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Corporate Investor Presentation
March 2018
V030918
Disclaimer
Certain statements contained in this presentation or in other documents of Sorrento Therapeutics, Inc. (the “Company”) and of any of its affiliates, along with certain
statements that may be made by management of the Company orally in presenting this material, may contain “forward-looking statements” as defined in the Private
Securities Litigation Reform Act of 1995. These statements can be identified by the fact that they do not relate strictly to historic or current facts. They use words such as
"estimate," "expect," "intend," "believe," "plan," "anticipate," “projected” and other words and terms of similar meaning in connection with any discussion of future
operating or financial performance or condition. These statements are based upon the current beliefs and expectations of the Company's management and are subject to
significant risks and uncertainties. Statements regarding future action, future performance and/or future results including, without limitation, those relating to the timing
for completion, and results of, scheduled or additional clinical trials and the FDA’s or other regulatory review and/or approval and commercial launch and sales results (if
any) of the Company’s formulations and products and regulatory filings related to the same, and receipt by the Company of milestone and royalty payments may differ
from those set forth in the forward-looking statements. Peak sales and market size estimates have been determined on the basis of market research and comparable
product analysis, but no assurances can be given that such sales levels will be achieved, if at all, or that such market size estimates will prove accurate.
The Company assumes no obligation to update forward-looking statements as circumstances change. Investors are advised to consult further disclosures that the
Company makes or has made on related subjects in the Company's Form 10-K, 10-Q and 8-K reports.
In presenting this material or responding to inquiries in connection with a presentation, management may refer to results, projections or performance measures that are
not prepared in accordance with U.S. Generally Accepted Accounting Principles (“GAAP”) as reported in the Company’s SEC filings. These results, projections or
performance measures are non-GAAP measures and are not intended to replace or as a substitute for results measured under GAAP, but rather as supplement to the
GAAP reported results.
Because actual results are affected by these and other potential risks, contingencies and uncertainties, the Company cautions investors that actual results may differ
materially from those expressed or implied in any forward-looking statement. It is not possible to predict or identify all such risks, contingencies and uncertainties. The
Company identifies some of these factors in its Securities and Exchange Commission (“SEC”) filings on Forms 10-K, 10-Q and 8-K, and investors are advised to consult the
Company’s filings for a more complete listing of risk factors, contingencies and uncertainties effecting the Company and its business and financial performance.
Sorrento® and the Sorrento logo are registered trademarks of Sorrento Therapeutics, Inc.
ZTlido™ and G-MAB™ are trademarks owned by Scilex Pharmaceuticals, Inc. and Sorrento, respectively.
Seprehvir®, is a registered trademark of Virttu Biologics Limited, a wholly-owned subsidiary of TNK Therapeutics, Inc. and part of the group of companies owned by
Sorrento Therapeutics, Inc.
All other trademarks are the property of their respective owners.
2
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Recent Milestone: 02/28/18 US FDA APPROVAL
3
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Immuno-Oncology and Non-Opioid Pain Management
4
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
CAR-T Immune Therapies for Hematological Malignancies
› CAR-T cell therapies are the “game-changer” therapeutic modalities against hematological malignancies …
› Treatment pricing (per patient) in the $350K to $500K range.
