Exhibit 99.1

January 2022 B. Riley Securities Oncology Investor Conference

Forward - Looking Statements This presentation includes forward - looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 , as amended, concerning Synthetic Biologics and VCN Biosciences (“VCN”) . In some cases forward - looking statements can be identified by terminology such as "may," "should," "potential," "continue," "expects," "anticipates," "intends," "plans," "believes,“ "estimates,” “indicates,” and similar expressions . These statements are based upon management’s current beliefs, expectations and assumptions and are subject to a number of risks and uncertainties, many of which are difficult to predict and include statements regarding the proposed acquisition of VCN by Synthetic Biologics, the timing of such acquisition and the various timelines for development of VCN’s product candidates . The forward - looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those set forth or implied by any forward - looking statements . Important factors that could cause actual results to differ materially from those reflected in Synthetic Biologics’ forward - looking statements include, among others, the risk a ssociated with Synthetic Biologics’ and VCN’s ability to satisfy the conditions to consummate the proposed acquisition, including obtaining necessary governmental approvals, the timing of the closing of the proposed acquisition, the occurrence of any event, change or other circumstance or condition that could give rise to the termination of the Stock Purchase Agreement between the shareholders of VCN and Synthetic Biologics, unanticipated difficulties or expenditures relating to the proposed acquisition or development of VCN’s drug candidates , the response of business partners and competitors to the announcement of the proposed acquisition, and/or potential difficulties in employee retention as a result of the announcement and pendency of the proposed acquisition, whether the combined business of Synthetic Biologics and VCN will be successful, Synthetic Biologics’ and VCN’s product candidates demonstrating safety and effectiveness, as well as results that are consistent with prior results, the ability to initiate clinical trials and if initiated, the ability to complete them on time and achieve the desired results and benefits continuing 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 Synthetic Biologics’ and VCN’s ability to promote or commercialize their product candidates for the specific indications, acceptance of product candidates in the marketplace and the successful development, marketing or sale of Synthetic Biologics’ and VCN’s products, developments by competitors that render such products obsolete or non - competitive, Synthetic Biologics’ and VCN’s ability to maintain license agreements, the continued maintenance and growth of Synthetic Biologics’ and VCN’s patent estate, and other factors described in Synthetic Biologics’ annual report on Form 10 - K for the year ended December 31 , 2020 , subsequent quarterly reports on Form 10 - Qs and any other filings we make with the SEC . Synthetic Biologics can give no assurance that the conditions to the acquisition will be satisfied . The information in this presentation is provided only as of the date presented, and Synthetic Biologics undertakes no obligation to update any forward - looking statements contained in this presentation on account of new information, future events, or otherwise, except as required by law . 2

• Synthetic Biologics (NYSE American: SYN ) advancing into oncology with the acquisition of Barcelona - based VCN Biosciences S.L. • Transaction announced 14 December 2021 (closing subject to conditions including Spanish government approval) ¹ • VCN is developing unique oncolytic viruses ( OVs ) optimized for intravenous administration and maximum tumor destruction • Lead clinical product VCN - 01 poised to enter a Phase 2 clinical study in patients with newly - diagnosed metastatic pancreatic ductal adenocarcinoma ( PDAC ) and a Phase 2/3 study in retinoblastoma • Compelling platform of next - generation OVs ( VCN - 11 family ) designed to address additional hard - to - treat cancers with high unmet need Synthetic Biologics and VCN Biosciences S.L. 3 ¹Foreign direct investment (FDI) approval anticipated within 60 days from signing.

• Synthetic Biologics (NYSE American: SYN ) to acquire 100% outstanding equity of VCN • Total upfront consideration for the acquisition is $4.7M in cash • Shares of SYN common stock equal to 19.99% of the outstanding shares of common stock distributed to VCN • Up to $70.25M total cash milestone payments • Backend loaded predominantly based on future Phase 2/3 clinical and regulatory milestones • No royalties or commercial sales milestones to sellers • VCN to maintain current legal structure, operate as a wholly owned subsidiary of SYN • Closing subject to conditions including Foreign Direct Investment (FDI) approval by the Spanish government ¹ SYN - VCN Transaction Summary 4 ¹FDI approval anticipated within 60 days from signing.

• OVs are a Promising Cancer Therapeutic Approach • Combine the natural ability of certain viruses to cause immunogenic cell death, induce inflammatory responses and trigger immune cell infiltration into treated tumors • Can be combined with other therapeutic modalities (e.g. chemotherapy, checkpoint inhibitors and CAR - T cells) • OVs have Typically been Limited to Intratumoral Injection • Metastases are not addressed by localized intratumoral injection • Certain tumors are difficult to directly inject safely and repeatedly (e.g. lung, pancreatic) • VCN is Addressing Key Challenges to Systemic OV Therapy • Improving manufacturing yields to enable higher systemic doses • Avoiding OV off - target effects and toxicities • Overcoming the poorly penetrable, antiviral and immunosuppressive tumor stroma Oncolytic Virus Features and Challenges 5

VCN - 01 Oncolytic Adenovirus • SYSTEMIC • Highly replicating • Decreased liver tropism • Treatment of primary and metastatic lesions • SELECTIVE • Increased tumor penetration • Only replicates in tumors (defective Rb - E2F pathway) ¹ • Transgene only expressed after virus replication - provides a built - in biomarker² • STROMA DEGRADING • Degrades hyaluronic acid in the stroma ( PH20 ) ³ • Increases dissemination of virus and co - administered therapeutics within the tumor • Increases tumor immunogenicity and immune cell infiltration 6 ¹Most if not all solid tumors; Giacinti (2006) Oncogene 25: 5220; Polager (2009) Nat Rev Cancer 9: 738. ²Transgene expression under control of virus major late promoter ( MLP ). ³PH20 is human testicular hyaluronidase enzyme. For additional details and references see Appendix. IMAGE CREDIT: https://microbewiki.kenyon.edu/index.php/Adenovirus - based_Gene_Therapy:_a_Promising_Novel_Cancer_Therapy E2F + E1a - Δ24  [MLP]  PH20 Genetic modifications  RGDK modification to fiber shaft AdV5 (Group C) RGD retained in penton base

