❖ GL-ONC1 treatments are well tolerated, with transient overnight flu-like

symptoms. Daily i.v. hydration during treatment relieved symptoms

and prevented dehydration.

❖ Mechanisms of Action are demonstrated:

➢ Direct lysis: Virus colonized and replicated in the tumor, killing of

tumor cells in ascites, and reduced circulating tumor cells.

➢ Immunotherapy: Virus-induced immune activation with enhanced

tumor infiltration of CD8+ T cells and generation of tumor-specific T-

cell response were observed.

❖ Clinical significant disease control (including objective response) and

extended PFS were documented at both dose levels.

❖ Phase 2 trial (VIRO-15) in ROC pts with adequate nutritional & immune

status is currently enrolling at Cohort 1 dose level.

#5577 Phase 1b Study of Oncolytic Vaccinia Virus GL-ONC1 in Recurrent Ovarian Cancer

RESULTS

❖ Primary

Analysis of adverse events

❖ Secondary

Anti-tumor response by RECIST1.1 & survival (PFS/OS)

❖ Translational

Evaluate virus-encoded transgene expression, tumor biomarkers, circulating

tumor cells (CTCs), TILs in tumor biopsy, tumor-specific T-cell response in

peripheral blood, cytology in ascites, immunohistochemistry of PD-L1 expression

in tumor biopsies pre- and post-GL-ONC1 Tx.

OBJECTIVES

CONCLUSIONS

Acknowledgement: All staff at Genelux for support; Prof. Lisa Butterfield

lab at Univ. of Pittsburg for ELISPOT analysis. Funding for this research

was provided by Genelux Corporation, San Diego, California, USA

June 1-5, 2018; Chicago, IL, USA; Corresponding author: robhollowaymd@gmail.com

Patient CharacteristicsEleven heavily pretreated end-stage ROC pts were enrolled:

❖ Characteristics related to prior platinum Tx:

Platinum-resistant (n=9; 82%), Platinum-refractory (n=1;

9%), Intermediate platinum-sensitive (n=1; 9%)

❖ # of prior lines therapy: 3-4 (n=3; 27%), ≥ 5 (n=8; 73%)

❖ ECOG 0 (n=7; 64%) or 1 (n=4; 36%)

❖ With ascites/pleural effusion at baseline (n=9; 82%)

❖ Progressive disease (PD) at baseline (n=10; 91%)

❖ Cohort 1: 3 × 109 pfu (n=6); Cohort 2: 1 × 1010 pfu (n=5)

Protocol #: GL-ONC1-015; ClinicalTrials.gov Identifier: NCT02759588; Copyright © 2018 Genelux Corp. All rights reserved.

ABSTRACT

Safety

Tumor Infiltrating Lymphocytes (TILs)

Anti-Tumor Response & Disease Control Observed

Distal Anti-tumor Effects from i.pe. Route of Delivery

Case Report (Ch1: #15A-05): OR & Tumor-specific T-cell Response

Clinical trial design considerations:

➢ I.pe. route of drug delivery is relevant

to ovarian cancer (OC)

➢ OCs are immunogenic → VACV is

excellent adjuvant for tumor antigen

presentation

➢ High tumor-infiltrating lymphocytes

(TILs) favors survival → Oncolytic

VACV stimulates TILs

➢ Oncolytic VACV may overcome

chemo- and/or radiation-resistance

➢ For patients with chemo resistant

ovarian cancer that would otherwise

consider palliative care or use of drugs

with poor Response Rate

❖ Disease Control Rate (DCR = OR + SD≥15 wks) = 55 % in 6/11 evaluable

pts (4 in Ch1, 2 in Ch2).

❖ Extended PFS of 23, 35, 59 (with confirmed PR) & 71 wks observed in 4

pts (3 in Ch1, 1 in Ch2).

❖ More than doubling of PFS compared to the last chemotherapy regimen

was recognized in 4/11 (36%) pts (2 in Ch1, 2 in Ch2).