› Anti-CD19 CAR-T Cell Therapies:
• Kymriah™ (Novartis): ALL in children and young adults
• Yescarta™ (Kite/Gilead): Certain B cell lymphomas
• $$$ Gilead acquired Kite for $11.9B (2017)
• $$$ Celgene acquired Juno for $9B cash (2018)
Global Data Reports, Company websites, Stock Market Historical data 5
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Future Outlook on CAR-T Therapies (Competition)
CD19 BCMA CD38
SORRENTO
is the future
Celularity, Cellectis/Pfizer
SRNE
Allogeneic
CAR-T
Autologous
CAR-T
BlueBird, Juno, Kite, GenScript
SRNE
6
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Outlook on SRNE Next-Generation CAR-T Technology
77
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
CAR-T (Current)
• Autologous
• Viral Transduction
CAR-T (2.0)
• Autologous
• Non-viral (KOKI*)
CAR-T (3.0)
• Allogeneic
• Non-viral (KOKI*)
* KOKI = “Knock-Out/Knock-In” non-viral technology proprietary to Sorrento therapeutics for non viral CAR-T manufacturing
Industry-Leading CD38 CAR-T Program
8
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Hematological Malignancies in the US
9
82K ALL Patients (US)
2024 market forecast: $1B
CD19: Novartis (Kymriah™)
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
* Global Data reports 2016 (market forecast) and NIH Cancer Institute Statistical Facts (Disease incidence and prevalence)
662K NHL Patients (US)
2024 market forecast: $5.4B
CD19: Kite (Yescarta™)
120K MM Patients (US)
2023 market forecast: $22.6B
CD38: Janssen/GenMab (Darzalex®)
CD38: Sorrento (CD38 CAR-T)
BCMA: Bluebird Bio
(bb2121 for BCMA CAR-T)
CD38 CAR-T for Multiple Myeloma
› CD38 is a Validated, High Priority Target for MM Immunotherapies:
• Darzalex® mAb (Janssen). License from Genmab.
• $$$ GenMab Market cap: $12.65B (March 2018)
• $$$ Darzalex expected 2022 sales of $5.8B in MM
Global Data Reports, Company websites, Stock Market Historical data 10
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Sorrento CD38 CAR-T Program: A Very Big Opportunity
› Addressing Multiple Myeloma indication => $22 B market opportunity
› Targeting validated, high value CD38 target (Darzalex®; anti-CD38 mAb approved for MM treatment)
› Proven CAR-T cell therapy modality for hematologic malignancies (Kymriah™ & Yescarta™ for CD19 CAR-T)
› Development overseen by a seasoned clinical team, with success track record in MM
› cGMP facilities and manufacturing ready for clinical trials
› Most advanced CD38 CAR-T program in the industry
11
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Sorrento – Most Advanced CD38 CAR-T Program in Development
› CAR based on fully human anti-CD38 antibody
o Different binding site than Darzalex® on CD38
o Different kinetic binding profile
o Preference for high-expressing CD38 cells
• High density expression found in:
• Multiple myeloma
• Other B cell malignancies
• Activated T cells
• T cell malignancies
› Late stage IND-enabling studies
o IND filing: 1Q18
› Multiple Myeloma is lead indication
o First-patient-in: 1H18
12
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Anti-Myeloma Activity of CD38 CAR-T Cells In Mouse Model
› On Day -23, immunodeficient NSG
mice were infused with human
RPMI8226 MM tumor cells
› On Day 0, CAR-T cells were
administered i.v.
› Re-dosing was performed every 3
weeks (total of 3 CAR-T doses)
Anti-CD38 CAR-T Cells Eradicated CD38 Positive Human Multiple Myeloma in NSG Mice
13
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
CRITICAL ASSET = “CAR-T” cGMP Manufacturing Capabilities (2 Sites)
Providence
San Diego
WestCoast
EastCoast
Expected capacity:
> 300 patients per year
14
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
CRITICAL ASSET = “Industry Leading MM Expert” Clinical Development Team
› Track record of success
› Led development of MM drugs
o IMIDs (more than $8B in revenue)
• Thalomid® (Thalidomide)
• Revlimid® (Lenalidomide)
• Pomalyst® (Pomalidomide)
Name Position(s)
Jerome B. Zeldis, M.D.,
Ph.D.
Chief Medical Officer
& President of Clinical Development
Ken Takeshita, MD Sr VP Clinical Research
Robert Knight, MD Sr VP Clinical Research
Mark Brunswick, Ph.D. VP Regulatory Affairs and Quality
Stephen L Klincewicz, DO,
MPH, JD
VP Pharmacovigilance
and Clinical Operations
15
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
SRNE Next-Generation CAR-T Therapies
What’s Next?
16
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Future Direction for CAR-T & CAR-NK Therapies
o “Viral-Free” CAR Expression
o “Off-the-Shelf” (allogeneic)
o Solid Tumor:
o Local Infusion
o “Combo” with Other Modalities
17
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Next-Generation SRNE CAR-T Therapies: potentially faster, cheaper and easier to make!
