Investor Presentation October 2016 Chris Lowe OTCQB: NSPX - - PowerPoint PPT Presentation

Investor Presentation October 2016 OTCQB: NSPX www.inspyrtx.com Chris Lowe President & CEO

Any statements that are not historical facts are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from those in the forward-looking statements, which may include, but are not limited to, factors related to Inspyr Therapeutics anticipated growth strategies, the outcome of its clinical trials, future business development, ability to develop new products, expand to other related industries or markets in

• ther geographical locations, and other information detailed from time to time in the Company's filings and future

filings made with the U.S. Securities and Exchange Commission. Readers are advised that this information is intended for the use of investment professionals. Anyone interested in obtaining information on Inspyr Therapeutics should contact Inspyr Therapeutics directly. This presentation was developed by Inspyr Therapeutics and is intended solely for informational purposes and is not to be construed as an offer to sell or the solicitation of an offer to buy the Company's stock. This presentation is based upon information available to the public, as well as other information from sources management believes to be reliable, but is not guaranteed by the Company as being accurate nor does it purport to be complete. Opinions expressed herein are those of management as of the date of the presentation and are subject to change without notice.

Forward Looking Statements

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Investment Highlights

• Prodrug, masked by peptide, precisely targets PSMA and activates upon contact
• MOA models, conducted by Johns Hopkins University, provide foundation for consistent safety

profile

• Potential broad utility across solid tumor types
• Near term initiation of additional Phase 2 trials in HCC, GBM
• Orphan Drug designation in HCC, other opportunities

New, Experienced Team Focused on Building Value

• Focused on development of lead asset, opportunities for business development
• Multifaceted IP portfolio, royalty free
• Optionality to out-license in a variety of structures

Well-defined Development, Regulatory Paths Mipsagargin, Precision- Targeting Prodrug Validated Mechanism Compelling Phase 2 Data Robust Safety Package

• Prolonged disease stabilization observed in advanced cancer patients
• Potential to improve survival
• Attractive safety profile compared to other oncology therapeutics

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New Leadership

Management Chris Lowe, MBA President & CEO Ronald Shazer, M.D., MBA Senior VP & Chief Medical Officer Russell Richerson, Ph.D. COO and Corporate Secretary Michael A. Elliott, MA VP Clinical Operations Board of Directors Peter Grebow, Ph.D. Interim Chairman Bo Jesper Hansen, M.D., Ph.D. Director Richard Buller, M.D. Ph.D Director Claire M. Thom, Pharm.D. Director Scott Ogilvie Director

AFIN International, Inc. Gulf Enterprises International, Ltd.

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Advancing Mipsagargin’s Development

Inspyr Trials

HCC* Monotherapy (Partner) HCC* Monotherapy (Second-line) HCC* Combination GBM Combination Therapy

Phase 1 Phase 2 Phase 3 Preclinical

Initiate 1H17

Planned

Initiate 2H17 Data 2017

ISTs

GBM (Recurrent) GBM (Recurrent) Prostate (Neo-adjuvant) RCC (Refractory)

Initiate 4Q16 Data 2H17 Initiate 1H17 Initiate 2H17 Data 2H17

* Mipsagargin for HCC has U.S. Orphan Drug designation

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PSMA Expression Provides Validated Target

• PSMA reaction to prodrug creates reliable delivery mechanism

10 20 30 40 50 60 70 80 90 100 Normal Liver Normal Kidney Normal Breast Normal Bladder

HCC Renal Colorectal Breast Ovarian Gastric Melanoma

Negative PSMA Positive PSMA

Source: Denmeade, S. et al. Engineering a prostate-specific membrane antigen–activated tumor endothelial cell prodrug for cancer therapy. Science Translational Medicine. 27 June 2012. doi: 10.1126/scitranslmed.3003886

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Mipsagargin, Precision Targeting by Design