❖ Heavily treated w/ 9 prior regimens of chemo; no Tumor-specific T-cell response at baseline

❖ Documented Objective Response (OR) from GL-ONC1 Tx after Failure of Last Chemotherapy

❖ Favorable & long-lasting Tumor-specific T-cell Response (TSTcR) by ELISPOT analysis

Exemplary IHC analysis - pt.#15A-06, with PFS of 71 weeks:

Significant infiltration of CD8+ cytotoxic T cells into tumors

after virus treatment indicates activation of immunosurveillance

Clinically Significant Results

Immune Modulation

peritoneal fluid

Prior to 1st dose

W2D17

W2D12

pleural fluid

W2D9

W2D15

W2D17

Robust lymphocyte count increase

(immune activation)

Direct lysis of cancer cells &

immune activation in different

cavities

Tumor cell clusters present

Tumor cell clusters absent

Decrease of

Circulating Tumor

Cells (CTCs)

may indicate systemic

effect against metastases

Baseline 5-mon post Tx

Objective response (OR) of metastatic lesions

pancreatic met.

liver met.

No any other Tx in the meantime0

5

10

15

20

25

30

35

40

45

CT

C C

OU

NT P

RE-

& P

OST T

X

baseline post Tx

Flu-like symptoms in general;

lasting a few hours overnight

post each Tx

No DLT; MTD not reached

No discontinuation due to

treatment-related AEs

Summary:

GL-ONC1 Tx is well tolerated.

baseline Week 36

CD3 CD8

Baseline 2.94 0.58

Week 36 5.06 3.54

0

1

2

3

4

5

6

Cel

l Co

un

ts P

er

80

x Fi

eld

Immune Cell Counts in Tumor biopsies

p<0.001

CD3+

CD8+

p<0.001

Acute inflammatory responses and PD-L1 upregulation in tumors by oncolytic

virus GL-ONC1 can sensitize tumors to PD-1/PD-L1 blockade.

Adverse Events # of Pts (n=11)

Grades 1 & 2 AEs (occurred in ≥ 3 patients)

Chills 7 (63.6%)

Nausea 7 (63.6%)

Fever 6 (54.5%)

Abdominal distention 4 (36.4%)

Abdominal pain 4 (36.4%)

Vomiting 3 (27.3%)

Grade 3 AEs (occurred in the same patient)

Nausea 1 (9.1%)

Vomiting 1 (9.1%)

No Grade 4 AEs

Robert W Holloway1, James E Kendrick1, Amanda J Stephens1, Jessica A Kennard1, Jeremy Burt2, Jane LeBlanc3, Karen Sellers3, Jamie Smith3, and Susan Coakley3

1Gynecologic Oncology Program, Florida Hospital Cancer Institute, Orlando, Florida; 2Department of Radiologic Services, Florida Hospital, Orlando, Florida; 3Office of Clinical Research, Florida Hospital Cancer Institute, Orlando, Florida

0 10 20 30 40 50 60 70 80 90 100

Swim Lane Plot of Survival & Tumor Response by RECIST 1.1

PRSDPDAlive

WEEKS

1Y

ear

Wee

k 2

4

15A-0515A-0615A-0915A-0415A-1515A-0215A-0115A-1015A-0315A-1315A-07

Cohort 1

Cohort 2

(Data cut off: April 17, 2018)

Prophylactic hydrations given

daily to avoid dehydration, and

to reduce symptoms

Background: Immunotherapy can trigger immune activation including tumor-infiltrating

CD8+ T cells, leading to antitumor response and survival benefits. Immunotherapeutic

GL-ONC1 (modified vaccinia virus (VACV)) causes oncolysis, immune activation and

durable anti-cancer memory.

Methods: Intraperitoneal (i.pe.) infusion of GL-ONC1 monotherapy was given at high

repeated doses in patients (pts) with platinum refractory/resistant disease. Primary

endpoint: adverse events; Secondary endpoints: anti-tumor response by RECIST1.1 &

survival. Eleven heavily pretreated pts with end-stage recurrent ovarian cancer (ROC)

were enrolled: 3-4 prior lines (n=3), ≥ 5 lines (n=8), ECOG 0 (n=7) or 1 (n=4),

ascites/pleural effusion (n=9) & progressive disease (PD) at baseline (n=10). There

were two dose cohorts: 3 × 109 (Cohort 1: n=6) or 1 × 1010 (Cohort 2: n=5) plaque

forming units/day on 2 consecutive days.

