Viral Immunotherapies for Cancer - NASDAQ: ONCR Corporate Presentation - Investor ...
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NASDAQ: ONCR
Viral Immunotherapies
for Cancer
Corporate Presentation
November 2021
1
Disclaimer and Forward -Looking Statements
This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, that reflect the current beliefs, expectations
and assumptions of Oncorus, Inc. (the “Company”) regarding the future of its business, its future plans and strategies, clinical results, future financial condition and other future conditions,
including, without limitation, implied and express statements regarding: the Company’s ability to advance its clinical and preclinical pipelines, including statements regarding the clinical
development of ONCR-177 and the timing of anticipated further data read-outs for the ongoing Phase 1 clinical trial; ONCR-177’s therapeutic potential and clinical benefits and the utility
and potential of the Company’s HSV platform generally; the Company’s expectations regarding upcoming milestones for its product candidates, including the expected timing of IND
submissions for ONCR-021 and ONCR-GBM, as well as the product candidates’ therapeutic potential and clinical benefits and the utility and potential of the Company’s Synthetic vRNA
immunotherapy platform; the Company’s expectations around its GMP facility being fully operational and the benefits of developing in-house manufacturing capabilities and their impact
on the Company’s ability to achieve its clinical milestones; and the Company’s belief that its current cash resources will be sufficient to fund its operations and capital expenditure
requirements into late 2023. The words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,”
“project,” “potential,” “continue,” “target” and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these
identifying words. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and
important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including,
without limitation, risks associated with: the impact of COVID-19 or variants thereof on the Company’s operations and the timing and anticipated results of its ongoing and planned
preclinical studies and clinical trials; the risk that the preliminary results of preclinical studies or clinical trials may not be predictive of results in future preclinical studies or clinical trials;
the Company’s ability to successfully demonstrate the safety, tolerability and efficacy of ONCR-177; the Company’s ability to obtain regulatory approval for ONCR-177 or any of its product
candidates; the Company’s ability to advance its preclinical and clinical activities in a timely and cost-effective manner; the Company’s ability to obtain, maintain and protect its intellectual
property; the adequacy of the Company’s cash resources and availability of financing on commercially reasonable terms; the accuracy of the Company’s estimates regarding expenses,
future revenue, capital requirements and needs for additional financing; the Company’s financial performance; the sufficiency of the Company’s existing capital resources to fund future
operating expenses and capital expenditure requirements; and the Company’s anticipated use of existing resources. These and other risks and uncertainties are described in greater detail
in the section entitled “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2020, which was filed with the Securities and Exchange Commission
on March 10, 2021, as well as discussions of potential risks, uncertainties, and other important factors in the other filings that the Company makes with the Securities and Exchange
Commission from time to time. These documents are available under the “SEC filings” page of the Investors section of the Company’s website at http://investors.oncorus.com. Any
forward-looking statements in this presentation represent the Company’s views only as of the date of this presentation and should not be relied upon as representing its views as of any
subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. No
representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal
estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no
representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. Finally, while the Company believes its own internal research
is reliable, such research has not been verified by any independent source.
This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently
limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated.
2
O ve r v i e w
Our Mission is to realize the full promise of viral immunotherapy for cancer
Developing two platforms to drive systemic activity
Building in house manufacturing for timely delivery of clinical programs
Multiple upcoming catalysts
3
V i ra l i m m u n o t h e ra p i e s s e l e c t i ve l y re p l i c ate d i n a n d k i l l t u m o r
c e l l s a n d a c t i vate m u l t i p l e a r m s o f t h e i m m u n e sy ste m
Selective
replication1
Immunogenic
oncolysis2
Broad immune
stimulation
1. Ehrlich & Bacharach, Cancers, (2021); 2. Pol, et al., Cytokine Growth Factor Rev (2020)
4
I m p ro ve m e nt s ove r E x i st i n g V i ra l I m m u n o t h e ra p i e s i n Sy ste m i c
I m m u n e A c t i vat i o n & Tu m o r K i l l i n g
Herpes Simplex Viruses
• Armed with multiple
immunomodulatory payloads
• miR-based safety strategies to
Intratumoral
control replication
Synthetic RNA Viruses
• Viral RNA (vRNA) genomes
encapsulated within LNPs to
enable repeat IV administration Intravenous
5
Pipeline
IND-
Candidate Platform RoA Indications Discovery Enabling Phase 1 Phase 2 Phase 3
ONCR-177 Head & Neck • Mid ‘22: additional monotherapy &
IL-12, FLT3L, CCL4, HSV iTu Melanoma Monotherapy and combination with preliminary combination & visceral data
aPD-1 & aCTLA-4 Triple Neg. Breast • Late ’22: visceral & combination data
Non-small cell lung
ONCR-021 Renal cell IND in 1H’23*
vRNA IV Melanoma
Synthetic CVA21
Hepatocellular
ONCR-GBM HSV iTu Glioblastoma IND in 2H’23*
Multiple payloads
Small cell lung
ONCR-788 vRNA IV NE prostate
Synthetic SVV
Merkel cell
Oncorus retains worldwide rights to all programs. RoA=route of administration; iTu=intratumoral injection; NE=neuroendocrine 6
*contingent upon availability of future funding
ONCR-177
7
P ro p r i eta r y H SV P l at fo r m
Selective replication... …enables… …to allow for…
Retention of Interferon
g34.5 resistance
• Most HSVs delete g34.5
Tumor-specific, • Safety & tolerability similar
miRs
unencumbered replication + to other iTu approaches
• Improved outcomes
• Alnylam-like RNA silencing via RISC/Ago2
• Few other OVs use miR attenuation
Arming with
5 multiple payloads
• To drive immune response
• mRNA-2752 & RP3 only contain
3 immunomodulatory payloads
8
O N C R - 1 7 7 : m i R N A - Atte n u ate d H e r p e s S i m p l ex V i r u s - 1
reta i n s g 3 4 . 5 & a r m e d w i t h 5 I m m u n o m o d u l ato r y Pay l o a d s
Oncorus HSV Platform ONCR-177
Orthogonal Safety • Attenuation in normal cells by microRNAs
Strategies • UL37 mutations to protect neurons against infection
Full Replication • g34.5 enables replication in the presence of interferon
Competency and
Enhanced Potency • gB:N/T mutations enhance infectivity & entry rate
Rationally Designed • IL-12 (NK & T cells), FLT3L (cDCs) & CCL4 (trafficking)
Payloads • Anti-CTLA-4 & anti-PD-1 to counteract checkpoint upregulation
ONCR-177=HSV-1, ICP34.5+, ICP47-, gB N/T mutation, UL37 mutations, multiple miRs, IL-12, FLT3L, CCL4, anti-PD-1 & anti-CTLA-4; Note: the null mutations in ICP47 improve
antigen presentation in addition to broaden tropism & improved infectivity via gB-N/T surface fusion protein mutation (allows for infection via not only HVEM & nectin-1 but also 9
nectins-2, 3 & 4 (Uchida, 2010)); Nectin-4 has been reported to be expressed on a wide variety of tumors (Challita-Eid, Cancer Res, 2016))
Key F i n d i n g s , a s o f N ove m b e r 8 , 2 0 2 1
• ONCR-177 has been well-tolerated with no dose-limiting toxicities
• Surface lesion monotherapy dose escalation completed (n=14)
‒ Surface lesion dose expansion monotherapy cohorts initiated
