Nuvation Bio Inc. · NYSE:NUVB
Nuvation Bio — Investor Presentation (November 2023)
28 slides from Nuvation Bio's investor presentation, November 2023
Slide 1: Driven by Science, Focused on Life
DRIVEN BY SCIENCE FOCUSED ON LIFE November 2023
Slide 2: Forward looking statements
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 statemen
Slide 3: Pipeline of wholly-owned candidates tackling the greatest unmet needs in oncology
Pipeline of wholly-owned candidates tackling the greatest unmet needs in oncology CURRENT STAGE ANTICIPATED MILESTONES & PROGRAM POTENTIAL INDICATION(S) RECENT UPDATES PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Advanced NUV-868 Treatment ongoing in Phase 1 dose escalation solid tumors Ovarian, TNBC, NUV-86
Slide 4: NUV-868 | BETi
NUV-868 | BETi Advanced solid Treatment ongoing in tumors Phase 1 monotherapy Ovarian, TNBC, Treatment ongoing in pancreatic, mCRPC & Phase 1b combination other solid tumors 4
Slide 5: First generation BET inhibitors have been toxic and poorly effective against solid tumors
First generation BET inhibitors have been toxic and poorly effective against solid tumors Limitations of first generation BET inhibitors BRD4 Affinity2 • BET proteins regulate the expression of many BD2 BD1 Selectivity oncogenes, including cMYC – an oncogene that (nM) (nM) has not been targetable di
Slide 6: BD1 and BD2 play very different roles in gene regulation
BD1 and BD2 play very different roles in gene regulation1 Key takeaways • BD1 and BD2 enable chromatin binding to facilitate transcription DRUG DISCOVERY • BD1 primarily mediates steady-state gene expression, whereas BD2 primarily mediates the rapid induction of gene expression Selective targeting o
Slide 7: BD1 inhibition disrupts steady state gene expression and increases toxicity
BD1 inhibition disrupts steady state gene expression and increases toxicity BD1 inhibition BD2 inhibition • Regulates steady state gene expression • Regulates rapid gene induction • Displaces BET proteins already associated with histones • Prevents BET proteins from becoming associated with histones
Slide 8: BD2-selective BET inhibitor (ABBV-744) causes less thrombocytopenia and GI toxicity
BD2-selective BET inhibitor (ABBV-744) causes less thrombocytopenia and GI toxicity than BET inhibitors that potently inhibit BD1 (e.g. ABBV-075) ABBV-744 demonstrates a superior therapeutic window Less GI tox at efficacious dose (AR+ PC) with ABBV-744 compared to pan-BET inhibitors Less effect on p
Slide 9: NUV-868 inhibits BD2 almost 1,500 times more potently than BD1
NUV-868 inhibits BD2 almost 1,500 times more potently than BD1, which may improve efficacy and tolerability NUV-868 is the most selective BD2 vs BD1 BET inhibitor in development BRD4 Affinity2 BD2 BD1 Selectivity (nM) (nM) NUV-868* 2 2920 1460x ABBV-7443 1.05 340 324x PLX-28534 Modest BD2 selectivit
Slide 10: NUV-868: Less bone marrow toxicity in animal models
NUV-868: Less bone marrow toxicity in animal models MV4-11 AML xenograft hematology panel Rat 14-day repeat dose study 24-hours post final dose on Day 21 24-hours post final dose on Day 14 Dose RBC PLT NEUT LYM RET Dose RBC PLT NEUT HGB HCT Sex (mg/kg) (106/ul) (103/ul) (103/ul) (103/ul) (109/L) mg/
Slide 11: NUV-868: Reduced gut toxicity compared with non-selective BET inhibitors
NUV-868: Reduced gut toxicity compared with non-selective BET inhibitors ABBV-075 (dual BD1 / BD2) NUV-868 (BD2 selective) may avoid GI toxicity A non-selective inhibitor (ABBV-075) leads to marked Treatment of mice for 10 days with BD2 selective compound reduction in rat small intestine goblet
Slide 12: NUV-868: Plasma exposures provide robust, selective BD2 inhibition
NUV-868: Plasma exposures provide robust, selective BD2 inhibition Dog 28-day dog toxicology study 1 mg/kg 4 mg/kg 8 mg/kg 1 mg/kg 4 mg/kg 8 mg/kg 100 100 75 75 % inhibition BD1 % inhibition BD2 50 50 25 25 0 0 0 4 8 12 16 20 24 0 4 8 12 16 20 24 Time (hours) Time (hours) Dose-dependent, robust inhi
Slide 13: NUV-868 down regulates BCL-2 and MYC and up regulates Hexim-1
NUV-868 down regulates tumor promoting oncogenes BCL-2 and MYC and up regulates tumor suppressor gene Hexim-1 Pharmacodynamic markers AML CDX (Kasumi-1) Vehicle NUV-868 20 mg/kg BCL-2 cMYC Hexim-1 2500 Tumor Volume (mm3) 2000 1.5 1.5 3.5 1500 Effects of gene expression relative to vehicle Effects of
Slide 14: NUV-868 converts enzalutamide-resistant prostate cancer xenografts to sensitive
NUV-868 treatment converts enzalutamide-resistant patient derived prostate cancer xenografts to again be enzalutamide-sensitive Individual animal tumor volume Change in tumor volume (%) Vehicle Enzalutamide NUV-868 NUV-868 NUV-868 NUV-868 10mg/kg 10mg/kg + 30mg/kg 30mg/kg + Enzalutamide Enzalutamide
Slide 15: Efficacious NUV-868 doses provide selective coverage for BD2 inhibition