Current Limitation Next-generation Solutions
Viral vector-based transduction Non-viral genetic modification
 Time to manufacture and release virus cGMP material  Faster preclinical development
 Faster cGMP manufacturing steps (time & cost savings)
Autologous (patient-derived) cells Allogeneic (“off-the-shelf”) donor cells
 Weeks until therapy manufactured
 Not all patients qualify for autologous approach
 Manufacturing costs (GMP per patient)
 Available to patients immediately
 Scalable manufacturing (many doses)
Focus on hematological malignancies Combination therapy to treat solid tumors
 Cleaner target (lineage-restricted antigens)
 Easier access of CAR-T cells to tumor cells
 Fewer immunosuppressive effects from tumor
microenvironment (TME)
 Loco-regional administration of CAR-T cells to avoid
systemic exposure
 Synergy from combination therapy
(immuno-oncology mAb, oncolytic virus)
 Genetically-engineered T cells resistant to
immunosuppression
1818
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Sorrento
KOKI™
CAR-T Technology
Non-Viral KOKI CAR-T Technology
19
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
* KOKI = “Knock-Out/Knock-In” non-viral technology proprietary to Sorrento therapeutics for non viral CAR-T manufacturing
Non-Viral KOKI CD38-CAR-T Cells are Functionally Similar to retrovirally-transduced CD38-CAR-T Cells
20
Donor A (#1) Cytokine analysis: 24 hours co-cultured with K562 or RPMI8226
Donor A (#1) Cytotoxicity: 3 days co-cultured with K562 and RPMI8226
0
500
1000
1500
2000
2500
3000
3500
4000
4500
pg/mL
K562 RPMI8226
Cytokine Release
(Interferon-γ)
0
20
40
60
80
100
Cytotoxicity(%)
E:T ratio
600bp HA knockin CART RV CART TCR KO ATCKOKI CART
Target Specific Cytotoxicity
Donor CAR expression
(KOKI)
CAR expression
(RV)
A (exp. #1) 57% 78%
A (exp. #2) 80% 71%
B 72% 48%
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
CAR Expression
Day 0
Week 1
Week 2
Week 3
Untreated Activated T RV CAR-T TCR KO-T KOKI CAR-T
Anti-Tumor Activity of non-viral KOKI CD38 CAR-T Cells in RPMI8226 Model (ongoing)
21
Week 4
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Non-Viral KOKI CAR-T Technology (Summary)
› Genetic modification
o results in up to 40-80% CAR-positive T cells (comparable to RV transduction)
o Knock-out of TCR
› Proof-of-concept for 2 different CARs
o anti-CD38
o anti-CD19
› In vitro activity comparable RV-transduced CAR-T
› In vivo evaluation is ongoing
› IND filing planned for 2H 2018
22
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Sorrento
CD38 CAR-T “CBA”
(Cord Blood Allogeneic)
Off-the-Shelf CD38 CAR-T Program – “CBA” (Cord Blood Allogeneic)
23
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
-T
Eradication of CD38+ Human Multiple Myeloma in NSG Mice by Anti-CD38 CAR-T CBA Cells
› CAR-T cells were successfully generated from Cord Blood.
› CB-CAR-T cells produced less cytokines than PB-CAR-T cells when
activated by targeted antigen.
o Potentially lower risk of severe cytokine release syndrome (CRS).
› CB-CAR-T cells exhibited similar specific anti-tumor cytotoxicity as
PB-CAR-T in vitro.
› CB-CAR-T cells demonstrated anti-tumor activity against MM
tumor cells in an animal model.
Our results indicate that anti-CD38 CB-CAR-T cells exhibit strong
CD38-specific anti-MM tumor activity in vitro and in vivo.
24
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Allogeneic Cell Therapies – Sorrento’s Strategic Partner: Celularity
› Utilizes cells derived from cord blood or placental tissue
o Celularity raised $250M in funding; Sorrento holds 25% equity stake
o assets contributed by Sorrento, Celgene Corporation (CELG), United Therapeutics (UTHR) and Human
Longevity, Inc.
o only company with an allogeneic placental cell platform
o placental stem cells are uniquely immune privileged not requiring cells to be engineered or matched for
each individual patient.