‒ Recommended Phase 2 dose (RP2D) was determined to be 4x108 PFU in 4 mL
‒ At RP2D, manageable inflammatory symptoms in line with other viral immunotherapies were reported
• Of the eight evaluable patients treated at the recommended Phase 2 dose of ONCR-177,
three patients observed clinical benefit after two doses. These include:
‒ A RECIST 1.1-measured partial response in a patient with cutaneous melanoma (prior adjuvant nivolumab)
‒ An investigator-reported clinical response in a patient with squamous cell carcinoma of the head & neck (prior
RT + cetuximab; carboplatin + fluorouracil + pembrolizumab; paclitaxel)
‒ An investigator-reported clinical benefit in a patient with mucosal melanoma (prior ipilimumab + nivolumab)
• Preliminary, biomarker-driven evidence of ONCR-177-mediated immune activation
10O N C R - 1 7 7 P h a s e 1 ( K E Y N OT E - B 7 3 ) & D e ve l o p m e nt P l a n
Phase 1 Phase 2/3
Location Treatment Escalations Expansions Registration Trials
Breast
Part A: Dose
✓RP2D Melanoma & NMSC
Monotherapy Escalation1 Head & Neck
Surface
Lesions 2L TNBC
Part B: 2L Melanoma Randomized Trial(s)
Combination with 2L Head & Neck
Part A: Dose
3L MSS CRC
Escalation2 ❑ RP2D
Visceral Monotherapy
Lesions Part B:
3L liver metastases2
Combination with
ONCR-177 is dosed iTu every 2 weeks for up to 26 doses (NCT04348916); RP2D=Recommended Phase 2 Dose = 4E8 for surface lesions;
NMSC = non-melanoma skin cancer; MSS CRC = microsatellite stable colorectal cancer; TNBC = triple negative breast cancer 11
1. Basket study including breast, squamous cell carcinoma of the head and neck (SCCHN) and melanoma; 2. Any liver metastases.ONCR-177-101 Study Design
Key Objectives
• Assess the safety and tolerability of
ONCR-177
• Determine the Recommended Phase 2
Dose (RP2D)
Surface Lesion Dose Escalation (N=14)
• Assess the anti-tumor activity of • Up to 6 doses every 2 weeks
ONCR-177 • No intrapatient dose escalation
• Safety & Exploratory biomarkers: • Cohort 1: 1x106 PFU in 1 mL (N=3)
• Cohort 2: 1x107 PFU in 1 mL (N=4)
‒ ONCR-177 detection, anti-HSV-1
antibodies • Cohort 3: 1x108 PFU in 1 mL (N=3)
• Cohort 4: 4x108 PFU in 4 mL (N=4)
‒ ONCR-177 payloads
→ Determined RP2D
‒ Immune infiltration and activation
markers
12D e m o g ra p h i c s a n d B a s e l i n e Pat i e nt C h a ra c te r i st i c s
ONCR-177 Monotherapy (N=19)
Median age, years (range) 67 (46-77)
Female, n (%) 10 (52.6)
Male, n (%) 9 (47.4)
• Patients with heavily pre-treated, advanced
ECOG Performance Status, n (%) 0 4 (21.1) solid tumors were enrolled, with a range of
1 15 (78.9) tumor types
Number of prior therapies, median (range) 3 (2-11)
Number of patients with prior I/O therapy, n (%) 15 (78.9)
• All but one HSV seronegative patients
HSV-1 Serostatus, n (%) Seropositive 11 (57.9)
seroconverted by the third ONCR-177 dose in
Seronegative 7 (36.8)
Unknown 1 (5.3)
the dose escalation cohorts
Tumor Types, n (%) Melanoma 6 (31.6)
Triple negative breast cancer 3 (15.8)
Oropharyngeal squamous cell carcinoma 2 (10.5) • To date, a difference in tolerability based on
ER+/PR+ breast cancer 1 (5.3) HSV serostatus has not been shown at any
Anal squamous cell carcinoma 1 (5.3) dose level
Lung adenocarcinoma 1 (5.3)
Duodenal adenocarcinoma 1 (5.3)
Basaloid Carcinoma 1 (5.3)
Chondrosarcoma 1 (5.3)
Thyroid cancer 1 (5.3)
Papillary renal cell carcinoma 1 (5.3)
Data cutoff: 22 Oct 2021
13O N C R - 1 7 7 S a fet y O ve r v i e w
Treatment-Related Adverse Events: Monotherapy Dose Escalation and Dose Expansion
106, 107, 108 4x108 (RP2D) 106, 107, 108 4x108 (RP2D)
• ONCR-177 is well tolerated,
N=10 N=9 N=10 N=9
Grades 1-2 Grades 1-2 Grades 1-2 Grades 1-2 with side effects as expected
Preferred Term N (%) N (%) Preferred Term N (%) N (%) for a viral immunotherapy
Any Event 7 (70) 7 (77.8) Headache 1 (10) 1 (11.1)
Fatigue 1 (10) 4 (44.4) Blister 1 (10) • No DLTs were observed in
Injection site pain 1 (10) 1 (11.1) Erythema 1 (10) surface lesion dose escalation
Fever 1 (10) Pruritus 1 (10)
Diarrhea 1 (10) 1 (11.1) Rash vesicular 1 (11.1) • No Grade ≥3 TRAEs
Vomiting 1 (11.1) Skin infection 1 (10)
Decreased 1 (11.1) • Increase in Grade 1-2 events