Efficacious NUV-868 doses provide selective coverage for BD2 inhibition Prostate PDX model 10 mg/kg 10 mg/kg + enzalutamide 10 mg/kg 10 mg/kg + enzalutamide 100 100 75 75 % inhibition BD1 % inhibition BD2 50 50 25 25 0 0 0 4 8 12 16 20 24 0 4 8 12 16 20 24 Time (hours) Time (hours) Inhibition of BD2
Slide 16: BD2 selectivity blocks cancer cells inducing resistance pathways
BD2 selectivity blocks the ability of cancer cells to induce resistance pathways, and by avoiding BD1 inhibition, increases tolerability BD1 inhibition BD2 inhibition • Regulates steady state gene expression • Regulates rapid gene induction • Displaces BET proteins already associated with histones •
Slide 17: NUV-868 significantly delays emergence of enzalutamide resistance in xenografts
NUV-868 significantly delays the emergence of enzalutamide resistance in prostate cancer xenografts Individual animal tumor volume: enzalutamide only (n=35) 4000 Tumor volume (mm3) 3000 2000 1000 0 0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 Day Individual animal tumor volume: enzalutamide + NUV-
Slide 18: NUV-868 reduces PARP inhibitor resistance by preventing alternative DNA repair
NUV-868 reduces PARP inhibitor resistance possibly by preventing the induction of alternative DNA repair pathways Limitations of PARP inhibition Benefits of PARP and BET inhibition in combination • Genes will find other ways to repair themselves even in presence • BET inhibitors prevent genes from i
Slide 19: NUV-868 increases effectiveness of olaparib in HR proficient ovarian cancer xenografts
NUV-868 increases effectiveness of olaparib in HR proficient ovarian cancer xenografts: Does NUV-868 inhibit induction of DNA repair pathways? HR-proficient ovarian cell line xenograft Tumor DNA damage 2500 Vehicle 2000 yH2AX Tumor Volume (mm3) 1500 GAPDH 1000 NUV-868 + olaparib 500 0 yH2AX 0 7 14 2
Slide 20: Modified NUV-868 Phase 1 and Phase 1b development plan
Modified NUV-868 Phase 1 and Phase 1b development plan expedites ability to reach larger number of patients and determine RP2D/RP2cD Phase 1 monotherapy Phase 1b combination therapy NUV-868 Regimen 1: NUV-868 + olaparib Regimen 2: NUV-868 + enzalutamide Dose escalation1 Dose escalation Backfill coho
Slide 21: Phase 2 study will evaluate NUV-868 in six expansion cohorts
Phase 2 study will evaluate NUV-868 in combination with olaparib and enzalutamide in six solid-tumor specific expansion cohorts Regimen 1: NUV-868 + olaparib Regimen 2: NUV-868 + enzalutamide 1 5 Ovarian cancer Enzalutamide-naïve mCRPC Randomized to: 1) NUV-868 monotherapy 2 2) Enzalutamide monother
Slide 22: Drug-Drug Conjugate (DDC) Platform
Drug-Drug Conjugate (DDC) Platform Year end 2023: Solid Tumors Submit IND filing 22
Slide 23: The DDC platform is a potentially revolutionary advance beyond ADCs
The drug-drug conjugate (DDC) platform is a potentially revolutionary advance beyond ADCs Antibody-drug conjugates Drug-drug conjugates ✓ Improves therapeutic index vs. untargeted ✓ Tissue-selective targeting improves warhead therapeutic index vs. untargeted warhead IV delivery ✓ Oral or IV delive
Slide 24: DDCs are designed to bind TWO different targets simultaneously
DDCs are designed to bind TWO different targets simultaneously Two separate drugs with two separate targets Fuse Binding Domains Drug Target X Drug Target Y Drug X Drug Y Drug Target X Drug Target Y Drug X Drug Y 24
Slide 25: DDC #1 suppresses prostate and breast cancer growth in xenografts
DDC #1, a DDC derivative of a widely used chemo agent, suppresses prostate and breast cancer growth in xenografts Prostate cancer CDX (LNCAP) ER+ Breast cancer CDX (T47D) 2500 1000 2000 750 Tumor Volume (mm3) Tumor Volume (mm3) 1500 500 1000 250 500 0 0 0 7 14 21 28 35 0 7 14 21 28 35 Day Day 25 ER:
Slide 26: Intermittent dosing of DDC #1 leads to sustained tumor inhibition
Intermittent dosing of DDC #1 leads to sustained tumor inhibition for weeks 2000 1500 Tumor Volume (mm3) 1000 500 0 0 7 14 21 28 Day Vehicle Chemo dose regimen 1 Chemo dose regimen 2 DDC #1 dose regimen 1 DDC #1 dose regimen 2 26
Slide 27: Other novel DDCs also cause tumor regression in xenograft models
Other novel DDCs also cause tumor regression in various xenograft models DDC #2: ER+ Breast cancer CDX (T47D) DDC #3: HR+ Breast cancer CDX (T47D) 1250 1250 1000 1000 Tumor Volume (mm3) Tumor Volume (mm3) 750 750 500 500 250 250 0 0 0 7 14 21 28 0 7 14 21 28 Day Day Vehicle DDC #2 Vehicle DDC #3 27
Slide 28: Committed team tackling the greatest unmet needs in oncology
Committed team tackling the greatest unmet needs in oncology Experienced biotech leadership team Broad wholly-owned pipeline • Founded in 2018 by Dr. David Hung, previously • Treatment ongoing in Phase 1 monotherapy and the founder and CEO of Medivation and Phase 1b combination studies of NUV-868, a