o placental stem cells allow for unprecedented scalability of Celularity's CAR-T and CAR-NK platforms
2525
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
CEA CAR-T for
Liver Metastases
Loco-Regional CAR-T Cell Infusion for Solid Tumors
26
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
HITM Phase 1: Patient 5 Clinical Summary
BL Post-Infusion
Pre-enrollment history
›Liver-only metastatic colon cancer
›Failed 3 lines of conventional chemotherapy and ablation
On study events
›No detectable serum CEA; expression confirmed on tumor
biopsy specimens
›Grade 1 fever and grade 3 emesis
›Liver metastasis metabolic response on PET
›No extrahepatic disease developed
Follow-up
›Excellent post-study quality of life
›51 month survival
27
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
HITM-SURE Phase 1b (initial first 3 patient data)
“One subject with stage IV pancreas cancer has no viable
liver metastases by PET scan 11 months after treatment”
28
Press Release 03/05/18
CAR-T
+
Oncolytic Virus
Combination Therapies
29
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
and
Oncolytic Viruses: Potential Synergy with Cell-Based Immuno-Therapeutics
30
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
SEPREHVIR: Leading Next-Generation HSV-1 based Oncolytic Virus Immunotherapy
TRL UL IRL IRS TRSUS
Deleted ICP34.5 Deleted ICP34.5
 Seprehvir (HSV1716) is a Phase II-ready HSV-1 based immuno-
oncolytic therapy with over 100 patients treated to date
 Designed with the ability to specifically target and destroy
tumor cells while also stimulating an anti-tumor T-cell mediated
immune response
 5 Phase I Trials: High Grade Glioma, SCCHN, melanoma,
mesothelioma, pediatric neuroblastoma/osteosarcoma
 Well tolerated, no toxicity and expected AEs have been mild and
transient
 Ability to be delivered intratumorally and systemically could
provide administration advantages versus recently approved
HSV-1 oncolytic viral immunotherapy, IMLYGIC™ (Amgen)
 Phase II trial in planning phase
31
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Leading Players in the CAR-T Space
$9 B (01/22/18)
$11.8 B (2017)
JUNO
CD19 CAR-T
KITE
CD38 CAR-T
$0.6 B
(03/08/18)
SRNE
BCMA CAR-T
$11.3 B
(03/08/18)
BLUE
32
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Timetable and Upcoming Milestones
› CD38 CAR-T
o 1Q18 = IND filing
o 1H18 = Phase 1 and First-in-Human
› CD38 ADC
o 2H18 = IND filing
› RTX (resiniferatoxin)
o 1H18 Phase 1 intractable cancer pain (epidural) first patient treated
o 1Q18 IND filing (Phase 1) for osteoarthritis pain (intra-articular) + 2Q18 (First in Human) for osteoarthritis pain (intra-articular)
› ZTlido™ (lidocaine topical system 1.8%)
o 2019 European approval
33
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
Lead Development Programs IND Phase 1 Phase 2 Phase 3 NDA submission
CD38 CAR-T (Multiple Myeloma) 1H18
CD38 ADC (Multiple Myeloma) 2H18
RTX (resiniferatoxin) - intractable pain (terminal cancer) 1H18
RTX (resiniferatoxin) - articular pain (osteoarthritis) 1H18
Sorrento’s Senior Leadership Team
Name Position(s)
Henry Ji, Ph.D. Chairman & CEO
George Ng, J.D.
EVP, Chief Administrative Officer & Chief
Legal Officer
Dean Ferrigno
VP Finance
and Chief Accounting Officer
Alexis Nahama, DVM
VP Corporate Development
and President Ark Animal Health
Hui Li, PhD
VP Business Development
and General Manager China Operations
Bill Farley VP Business Development, Corp Dev
Name Position(s)
Jerome B. Zeldis, M.D.,
Ph.D.
Chief Medical Officer
& President of Clinical Development
Mark Brunswick, Ph.D. VP Regulatory Affairs and Quality
Robert Knight, MD Sr VP Clinical Research
Ken Takeshita, MD Sr VP Clinical Research
Stephen L Klincewicz, DO,
MPH, JD
VP Pharmacovigilance
and Clinical Operations
Gunnar F. Kaufmann, Ph.D.
