Advancing novel HPLN (Hybrid Polymerized Liposomal

Nanoparticle) based ADC (Antibody-Drug Conjugate)

products for cancer and other medical needs

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reflect the Company’s or, as appropriate, the Company’s directors’ current expectations and

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financial effects of the plans and events described herein. A multitude of factors including, but

not limited to, competitive technology, availability of investment capital, changes in market

demand, and changes in regulatory requirements, can cause actual events, performance or

results to differ significantly from any anticipated development. Forward looking statements

contained in this presentation regarding past trends or activities should not be taken as a

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occurrence of the forecasted developments. You should not place undue reliance on forward-

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Overview

COMPANY: NanoValent Pharmaceuticals, Inc. (NVP), is a privately-held company working

in close collaboration with Children’s Hospital Los Angeles (CHLA).

MISSION: Advancement of HPLN (Hybrid Polymerized Liposomal Nanoparticle) based

ADC candidates in diseases with significant unmet need.

TECHNOLOGY: Next generation, highly stable and flexible nanoparticle based ADCs

targeted to specific cell surface antigens. The targeting is antibody specific and the HPLN

payloads include cytotoxic drugs, small molecules, nucleic acid based therapeutics or other

new chemical entities.

STATUS: Current lead validation programs are in Oncology.

◦ NV101 (doxo-anti-CD99) completed preclinical validation and ready to enter IND enabling

studies for Phase 1 trials in Ewing Sarcoma (and other applications).

◦ NV102 (doxo-anti-CD19) completed preclinical validation and ready to enter IND enabling work

for Phase 1 trials in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)

pending future funding.

◦ NV103 (irinotecan-anti-CD99) completed preclinical validation and ready to enter IND enabling

work for Phase 1 trials in Ewing Sarcoma (and other applications).

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Strategic Objectives

Delivery To tumor cells, not normal cells with proven cancer

drugs - initially in pediatric cancer

Toxicity / Safety Reduce toxicity. Increase safety

Targeting /

Effectiveness

Improve tumor kill and minimize off-target effects with a

user-defined tumor-specific targeting mechanism

Stability Enable much improved in-vivo performance versus

conventional liposomes and untargeted nanoparticles

Flexibility Develop a therapeutic platform that can deliver various

encapsulated therapeutics - established as well as newly

emergent biologics, nucleic acids, and gene editing

Potential A platform not just for broad oncology but also for

other therapeutic indications plus diagnosis and imaging

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B. Targeting

agents

A. Encapsulated

drug

C. Advanced

polymer shell

8.40 nm

Patented HPLN Platform Versatility

A. Entities so far encapsulated and delivered:

Cytotoxics, small molecules, siRNA, ASOs, and CRISPR-Cas9 plasmids

B. Targeting agents that we have conjugated with:

human and mouse Mo Abs e.g. CD99, CD19, peptides, proteins and

carbohydrates

C. The HPLN shell can be customized by adjusting polymer content to provide

custom-designed stability and optimal delivery properties.

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~12,000 irinotecan

drug molecules

encapsulated in

a single

HPLN (~50mg/mL

internal drug conc.)

~ 400

monoclonal

targeting

antibodies

on a single

HPLN

Conventional vs. HPLN ADC

Drug Molecules/Binding Site & Total Binding Sites

• 1 IgG, 2 Fabs (binding sites)

• 2-4 small molecules

• Ratio: 1:1 to 1:2

• 400 IgGs, 800 Fabs (binding sites)

• 12,000 small molecules

• Ratio: 1:15

A: HPLN enables much increased drug per antibody binding site with increased binding

avidity but also…..

B: Antibody binding avidity increases exponentially with increased binding sites.

e.g. IgG, 2 Fabs (Ka=107) vs IgM, 10 Fabs (Ka=1011), or 10,000 times the avidity*.

