Sorrento Therapeutics, Inc. - FORM 8-K - EX-99.2

Attached files

file	filename
8-K - FORM 8-K - Sorrento Therapeutics, Inc.	d805086d8k.htm
EX-99.1 - EX-99.1 - Sorrento Therapeutics, Inc.	d805086dex991.htm

Next-Generation

Cancer Therapeutics

October 2014

Exhibit 99.2

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.

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, and by all other matters specified in

Company's filings with the Securities and Exchange Commission, as well as risks inherent in

funding, 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™.

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.

intend

that

all

forward-looking

statements

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

These

Henry Ji, PhD

President,

CEO & Director

Inventor

G-MAB

Technology

President & CEO of Stratagene Genomics

VP of CombiMatrix and Stratagene

George Uy

EVP & CCO

Directed

the

launches

Abraxane,

Xeloda

Fusilev

Responsible for building Spectrum Pharma commercial

organization

Responsible for M&A of Igdrasol

David Miao, PhD

CTO

President and CSO of Concortis BioSystems

Co-inventor of IP covering ADC technologies

Head of Chemistry at Ambrx

Richard Vincent

EVP & CFO

$430M sale of Elevation to Sunovion-Dainippon

Meritage Pharma option agreement with Shire

($90M upfront + milestones)

$310M sale of Verus asthma program to AstraZeneca

Elan: various acquisitions and divestitures with aggregate

values more than $300M

Mike Royal, MD JD

EVP, Clinical &

Regulatory Affairs

Key contributor to over a dozen ANDAs and several NDAs

Managed clinical operations and regulatory activities

across multiple trials worldwide for both small molecule

and biologic products

Management Team

Board of Directors

William S. Marth -

Chairman

Albany Molecular (President & CEO)

Teva –

Americas (former President & CEO)

Mark Durand

Radius Health (CCO)

Watson, Teva –

Americas (former CFO)

Douglas Ebersole

PDL (former SVP, Corporate Development

& Legal)

Kim D. Janda, PhD

The Scripps Research Institute (Professor)

Henry Ji, PhD

Sorrento (President & CEO)

Jaisim Shah

Semnur Pharmaceuticals (CEO)

PDL (former CBO)

RTX

Positive Phase 1/2 data

New cohorts being enrolled

Pivotal Phase 2: 2015

TUMOR

AfDC

MYC Inhibitor

Cynviloq

>1,200 pts treated in clinical trials

Initial PK data suggest BE

to albumin-bound paclitaxel

TRIBECA Completion: Q1 2015

NDA Submission: Q3 2015

Next-Generation Cancer Therapeutics

G-MAB

onjugate

rug

ntibody

ADC:

*Abraxane

(paclitaxel albumin-bound particles for injectable suspension) (albumin-bound), registered trademark of and marketed by Celgene Corp.

INDICATION > TARGET

CYNVILOQ™

G-MAB &

Bi-Specific AB

ADC

RTX

Oncology

> PD-L1

Oncology/Inflammation > CCR2, CXCR3

Oncology > VEGFR2, c-MET, CXCR5

Oncology

> PD-1

Intractable Cancer Pain

INDICATION

Metastatic Breast Cancer

Non-Small Cell Lung Cancer

Bladder Cancer (sNDA)

Ovarian Cancer (sNDA)

505(b)(2) Seeking Bioequivalence

versus Albumin-bound paclitaxel*

Pancreatic Cancer (sNDA)

PHASE 3

PHASE 2

PHASE 1

PRECLINICAL

Multiple Commercialization

& Partnership Opportunities

MYC Inhibitor

Oncology

Recent Corporate Events

Positive PK data from first 8 unblinded patients suggest BE between Cynviloq and albumin-

bound paclitaxel

Positive data from RTX Phase I/II cancer pain trial

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

National Institute of Health (NIH) grants to fund development of:

(i)

anti-MRSA bacterial bi-specific antibodies

(ii)

antibody

formulated

drug

conjugates

(AfDCs)

against

aeruginosa

infections

(iii)

immunotherapy targeting Idiopathic Pulmonary Fibrosis (IPF)

