Slide 1: Pioneering Gene Therapies for Patients in Need
€) Genprex’ Pioneering Gene Therapies for Patients in Need October 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements “Yorwordiooing semen within de meaning fhe Private Scuties Ligation Refem Aa of 1995 Becnuce uch savers are subjectto ris anduncrece, cul ests may der raters fam the expend or pled auc foaresking erent Such aatements Include but are nat ited, saxerent tering ur expected sp
Slide 3: Our Mission
Our Mission Advancing novel gene therapies for patients afflicted with cancer or diabetes. © Genprex’
Slide 4: Program Highlights
Program Highlights ONCOLOGY (@) Non-viral gene therapy platform Novel approach using systemic gene therapy to replace tumor suppressor genes for cancer in humans ‘Two FDA Fast Track Designations, one Orphan Drug Designation and two lung cancer trials (@) Clinical achievement in Ph 1 and Ph 2 studies
Slide 5: Research and Development Pipeline
Research and Development Pipeline
Slide 6: Oncology
Q ONCOLOGY REPROGRAMMING THE COURSE OF CANCER Cry} www.genprex.com
Slide 7: Why TUSC2?
Why TUSC2? Discovery Tumor Suppressor Candidate 2 {Chromosome 3p21.3 deleted gene Previously called FUS1 NPRL2 is in the same area of the chromosome © Genprex Tumor Suppressor Gene TUSC2 restoration in cancer cells in vitro inhibits cell growth and induces apoptosis TUSC2 is encoded by nuclear DNA b
Slide 8: Tumor Suppressor Genes Deleted During Cancer Development
Tumor Suppressor Genes Deleted During Cancer Development ‘© Tumor suppressor genes are deleted early during cancer development. © 82% of all non-small cell tung cancers and 100% of all small-cell lung cancers express decreased amounts of TUSC2 ‘tumor suppressor protein + Loss or reduction of TUSC2 e
Slide 9: Oncoprex Non-viral Delivery System
Oncoprex® Non-viral, positively-charged lipid-based nanoparticle in a lipoplex form is systemically Delivery System delivered. NON-VIRAL DELIVERY OF TUMOR SUPPRESSOR GENE O Genprex Cationic lipoplex carries drug to tumors.
Slide 10: Our Cancer Treatment Approach
Our Cancer Treatment Approach ‘Tumor Suppressor Gene in a DNA Plasmid Tumor suppressor genes are deleted early during cancer development. + Our method of treating cancer is to reintroduce tumor ; ee suppressor genes to patients. Systemic Patient Administration See eae cancer cal. pecfically targets
Slide 11: Novel Platform to Treat Cancer
Novel Platform to Treat Cancer © Genprex Systemic Gene Therapy Platform: Oncoprex® Delivery System Genes Allows for delivery of TUSC2 and NPRL2 genes and potentially a variety of other genes Syner Can be used in combination with other cancer therapies such as Tagrisso® and Tecentriq?® Cancers Could
Slide 12: Reqorsa Targets Cancer At Its Core
Regorsa® Targets Cancer At Its Core (i | eS Controls Cell Signaling Tyrosine kinase inhibition decreases cancer cell proliferation © Genprex’ Stimulates Apoptotic Pathways Leads to programmed cancer cell death Multiple anti-cancer mechanisms of action. oe Modulates Immune Response Promotes immune ac
Slide 13: Reqorsa Reduces Glycolysis in Cancer Cells
o ' Regorsa Reduces Glycolysis REQORSA Reverses Fundamental in Cancer Cells Characteristic of Cancer Glycotytic Function —-@- As49con geo '& A549 0 oveo Cancers are detected by PET scans bl : + PET scanning is based on increased Feel tucose Og 6-206 glucose uptake in cancer cells 3 \ + Due to high r
Slide 14: Lung Cancer: By the Numbers
