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DRIVEN BY SCIENCE, FOCUSED ON LIFE David Hung, M.D. Founder, President, & CEO J.P . Morgan Healthcare Conference January 2025
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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, our expectations the timing of FDA approval and commercial launch, expectations and timing of establishing a commercial organization, a full NDA approval for taletrectinib for the treatment of advanced ROS1+ NSCLC (line agnostic), the potential for taletrectinib to become a new therapeutic option for ROS1+ NSCLC, taletrectinib’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, sufficiency of Nuvation Bio’s current cash balance to support operations in the near term, clinical studydesign, or the potential of the DDC platform. 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 November 6, 2024 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. 2
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Nuvation Bio is tackling some of the greatest unmet needs in oncology 3 Taletrectinib is a 3rd generation, potentially best-in-class ROS1 inhibitor approved for advanced ROS1+ NSCLC in China; NDA accepted by U.S. FDA for priority review (line agnostic) with PDUFA date of 6/23/25 Global oncology company aimed at making best-in-class drugs by improving validated mechanisms that have encountered safety liabilities or limitations in efficacy 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 Robust cash balance of $549 million as of 9/30/24 and taletrectinib PDUFA date of 6/23/25 position Nuvation Bio to potentially become a U.S. commercial stage organization as early as June 2025 Safusidenib is a potentially best-in-class, brain penetrant, mIDH1 inhibitor entering pivotal studies for diffuse IDH1-mutant glioma
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Nuvation Bio has four differentiated oncology programs ranging from China approval / U.S. NDA under review, to Phase 1 ongoing 4 Program Potential Indication(s) Current Stage of Development Anticipated Milestones & Recent Updates Preclinical Phase 1 Phase 2 Pivotal NDA Review Taletrectinib1 (ROS1) Advanced ROS1+ NSCLC (treatment line agnostic) • NDA accepted by U.S. FDA for priority review (line agnostic) • Approved by China’s NMPA for advanced ROS1+ NSCLC5 • Pooled data from pivotal TRUST-I & TRUST-II studies presented at ESMO in September 2024 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; PDUFA: Prescription Drug User Fee Act; ROS1+: c-ros oncogene 1- positive; 1. Taletrectinib has been granted Orphan Drug Designation from the U.S. FDA for the treatment of patients with ROS1+ NSCLC and other NSCLC indications, and Breakthrough Therapy Designations by both the U.S. FDA and China’s NMPA for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC; worldwide development and commercial rights in-licensed from Daiichi Sankyo; rights to taletrectinib have been out-licensed in China and Japan. 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. 4. Nuvation Bio has decided not to initiate a Phase 2 study of NUV-868 as a monotherapy or in combination with olaparib or enzalutamide in the advanced solid tumor indications that were part of the Phase 1 and Phase 1b study designs. The Company is evaluating next steps for the NUV-868 program, including further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients. 5. Based on results of the TRUST-I clinical study, China’s NMPA approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC who have or have not previously been treated with ROS1 TKIs. Approved for advanced ROS1+ NSCLC in China; NDA accepted for priority review in U.S. with PDUFA date of 6/23/25
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Taletrectinib | ROS1i 5 Advanced ROS1+ NSCLC NDA accepted by U.S. FDA for priority review in December 2024
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Taletrectinib has the highest overall response rate and median progression- free survival of any ROS1 inhibitor in the first line (TKI-naïve) setting Taletrectinib2 Repotrectinib3 Entrectinib4 Crizotinib5 n cORR Median DOR Median PFS IC-cORR1 Pooled TRUST-I & TRUST-II TRIDENT-1 ALKA-372-001, STARTRK-1, STARTRK-2 PROFILE 1001 160 89% 44 months 46 months 77% (13/17) 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 he ad-to-head studies have been conducted. Comparisons in a head -to-head study may yield different results. cORR: confirmed Overall response rate; DOR: Duration of response; IC -cORR: Intracranial confirmed overall response rate ; PFS: Progression free survival. 1. Reflects IC -cORR in patients with measurable CNS tumors. 2. Perol et al., ESMO Presentation, 2024. 3. AUGTYRO prescribing information and Drilon et al., New England Journal of Medicine , 2024. 4. Drilon et al., JTO Clinical Research Reports , 2022. 5. XALKORI prescribing information and Shaw et al., Annals of Oncology , 2019. 6
