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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): 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
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 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:
VCN-01 induced upregulation of PD-L1, which correlated with enhanced patient survival. |
| · | In
the concomitant (CS) cohort at the 3.3×1012 viral particles (vp) dose, overall survival
(OS) was 10.4 months and progression free survival (PFS) was 1.7 months. |
| · | In
the sequential (SS) cohort at the 3.3×1012vp dose OS was 15.5 months and PFS was
3.7, whereas in the SS cohort at the 1×1013 vp dose OS was 17.3 months and PFS was
2.1 months. |
| · | VCN-01
induces changes in the immune status of tumors |
| · | VCN-01
combined with durvalumab increased CD8 T cells, a marker of tumor inflammation and the expression of PD(L)-1 in tumors. An increase of
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. |
| · | VCN-01
alone increased the CPS score of tumor biopsies at day 8 after administration by 62.5% in the sequential arm. |
| · | VCN-01
induced PD(L)-1 upregulation with enhanced patient survival. A statistical correlation was observed between CPS on day 8 and patient
OS (p=0.005). |
| · | Pharmacodynamics
and shedding of VCN-01 |
| · | PH20
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
demonstrated viral shedding that peaked at day 8. |
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:
VCN-01 induced upregulation of PD-L1, which correlated with enhanced patient survival. |
| · | In
the concomitant (CS) cohort at the 3.3×1012 viral particles (vp) dose, overall survival
(OS) was 10.4 months and progression free survival (PFS) was 1.7 months. |
| · | In
the sequential (SS) cohort at the 3.3×1012vp dose OS was 15.5 months and PFS was
3.7, whereas in the SS cohort at the 1×1013 vp dose OS was 17.3 months and PFS was
2.1 months. |
| · | VCN-01
induces changes in the immune status of tumors |
| · | VCN-01
combined with durvalumab increased CD8 T cells, a marker of tumor inflammation and the expression of PD(L)-1 in tumors. An increase of
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. |
| · | VCN-01
alone increased the CPS score of tumor biopsies at day 8 after administration by 62.5% in the sequential arm. |
| · | VCN-01
induced PD(L)-1 upregulation with enhanced patient survival. A statistical correlation was observed between CPS on day 8 and patient
OS (p=0.005). |
| · | Pharmacodynamics
and shedding of VCN-01 |
| · | PH20
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
demonstrated viral shedding that peaked at day 8. |
Item 9.01. Financial Statements and Exhibits.
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: October 23, 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 Presents Survival Outcomes
Data from Phase 1 Study Evaluating VCN-01 in Combination with Durvalumab in Patients with Recurrent/Metastatic Squamous Cell Carcinoma
of the Head and Neck at ESMO Congress 2023
-Results show 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-
-Key Opinion Leader (KOL) webinar featuring
expert 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:
VCN-01 induced upregulation of PD-L1, which correlated with enhanced patient survival. |
| · | In
the concomitant (CS) cohort at the 3.3×1012 viral particles (vp) dose, overall survival
(OS) was 10.4 months and progression free survival (PFS) was 1.7 months. |
| · | In the sequential (SS) cohort at the 3.3×1012vp dose
OS was 15.5 months and PFS was 3.7, whereas in the SS cohort at the 1×1013 vp dose
OS was 17.3 months and PFS was 2.1 months. |
| · | VCN-01
induces changes in the immune status of tumors |
| · | VCN-01
combined with durvalumab increased CD8 T cells, a marker of tumor inflammation and the expression of PD(L)-1 in tumors. An increase of
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. |
| · | VCN-01
alone increased the CPS score of tumor biopsies at day 8 after administration by 62.5% in the sequential arm. |
| · | VCN-01
induced PD(L)-1 upregulation with enhanced patient survival. A statistical correlation was observed between CPS on day 8 and patient
OS (p=0.005). |
| · | Pharmacodynamics
and shedding of VCN-01 |
| · | PH20
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
demonstrated viral shedding that peaked at day 8. |
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 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 VCN-01 based combinations addressing the need for improved treatments with the potential to overcome
previous resistance to anti-PD-(L)1 therapies in patients with R/M HNSCC. 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 Company’s ability to complete enrollment in its trials when anticipated, the Company’s
ability to address the unmet medical needs for treatment of cancer and related diseases, the Company’s ability to take advantage
of the potential benefits of orphan drug designation, the Company’s ability to reach clinical milestones when anticipated, the Company’s
ability to successfully operate the combined US and Spanish business entities , the Company’s product candidates 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 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 products, developments by competitors that render such products
obsolete or non-competitive, the Company’s ability to maintain license agreements, the continued maintenance and growth of the Company’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, 2022 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
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.
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