Sorrento Therapeutics, Inc. · OTC:SRNE
Sorrento Therapeutics — Technical Presentation (June 2019)
26 slides from Sorrento Therapeutics's technical presentation, Jun 19, 2019
Slide 1: CD38 Immunotherapies June 2019
CD38 Immunotherapies June 2019 NON - CONFIDENTIAL
Slide 2: Disclaimer
Disclaimer Certain statements contained in this presentation or in other documents of Sorrento Therapeutics, Inc . (the “Company” or “Sorrento”) and of any of its affiliates, along with certain statements that may be made by management of the Company orally in presenting this material are, or may be
Slide 3: CD38 Immunotherapies
CD38 Immunotherapies 3 3 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 4: CD38 Biology Background
CD38 Biology Background › CD38 is a single chain type II transmembrane glycoprotein (45kDa) › CD38 is detectable at low levels in mature lymphocytes or in non - hematopoietic tissues › Highly and ubiquitously expressed on Multiple Myeloma (MM) cells and overexpressed by the majority of Acute Lymphob
Slide 5: CD38 Therapeutics Business Unit - Immunotherapy Pipeline
CD38 Therapeutics Business Unit - Immunotherapy Pipeline › The Business Unit focuses on the development of a CD38 - directed product suite with potential out - licensing, collaboration and/or other strategic considerations › CD38 CAR - T: Phase 1 Clinical Trial – Ongoing › Next - gen CD38 DAR - T Ce
Slide 6: Anti-CD38 mAb A2
Anti - CD38 mAb A2 6 6 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 7: CD38 Monoclonal Antibody A2 Possesses Unique CD38-binding Properties
CD38 Monoclonal Antibody A2 Possesses Unique CD38 - binding Properties › The anti - CD38 mAb A2 mAb is a fully human antibody selected from our GMAB™ library › CD38A2 and Daratumumab have nanomolar affinities for the CD38 protein › CD38A2 exhibits fast - on/fast - off binding kinetics o Most likely
Slide 8: CD38A2-based immunotherapies are active against Daratumumab-resistant MM patient tumor cells
CD38A2 - based immunotherapies are active against Daratumumab - resistant MM patient tumor cells 8 8 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 9: CD38A2 Immunotherapies are Active Against Dara-refractory MM Patient Tumor Cells
CD38A2 Immunotherapies are Active Against Dara - refractory MM Patient Tumor Cells Patients: › Cells from 3 Dara - sensitive MM patients were tested › Cells from 6 Dara - resistant MM patients were tested › All patients were MM patients that received Daratumumab 16 mg subcutaneously at least 8 times
Slide 10: Determination of Daratumumab-Responsiveness in MM Patients
Determination of Daratumumab - Responsiveness in MM Patients › Daratumumab resistance was assessed at the end of 8 cycles of treatment. › M - component relative changes in the patients included in the CD38 immunotherapy in vitro experiments are shown. Dara - resistant #1 #2 #4 #5 #6 #3 Patient 10 10
Slide 11: CD38-ADCs and Daratumumab Exert Cytotoxicity against Tumor Cells from Dara-Responsive MM Patients
CD38 - ADCs and Daratumumab Exert Cytotoxicity against Tumor Cells from Dara - Responsive MM Patients › Primary MM cells MACS separated and frozen (5x10e6 cells) › Thawed 6 patients CD138+ fractions o 5 patient samples could be evaluated › Dara samples cultured with 2x10e5 PBMCs (E:T ratio 10) for 2
Slide 12: CD38-ADCs Exert Cytotoxicity against Tumor Cells from Dara-Resistant MM Patients
CD38 - ADCs Exert Cytotoxicity against Tumor Cells from Dara - Resistant MM Patients • Primary MM cells MACS separated and frozen (5x10 e6 cells) • Thawed 6 patients CD138+ fractions • 4 patient samples could be evaluated • Dara samples cultured with 2X10 e5 PBMCs (E:T ratio 10) from Day 5 • Each li
Slide 13: CD38-CAR-T
CD38 - CAR - T 13 13 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 14: Dose-Dependent In Vivo Anti-Tumor Efficacy of CD38 CAR-T Cells in Multiple Myeloma Model
Dose - Dependent In Vivo Anti - Tumor Efficacy of CD38 CAR - T Cells in Multiple Myeloma Model 14 14 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 15: CD38 CAR-T: Phase 1 Clinical Trial - Ongoing
CD38 CAR - T: Phase 1 Clinical Trial - Ongoing › Patients dosed at two US Clinical Sites o Currently continuing enrollment o Additional clinical sites will be activated soon › Manufacturing successfully performed at our CAR - T cGMP facility in San Diego, CA 15 15 © 2019 Sorrento Therapeutics, Inc.