Lung Cancer: By the Numbers 124K $48B 27% e e e e U.S. Annual Global Lung Global U.S. Lung U.S. Average Mortality Cancer Incidence Market Cancer Incidence Lung Cancer Survival Rate Global market is projected togrow from $18.3bilion inca 2018 to $48.7 ilion by 2026 per year in the US' per year in the
Slide 15: Reqorsa Monotherapy ONC-001 Trial
Reqorsa® Monotherapy ONC-001 Trial DOSE ESCALATION STUDY Explored toxicity and tolerability in patients. Phase 1 monotherapy results: + 31 Stage IV lung cancer patients + 0.01 - 0.09 ma/kg + 23 patients evaluable + 5 patients had stable disease + 2 patients had tumor shrinkage + Generally well-toler
Slide 16: Selective Uptake of Reqorsa
Selective Uptake REQORSA Targets Cancer Cells of Regorsa® Pretreatment Biopsies Posttreatment Biopsies REQORSA is designed to detiver functioning TUSC2 gene to cancer minimizing its uptake by norm: > Patient 1 (02 mg/kg) (ow that, in three the expression of TUSC ed 1 day after REQC Patient 2 treat (
Slide 17: Reqorsa + Tarceva ONC-002 Phase 1/2 Trial
® Regorsa® + Tarceva ONC-002 Phase 2 Trial Met Simon 2-stage criteria to enroll the full 39 subjects, but was discontinued to start study with Tagrisso. Wetegeonae soeet twron Geman) 2 eegenen soos Negrve Ceroiameo vssegtaone 2 tye css, i : eetinene 2 soe fe) (em 2 soot see ome 2 FA soe ne creme ‘ ©
Slide 18: Drug resistance to Tagrisso and Tecentriq is inevitable
For most patients, drug resistance to Tagrisso® and Tecentrig® is inevitable. 2? Our approach is designed to address drug resistance. REQORSA Immunogene Therapy may be complementary with targeted drugs and immunotherapies. REQORSA's multimodal activity may block emerging bypass pathways, thereby pot
Slide 19: AACR 21: Reqorsa + Tagrisso Reduce Tumor Growth
AACR 21: Regorsa® + Tagrisso Reduce Tumor Growth in Tagrisso Resistant Tumors Enhanced Anti-Tumor Activity ‘OsimertinbsTUSC2 REQORSA in combination with Tagrisso demonstrated ; ro significantly increased anti-tumor i. * i efficacy in EGFR mutant Tagrisso 4 10 4 } resistant NSCLC tumors in H1975- itr
Slide 20: Acclaim-1: Reqorsa with Tagrisso for NSCLC
Patients with advanced, EGFR mutant NSCLC whose disease Fe oe eg eee aera eee oraien ripe. Hoogy Al int FDA Fast Track Designation bf ded ee Acclaim - 1 © Phase 1 Dose Escalation: 12 patients (completed) © Phase 2a Expansion: ~33 patients (currently enrolling) ° Phase 2b: ~74 patients Phase 2a Expan
Slide 21: Phase 1 Dose Escalation
Phase 1 Dose Escalation Enrollment and Dose Limiting Toxicities 206matg ——0BmpNg «OR mag Total Patate 3 * Ey 2 Medan Aoeane) 5915060) S186 S07-7 59879 bute ° ° ° ° Progression Free Survival by Dose Group FS (days) {stat mar nd tert nas a oow ip bee coneng frat ey and ree wore rt eae PFS Donets sy Vo
Slide 22: Reqorsa in Small Cell Lung Cancer
Regorsa® in Small Cell Lung Cancer Targeting Small Cell Lung Cancer (in addition to NSCLC) allows Genprex to address virtually the entire lung cancer market. ‘Small Cell Lung Cancer: Consistently has low TUSC2 protein levels 2 Documented to often have deletion of at least one TUSC2 gene allele ‘Sal
Slide 23: SCLCs Express Low Levels of TUSC2 Protein
SCLCs Express Low Levels Of TUSC2 Protein IHC analysis of tumor specimens Since all SCLCs have reduced or no TUSC2 41% of SCLC have no TUSC2 protein expression protein expression, re-expressing TUSC2 100% of SCLC have reduced or no TUSC2 protein protein may lead to clinical efficacy. expression Hist