Antibody-Drug Conjugate HPLN Antibody-Drug Conjugate

6 * Hong et al; Chemistry & Biology 14, 107–115, January 2007

HPLN Payload Delivery CRISPR/Cas9 Cytotoxics siRNA or ASOs

DNA Small Molecules RNA

Adapted from Shi et al Nature Reviews

Cancer Nanomedicine Nov 2016

7 7

Product & Project Pipeline

R & D Preclinical

Validation

IND

Enabling P 1 P Ib

NV103 (CD99/Irinotecan): Ewing Sarcoma

NV103: Neuroendocrine

NV102 (CD19/Doxorubicin): ALL

NV102: AML

NCI Grant, Surgical Adhesions

NV101 (CD99/Doxorubicin): Ewing Sarcoma

NCI STTR Phase II/IIb NCI STTR,Ewing Sarcoma

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Why Ewing Sarcoma? Our funding so far has been oriented towards pediatric oncology.

Ewing sarcoma is a rare childhood bone cancer (2nd most common

bone/soft tissue pediatric tumor) with an often dismal treatment

prognosis and 10% 5-year survival rate upon relapse, unchanged in

decades despite use of a 7-drug regimen.

The primary disease afflicts approximately 3000 patients annually in the

U.S., 1,500 of which are at high risk for relapse.

Current standard therapies include Cytarabine, Dactinomycin,

Doxorubicin, Vincristine, Ifosfamide, Cyclophosphamide, Etoposide, and

most recently Irinotecan.

Refractory Pediatric Ewing Sarcoma would qualify for an “Orphan

Designation” and priority FDA regulatory review.

Therapeutic approval in this indication confers a Rare Pediatric Disease

Priority Review Voucher (program renewed 12/2016).

AND…….

Demonstrated clinical efficacy of NV103 (CD99/Irinotecan) or NV101

(CD99/Doxorubicin) in Ewing Sarcoma will effectively validate the HPLN

platform for other adult and pediatric cancers.

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CH

LA

9

CH

LA

10

TC

32

TC

71

CH

LA

258

A673

A457

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CD99 b-actin

Expression of CD99

in Ewing tumor cell lines

HPLN targeted with

anti-CD99 antibodies

HPLN (untargeted)

Tumor Cell Binding:

Targeted vs. Untargeted

Ewing Sarcoma Studies

HPLN binding to TC32 Ewing cells

% b

indin

g

fluorescence

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NV101 (CD99/Dox) vs. ‘Doxil™’

NV101 Untargeted

NV101

Conventional

‘Doxo liposome’ Doxo

IC50 (nM) 2.2 42 87.9 155.7

Conclusion: NV101 improves potency • 20x versus untargeted and

• >40x versus conventional liposomal doxorubicin

IC50 TC32 Ewing

Sarcoma Cell Line

Dosing Escalation

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D o x (n M )

Re

l. V

iab

ilit

y

0 .0

0 .5

1 .0

U n ta r g e te d N V 1 0 1

N V 1 0 1

C o n v e n t io n a l (u n ta r g e te d ) D o x o l ip o s o m e

D o x o

10 100

Ewing Sarcoma:

NV101(CD99/Dox) Efficacy

Xenograft mice receiving Human Ewing sarcoma cells (TC71-Luc)

intravenously (through tail vein)

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NV102 (CD19/Dox) Efficacy in Leukemia

Xenograft mice receiving

Human leukemia cells

Ph

oto

ns/s

ec

No Treatment

HPLN/Dox

Human antiCD19 HPLN/Dox

Day 24

Dorsal Ventral

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NV102 Eradication of Relapsed and

Treatment Resistant Adult ALL

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Ewing Sarcoma: Superior Efficacy of NV103 (CD99/Irinotecan)

And the only

group with

100% survival

at 63 days

No detectable

tumor after 63

days, with no

toxicity

Tumor burden

2 0 3 0 4 0 5 0 6 0

0

1 0 0 0

2 0 0 0

3 0 0 0

4 0 0 0

5 0 0 0

D a y s a fte r In je c t io n o f T C 7 1

Tu

mo

r V

ol.

