#1Nuvectis Pharma, Inc. Innovative Precision Medicine for Serious Conditions of Unmet Medical Need in Oncology January 2024 NuvectisPharma, Inc. V₂ (NASDAQ: NVCT)#2Forward Looking Statements Nuvectis Pharma, Inc. Certain statements in this presentation constitute "forward-looking statements" within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will," "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Nuvectis Pharma, Inc.'s current expectations, estimates, and projections about future events and trends that we believe may affect our business, financial condition, results of operations, prospects, business strategy, and financial needs. The outcome of the events described in these forward-looking statements are subject to inherent uncertainties, risks, assumptions, market and other conditions, and other factors that are difficult to predict and include statements regarding the preclinical data generated to date for NXP800 and NXP900, the Phase 1a data generated for NXP800 and the clinical expectations for the NXP800 Phase 1b study, including statements regarding NXP800's potential ability to become a therapeutic option for the treatment of platinum-resistant, ARID1a-mutated ovarian carcinoma, gastric carcinoma, cholangiocarcinoma, and potentially other cancer indications, and timing of and expectations for the Phase 1a study for NXP900. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are subject to market and other conditions and described more fully in the section titled "Risk Factors" in our 2022 Form 10-K filed with the Securities and Exchange Commission ("SEC"). However, these risks are not exhaustive and new risks and uncertainties emerge from time to time, and it is not possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements contained in this press release or other filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date of this press release. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law, and we claim the protection of the safe harbor for forward- looking statements contained in the Private Securities Litigation Reform Act of 1995.#3Nuvectis Pharma - Key Highlights Our Approach to Precision Medicine NXP800 NXP900 Management Team with Strong Track Record Select and acquire novel, rationally-designed drug candidates → Focus on drug development for serious conditions of unmet need in oncology * Ongoing expansion cohorts: ◆ ARID1a-mutated, platinum resistant ovarian carcinoma (Fast Track Designation) * Cholangiocarcinoma (Orphan Drug Designation) 7 Phase 1a dose escalation ongoing First potential indications: YES1/SRC-driven solid tumors ❖ 3 approved drugs in 4 indications in the US and EU and multiple strategic deals Cash runway into 1H2025 3#4Management Team Track record of success Ron Bentsur Chairman & Chief Executive Officer Auryxia (ferric citrate) tablets NuvectisPharma, Inc. KERYX BIOPHARMACEUTICALS, INC Enrique Poradosu, PhD Chief Scientific & Business Officer JelmytoⓇ (mitomycin) UroGen Pharma Shay Shemesh Chief Development & Operations Officer ✔ ELZONRIS® (tagraxofusp-erzs) Injection Stemline#5Nuvectis Precision Medicine Pipeline Drug Candidate Indication NXP800 a GCN2 Activator NXP900 b SRC/YES1 inhibitor ◆ ARID1a-mutated ovarian cancer ● Ovarian clear cell carcinoma Ovarian endometrioid carcinoma → Cholangiocarcinoma (IST) ❖ Squamous cancers (cervical, esophageal, etc.) NuvectisPharma, Inc. YES1/SRC-driven solid tumors a. Exclusive worldwide rights acquired from the Institute of Cancer Research, UK. b. Exclusive worldwide rights acquired from the University of Edinburgh Phase 1a Fast Track Designation Orphan Designation Phase 1b Phase 2 ENGOT GOG European Network of Gynaecological Oncological Trial groups MAYO CLINIC Phase 3 FOUNDATION" Transforming the standard of care 5#6About NXP800#7NXP800 Mechanism of Action NXP800 is a GCN2 kinase activator Non-acylated tRNA GCN2 GCN2 Stalled ribosome NXP800 GCN2 activation NXP800 activates the GCN2 kinase NuvectisPharma, Inc. elF2a phosphorylation P elF2a ↓ ATF4 translation ATF4 Dimerization partner ATF4 Created with BioRender.com Cap-dependent translation Chronic activation: Induction of cell death Stress- induced genes C Inhibition of cap-dependent translation and chronic activation of the integrated stress response (ISR) ➜ Cancer cell death ❖ ARID1a-mutated tumors display an increased dependence on translation Cell proliferation (% of vehicle control) 150 100- 50- ICH 10 NXP800 NXP800 + A92 (GCN2 inhibitor) 100 NXP800 (NM) 1000 10000 Target validation The GCN2 inhibitor A92 antagonizes the antiproliferative effect of NXP800 in ARID1a- mutated SKOV3 cells (approx. 