Unique Mechanism of Action for VCN Products 7

VCN - 01 Clinical Trials Location Phase Indication Co - therapy Route (n) Status NCT or EudraCT Multicenter (ESP) 1 Part I: Solid tumor Part II: PDAC Part III: PDAC Part I: None Parts II,III: Gemcitabine + nab - Paclitaxel Part I: IV (16) Part II: IV (12) Part III: IV (14) Complete ¹ NCT02045602 Multicenter (ESP) 1 PDAC Gemcitabine + nab - Paclitaxel IT (8) Complete² NCT02045589 Hospital Sant Joan de Déu, Barcelona 1 Retinoblastoma None IVit (4) On - going partial data NCT03284268 Institut Català d'Oncologia (ICO) 1 HNSCC Durvalumab IV (16) On - going data not yet available NCT03799744 U. Leeds 1 Adult brain tumors None IV (12) IND open, trial initiating 2020 - 003405 - 59 U. Pennsylvania 1 PDAC, Ovarian huCART - meso³ IV (12) IND open, trial initiating NCT05057715 U. Navarra 1 Pediatric brain tumors None IC (9 - 18) Pre - IND 2020 - 002860 - 30 8 ¹ Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271. Link to full ESMO 2019 poster provided on Appendix Slide 31. ²Bazan - Peregrino (2021) J Immunother Cancer 9: e003254. ³ huCART - meso are autologous T cells engineered to express an extracellular single chain variable fragment (scFv) with mesothelin specificity. HNSCC head and neck squamous cell carcinoma. IC intracranial. IV intravenous. IT intratumoral. IVit intravitreal. VCN is collaborating with world - leading clinical research institutions, 70 patients treated to date

• PDAC accounts for 3 rd highest cause of cancer - associated deaths in US (4 th in EU) ¹ - ³ • North America ~63,000 new cases and 53,000 deaths each year • Western Europe ~46,000 new cases and 43,000 deaths each year • PDAC h as the lowest survival rate of all major organ cancers • Median survival 4 - 6 months from diagnosis , 1 - year survival 24% • Treatment options for metastatic PDAC are limited ³ • First - line therapies include (m)FOLFIRINOX, gemcitabine + nab - paclitaxel • Checkpoint inhibitors have been largely ineffective • PDAC stroma is a physical and immunosuppressive barrier to therapy • Stromal hyaluronan accumulation is associated with low immune response and poor prognosis ⁴ Pancreatic Ductal Adenocarcinoma (PDAC) 9 ¹ Bengtsson (2020) Sci Rep 10: 16425. ² Carioli (2021) Ann Oncol 32: 478. ³For additional details and references see Appendix. ⁴ Tahkola (2021) Sci Rep 11: 12216. (m)FOLFIRINOX (modified) leucovorin + 5 - FU + irinotecan + oxaliplatin. nab - Paclitaxel nanoparticle albumin - bound paclitaxel. IMAGE: Dragovich T. et al. “Pancreatic Cancer: Practice Essentials”. Medscape, 2021. https://emedicine.medscape.com/article/280605 - ove rview Pancreatic adenocarcinoma resected from the pancreas body and tail

• Multicenter, open - label, dose escalation study of single IV doses of VCN - 01 “ gemcitabine/Abraxane ® ( G/A )¹ • ARM I Monotherapy VCN - 01 dose finding, primarily colorectal cancer (12) • ARM II Concomitant VCN - 01 same day as first dose of G/A in PDAC patients (16) • ARM III Sequential VCN - 01 7 - days before first dose of G/A in PDAC patients (14)² • Promising antitumor activity and appropriate safety/tolerability at RP2D • Sequential regimen to be advanced to Phase 2 clinical trials VCN - 01 Clinical Data Encourage PDAC Phase 2 10 ¹NCT02045602. ²Two incorrectly enrolled patients in the 3.3x10¹² vp group were replaced and excluded from endpoint analysis b ut are included in the safety analysis. ³ Von Hoff (2013) NEJM 369: 1691. G/A administered IV on days 1, 8 and 15 of each chemotherapy cycle with cycles repeated every 28 - days . RP2D recommended phase 2 dose. vp virus particles. Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271. Link to full ESMO 2019 poster provided on Appendix Slide 31. Favorable Survival with VCN - 01 vs Published Standard - of - Care VCN - 01 ARM III (Sequential) VCN - 01 + G/A Published G/A alone ³ Overall Survival, median months (n) 3.3x10¹² vp/patient (6) 13.1 1.0x10¹³ vp/patient (6) 20.8 Combined (both doses) (12) 13.5 8.5 Overall Response Rate (n) 3.3x10¹² vp/patient (6) 16.7% (1) 1.0x10¹³ vp/patient (6) 83.3% (5) Combined (both doses) (12) 50% (6) 23% Survival > 12 months 8 (75%) Survival > 27 months 3 (25%)

Most Common IV VCN - 01 Related AEs (Multicenter ESP ¹ ) 11 ¹ NCT02045602. ²Concomitant IV VCN - 01 3.3x10¹² or 1.0x10¹³ vp/patient administered same day as first dose of Gemcitabine/Abraxane® ( G/A ). ³Sequential IV VCN - 01 3.3x10¹² or 1.0x10¹³ vp/patient administered 7 - days prior to first dose of G/A. Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271. L ink to full ESMO 2019 poster provided on Appendix Slide 31. Adverse Events Part I (Alone, n=16) Part II (Concomitant, 12)² Part III (Sequential, 14)³ CTCAE Grade Grade 1 - 2 Grade ≥3 Grade 1 - 2 Grade ≥3* Grade 1 - 2 Grade ≥3 Febrile neutropenia - - - 2 (16.7%) - - Neutropenia/Neutrophil count decreased 2 (12.5%) - 1 ( 8.3%) 1 ( 8.3%) - - Thrombocytopenia/Platelet count decreased 1 ( 6.3%) 1 ( 6.3%) 3 (25.0%) 4 (33.3%) 2 (14.3%) - Diarrhea 3 (18.8%) - 1 ( 8.3%) - - 1 (7.1%) Nausea 2 (12.5%) - 3 (25.0%) - 3 (21.4%) - Vomiting 3 (18.8%) - 2 (16.7%) - 3 (21.4%) - Asthenia/Fatigue 2 (12.5%) - 5 (41.7%) 1 ( 8.3%) 3 (21.4%) - Pyrexia/Influenza - like Illness 12 (75.0%) 1 ( 6.3%) 8 (66.7%) - 12 (85.7%) - Transaminase increases (ALT, AST) 2 (12.5%) 3 (18.8%) 1 ( 8.3%) 1 ( 8.3%) 2 (14.3%) 2 (14.3%) Pancreatic enzyme increase (lipase, amylase) 1 ( 6.3%) 3 (18.8%) - - - - Decreased appetite 3 (18.8%) - 3 (25.0%) - - - Arthralgia 2 (12.5%) - - - - - Musculoskeletal pain 3 (18.8%) - 4 (33.3%) - - - Dizziness 1 ( 6.3%) - 1 ( 8.3%) - - - Headache 1 ( 6.3%) - 1 ( 8.3%) - 1 (7.1%) - Dyspnoea 2 (12.5%) - - - - - Hypotension 2 (12.5%) - 1 ( 8.3%) - - - *Part II: one patient at the highest dose (1x10 ¹³ vp) died from a combination of thrombocytopenia (Grade 4) and enterocolitis (Grade 5)

