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DRIVEN BY SCIENCE FOCUSED ON LIFE June
Forward-looking statements Certain
statements included in this presentation (this "Presentation") that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of
1995. Forward-looking statements are sometimes accompanied by words such as "believe," "may," "will," "estimate," "continue," "anticipate," "intend,"
"expect," "should," "would," "plan," "predict," "potential," "seem," "seek," "future," "outlook" and similar expressions that
predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, IBTROZI's commercial opportunity, IBTROZI's and safusidenib's
best-in-class therapeutic potential, potential therapeutic benefit of Nuvation Bio's product candidates and planning and advancement of clinical studies for such product candidates, success of clinical study design, the potential of the DDC
platform, and strength of pro forma cash position providing a path to profitability without need to raise additional capital. These statements are based on various assumptions, whether or not identified in this Presentation, and on the current
expectations of the management team of Nuvation Bio and are not predictions of actual performance. These forward-looking statements are subject to a number of risks and uncertainties that may cause actual results to differ from those anticipated by
the forward-looking statements, including but not limited to the challenges associated with conducting drug discovery and initiating or conducting clinical studies due to, among other things, difficulties or delays in the regulatory process,
enrolling subjects or manufacturing or acquiring necessary products; the emergence or worsening of adverse events or other undesirable side effects; risks associated with preliminary and interim data, which may not be representative of more mature
data; and competitive developments. Risks and uncertainties facing Nuvation Bio are described more fully in its Form 10-Q filed with the SEC on May 7, 2025 under the heading "Risk Factors," and other documents that Nuvation Bio has filed
or will file with the SEC. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this Presentation. Nuvation Bio disclaims any obligation or undertaking to update, supplement or revise
any forward-looking statements contained in this Presentation.
Nuvation Bio is focused on tackling
the greatest challenges in cancer treatment IBTROZITM (taletrectinib) is a next generation, potentially best-in-class ROS1 inhibitor recently approved for advanced ROS1+ NSCLC in the U.S. and in China Global, commercial-stage oncology
company focused on innovating and developing first- or best-in-class medicines for diseases that represent particularly large unmet patient needs NUV-1511, the Company's first clinical-stage drug-drug conjugate (DDC), is being evaluated
in a Phase 1/2 study; NUV-868 is a BD2-selective BET inhibitor that has completed Phase 1 and Phase 1b studies Safusidenib is a potentially best-in-class, brain penetrant, mIDH1 inhibitor entering pivotal studies for diffuse IDH1-mutant glioma
Robust cash balance of $462 million as of 3/31/25 plus up to $250 million1 in non-dilutive capital from Sagard Healthcare Partners provides path to profitability without need for additional funding 1. Includes $150 million of royalty interest
financing and $50 million of debt funded after U.S. FDA approval of IBTROZI. An additional $50 million in debt is available at the company's option for 12 months following first commercial sale.