50-fold change in Gl50) Powers et al., AACR 2023 7#8Loss of ARID1a Sensitizes Cells to NXP800-induced Apoptosis Isogenic HCT116 Cell Model Wildtype Heterozygote Homozygote 0 2 6 24 0 2 6 24 0 2 6 24 Paul Workman, Molecular targets and Cancer Therapeutics, oral presentation, 2023 NuvectisPharma, Inc. ATF4 ATF3 CHAC1 Cleaved PARP Activation of the ATF4/ATF3/ CHAC1 cascade in the ARID1A wildtype, heterozygote and homozygote HCT116 human colorectal cancer cells. * Expression of cleaved PARP, an apoptotic marker, is markedly induced only in heterozygote and homozygote ARID1a mutant HCT116 cells 8#9Substantial Antitumor Activity in ARID1a-Mutated Ovarian Carcinoma Xenografts (NXP800 vs. Cisplatin) Preclinical proof of concept leading to selection of initial target indications Tumor Volume (mm³) SKOV-3 (Cisplatin Resistant) 400 300 200 100 0 Day 2 Baseline Vehicle Cisplatin (4 mg/kg) NXP800 (35 mg/kg) Day 5 Day 7 Day 9 Day 13 Day 16 NuvectisPharma, Inc. Day 19 Day 21 Day 28 Day 23 Day 26 Day 30 Tumor Volume (mm³) TOV-21G (Cisplatin Sensitive) 500 400 300 200 100 Baseline Vehicle Cisplatin (4 mg/kg) NXP800 (35 mg/kg) Day 5 Day 7 Day 15 Day 12 Day16 Day 19 Day 21 Day 23 Day 26 Day 28 Disease Ovarian Clear Cell Carcinoma Ovarian Endometrioid Carcinoma Est. Total Incidence (US) a 2,200 2,200 Est. # of Patients w/ ARID1a Deficiency a. Based on data from the American Cancer Society, 2022 1,320 660 9#10Substantial Antitumor Activity in Cholangiocarcinoma Additional potential development opportunities Cholangiocarcinoma (CCA) is a lethal malignancy with poor prognosis arising from the biliary tree Approx. 10,000 new cases/year in the US a a. The cholangio cinoma foundation, olangiocarcinoma.org/key-statistics NuvectisPharma, Inc. Delta in Tumor Volume (mm³) Patient Resection and PDX Implantation 1000- 500- Vehicle NPX800 CCA Tumor 12 Treatment days 15 18 27 NXP800 Treatment Initiation Day 0 Treatment 5 days on, 2 days off Vehicle NXP800 D Carlson, 2023 American Association for Cancer Research PDX Euthanasia Day 22-30 | 10#11Tumor Volume (mm³) Potent Antitumor Activity in ARID1 a/ARID1b Mutated Endometrial Carcinoma Xenografts ARID1a is the most frequently mutated SWI/SNF subunit with an estimated prevalence of 35% in endometrial carcinomas. Inactivation of ARID1b is highly prevalent in undifferentiated and dedifferentiated endometrial cancers (approx. 36%), often concurrent with ARID1a, and is associated with an aggressive phenotype. T 800 600 400 200 Day 0 NXP800 demonstrated robust antitumor activity in ARID1a and ARID1b mutated xenografts of endometrial carcinoma, at a well- tolerated dose, including in models of poorly differentiated tumors, supporting the clinical development of NXP800 in endometrial cancer. RL95-2 (ARID1a/ARID1b concurrent mutation) Vehicle NXP800 (35 mg/kg) Day 3 Day 5 Day 7 Day 12 Day 10 Day 14 NuvectisPharma, Inc. Day 17 Day 19 Day 21 Day 24 Day 26 Day 28 Day 32 Tumor Volume (mm³) 250 200 150 100 50 0 Day 0 KLE (ARID1b mutation/poorly differentiated) Day 3 Vehicle NXP800 (35 mg/kg) Day 5 Day 7 Day 12 Day 10 Day 14 Day Day 21 Day 19 Day 26 Day 24 Day 28 Day 32 Tumor Volume (mm³) 500 400 300 200 100 Vehicle NXP800 (35 mg/kg) Day 0 Day 2 Day 5 Day 7 (ARID1a mutation) SNG-M Day 9 Day 13 Day 16 Day 21 Day 19 Day 23 Day 26 Day 28 Day 30 11#12NXP800 Potential Opportunity in Multiple Cancers ARID1a is an important mutation that can be used as a patient selection strategy Indication Ovarian Cancer (Clear Cell and Endometrioid) Endometrial