(mm

3)

N o T re a tm e n t

U n ta rg e te d H P L N /D o x

T a rg e te d H P L N /D o x

T a rg e te d H P L N /Ir i

0 2 0 4 0 6 0

0

5 0

1 0 0

S u r v iv a l o f D a y 6 3

D a y s a fte r In je c t io n o f T C 7 1

Pe

rc

en

t s

urv

iva

l N o T re a tm e n t

U n ta rg e te d H P L N /D o x

T a rg e te d H P L N /D o x

T a rg e te d H P L N /Ir i

15

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Day 35

Day 56

Day 63

Day 70

NV103 Treated vs. Untreated

Control / untreated animals all

died by day 45

Treated animals

Comparison of the liver and kidney enzyme function in mice treated

with targeted, doxorubicin-loaded NV102, doxorubicin alone and

untreated control animals. The treated animals were given the highest

dose tested of 2.0 mg/kg doxorubicin two times per week for 4 weeks.

Safety Demonstrated

No treatment

NV102 (CD19/Doxo)

Doxorubicin alone

Liver and kidney function (serum chemistry)

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Platform R & D

Signed MTA with NCI for Englerin A ◦ small molecule Rx for Ewing Sarcoma

Signed MTA with MSK for Morpholino (ASO) ◦ EWS-FLI1 chimeric gene in Ewing sarcoma

Signed MOU with NCI PPTP to evaluate HPLNs in pediatric

cancer ◦ IND-compatible data to be generated

Pending proposal for HPLN clinical characterization by

NCL/NCI

Next Generation Therapeutic Delivery ◦ CRISPR/Cas9 delivery

◦ lncRNA directed ASO delivery

Surgical Adhesions Diagnostic Imaging ◦ $240k + NCI Grant

Non-Oncology Applications

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CRISPR/Cas9/gRNA + EGFP Construct

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High Efficiency Delivery of CRISPR/Cas9

EWS-FLI1 gRNA Plasmids in Ewing Tumor Targ

ete

d

Un

targ

ete

d

Fluorescence Light Microscope Combined

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Immediate Corporate Strategy Finance and validate pivotal lead programs in clinical oncology settings

and start to develop others:

◦ NV101: Ewing sarcoma / CD99 expressing tumors

◦ NV102: Adult leukemia / CD19 expressing tumors

◦ NV103: Ewing sarcoma / CD99 expressing tumors

Use grants and strategic partnering to further exploit the technology

platform with:

◦ New oncology applications (in very early discussion with several pharma groups:

◦ ‘Difficult to deliver’ emerging applications (e.g. CNS)

Operate with minimal infrastructure & overhead whilst harnessing proven

support:

◦ R & D (in vitro and in vivo): CHLA and TD2 (TBC)

◦ Regulatory, IND enabling: TD2 (Dan Von Hoff) (TBC)

◦ Contract GMP Manufacturing: EU based supplier selected (TBC)

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NV101/NV103 Milestones

Action Initiation

GMP/CMC* confirmation including NCL support

program

Underway

Initiate pre-IND process Initial Q1 2017

meeting fixed

IND-enabling studies*

• Toxicology: Monkey and rats/dogs

• PKDM studies and bioanalysis

Q2-3 2017

Phase I “all comers” dose escalation with any CD99+

tumor (e.g. neuroendocrine) **

2018

Phase Ib CD99+ Ewing Sarcoma** 2018-9

*Subject to Financing. LOI with TD2 in place.

