Theriva Biologics, Inc. · AMEX:TOVX
Theriva Biologics — Synthetic Biologics — Technical Presentation (January 2022)
16 slides from Theriva Biologics's technical presentation, Jan 27, 2022
Slide 1: VCN-01 is an encouraging therapy against retinoblastoma
VCN - 01 is an encouraging therapy against retinoblastoma IOVC 2021 1 Guillem Pascual - Pasto, Miriam Bazan - Peregrino , Ana Mato - Berciano, Genoveva Correa, Maria Cuadrado - Vilanova, Víctor Burgueño - Sandoval, Patricia Alonso - Lopez, Silvia Torres - Manjon , Rafael Moreno, Jaume Catalá - Mora,
Slide 2: Retinoblastoma overview
2 ▪ Developmental intraocular tumor of the retina of the young child ▪ Average age at diagnosis: 2 years ▪ It rarely occurs in those older than 6 years ▪ Incidence 1 / 18,000 newborns ▪ Cause: biallelic mutation of the Rb1 gene ▪ Bilateral RB (with germline Rb1 mutation) 35%, unilateral RB (sporadic
Slide 3: Retinoblastoma orthotopic models
3 Retinoblastoma orthotopic models H&E Anti - human Nuclei Optic nerve invasion Retinal tumor invasion
Slide 4: First-in-class oncolytic adenovirus that remodels tumour matrix
4 VCN - 01 “First - in - Class oncolytic adenovirus that remodels tumour matrix” Replication restricted to tumor cells with dysregulated pRB pathway Integrin targeting Degradation of hyaluronic acid to enhance viral spreading and increase antitumor activity
Slide 5: VCN-01 improves ocular survival and inhibits metastasis in retinoblastoma xenografts
5 VCN - 01 improves ocular survival and inhibits metastasis in retinoblastoma xenografts
Slide 6: Clinical trial of intravitreal VCN-01 in retinoblastoma
6 D1 D15 D28 D45 D180 MRI - MDD Oft - ERG Safety visit 6 months Follow - up VCN - 01 Oft - Lab ERG VCN - 01 MRI - MDD Oft - ERG Children (2 - 6 years) with retinoblastoma Two intravitreal administrations 2 weeks interval Endpoints: Safety profile and Antitumoural Activity (retardation of enucleation
Slide 7: Safety of VCN-01 in RB: clinical trial
7 Stable Electroretinographic signals NCT03284268 x VCN - 01 is well tolerated after intravitreal administration, although some degree of turbidity and vitritis associated to intravitreal inflammation is observed . x Inflammation is managed with local and systemic administration of anti - inflammato
Slide 8: Selective replication in RB patients
8 E 1 A protein expression is associated with tumour necrosis Lack of E 1 A expression in normal retina confirms selective VCN - 01 replication Selective VCN - 01 replication in RB patients NCT03284268 First patient 2 years - old patient Dose: 2E9 vp /eye Eye was enucleated 28 days after 2 nd VCN -
Slide 9: VCN-01 significantly reduces the number of vitreous seeds
VCN - 01 significantly reduces the number of vitreous seeds 9 Patient & Dose 1st 2E+9vp 2nd 2E+10vp 3rd 2E+10vp 4th 2E+10vp D14 D28 D0 D14 D28 D0 D64 M8 D0 N/A D53 D0 Enucleation Date Enucleation Reason Clinical Evaluation D42 Vitritis - associated turbidity precluding monitoring the tumor activity
Slide 10: VCN-01 is clinically effective in pediatric retinoblastoma patients
10 D1 D15 D28 D64 VCN - 01 VCN - 01 VCN - 01 Previous treatments : - Systemic chemotherapy CBP/VP - 16 /VCR (followed by intraarterial dosing of topotecan/melphalan) . - Tumor relapse 9 months later Intravitreous melphalan : NO RESPONSE - Chemotherapy STOP . Active Tumor (vitreous seeds) 6 months
Slide 11: VCN-01 replicated within retinoblastoma tumors over time
11 VCN - 01 replicated within retinoblastoma tumors over time COMPLETE REGRESSION 3 rd patient 0 50 100 150 200 10 0 10 1 10 2 10 3 10 4 10 5 10 6 10 7 10 8 Viral particles at aqueous humor Days v p / m L @ a q u e o u s h u m o r 1st Patient 2nd Patient 3rd Patient 4th Patient Viral particles at aq
Slide 12: The Retinoblastoma Team
12 Manel Cascalló Chief Executive Officer VCN Biosciences SL www.vcnbiosciences.com phone: +34 93 571 2359 / + 34 609432375 mcascallo@vcnbiosciences.com The Retinoblastoma Team Angel M. Carcaboso Guillermo Chantada Guillem Pascual - Pasto Manel Cascallo Miriam Bazan - Peregrino Jaume Català - Mora M
Slide 13: Slide 13
Slide 14: Efficacy of single and double intravitreous VCN-01 in orthotopic xenografts
14 Single Efficacy of single & double intravitreous VCN - 01 in orthotopic retinoblastoma xenografts Double HSJD-RBT-002 0 50 100 150 0 50 100 Control VCN-01 P=0.135 Days E y e s u r v i v a l HSJD-RBT-002 0 50 100 0 50 100 Controls VCN-01 P<0.0001 Days E y e s u r v i v a l
Slide 15: Patient 5 enucleation findings
Patient 5. Received both doses of VCN - 01 ITV and was enucleated on D53 due to retinal detachment associated to previous chemotherapies. No tumor was found at enucleation .
Slide 16: Viral particles, reflux and NAbs titer after administration
0 10 20 30 40 50 0.0 0.2 0.4 0.6 0.8 1.0 vp/mL of Blood Days v p / m L 1 2 4 5 No virus is detected in blood after intravitreal adminsitration 0 5 10 15 20 10 0 10 1 10 2 10 3 10 4 10 5 10 6 10 7 10 8 Viral particles at eye surface (reflux) Days v p @ e y e s u r f a c e d u e t o r e f l u x a f t
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