Slide 16: Next-Gen Anti-CD38 KOKI DAR-T
Next - Gen Anti - CD38 KOKI DAR - T 16 16 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 17: From CAR to DAR
From CAR to DAR TM scFv Fab TM Chimeric Antigen Receptor (CAR) scFv - based Dimeric Antigen Receptor (DAR) Fab - based linker Hinge Disulfide bond 17 17 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38
Slide 18: At Lower Dose, CD38 DAR-T Cells are more Potent than CD38 CAR-T Cells
At Lower Dose (4x10e6 Cells), CD38 DAR - T Cells are more Potent than CD38 CAR - T Cells 18 18 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 19: Comparison of DAR-T Cell and CAR-T Cell cGMP Manufacturing Processes
Illustrative/Potential Comparison of DAR - T Cell and CAT - T Cell cGMP Manufacturing Processes Autologous CAR - T Cell Manufacturing Allogeneic DAR - T Cell Manufacturing 19 19 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without
Slide 20: Evolution of the Platform from Auto-CAR-T to Allo-DAR-T
Evolution of the Platform from Auto - CAR - T to Allo - DAR - T (drug) Targeting CD38 Clinical Proof - of - Concept CD38 CAR - T Potential Product KOKI CD38 DAR - T Advantages of DAR - T over CAR - T Chimeric Antigen Receptor (CAR) Dimeric Antigen Receptor (DAR) Increased potency Proprietary constru
Slide 21: Anti-CD38 ADC
Anti - CD38 ADC 21 21 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 22: Anti-CD38 ADC
Anti - CD38 ADC › Product candidate: CD38 - 077 ADC o IND filing: H2 2019 › Antibody (CD38 A2): Identified from Sorrento Therapeutics fully human G - MAB™ library (IgG1) › Payload: Duostatin - 5. Proprietary microtubule inhibitor. Patent application filed › Duostatin - 5 has been used for other part
Slide 23: CD38A2-ADC Exerts Strong Anti-tumor Activity in Myeloma Mouse Model
CD38A2 - 077 ADC Exerts Strong Anti - tumor Activity in Myeloma Mouse Model 23 23 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 24: CD38/CD3 Bispecific Antibody
CD38/CD3 Bispecific Antibody 24 24 © 2019 Sorrento Therapeutics, Inc. All Rights Reserved. NON - CONFIDENTIAL. Do not copy, distribute, or reproduce without express permission. CD38 Immunotherapies – June 2019
Slide 25: CD38/CD3 BsAb Mediates CD38-dependent Cytotoxicity with Sub-nanomolar Potency in vitro
CD38/CD3 BsAb Mediates CD38 - dependent Cytotoxicity with Sub - nanomolar Potency in vitro › CD38A2/CD3 BsAb shows potent CD38 - dependent tumor cell killing compared to non - specific BsAb control and parental mAb co - administration CD38/CD3 BsAb control BsAb CD38 IgG + CD3 IgG 25 25 © 2019 Sorren
Slide 26: Pilot In vivo Study: Head-to-head Comparison of CD38/CD3 BsAb and CD38 DAR-T
Pilot In vivo Study: Head - to - head Comparison of CD38/CD3 BsAb and CD38 DAR - T Cell Therapy 2 doses of CD38/CD3 BsAb + T cells show potent anti - tumor activity – comparable to 1 dose of CD38 T cell therapy Dose 1 1 µg BsAb + 10 6 T cells/mouse or 10 6 DAR - T cells/mouse Dose 2 1 µg BsAb + 10 6
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