EX-99.3 4 tm224581d1_ex99-3.htm EXHIBIT 99.3

 

Exhibit 99.3

 

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, Ramón Alemany, Manel Cascalló , Guillermo L. Chantada, Angel M. Carcaboso.

 

 

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 mutation) 65%

 

 

3 Retinoblastoma orthotopic models H&E Anti - human Nuclei Optic nerve invasion Retinal tumor invasion

 

 

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

 

 

5 VCN - 01 improves ocular survival and inhibits metastasis in retinoblastoma xenografts

 

 

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) Dose escalation in monotherapy: • 2 E9 vp /eye 1 patient • 2 E10 vp /eye 3 patients  3 • 2 E10 vp /eye 1 - 3 patients  ongoing POPULATION Recruitment ongoing DOSAGE VCN - 01 in Retinoblastoma: Clinical trial Intravitreal administration of VCN - 01 in patients NCT03284268

 

 

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 - inflammatory drugs . x VCN - 01 does not change the retinal function . Safety of VCN - 01 in RB: Clinical trial Safety FSJD - RTB Trial All grades Grade ≥3 Adverse Reaction (Preferred Term) Nº patients treated* Nº patients observed % Nº patients observed % Uveitis 4 2 50% 2 50% Periflebitis 4 1 25% 0 0% 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

 

 

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 - 01 admin Necrotic tumor Conserved retina a - E1A IHC

 

 

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 Necrosis without clear evidence of tumor seed reduction D61 Vitritis - associated turbidity precluding monitoring the tumor activity Reduction of tumoral vitreous seeds in size and number - - Complete Regression D53 Retinal detachment associated to previous chemotherapies No viable tumor was found at enucleation NCT03284268

 

 

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 COMPLETE REGRESSION Intravitreous Administration (2E+10 vp /dose) Topotecan treatment re - initiation 9 months Sustained complete Response 3 rd Patient 3 - years old ƃ Bilateral retinoblastoma (with germline Rb 1 mutation), with 1 st eye already enucleated . Calcified Tumor (from previous treatments) VCN - 01 is clinically effective in pediatric retinoblastoma patients D45 NCT03284268

 

 

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 aquous humor are observed over long periods of time, suggesting viral replication. 14 64 NCT03284268

 

 

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 Miriam Bazan - Peregrino R&D Director VCN Biosciences SL www.vcnbiosciences.com phone: +34 93 571 2534 mbazan@vcnbiosciences.com Ramon Alemany

 

 

 

 

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

 

 

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 .

 

 

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 e r i n t r a v i t r e a l i n j e c t i o n 1 2 4 5 Viral reflux is observed at the eye surface after intravitreal administration 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 1 2 4 5 Viral particles at aquous humos are observed over long periods of time, suggesting viral replication. 14 64 0 10 20 30 40 50 1 10 100 1000 10000 100000 NAbs titer Days N A b s t i t e r ( 1 / d i l u t i o n ) NAbs titer is increased after VCN-01 administration 1 2 4 5