(iv)

small molecule MYC inhibitor

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 to 435 mg/m

)

Albumin-bound

paclitaxel

Mean size

130 nm

Biological

polymer:

Donor-derived human

serum albumin (HSA)

260 mg/m

Taxol

paclitaxel

Cremophor EL

excipient:

Polyoxyethylated

castor oil

Formulation

Generation

175 mg/m

Maximum

Tolerated Dose

Peak

Product Sales

~ $1.6B (WW in 2000)

$1.5-2.0B* (2017)

MBC, NSCLC, PC

Conversion of

paclitaxel sales +

new indications

*Celgene Presentation at UBS Global Healthcare Conference, May 19, 2014 pp.9

Cynviloq: Next Generation Paclitaxel Therapy

Cynviloq Clinical 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/m

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. An Open-label, Randomized, Parallel, Phase 3 Trial to Evaluate the Efficacy and Safety of Cynviloq compared

to 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

Phase 3 MBC Clinical Results

* Trieu et al. 2013. IG-001 for Metastatic Breast Cancer-

Interim Analysis of a Phase 3 Trial. 4 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.

Bioequivalence = Potential Pathway to Market

Albumin-bound

paclitaxel

(n = 27)*

Cynviloq

(n = 27)*

Cynviloq

Albumin-bound

paclitaxel

Key Parameters:

Dose: 260 mg/m

Infusion time: 30 min

Duration: 3 weeks +

crossover for 3 weeks

Endpoints: AUC and

max

(90% CI)

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 on the recent positive initial PK data, 53 patients may be, subject to FDA guidance, sufficient

to establish BE.

T R I B E C A™

Initial 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

0 to

)

N = 53 with 90% power

BE Assessment and Sample Size Estimate

Differences in Formulations of Paclitaxel

Cynviloq

Albumin-bound Paclitaxel

Taxol®

Formulation

Nanoparticle co-polymer (poly-lactide

and polyethylene glycol di-block)

encapsulated paclitaxel

Donor derived human serum

albumin

encapsulated paclitaxel

Solvent-based (Cremophor EL)

paclitaxel

Mechanism of

Action

Rapid nanoparticle dissociation to

release paclitaxel which binds to

albumin in plasma

Tumor uptake via albumin transport

pathway

Rapid nanoparticle dissociation to

release paclitaxel which binds to

albumin in plasma

Tumor uptake via albumin transport

pathway

Slow release of paclitaxel due to

Cremophor entrapment

Freed paclitaxel binds to albumin in

plasma, tumor uptake via albumin

transport pathway

Maximum Tolerated

Dose (mg/m

)

>300

260

175

Reconstitution

No foaming or clumping

Foaming or clumping can occur

which requires standing vial for

15 minutes

Solution may show haziness

Should be administered through an

in-line filter with a microporous

membrane

0,22 microns)

Stability of reconstituted

vial

Stable at ambient temperature, use

within 24 hours

Needs refrigeration (2

C -

Use within 8 hours

Stable at ambient temperature

(~25

C) for up to 27 hours

Human serum albumin

(HSA)

HSA-free

HSA carries ‘theoretical risk of

viral/prion transmission’

HSA-free

1) Motamed

al.

IG-001

Non-Biologic Nanoparticle Paclitaxel for the Treatment of Solid Tumors. Jan 7, 2014. J Nanomat Mol Nanotech.

http://www.scitechnol.com/ig-a-nonbiologic-nanoparticle-paclitaxel-for-the-treatment-of-solid-tumors-zEUl.php?article_id=1834

2) Neil Desai-

Food and Drug Administration-Regulated Products Containing Nanotechnology Materials ; Public Meeting, October 10th, 2006.

DA Yardley. nab-paclitaxel mechanisms of action and delivery. 2013. J Control Release. 170:365-72.

3) Kim et al. Clin Cancer Res. 2004. 10:3708-16.

4) Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) Product Insert.