Nuvation Bio has four differentiated
oncology programs ranging from approved in the U.S. and China to Phase 1 ongoing Program Target Indication(s) Current Stage of Development Anticipated Milestones & Recent Updates Program Potential Indication(s) Preclinical Phase 1 Phase 2
Pivotal Approved Anticipated Milestones Advanced ROS1+ NSCLC (treatment line agnostic) Approved by the U.S. FDA and China's NMPA Marketing Authorization Application under review in Japan Safusidenib2 (mIDH1) Diffuse IDH1-mutant glioma Entering
pivotal studies in 2025 Phase 2 study ongoing NUV-1511 (DDC) Advanced solid tumors3 Phase 1/2 dose escalation study ongoing NUV-868 (BET) Currently under internal evaluation4 Completed Phase 1 monotherapy and Phase 1b combination studies in advanced
solid tumors BET: Bromodomain and Extra-Terminal motif; ESMO: European Society of Medical Oncology Congress; mIDH1: mutant isocitrate dehydrogenase 1; NSCLC: Non-small cell lung cancer; ROS1+: c-ros oncogene 1-positive; 1. Worldwide development and
commercial rights in-licensed from Daiichi Sankyo; rights to IBTROZI have been out-licensed in China (Innovent Biologics) and Japan (Nippon Kayaku). 2. Worldwide development and commercial rights in-licensed from Daiichi Sankyo, excluding Japan
where Daiichi Sankyo retains development and commercial rights. 3. Includes patients with advanced solid tumors who previously received and progressed on or after treatment with Enhertu and/or Trodelvy per approved U.S. FDA labeling,
human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, metastatic castration-resistant prostate cancer (mCRPC), advanced pancreatic cancer, and platinum-resistant ovarian cancer. Approved for advanced ROS1+ NSCLC in the
IBTROZI | ROS1i Advanced ROS1+ NSCLC
Approved by U.S. FDA in June 2025
IBTROZI is a next generation,
potentially best-in-class ROS1 TKI obtained from the April 2024 acquisition of AnHeart Therapeutics 1. IBTROZI prescribing information; Perol et al., Journal of Clinical Oncology, 2025. 2. Worldwide development and commercial rights in-licensed from
Daiichi Sankyo; rights to IBTROZI have been out-licensed in China (Innovent Biologics) and Japan (Nippon Kayaku). Approved in the U.S. and in China for advanced ROS1+ NSCLC (line agnostic) Previously received Breakthrough Therapy Designations in 1L
& 2L (U.S. and China) AnHeart in-licensed IBTROZI from Daiichi Sankyo in 2018 Maintain global rights except in China and Japan where rights have been out-licensed2 Commercial opportunity Potentially best-in-class efficacy and safety profile
Durable responses and prolonged progression-free survival Highly brain penetrant and active against common mutations Differentiated profile1 Strong partnerships
Repotrectinib1 Entrectinib2
Crizotinib3 n ORR Median DOR Median PFS IC-ORR1 TRIDENT-1 ALKA-372-001, STARTRK-1, STARTRK-2 PROFILE 1001 71 79% 34 months 36 months 89% (8/9) 168 68% 21 months 16 months 80% (20/25) 53 72% 25 months 19 months N/A Study Note: These data are derived
from different clinical studies, with differences in study design and patient populations. No head-to-head studies have been conducted. Comparisons in a head-to-head study may yield different results. ORR: confirmed Overall response rate; DOR:
Duration of response; IC-ORR: Intracranial overall response rate; PFS: Progression free survival. 1. AUGTYRO prescribing information and Drilon et al., New England Journal of Medicine, 2024. 2. Drilon et al., JTO Clinical Research Reports, 2022. 3.
XALKORI prescribing information and Shaw et al., Annals of Oncology, 2019. 4. Zidesamtinib is not approved and still in clinical development; Besse et al., ESMO Presentation, 2024; includes 20 response evaluable patients who received 1 prior ROS1