VCN - 01 Remodels the PDAC Tumor Matrix 12 IHC immunohistochemical staining IDO indoleamine 2,3 - dioxygenase. Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271 . L ink to full ESMO 2019 poster provided on Appendix Slide 31. CD8 + lymphocyte infiltration IDO upregulation Built - in biomarker: hyaluronidase (PH20) levels in patient sera are linked to viral replication and demonstrate sustained VCN - 01 activity in tumors (Figure 1) Turns cold tumors “hot”: VCN - 01 remodels the tumor matrix and the immunological environment and promotes tumor inflammation (Figure 2) Figure 1: Serum PH20 levels in patients treated with IV VCN - 01 (Parts I - III) Figure 2: IHC of biopsies from hepatic metastases of a PDAC patient treated with IV VCN - 01 VCN - 01 3.3x10 ¹² vp/patient VCN - 01 1.0x10 ¹³ vp/patient Pre - Dose Day 8 Pre - dose Day 28 Pre - dose Day 28

• Retinoblastoma ( Rb ) is an orphan indication that accounts for ~2 - 3% of all childhood cancers¹ • 200 - 300 cases each year in the USA, EU ² - ⁴ • VCN - 01 selectivity enables development as an intravitreal treatment for Rb patients • VCN - 01 could be used in combination with chemotherapy to potentially improve outcomes • VCN - 01 could be used as a rescue therapy for patients who fail standard therapy Retinoblastoma, a Rare Pediatric Malignancy 13 ¹https://www.cancer.org/cancer/retinoblastoma/about/key - statistics.html. ²Stacey (2021) Ophthalmology 128: 1369. ³One Retinoblastoma World Map https://map.1rbw.org/. ⁴For additional details and references see Appendix. IMAGE: Courtesy of Hospital Sant Joan de Déu, Barcelona

VCN - 01 in Retinoblastoma • Single center, open - label dose escalation study of intravitreal ( IVT ) VCN - 01¹ - ³ • Children aged 1 - 12 years (n=4 to date) • Retinoblastoma that is recurrent or refractory to chemotherapy and for whom enucleation is the best treatment option • VCN - 01 doses of 2.0x10⁹ vp per eye (n=1) or 2.0x10¹º vp per eye (n=3) on days 1 and 15 • Promising antitumor activity and appropriate safety/tolerability at RP2D • Enucleation avoided in 1 of 4 patients • Low VCN - 01 dose and/or damage from prior chemotherapy meant eye could not be saved in 3 patients • Earlier VCN - 01 intervention anticipated to have better outcomes 14 ¹EudraCT 2016 - 001060 - 11. NCT03284268. ²Pascual Pasto (2019) Sci Transl Med 11: eaat9321. ³ Data presented at International Oncolytic Virus Conference IOVC2021, 07 November 2021, Sedona, AZ. Link to IOVC2021 slide deck provided on Appendix Slide 31 . RP2D recommended phase 2 dose. vp virus particles. Promising Results in 2 of the 3 Patients Treated with High Dose VCN - 01 Pt 2 2 Pt 3 Reduced number and size of tumor vitreous seeds following VCN - 01 administration² Complete tumor regression³ D14 D28 D0 D64 M8 D0

Two Intravitreal VCN - 01 Doses of 2.0x10⁹ or 2.0x10¹º vp per eye¹ Interim Safety Data for Intravitreal VCN - 01 15 ¹ NCT03284268. ²I ntravitreal VCN - 01 doses of 2.0x10⁹ virus particles ( vp ) per eye (Patient 1) or 2.0x10¹º vp per eye (Patients 2 - 4) administered on days 1 and 15. Data presented at International Oncolytic Virus Conference IOVC2021, 07 November 2021, Sedona, AZ. Link to IOVC2021 slide deck provided on Appendix Slide 31 . Adverse Reaction Pts All Grades Grade ≥3 CTCAE grade N n % n % Uveitis 4 2 50% 2 50% Periphlebitis 4 1 25% 0 0% Stable Electroretinographic Signals P r i o r t o i n j e c t i o n D u r i n g t r e a t m e n t A f t e r t r e a t m e n t 1 10 100 1000 A m p l i t u d e ( µ V ) 1st Patient Control 1st Patient Treated 2nd Patient Treated 4th Patient Control 4th Patient Treated • VCN - 01 was reasonably well tolerated after intravitreal administration², although some turbidity and vitritis associated with intravitreal inflammation was observed. • Intravitreal inflammation was managed with local and systemic administration of anti - inflammatory drugs • VCN - 01 did not appear to change retinal function (electroretinographic signaling)

• PDAC Phase 2 Clinical Trial • Finalizing protocol for a multinational, multicenter, study evaluating IV VCN - 01 with gemcitabine/nab - paclitaxel compared to gemcitabine/nab - paclitaxel alone • Newly - diagnosed metastatic PDAC patients treated with gemcitabine/nab - paclitaxel first line therapy • Principal Investigator Dr. Manuel Hidalgo Medina, MD PhD ‒ Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine/New York - Presbyterian Hospital ‒ Member of the Board of Directors, Bristol Myers Squibb • Rb Phase 2/3 Pivotal Trial • Developing a protocol for a multinational, multicenter, study evaluating intravitreal VCN - 01 • Principal Investigator: Dr. Guillermo Chantada, MD PhD ‒ Principal Researcher, Associate Physician, Hospital Sant Joan de Déu, Barcelona, Spain; National Council of Research in Argentina (CONICET); Scientific Director, Pediatric Hemato - Oncology Service of the Hospital Universitario Austral, Argentina and Hospital Pereira Rossell , Montevideo, Uruguay ‒ President, International Society of Paediatric Oncology VCN - 01 Next Steps 16

Albumin Shield Œ to Expand the VCN Platform • VCN has developed the Albumin Shield technology to protect OVs as they travel to the tumors¹ , ² • Albumin Shield modified OVs are coated by albumin and protected from circulating antibodies in cancer patients pre - exposed to adenovirus • Albumin Shield may enable multiple intravenous administrations for hard - to - treat patients • Albumin Shield first candidate VCN - 11 is being prepared for a Phase 1 clinical trial in ovarian cancer and other solid tumors 17 ¹Rojas (2016) J Control Rel 237:78; ABD binds mouse and human serum albumin, but not bovine; ²Mato - Berciano (2021) J Control Rel 332: 517. Albumin Shield modified OVs express an albumin binding domain (ABD) on the virus surface ( hexon ) that binds host serum albumin. The modification allows parent and the progeny to be albumin coated for continued protection Hexon

