Nuvation Bio Inc. · NYSE:NUVB
Nuvation Bio — Investor Presentation (January 2022)
55 slides from Nuvation Bio's investor presentation, Jan 10, 2022
Slide 1: Driven by Science, Focused on Life
DRIVEN BY SCIENCE FOCUSED ON LIFE January 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: Recent accomplishments and potential 2022 milestones
Recent accomplishments and potential 2022 milestones Recent Accomplishments First patient treated with NUV-422 in high grade glioma (HGG) trial in December 2020 Dose escalation ongoing in Phase 1 study in High Grade Glioma (HGG), breast and prostate cancer IND accepted for advanced Beast Cancer (aBC
Slide 4: NUV-422 | CDK 2/4/6i
rGBM HR+ aBC mCRPC Dec 2020 First patient dosed Phase 2 Initiation by Year End 2022 Phase 2 Initiation by Year End 2022 NUV-422 | CDK 2/4/6i
Slide 5: CDK2 drives resistance to CDK4/6 inhibitors
TUMOR GROWTH SIGNALING No Pharmacological Intervention CDK2 CDK4/6 CDK2 TUMOR GROWTH SIGNALING In Presence of First Generation CDK4/6 CDK2 Drives Resistance to CDK4/6 Inhibitors CDKN2A Deletion or alterations commonly Drive Cancer growth Through CDK2/4/6 CDK4/6 CDK2 CDK4/6 CDK2 Nuv-422 selectively t
Slide 6: CDK2/4/6 inhibition that avoids CDK1
1st Generation CDK 4 CDK 6 CDK 2 2 2 10000 4 2 2470 2 10 504 2nd Generation CDK 4 CDK 6 CDK 2 PF-06873600 2 4 0.3 NUV-422 2 1 7 CDK 1 2 73 CDK2/4/6 inhibition that avoids CDK1 may be associated with better efficacy and tolerability DRIVES EFFICACY CAUSES TOXICITY IC50 (nM) METASTATIC Monotherapy Lab
Slide 7: NUV-422-02 phase 1/2 monotherapy study
Isocitrate dehydrogenase wild-type glioblastoma (IDHwt) rGBM COHORT 1: Up to 40 pts with measurable disease HR+/Her2- aBC post CDK4/6i COHORT 2: Up to 40 pts with measurable disease COHORT 4: Up to 40 pts with active brain mets mCRPC post Androgen Receptor Therapy (AR) & taxane COHORT 3: Up to 40 pt
Slide 8: Glioblastoma
Glioblastoma sBRB ee Nuvation Bio PAs
Slide 9: CDKN2A deletion and CDK2 overexpression associated with worse survival in gliomas
CDKN2A deletion and CDK2 overexpression associated with worse survival in primary high-grade gliomas CDKN2A Deletion is Associated With Worse Survival1 CDK2 Expression Is Associated With Lower Overall Patient Survival2 (1) 1Appay et al., 2020 2Wang et al., 2016 CDKN2A -/- with MVP and or necrosis CD
Slide 10: NUV-422 is superior to temozolomide in GBM xenograft model
NUV-422 is superior to standard of care temozolomide in xenograft model of GBM Tumor Volume NUV-422 30 mg/kg PO QD
Slide 11: NUV-422-02 rGBM monotherapy phase 1/2
NUV-422-02 rGBM monotherapy phase 1/2 Phase 1 Dose Escalation Data By Year End PHASE 1 Dose Escalation PRIMARY OBJECTIVE: safety, tolerability, RP2D RP2D HGG, including rGBM Dose Escalation & Dose Backfill IDHwt rGBM CDKN2A known status Up to 40 patients Surgical Substudy: rGBM PRIMARY OBJECTIVE: PK
Slide 12: Breast Cancer
Breast Cancer sBRB ee Nuvation Bio PAs
Slide 13: NUV-422 potency in palbociclib-sensitive and -resistant cells
NUV-422 has similarly strong potency in palbociclib-sensitive and palbociclib-resistant cells Cyclin E predicts resistance to palbociclib NUV-422 inhibits growth of palbociclib-resistant ER+ breast cancer cells with high CDK2/Cyclin E Proliferation Inhibition IC50 (nM) Compound Palbociclib-sensitive
Slide 14: NUV-422 activity across ER+ breast cancer xenografts
NUV-422 shows activity across ER+ breast cancer xenografts ER+ breast cancer xenograft ER+ CDK4/6 inhibitor and fulvestrant resistant patient derived breast cancer xenograft harboring an ESR1 mutation ER+ fulvestrant-resistant patient derived breast cancer xenograft NUV-422 30 mg/kg PO QD