TKI; includes nine confirmed partial responses in patients previously treated with: crizotinib (n=11), entrectinib (n=6, implied based on standard medical practices and available data), and repotrectinib (n=3); median DOR and median PFS
"N/A" for subgroup of all patients who received 1 prior ROS1 TKI; G2032R cORR and IC-cORR include patients that received 2 prior ROS1 TKIs. First-line (TKI-na ve) Repotrectinib1 Zidesamtinib4 TRIDENT-1 ARROS-1 56 38% 15
months 9 months 38% (5/13) 59% (10/17) 17 53% N/A N/A 50% (4/8) 62% (16/26) 3 0% Crizotinib & entrectinib Repotrectinib Second-line (TKI-pre-treated) G2032R ORR -- -- -- While ROS1+ NSCLC treatment has evolved since IO/chemo, there remains an
opportunity to improve upon the current landscape
Dose modification rates of previously
approved TKIs are elevated, while neurological AEs remain a significant issue for patients in the real-world setting Repotrectinib Entrectinib Crizotinib Note: These data are derived from different clinical studies, with differences in study design
and patient populations. No head-to-head studies have been conducted. Comparisons in a head-to-head study may yield different results. AE: Adverse Event. Sources: AUGTYRO prescribing information (includes patients with NTRK+ solid tumor), ROZLYTREK
prescribing information (includes patients with NTRK+ solid tumor), and XALKORI prescribing information (combined analysis of Study 1 & 2 of patients with ALK+ NSCLC patients; Headache adverse event rate from Study 1 only). Dose Modification
Neurological Adverse Events Interruption Reduction Discontinuation Dizziness Dysgeusia Headache
IBTROZI demonstrated high and
durable responses in TKI-na ve patients, but latest durability metrics now reflect median not reached with even longer follow-up cORR: confirmed Overall response rate; DOR: Duration of response; IC-cORR: Intracranial confirmed overall response
rate; PFS: Progression free survival. 1. Perol et al., Journal of Clinical Oncology, 2024; Median duration of follow-up of 20.7 months for the pooled data set. 2. IBTROZI prescribing information, excluding median PFS; IC-cORR is not broken out by
TRUST-I and TRUST-II study in the IBTROZI prescribing information and includes patients who had measurable CNS metastases at baseline as assessed by BICR and had not received radiation therapy to the brain within 2 months prior to study entry;
Median duration of follow-up of 40.9 and 20.5 months in TRUST-I and TRUST-II, respectively. Pooled (JCO publication)1 TRUST-I (label)2 TRUST-II (label)2 n cORR Median DOR Median PFS IC-cORR 160 89% 44 months 46 months 77% (13/17) 103 90% Not Reached
Not Reached 88% (7/8) 54 85% Not Reached Not Reached 57% (4/7) June 2024 data cutoff October 2024 data cutoff
No drugs in solid tumor oncology
have demonstrated the combined efficacy profile seen with IBTROZI in the first line (TKI-na ve) setting RETEVMO (selpercatinib)1 84% 22 months 20 months AUGTYRO (repotrectinib)2 79% 36 months 34 months ALECENSA (alectinib)3 79% 26 months <
18 months TAGRISSO (osimertinib)4 77% 19 months 17 months VITRAKVI (larotrectinib)5 75% -- 33 months XTANDI (enzalutamide)6 59% 20 months -- Program ORR Note: Each product is approved for use in their respective indications and the data shown are
derived from different clinical studies with differences in cancer types, study design and patient populations. mDOR: median Duration of response; ORR: Overall response rate; mPFS: median Progression-free survival. Source: 1. RETEVMO prescribing
information; Drilon et al., Journal of Clinical Oncology, 2022. 2. AUGTYRO prescribing information; Drilon et al., New England Journal of Medicine, 2024. 3. ALECENSA prescribing information. 4. TAGRISSO prescribing information; Soria et al., New
