Sorrento Therapeutics, Inc. - FORM 8-K - EX-99.1

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8-K - 8-K - Sorrento Therapeutics, Inc.	d867736d8k.htm

Next-Generation

Cancer Therapeutics

February 2015

Exhibit 99.1

Safe Harbor Statement NASDAQ: SRNE

This presentation contains "forward-looking statements" as that term is defined under the Private Securities Litigation

Reform Act of 1995 (PSLRA), including statements regarding expectations, beliefs or intentions regarding our business,

technologies and products strategies or prospects. Such forward-looking statements are characterized by future or

conditional verbs such as “may,”

“will,”

“expect,”

“intend,”

“anticipate,”

“believe,”

“estimate”

and “continue”

or similar

verbs. Actual results may differ from those projected due to a number of risks and uncertainties, including, but not

limited to, the possibility that some or all of the pending matters and transactions being considered by the Company

may not proceed as contemplated, as well as risks inherent in additional financing, developing and obtaining regulatory

approvals of new, commercially-viable and competitive products and product candidates, including timelines, the size of

clinical trials, sufficiency of data from those trials and the requirements of the FDA for potential approval of Cynviloq™

and

all

other

matters

described

the

Company's

filings

with

the

Securities

and

Exchange

Commission,

including

the

risk factors

set

forth

therein.

These

statements

are

made

based

upon

current

expectations that are subject to risk and

uncertainty and information available to the Company as of the date of this presentation. The Company does not

undertake to update forward-looking statements in this presentation to reflect actual results, changes in assumptions or

changes in other factors affecting such forward-looking information. Assumptions and other information that could

cause results to differ from those set forth in the forward-looking information can be found in the Company's filings with

the Securities and Exchange Commission, including its most recent periodic report. We intend that all forward-looking

statements be subject to the safe-harbor provisions of the PSLRA.

Cytotoxics

CYNVILOQ™

Targeted Therapy

MYC inhibitor

TRAIL modulator

Immunotherapy

PD-1, PD-L1, CTLA-4

Bispecific Abs

Targeted Therapy

Anti-VEGFR2 ADC

Anti-c-MET ADC

Bispecific ADC

Adoptive Cellular

Immunotherapy

Chimeric Antigen Receptor

Tumor-attacking

Neukoplast

(Partnership with Conkwest)

RTX

Intractable

Cancer Pain

A Comprehensive Oncology Company

Deep and Complementary Pipeline Creates Significant Opportunities-

Novel breakthrough combination therapeutic regimens and modalities to attack cancer

Significant reduction in clinical development costs and timeline

Significant commercial edge in future drug pricing

CYNVILOQ, CAR.TNK, CAR.TNK (Chimeric Antigen Receptor Tumor-attacking Neukoplast) are trademarks owned by Sorrento Therapeutics, Inc.

Neukoplast is a trademark owned by Conkwest, Inc.

Small

Molecules

Biologics

Cell

Therapy

Supportive

Care

Corporate Events Validate and Advance Sorrento

Pipeline Unlocking Significant Value

“The

Immunotherapy

Antibody

Company”

Exclusive global partnership with Conkwest to develop next generation anti-cancer

cellular

immunotherapy

with

"Off-the-Shelf"

CAR.TNK™

(Chimeric

Antigen

Receptor

Tumor -attacking

Neu Koplast)

First joint venture with NantWorks and Abraxis BioScience Inc. founder, Dr. Patrick Soon-

Shiong,

to develop next generation immunotherapies for the treatment of cancer and

autoimmune disease.

G-MAB

ADC

Licensing agreement to develop and commercialize anti-PD-L1 mAb with Lee’s

Pharmaceutical for greater Chinese Market

Exclusive research and option agreement to generate and develop antibody-drug

conjugates (ADCs) with Morphotek / Eisai

CYNVILOQ

Patient enrollment in TRIBECA registration trial completed. Pilot PK suggests

bioequivalence (BE) between Cynviloq and albumin-bound paclitaxel

Deep and Complementary Pipeline Creates

Significant Opportunities

TRIBECA

505

(b)(2)

Bioequivalence

trial

versus

albumin-bound

paclitaxel

(Abraxane

)

(paclitaxel

albumin-bound

particles

for

injectable

suspension)

(albumin-

bound), Abraxane®

is a registered trademark of and marketed by Celgene Corp.

PDL1.TNK,

CD123.TNK,

ROR1.TNK,

PSMA.TNK

are

trademarks

owned

Sorrento

Therapeutics,

Inc.