Sr VP of Immunotherapy,
Head of Research and Global Partnerships
34
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved
(858) 203-4100
investors@sorrentotherapeutics.com
4955 Directors Place, San Diego, CA 92121
35
© 2018 Sorrento Therapeutics, Inc. All Rights Reserved

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Sorrento Investor Presentation

  • 2. Disclaimer Certain statements contained in this presentation or in other documents of Sorrento Therapeutics, Inc. (the “Company”) and of any of its affiliates, along with certain statements that may be made by management of the Company orally in presenting this material, may contain “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995. These statements can be identified by the fact that they do not relate strictly to historic or current facts. They use words such as "estimate," "expect," "intend," "believe," "plan," "anticipate," “projected” and other words and terms of similar meaning in connection with any discussion of future operating or financial performance or condition. These statements are based upon the current beliefs and expectations of the Company's management and are subject to significant risks and uncertainties. Statements regarding future action, future performance and/or future results including, without limitation, those relating to the timing for completion, and results of, scheduled or additional clinical trials and the FDA’s or other regulatory review and/or approval and commercial launch and sales results (if any) of the Company’s formulations and products and regulatory filings related to the same, and receipt by the Company of milestone and royalty payments may differ from those set forth in the forward-looking statements. Peak sales and market size estimates have been determined on the basis of market research and comparable product analysis, but no assurances can be given that such sales levels will be achieved, if at all, or that such market size estimates will prove accurate. The Company assumes no obligation to update forward-looking statements as circumstances change. Investors are advised to consult further disclosures that the Company makes or has made on related subjects in the Company's Form 10-K, 10-Q and 8-K reports. In presenting this material or responding to inquiries in connection with a presentation, management may refer to results, projections or performance measures that are not prepared in accordance with U.S. Generally Accepted Accounting Principles (“GAAP”) as reported in the Company’s SEC filings. These results, projections or performance measures are non-GAAP measures and are not intended to replace or as a substitute for results measured under GAAP, but rather as supplement to the GAAP reported results. Because actual results are affected by these and other potential risks, contingencies and uncertainties, the Company cautions investors that actual results may differ materially from those expressed or implied in any forward-looking statement. It is not possible to predict or identify all such risks, contingencies and uncertainties. The Company identifies some of these factors in its Securities and Exchange Commission (“SEC”) filings on Forms 10-K, 10-Q and 8-K, and investors are advised to consult the Company’s filings for a more complete listing of risk factors, contingencies and uncertainties effecting the Company and its business and financial performance. Sorrento® and the Sorrento logo are registered trademarks of Sorrento Therapeutics, Inc. ZTlido™ and G-MAB™ are trademarks owned by Scilex Pharmaceuticals, Inc. and Sorrento, respectively. Seprehvir®, is a registered trademark of Virttu Biologics Limited, a wholly-owned subsidiary of TNK Therapeutics, Inc. and part of the group of companies owned by Sorrento Therapeutics, Inc. All other trademarks are the property of their respective owners. 