1 (10) Procedural pain 1 (10)
appetite with dose escalation, all
Dehydration 1 (10) Myalgia 1 (10) treatment-related AE’s
Hyponatremia 1 (11.1) Nipple pain 1 (10) being Grade 1 or 2 at RP2D
1 (11.1) Cytokine Release
Cellulitis of face 2 (22.2)*
Syndrome • No patients discontinued due
Pain in knee 1 (11.1) Chills 4 (44.4)* to a treatment-related adverse
Eyelid twitching 1 (11.1) Nausea 3 (33.3)* event
Dry skin face 1 (11.1) Hypotension 2 (22.2)*
*At RP2D: inflammatory symptoms including chills, nausea, hypotension and cytokine release syndrome have been reported in
66.7% of patients. These have been considered related to ONCR-177 but have been ≤ Grade 2
Data cutoff: 01 Oct 2021
14O N C R - 1 7 7 D u rat i o n o f Tre at m e nt a n d O u tc o m e
Cohort 1 (1x106 PFU in 1mL)
Cohort 2 (1x107 PFU in 1mL) *
Dose Escalation
CR
Cohort 3 (1x108 PFU in 1mL) PR
SD
PD
Cohort 4 (4x108 PFU in 4mL) Death
RP2D Ongoing
Not Evaluable
Dose Expansion Cohorts (4x108 PFU in 4mL)
RP2D
Duration of Treatment (Months)
Cut off date: 01Nov2021
*Patient 2-2: Basaloid carcinoma; resolution of tumor drainage, improvement of symptoms but not 15
evaluable on RECIST; off study having received 6 total dosesRe s p o n s e D ata fo r R P 2 D Pat i e nt s
patient Disease Diagnosis Prior Therapies Disease Sites Injection Site ONCR-177 RECIST v1.1
Number Doses Response
4-1 Anal Squamous Cell 5FU + mitomycin C; FOLFIRINOX; nivolumab; carboplatin + paclitaxel; Anus, pelvis, lymph node Inguinal Lymph Node 4 PD
Carcinoma RT; surgery
Escalation
4-2 Melanoma Ipilimumab + nivolumab; OV + cemiplimab; surgery Left thigh, lymph nodes Subcutaneous Nodule 4 PD
4-3 Triple Negative Doxorubicin + cyclophosphamide + paclitaxel; palliative RT; carboplatin Chest wall, lymph nodes Right Posterolateral 12 PD
Breast Cancer + gemcitabine; adjuvant RT; durvalumab + tremelimumab; eribulin; Chest Wall
doxil; surgery
4-4 Melanoma Pembrolizumab; ipilimumab + nivolumab; surgery Skin, lung, bone, liver Posterior Lower Neck 2 PD
Subcutaneous Lesion
4-5 Melanoma Nivolumab; RT; ipilimumab; RO7293583 (CD3-TYRP1); surgery Skin, lung Inguinal Lymph Node 2 PD
4-6 Melanoma Ipilimumab; nivolumab (neoadjuvant and metastatic); RT; surgery Vaginal primary, lymph Inguinal Lymph Node 6 (ongoing) SD
nodes, possible lumbar and Vaginal Wall
Expansions
vertebrae
4-7 Oropharyngeal, RT + cetuximab; carboplatin + fluorouracil + pembrolizumab; Neck, lymph nodes Right Neck 5 (ongoing) PD*
squamous cell paclitaxel; surgery
4-8 Melanoma Nivolumab (adjuvant); surgery Right arm, Right arm 5 (ongoing) PR
subcutaneous, lymph
nodes
4-9 TNBC Doxorubicin + cyclophosphamide + paclitaxel; docetaxel + carboplatin; Chest wall, lung, bone, Chest Wall 1 Off study/Not
eribulin; FLX475; pembrolizumab; sacituzumab govitecan; trastuzumab lymph nodes Evaluable
deruxtecan; adjuvant RT; surgery
*Detailed on following slides. Clinical response in injected lesion, progression of non-target lesions;
16Pa r t i a l Re s p o n s e i n M e l a n o m a Pat i e nt
Patient 4-8 (Melanoma) Treated at RP2D
• Prior Tx: Relapse after adjuvant
nivolumab
• ONCR-177 Tx: Initial therapy for
relapse after adjuvant
‒ Two lesions injected C1D1 Blacked out portion is patient identifiable information (tattoo) C4D1
• Current Time on Tx: Week 8, ongoing
• Week 4 Classification: Tumor
regression in both lesions, partial
response in larger lesion (measurable 70% reduction
per RECIST) in TL01
• Current Status: Partial response, Lower limit of quantitation by calipers
as measured by RECIST
17I nve st i gato r Re p o r te d Tu m o r Re g re s s i o n i n S C C H N Pat i e nt
Patient 4-7 (SCCHN) Treated at RP2D
• Prior Tx: heavily pre-treated, including
pembrolizumab + platinum
• ONCR-177 Tx: 4th line therapy
‒ Initially 1 target lesion injected
‒ Now injecting other lesions C1D1 C2D1 C3D1 C4D1
• Current Time on Tx: Week 10, ongoing
PET CT
• Week 4 Classification: Investigator
Fusion
reported clinical response in injected
lesion (-28% short axis, -47% long axis)
Injected
• Current Status: Progressive disease Tumor
(non-target lesions), as measured by