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Few drugs in oncology have matched the 89% ORR and 46-month mPFS seen with taletrectinib in the first line (TKI-naïve) setting Taletrectinib1 89% 46 months 44 months RETEVMO (selpercatinib)2 84% 22 months 20 months AUGTYRO (repotrectinib)3 79% 36 months 34 months ALECENSA (alectinib)4 79% 26 months < 18 months TAGRISSO (osimertinib)5 77% 19 months 17 months VITRAKVI (larotrectinib)6 75% -- 33 months XTANDI (enzalutamide)7 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. Perol et al., ESMO Presentation, 2024. 2. RETEVMO prescribing information; Drilon et al., Journal of Clinical Oncology, 2022. 3. AUGTYRO prescribing information; Drilon et al., New England Journal of Medicine, 2024. 4. ALECENSA prescribing information. 5. TAGRISSO prescribing information; Soria et al., New England Journal of Medicine, 2018. 6. VITRAKVI prescribing information. 7. Beer et al., New England Journal of Medicine, 2014; Beer et al., European Urology (Final Analysis of PREVAIL study), 2016. mPFS mDOR 7
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The mPFS of patients given 1st and then 2nd gen. ROS1 inhibitors is still 18-21 months shorter than the mPFS of taletrectinib in the 1st line setting 8 First line1 Second line2 Crizotinib3 mPFS: 19 mos. Entrectinib4 mPFS: 16 mos.– Current patient journey Repotrectinib5 mPFS: 9 months Taletrectinib mPFS: 46 months in the first line setting Taletrectinib6 Total mPFS: 28 – 25 months First + Second line Note: These data are derived from different clinical studies, with differences in study design and patient populations. No he ad-to-head studies have been conducted. Comparisons in a head -to-head study may yield different results. mPFS: Median progression -free survival; TKI: tyrosine kinase inhibitor. 1. Represents TKI -naïve patients. 2. Represents TKI-pretreated patients. 3. Shaw et al., Annals of Oncology , 2019. 4. Drilon et al., JTO Clinical Research Reports, 2022. 5. Drilon et al., New England Journal of Medicine , 2024. 6. Perol et al., ESMO Presentation, 2024 - median follow -up: 21 months (range: 4 -47 months in the TKI -naïve population, data cutoff June 7, 2024).
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Taletrectinib has the highest overall response rate and median progression- free survival of any ROS1 inhibitor in the second line (TKI-pretreated) setting Taletrectinib2 Repotrectinib3 Zidesamtinib4 n cORR Median DOR Median PFS IC- cORR1 Pooled TRUST-I & TRUST-II TRIDENT-1 ARROS-1 113 56% 17 months 10 months 66% (21/32) 56 38% 15 months 9 months 38% (5/13) Study G2032R cORR 62% (8/13) 59% (10/17) 17 53% N/A N/A 50% (4/8) 62% (16/26) Note: These data are derived from different clinical studies, with differences in study design and patient populations. No he ad-to-head studies have been conducted. Comparisons in a head -to-head study may yield different results. cORR: confirmed Overall response rate; DOR: Duration of response; IC -ORR: Intracranial confirmed overall response rate; PFS: Pro gression free survival. 1. Reflects IC -cORR in patients with measurable CNS tumors. 2. Perol et al., ESMO Presentation, 2024; includes patients previously treated with crizotinib or entrectinib. 3. Drilon et al., New England Journal of Medicine , 2024; includes 98% of patients previously treated with crizotinib or entrectinib. 4. Besse et al., ESMO Presentation, 2024; includes 20 response evaluable patients who received 1 prior ROS1 TKI; includes nine confirmed partial re sponses 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. 9 3 0% Crizotinib & entrectinib Repotrectinib
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Taletrectinib data show an encouraging safety profile relative to approved ROS1 TKIs, including fewer dose modifications and low rates of neuro AEs Taletrectinib1 Repotrectinib2 Entrectinib2 Crizotinib2 Note: These data are derived from different clinical studies, with differences in study design and patient populations. No he ad-to-head studies have been conducted. Comparisons in a head -to-head study may yield different results. AE: Adverse Event. 1. Perol et al., ESMO Presentation, 2024. 2. 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 f rom Study 1 only). 10 41% 29% 7% 50% 38% 7% 46% 29% 9% N/A 11% 12% 0% 20% 40% 60% 80% Interruption Reduction Discontinuation Dose Modification Neurological AEs 21% 15% 10% 65% 54% 19% 38% 44% 18% 20% 26% 22% 0% 20% 40% 60% 80% Dizziness Dysgeusia HeadacheInterruption Reduction Discontinuation Dizziness Dysgeusia Headache