2 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 3. Recent Milestone: 02/28/18 US FDA APPROVAL 3 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 4. Immuno-Oncology and Non-Opioid Pain Management 4 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 5. CAR-T Immune Therapies for Hematological Malignancies › CAR-T cell therapies are the “game-changer” therapeutic modalities against hematological malignancies … › Treatment pricing (per patient) in the $350K to $500K range. › Anti-CD19 CAR-T Cell Therapies: • Kymriah™ (Novartis): ALL in children and young adults • Yescarta™ (Kite/Gilead): Certain B cell lymphomas • $$$ Gilead acquired Kite for $11.9B (2017) • $$$ Celgene acquired Juno for $9B cash (2018) Global Data Reports, Company websites, Stock Market Historical data 5 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 6. Future Outlook on CAR-T Therapies (Competition) CD19 BCMA CD38 SORRENTO is the future Celularity, Cellectis/Pfizer SRNE Allogeneic CAR-T Autologous CAR-T BlueBird, Juno, Kite, GenScript SRNE 6 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 7. Outlook on SRNE Next-Generation CAR-T Technology 77 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved CAR-T (Current) • Autologous • Viral Transduction CAR-T (2.0) • Autologous • Non-viral (KOKI*) CAR-T (3.0) • Allogeneic • Non-viral (KOKI*) * KOKI = “Knock-Out/Knock-In” non-viral technology proprietary to Sorrento therapeutics for non viral CAR-T manufacturing
  • 8. Industry-Leading CD38 CAR-T Program 8 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 9. Hematological Malignancies in the US 9 82K ALL Patients (US) 2024 market forecast: $1B CD19: Novartis (Kymriah™) © 2018 Sorrento Therapeutics, Inc. All Rights Reserved * Global Data reports 2016 (market forecast) and NIH Cancer Institute Statistical Facts (Disease incidence and prevalence) 662K NHL Patients (US) 2024 market forecast: $5.4B CD19: Kite (Yescarta™) 120K MM Patients (US) 2023 market forecast: $22.6B CD38: Janssen/GenMab (Darzalex®) CD38: Sorrento (CD38 CAR-T) BCMA: Bluebird Bio (bb2121 for BCMA CAR-T)
  • 10. CD38 CAR-T for Multiple Myeloma › CD38 is a Validated, High Priority Target for MM Immunotherapies: • Darzalex® mAb (Janssen). License from Genmab. • $$$ GenMab Market cap: $12.65B (March 2018) • $$$ Darzalex expected 2022 sales of $5.8B in MM Global Data Reports, Company websites, Stock Market Historical data 10 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 11. Sorrento CD38 CAR-T Program: A Very Big Opportunity › Addressing Multiple Myeloma indication => $22 B market opportunity › Targeting validated, high value CD38 target (Darzalex®; anti-CD38 mAb approved for MM treatment) › Proven CAR-T cell therapy modality for hematologic malignancies (Kymriah™ & Yescarta™ for CD19 CAR-T) › Development overseen by a seasoned clinical team, with success track record in MM › cGMP facilities and manufacturing ready for clinical trials › Most advanced CD38 CAR-T program in the industry 11 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 12. Sorrento – Most Advanced CD38 CAR-T Program in Development › CAR based on fully human anti-CD38 antibody o Different binding site than Darzalex® on CD38 o Different kinetic binding profile o Preference for high-expressing CD38 cells • High density expression found in: • Multiple myeloma • Other B cell malignancies • Activated T cells • T cell malignancies › Late stage IND-enabling studies o IND filing: 1Q18 › Multiple Myeloma is lead indication o First-patient-in: 1H18 12 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 13. Anti-Myeloma Activity of CD38 CAR-T Cells In Mouse Model › On Day -23, immunodeficient NSG mice were infused with human RPMI8226 MM tumor cells › On Day 0, CAR-T cells were administered i.v. › Re-dosing was performed every 3 weeks (total of 3 CAR-T doses) Anti-CD38 CAR-T Cells Eradicated CD38 Positive Human Multiple Myeloma in NSG Mice 13 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 14. CRITICAL ASSET = “CAR-T” cGMP Manufacturing Capabilities (2 Sites) Providence San Diego WestCoast EastCoast Expected capacity: > 300 patients per year 14 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 15. CRITICAL ASSET = “Industry Leading MM Expert” Clinical Development Team › Track record of success › Led development of MM drugs o IMIDs (more than $8B in revenue) • Thalomid® (Thalidomide) • Revlimid® (Lenalidomide) • Pomalyst® (Pomalidomide) Name Position(s) Jerome B. Zeldis, M.D., Ph.D. Chief Medical Officer & President of Clinical Development Ken Takeshita, MD Sr VP Clinical Research Robert Knight, MD Sr VP Clinical Research Mark Brunswick, Ph.D. VP Regulatory Affairs and Quality Stephen L