Targeted Approach for Improved Tumor Kill

• Potent therapeutic (thapsigargin

derivative, 12ADT) is combined with a protective peptide

• Peptide targets the PSMA enzyme, highly

expressed on tumor vasculature surface

• PSMA removes the peptide, releasing

therapeutic that kills blood vessels feeding tumor

• 12ADT inhibits SERCA pump leading to

apoptosis independent of growth rate

Targeted Approach for Safer Profile

• Manageable side effect profile
• No impact on bone marrow observed to

date

• Combination therapy options available

Blood vessels feed living tumor Drug circulates in bloodstream in benign fashion PSMA enzyme within tumor blood vessels activates drug Activated drug kills blood vessels in the tumor Death of tumor

• Potential for improved tumor kill and

fewer side effects

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Compelling Safety Profile

• No observed effect on cardiovascular system
• No observed effect on bone marrow
• No immunosuppression
• No anemia
• Increased creatinine levels on dosing days, remediated with hydration
• Clinical experience to date indicates improved safety profile over standard of care in HCC
• Clinical experience should translate to similar experiences in additional indications
• Compelling preclinical data provided foundation for Phase 1 study

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Mipsagargin in Solid Tumors

Key inclusion criteria:

Advanced, refractory solid tumor ECOG PS ≤ 2 Life expectancy >3 months Acceptable liver and renal function

First Patient Study Completed in Solid Tumors

Mipsagargin

(One-hour IV infusion in saline) Days 1, 2, 3 of 28-day cycle

Advanced patients (N=44)

Multicenter (3 U.S. centers) Dose escalation 3+3 dose escalation design

Primary Endpoints:

MTD and DLT(s), recommended dose for Phase 2, PK Secondary Endpoints: Safety, anti-tumor activity (response rate, disease stability, PFS, OS)

P h a s e 1 S t u d y

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• 44 Patients
• 8 dose levels + expansion cohort
• 35 patients received at least 2 cycles
• 2 patients discontinued due to AEs
• Only 1 DLT (66.8 mg/m2), Grade 3 rash
• Protocol-defined MTD not identified
• MAD was 88/88/88 mg/m2
• Recommended Phase 2 dose:

40/66.8/66.8 mg/m2

• Increased tolerability
• Significant decrease in day 1 infusion

reaction

Phase 1 Study: Overall Results

Dose Level (mg/m2) 1.2 N=3 2.5 N=3 5 N=3 10 N=3 20 N=3 40 N=4 66.8 N=6 88 N=3 40/66.8/66.8 N=16 Sex: Male Female 3 2 1 2 1 3 1 2 4 4 2 3 13 3 Race: White/Caucasian Hispanic/Latino Eastern European 3 3 3 2 1 3 4 5 1 2 1 10 6 Median Age (Range) 61 (57-71) 64 (57-69) 59 (48-76) 70 (64-70) 62 (54-62) 71 (49-81) 60 (52-79) 69 (58-71) 68 (50-83) ECOG PS 1 1 2 3 3 1 2 3 1 3 2 4 3 3 13 Primary Tumor Type: Bladder Cholanglocarcinoma Colorectal Endometrial Esophageal Head and Neck Hepatocellular Lung (NSCLC) Pancreas Prostate Renal Unknown Primary Urothellal 1 1 1 1 1 1 3 1 1 1 3 1 1 1 1 4 1 1 1 1 1 2 1 5 1 7

Patient Demographics and Baseline Characteristics

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• 42 patients evaluable for efficacy
• 28.6% (12 patients) DCR
• 3 of 5 HCC patients, refractory to Nexavar therapy,

demonstrated:

• Prolonged disease stabilization
• 4.4 months median PFS (range 34-336 days)

Phase 1 Efficacy: Prolonged Disease Stabilization, PFS

Patient Number Tumor Type Dose Level (mgm -2) (Day 1/2/3) Progression-free Survival (Days) 01-002 Prostate 1.2 112 01-006 Cholangiocarcinoma 2.5 89 01-010 Colorectal 5 112 01-012 Non-small cell lung 10 52a 01-017 Pancreas 40 57a 01-022 Adenocarcinoma 66.8 63a 03-029 Prostate 88 119 03-031 Endometrial 40/66.8/66.8 77a 03-036 Hepatocellular 40/66.8/66.8 336 03-037 Prostate 40/66.8/66.8 121a 03-043 Hepatocellular 40/66.8/66.8 133 03-044 Hepatocellular 40/66.8/66.8 277a