CYNVILOQ™

G-MAB

Bi-Specific Ab

RTX

Immuno-oncology

> PD-L1, PD1, CD47, CD137

VEGFR2, c-MET, CXCR5

Intractable Cancer Pain

INDICATION

TARGET

Metastatic Breast Cancer

Non-Small Cell Lung Cancer

T R I B E C A*

Registration trial completed

PHASE 3

PHASE 2

PHASE 1

PRECLINICAL

Solid tumors and hematological malignancies

ADC

MYC Inhibitor

PD-L1.TNK, CD123.TNK, ROR1.TNK, PSMA.TNK

PD-L1/c-MET; PD-L1/CTLA-4, PD-L1/EGFR

Lead Oncology Product Opportunity

Cynviloq

Registration

Trial

(Paclitaxel polymeric

micelle)

Mean size

~25 nm

Cynviloq

paclitaxel

polymeric micelle

Chemical

polymer:

Poly-lactide and

polyethylene glycol

diblock copolymer

>300

mg/m

(up

435

mg/m

)

Albumin-bound

paclitaxel

Mean size

130 nm

Biological

polymer:

Donor-derived human

serum albumin (HSA)

260

mg/m

Taxol

paclitaxel

Cremophor

excipient:

Polyoxyethylated

castor oil

Formulation

Generation

175

mg/m

Maximum

Tolerated Dose

Peak

Product Sales

~ $1.6B (WW in 2000)

$ 2.2 B* (2020)

MBC, NSCLC, PC

Conversion of

paclitaxel sales +

new indications

*Celgene Presentation at JPM Healthcare Conference Jan 2015

Cynviloq: Next Generation Paclitaxel Therapy

Cynviloq Clinical Development Summary

Phase 1:

Trials

established

MTD

>300

mg/m

Dana

Farber

Cancer

Inst,

Russia,

Korea

(total n=80)

>300

mg/m

(q3w)

vs.

175

mg/m

(Taxol;

weekly)

Phase 2:

Completed

trials

MBC,

NSCLC,

PC,

OC,

BC;

Yale

Cancer

Center,

Russia,

Korea

(total

n=259)

Possible Phase 3 sNDA programs in these tumor types

Phase 2b*:

Chemo-naïve Stage IIIb/IV NSCLC vs Taxol in S. Korea (total n=276; Cynviloq n=140)

230

mg/m²

cis

(q3w)

vs.

Taxol

175

mg/m

cis;

non-inferiority

established

Phase 2*:

1st line treatment of OC vs Taxol in S. Korea (total n=100; Cynviloq n=50)

260

mg/m

carbo

(q3w)

vs.

Taxol

175

mg/m

carbo;

non-inferiority

established

Phase 3:

MBC in S. Korea (total n=209; Cynviloq n=105 vs Taxol n=104)

GPMBC301.

Open-label,

Randomized,

Parallel,

Phase

Trial

Evaluate

the

Efficacy

and

Safety

Cynviloq

compared

Genexol®

(Paclitaxel with Cremophor EL) in Subjects with Recurrent or Metastatic Breast Cancer)

PM-Safety:

Completed for MBC and NSCLC (total n=502)

Efficacy and safety data supportive of 505(b)(2) submission

Total number of patients across all trials: 1,260

Data on file; * Investigator Initiated Study

Comparative Phase 3 MBC Clinical Results

* Trieu

al.

2013.

IG-001

for

Metastatic

Breast

Cancer-

Interim

Analysis

Phase

Trial.

Nanomedicine

Conference,

Sydney,

Australia.

** Gradishar et al. 2005. J Clin Oncol, 23:7794-7803.

*** Guan et al. 2007. ASCO Annual Meeting Proceedings Part I. Jun 20;25 (Suppl 18):1038.

Overall

Response

Rate (%)

Bioequivalence = Accelerated Pathway to Market

T R I B E C A™

Albumin-bound

paclitaxel

(n = 27)*

Cynviloq

(n = 27)*

Cynviloq

Albumin-bound

paclitaxel

Key Parameters:

Cycle 1

Cycle 2

Patients with MBC

Note:

trial

size

estimate

100

patients

was

based

simulation

albumin-bound

paclitaxel

and

Cynviloq

historical

data

with

both

drugs

given

different

doses

and

infusion

rates.

Based

the

recent

positive

initial

data

and

subject

FDA

guidance,

patients

may

sufficient

establish

BE.