Slide 15: NUV-422-02 2L+ aBC monotherapy phase 1/2
NUV-422-02 2L+ aBC monotherapy phase 1/2 5 Phase 1 Dose Escalation Data By Year End PHASE 1 Dose Escalation PRIMARY OBJECTIVE: safety, tolerability, RP2D RP2D HR+/HER2- aBC 2L+ Dose Escalation & Dose Backfill HR+/Her2- aBC post CDK4/6i COHORT 2: Up to 40 pts with measurable disease HR+/Her2- aBC wit
Slide 16: NUV-422-03 phase 1b/2 aBC study with fulvestrant
NUV-422-03 phase 1b/2 aBC study NUV-422 in combination with fulvestrant Phase 1b Safety Run-in HR+/HER2- aBC Primary Endpoint: Safety; RP2cD Randomized Phase 2 HR+/HER2- aBC with prior CDK4/6i Primary Endpoint: ORR Stage 1: 20 pts Stage 1: 20 pts Randomize 2:1:1 Stage 2: ~50 pts NUV-422 monotherapy
Slide 17: Xenograft data in endocrine-independent breast cancer
Additional xenograft data suggests broad potential for NUV-422 in endocrine-independent breast cancer Tumor Volume (mm3) Days Tumor Volume Days ER-Negative/HER2-Positive Breast Cancer Xenograft Vehicle NUV-422 Tucatinib NUV-422 + tucatinib Tumor Volume (mm3) Vehicle NUV-422 Tucatinib NUV-422 + tucat
Slide 18: Prostate Cancer
Prostate Cancer sBRB ee Nuvation Bio PAs
Slide 19: Advanced prostate cancer is associated with CDK2 overexpression
Advanced prostate cancer is associated with CDK2 overexpression Role of CDK2/4/6 in mCRPC 1 Brighi et al, 2021; Schiewer et al, 2012 2Yin, et al 2018 3 Jorda et al, 2018]. CDK2 expression increases with progression of prostate cancer and is associated with worse prognosis2 CDK2 can phosphorylate and
Slide 20: NUV-422 tumor regression in enzalutamide-resistant xenograft
NUV-422 causes tumor regression in an enzalutamide-resistant patient derived prostate tumor xenograft Individual animal tumor volume NUV-422 30 mg/kg PO QD
Slide 21: NUV-422 activity in ARV-7 prostate cancer model
NUV-422 shows activity in a prostate cancer model resistant to standard of care Prostate cancer ARV-7 xenograft that is resistant to standard of care anti-androgen therapies NUV-422 30 mg/kg PO QD
Slide 22: NUV-422-02 mCRPC monotherapy phase 1/2
NUV-422-02 mCRPC monotherapy phase 1/2 Phase 1 Dose Escalation Data By Year End PHASE 1 Dose Escalation PRIMARY OBJECTIVE: safety, tolerability, RP2D RP2D Recurrent/Refractory mCRPC Dose Escalation & Dose Backfill PHASE 2 Dose Expansion PRIMARY OBJECTIVE: efficacy; ORR & DOR; PSA Decline mCRPC post
Slide 23: NUV-422-04 phase 1b/2 study in mCRPC with enzalutamide
NUV-422-04 phase 1b/2 study in mCRPC: NUV-422 combination with enzalutamide Phase 1b Safety Run-in mCRPC Primary Endpoint: Safety; RP2cD Phase 2 mCRPC: Measurable & Unmeasurable Disease Primary Endpoint: ORR; PSA Response Rate Phase 1b Initiation Mid-2022 mCRPC with prior abiraterone acetate NUV-422
Slide 24: NUV-868 | BETi
NUV-868 | BETi Advanced Solid Tumors Phase 1 Initiation Mid-2022
Slide 25: BET: Bromodomain and extra-terminal motif proteins
BET: Bromodomain and extra-terminal motif proteins BET are a family of proteins (e.g., BRD4) with two bromodomains (BD1 and BD2)1 BET family of proteins have critical biological functions and are found to be altered in many human cancers2 BET proteins play a critical role in gene transcription1 To d
Slide 26: NUV-868 is a highly selective BD2 BET inhibitor
BET: Bromodomain and extra-terminal motif proteins BET are a family of proteins with two bromodomains (BD1 and BD2) BET proteins can induce the expression of a number of oncogenes, including MYC – an oncogene that cannot be targeted directly with a drug To date, BET inhibitors have largely focused o
Slide 27: NUV-868 down regulates BCL-2 and MYC