VCN Albumin Shield Platform Candidates 18 CLINICALLY - TESTED ADENOVIRUS EXPRESSING PH20 HYALURONIDASE TO DEGRADE STROMA + ALBUMIN SHIELD ΠTO PREVENT NEUTRALIZATION BY CIRCULATING ANTI - VIRAL ANTIBODIES TO FACILITATE IV MULTIDOSING + UNIQUE MULTIFUNCTIONAL PROTEINS TO TURN COLD TUMORS HOT VCN - 11: Hyaluronidase alone Hyaluronidase + Bispecific Engagers Hyaluronidase + Toxins Hyaluronidase + Immunomodulators COMMON FEATURES PRODUCT SPECIFIC FEATURES Albumin Shield platform invites potential licensing opportunities

• VCN OVs ARE OPTIMIZED FOR SYSTEMIC DELIVERY • Opportunity for virus to pursue metastatic lesions in addition to primary tumors • Selectivity has the potential to improve safety and pharmacokinetics (liver sequestration  tumor penetration  ) • VCN OVs ARE HIGHLY REPLICATIVE • Fulfilling systemic dosing requirements • Potent transgene expression is a built - in biomarker for tracking viral replication in the tumor • VCN OVs EXPRESS HYALURONIDASE to DEGRADE TUMOR STROMA • Increased tumor dissemination allowing co - administered chemotherapies and immunotherapies (CAR - T, CPI) • Improved infiltration of anti - tumor immune responders to improve efficacy • VCN OVs ENABLE MULTIDOSING in HARD - TO - TREAT TUMORS • Preclinically validated platform with decreased NAb susceptibility for systemic re - administration • Co - delivery of hyaluronidase and additional therapeutic transgenes VCN Potential Competitive Advantages 19 CAR - T chimeric antigen receptor T - cell. CPI checkpoint inhibitor. NAb neutralizing antibody. Rb - E2F pathway reviewed in Giacinti (2006) Oncogene 25: 5220 and Polager (2009) Nat Rev Cancer 9: 738.

Pipeline and Milestones

SYN and VCN Pro Forma Combined Pipeline After Acquisition IND - enabling Phase 3 Phase 2 Phase 1 β - lactamase SYN - 004 Hyaluronidase Technology (HT) VCN - 01 VCN - 01 VCN - 01 Prevention of aGVHD in allogeneic HCT recipients Pancreatic Cancer (IV) േ GEM/nab - paclitaxel Retinoblastoma ( IVit ) Combination Therapy with CPI bIAP SYN - 020 Radiation enteritis + other indications HT+Albumin Shield VCN - 11 Solid tumors Candidate aGVHD acute graft - vs - host disease; allogeneic HCT allogeneic hematopoietic cell transplant. bIAP bovine intestinal alkaline phosphatase. CPI immune checkpoint inhibitor. GEM/ nab+paclitaxel Gemcitabine + Abraxane ® . IT intratumoral. IV intravenous. IVit intravitreal. 21

Upcoming News and Potential Milestones After Acquisition H1 2023 Q2 2022 Q3 2022 Q4 2022 • SYN+VCN merger closing • VCN - 01 U. Leeds ISS first patient dosed • VCN - 01 UPenn ISS first patient dosed • SYN - 020 Phase 1 MAD topline data • SYN - 004 Phase 1b/2a data 1 st antibiotic cohort • SYN - 020 Phase 2a initiation (indication TBD) • SYN - 004 Phase 1b/2a 2 nd cohort begins dosing • Initiation of VCN - 01 PDAC Phase 2 • SYN - 020 Phase 2a data (indication TBD) • SYN - 004 Phase 1b/2a data 2 nd antibiotic cohort • VCN - 01 RB proposed pivotal trial initiation • VCN - 11 IND Filing 22 Q1 2022

• Advanced Clinical Oncology Pipeline and Platform • Multiple SYN and VCN clinical assets • Lead orphan cancer indications with critical unmet medical need • Continued expansion of the pipeline with joint discovery programs • Synergies Between Teams • Complementary skill sets and experience in OVs, gene therapy, CMC, and product development • Immediate access to laboratory facilities and personnel for joint discovery and development • Shared international clinical trial expertise • Multinational Presence • Facilitates access to clinical study sites, patients, regulatory agencies • Establishes a footprint in key EU market for partnering and commercialization • Access to US financial markets SYN - VCN: Accelerating the Pathway to Value 23

Appendix

VCN Oncolytic Virus Genetic Modifications L5 L5 Fiber Shaft RGDK L3 Hexon ABD SA K pA PH20 2 5 ¹ Since this is a transgene, progeny virus will also be albumin coated. ²MLP control means transgenes will only be expressed af ter replication, which occurs selectively in tumor cells. Transgene expression (PH20 in blood) can be a biomarker for viral replication in the tumor . ³PH20 cassette inserted downstream of the fiber gene contains a splice acceptor ( SA ), a kozak sequence ( K ) and a polyadenylation stop sequence ( pA ) 25 VCN - 01 VCN - 11 Ad5 wild type | Reduces Liver Tropism Fiber Shaft KKTK  Host albumin | Enables replication in normal cells | Facilitates liver sequestration | Replication restricted to tumor cells (Rb - E2F mutated) ABD albumin binding domain ( streptococcal protein G)¹ Ad5 Adenovirus type 5 E1a - Δ24 deletion of 24 base pairs within the E1a promoter; further modified by insertion of 8 extra E2F binding sites and one Sp1 - binding site at nucleotide site 415 ( 415p ) MLP major late promoter² PH20 soluble human testicular hyaluronidase³ KKTK Lys - Lys - Thr - Lys putative HSPG binding domain on fiber shaft RGDK Arg - Gly - Asp - Lys inserted in place of KKTK on fiber shaft VCN - 12 VCN - 11 armed with additional therapeutic transgene Degrades tumor stroma RGDK SA K pA PH20 | Binds host albumin to protect against neutralizing antibodies

IV VCN - 01 Clinical Trial Population (Multicenter ESP ¹ ) 26 ¹ NCT02045602. ²Concomitant VCN - 01 administered same day as first dose of Gemcitabine/Abraxane® ( G/A ). ³Sequential VCN - 01 administered 7 - days prior to first dose of G/A. Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271 . L ink to full ESMO 2019 poster provided on Appendix Slide 31. Characteristics Part I (VCN - 01 Alone) Part II (Concomitant)² Part III (Sequential)³ Dose, vp/patient 1.0x10¹¹ 1.0x10¹² 3.3x10¹² 1.0x10¹³ 3.3x10¹² 1.0x10¹³ 3.3x10¹² 1.0x10¹³ No Patients, n 3 4 3 6 6 6 8* 6 Median Age, years 67 70 72 54 61 59 62 63 Male / Female 2 / 1 3 / 1 2 / 1 5 / 1 3 / 3 4 / 2 1 / 7 2 / 4 ECOG Status 0 1 2 1 1 2 2 4 2 1 2 2 2 5 4 4 4 4 Primary Disease Colorectal Cancer (IV) 3 4 3 5 - - - - Head and Neck - - - 1 - - - - Pancreatic (III) - - - - 1 1 2 - Pancreatic (IV) - - - - 5 5 6 6 Site of Metastasis Liver ± other organ 2 2 1 6 5 5 5 6 Other 1 2 2 - - - 1 - * Two incorrectly enrolled patients were replaced and excluded from endpoint analysis but are included in the safety analysis ( ESM O 2019)

