Nuvation Bio Inc. · NYSE:NUVB
Nuvation Bio — Investor Presentation (December 2022)
33 slides from Nuvation Bio's investor presentation, Dec 23, 2022
Slide 1: Driven by Science, Focused on Life
DRIVEN BY SCIENCE FOCUSED ON LIFE December 2022 Exhibit 99.1
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 PROGRAM POTENTIAL INDICATION(S) CURRENT STAGE ANTICIPATED MILESTONES & RECENT UPDATES Program Potential Indication(s) PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Anticipated Milestones NUV-868 (BET) Advanced solid tumors NUV-8
Slide 4: NUV-868 | BETi
NUV-868 | BETi Advanced solid tumors Enrollment ongoing in Phase 1 monotherapy Ovarian, TNBC, pancreatic, mCRPC & other solid tumors Enrollment ongoing in Phase 1b combination
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 BET proteins regulate the expression of many oncogenes, including cMYC – an oncogene that has not been targetable directly with a drug Non-selective BD1/2-inhibitors have been associated with tolerability issue
Slide 6: BD1 and BD2 play very different roles in gene regulation
BD1 and BD2 play very different roles in gene regulation1 Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation Gilan et al, Science 368, (2020) DRUG DISCOVERY 1. Gilan et al, Science 368, (2020). Key takeaways BD1 and BD2 enable chromatin binding to facilitate tran
Slide 7: BD1 inhibition disrupts steady state gene expression and increases toxicity
BD1 inhibition disrupts steady state gene expression and increases toxicity BD2 inhibition BD1 inhibition Ac: Acetylated chromatin MTD: Maximum tolerated dose Regulates steady state gene expression Displaces BET proteins already associated with histones Toxicity minimizes the therapeutic window Regu
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 has much more targeted anti-proliferative effects than pan-BET inhibitors; mainly effective in AML and AR-dependent prostate cancer AR-dependent
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 BRD4 Affinity2 BD2 (nM) BD1 (nM) Selectivity NUV-868* 2 2920 1460x ABBV-7443 1.05 340 324x PLX-28534 Modest BD2 selectivity CPI-06103 17 85 5x ABBV-0751 3 11 3.7x MK-8628/OTX-0155 17 26 1.5x B
Slide 10: NUV-868: Less bone marrow toxicity in animal models
NUV-868: Less bone marrow toxicity in animal models Dose (mg/kg) RBC (106/ul) PLT (103/ul) NEUT (103/ul) LYM (103/ul) RET (109/L) Vehicle - 10.4 842 0.20 7.45 361 NUV-868 5 9.6 893 0.19 3.98 438 NUV-868 10 10.2 1290 0.15 5.53 463 NUV-868 20 10.2 1460 0.07 5.93 505 24-hours post final dose on Day 21
Slide 11: NUV-868: Reduced gut toxicity compared with non-selective BET inhibitors
NUV-868: Reduced gut toxicity compared with non-selective BET inhibitors Vehicle NUV-868 Treatment of mice for 10 days with BD2 selective compound NUV-868 shows no evidence of goblet cell loss Vehicle ABBV-075 A non-selective inhibitor (ABBV-075) leads to marked reduction in rat small intestine gobl
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 Dose-dependent, robust inhibition of BD2 Negligible BD1 inhibition even at high dose
Slide 13: NUV-868 down regulates oncogenes 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 AML CDX (Kasumi-1) Pharmacodynamic markers AML CDX (MV-4-11) BCL-2 cMYC Hexim-1 Vehicle NUV-868 Note: Experiments conducted using BID dosing.
Slide 14: NUV-868 converts enzalutamide-resistant xenografts to enzalutamide-sensitive
NUV-868 treatment converts enzalutamide-resistant patient derived prostate cancer xenografts to again be enzalutamide-sensitive Vehicle Enzalutamide NUV-868 10mg/kg NUV-868 10mg/kg + Enzalutamide NUV-868 30mg/kg NUV-868 30mg/kg + Enzalutamide Individual animal tumor volume Change in tumor volume (%)
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 Inhibition of BD2 as monotherapy and in combination with enzalutamide Negligible inhibition of BD1 as monotherapy and in combination with enzalutamide Note: Experiments conducted using BID dosing.