Slide 24: Atezolizumab (Tecentriq) SCLC Approval Trial
Atezolizumab (Tecentriq®) SCLC Approval Trial IMpower133 Study Adding Tecentriq to standard therapy improves survival in SCLC and establishes a new standard therapy for ES-SCLC. © Untreated, extensive stage SCLC © Carboplatin & etoposide chemotherapy + atezolizumab or placebo + 4cycles, then atezoli
Slide 25: Atezolizumab Maintenance Therapy
Atezolizumab Maintenance Therapy Once patients begin maintenance therapy with Tecentriq, Progression Free Survival is very short (2.6 mos). poll Unstatied HR, 0.66 (05% Cr: 052-088 Atezolizumab vs placebo AILCR, PR, and SD patients received maintenance therapy + Endpoints measured from the start of
Slide 26: Reqorsa Adds Significantly to Tecentriq Treatment
Reqorsa® Adds Significantly to Tecentriq Treatment CONTROL REQORSA H841 SCLC cell xenografts in humanized mice REQORSA + Atezo on H841 SCLC ‘Lung Met in Humanized Mice [003 CConvol —AtezoREQORSA Combination At Week #3
Slide 27: Increased Immune Response with Reqorsa and Tecentriq
Increased Immune Response with Regorsa® and Tecentriq © Genprex
Slide 28: Acclaim-3: Reqorsa with Tecentriq for ES-SCLC
Patients with ES-SCLC who did not develop tumor progression after receiving Tecentriq® and chemotherapy 1] « Fast Track Designation and Orphan Drug Designation Accl 3 $ A10-15US. stes cciaim © ~62 patients © Phase 1 Dose Escalation: (completed) © Phase 2: ~50 patients (currently enrolling) © Phase 2
Slide 29: Reqorsa in Ras Inhibitor Resistant Lung Cancer
Regorsa® in Ras Inhibitor Resistant Lung Cancer 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics + TUSC2 transfection significantly reduced colony formation in two Acquired Resistant (AR) cell nes ‘+ Transfection of TUSC2 also markedly increased apoptosis in AR cells + Trea
Slide 30: Reqorsa in ALK-EML4 Positive Translocated Lung Cancer
Regorsa® in ALK-ELM4 Positive SRA with The University of Michigan Rogel Cancer Center Translocated Lung Cancer and Collaboration with ALK- Positive Advocacy Group 2024 AACR Annual Meeting: ALK-Positive Collaboration: REQORSA induced apoptsisinalectn < Now profit patent tien research reactant EMLAALK
Slide 31: Reqorsa in Mesothelioma
Regorsa® in Mesothelioma 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics + Researchers investigated whether + Researchers demonstrated that TUSC2 transfection could modulate REQORSA treatment resulted in: MPM agaressive properties + Significant decrease in cell Fee MPM cal
Slide 32: NPRL2 Induces Anti-tumor Activity in NSCLC
NPRL2 Induces Anti-tumor Activity in NSCLC Further Evidence of Oncoprex® Delivery System as a Platform for Treatment Using Tumor Suppressor Genes Study investigated the antitumor responses to NPRL2 gene therapy on anti-PD1 resistant KRAS/STK11 mutant NSCLC in a humanized mouse model Humanized mice w
Slide 33: Combined TUSC2 and NPRL2 Re-Expression in SCLC
Combined TUSC2 and NPRL2 Re-Expression in SCLC H841 lacks both TUSC2 and NPRL2 protein Increased control of xenograft growth compared to: Controt + TUSC2 re-expression alone NPRL2 re-expression alone © Genprex “Tumor Volume (mm) TUSC2+NPRL2 Dual Gene Therapy Combination on inflamed H841 Tumors in Hu
Slide 34: Diabetes
Q DIABETES www.genprex.com
Slide 35: Diabetes: By the Numbers
Diabetes: By the Numbers 38M $966B $24B Diabetes U.S.* Diabetes Global? Global Diabetes 12D Global Market T1D Global Market Prevalence Prevalence Expenditures (6.7% CAGR‘) (17.2% CAGRS) JUS.
