Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — Merger or Acquisition (December 2021)
37 slides from Theriva Biologics's merger presentation, Dec 14, 2021
Slide 1: December 14, 2021 Business Update
December 14, 2021 Business Update
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: VCN Biosciences overview
• Founded in Barcelona, Spain in 2009 by Drs. Ramon Alemany, Gabriel Capellà and Manel Cascalló • Developing unique oncolytic viruses ( OVs ) optimized for intravenous administration and maximum tumor destruction • Evaluating first product, VCN - 01, as monotherapy and combination therapy with 70 ca
Slide 4: VCN Experienced Management Team
VCN Experienced Management Team • Dr. Cascalló will assume the role of Managing Director in the Synthetic Biologics EU subsidiary • More than 12 years experience as CEO of biotech companies • Expert in clinical development of oncolytic adenovirus and author of many peer - reviewed scientific publica
Slide 5: 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 6: 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 7: VCN Technologies
Ven BIOSCIENCES Synthetic ) BIOLOGICS VCN Technologies
Slide 8: Oncolytic Viruses are a Promising Therapeutic Approach
• Oncolytic Viruses are a Promising Therapeutic Approach • Combines 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 therapies to treat cancer more effectively (
Slide 9: Unique Mechanism of Action for VCN Platform
Unique Mechanism of Action for VCN Platform 9
Slide 10: VCN - Oncolytic Adenovirus
VCN - 01 Oncolytic Adenovirus • SYSTEMIC • Increased affinity for tumor cells • Reduced liver tropism • Highly replicating • SELECTIVE • Replication only in tumor cells with defects in the retinoblastoma Rb - E2F pathway ¹ • Transgenes only expressed after virus replication² • STROMA DEGRADING • Deg
Slide 11: Pancreatic Ductal Adenocarcinoma (PDAC)
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 a
Slide 12: VCN-PDAC Clinical Data Encourage Phase 2
VCN - 01 PDAC Clinical Data Encourage Phase 2 • Multicenter, open - label, dose escalation study of a single IV dose of VCN - 01 “ gemcitabine/Abraxane® ( G/A )¹ • 42 patients treated with different dosing regimens, including monotherapy; concomitant treatment; and sequential treatment ² • Outcomes
Slide 13: VCN Remodels the PDAC Tumor Matrix
VCN - 01 Remodels the PDAC Tumor Matrix 13 Sustained hyaluronidase quantification in patient sera is linked to viral activity and can be used for tracking effective VCN - 01 replication Hepatic metastasis of PDAC patient a - CD8 a - IDO VCN - 01 remodels pancreatic tumor matrix and the immunological
Slide 14: 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 can be used in combination with chemotherapy to pote
Slide 15: VCN in Retinoblastoma
VCN - 01 in Retinoblastoma • Single center, open - label dose escalation study of intravitreal ( IVT ) VCN - 01 ¹ , ² • Children aged 1 - 12 years • Rb that is recurrent or refractory to chemotherapy and for whom enucleation is the best treatment option • VCN - 01 (2.0x10 ⁹ or 2.0x10 ¹º vp per eye)
Slide 16: Exploring Expanded Indications for VCN-01
Exploring Expanded indications for VCN - 01 Location Phase Indication Co - therapy Route (n) Status NCT or EudraCT Multicenter (ESP) 1 PDAC Gemcitabine + nab - Paclitaxel IT (8) Complete¹ NCT02045589 Institut Català d'Oncologia (ICO) 1 HNSCC Durvalumab IV (11) On - going NCT03799744 U. Leeds 1 Adult
Slide 17: Planned Phase 2 PDAC and Phase 2/3 Rb 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 18: 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 19: VCN Albumin Shield Platform Candidates
VCN Albumin Shield Platform Candidates 19 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 20: VCN OV platform key features
• VCN OVs ARE OPTIMIZED FOR SYSTEMIC DELIVERY • Treatment of primary and metastatic lesions for multiple solid tumor types (Rb - E2F defective in most solid tumors) • Extremely selective with improved safety and pharmacokinetics (liver sequestration tumor penetration ) • VCN OVs ARE HIGHLY REPLICATI
Slide 21: Pipeline and Milestones
Ven BIOSCIENCES Synthetic ) BIOLOGICS Pipeline and Milestones
Slide 22: SYN and VCN Combined Pipeline
SYN and VCN Combined Pipeline 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 (IVT) Combination Therapy with CPI bIAP
Slide 23: Upcoming News and Potential Milestones
Upcoming News and Potential Milestones H1 2023 Q4 2021 Q2 2022 Q3 2022 Q4 2022 • VCN - 01 U. Leeds ISS first patient dosed • SYN+VCN merger closing • VCN - 01 UPenn ISS first patient dosed • SYN - 004 Phase 1b/2a data 1 st antibiotic cohort • SYN - 020 Phase 1 MAD topline data • SYN - 004 Phase 1b/2
Slide 24: Appendix
Ven BIOLOGICS BIOSCIENCES Synthetic ) Appendix
Slide 25: 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 26: Adenovirus Overview
Adenovirus Overview 26 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 CREDIT: https://micro
Slide 27: Oncolytic Adenoviruses
Structural features determining virus viability, tumor access and efficacy¹ - ⁴ Oncolytic Adenoviruses 27 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 28: VCN Oncolytic Virus Genetic Modifications
VCN Oncolytic Virus Genetic Modifications L5 L5 Fiber Shaft RGDK L3 Hexon ABD SA K pA PH20 2 8 ¹ Since this is a transgene and not a chemical/physical coating, progeny virus will also be albumin coated. ²MLP control means tra nsgenes will only be expressed after replication, which occurs selectively
Slide 29: 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 30: Pancreatic Cancer staging and survival
¹ PDAC pancreatic ductal adenocarcinoma. Cancers in the pancreas head (~70%) are diagnosed earlier than cancers in the body or tail (e ach ~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 31: 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 32: Tumor Stroma Barriers to Therapy
Tumor Stroma Barriers to Therapy Pancreatic Ductal Cell Carcinoma (PDAC) 32 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 33: 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 34: Rb Cases - One Retinoblastoma World Map
Rb Cases - One Retinoblastoma World Map ¹ 34 ¹Reported number of retinoblastoma cases from One Retinoblastoma World Map https://map.1rbw.org/.
Slide 35: 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 36: Retinoblastoma Treatment
Retinoblastoma Treatment Bilateral or germline RB1 Group A Unilateral Group B Group C Group D Group E 36 Extraocular IAC Cryo or ITT GLOBE SALVAGE Consolidation Cryo or TTT; IAC; IvitC ; IcamC Plaque radiotherapy (brachytherapy; rare) ENUCLEATION ± High Dose IVC IVC, IAC Macula Involved Adapted from
Slide 37: References
• Bayo - Puxan N et al. (2006) Role of the putative heparan sulfate glycosaminoglycan - binding site of the adenovirus type 5 fiber shaft on liver detargeting and knob - mediated retargeting. J Gen Virol 87:2487 – 2495 • Rojas J et al. (2012) Improved systemic antitumor therapy with oncolytic adenov
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