Part II: All AEs Regardless of Relatedness to VCN - 01 (ESMO 2019)¹ Concomitant IV VCN - 01 & G/A in PDAC (Multicenter ESP ¹ ) 27 ¹ NCT02045602. G/A Gemcitabine/Abraxane® (nab - paclitaxel). PDAC pancreatic ductal adenocarcinoma. vp virus particle. Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271 . L ink to full ESMO 2019 poster provided on Appendix Slide 31. Adverse Reaction Pts All Grades Grade ≥3 Adverse Reaction All Grades Grade ≥3 Preferred Term N n % n % Preferred Term n % n % Pyrexia 12 8 66.7% 0 0.0% Bacteremia 1 8.3% 1 8.3% Thrombocytopenia 12 7 58.3% 4 33.3% Enterocolitis* 1 8.3% 1 8.3% Asthenia 12 6 50.0% 1 8.3% Hepatitis, acute 1 8.3% 1 8.3% Musculoskeletal pain 12 4 33.3% 0 0.0% Chills 1 8.3% 0 0.0% Neutropenia 12 3 25.0% 2 16.7% Diarrhea 1 8.3% 0 0.0% Decreased appetite 12 3 25.0% 0 0.0% Dizziness 1 8.3% 0 0.0% Nausea 12 3 25.0% 0 0.0% Headache 1 8.3% 0 0.0% Febrile neutropenia 12 2 16.7% 2 16.7% Hypotension 1 8.3% 0 0.0% Transaminase increase 12 2 16.7% 1 8.3% Myalgia 1 8.3% 0 0.0% Vomiting 12 2 16.7% 0 0.0% Productive cough 1 8.3% 0 0.0% Combined data for 3.3x10¹² and 1.0x10¹³ vp/patient VCN - 01 IV doses administered on the same day as the first dose of G/A. Two DLTs at 1x10 ¹³ vp/patient dose: one patient suffered febrile neutropenia (Grade 4); a second patient died from combined acute hepatitis + thrombocytopenia + enterocolitis (Grade 5)*

Part III: All AEs Regardless of Relatedness to VCN - 01 (ESMO 2019)¹ Sequential IV VCN - 01 then G/A in PDAC (Multicenter ESP ¹ ) 28 ¹ NCT02045602. DLT dose limiting toxicity. G/A Gemcitabine/Abraxane® (nab - paclitaxel). PDAC pancreatic ductal adenocarcinoma. Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271 . L ink to full ESMO 2019 poster provided on Appendix Slide 31. Adverse Reaction Pts All Grades Grade ≥3 Adverse Reaction All Grades Grade ≥3 Preferred Term N n % n % Preferred Term n % n % Pyrexia 14 9 64.3% 0 0.0% Anaemia 2 14.3% 0 0.0% Nausea 14 4 28.6% 0 0.0% Neutropenia 1 7.1% 0 0.0% Vomiting 14 3 21.4% 0 0.0% Thrombocytopenia 1 7.1% 0 0.0% Influenza - like Illness 14 3 21.4% 0 0.0% Cough 1 7.1% 0 0.0% Diarrhea 14 2 14.3% 1 7.1% Headache 1 7.1% 0 0.0% Asthenia 14 2 14.3% 0 0.0% Herpes Simplex 1 7.1% 0 0.0% Transaminase increase 14 2 14.3% 0 0.0% Rhinorrhoea 1 7.1% 0 0.0% ALT increase 14 1 7.1% 1 7.1% AST increase 14 1 7.1% 1 7.1% Combined data for 3.3x10¹² and 1.0x10¹³ vp/patient VCN - 01 IV doses administered 7 - days prior to first dose of G/A. One AE of diarrhea (Grade 3) at the 1x10¹³ vp/patient dose was incorrectly reported a s a DLT but subsequently reclassified.

Adverse Events Treatment Related AEs (8) CTCAE Grade Grade 1 - 2 Grade ≥3* Anemia 1 (12.5%) - Leukopenia - 1 (12.5%) Neutropenia 2 (25.0%) - Thrombocytopenia 2 (25.0%) - Constipation 2 (25.0%) - Dyspepsia 1 (12.5%) - Melena 1 (12.5%) - Nausea 2 (25.0%) - Vomiting 1 (12.5%) - Asthenia/Fatigue 5 (62.5.0%) 1 (12.5%) Pyrexia 4 (50.0%) - Transaminase increased 1 (12.5%) 2 (25.0%) GGT increased 1 (12.5%) - Decreased appetite/Anorexia 2 (25.0%) - Hypophosphatemia - 1 (12.5%) Arthralgia / Musculoskeletal Pain 2 (12.5%) - Dysgeusia 1 (12.5%) - Epistaxis 1 (12.5%) - Intratumoral VCN - 01 In PDAC (Multicenter ESP¹) • Multicenter, open - label, dose escalation study of intratumoral ( IT ) VCN - 01 with IV chemotherapy ² • Level I VCN - 01 1 î 10¹º vp on days 1, 22, 43 and gemcitabine ( G ) on days 1, 8, 15, 22, 29, 35, 43 (n=2) • Level II VCN - 01 1 î 10¹¹ vp on days 1, 29, 57 and gemcitabine/Abraxane ® ( G/A ) on days 1,8, 15 and then every 4 weeks (n=6) • VCN - 01 replicated in tumors, expressed the PH20 transgene, and reduced tumor stiffness in evaluated patients • Detailed study results published ² • VCN - 01 IT administration is not currently being pursued • IV administration preferred 29 ¹ NCT02045589. ² Bazan - Peregrino (2021) J Immunother Cancer 9: e003254. Abraxane ® nab - paclitaxel. * O ne patient at the 1x10 ¹¹ vp dose died from localized abdominal fluid collection associated with gastric necrotic ulcer and upper GI bleeding (grade 5)