A™

(TRIal

establishing

BioEquivalence

between

Cynviloq™

and

Albumin-bound

paclitaxel)

trademark

owned

Sorrento

Therapeutics,

Inc.

•

Dose:

260

mg/m

•

Infusion time: 30 min

•

Duration: 3 weeks +

crossover for 3 weeks

•

Endpoints:

AUC

and

max

(90% CI)

(TRIal establishing BioEquivalence between Cynviloq™ and Albumin-bound paclitaxel)

Pilot PK Data Analyses Suggest

BE vs.

Albumin-Bound Paclitaxel

Parameters

Ratio of Cynviloq/

Albumin-bound paclitaxel

(%)

90% CI

Ln(AUC

0 to

)

109.1

93.98 –

126.58

Ln(C

max

)

102.5

83.10 –

126.35

Point estimate

110

Ln(AUC

)

N = 53 with 90% power

BE Assessment and Sample Size Estimate

Log

-linear Plot (n=8)

TRIBECA Patient Enrollment Completed

54 pts

Patients from recruited from sites in East Europe, USA and Asia

Total 111 patients enrolled (expanded safety data)

Initial reported AEs consistent with historical nab-paclitaxel toxicity profile

Estimated Timeline and Next Steps*

First patient dosed: March 31,

2014

Last patient in: January 2015

NDA filing:

2015

Product launch (MBC and NSCLC):

2016

Study

2014

2015

NDA

Filing

2016

FDA

Approval

LAUNCH

2016

*Estimates, subject to discussions with the FDA.

Intractable

Cancer

Pain

Resiniferatoxin (RTX): A Novel, Non-opiate Analgesic

RTX

Intraganglionic:

injection

into

near the dorsal root ganglion

Intrathecal:

injection

into

the

cerebrospinal fluid space

Two Injection Sites =

Two Products for Human Use

Cross Sections of

spinal cord*

Absence of TRPV1-

positive cells after RTX

treatment

TRPV1-positive cells

(dark brown)

* Adapted from Karai et al., 2004

Dorsal root ganglion

Summary of Interim Data from the Phase 1/2 NIH

Sponsored Trial

No unexpected

toxicities

All 6 patients had near

complete relief post-

injection

100% of non-ambulatory

patients could walk post

injection (n=2)

MTD not reached,

additional dose

optimization being

explored

RESULTS

Clinically meaningful

improvement in QOL

Improved pain scores with

increased activity

DESIGN OVERVIEW

6 advanced cancer patients with severe refractory pain received a single injection of RTX.

Neuropathic

pain,

visceral

and

bone

pain

bone

metastases

(49-61 years; 4 M/ 2F, MBC, H&N, pancreatic, lymphoma, SCLC, endometrial cancer).

Next Steps for RTX Development

~3 years for clinical development

Complete intractable cancer pain clinical Phase 1/2

trial (intrathecal injection) under Sorrento IND;

n=45-60 patients; optimization of dosing study

End of Phase 2 meeting with FDA (for intrathecal injection)

Initiate Phase 3 (intrathecal injection)

Phase 1/2 trial(s) (intraganglionic injection)

End of Phase 2 meeting with FDA (for intraganglionic injection)

OBJECTIVES

for

2015 and 2016

Immunotherapy Programs

G-MAB

+ Neukoplast

+ Proprietary Toxins &

Conjugation Chemistries

G-MAB: Library of Therapeutic Antibodies

High Value Oncology Targets:

Immune

modulation:

PD-1,

PD-L1,

CD47

Antibody

Drug

Conjugates:

VEGFR2,

c-Met

Size of Target Antigen

Proprietary technology:

RNA amplification used for library

generation

Freedom-To-Operate

Very high library diversity:

2.1

distinct

antibodies

Fully human antibodies

High successful screening hit rate

(over 70 targets screened)

Ideal for CAR-Generation

Difficult Targets:

Small Peptides

Most Difficult Targets:

G Protein-Coupled Receptors (GPCRs)

No stacking royalties

Anti-PD-L1 mAb Exhibits Potent Activity

Immune Modulation*

Tumor Mouse Model**

***

* mAbs @ 0.05 mg/mL

** xenograft model using H1975 human NSCLC cells; % inhibition relative to control mAb treatment

*** p<0.05, mean tumor volumes are significantly reduced in STI-A1010 group versus control groups as determined by Mann-Whitney u-test