Carcinoma Cholangiocarcinoma Urothelial Hepatocellular Gastric Estimated Incidence NuvectisPharma, Inc. (US) 4,350 66,200 8,000 75,350 34,000 26,550 ARID1a mutation prevalence 52.9% 35.6% 17.5% 34.0% 26.7% 24.9% a. The ARID1a mutation detection assay is a standard part of commercially and clinically available NGS panels. b. Estimate based on a weighted average of the ARID1a mutation prevalence within the major endometrial histology subtypes. a Estimated Number of Patients with ARID1a protein loss (US) 2,300 23,600 b 1,400 25,600 9,070 6,600 12#13NXP800: Phase 1b Underway, Fast Track Designation Enrolling patients with platinum-resistant, ARID1a mutated ovarian cancer (target population) Clinical trials.gov NCT05226507 Phase 1a: Dose Escalation - Completed Patients with advanced solid tumors (all comers) Primary Objectives: Select doses/schedules for Phase 1b Key Endpoints: Assess Pharmacokinetics, pharmacodynamics, lab abnormalities, dose limiting toxicities NuvectisPharma, Inc. Phase 1b: Dose Expansion - Enrolling Patients in the target population - 2 cohorts of 20-25 patients, 2 dosing regimens (50 mg and 75 mg QD) Primary objectives: Establish RP2D Key Endpoints: Preliminary Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Initial Phase 1b Data Read-Out Expected in 1Q2024 13#14About NXP900#15NXP900 Key Highlights Precision Medicine Approach Differentiated Features Strong Preclinical Proof of Concept Phase 1 Program NuvectisPharma, Inc. * Discovered at the University of Edinburgh, Scotland * A potent, novel, small molecule inhibitor of YES1/SRC signaling ◆ YES1-Hippo pathway alteration associated with sensitivity to NXP900 in squamous cell models Highly selective Unique mechanism of action - Complete shut-down of the SRC pathway by scaffold and catalytic domain inactivation POC in multiple xenograft models - significant single-agent activity in squamous cell cancer models * Ability to re-sensitize resistant NSCLC cells to osimertinib Ability to reverse resistance to enzalutamide in vivo in mCRPC ★ Phase 1a dose escalation clinical trial ongoing 15#16NXP900 Kinome Profiling Demonstrates High Selectivity NuvectisPharma, Inc. TK CMGC NXP900 CAMK TKL STE CK1 AGC TK CMGC Dasatinib CAMK TKL Note: Dasatinib data from Remsing Rix et al., Leukemia 23, 477-485 (2009), NXP900 data from AACR 2022. STE CK1 AGC 16#17NXP900 Completely Shuts Down Signaling of Non-receptor Tyrosine Kinases of the SRC Family Differentiated vs. other multi-kinase inhibitors that only achieve a partial SRC pathway shut down NXP900: Complete shutdown of the SRC pathway SH3 SH2 P pY530 NuvectisPharma, Inc. NON- FUNCTIONAL scaffolding site C-helix E313 NXP900 Y419 Kinase Closed, inactive conformation locked by NXP900 NXP900 Oncogenic signal No inhibitor: Fully active SRC Y530 SH3 SH2 C-helix E313 Fully functional scaffolding site - Binding to YAP, FAK, CAS, paxillin pY419 Kinase Open, active conformation no inhibitor Other multi-kinase inhibitors Other multi-kinase inhibitors: Partial shutdown of the SRC pathway } Y530 SH3 SH2 C-helix E313 Fully functional scaffolding site - Binding to YAP, FAK, CAS, paxillin Kinase Other multi-kinase inhibitors Y419 Open, active conformation stabilized by other multi-kinase inhibitors 17#18Targeting YES1 in Cancers of Squamous Cell Origin Single agent development strategy YES1/SRC "off" SH3 SH2 PYS30 NOP900 1419 Kinase V530 SH2 E YES1/SRC "on" P PY419 Kinase Created with BioRender.com NuvectisPharma, Inc. P- Tyr Rassf YAP/TAZ P. Tyr YAP/TAZ TEAD хото P P FRMD6 KIBRA MST1/2 SAV1 LATS1/2 MOB1 FAT 1-4 14-3-3 P YAP/TAZ Merlin P P- Ser (80) Targets involved in organ size, stem cell renewal, replication, and survival: • ID1 • MYC abox. FGF1 Degradation • CTGF • Cyclin D . AREG • SMAD High Nuclear YAP Cells Per Well (%) Low Nuclear YAP -5.0 High Nuclear YAP NXP900 - IC50 for YAP1 nuclear localization: 24.3nM I -2.5 log(Concentration [M]) 25 Genetic alterations in the hippo pathway (FAT1-4, YAP1, TAZ) are highly prevalent in cancers of squamous cell origin and confer sensitivity to NXP900 YES1 drives