All AEs Regardless of Relatedness to VCN - 01 (ESMO 2019)¹ Intratumoral VCN - 01 in PDAC (Multicenter ESP ¹ ) 30 ¹ NCT02045589 . DLT dose limiting toxicity. G/A Gemcitabine/Abraxane® (nab - paclitaxel). PDAC pancreatic ductal adenocarcinoma. Manuscript submitted ; data presented in part at ESMO 2019 Garcia - Carbonero (2019) Ann Oncol 30(S5): v271 . data presented at ESMO 2019 Hidalgo (2019) Ann Oncol 30(S5):v171 . L ink to full ESMO 2019 poster provided on Appendix Slide 31. Adverse Reaction Pts All Grades Grade ≥3 Adverse Reaction All Grades Grade ≥3 Preferred Term N n % n % Preferred Term n % n % Asthenia/Fatigue 8 6 75.0% 1 12.5% Localized intraabdom . fluid collection 1 12.5% 1* 12.5% Pyrexia 8 4 50.0% 0 0.0% Febrile Neutropenia 1 12.5% 1 12.5% Hypertransaminemia 8 3 37.5% 2 25.0% Hypophosphatemia 1 12.5% 1 12.5% Neutropenia 8 3 37.5% 1 12.5% Anemia 1 12.5% 0 0.0% Thrombocytopenia 8 2 25.0% 0 0.0% Leucopenia 1 12.5% 0 0.0% Anorexia 8 2 25.0% 0 0.0% GGT increased 1 12.5% 0 0.0% Arthromyalgia 8 2 25.0% 0 0.0% Diarrhea 1 12.5% 0 0.0% Neurotoxicity 8 2 25.0% 0 0.0% Nausea 1 12.5% 0 0.0% Constipation 8 2 25.0% 0 0.0% Vomiting 1 12.5% 0 0.0% Epistaxis 1 12.5% 0 0.0% Combined data for VCN - 01 1.0 x10¹º vp/dose IT x 3 + IV Gemcitabine ( G ; n=2) and VCN - 01 1.0x10¹¹ vp/dose x 3 + IV Gemcitabine/ Abraxane ® ( G/A ; n=6). Two DLTs observed at 1x10 ¹¹ vp/patient dose: two patients had transaminase increases (Grade 3 - 4) ; a third patient died from intraabdominal fluid collection associated with gastric necrotic ulcer and upper GI bleeding (Grade 5)*

• Bayo - Puxan N et al. (2006) Role of the putative heparan sulfate glycosaminoglycan - binding site of the adenovirus type 5 fiber sh aft on liver detargeting and knob - mediated retargeting. J Gen Virol 87: 2487 – 2495 • Rojas J et al. (2012) Improved systemic antitumor therapy with oncolytic adenoviruses by replacing the fiber shaft HSG - binding d omain with RGD. Gene Ther 19: 453 – 457 • Rodríguez - García A et al. (2015) Safety and efficacy of VCN - 01, an oncolytic adenovirus combining fiber HSG - binding domain repla cement with RGD and hyaluronidase expression. Clin Cancer Res 21: 1406 - 18 • Pascual Pasto G et al. (2019) Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN - 01. Sci Transl Med 11: eaat9321 • Martínez - Vélez N et al. (2019) The oncolytic adenovirus VCN - 01 as therapeutic approach against pediatric osteosarcoma. Clin Cancer Res 22: 2217 - 25 • Bazan - Peregrino M et al. (2021) VCN - 01 disrupts pancreatic cancer stroma and exerts antitumor effects. J ImmunoTher Cancer 9: e003254. • Rojas LA et al. (2016) Albumin - binding adenoviruses circumvent pre - existing neutralizing antibodies upon systemic delivery. J Control Rel 237: 78 – 88 • Mato - Berciano A et al. (2021) Oncolytic adenovirus with hyaluronidase activity that evades neutralizing antibodies: VCN - 11. J Control Rel 332: 517 - 528 • Hidalgo M et al. (2019) Poster 5465: Proof of concept clinical study by EUS - guided intratumor injection of VCN - 01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer. European Society for Molecular Oncology conference ESMO 2019, 28 September 201 9, Barcelona, Spain Poster available at: http://www.vcnbiosciences.com/images/pdfs/ESMO2019%20Poster%20MoA%20VCN - 01%20vFinal.pdf • Garcia - Carbonero et al. (2019) Poster 5185: Systemic administration of the hyaluronidase - expressing oncolytic adenovirus VCN - 01 in patients with advanced or metastatic pancreatic cancer: first - in - human clinical trial. European Society for Molecular Oncology conference ESMO 2019, 29 September 2019, Barcelona, Spain. Poster available at: http://www.vcnbiosciences.com/images/pdfs/ESMO%202019%20Poster%20VCN - 01%20IV%20vFinal.pdf • Pascual - Pasto G et al. (2021) Presentation: VCN - 01 is an encouraging therapy against retinoblastoma. International Oncolytic Vi rus Conference IOVC2021, 07 November 2021, Sedona, AZ. Slides available at: http://www.vcnbiosciences.com/images/pdfs/Retinoblastoma_IOVC_2021v1.pdf VCN Biosciences Key Publications 31 VCN Scientific Publications http://www.vcnbiosciences.com/index.php/technologies/scientific - publications.

• Oncolytic viruses ( OVs ) infect and lyse cancer cells without harming normal cells • Can be naturally occurring or genetically engineered to improve selectivity, safety and efficacy • Can be developed from multiple virus types, including adenovirus , herpes simplex (HSV), measles, parvovirus, reovirus, and vaccinia • OV tumor cell lysis can reverse immune tolerance to tumors • Exposes tumor - specific and tumor - associated antigens (turning “cold” tumors “hot”) • Retarget the adaptive immune system to induce a long - lasting anti - tumor response • OVs face multiple challenges to systemic delivery • Poorly penetrable, antiviral and immunosuppressive tumor stroma • Host anti - OV immune responses • Sequestration of OV in the spleen and liver ¹ Oncolytic Viruses 32 Reviewed in: Balachandran (2019) Gastroenterology 156: 2056. Gonzalez - Pastor (2021) Cancer Gene Ther 28: 375. Hemminki (2020) J Hematol Oncol 13: 84. Martinez - Quintanilla (2019) J Clin Invest 129: 1407. Ungerechts (2016) Mol Ther Methods Clin Dev 3: 16018. Can be associated with liver toxicity and increases in liver enzymes.