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ROS1+ NSCLC market represents a sizeable commercial opportunity; 1st generation ROS1 TKIs with ~1.5-year mPFS still sold ~$500 million in 2023 11 mPFS: median progression-free survival; TKI: tyrosine kinase inhibitor. 1. American Cancer Society (2024). 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 Key takeaways Estimated newly diagnosed patient population ~1,000-2,0002,6 • NSCLC accounts for ~80-85%1 of all lung cancers • ROS1+ lung cancer represents ~2%2 of new NSCLC cases • 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 generation 2nd generation
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Taletrectinib’s median progression-free survival of almost four years generates a potentially substantial market opportunity 12NSCLC: Non-small cell lung cancer. Note: Based on median progression-free survival demonstrated by taletrectinib in the first line setting, as presented at ESMO 2024 (Perol, et al.). 1. Reflects midpoint of epidemiology assumptions based on ROS1+ lung cancer representing approximately 2% of new NSCLC cases annually ; American Cancer Society (2024), National Center for Biotechnology Information: Gendarme et al., Curr Oncol (2022). 2. Redbook Access as of August 2024. 3. Reflects full market potential for 10 of 12 months in final year given median progression -free survival of 46 months. 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 • Pricing: ~$350,0002 per year, based on gross repotrectinib annual price • Does not incorporate product market share or other factors impacting potential revenue including product adoption, access and reimbursement, and persistency
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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 associated with less benefit from PD-1/PD-L1 inhibitors. 13
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Taletrectinib has greater numerical benefits over its competitors than the leaders of the EGFR and ALK markets over their nearest competitors Precedent NSCLC markets (1L)1 ROS1+ NSCLC (1L)2 ALK+ NSCLC Note: These data are derived from different clinical studies, with differences in study design and patient populations. No he ad-to-head studies have been conducted. Comparisons in a head -to-head study may yield different results. ORR: Overall response rate; mPFS: median Progression -free survival. 1. ALECENSA prescribing information (ALEX study res ults comparing alectinib to crizotinib); LORBRENA prescribing information; TAGRISSO prescribing information. 2. Perol et al., ESMO Presentation, 2024; AUGTYRO prescribing information and Drilon et al., New England Journal of Medicine , 2024; Drilon et al., JTO Clinical Research Reports , 2022; XALKORI prescribing information and Shaw et al., Annals of Oncology , 2019. EGFR+ NSCLC mPFS ORR mPFS (2nd gen.) 36 mo. 46 mo. 10 mo. 26 mo. 26 mo. NR @ 5-yrs 10 mo. 19 mo. 46 mo.19-16 mos. mPFS (1st gen.) 72% 79% 79% 76% 69% 77% 79% 89% 89%72-68% ORR (2nd gen.) ORR (1st gen.) Taletrectinib Taletrectinib Taletrectinib Taletrectinib 14
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$80 $139 $195 $231 $251 $223 $158 $149 $138 $102 $105 $100 $85 $199 $327 $378 $394 $421 $521 $537 $18 $31 $34 $38 $44 $52 $60 $77 $112 $141 $177 $224 $80 $139 $195 $231 $336 $440 $516 $638 $683 $707 $855 $921 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 Good, but not great drugs (neither alectinib or lorlatinib have best-in-class efficacy and safety), have still increased the ALK market ~4x Source: Evaluate Pharma, Earning Reports from Pfizer (crizotinib, lorlatinib), Roche (alectinib), Takeda (brigatinib) from 2012 to 2023. Notes: Total U.S. crizotinib net revenue shown for illustrative purposes (approved for ALK-positive NSCLC in 2011 and ROS1-positive NSCLC in 2016). Net revenue of ceritinib in ALK+ NSCLC is minimal and not broken out by U.S. only – therefore not included in this analysis. Total Net U.S. Revenue (ALK+ NSCLC TKIs) Alectinib Crizotinib BrigatinibLorlatinib Alectinib approved in 1L setting Lorlatinib approved in 2L setting Alectinib approved in 2L setting post-crizotinib Lorlatinib approved in 1L setting $ in millions Alectinib TKI Market Share: Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 0% 19% 37% 54% 55% 56% 55% 57% 15