Competitor mAb

Sorrento mAb

Day

Competitor mAb

Sorrento mAb

Anti-PD1 mAb Exhibits Excellent Activity

Immune Modulation*

Target Specificity

Control

Sorrento mAb

Human

PD1

Cyno

PD1

Human

CTLA-4

Human

CD28

Human

ICOS

PBS

control

K-Lock

C-Lock

C-Lock conjugation

Enhances ADC stability

Prolongs PK profile

Reduces off-target effects

Maleimide

conjugation

Destabilizes antibody structure

Drug-antibody linkage not stable

Altered PK profile

Off-target drug effects

Proprietary K-Lock and C-Lock Conjugation

Chemistries Enable Homogeneous ADCs

Proprietary High Potency Duostatin Toxins

(pM)

Cancer

Her-2

DM1

MMAE

Duostatin 3

SBKR3

Breast

+++

HCC1954

Breast

+++

124

BT474

Breast

+++

818

126

214

MDA-MB-361

Breast

+++

218

151

ZR75

Breast

+++

215

298

264

HCC1419

Breast

+++

391

271

332

MDA-MB-453

Breast

1,877

>100,000

452

MDA-MB-175

Breast

>100,000

1,348

425

N87

Gastric

+++

368

139

260

OE-19

Gastric

+++

176

164

130

SKOV-3

Ovarian

+++

150

251

144

Trastuzumab was used as targeting mAb

VEGFR2-ADC STI-D0168

c-MET-ADC STI-D0602

In Vivo Proof-of-Concept of Sorrento ADCs

A431 squamous-cell carcinoma cells; ^indicates dosing

U87 xenograft; dosing twice weekly; maytansinoid drug conjugates

“The Immunotherapy Antibody JV Company”

Independent company focused

on advancing next generation immunotherapies against cancer and auto-

immune diseases.

Both companies will contribute to its pipeline of clinical and preclinical

assets of novel and proprietary immunotherapies, ADCs, and bispecific

antibodies.

Joint venture will draw from NantWorks’

proteomic and genomic

capabilities and Sorrento’s industry-leading, highly diverse G-MAB library.

AN EXCLUSIVE JOINT PARTNERSHIP

CAR.TNK is a trademark owned by Sorrento Therapeutics, Inc.

Neukoplast is a trademark owned by Conkwest, Inc.

Advancing Cellular Immunotherapy

Beyond CAR-T Cell Therapies

Neukoplast®

NK cell line

(“off-the-shelf”)

Broad anti-cancer activity in

solid

and liquid tumors

No clinical DLTs/SAEs in

over 40 patients treated

Advanced proteomics platform

Proprietary gene insertion

(without use of lentiviruses)

‘GMP in a Box’

production

technology

G-MAB

High successful screening rate

(over 70 targets screened)

Proprietary technologies with

FTO

Vast diversity human antibody

library

CAR.TNK vs CAR-T: Key Differentiators

Simple:

Off-the-shelf

universal

product

CAR-modified Neukoplast cells

Cell Production

Transduction

characteristics

100%:

Master

cell

bank

with

100% of cells expressing CAR

MOA

Broad:

Multiple

MOAs,

targeting

and

killing through CAR-dependent and

innate

mechanisms

(“off-target

on-tumor”)

Safety

Good:

On-target

off-tumor

effects

limited due to short half life and lack

of IL-6 production

COGS

Low:

large

scale

bioreactor

manufacturing for many patients

Invasive:

Autologous

(patient-derived)

invasive procedure/leukapheresis

Variable

CAR

transfection & expression

Limited:

Requires

co-stimulators

(CD80, CD86) not present in many

solid tumors

Poor:

Cytokine

release

syndrome,

ICU;

Prolonged bone marrow suppression;

Cardiotoxicity; Reported cases of

encephalitis; Death

High:

requires

individual

patient

processing

CAR.TNK

CAR-T

Unmodified Neukoplast Clinically Validated In Several

Phase 1 Studies

More than 40 patients treated

Advanced metastatic disease refractory to chemo, biologics, cytokines,

radiation, and surgery

Many patients received multiple dosing regimens (up to 6 months)

Promising activity against different cancer types, including acute myelogenous

leukemia (AML), lymphoma (NHL, HL), melanoma, renal cell cancer (RCC), and lung

cancers (SCLC, NSCLC)

No DLTs; only 1 “grade 4 SAE”

(hypoglycemia likely related to tumor lysis)

