumor biopsies after and post-treatment. Upper table shows % of samples showing modulation (positive / total analyzed samples). IHC analysis of PDL1 (CPS score, left graph) and CD8 immune markers (right graph) in tumor biopsies at day 0 (pre-treatment, SCR) and day 8 or day 28 (Peak) after VCN-01 intravenous administration. Wilcoxon matched-pairs signed rank test was used to determine statistical significance against pre-treatment expression levels. Lower graph: Dynamic change of CPS (left graph) and CD8 (right graph) intratumoral expression for each patient between pre-treatment and D8 or D28 (Peak). Expression increases are indicated in green lines and expression reductions are indicated in black lines. VCN-01 combined with Durvalumab increases the expression of PD-L1 and CD8 in tumor cells Figure 7: Increase of PD-L1 expression in tumor biopsies after VCN-01 treatment but in the absence of Durvalumab (Day 8, Sequential arm). Upper table shows % of samples showing modulation (positive / total analyzed samples). Only paired samples were included in the analysis. IHC of PD-L1 in tumor biopsies for PD-L1 at day 0 (pre-treatment) day 8 after VCN-01 intravenous administration only in the Sequential arm. 8 out of 12 patients in the Sequential arm had paired biopsies at day 0 and day 8 (n=8). % of samples showing modulation (positive / total analyzed samples). Anti-PD-L1 IHC images of tumor biopsies from patient 1-S-03 at day 0 and day 8 (5x and 20x of magnification). PD-L1 CPS ( Only sequential Arm) D8 (before Durvalumab dosing) 62.5% ↑ (5/8) VCN-01 alone increases the CPS score of tumor biopsies at day 8 after administration Initial evidence suggests that VCN-01 induced PD-L1 upregulation could enhance patient survival 0 20 40 60 80 100 0 10 20 30 40 50 0.1114 OS vs CPS SCR CPS score OS (months) Spearman r 0 20 40 60 80 100 0 10 20 30 40 50 OS vs CPS D8 CPS score OS (months) Spearman r 0.7676 P (two-tailed) 0.0050 ** Figure 8: Association between the OS and the CPS score. Association between the OS and the CPS score at day 0 (pre-treatment) and day 8 (8 days after VCN-01 intravenous administration) for all the patients. Data was assessed by Spearman’s correlation. The correlation coefficient (r) and the p-value are in the graph. PD-L1 CPS CD8 D8 (all arms) 73% ↑ (8/11) 64% ↑ (7/11) D28 (all arms) 80% ↑ (8/10) 50% ↑ (5/10) Figure 3: Swimmer plot depicting clinical course of enrolled patients in the NCT03799744 trial. A) Concomitant arm 3.3E1 vp/patient of VCN-01; B) Sequential arm 3.3E12 vp/patient of VCN-01; C) Sequential arm 1E13 vp/patient of VCN-01. Each bar represents 1 patient and extends for the length of its overall survival. Best observed responses are indicated as SD (stable disease), PR (partial response), PD (progressive disease). Patients experiencing dose-limiting toxicities are indicated as DLT. The subsequent lines of treatment after PD in NCT03799744 trial are indicated with color symbols (graph legend). CX-2029 (Probody drug –Conjugate Anti-CD71); MTX (Methotrexate); T. TheraT® (T. TheraT® Vectors Expressing HPV16 Specific Antigens); GE (Gemcitabine); CBDCA (Carboplatin); CET (Cetuximab); CDDP (Cisplatin); PTX (Paclitaxel). * HPV positive VCN-01 combined with Durvalumab showed encouraging OS in patients who previously progressed on Anti-PD(L)-1 therapy Acknowledgements A B C Dr. Jove: Speaker’s bureau: AstraZeneca, MSD; travel and accommodation support: MSD, Roche, AstraZeneca. Dr. Mesia: Advisory role with honoraria:Merck, Nanobiotix, MSD, BMS, Roche, Seagen (formerly Seattle Genetics), AZ, Pfizer, Boehringer, PDS. Speaker bureau with honoraria: Merck, MSD, Boehringer. Mato-Berciano,A; Maliandi,MV; Le,C; Alemany,R; Blasco,C. & Cascallo,M are employees and stock owners of Theriva Biologics. Survival Figure 5: Quantification of PH20 expression in serum (upper graph). PH20 expresión was measured on serum by ELISA in serum from treated patients (Concomitant Arm and Sequential Arm Low dose) at different time points. PH20 expression is expressed as pg/mL minus background levels detected for each sample at day 0 (pre-treatment). Quantification of VCN-01 genomes in stool (lower graph). VCN-01 viral genomes were detected in stool at different times after administration. VCN-01 genomes were quantified by qPCR, in both arms, sequential and concomitant. The study team thanks patients and their caregivers for their willingness to participate in this clinical trial. The authors thank the investigators and research staff in participating institutions, and the Epithelial Carcinogenesis Group at CNIO (Spain) for technical support. Disclosure