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$15 $254 $405 $869 $1,268 $1,566 $1,780 $2,007 $2,276 $689 $731 $727 $638 $521 $266 $6 $23 $39 $26 $17 $14 $11 $9 $3 $689 $731 $748 $915 $965 $1,161 $1,285 $1,580 $1,791 $2,016 $2,279 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 Osimertinib captured >90% market share after only increasing mPFS by ~9 months and ORR by ~8%; US EGFR market has grown ~3x since its launch Source: Evaluate Pharma, Earning Reports from AstraZeneca (Osimertinib, erlotinib) and Roche (gefitinib) from 2013 to 2023. Notes: Net revenue of afatinib are not available as Boehringer Ingelheim is a private company. Net revenue of dacomitinib in EGFR+ NSCLC is minimal and therefore not included in this analysis. Total Net U.S. Revenue (EGFR+ NSCLC TKIs) Osimertinib Erlotinib Gefitinib Osimertinib approved in 1L setting Erlotinib patent expiry Osimertinib approved in 2L setting Osimertinib approved in adjuvant setting $ in millions Osimertinib TKI Market Share: Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 1% 21% 32% 61% 83% 92% 95% 95% 16
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Safusidenib | mIDH1i 17 Diffuse IDH1-mutant glioma Entering pivotal studies in 2025
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IDH mutations in glioma lead to accumulation of oncometabolite 2-HG, which drives cancer growth and creates an immunosuppressive tumor microenvironment • Gain-of-function mutation confers novel enzymatic activity, which convert α-KG to 2-HG • Epigenetic dysregulation with genome-wide hypermethylation (G-CIMP) • 2-HG impairs cellular differentiation • 2-HG creates an immunosuppressive tumor microenvironment • Grade 2 and 3 glioma: • 95-97% IDH1 mutations • 3 – 5% IDH2 mutations Mechanism of Action: IDH mutations Source: Carosi, et al., Cancers, 2024. 18
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Safusidenib crosses the blood-brain-barrier, inhibits mIDH1, and suppresses 2-HG levels Source: Whittle et al., Neuro-Oncology, 2024. *Asterix denotes normal brain sample for patient A-04. 19
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The diffuse IDH1-mutant glioma market represents a sizeable commercial opportunity, particularly because patients can remain on drug for years 20 ~13.3K – 18.3K people living with diffuse IDH1- mutant glioma in the U.S. Grade 2: ~63% Grade 3 ~37% Source: CBTRUS Statistical Report: U.S. Cancer Statistics – NPCR and SEER, 2018-2020.
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Royalty Pharma’s acquisition of rights to Agios Pharmaceuticals’ royalty on U.S. net sales of vorasidenib validates safusidenib’s market potential 21 • In May 2024, Royalty Pharma announced it acquired an interest in Agios Pharmaceuticals’ royalty on U.S. net sales of Servier’s vorasidenib • Royalty Pharma paid Agios $905 million in cash upon FDA approval of vorasidenib for a 15% royalty on annual U.S. net sales up to $1 billion • Will receive a 12% royalty and Agios will retain a 3% royalty on potential U.S. net sales >$1 billion • Royalty Pharma forecasts vorasidenib peak U.S. net sales of >$1 billion • Implies vorasidenib valuation of ~$6 billion Source: Royalty Pharma plc press release, Royalty Pharma investor presentation, and Agios Pharmaceuticals press release. Transaction Overview
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0% 18% ORR 0% 20% 40% 17% 33% 0% 20% 40% ORR Safusidenib early-stage data showed higher response rates than vorasidenib in low-grade (non-enhancing) and high-grade (enhancing) diffuse mIDH1 glioma 22 Enhancing glioma n=35 Non-enhancing glioma n=12 Enhancing glioma n=30 Non-enhancing glioma n=22 ORR: Overall response rate. Note: Information depicts response rates with IDH inhibitor in IDH1 -mutant gliomas in Phase 1 studie s; Enhancing and non -enhancing glioma was assessed by Response Assessment in Neuro -Oncology (RANO) and RANO -LGG, respectively. Contrasting enhancement is generally associated with a higher degree of malignancy. These dat a 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. 1. Na tsume et al., Neuro-Oncology, 2023. 2. Mellinghoff et al., Clinical Cancer Research , 2021 and Mellinghoff et al., New England Journal of Medicine , 2023. Enhancing Non-enhancing Safusidenib1 Vorasidenib2 11% Phase 1 study Pivotal study (INDIGO)