-5000

5000

10000

15000

20000

25000

30000

35000

PHA

Allogeneic Donor

NK-92

CPM

Lymphocytes from 2 healthy donors co-cultured with each other

vigorous proliferation

Co-cultured with Neukoplast (7 days)

no proliferation

Gold: Donor 1

Aqua: Donor 2

T cell Proliferation measured using

Mixed Lymphocyte Reaction (MLR) Culture Assay

Neukoplast do not stimulate allogeneic T cells

Neukoplast

PHA

Allogeneic Donor

CAR.TNK: CAR-modified Neukoplast

Clonal cell lines expressing one or more CARs to establish a range of distinct products

Multiple

killing

mechanisms

CAR-targeted

well

broad

intrinsic

anti-cancer

activity of Neukoplast (“off-target / on-tumor”)

Engages the adaptive immune system through cytokine secretion and immune cell

recruitment

Titratable: repeat dosing option; controllable dose exposure to manage safety risk

Serial Killing of Her2+ Cells by Her2.TNK Cells

Homing to Her2 expressing tumors

Inhibition of Her2+ RCC metastasis

Selective cytotoxicity (spares normal cells)

Schoenfeld et al. Mol Therapy, in press

IN VIVO PRECLINICAL MOUSE DATA

Growth inhibition and killing correlate

with Her2 expression levels

“Serial killing”

of Her2+ target cells

even after gamma radiation with 10 Gy

Her2.TNK Demonstrate Tumor Homing and Potent

Anti-Glioma Activity in Mice

Schoenfeld et al. Mol Therapy, in press

Tumor homing of CAR.TNKs

Intracranial LN-319 glioblastoma

xenografts in NSG mice

Prospective CAR.TNKs for Development

(Initial List)

Target

Potential Indication(s)

EGFRviii.TNK

Glioma

EphA3.TNK

Glioma, AML

L1CAM.TNK

Gastric, pancreatic, NSCLC

CSPG4.TNK

H&N, breast, mesothelioma

BCMA.TNK

Myeloma

ROR1.TNK

CLL, ALL, MCL, breast, lung, pancreas

PSMA or

PSCA.TNK

Prostate

PDL1.TNK

Myeloma, RCC, NSCLC, TNBC

CS1.TNK

Myeloma

CD123.TNK

AML

CD19.TNK

CLL, ALL

CD22.TNK

CLL, ALL

CAR targets jointly selected by the

Steering Committee

Lead company will be responsible for

all pre-clinical and clinical development,

regulatory filings, and

commercialization

Profit sharing on all CAR.TNKs

revenues proportional to contribution

EGFRviii.TNK, EphA3.TNK, L1CAM.TNK, CSPG4.TNK, BCMA.TNK, ROR1.TNK, PSMA.TNK, PCMA.TNK, PDL1.TNK, CS1.TNK, CD123.TNK, CD19.TNK, CD22.TNK are trademarks owned by Sorrento Therapeutics, Inc.

Next Steps for CAR.TNK Development

H1 2015

Generation of CARs

H2 2015

Generation and evaluation of stable CAR.TNK cell lines

2016

IND-enabling studies, IND submission, and initiation of Phase 1 studies

Cytotoxics

CYNVILOQ™

Targeted Therapy

MYC inhibitor

TRAIL modulator

Immunotherapy

PD1, PD-L1, CTLA-4

Bispecific Abs

Targeted Therapy

Anti-VEGFR2 ADC

Anti-CMET ADC

Bispecific ADC

Adoptive Cellular

Immunotherapy

Chimeric Antigen Receptor

Tumor-attacking

Neukoplast

(Partnership with Conkwest)

RTX

Intractable

Cancer Pain

A Comprehensive Oncology Company

Deep and Complementary Pipeline Creates Significant Opportunities-

Novel breakthrough combination therapeutic regimens and modalities to attack cancer

Significant reduction in clinical development costs and timeline

Significant commercial edge in future drug pricing

CYNVILOQ, CAR.TNK, CAR.TNK (Chimeric Antigen Receptor Tumor-attacking Neukoplast) are trademarks owned by Sorrento Therapeutics, Inc.

Neukoplast is a trademark owned by Conkwest, Inc.

Small

Molecules

Biologics

Cell

Therapy

Supportive

Care

Next-Generation

Cancer Therapeutics

Henry Ji, Ph.D.

President and CEO

hji@sorrentotherapeutics.com

(858) 668-6923

George Uy

Executive Vice President and CCO

guy@sorrentotherapeutics.com

(661) 607-4057

CONTACT:

Sorrento Therapeutics, Inc. - FORM 8-K - EX-99.1 - February 9, 2015

Attached files

Sorrento Therapeutics, Inc. Reports