Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — B. Riley Securities Oncology Investor Conference January 2022
42 slides from Theriva Biologics's conference presentation, Jan 27, 2022
Slide 1: B. Riley Securities Oncology Investor Conference
January 2022 B. Riley Securities Oncology Investor Conference
Slide 2: Forward-Looking Statements
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 t
Slide 3: Synthetic Biologics advancing into oncology with VCN acquisition
• 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 ) opt
Slide 4: SYN-VCN Transaction Summary
• 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 paym
Slide 5: Oncolytic Virus Features and Challenges
• 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, checkpoin
Slide 6: Oncolytic Adenovirus
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 b
Slide 7: Unique Mechanism of Action for VCN Products
Unique Mechanism of Action for VCN Products 7
Slide 8: Clinical Trials
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 Mul
Slide 9: Pancreatic Ductal Adenocarcinoma (PDAC)
• 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
Slide 10: Clinical Data Encourage PDAC Phase 2
• 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 -
Slide 11: Most Common IV Related AEs
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
Slide 12: Remodels the PDAC Tumor Matrix
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
Slide 13: Retinoblastoma, a Rare Pediatric Malignancy
• 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 po
Slide 14: Intravitreal Study in Retinoblastoma
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
Slide 15: Interim Safety Data for Intravitreal
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
Slide 16: Planned Phase 2 and Phase 2/3 Trials
• 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 therap
Slide 17: Albumin Shield to Expand the VCN Platform
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
Slide 18: VCN Albumin Shield Platform Candidates
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
Slide 19: VCN Potential Advantages
• 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
Slide 20: Pipeline and Milestones
Ven BIOSCIENCES Synthetic ) BIOLOGICS Pipeline and Milestones
Slide 21: SYN and VCN Pro Forma Combined Pipeline
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 ) Com
Slide 22: Upcoming News and Potential Milestones After Acquisition
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
Slide 23: SYN-VCN: Accelerating the Pathway to Value
• 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,
Slide 24: Appendix
Synthetic (G5) cs Appendix
Slide 25: VCN Oncolytic Virus Genetic Modifications
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 expressio
Slide 26: IV Clinical Trial Population
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 G
Slide 27: Part II: All AEs Regardless of Relatedness
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 ES
Slide 28: Part III: All AEs Regardless of Relatedness
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 i
Slide 29: Intratumoral in PDAC Adverse Events
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
Slide 30: All AEs Regardless of Relatedness, Intratumoral in PDAC
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
Slide 31: References
• 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 aden
Slide 32: Oncolytic Viruses
• 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, reo
Slide 33: Adenovirus Overview
• 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
Slide 34: Oncolytic Adenoviruses
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 u
Slide 35: Pancreatic Cancer Cases and Deaths 2020
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
Slide 36: Pancreatic Cancer
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 pers
Slide 37: Pancreatic Cancer Treatment
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 per
Slide 38: Tumor Stroma Barriers to Therapy
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) Biomedicine
Slide 39: Retinoblastoma overview
• 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, t
Slide 40: Rb Cases - One Retinoblastoma World Map
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)
Slide 41: Retinoblastoma Staging
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 Internationa
Slide 42: Retinoblastoma Treatment
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:
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