• Adenoviruses ( AdV ) are medium - sized (90 – 100 nm), non - enveloped viruses with icosahedral shaped capsids containing a double - stranded DNA ( dsDNA ) genome typically 30 - 36 kb in length¹ - ³ • There are at least 57 AdV serotypes classified into 7 subgroups (A to G)² • AdV2 and AdV5 (Group C) are the most commonly - used viruses for OV design ¹ - ⁴ • Large packaging capacity ⁵ • Infect both dividing and non - dividing cells • Lack of integration into the host genome • Mild nature of illness after infection Adenovirus Overview 33 ¹Charman (2019) FEBS Lett 593: 3531. ²Hemminki (2020) J Hematol Oncol 13: 84. ³Hajeri (2020) Cancers 12: 1504. ⁴Gonzalez - Pastor (2021) Cancer Gene Ther 28: 375 – 89. ⁵Recombinant Ad5 genomes can be up to 105% of the 36 kb genome of the native Ad5. IMAGE: https://microbewiki.kenyon.edu/index.php/Adenovirus - based_Gene_Therapy:_a_Promising_Novel_Cancer_Therapy

Structural features determining virus viability, tumor access and efficacy¹ - ⁴ Oncolytic Adenoviruses 34 ¹Hajeri (2020) Cancers 12: 1504. ²Gonzalez - Pastor (2021) Cancer Gene Ther 28: 375. ³Yamamoto (2017) Cancer Sci 108: 831. ⁴ Khare (2012) J Virol 86: 2293, as much as 95 - 98% of an IV dose of unmodified Ad5 is trafficked to the liver where ~90% of the dose is sequestered and des troyed by resident liver macrophages called Kupffer cells. IMAGE: https://microbewiki.kenyon.edu/index.php/Adenovirus - based_Gene_Therapy:_a_Promising_Novel_Cancer_Therapy Virus attaches to target cell by interaction between the fiber knob and the host cell coxsackievirus and adenovirus receptor ( CAR ) Virus internalized into target cell by interaction between the penton base and target cell αvβ3 and αvβ5 integrins Genetic engineering can confer tumor selectivity and improve therapeutic efficacy² , ³ • Conditionally replicate only in tumor cells • Express therapeutic payloads that elicit or enhance anti - tumor effects • Avoid host and tumor defense mechanisms Hexon components can interact with host neutralizing antibodies, receptors, proteins, and cells and elicit an AdV - specific T - cell response Fiber shaft can bind to heparan sulphate proteoglycans ( HSPG ) and facilitate uptake into the liver ⁴

Pancreatic Cancer Cases and Deaths 2020 ¹ REGION ALL Male Female New Cases Deaths New Cases No. per 100,000 Deaths New Cases No. per 100,000 Deaths Caribbean 2,746 2,668 1,479 5.1 1,440 1,267 3.6 1,228 Central America 6,576 6,244 3,232 3.8 3,111 3,344 3.2 3,133 South America 28,030 27,118 13,766 5.4 13,346 14,264 4.3 13,772 Northern America 62,643 53,277 32,938 9.3 27,888 29,705 6.9 25,389 Eastern Asia 181,450 173,212 98,421 7.0 93,135 83,029 4.8 80,077 South - Eastern Asia 16,485 16,167 9,458 2.9 9,309 7,027 1.8 6,858 South - Central Asia 21,954 21,144 13,634 1.5 13,089 8,320 0.9 8,055 Western Asia 13,812 13,511 7,975 7.1 7,804 5,837 4.4 5,707 Central & Eastern Europe 44,371 42,788 22,576 9.9 21,812 21,795 5.6 20,976 Western Europe 45,461 43,336 22,672 9.9 21,684 22,789 7.4 21,652 Southern Europe 30,836 28,517 15,250 8.4 14,409 15,586 6.2 14,108 Northern Europe 19,448 17,493 9,712 8.3 8,793 9,736 6.7 8,700 Australia and New Zealand 4,674 3,776 2,370 7.9 1,952 2,304 6.7 1,824 WORLD 495,773 466,003 262,865 5.7 246,840 232,908 4.1 219,163 35 ¹Data from The Global Cancer Observatory, GLOBOCAN International 2020 survey of persons 0 - 74 years. https://gco.iarc.fr/today/data/factsheets/cancers/13 - Pancreas - fact - sheet.pdf . For additional US specific data see da Costa (2020) JNCI Cancer Spectrum 4: pkaa033.

¹ PDAC pancreatic ductal adenocarcinoma. Cancers in the pancreas head (~70%) are diagnosed earlier than cancers in the body or tail (ea ch ~15%), which have a worse prognosis, Sarantis (2020) World J Gastrointest Oncol 12: 173 - 181. ²Bengtsson (2020) Sci Rep 10: 16425. ³GLOBOCAN 2020 survey of persons 0 - 74 years. Ushio (2021) Diagnostics 11: 562. ⁴ Toesca (2018) Int J Radiation Oncol Biol Phys 100: 1155 - 1174. ⁵American Joint Committee on Cancer T umor size, N odal involvement, M etastasis. ⁶Yu (2015) Gut 64: 1783 - 9. Pancreatic Cancer Resectable Borderline Resectable Metastatic / Recurrent (unresectable) Stage I Stage II Stage III Stage IV PDAC >90% pancreatic cancer¹; median age 67 - 68 yr ; 51% male² 1 - year (5 - year) overall survival 24% (9%)³; median 4 - 6 months² Locally Advanced (unresectable) Differentiated by tumor involvement with vasculature⁴ AJCC Stage IA IB IIA IIB III IV T - N - M⁵ T1 N0 M0 T2 N0 M0 T3 N0 M0 T1 - 3 N1 M0 T1 - 3 N2 M0 T4 NX - 2 M0 TX - 4 NX - 2 M1 Median Age, yr (range) ⁶ 66 (30 - 88) 66 (31 - 89) 68 (31 - 93) 66 (30 - 95) 67 (31 - 94) 67 (30 - 95) Male (Female), %⁶ 51 (49) 48 (52) 50 (50) 51 (49) 50 (50) 54 (46) Proportion of PDAC, %² 1.3% 4.4% 11.5% 16.3% 10.6% 56.0% 5 - Year Survival, %² 31.7% 11.8% 9.0% 8.7% 1.9% 0.5% Pancreas Head, %⁶ 61% 58% 77% 85% 75% 55% Male (per 100,000)³ N. America 9.3; W. Europe 9.9; E. Asia 7.0 Female (per 100,000)³ N. America 6.9; W. Europe 7.4; E. Asia 4.8 36 Pancreatic Cancer Staging

¹Radiotherapy is used in <20% of PDAC cases as most present at a late stage. ²Neoadjuvant chemotherapy - if indicated - is ident ical to first - line chemotherapy. ³Patients with good performance status ECOG 0 - 1. ⁴Patients with good to moderate performance status ECOG 0 - 2.⁵Patients with poor performance status ECOG 3 - 4. ⁶Checkpoint inhibitor ( CPI e.g. pembrolizumab) added in some cases but CPIs have had very limited efficacy in PDAC to date. (m)FOLFIRINOX (modified) leucovorin + 5 - FU + irinotecan + oxaliplatin. nab - Paclitaxel nanoparticle albumin - bound paclitaxel. Tempero (2021) J Natl Compr Canc Netw 19: 439. Pancreatic Cancer Treatment 37 Resectable Borderline Resectable Metastatic / Recurrent (unresectable) Locally Advanced (unresectable) Differentiated by tumor involvement with vasculature⁴ (m)FOLFIRINOX³ Gemcitabine + nab - Paclitaxel⁴ OR FOLFIRI(NOX)³ Gemcitabine + nab - Paclitaxel⁴ 5 - FU + Leucovorin + Liposomal Irinotecan⁴ Radiotherapy if  resection margins¹ Neoadjuvant² Gemcitabine ± erlotinib ; single agent capecitabine or 5 - FU; ± CPI⁶ Single agent g emcitabine , capecitabine or 5 - FU⁵ First - Line Progression or Recurrence 37 Stage I Stage II Stage III Stage IV Differentiated by tumor involvement with vasculature⁴ VCN - 01