Klincewicz, DO, MPH, JD VP Pharmacovigilance and Clinical Operations 15 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 16. SRNE Next-Generation CAR-T Therapies What’s Next? 16 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 17. Future Direction for CAR-T & CAR-NK Therapies o “Viral-Free” CAR Expression o “Off-the-Shelf” (allogeneic) o Solid Tumor: o Local Infusion o “Combo” with Other Modalities 17 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 18. Next-Generation SRNE CAR-T Therapies: potentially faster, cheaper and easier to make! Current Limitation Next-generation Solutions Viral vector-based transduction Non-viral genetic modification  Time to manufacture and release virus cGMP material  Faster preclinical development  Faster cGMP manufacturing steps (time & cost savings) Autologous (patient-derived) cells Allogeneic (“off-the-shelf”) donor cells  Weeks until therapy manufactured  Not all patients qualify for autologous approach  Manufacturing costs (GMP per patient)  Available to patients immediately  Scalable manufacturing (many doses) Focus on hematological malignancies Combination therapy to treat solid tumors  Cleaner target (lineage-restricted antigens)  Easier access of CAR-T cells to tumor cells  Fewer immunosuppressive effects from tumor microenvironment (TME)  Loco-regional administration of CAR-T cells to avoid systemic exposure  Synergy from combination therapy (immuno-oncology mAb, oncolytic virus)  Genetically-engineered T cells resistant to immunosuppression 1818 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 19. Sorrento KOKI™ CAR-T Technology Non-Viral KOKI CAR-T Technology 19 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved * KOKI = “Knock-Out/Knock-In” non-viral technology proprietary to Sorrento therapeutics for non viral CAR-T manufacturing
  • 20. Non-Viral KOKI CD38-CAR-T Cells are Functionally Similar to retrovirally-transduced CD38-CAR-T Cells 20 Donor A (#1) Cytokine analysis: 24 hours co-cultured with K562 or RPMI8226 Donor A (#1) Cytotoxicity: 3 days co-cultured with K562 and RPMI8226 0 500 1000 1500 2000 2500 3000 3500 4000 4500 pg/mL K562 RPMI8226 Cytokine Release (Interferon-γ) 0 20 40 60 80 100 Cytotoxicity(%) E:T ratio 600bp HA knockin CART RV CART TCR KO ATCKOKI CART Target Specific Cytotoxicity Donor CAR expression (KOKI) CAR expression (RV) A (exp. #1) 57% 78% A (exp. #2) 80% 71% B 72% 48% © 2018 Sorrento Therapeutics, Inc. All Rights Reserved CAR Expression
  • 21. Day 0 Week 1 Week 2 Week 3 Untreated Activated T RV CAR-T TCR KO-T KOKI CAR-T Anti-Tumor Activity of non-viral KOKI CD38 CAR-T Cells in RPMI8226 Model (ongoing) 21 Week 4 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 22. Non-Viral KOKI CAR-T Technology (Summary) › Genetic modification o results in up to 40-80% CAR-positive T cells (comparable to RV transduction) o Knock-out of TCR › Proof-of-concept for 2 different CARs o anti-CD38 o anti-CD19 › In vitro activity comparable RV-transduced CAR-T › In vivo evaluation is ongoing › IND filing planned for 2H 2018 22 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 23. Sorrento CD38 CAR-T “CBA” (Cord Blood Allogeneic) Off-the-Shelf CD38 CAR-T Program – “CBA” (Cord Blood Allogeneic) 23 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 24. -T Eradication of CD38+ Human Multiple Myeloma in NSG Mice by Anti-CD38 CAR-T CBA Cells › CAR-T cells were successfully generated from Cord Blood. › CB-CAR-T cells produced less cytokines than PB-CAR-T cells when activated by targeted antigen. o Potentially lower risk of severe cytokine release syndrome (CRS). › CB-CAR-T cells exhibited similar specific anti-tumor cytotoxicity as PB-CAR-T in vitro. › CB-CAR-T cells demonstrated anti-tumor activity against MM tumor cells in an animal model. Our results indicate that anti-CD38 CB-CAR-T cells exhibit strong CD38-specific anti-MM tumor activity in vitro and in vivo. 24 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 25. Allogeneic Cell Therapies – Sorrento’s Strategic Partner: Celularity › Utilizes cells derived from cord blood or placental tissue o Celularity raised $250M in funding; Sorrento holds 25% equity stake o assets contributed by Sorrento, Celgene Corporation (CELG), United Therapeutics (UTHR) and Human Longevity, Inc. o only