RECIST, continuing on study
PET Images received directly
18
Pre-Tx Week 8 from clinical investigatorC l i n i c a l B e n ef i t i n M e l a n o m a a n d T N B C Pat i e nt s
Patient 4-6 (Melanoma, Vaginal) Treated at RP2D Patient 4-3 (TNBC) Treated at RP2D
• Prior Tx: ipilimumab + nivolumab, nivolumab • Prior Tx: 5 lines of systemic therapy, including
durvalumab + tremelimumab
• ONCR-177 Tx: 3rd line therapy
‒ Initially lymph node (LN) injected • ONCR-177 Tx: 6th line therapy
‒ Now split dosing b/t LN and vaginal ‒ 12 injections tolerated
lesion (now accessible) ‒ Grade 2 CRS, successfully managed
‒ IFN-g and Ki67 in T cells significantly
• Current Time on Tx: Week 10, ongoing increased from baseline
• Week 4 Classification: Decrease in multiple • Current Time on Tx: Week 23, off treatment
symptoms (before vaginal lesion injection),
including: • Week 22 Classification: Stable disease for 5.5
Vaginal bleeding, discharge months
Vaginal and pelvic cramping
Pain on exam • Current Status: Progressive disease, as measured
by RECIST
• Current Status: Stable disease in nodes; vaginal
lesion not measurable by RECIST
19Key Takeaways
• ONCR-177 at RP2D was well tolerated in advanced, heavily pre-treated patients
‒ No DLTs, RP2D determined at 4x108 PFU in 4 mL
• Demonstrated clinical benefit in heavily pre-treated patients in multiple tumor
types, including in post PD-1/CTLA-4 settings
• Findings validate further development of ONCR-177 both as a single agent and in combo
‒ Enrollment is ongoing in surface lesion monotherapy expansion
‒ Combination with pembrolizumab anticipated to begin enrolling by year end 2021
‒ Visceral dose escalation (monotherapy) also to begin enrolling by year end 2021
• Data strongly support Oncorus' innovative approach to viral immunotherapy
20O N C R - 1 7 7 P h a s e 1 ( K E Y N OT E - B 7 3 ) & D e ve l o p m e nt P l a n
Phase 1 Phase 2/3
Location Treatment Escalations Expansions Registration Trials
Breast
Part A: Dose
✓RP2D Melanoma & NMSC
Monotherapy Escalation1 Head & Neck
Surface
Lesions 2L TNBC
Part B: 2L Melanoma Randomized Trial(s)
Combination with 2L Head & Neck
Part A: Dose
3L MSS CRC
Escalation2 ❑ RP2D
Visceral Monotherapy
Lesions Part B:
3L liver metastases2
Combination with
Add’l monotherapy & preliminary combination & visceral data in mid’22; visceral & combination data in late ‘22
ONCR-177 is dosed iTu every 2 weeks for up to 26 doses (NCT04348916); RP2D=Recommended Phase 2 Dose = 4E8 for surface lesions;
NMSC = non-melanoma skin cancer; MSS CRC = microsatellite stable colorectal cancer; TNBC = triple negative breast cancer 21
1. Basket study including breast, squamous cell carcinoma of the head and neck (SCCHN) and melanoma; 2. Any liver metastases.ONCR-021
Synthetic Coxsackievirus A21
22W h at i f t h e re wa s a n R N A - b a s e d c a n c e r t h e ra p y t h at :
IV
RNA
Could be delivered Is capable of selective self-amplification Causes immunogenic
IV repeatedly? cell death?
and
Encodes a payload that is a living therapy?
23V i ra l R N A ( v R N A ) p a c ka ge d i n a L N P fo r re p e at I V a d m i n .
Synthetic RNA virus Polynucleotides that encode for viral genome (living payload)
Viral RNA (vRNA)
genome
Encapsulated in proprietary lipid nanoparticle (LNP)
Lipid nanoparticle
(LNP)
Avoids neutralizing antibodies when delivered IV
PEG Lipid
Self-amplifies in tumors and produces oncolytic virions
24V i ra l R N A p a c ka ge d i n L N Ps e n a b l e I V a d m i n i st rat i o n
RNA Virus Synthetic RNA virus
Viral RNA (vRNA)
genome
Lipid nanoparticle
Viral capsid proteins (LNP)
Antibody response
PEG Lipid
Selectively self amplifies and
spreads in tumor cells
Potential to evade
neutralizing antibodies
25I V - a d m i n i ste re d Sy nt h et i c v R N A I m m u n o t h e ra p i e s :
A potential new class of medicines for cancer patients
Animated walkthrough of the mechanism here
1. Ehrlich & Bacharach, Cancers, (2021); 2. Pol, et al., Cytokine Growth Factor Rev (2020) 26C oxs a c k i e v i r u s A 2 1 : e v i d e n c e o f c l i n i c a l a c t i v i t y, b u t
