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

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

Forward Looking Statements 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 other 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. 2

Investment Highlights  Prodrug, masked by peptide, precisely targets PSMA and activates upon contact Mipsagargin, Precision-  MOA models, conducted by Johns Hopkins University, provide foundation for consistent safety Targeting Prodrug profile Validated Mechanism  Potential broad utility across solid tumor types  Prolonged disease stabilization observed in advanced cancer patients Compelling Phase 2 Data  Potential to improve survival Robust Safety Package  Attractive safety profile compared to other oncology therapeutics  Near term initiation of additional Phase 2 trials in HCC, GBM Well-defined Development,  Regulatory Paths Orphan Drug designation in HCC, other opportunities  Focused on development of lead asset, opportunities for business development New, Experienced Team  Multifaceted IP portfolio, royalty free Focused on Building Value  Optionality to out-license in a variety of structures 3

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 Gulf Enterprises Director AFIN International, Inc. International, Ltd. 4

Advancing Mipsagargin’s Development Phase 1 Phase 2 Preclinical Phase 3 Inspyr Trials Initiate 1H17 HCC* Monotherapy (Partner) Initiate 1H17 HCC* Monotherapy (Second-line) Initiate 2H17 HCC* Combination Initiate 2H17 GBM Combination Therapy ISTs Data 2017 GBM (Recurrent) Initiate 4Q16 GBM (Recurrent) Prostate (Neo-adjuvant) Data 2H17 RCC (Refractory) Data 2H17 Planned * Mipsagargin for HCC has U.S. Orphan Drug designation 5

PSMA Expression Provides Validated Target Negative PSMA Positive PSMA 100 90 80 70 60 50 40 30 20 10 0 HCC Renal Colorectal Breast Ovarian Gastric Melanoma Normal Normal Normal Normal Liver Kidney Breast Bladder  PSMA reaction to prodrug creates reliable delivery mechanism Source: Denmeade, S. et al. Engineering a prostate-specific membrane antigen–activated tumor endothelial cell prodrug for cancer therapy. 6 Science Translational Medicine. 27 June 2012. doi: 10.1126/scitranslmed.3003886

Mipsagargin, Precision Targeting by Design Targeted Approach for Improved Tumor Blood vessels Kill feed living  Potent therapeutic (thapsigargin tumor derivative, 12ADT) is combined with a protective peptide  Peptide targets the PSMA enzyme, highly Drug circulates in bloodstream in benign fashion expressed on tumor vasculature surface  PSMA removes the peptide, releasing therapeutic that kills blood vessels feeding tumor Activated drug kills blood PSMA enzyme within tumor vessels blood vessels activates drug  12ADT inhibits SERCA pump leading to in the tumor apoptosis independent of growth rate Death of tumor Targeted Approach for Safer Profile  Manageable side effect profile  No impact on bone marrow observed to date  Potential for improved tumor kill and  Combination therapy options available fewer side effects 7

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 8

Mipsagargin in Solid Tumors 9

First Patient Study Completed in Solid Tumors P h a s e 1 S t u d y Advanced patients (N=44) Multicenter (3 U.S. centers) Key inclusion criteria: Dose escalation  Advanced, refractory solid tumor 3+3 dose escalation design  ECOG PS ≤ 2  Life expectancy >3 months Mipsagargin  Acceptable liver and renal function (One-hour IV infusion in saline) Days 1, 2, 3 of 28-day cycle Primary Endpoints: MTD and DLT(s), recommended dose for Phase 2, PK Secondary Endpoints: Safety, anti-tumor activity (response rate, disease stability, PFS, OS) 10

Phase 1 Study: Overall Results Patient Demographics and Baseline Characteristics  44 Patients  8 dose levels + expansion cohort 1.2 2.5 5 10 20 40 66.8 88 40/66.8/66.8 Dose Level (mg/m2) N=3 N=3 N=3 N=3 N=3 N=4 N=6 N=3 N=16  35 patients received at least 2 cycles Sex: Male Female 3 2 2 3 1 4 4 3 13  2 patients discontinued due to AEs 0 1 1 0 2 0 2 0 3 Race:  Only 1 DLT (66.8 mg/m 2 ), Grade 3 rash White/Caucasian 3 3 3 2 3 4 5 2 10 Hispanic/Latino 0 0 0 0 0 0 1 1 6 Eastern European  Protocol-defined MTD not identified 0 0 0 1 0 0 0 0 0  MAD was 88/88/88 mg/m 2 61 64 59 70 62 71 60 69 68 Median Age (57-71) (57-69) (48-76) (64-70) (54-62) (49-81) (52-79) (58-71) (50-83) (Range)  Recommended Phase 2 dose: 40/66.8/66.8 mg/m 2 ECOG PS 0 1 1 0 0 1 0 1 2 0 3  Increased tolerability 2 3 3 2 3 3 4 3 13 Primary Tumor Type:  Significant decrease in day 1 infusion Bladder 0 1 0 0 0 1 0 0 0 Cholanglocarcinoma 0 1 0 0 0 0 0 0 0 reaction Colorectal 1 0 3 1 3 0 4 0 2 Endometrial 0 0 0 0 0 0 0 0 1 Esophageal 1 0 0 0 0 0 0 0 0 Head and Neck 0 0 0 0 0 1 0 0 0 Hepatocellular 0 0 0 0 0 0 0 1 5 Lung (NSCLC) 0 0 0 1 0 0 0 0 1 Pancreas 0 0 0 0 0 1 1 1 0 Prostate 1 0 0 0 0 0 0 1 7 Renal 0 0 0 0 0 1 0 0 0 Unknown Primary 0 0 0 1 0 0 1 0 0 Urothellal 0 1 0 0 0 0 0 0 0 11

Phase 1 Efficacy: Prolonged Disease Stabilization, PFS Progression-free Survival in Patients with SD as  42 patients evaluable for efficacy best response  28.6% (12 patients) DCR Patient Tumor Type Dose Level Progression-free Number (mgm -2) Survival (Days)  3 of 5 HCC patients, refractory to Nexavar therapy, (Day 1/2/3) demonstrated: 01-002 Prostate 1.2 112  Prolonged disease stabilization 01-006 Cholangiocarcinoma 2.5 89  4.4 months median PFS (range 34-336 days) 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 Abbreviation: SD = stable disease. (a) Censored observation 12

Phase 1 Safety: Well Tolerated and Manageable SAE were Grade 1-3 with one Grade 4 event of thrombocytopenia • Renal events were primarily creatinine elevations that resolved with • hydration  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 13

Mipsagargin in Hepatocellular Carcinoma (HCC) 14