Progression-free Survival in Patients with SD as best response

Abbreviation: SD = stable disease. (a) Censored observation

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Phase 1 Safety: Well Tolerated and Manageable

• Most frequently observed treatment-related AEs were fatigue, rash, nausea,

infusion reactions (primarily day 1) and transient creatinine elevation

• No observed neuropathy, bone marrow suppression
• SAE were Grade 1-3 with one Grade 4 event of thrombocytopenia
• Renal events were primarily creatinine elevations that resolved with

hydration

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Mipsagargin in Hepatocellular Carcinoma (HCC)

Key eligibility criteria:

 HCC  ECOG PS of 0 or 1  Child-Pugh A or B7  Disease progression on Nexavar  Measurable disease  Adequate liver and kidney function  No limit on number of prior therapies  Not candidate for transplant  No known CNS metastasis

Phase 2 Study in HCC Patients Refractory to Nexavar

Cohort 1 (n=3) Mipsagargin

(One-hour IV infusion in saline) 40 mg/m2 on days 1, 2 and 3

• f 28-day cycle

HCC patients refractory to Nexavar (N=25)

Multicenter (4 U.S. centers)

Primary efficacy endpoint:

TTP Secondary efficacy endpoints: Tumor response rate, PFS, OS, PD markers (optional) Cohort 2 (n=6) Mipsagargin

(One-hour IV infusion in saline) 40 mg/m2 on day 1, 66.8 mg/m2 on days 2 and 3

• f 28-day cycle

Expansion (n=16) Mipsagargin

(One-hour IV infusion in saline) 40 mg/m2 days 1, 2 and 3

• f 28-day cycle

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Phase 2 Efficacy: 4.5 Months TTP in Advanced HCC

Efficacy (N=25 patients) Results

Evaluable for Response 19 Patients (76%) 24% had received 2 or more prior systemic therapies Best Response CR + PR 0 Patients SD 12 Patients (63%) Tumor reduction 8 Patients (42%) Time to Progression (TTP) 134 days (4.5 months; Range: 50 – 421 days) Overall Survival (OS) 205 days (6.8 months; Range: 74 – 211 days) Progression-Free Survival (PFS) 129 days (4.3 months; Range: 50 – 421 days)

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• Primary endpoint demonstrated:
• 4.5 months TTP (median) for Mipsagargin in

Nexavar-refractory patients

• By comparison:
• 5.5 months TTP (median) for Nexavar in

treatment-naïve patients

• 2.7 months TTP (median) for historical

control in Nexavar-refractory patients

• 63% of patients experienced disease

stabilization

• 37% of patients showed prolonged disease

stabilization (≥5 months) Clinical Activity Observed

Mipsagargin Stivarga (Regorafenib)

Phase 2 Phase 21 Phase 32 Mipsagargin Stivarga Stivarga Placebo Size (N) 25 36 379 194 ECOG PS 0-1 0-1 0-1 Child-Pugh 5-7* 5-6† 5-6 mTTP (months) 4.5 4.3 3.2 1.5 mPFS (months) 4.3

• 3.1

1.5 mOS (months) 6.8 13.8 10.6 7.8 ORR 0% 3% (1 PR) 10.6% 4.1% SD 63% 69% 65.2%§ 36.1%§ Patients with tumor reduction 42% 39%

• *60% ≥ 6 Child-Pugh score

†25% = 6 Child-Pugh score

§Disease Control Rate (DCR): SD+PR+CR

1 Bruiz J et al. 2013 Eur J of Cancer 2 Bruiz J et al. RESORCE trial. 2016 Ann of Oncol Abstract

Advanced HCC: Mipsagargin Compares Favorably to Regorafenib

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Phase 2 Safety: Well Tolerated and Manageable

Adverse Event n (%) Creatinine Increased 17 (68) Fatigue 11 (44) Nausea 9 (36) ALT increased 8 (32) Pruitis 8 (32) Rash 8 (32) AST Increased 7 (28) Blood Urea Increased 6 (24) Decreased Appetite 6 (24) Hyperbilirubinemia 6 (24) LDH Increased 6 (24) Thrombocytopenia 6 (24) Vomiting 6 (24)