Results: (1) Adverse reactions included Grade 1-2 chills (n=7), nausea (7), fever (6),

abdominal pain/distention (4), & vomiting (3). There were no differences in toxicity for

the two dose levels. (2) GL-ONC1 colonized and replicated in the tumor, as indicated by

a virus-encoded glucuronidase (GusA) assay. (3) Clearance of tumor cells in ascites

with induction of lymphocyte infiltration was shown in 5 pts with ascites. (4) Reduction of

circulating tumor cells (CTC) was identified in 6/8 (75%) pts who had baseline CTC,

ranging 1-42 per 7.5 mL blood. (5) Enhanced infiltration of CD8+ T cells into tumor

tissue was demonstrated by repeat biopsy. (6) A tumor-specific T cell response was

absent at baseline but confirmed at Week-30 in patient with objective response (OR) by

IFN-γ ELISPOT assay. (7) Disease Control Rate (DCR = OR + stable disease (SD) ≥ 15

weeks) was 6/11 (55%). (8) Extended progression-free survival (PFS) of 23, 35, 59

(with confirmed PR) & 71 weeks were observed in 4 pts, respectively. (9) More than

doubling of PFS compared to the last chemotherapy regimen was recognized in 4/11

(36%) pts.

Conclusions: Promising safety data, anti-tumor activity, and immune activation

mechanisms were documented in this Ph1b trial, and a Ph2 trial (VIRO-15) is currently

enrolling. Future studies combining GL-ONC1 and other immune therapies and/or

chemotherapy are under consideration.Biomarkers

1.0E-04

1.0E-03

1.0E-02

1.0E-01

1.0E+00

1.0E+01

1.0E+02

0 2 4 6 8 10 12 14

Gu

sA a

ctiv

ity

in b

loo

d [

un

its/

mL]

DaysLOD: limit of detection

Virus-encoded glucuronidase

LOD

-70

-60

-50

-40

-30

-20

-10

0

10

20

Be

st c

han

ge o

f C

A-1

25

fro

m

bas

elin

e (

%)

9/11 (82%) pts experienced

CA-125 reduction

Cohort 1Cohort 2

Tumor shrinkage observed

by RECIST1.1

-40

-30

-20

-10

0

10

20

30

40

Be

st c

han

ge o

f SL

D f

rom

bas

elin

e (

%)

Partial response

Progressive disease

Individual target lesion changeTarget lesion SLD change overtime

➢ 17/38 (45 %) individual target lesions had size

reduction

➢ In 4 pts with SLD reduction, all individual target

lesions had reduction in size

-70-60-50-40-30-20-10

0102030405060708090

100

13

15 7 7

15

10 3

15 7 3 7 6 9

10 3 7

10

15

13

13 2

13

10 4 4 4

13 4 2 2 1 5 1 5 4 5 5 5

Be

st c

han

ge o

f in

div

idu

al t

arge

t le

sio

n s

ize

fro

m b

ase

line

(%

)

Patient ID #

Progressive disease

Partial response

-40

-30

-20

-10

0

10

20

30

40

0 5 10 15 20 25 30 35 40 45

Ove

rtim

e c

han

ge o

f SL

D f

rom

bas

elin

e (

%)

WEEKS

PDSDPRCohort 1

Cohort 2

Strong PD-L1 staining at the

tumor-stromal interface

Baseline

GL-ONC1 Upregulates

Immunomodulatory Target

Proteins, such as PD-L1

20 days post Tx

SLD: sum of longest diameters

120

140

160

180

200

220

240

260

280

300

SLD

(m

m)

SLD of target lesions over time

pemetrexed

GL-ONC1 Tx

+ 90% PD

- 34% PR

Wks

Last Chemotherapy: Pemetrexed

3/30-5/18/2016

Progressive disease (PD)

(CT scans on 6/30/2016 & 8/30/2016)

GL-ONC1 Tx

Partial response

(confirmed on Week 24 & 36; durable)

Stable disease @ Week 48

(-27% compared to baseline)

Confirmed

TSTcR

No TSTcR

0 18 36-24