company with an allogeneic placental cell platform o placental stem cells are uniquely immune privileged not requiring cells to be engineered or matched for each individual patient. o placental stem cells allow for unprecedented scalability of Celularity's CAR-T and CAR-NK platforms 2525 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 26. CEA CAR-T for Liver Metastases Loco-Regional CAR-T Cell Infusion for Solid Tumors 26 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 27. HITM Phase 1: Patient 5 Clinical Summary BL Post-Infusion Pre-enrollment history ›Liver-only metastatic colon cancer ›Failed 3 lines of conventional chemotherapy and ablation On study events ›No detectable serum CEA; expression confirmed on tumor biopsy specimens ›Grade 1 fever and grade 3 emesis ›Liver metastasis metabolic response on PET ›No extrahepatic disease developed Follow-up ›Excellent post-study quality of life ›51 month survival 27 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 28. HITM-SURE Phase 1b (initial first 3 patient data) “One subject with stage IV pancreas cancer has no viable liver metastases by PET scan 11 months after treatment” 28 Press Release 03/05/18
  • 29. CAR-T + Oncolytic Virus Combination Therapies 29 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 30. and Oncolytic Viruses: Potential Synergy with Cell-Based Immuno-Therapeutics 30 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 31. SEPREHVIR: Leading Next-Generation HSV-1 based Oncolytic Virus Immunotherapy TRL UL IRL IRS TRSUS Deleted ICP34.5 Deleted ICP34.5  Seprehvir (HSV1716) is a Phase II-ready HSV-1 based immuno- oncolytic therapy with over 100 patients treated to date  Designed with the ability to specifically target and destroy tumor cells while also stimulating an anti-tumor T-cell mediated immune response  5 Phase I Trials: High Grade Glioma, SCCHN, melanoma, mesothelioma, pediatric neuroblastoma/osteosarcoma  Well tolerated, no toxicity and expected AEs have been mild and transient  Ability to be delivered intratumorally and systemically could provide administration advantages versus recently approved HSV-1 oncolytic viral immunotherapy, IMLYGIC™ (Amgen)  Phase II trial in planning phase 31 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 32. Leading Players in the CAR-T Space $9 B (01/22/18) $11.8 B (2017) JUNO CD19 CAR-T KITE CD38 CAR-T $0.6 B (03/08/18) SRNE BCMA CAR-T $11.3 B (03/08/18) BLUE 32 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 33. Timetable and Upcoming Milestones › CD38 CAR-T o 1Q18 = IND filing o 1H18 = Phase 1 and First-in-Human › CD38 ADC o 2H18 = IND filing › RTX (resiniferatoxin) o 1H18 Phase 1 intractable cancer pain (epidural) first patient treated o 1Q18 IND filing (Phase 1) for osteoarthritis pain (intra-articular) + 2Q18 (First in Human) for osteoarthritis pain (intra-articular) › ZTlido™ (lidocaine topical system 1.8%) o 2019 European approval 33 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved Lead Development Programs IND Phase 1 Phase 2 Phase 3 NDA submission CD38 CAR-T (Multiple Myeloma) 1H18 CD38 ADC (Multiple Myeloma) 2H18 RTX (resiniferatoxin) - intractable pain (terminal cancer) 1H18 RTX (resiniferatoxin) - articular pain (osteoarthritis) 1H18
  • 34. Sorrento’s Senior Leadership Team Name Position(s) Henry Ji, Ph.D. Chairman & CEO George Ng, J.D. EVP, Chief Administrative Officer & Chief Legal Officer Dean Ferrigno VP Finance and Chief Accounting Officer Alexis Nahama, DVM VP Corporate Development and President Ark Animal Health Hui Li, PhD VP Business Development and General Manager China Operations Bill Farley VP Business Development, Corp Dev Name Position(s) Jerome B. Zeldis, M.D., Ph.D. Chief Medical Officer & President of Clinical Development Mark Brunswick, Ph.D. VP Regulatory Affairs and Quality Robert Knight, MD Sr VP Clinical Research Ken Takeshita, MD Sr VP Clinical Research Stephen L Klincewicz, DO, MPH, JD VP Pharmacovigilance and Clinical Operations Gunnar F. Kaufmann, Ph.D. Sr VP of Immunotherapy, Head of Research and Global Partnerships 34 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved
  • 35. (858) 203-4100 investors@sorrentotherapeutics.com 4955 Directors Place, San Diego, CA 92121 35 © 2018 Sorrento Therapeutics, Inc. All Rights Reserved