n e u t ra l i z i n g a nt i b o d i e s d e ve l o p ra p i d l y
Neutralizing antibodies observed after IV
administration of CAVATAK
• Safety (IV) and efficacy (iTu) demonstrated by
Merck’s V937 (CAVATAK) in melanoma
‒ CAVATAK (iTu) + pembro = 61% ORR
‒ CAVATAK (iTu) + ipilimumab = 57% ORR
• Neutralizing antibodies likely inhibit activity of
later IV doses
Pandha, H., et al., Abstract CT115, slide #18, AACR, 2017
27O N C R - 0 2 1 v i ra l st ra i n i s m o re p o te nt t h a n M e rc k ’s st ra i n
• Merck's CAVATAK uses CVA21 KuyKendall strain
• Oncorus’ strain selected for superior oncolytic potency
across NSCLC tumor cell lines
• Broad oncolytic activity observed across multiple
indications
Lower IC50 indicates more potent oncolytic activity
28O N C R - 0 2 1 e n h a n c e d p o te n c y t ra n s l ate s to s u p e r i o r a c t i v i t y
i n N S C LC m o d e l s
NSCLC tumor model NCI-H1299 NSCLC tumor model NCI-H2122
ONCR-021 and Synthetic Kuykendall vRNA use the same LNP formulation
RNA-Neg is a vRNA with viral kick-off inhibiting mutations 29O N C R - 0 2 1 i s we l l to l e rate d w i t h m i n i m a l re p l i c at i o n i n
normal tissues
Well tolerated in huICAM-1 transgenic mouse model Minimal replication in normal tissues
No effects on body weight
No adverse elevation of
liver enzymes
No adverse pathology after single or repeat administration
hICAM-1 transgenic mouse model. (-) negative strand RNA indicates active replication. 30C VA 2 1 e nt r y re c e p to r I C A M 1 i s a s s o c i ate d w i t h a c t i v i t y
ICAM1 expression is associated ICAM1 expression is prevalent in
with oncolytic activity ONCR-021 selected clinical indications
Patient Samples
Indications ICAM+ Prevalence
Tested (N)
NSCLC 97 72%
HCC 69 72%
RCC 67 79%
NSCLC HCC RCC
In vitro cytotoxic screen in 130 human cell lines. 200 um
200 um
Sensitive: TCID50 0.5 200 um
31O N C R - 0 2 1 C l i n i c a l D e ve l o p m e nt P l a n
Phase 1 Phase 2/3
Histology Treatment Escalations Expansions Registration Trials
Non-small cell lung
Dose Renal cell
❑ RP2D
Monotherapy Escalation* Melanoma
NSCLC ICAM1+ tumors
RCC
Non-small cell lung
Melanoma
Combination Renal cell
Randomized Trial(s)
with anti-PD-(L)1 Melanoma
ICAM1+ tumors
Dose
Hepatocellular Monotherapy Escalation ❑ RP2D HCC
Carcinoma
(HCC) Combination
HCC
with anti-PD-(L)1
IND filing 1H’23 with translational Proof of Concept as early as 2H’23
*Basket study including non-small cell, renal cell and melanoma; RP2D=Recommended Phase 2 Dose 32C o r re l at i ve st u d i e s m ay ra p i d l y s h o w P ro o f o f C o n c e p t fo r
ONCR-021 in the clinic
These include:
• Seroconversion, as measured by detection of antibodies
• Virus and/or (-) strand RNA quantified from tumor
• Oncolysis of tumor cells & immune infiltration in the tumor
microenvironment
• Continued oncolytic & clinical activity after seroconversion
• Clinical benefit as measured by responses or prolonged survival
ONCR-021 is 1st vRNA program, therefore Proof of Concept will = Proof of Platform
Rapid execution of ONCR-021 enables Proof of Platform as early as 2H’23
33Sy nt h et i c v i r u s e s m ay a d d re s s u n m et n e e d s i n o n c o l o g y
• Delivered to all tumors & metastatic sites, throughout the body
• Inflame the tumor microenvironment
• Can combine with other IO therapies
• May be repeatedly dosed without loss of activity
• Tumor selection strategies are under development
• Robust correlates available to demonstrate PoC
34O n c o r u s ’ p ro p r i eta r y L N P p l at fo r m
vRNA Novel Ionizable Helper Novel PEG Sterol
Lipid Lipid Lipid
DSPC Cholesterol
Oncorus Optimized Formulation and Process
High encapsulation efficiency of vRNA (>95%)
Small LNP size (85 nm) and desirable physio-chemical properties
Improved activity and tolerability vs. industry standard (Onpattro’s MC3 lipid)
Stability at -20°C
Scalable LNP Process
35Re a l i z i n g t h e p o te nt i a l o f R N A m e d i c i n e s fo r c a n c e r
Novel synthetic vRNA platform enables repeat, IV dosing of tumor-specific infections