5) Profile based on Genexol-PM Product Insert in S Korea.. Cynviloq is marketed as Genexol-PM in S Korea.

6) Taxol Package Insert, Registered trademark of BMS.

Estimated Timelines and Next Steps*

First patient dosed: March 31,

2014

Last patient out: January 2015

NDA filing:

2015

Product launch (MBC and NSCLC):

2016

sNDA planning for label expansion into

pancreatic, bladder, and ovarian cancers

Study

*Estimates, subject to discussions with the FDA.

LAUNCH

2016

FDA

Approval

2016

NDA

Filing

2015

2014

Resiniferatoxin (RTX): A Novel, Non-opiate

Analgesic

RTX

Intractable

Cancer

Pain

RTX in action

Intraganglionic:

(injection into or

near the dorsal root ganglion [DRG])

Intrathecal:

(injection into the

cerebrospinal fluid space)

Two Injection Sites =

Two Products for Human Use

RTX Ablates TRPV1-positive Neurons

after Intrathecal Injection

Fore limb

TRPV1-positive cells

(dark brown)

Hind limb

Absence of TRPV1-

positive cells after

RTX treatment

Adapted from Karai et al. 2004

TRPV1

Brown et al, Anesthesiology 2005

n=18

n=8

n=5

n=4

Weeks

(p < 0.0001 for all time points)

100% response rate with single

intrathecal injection

12 dogs reduced or discontinued

analgesics

Dogs passed away due to underlying

osteosarcoma, not RTX treatment

Permanent analgesic effect

Personality intact

Gait and mood visibly improved

Lack of serious adverse events

No opioid-like side effects

Animal health market represents

separate licensing opportunity

Intractable pain due to osteosarcoma

Open-Label Study in Companion Dogs

Intraganglionic injection is a potential new

delivery modality for RTX

Adapted from Tender et al. 2005

Nociceptive neuron-mediated

neurogenic inflammation

(Evans blue)

Unilateral injection of RTX into only a single trigeminal neuron,

not only resulted in a local functional difference, but also resulted in a

local reduction of neurogenic inflammation

RTX

control

Left eye (blue) vs

Right eye (red)

100

120

140

160

Interim Data from the Phase 1/2 NIH

sponsored trial

•

6 advanced cancer pts

with severe refractory

pain dosed with no

unexpected toxicity

•

All 6 pts had near

complete relief post-

injection

•

MTD not reached,

additional dose

escalation being

explored

•

Clinically meaningful

improvement in QOL

•

Improved pain scores

with increased activity

Data presented May 1, 2014 at 33

Annual Scientific Meeting of the

American Pain Society; Tampa, FL

Demographics at Study

Entry

Cancer Diagnosis

Target Pain Area

49 y (f)

Metastatic breast cancer

Low back and bilateral leg pain 2

bone mets

56 y (m)

Metastatic supraglottic squamous cell

cancer

Low back and bilateral hip pain 2

bone mets

57 y (m)

Metastatic pancreatic cancer

Bilateral abdominal (visceral) Pain

68 y (m)

Lymphoma, small fiber monoclonal

gammopathy

Bilateral hip and buttocks

(neuropathic) pain

55 y (m)

Metastatic small cell lung cancer

Left hip pain 2 bone mets

61 y (f)

Metastatic endometrial cancer

Low back and left hip/groin pain 2

bone mets

Patient

Pre

RTX

Injection

Date

Last NRS

PI score

%NRS PI

improvement

Details

7.3

5/9/11

6.1 (6 mo)

15.5

Bedridden to walking; nearly Y3 post RTX;

cancer has progressed

8.3

5/10/12

3.8 (2 wk)

54.0

Died D35 of pneumonia 2 cancer

8.4

8/3/12

6.0 (1 mo)

28.8

Died just past D30 of cancer

8.0

10/23/12

5.4 (6 mo)

32.1

Wheelchair-bound to walking; Y1.5 post

RTX; cancer has progressed

9.0

2/13/13

8.1 (1 mo)

9.6

Died W6 of cancer

8.6

9/23/13

7.9 (1 mo)

8.3

Breakthrough pain meds reduced by half

by M1; ET from study just after M1 due to

cancer progression; died just after M3

Baseline average

NRS = 8.27

Average NRS reduction =

2.05

(24.7% Improvement)

Average 1.6 point improvement across BPI

pain interference items.