England Journal of Medicine, 2018. 5. VITRAKVI prescribing information. 6. Beer et al., New England Journal of Medicine, 2014; Beer et al., European Urology (Final Analysis of PREVAIL study), 2016. mPFS mDOR
IBTROZI demonstrated striking
results in the TKI-pretreated setting, especially in the majority western TRUST-II study which is still maturing cORR: confirmed Overall response rate; DOR: Duration of response; IC-cORR: Intracranial confirmed overall response rate; PFS:
Progression free survival. 1. Perol et al., Journal of Clinical Oncology, 2024; Median duration of follow-up of 21.0 months for the pooled data set. 2. IBTROZI prescribing information, excluding median PFS and median DOR (median DOR excluded from
the label due to immature follow-up); prescribing information includes response after resistance mutations in addition to G2032R (n=15); IC-cORR is not broken out by TRUST-I and TRUST-II study in the IBTROZI prescribing information and includes
patients who had measurable CNS metastases at baseline as assessed by BICR and had not received radiation therapy to the brain within 2 months prior to study entry; Median duration of follow-up of 35.1 and 20.4 months in TRUST-I and TRUST-II,
respectively. n cORR Median DOR Median PFS IC-cORR 113 56% 17 months 10 months 66% (21/32) 66 52% 13 months 8 months 75% (9/12) 47 62% 19 months 12 months 50% (6/12) G2032R cORR 62% (8/13) 62% (8/13) Pooled (JCO publication)1 TRUST-I (label)2
TRUST-II (label)2 June 2024 data cutoff October 2024 data cutoff
IBTROZI's safety profile
remained favorable with low incidence of neuro TEAEs; only 7% of patients had a TEAE leading to drug discontinuation Adverse Reaction: n (%) Any grade Grade 1 Grade 2 Grade 3 Diarrhea 214 (64) 169 (50) 38 (11) 7 (2) Nausea 159 (47) 123 (36)
31 (9) 5 (1) Vomiting 146 (43) 114 (34) 27 (8) 5 (1) Rash 75 (22) 43 (13) 26 (8) 6 (2) Dizziness 75 (22) 67 (20) 7 (2) 1 (0) Constipation 71 (21) 61 (18) 10 (3) 0 (0) Fatigue 67 (20) 49 (15) 15 (4) 3 (1) Commentary Source: IBTROZI prescribing
information. ALT: alanine aminotransferase; AST: aspartate aminotransferase; CPK: creatinine phosphokinase; TEAE: treatment-emergent adverse event. 1. The denominator used to calculate the rate varied from 149 to 336 based on the number of patients
with a baseline value and at least one post-treatment value. Includes 337 patients with ROS1+ NSCLC who received >1 dose of IBTROZI (600mg) Dose modifications driven by elevated liver function tests, which oncologists are familiar with treating:
Dose interruption due to TEAE: 41% Dose reduction due to TEAE: 29% >90% of dizziness was grade 1 and transient, lasting ~3 days IBTROZI label does not include any warnings or precautions related to CNS effects ~80% of diarrhea was grade 1,
occurred within ~2 days of starting therapy, and resolved in ~1 day Lab Abnormality: n (%) Any grade Grade 1 Grade 2 Grade 31 AST Increased 293 (87) 191 (57) 68 (20) 34 (10) ALT increased 284 (85) 170 (51) 70 (21) 44 (13) CPK increased 179
(53) 55 (37) 16 (11) 8 (5) Neutrophils decreased 81 (25) 123 (37) 31 (9) 18 (5) Select Adverse Reactions 20% Select Laboratory Abnormalities1 (Grade 3/4 5%)
selectivity for ROS1 over TRKb in enzymatic assays and cell growth inhibition assays IC50 nM Fold selectivity CD74-ROS1 SLC34A-ROS1 GOPC-ROS1 ROS1 average ETV6-NTRK2 (TRKb) IBTROZI 1.7 11.1 3.8 5.5 103 19x Repotrectinib 0.8 6.5 2.2 3.2 3.3 1x IC50
nM Fold selectivity ROS1 TRKb IBTROZI1 0.207 2.28 11x IBTROZI2 0.073 1.47 20x Repotrectinib3 1.1 1.2 1x Kinase selectivity In vitro cell growth inhibition in ROS1 and TRKb-fusion driven cell lines Source: Nuvation Bio internal preclinical research
data on file; Katayama et al, Nature Communications, 2019. 1. ATP concentration at Km. 2. ATP concentration at 10 uM. 3. ATP concentration at 1 mM.