Synthetic vRNA platform could satisfy many unmet needs in lung and other cancers
Clinical development plan includes rapid proof of principle readout
In-house manufacturing facility to couple process development improvements
with GMP processes and allow for timely delivery of multiple clinical programs
36ONCR-GBM
37O N C R - G B M : ex p a n d i n g t h e H SV p l at fo r m
HSV + Payloads +
18,000 microRNA atten. 2H’23
newly diagnosed patients Leverage Oncorus’ HSV Platform IND filing expected 2H'23
annually with Glioblastoma • Tailored microRNA attenuation for brain • Initiated payload screening
Multiforme (GBM) cancer • Initiated micro-RNA target
• Payload selection to target immune selection
suppressive mechanisms
38P ro o f o f C o n c e p t fo r o H SV P l at fo r m i n G B M
Company Asset Modifications Setting Results Historical Control
Daiichi Sankyo Delytact* g34.5, ICP6, ICP47 deficient Recurrent GBM 1 yr OS 92% 1 yr OS 15%
Candel CAN-3110 Nestin-directed g34.5 Recurrent GBM mOS 11.7 months mOS 7-9 months
Treovir G207 g34.5 & ICP6 deficient Recurrent ped. GBM mOS 12.2 months mOS 5.6 months
*Approved in Japan
ONCR-GBM differentiation
• Encodes immunostimulatory payloads for enhanced activity
• IFN resistance to promote replication only in tumor cells
• miR cassettes for tumor selective replication and enhanced safety
Chiocca, et al. ASCO 2021. J Neurooncol. 2017; 135(1): 183–192. N Engl J Med. 2021 Apr 29;384(17):1613-1622. Gene Therapy (2000) 7, 867–874. 39P ro l o n ge d s u r v i va l w i t h t ra n s ge n e ex p re s s i n g O N C R - G B M i n
m u r i n e sy n ge n e i c g l i o m a s
ONCR-GBM engineered to express transgenes IL-12 and anti-PD-1, which significantly prolong survival
Oncorus thanks Francisco Quintana and Federico Giovannoni, of Harvard medical school for conducting these experiments which
confirm previous work from Joseph Jackson and Joseph Glorioso at the University of Pittsburgh
Strathdee C, et al. IOVC. 2021. 40ONCR-788
Synthetic Seneca Valley Virus
41SV V to l e rate d i n P h a s e 1 , c l i n i c a l a c t i v i t y m ay h ave b e e n
l i m i te d b y n e u t ra l i z i n g a nt i b o d i e s
Neutralizing antibodies, against capsid,
detected in all patients after IV injection
Adverse Events Reported from Phase 1 Study of
SVV-001 (Seneca Therapeutics)
Grade 1 Grade 2 Grade 3
Pyrexia 33% 7% 0%
Fatigue 23% 7% 0%
Headache 7% 7% 0%
Lymphopenia 0% 3% 3%
Muscle Spasms 0% 3% 0%
Cough 0% 3% 0%
Doses of 107 – 1011 viral particles/kg; n=30
Development of SVV-001 neutralizing antibodies
Rudin et al., Clin Cancer Res. 2011. 42O N C R - 7 8 8 a l l o w s fo r re p e at I V a d m i n i st rat i o n i n t h e
p re s e n c e o f n e u t ra l i z i n g a nt i b o d i e s
SVV neutralizing antibodies inhibit efficacy of IV-injected SVV but have no effect on activity of ONCR-788
1750
Tumor volume (mm3) 1500
1250 Vehicle + control Ab
SVV-virion + control Ab
1000
SVV-virion + neutralizing Ab
750 ONCR-788 + control Ab
500 ONCR-788 + neutralizing Ab
Ab injection
250
**** SVV-virus, ONCR-788 IV injection
****
****
0
0 5 10 15 20 25
Days on Study
43
NCI-H446 orthotopic SCLC tumor modelO N C R - 7 8 8 i n d u c e s t u m o r re g re s s i o n a n d i m p ro ve s s u r v i va l
i n c h a l l e n g i n g S C LC xe n o g ra f t m o d e l s
Survival SCLC Orthotopic Tumor Model
SCLC PDX Tumor Model
2500 100 PBS
Percent survival
PBS Synthetic RNA-Neg
Tumor Volume (mm3)
2000
Synthetic RNA Neg ONCR-788
1500 ONCR-788 50 IV dose 1mg/kg
1000 IV dosing 1 mg/kg
500 ***
0 ****
0 0 50 100 150
0 10 20 30 Days post Tumor implantation
Days on Study Long-rank (Mantel-Cox) test vs. ONCR-788
*** p=0.0003; ****pO N C R - 7 8 8 s e l e c t i ve l y s p re a d s i n t u m o r b u t d o e s n o t
re p l i c ate i n n o r m a l t i s s u e s
PCR and ISH demonstrate SVV spread and long
replication kinetics in tumors but not in normal tissues
LOD
Each histogram represents a dosed animal. SVV Neg = non-replicating SVV control; SVV-wt = active,
vRNA detection by ISH in tumor wild-type synthetic SVV; cDNA = complementary DNA; (-)ssRNA = negative single strand RNA.