tumor growth via phosphorylation and nuclear localization of YAP1 Significant unmet medical need opportunities within the squamous cancer universe ➜ Regulatory opportunity 18#19Potent Single Agent Activity in Squamous Cell Cancers Average Tumor Volume (mm³) 700 600 500 400 300 200 100 0 Esophageal Cancer Day 3 Baseline Vehicle Control NXP900 (40 mg/kg) NuvectisPharma, Inc. Day 6 Day 8 Day 10 Day 15 Day 13 Day 17 Time Day 20 Day 22 Day 24 KYSE70 cells (YES1 gene amplification) Day 27 Head and Neck Cancer (tongue) Average Tumor Volume (mm³) 700 600 500 400 300 200 100 0 Vehicle Control NXP900 (40 mg/kg) Baseline Day 3 Day 6 Day 8 Day 10 Day 13 Day 15 Day 17 Day 20 Time Day 22 Day 24 Day 27 Cal27 cells (Heterozygous FAT1 copy loss) 19#20Potential Combination Strategies YES1 (in NSCLC) and SRC (in mCRPC) are implicated in development of resistance to osimerinib (Tagrisso) and enzalutamide (Xtandi) NXP900 in combination with osimertinib overcomes resistance in vitro Proliferation (% of DMSO control) 100 80- 60- 40- 20- Osimertinib resistance in PC-9 0.01 PC-9 PC-9 OR1 PC-9 OR3 NuvectisPharma, Inc. TII Proliferation (% of DMSO control) 10 Osimertinib re-sensitisation in PC-9 100 80- 60- 40- 20- 0 T 0.01 - PC-9 -PC-9 OR1 (Osi 160 nM) -PC-9 OR3 (Osi 160 nM) 0.1 1 ECF-506 (UM) F NXP900 in combination with enzalutamide overcomes resistance in vivo 10 Day -7 D 14 0.1 1 Osimertinib (UM) Nature Communications by the AstraZeneca R&D Group, April 2022 NSCLC = non=small cell lung cancer, mCRPC = metastatic castration resistant prostate cancer, eCF506 = NXP900 D 21 Enz -/eCF506 H 0 Enz 14 Enz eCF506 21BLI 1e04 5e05- Relative BLI signal Normalised to Day 14 1500 1000 500 JEM by UoE and MSKCC, February 2023 Enz Enz+eCF506 *** 14 18 21 Days after treatment 20#21NXP900 Potential Market Opportunity Squamous cancer cells with hippo pathway alterations and NF2 mutated cells demonstrate high sensitivity to NXP900 in vitro and in vivo Estimated Incidence Indication Cervical Esophageal Metastatic Anal NSCLC Head & Neck Mesothelioma (US) NuvectisPharma, Inc. 13,950 21,550 3,000 202,600 54,000 3,000 Squamous cell prevalence 90% 12,000 30% a 80% 25% 90% NF2 mutation prevalence 33% b 13% Estimated Addressable Patient Population (US) 12,500 6,500 2,400 50,650 Papillary Kidney Cancer a. The prevalence of ESCC ex-US is approximately 85%. b. The NF2 mutation is prevalent in approximately 1-3.6 % of patients in several additional solid tumors including breast, NSCLC, ovarian, bladder, melanoma and CRC 48,600 1,000 1,500 21#22NXP900: Phase 1a Ongoing Patients with advanced solid tumors NuvectisPharma, Inc. Clinicaltrials.gov NCT05873686 Phase 1a Dose Escalation Starting dose of 20 mg, QD Primary Objective: Select doses/schedules for Phase 1b Key Endpoints: Assess Pharmacokinetics, pharmacodynamics, lab abnormalities, dose limiting toxicities 22#23Financial and NVCT Stock Highlights Cash Runway into 1H2025 Ticker Cash NuvectisPharma, Inc. Financials NVCT $22.1M as of 09/30/2023 Insider Ownership Founders and >5% holders Research Coverage XH.C.WAINWRIGHT&CO. LADEN BURG THAL MANN ESTABLISHED 1876 T ROTH MKM 66% Joe Pantginis Aydin Huseynov Jonathan Aschoff 23#24Nuvectis Investment Highlights Precision medicine pipeline for serious conditions of unmet medical need in oncology 2024 Milestones NXP800 NXP900 Management Team with Strong Track Record NuvectisPharma, Inc. H x T Preliminary clinical data for NXP800 (ARID1a-mutated ovarian cancer and cholangiocarcinoma) and for NXP900 (Phase 1a study) Presentations at medical and scientific conferences ARID1a mutated, platinum resistant ovarian cancer - Phase 1b ongoing Cholangiocarcinoma - IST/Mayo Clinic commenced Highly selective compound, differentiated from other YES1/SRC-kinase inhibitors Phase 1a ongoing 3 approved drugs in 4 indications in the US, EU approvals and multiple strategic deals Generated significant shareholder value 24#25Nuvectis Pharma, Inc. Innovative Precision Medicine for Serious Conditions of Unmet Medical Need in Oncology January 2024 NuvectisPharma, Inc. V₂ (NASDAQ: NVCT)