Tumor Stroma Barriers to Therapy Pancreatic Ductal Cell Carcinoma (PDAC) 38 Graphic from ¹Balachandran (2019) Gastroenterology 156: 2056. ²Sarantis (2020) World J Gastrointest Oncol 12: 173. ³Orth (2019) Radiation Oncol 14: 141. ⁴Christenson (2020) Lancet Oncol 21 :e135. ⁵ Elsayed (2021) Biomedicines 9: 389. ⁶ Tahkola (2021) Sci Rep 11: 12216. • PDAC stroma can account for 50 - 70% of the total tumor mass¹ , ² (up to 90% of the tumor volume³ , ⁴) • PDAC stroma is characterized by dense immunosuppressive desmoplasia which stems from activated pancreatic stellate cells ( PSCs ) that produce collagens, laminin, and fibronectin¹ - ⁵ • Extracellular matrix components such as hyaluronic acid can creating a physical barrier to the delivery of chemotherapy and immunotherapeutics by elevating interstitial fluid pressures and collapsing intratumoral vasculature¹ - ⁵ • Malignant cells, fibroblasts, and myeloid cells secrete immunosuppressive cytokines and chemokines that prevent effective anti - tumor T cell responses • PDAC has remained almost completely resistant to immunotherapy (including checkpoint inhibitors)¹ , ³ • Stromal hyaluronan accumulation associated with low immune response and poor prognosis⁶ STROMA

• Retinoblastoma ( Rb ) is a rare pediatric malignancy accounting for ~2 - 3% of all childhood cancers¹ • Primarily diagnosed in children ≤2 years¹ • 200 - 300 cases each year in the USA, EU and >1,000 cases each in China and India² , ³ • Significant regional disparities in age/stage at diagnosis, treatment options, and mortality (40 - 70% mortality in low - income countries cf. 3 - 5% in high income countries)⁴ - ⁷ • Rb can be unilateral (60 - 70% of cases) or bilateral (30 - 40%)⁴ , ⁸ • Unilateral disease: 85% of cases have a somatic RB1 mutation, 15% have a germline (heritable) mutation • Bilateral disease: assumed that 100% have a germline mutation • Rb treatments vary with stage of disease⁴ • Prior to intraarterial chemotherapy ( IAC ), enucleation was the primary life - saving intervention for Rb patients • IAC, where available, has dramatically reduced enucleation rates (from >95% pre - IAC to <10%)⁹ • Multiple potential opportunities for VCN - 01 in Rb treatment • Improve outcomes of surgery and/or chemotherapy (potential reduction in intensity) • Rescue therapy to prevent enucleation Retinoblastoma 39 ¹https://www.cancer.org/cancer/retinoblastoma/about/key - statistics.html. ²Stacey (2021) Ophthalmology 128: 1369. ³One Retinoblastoma World Map https://map.1rbw.org/. ⁴For additional details and references see Appendix slides 34 - 36. ⁵ Tomar (2020) Ophthalmology 127: 1719. ⁶ Fabian (2020) JAMA Oncol 6: 685 . ⁷Canturk (2010) Br J Ophthalmol 94: 1432. ⁸https://eyewiki.org/Retinoblastoma. ⁹Abramson (2015) PLoS ONE 10: e0145436.

Rb Cases - One Retinoblastoma World Map ¹ 40 ¹Reported number of retinoblastoma cases from One Retinoblastoma World Map https://map.1rbw.org/ (accessed April - November 2021)

¹ Fabian (2020) JAMA Oncol 6 :685; m edian [IQR] age; ²Fabian ID (2018) Community Eye Health 31: 11. ³ Tomar (2020) Ophthalmology 127: 1719. HIC high income countries; ICRB International Classification of Retinoblastoma. IIRC International Intraocular Retinoblastoma Staging System. IRSS International Retinoblastoma Staging System. LIC low - income countries. Subret subretinal. Retinoblastoma Staging EXTRAocular IRSS² IIRC/ICRB² Group A INTRAocular Group B Group C Group D Group E Stage I Stage 0 Stage II Stage III Stage IV Metastatic (a) No CNS (b) CNS 0.5% 18.7% Enucleated Tumor completely resected 40.8% 33.8% Enucleated Microscopic r esidual t umor 0.6% 11.5% Regional Extension Orbit, cervical lymph nodes 0.5% 20.1% Intraocular Patient treated conservatively HIC 56.8% cases LIC 8.7% cases Very Low Risk of losing eye Tumor ≤3 mm Only retina No vitreous seeding 6.1%, 6.5% Low Risk of losing eye Tumor >3 mm Only retina No vitreous seeding 16.5%, 20.9% Moderate Risk of losing eye Discrete tumor Any location Focal vitreous or subret seeds 7.3%, 1.4% High Risk of losing eye Non - discrete Disseminated Diffuse vitreous or subret seeds 38.8%, 9.7% Very High Risk of losing eye Eye is anatomically or functionally destroyed 31.3%, 61.5% HIC: LIC: HIC 1.5% cases LIC 49.1% cases¹ HIC 98.5% cases LIC 50.9% cases¹ HIC Age 14.0 [6.2 - 26.6] mos at diagnosis¹ LIC Age 30.5 [18.3 - 45.9] mos at diagnosis UNILATERAL HIC 69.2% LIC 68.3%¹ BILATERAL HIC 30.8% LIC 31.7% IIRC, ICRB³ 41 RETINOBLASTOMA

Retinoblastoma Treatment Bilateral or germline RB1 Group A Unilateral Group B Group C Group D Group E 42 Extraocular IAC Cryo or ITT GLOBE SALVAGE Consolidation Cryo or TTT; IAC; IVC; IvitC ; IcamC ; radiotherapy/brachytherapy (rare) ENUCLEATION ± High Dose IVC IVC, IAC Macula Involved Adapted from: Ancona - Lezama (2020) Indian J Ophthalmol. 68: 2356. Cryo cryotherapy. IAC intra arterial chemotherapy ( melphalan ± topotecan , carboplatin). IcamC intra cameral chemotherapy (melphalan, topotecan). IVC intra venous chemotherapy ( vincristine+etoposide+carboplatin ). IvitC intra vitreal chemotherapy (melphalan, topotecan). TTT transpupillary thermotherapy. FAIL GLOBE SALVAGE 1 st Line FAIL FAIL RETINOBLASTOMA FAIL