Treatment-Related Adverse Events (>20%)

• Manageable side effects, including reversible creatinine

increase with no observed bone marrow effect or hypertension

• Most treatment-related AEs were Grade 1 or 2
• 5 patients (20%) discontinued for an AE
• By comparison, 32% discontinued for an AE in the Nexavar

pivotal study

Treatment-Related Serious Adverse Events

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Advancing Mipsagargin for HCC: Future Potential Studies

Lead-in Dose Optimization

• N = 6-12
• Two dose schedules
• Primary Endpoint: RP2D

Phase 2: Nexavar Refractory Patients

HCC (Nexavar Refractory)

• N = 30-40
• Primary Endpoint: PFS
• Secondary Endpoints: OS, TTP

Mipsagargin + Nexavar

Phase 1b  Phase 3 Preclinical

HCC (Nexavar Naïve) Phase 1b with expansion

• N = 40
• Primary Endpoint: MTD/RP2D/TTP

Phase 3

• N = 600-700
• Primary Endpoint: OS
• Secondary Endpoints: TTP, PFS

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Mipsagargin in Glioblastoma (GBM)

• At least 1 prior regimen required
• Up to 4 prior lines of therapy allowed
• 84% power for detecting a PFS6 rate of 35%

with an α of < 0.05 if PFS6 is only 15%

• Efficacy-evaluable patients defined as those

receiving two cycles of treatment followed by disease assessment

First Phase 2 IST in Recurrent GBM: Ongoing

Stage 1 Mipsagargin

n=11

Evaluate two dosing regimens and response If ≥ SD in at least 2 patients, move to Stage 2

Recurrent or progressive GBM patients (N=34)

Two-stage, single-arm, open-label, single-site

Primary endpoint:

6 month PFS rate Secondary endpoints:

Safety, efficacy, blood flow metrics, CSF and blood PK, molecular response correlates

P h a s e 2 S t u d y ( U C S D )

Stage 2 Mipsagargin

n=23

40 mg/m2 on day 1, 2 and 3

• f 28-day cycle selected

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Phase 2 IST in GBM: Initial Results Show Clinical Benefit

Stage One

• Patient enrollment initiated May 2015
• 2 of 11 evaluable patients showed clinical

benefit:

• 1 SD, 1 PR
• Stage one met requirement to open stage two

Stage Two

• 19 patients dosed (15 evaluable for efficacy)
• 1 SD
• Most common treatment-related grade 1 AE was

transient increase in creatinine (8 of 19 patients)

• Similar safety profile as in HCC

Treatment-Related AEs ≥ Grade 2, N=19

• Enrollment ongoing
• Top-line data expected 2017

Grade Adverse Effect 2 3 4 Nausea/Vomiting 1 1 1 Infusion Reaction 1 Fatigue 2 Reflux 1 Rash 2 Hyperglycemia 1 Increased ALT 1 1 Increased Creatinine 1 Diarrhea 1

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• PSMA+ GBM
• At least 1 prior regimen required
• Up to 4 prior lines of therapy allowed
• 84% power for detecting a PFS6 rate of 35%

with an α of < 0.05 if PFS6 is only 15%

• Efficacy-evaluable patients defined as those

receiving two cycles of treatment followed by disease assessment

Second Phase 2 IST in Recurrent GBM: Initiating

P h a s e 2 S t u d y ( J o h n Wa y n e C I )

• Enrollment begins September 2016

Stage 1 Mipsagargin

n=11

If ≥ SD in at least 2 patients, move to Stage 2

Recurrent or progressive PSMA+ GBM patients (N=34)

Two-stage, single-arm, open-label, single-site

Primary endpoint: 6 month PFS rate

Secondary endpoints: Safety, efficacy, blood flow metrics, CSF and blood PK, molecular response correlates

Stage 2 Mipsagargin

n=23 23

Advancing Mipsagargin for GBM: Future Potential Studies

Mipsagargin + XRT/Temozolomide (Temodar, TMZ)