**Subject to FDA INDA acceptance and definition

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Core Intellectual Property Issued Patent Applications Title First Date

5,512,294 Targeted Polymerized Liposome

Contrast Agents 4/30/96

6,090,480 Use of Polymerized Lipid Diagnostic

Agents 7/18/2000

6,132,764 Targeted Polymerized Liposome

Diagnostic and Treatment Agents 10/17/2000

WO 02/30473 A1 Targeted Therapeutic Agents 4/18/2002

6,569,451 Targeted Polymerized Liposome

Diagnostic and Treatment Agents 5/27/2003

7,285,289 Nanoparticle Vaccines 10/23/2007

Patent Applications Title Date

12/478,248 Stabilized Therapeutic and Imaging

Agents 5/6/2010

13/699,298 Polymerized Shell Lipid Microbubbles

and Uses Thereof

11/20/2012

PCT/US2012/037457

Enhanced Growth Inhibition of

Osteosarcoma by Cytotoxic

Polymerized Liposomal Nanoparticles

Targeting the ALCAM Cell Surface

Receptor

5/11/2012

PCT/US2015/023943 Targeted Polymerized Nanoparticles

for Cancer Treatment 4/1/2015

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Executive Management

Timothy L Enns, President & CEO

Mr. Enns is President and Chief Executive Officer of NanoValent. Mr. Enns has over 30 years experience in leadership roles within Pharmaceutical and Biotechnology companies. Prior to NanoValent he held senior executive roles at KineMed Inc, Astex Pharmaceuticals, Inc (now Otsuka) and Sequus Pharmaceuticals. Mr. Enns management roles have included Business Development, Corporate Communications and Investor Relations, Marketing and Sales. His prior experience includes most aspects of cancer therapeutic commercialization from start up through launch and partnering. Prior to Sequus he held senior positions at Trilex, Syncor, MGI Pharma and Upjohn. He has a BS in Nutritional Science & Biochemistry from UC Davis.

Jon Nagy, PhD, Chief Scientific Officer

Dr. Nagy is co-founder of NanoValent and received his PhD in synthetic organic chemistry from Iowa State University in 1983, and completed doctoral training at UC Berkeley. In 1990, Dr. Nagy joined Lawrence Berkeley National Laboratory where he generated seven issued patents and 15 scientific publications, including a paper in Science related to polymer films and nanoparticles. In 1999, Dr. Nagy joined LigoCyte Pharmaceuticals as Director of Chemistry and Nanoparticle research

Timothy Triche MD, PhD, Chief Medical Officer

Dr. Triche is co-founder of NanoValent and is board certified in pathology and is on the staff of Children’s Hospital Los Angeles and a professor at the University of Southern California. His expertise centers on pediatric and adult cancer genomics. He has received over $100M in peer-reviewed grant funding since leaving the NCI, where he held a tenured faculty position. Dr. Triche has been a principle and founder in several publicly traded companies that have raised over $200M in public markets. He was co-founder of OncorMed, a publicly traded company that was sold to Gene Logic. He is a co-founder of GenomeDx, a privately held urologic oncology company that provides CMMS reimbursed prostate cancer testing.

Mark Lewis, Chief Operating Officer

Mr. Lewis has over 30 years international experience in the pharmaceutical industry; 25 years with companies including Amersham International (now part of GE), Farmitalia (now part of Pfizer), Chiron (now part of Novartis), Groupe Servier, Ascalon and SuperGen (now Otsuka) in various international commercial and operational roles and 10 years as a management consultant (Quintiles, Hill & Knowlton) for a spectrum of pharmaceutical and biotechnology clients. With an honors degree in biochemistry and secondary business qualifications, Mr. Lewis has extensive strategic marketing, project management, development, commercial and operational skills, gained in several therapeutic areas primarily oncology but also respiratory, CNS, cardiology and endocrinology.

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Investment considerations

Phase I enabled drug

candidates

Key strategic partnerships in

place and operational readiness

Strong and

balanced

management

team

Broad technology

platform with IP

Interest from pharma on

development partnerships

Near term clinical POC enables low

risk/high return strategy

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Contact: Mark Lewis (COO) at

mlewis@nanovalent.com