Slide 16: BD2 selectivity blocks resistance pathways and increases tolerability
BD2 selectivity blocks the ability of cancer cells to induce resistance pathways, and by avoiding BD1 inhibition, increases tolerability Regulates steady state gene expression Displaces BET proteins already associated with histones Toxicity minimizes the therapeutic window Regulates rapid gene induc
Slide 17: NUV-868 significantly delays emergence of enzalutamide resistance
NUV-868 significantly delays the emergence of enzalutamide resistance in prostate cancer xenografts Individual animal tumor volume: enzalutamide only (n=35) Individual animal tumor volume: enzalutamide + NUV-868 (n=12) Day Tumor volume (mm3) Day Tumor volume (mm3) Note: Experiments conducted using B
Slide 18: NUV-868 reduces PARP inhibitor resistance
NUV-868 reduces PARP inhibitor resistance possibly by preventing the induction of alternative DNA repair pathways Genes will find other ways to repair themselves even in presence of PARP inhibitors; repaired DNA leads to cancer growth BET inhibitors prevent genes from inducing other repair pathways
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? Tumor DNA damage HR-proficient ovarian cell line xenograft NUV-868 + olaparib Vehicle yH2AX GAPDH yH2AX GAPDH HR: Homologous recombination. Note: Experiments
Slide 20: NUV-868-01 Phase 1/1b study: monotherapy & combination
NUV-868-01 Phase 1/1b study: monotherapy & combination NUV-868 + enzalutamide mCRPC NUV-868 + olaparib Ovarian, pancreatic, mCRPC, TNBC & other solid tumors Regimen 2 Regimen 1 Primary objective: safety, tolerability, RP2D Primary objective: safety, tolerability, RP2cD, drug interaction NUV-868 mono
Slide 21: NUV-868 will be explored in solid tumors as monotherapy and in combination
NUV-868 will be explored in solid tumors as monotherapy and in combination with Standard of Care NUV-868 RP2D Enrollment ongoing Dose escalation 3 + 3 study design (advanced solid tumors) Phase 1 monotherapy Enrollment ongoing Phase 1b combination Start after clearing DL1 in Phase 1 monotherapy NUV-
Slide 22: Drug-Drug Conjugate (DDC) Platform
Drug-Drug Conjugate (DDC) Platform Solid Tumors Year end 2023: Submit IND filing
Slide 23: The DDC platform is a potentially revolutionary advance beyond ADCs
Oral or IV delivery Improves therapeutic index vs. untargeted warhead IV delivery Limited to cell-surface targets Complex and expensive CMC Antibody-drug conjugate The drug-drug conjugate (DDC) platform is a potentially revolutionary advance beyond ADCs Drug-drug conjugates Drug-drug conjugates Anti
Slide 24: DDCs are designed to bind two different targets simultaneously
Drug Target X Drug Target Y Drug X Drug X Drug Y Drug Y Fuse Binding Domains DDCs are designed to bind TWO different targets simultaneously Drug Target X Drug Target Y Two separate drugs with two separate targets
Slide 25: NUV-1156 is a novel drug-drug conjugate that targets AR and PARP
PARP AR PARP PARP Inhibitory Warhead AR Targeting Small Molecule Fuse Binding Domains NUV-1156 is a novel drug-drug conjugate that targets AR and PARP AR Two separate drugs with two separate targets
Slide 26: NUV-1156 targets high AR-expressing tissue and avoids low AR-expressing tissue
NUV-1156 targets high AR-expressing tissue like prostate cancer and avoids low AR-expressing tissue like bone marrow and GI tract Bone Marrow Duodenum Small Intestines Colon Testis Prostate Epididymis Seminal Vesicle Fallopian Tube Breast Cervix Endometrium Androgen Receptor Expression Level Low AR
Slide 27: NUV-1156 potently kills enzalutamide-resistant prostate cancer cells
NUV-1156 potently kills enzalutamide-resistant prostate cancer cells (22RV1) which express AR, but not colon cells (IEC6), which have no AR Product / Candidate IC50 (nM) >30,000 7844 6152 NUV-1156 (PARP-AR DDC) 201 + Relative cell inhibition potency Enzalutamide-resistant prostate cancer cell line 2
Slide 28: NUV-1176 targets high ER-expressing tissue and avoids low ER-expressing tissue
NUV-1176 targets high ER-expressing tissue like breast cancer and avoids low ER-expressing tissue like bone marrow and GI tract Bone Marrow Duodenum Small Intestines Colon Smooth Muscle Fallopian Tube Breast Vagina Cervix Endometrium Estrogen Receptor Expression Level Low ER expression in gut and bo
Slide 29: NUV-1176, an ER-targeted DDC, potently kills ER+ breast cancer cells
NUV-1176, an ER-targeted DDC, potently kills both HR-D and HR-P ER+ breast cancer cells without killing healthy gut epithelial cells ER: Estrogen receptor; HR: Homologous recombination; IEC: Intestinal epithelial cells. Proliferation inhibition NUV-1176 ER+ Breast cancer cells Healthy colon cells HR
Slide 30: 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) ER: Estrogen receptor.
Slide 31: Intermittent dosing of DDC #1 leads to sustained tumor inhibition
Intermittent dosing of DDC #1 leads to sustained tumor inhibition for weeks
Slide 32: 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) ER: Estrogen receptor; HR: Homologous recombination.
Slide 33: Committed team tackling the greatest unmet needs in oncology
Committed team tackling the greatest unmet needs in oncology Broad wholly-owned pipeline Enrollment ongoing in Phase 1 monotherapy and Phase 1b combination studies of NUV-868, a BD2 selective BET inhibitor for patients with advanced solid tumors First clinical candidate selected from DDC platform Co