Phase 1b Preclinical

Advanced GBM N = 18-36 (6-12/arm) Arm A: Mipsagargin + TMZ Arm B: Mipsagargin + XRT/TMZ Arm C: Mipsagargin + Avastin Primary Endpoint: MTD Mipsagargin + Avastin Single-arm or Randomized 1st Recurrence: Mipsagargin + TMZ 1st Line: Mipsagargin + XRT/TMZ Avastin Naïve: Mipsagargin + Avastin

Phase 2

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Mipsagargin: Potent Therapy with Potential Broad Utility

• PSMA is expressed on tumor vasculature:
• 93% of HCC patients1 as PSMA ≥1+
• 91% of GBM patients2 as PSMA ≥2+
• MOA, models conducted by Johns Hopkins, foundation for consistent safety profile
• Synergistic MOA potential with standard-of-care treatments
• Expert input from Scientific Advisory Board Member, Board-certified Neurologist/

Neuro-oncologist Santosh Kesari, M.D., Ph.D., John Wayne Cancer Institute

• Well-defined, potentially expedited regulatory path in recurrent disease
• Broader development plans for combination therapy to move into earlier lines of treatment

Well-defined Development, Regulatory Paths Synergistic Mechanisms of Action Additive Clinical Benefit

• Attractive, consistent safety profile offers potential as monotherapy and in combination with

standard-of-care treatments, without adding to side effects

• Additive clinical benefit of potential disease stabilization beyond benefits of standard-of-care

treatments

1 Denmeade, S. et al. Engineering a prostate-specific membrane antigen–activated tumor endothelial cell prodrug for cancer therapy. Science Translational Medicine. 27 June 2012. doi:

10.1126/scitranslmed.3003886

2 Wernicke, A.G. et al. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Archives of Pathology & Laboratory Medicine.

November 2011. doi: http://dx.doi.org/10.5858/arpa.2010-0740-OA.

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Imaging Technology U.S. Patent 2030 Expiration 2nd Generation Commercial Technology

• Clinically used Mipsagargin covered in U.S. between 2018-2026
• 8 patent families
• 15 U.S. patents issued or with notice of allowance
• 43 applications worldwide currently in progress

1st Generation Mipsagargin 2018–2026 Expirations

Activated by PSMA

• Exp. 2023

Activated by Hk2

• Exp. 2026

Activated by PSA

• Exp. 2018

1 2 3

Product Families

Mipsagargin’s Multilayered Patent IP Platform

Commercial form for injectable Manufacturing process for injectable form Alternative manufacturing process 26

Elements to Build Value for Inspyr

New, experienced team focused on execution to build value Selectively adding leadership expertise

Orphan Drug designation in HCC, other

• pportunities

New Phase 1b/2 and Phase 2 trials initiating for Mipsagargin 4Q16/1H17 Phase 2 IST data flow for Mipsagargin 2017, 2018 New business development

• pportunities

Optionality with multifaceted IP portfolio

L e a d e r s h i p L e a d A s s e t M i p s a g a r g i n N e w O p p o r t u n i t i e s

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www.inspyrtx.com OTCQB: NSPX

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Backup Slides

Mipsagargin Pharmacokinetics

Cohort 2 3-6 patients

Bi-exponential Function (without weighting) Best Represented the Plasma Concentration Profiles

• Mipsagargin was measured in blood:



Prior to C1D1 dosing



After beginning C1D1 infusion (30, 60, 75, 90, 120 minutes)



2, 4, 8, 10-12 hours after completion of C1D1 infusion



Prior to C1D2



Prior to C1D3

• Data suggest a bi-exponential model

with time-invariant kinetics

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Preclinical Data Show Potent Anti-tumor Effect, Encouraging Safety

Pharmacological Efficacy  Complete tumor regression with monotherapy in mouse tumor models  Safety margin of 7-fold to 10-fold in mice  No acquired resistance to Mipsagargin Bioanalytical

 No released active 12ADT in blood, only intact,

inactive Mipsagargin

 Drug cleared primarily via liver

Anti-tumor activity of one 2-day course of Mipsagargin in MCF-7 human breast cancer xenografts Biodistribution of Mipsagargin and its Metabolite 12ADT-Asp 31