ROS1+ NSCLC market represents a
sizeable global commercial opportunity mPFS: median progression-free survival; TKI: tyrosine kinase inhibitor. 1. American Cancer Society (2025). 2. National Center for Biotechnology Information: Gendarme et al., Curr Oncol (2022). 3. Initially
approved by U.S. FDA in 2011 for the treatment of patients with advanced or metastatic ALK-positive NSCLC; later approved in 2016 for the treatment of patients with metastatic ROS1+ NSCLC. 4. Approved by U.S. FDA in 2019 for the treatment of
patients with metastatic ROS1+ NSCLC and the treatment of patients with neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation. 5. Approved by U.S. FDA in 2023 for the treatment of patients with
advanced or metastatic ROS1+ NSCLC. 6. National Cancer Center Japan (2019). 7. European Cancer Information Systems (2021). 8. Gao et al., J Thorac Oncol (2020). 9. Zhang et al., Thorac Cancer (2019). ~2,000-4,0001,2 ~2,600-5,2002,7 ~16,5008,9
~1,000-2,0002,6 NSCLC accounts for ~87%1 of all lung cancers ROS1+ lung cancer represents ~2%2 of new NSCLC cases each year There are currently three therapies approved in the U.S. to treat patients with ROS1+ NSCLC: Crizotinib (Pfizer, approved
20163) Entrectinib (Roche, approved 20194) Repotrectinib (Bristol-Myers Squibb, approved 20235) 1st gen. 2nd gen Key takeaways Estimated new cases per year
IBTROZI's strong clinical
profile turns the commercial opportunity from an incidence story to a prevalence story NSCLC: Non-small cell lung cancer. Note: Based on median progression-free survival demonstrated by IBTROZI in the first line setting (Pooled TRUST-I and TRUST-II
data: Perol et al., Journal of Clinical Oncology, 2024). 1. Reflects midpoint of epidemiology assumptions based on ROS1+ lung cancer representing approximately 2% of new NSCLC cases annually; American Cancer Society (2025), National Center for
Biotechnology Information: Gendarme et al., Curr Oncol (2022). 2. Nuvation Bio internal pricing information. 3. Reflects full market potential for 10 of 12 months in final year given median progression-free survival of 46 months as of June 7, 2024
data cutoff. Theoretical maximum U.S. ROS1+ NSCLC market opportunity Year 1 Year 2 Year 3 Year 4 ~$1 billion 3,000 patients X $350k per year ~$1 billion 3,000 patients X $350k per year ~$1 billion 3,000 patients X $350k per year ~$800 million3 3,000
patients X $350k per year ~$1 billion 3,000 patients X $350k per year ~$1 billion 3,000 patients X $350k per year ~$1 billion 3,000 patients X $350k per year ~$1 billion 3,000 patients X $350k per year ~$1 billion 3,000 patients X $350k per year ~$1
billion 3,000 patients X $350k per year Total: ~$1 billion Total: ~$2 billion Total: ~$3 billion Total: ~$3.8 billion Key assumptions and commentary Incidence: ~3,0001 newly diagnosed ROS1+ NSCLC patients in the U.S. each year based on current DNA
testing (RNA testing will detect ~30% more ROS1 fusions) Pricing: ~$350,0002 per year, based on gross IBTROZI annual price Does not incorporate product market share or other factors impacting potential revenue including product adoption, access and
reimbursement, and persistency
New NCCN Guidelines (as of January
7, 2025) now specifically contraindicate IO/chemo and recommend ROS1 TKIs for ROS1+ NSCLC Source: National Comprehensive Cancer Network 2025 and 2024. NCCN Guidelines 2024 NCCN Guidelines 2025 ROS1 Rearrangement: First Line Therapy ROS1
Rearrangement: First Line Therapy PD-L1 Positive (>1%): First Line Therapy PD-L1 Positive (>1%): First Line Therapy CONTRAINDICATIONS for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease
and/or current use of immunosuppressive agents; some oncogenic drivers (ie, EGFR exon 19 deletion or L858R; ALK, RET, or ROS1 rearrangements) have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors. CONTRAINDICATIONS for
treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents; some oncogenic drivers (ie, EGFR exon 19 deletion or L858R, ALK rearrangements) have been shown to be
Last updated: Jun 11, 2025