Next Steps for RTX Development

Under NIH CRADA

Intractable cancer pain clinical Phase 1/2 trial (intrathecal injection); n~13 patients

Phase 1/2 trial for osteosarcoma (intraganglionic injection); n~15 patients

Under Sorrento IND

Intractable cancer pain clinical Phase 1/2 trial (intrathecal injection); n~40 patients

Filing for MUMS designation for osteosarcoma in dogs

~3 years for clinical development

G-MAB

& ADC

Mono-

and Bi-

specific

Antibodies

Proprietary

Toxins

Immunotherapy Programs

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:

No stacking royalties

Very high library diversity:

2.1 x 10

distinct antibodies

Fully human antibodies

High successful screening hit rate

Difficult Targets:

Small Peptides

Most Difficult Targets:

G Protein-Coupled Receptors

(GPCRs)

RNA amplification used for

library generation

Freedom-To-Operate

Competitor mAb

Sorrento mAb

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

Day

Competitor mAb

Sorrento mAb

Anti-PD1 mAb Exhibits Excellent Activity

Control

Sorrento mAb

Immune Modulation*

Target Specificity

Antibody Drug Conjugates (ADCs)

Key Components:

Drug released in CANCER CELL

Target-specific internalizing antibody

Potent cytotoxic prodrugs

Linker and conjugation chemistries

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

Current industry

standard

Proprietary

K-Lock chemistry

Sorrento’s homogenous ADC

No need for:

K-Lock Conjugation Enables

Homogeneous ADCs

non-natural amino acids

genetic re-engineering

enzymatic posttranslational modification

Drug

Maleimide conjugation

Destabilizes antibody structure

Drug-antibody linkage not stable

Altered PK profile

Off-target drug effects

Antibody

C-Lock Conjugation Stabilizes ADCs

C-Lock conjugation

Enhances ADC stability

Prolongs PK profile

Reduces off-target effects

Proprietary ADC Screening Using Panels

Fast path to IND

Identification of optimal combination of linker, conjugation chemistry and

drug

payload

essential

for

efficient

and

expedited

development

from

hit

drug candidate

Efficacy of anti-VEGFR2-ADC STI-D0168

A431 squamous-cell carcinoma cells; ^indicates dosing

PBS

anti-VEGFR2 mAb (5 mg/kg)

STI-D0168 (1 mg/kg)

control ADC (5 mg/kg)

STI-D0168 (5 mg/kg)

PBS

control ADC (10 mg/kg)

anti-c-MET mAb (10 mg/kg)

D0602 (10 mg/kg)

D0602 (3 mg/kg)

U87 xenograft; dosing twice weekly; maytansinoid drug conjugates

Efficacy of anti-c-MET-ADC STI-D0602

Intractable Cancer Pain Treatment

Ongoing Phase 1/2 study

Orphan drug status received

Three potential drug products from same API

Targeted Cancer Immunotherapeutics

First therapeutic antibody candidate in clinic 1H 2016

Proprietary linker/conjugation chemistry for homogenous

ADC generation

First ADC in clinic 1H 2016

Bi-specific antibodies in development

Late-Stage Cancer Drug

NDA submission in Q3 2015

Product launch expected in 2016

Addresses multi-billion dollar paclitaxel market

Abbreviated

regulatory

pathway

(“bioequivalence”)

for

approval

Investment Highlights

Cynviloq

RTX

G-MAB

& ADC

Developing Therapeutic Solutions to Help

Man’s Life Companions

A Subsidiary of Sorrento

Contact:

Henry Ji, Ph.D.

President and CEO

hji@sorrentotherapeutics.com

(858) 668-6923

Next-Generation

Cancer Therapeutics

Attached files

Sorrento Therapeutics, Inc. Reports

Also read