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Two complete responses observed lasting 174 weeks (grade 4 astrocytoma) and 95 weeks (grade 3 oligodendroglioma), with patients still on treatment at data cutoff 23 Enhancing glioma n=35 Non-enhancing glioma n=12 Note: Information depicts response rates with IDH inhibitor in IDH1 -mutant gliomas in Phase 1 studies; Enhancing and non -enhancing glioma was assessed by Response Assessment in Neuro -Oncology (RANO) and RANO -LGG, respectively. Minor response not applicable in enhancing glioma patients assessed by RANO. Contrasting enhancement is general ly associated with a higher degree of malignancy. 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. 1. Natsume et al., Neuro -Oncology, 2023. 2. Two complete responses represent one complete response in a grade 4 astrocytoma and one complete response in the target lesions o f a grade 3 oligodendroglioma (with stable disease in non-target lesions). 3. Mellinghoff et al., Clinical Cancer Research, 2021. Safusidenib1 Vorasidenib3 RANO responses Enhancing n=35 Non-enhancing n=12 Overall response 6 (17%) 4 (33%) Complete response2 2 (6%) 0 (0%) Partial response 4 (11%) 1 (8%) Minor response N/A 3 (25%) Stable disease 11 (31%) 8 (67%) Progressive disease 17 (49%) 0 (0%) Not evaluable 1 (3%) 0 (0%) RANO responses Enhancing n=30 Non-enhancing n=22 Overall response 0 (0%) 4 (18%) Complete response 0 (0%) 0 (0%) Partial response 0 (0%) 1 (5%) Minor response N/A 3 (14%) Stable disease 17 (57%) 16 (73%) Progressive disease 12 (40%) 2 (9%) Not evaluable 1 (3%) 0 (0%)
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Another IDH1 inhibitor (ivosidenib) blocks 2-HG synthesis and increases tumor infiltrating CD8+ T cells, demonstrating augmentation of immunity ivosidenib ivosidenib + anti-CD8 vehicle Source: Wu et al., Cancer Discovery, 2022. 1. IHC staining for CD8 in CKIR132C subcutaneous allograft ICCs after 6 days treatment with vehicle or AG120; right: quantification. Data represents mean ± SD; **P<0.01; unpaired t-test. 2. Analysis of serial changes in tumor volume.N = 6 mice per group. Data represent means ± SEM; ***P<0.001; unpaired t-test. Ivosidenib promotes tumor CD8+ T-cell infiltration1 Depletion of CD8+ T-cells blocks anti-tumor activity of ivosidenib2 24
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Safusidenib, unlike vorasidenib, shows far greater activity in mice with an intact immune system rather than immunocompromised mice, suggesting immune MOA vehicle vehicle vehicle Safusidenib 50 mg/kg BID Safusidenib 150 mg/kg BID Safusidenib 200 mg/kg BID Safusidenib 200 mg/kg BID Doxorubicin Safusidenib 400 mg/kg QD Xenografts in immunocompetent mice SurvivalTumor Volume Tumor Volume (mm3) Tumor Volume (mm3) Days after start of treatment Days after start of treatment 2,500 0 50 1,000 1,500 2,000 0 2 4 6 8 10 12 14 0 200 300 400 500 100 0 7 14 21 28 Xenografts in immunodeficient mice Source: Nuvation internal preclinical research. 25 Vorasidenib 50 mg/kg QD
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TEAE: n (%); Preferred Term1,2 All grades Grade 3 Skin hyperpigmentation 25 (53) N/A Diarrhea 22 (47) 2 (4) Pruritus 14 (30) 0 Alopecia 13 (28) 0 Arthralgia 13 (28) 1 (2) Nausea 12 (26) 0 Headache 11 (23) 1 (2) Rash 11 (23) 0 Source: Natsume et al., Neuro-Oncology, 2023. 1. Safety analysis set (n=47). 2. Patients were only counted once even if the same adverse event was reported more th an once. Five of the top eight adverse events seen in a Phase 1 study of safusidenib are consistent with an immune-related MOA 26
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Committed team tackling the greatest unmet needs in oncology Broad pipeline across multiple stages of development • Taletrectinib | ROS1 inhibitor: NDA accepted for priority review (line agnostic, full approval) in December 2024 • Safusidenib | mIDH1 inhibitor: Phase 2 study ongoing • NUV-1511 | Drug-drug conjugate: Phase 1 dose escalation study ongoing • NUV-868 | BD2-selective BET inhibitor: Completed Phase 1 and Phase 1b studies Strong cash position to support operations in near term • $549.1 million as of September 30, 2024 Experienced biotech leadership team • Founded by Dr. David Hung, previously the founder and CEO of Medivation, who successfully developed and commercialized XTANDI® Potentially best-in-class candidates leveraging and improving validated mechanisms • Potential for better efficacy and tolerability 27 Potential to become a commercial stage organization in the U.S. as early as mid-2025 • NDA for taletrectinib accepted for priority review with PDUFA goal date of June 23, 2025 • Taletrectinib has been approved in China for the treatment of advanced ROS1+ NSCLC PDUFA: Prescription Drug User Fee Act.