Slide 36: Diabetes can cause serious complications
Diabetes can cause serious complications. In 2021, there was approximately 1 death every 5 seconds caused by diabetes worldwide. © Genprex
Slide 37: Diabetes Causes Serious Complications
Diabetes Causes Serious Complications Heart Disease Leading cause of death for men and women in US. Diabetics are 2x as lkely to have heart disease or a stroke. Chronic Kidney Disease ‘Approximately 1 in 3 adults with diabetes have CKD. Kidney diseases are the Sth leading cause of death in US. Nerve
Slide 38: Diabetic Patients Are In Need of Advanced Therapy
Diabetic Patients Are In Potential for disease modification Need of Advanced Therapy for long-term effectiveness. s Patients suffer compromised quality of life Despite certain advancements in treatment, quality, of fe remains highly compromised for many individuals with diabetes. hese cells resulted
Slide 39: Novel Gene Therapy Collaboration with University of Pittsburgh
Novel Gene Therapy Collaboration with University of Pittsburgh Diabetes Prog ram intends to address both T1D and T2D. 38M or 11.6% of Americans Have Diabetes! Type 1 Diabetes (5-10%) ———e ° Type 2 Diabetes (90-95%) Inability of the pancreas to produce enough Insulin due largely to resistance to insu
Slide 40: GPX-002 Replenishes Insulin Producing Cells
GPX-002 Replenishes Insulin Producing Cells Delivers Genes to the Pancreas n AAV ector to deliver the Hyperelycemia Reprograms Alpha Cells transforms alpha cells wea? Beta-cell Aeficiency Restores Blood Glucose Levels In vivo, preclinical studies show that GPX.002 restored normal blood glucose level
Slide 41: Reversed Drug-Induced Diabetes in T1D Mouse Model
Reversed Drug-Induced Diabetes in T1D Toxin-Induced Mouse Model Blood glucose (md) ‘beta cllmass g) : stloxan AAV-8 nection Untreated alloans alloxan ‘Group Reprogramed alpha cells into beta-like cells that appropriately produce insulin in response to glucose levels. Normalized blood glucose in beta
Slide 42: Restored Blood Glucose in T1D Autoimmune Mouse Model
Restored Blood Glucose in T1D In Autoimmune Mouse Model for Four Months The duration of restored blood 10 glucose levels in mice could r potentially translate to decades in humans. os beta cel maze (mg) One week in a mouse tends to correlate to about one year in humans. Blood glucose (mgt) NOD mice
Slide 43: Functional Insulin-Expressing Cells from Alpha Cells in Human Islets
Induced Generation of Functional Insulin-Expressing Cells from Alpha Cells in Human Islets Provides a potential basis for further investigation in human Type 1 diabetes Human islets treated with streptozotocin oo to to destroy beta-cells, then treated with either AAV-PM or AAV-GFP AAV treated islets
Slide 44: Non-Human Primate Model of T1D
Non-Human Primate Model of T1D Reduced Insulin Requirements © Genprex’ veatintiton f NHP 4 insulin / Carb isl ll | | | Mul alii 150 E 100 § 050 : 0.00 Viral Infusion NHP2 are | lh loi iii i $ 150 % 100 § 050 i 000 Data from University of Pittsburgh researchers show a marked reduction in insulin requ
Slide 45: ATTD 23: Decreased Insulin Requirements in NHPs
ATTD 23: Decreased Insulin Requirements and Improved Glucose Tolerance in NHPs Following the pancreatic intraductal infusion of the AAV engineered construct, the eight NHPs had: Decteased insulin requirements (p<0.001) Increased ¢-peptide levels (p<0.05) Improved glucose tolerance compared to baseli
Slide 46: NHP2 Three-Month Glucose Tolerance Test
NHP2 Three-Month Glucose Tolerance Test “© Pre Gene Therapy ‘Post Gene Therapy (3 months) Normal NHP- z 3 — eo ri ——+ 8 co . 2 oe 0 20 40 60 Time (min) © Genprex
Slide 47: IHC Eight Weeks After Gene Therapy
DAPI IHC Eight Weeks After Gene Therapy Normal NHP Genprex: Need at least 20% of normal beta cell mass to Diabetic NHP Without Gene Therapy maintain normoglycemia Diabetic NHP After Gene Therapy
Slide 48: Studying GPX-002 Using a Lipid Nanoparticle
Studying GPX-002 Using a ele Poteet Fe Dosing Ua Lipid Nanoparticle ee et Eaien Oaen New studies use an alternative second generation approach with a non-viral id nanoparticle delivery system First and only company to research diabetes gene therapy using a lipid nanoparticle in place of a viral AAV
Slide 49: Corporate
Q CORPORATE www.genprex.com
Slide 50: Our Team: Company Management
Our Team: Company Management 22 a ob
Slide 51: Our Team: Scientific Advisory Board
Our Team: Scientific Advisory Board George Simon George k Gates
Slide 52: Our Team: Clinical Advisory Board
Our Team: Clinical Advisory Board mM 2.