Sampling 4 days after the last dose
45O N C R - 7 8 8 a n d a nt i - P D - 1 c o m b i n at i o n i m p ro ve s re s u l t s i n
n e u ro b l a sto m a m o d e l
✱
Number of T cells/mg of tumor
6×10 5 1,800 IgG2a
PBS aPD1
5×10 5
ONCR-788
Tumor volume (mm3)
1,500 ONCR-788
4×10 5
ONCR-788 + aPD-1
3×10 5 1,200
IV dosing ONCR-788 (0.2 mg/kg)
2×10 5
900
1×10 5 IP dosing Ab (10 mg/kg)
0 600
CD4 CD8
300 *
✱
150 ***
Number of CD45- PD-L1+
# ##
PBS 0
cells/mg of tumor
ONCR-788 0 5 10 15 20
100
Days on treatment
50
0
*pO N C R - 7 8 8 C l i n i c a l D e ve l o p m e nt P l a n i n N e u ro e n d o c r i n e
C a n c e rs
Phase 1 Phase 2/3
Patients Treatment Escalations Expansions Registration Trials
Small cell lung
Dose
❑ RP2D Neuroendocrine prostate
Monotherapy Escalation*
Merkel cell
Adults
Small cell lung
Combinations with Neuroendocrine prostate Randomized Trial(s)
anti-PD-(L)1 ± chemo** Merkel cell
Dose
Monotherapy Escalation ❑ RP2D Neuroblastoma
Peds
Combinations with Neuroblastoma
anti-PD-(L)1 ± chemo**
Same PoC methodology as ONCR-021 will apply to ONCR-788
*Basket study including involving neuroendocrine (NE) tumors, RP2D=Recommended Phase 2 Dose; **chemo such as platinum + etoposide and/or αDLL3 47In House Process Development
and GMP manufacturing
48I n - h o u s e m a n u fa c t u r i n g c a p a b i l i t i e s e s s e nt i a l fo r s u c c e s s
• Robust supply chain is critical to the successful development of any drug candidate and will become a
strategic asset
‒ Better able to respond to unexpected volatility and pressure on supply chains – robustness
‒ Able to manage multiple programs simultaneously – critical to authentic platform companies
‒ Limit burdens of tech transfer and lead time – internal agility
• In-house manufacturing allows for
‒ Higher quality control and greater operational flexibility
‒ Improved control over supply chain
‒ Process development improvements can be more rapidly incorporated into GMP processes
‒ Create and Protect 'know-how' in new emerging techniques and process
In-house manufacturing to enable timely delivery of clinical programs
49A n d o ve r m a n u fa c t u r i n g fa c i l i t y
• Support clinical trials for both platforms
• Occupied in 3Q’21 and GMP operational in 1H’23
• Ultimately capable for initial commercial launch
QC Labs PD Labs 88,000 square feet overall, 41,000 square feet in GMP Unit
GMP Space GMP Warehouse
Open Office Conference Rooms Common Area
50Leadership and Upcoming
Catalysts
51L e a d e rs h i p
Ted Ashburn, Christophe Quéva, John McCabe, Stephanie John Goldberg, Steve Harbin Brett Belongia, Lorena Lerner, Brain Haines,
MD, PhD PhD MBA Duncanson, PhD MD PhD PhD PhD
President & CEO CSO CFO VP Strategy & BD SVP Clinical Dev. COO & Chief of Staff VP CMC Operations VP Molecular Biology VP Pharm. & Tox.
Board of Directors
Ted Ashburn, MD, PhD Mitchell (Mitch) Finer, PhD Mary Kay Fenton, MBA Eric Rubin, MD
President & CEO Executive Chairman & Co-Founder CFO, Talaris Therapeutics SVP Clinical Oncology, Merck & Co
xModerna Executive Partner, MPM Capital
xCOO/CFO, Semma/Vertex
Luke Evnin, PhD
Spencer Nam, MBA Scott Canute, MBA Barbara Yanni, JD
Co-Founder & Managing
Managing Partner, KSV Global xDirector, Immunomedics xChief Licensing Officer, Merck & Co
Director, MPM Capital xGenzyme, xLilly
52U p c o m i n g C ata l yst s
2021 2022 2023
ONCR-177 mono update,
ONCR-177 mono-tx early combo & ONCR-177 combo & visceral
data (2H) visceral data (mid '22) data (late '22)
HSV
ONCR-GBM IND (2H’23)
Synthetic CVA21 vRNA Candidate
Synthetic (ONCR-021) Nomination
RNA Viruses ONCR-021 IND (1H’23)
Synthetic SVV vRNA Candidate
(ONCR-788) Nomination
Initiate cGMP manufacturing buildout
Financial/ GMP Facility
Operational $57M Follow on Public Offering Operational (1H’23)
Cash Runway into late 2023
53
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