Slide 53: Our Team: Board of Directors
Our Team: Board of Directors - a) be “5 r a
Slide 54: Achievements & Upcoming Milestones
Achievements & Upcoming Milestones Acclaim -1 Acclaim -3 fer enrollmentin Open for enrollment in 2a Expansion Phase 2 Expansion portion of the trial ofthe trial Expect to open additional sites by the end of 2025, Complete enrollment of 25 patients in Phase 2 nsion portion of n Portion in 1H the tria
Slide 55: We believe in a future of transformational patient care
We believe in a future of transformational patient care. 21 Century Large Combination Two FDA Gene Markets & | Trials with Top Fast Track Therapies Unmet Need | SellingDrugs | Designations Exploring New Indications & Partnerships
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Slide 57: Research References
Research References Slide 7 1. Wistuba I, Behrens c Virani AK. etal. High resolution chromosome 3p <llelotypirg of human lung cancer and preneoplastcireinvasive bronchial ’epithelium reveals multple.dscontinuousstes ofp allele oss and three regions of frequent breskpoints. Cancer Res. 2000:60(71948-
Slide 58: Research References
Research References Slide 35 Centers for Disease Contvok:hitosu/bitvisages a International Diabetes Federator tas//BiN/a31shos IDF Diabetes Ais: hips. W/4aFeCup Research and Markets: hitps//onews.D1/3SS5VGu ‘Global Datachitos/ aL Matsurbt Slide 36 1. ID Diabetes Atlas: ups raiEUN Slide 37 1. Centers
Slide 59: Appendix
a) APPENDIX
Slide 60: Reqorsa + Keytruda Significantly Reduced Tumor Growth
Regorsa® + Keytruda® REQORSA increases immune response Significantly Reduced Tumor Sees Shee tenet Growth REQORSA + Keytruda® The independent immunologic effects of REQORSA and Keytruda markedly decrease tumor growth by increasing the immunologic attack on the tumor compared to PD-1 inhibition alone
Slide 61: AACR 21: Reqorsa May Enhance First-Line Standard of Care
AACR 21: Regorsa® May Enhance First-Line Standard of Care Reqorsa® + Keytruda® + Chemo fegonsa sxtor | Eoportono + Eiaspeebetncgonsa REQORSA enhances the efficacy of =| y, chemo-immunotherapy on KRAS-LKB1 (KL)-mutant lung metastases in humanized mice. Tota Fx fs) Triple combination demonstrated stro
Slide 62: Acclaim-2 is no longer enrolling new patients
Acclaim-2 is no longer enrolling new patients. Su : eer raat Acclaim “2 © Patients with advanced NSCLC whose disease progressed after treatment with Keytruda® . © FDA Fast Track Designation Regorsa" in combination with Merck & Co's Keytruda® for NSCLC Phase 2b: Comparing Progression Free Survival of