NUV-868 inhibits tumor growth by down regulating tumor promoting genes BCL-2 and MYC and up regulating tumor suppressor Hexim-1 Pharmacodynamic Markers AML CDX Tumor Volume AML CDX Tumor Volume Veh NUV-868 Veh NUV-868 Veh NUV-868 Bcl-2 cMyc Hexim-1
Slide 28: BD2 selectivity reduces gut toxicity
High selectivity for BD2 over BD1 significantly reduces the gut toxicity observed with other nonselective BET inhibitors NUV-868 (BD2 Selective) May Avoid GI Toxicity ABBV-075 (Dual BD1 / BD2) Vehicle NUV-868 Treatment of mice for 10 days with BD2 selective compound NUV-868 shows no evidence of gobl
Slide 29: NUV-868 tumor reductions in enzalutamide-resistant prostate xenograft
NUV-868 causes tumor reductions in an enzalutamide-resistant patient-derived prostate cancer xenograft model Enzalutamide-resistant prostate cancer xenograft NUV-868 20 mg/kg QD
Slide 30: BET inhibitors sensitize HR-proficient cancers to PARP inhibitors
BET inhibitors (BRD4) cause sensitization of HR-proficient cancers to PARP-inhibitors
Slide 31: NUV-868 + olaparib increases DNA breaks in ovarian tumor model
Combination of NUV-868 + olaparib increases double stranded DNA breaks (γH2AX) in an HR-proficient ovarian tumor model NUV-868 20 mg/kg QD
Slide 32: NUV-569 | WEE1i
NUV-569 | WEE1i Advanced Solid Tumors IND Submission by Year End 2022
Slide 33: Wee1 checkpoint and replication of damaged DNA
TUMOR GROWTH REPLICATING DAMAGED DNA CAUSES CELL DEATH Arrest their own replication Give them time to fix their damaged DNA Turn off their Wee1 to re-initiate growth Wee1 Checkpoint Wee1 Checkpoint Wee1 Checkpoint Wee1 Checkpoint Wee1 Inhibitor Wee1 Inhibitor Tumors activate their Wee1 checkpoint to
Slide 34: NUV-569 avoids PLK1, less toxicity
PLK1 is a ubiquitous cell kinase that may be responsible for gut and bone marrow toxicity NUV-569’s Highly Potent and Selective profile = less toxicity Compound Wee1 PLK1 IEC6 NUV-569 7 687 2362 AZD1775 4 15 251 IC50 (nM) NUV-569 is highly potent against Wee1 but avoids PLK1 unlike AZD1775 10X reduc
Slide 35: NUV-569 synergizes with gemcitabine and carboplatin
NUV-569 synergizes with SOC gemcitabine in pancreatic cancer cells and carboplatin in breast cancer cells to enhance cancer cell death Pancreatic Cancer Cell Lines Cell inhibition (%) Breast Cancer Cell Lines Cell inhibition (%)
Slide 36: NUV-569 with gemcitabine and radiation
NUV-569 further enhances cancer cell death in combination with both gemcitabine and radiation Pancreatic Cancer Cell Line Cell inhibition(%)
Slide 37: NUV-569 synergy in breast cancer xenografts
NUV-569 synergizes with SOC carboplatin and gemcitabine to inhibit tumor growth in breast cancer xenografts Tumor Volume Tumor Volume (mm3) Tumor Volume (mm3) Vehicle Carboplatin NUV-569 70 mg/kg + carbo NUV-569 30 mg/kg + carbo Vehicle Gemcitabine NUV-569 70mg/kg + gemcitabine Days Days
Slide 38: Drug-Drug Conjugate (DDC) Platform
Drug-Drug Conjugate (DDC) Platform Solid Tumors Clinical Candidate Selection By Year End 2022
Slide 39: Drug-Drug Conjugates vs. Antibody-Drug Conjugates
Drug-Drug Conjugates Tissue-selective targeting improves therapeutic index vs. untargeted warhead Oral or IV delivery Binds intracellular and cell membrane targets Highly cell permeable Simpler and less expensive to manufacture Antibody-Drug Conjugates Improves therapeutic index vs. untargeted warhe
Slide 40: DDCs bind two different targets simultaneously
Drug Target X Drug Target Y Drug X Drug Target X Drug X Drug Y Drug Y Fuse Binding Domains TWO SEPARATE DRUGS/ TWO SEPARATE TARGETS DDCs are designed to bind TWO different targets simultaneously Drug Target Y
Slide 41: NUV-1156 targets AR and PARP
PARP AR PARP TWO SEPARATE DRUGS/ TWO SEPARATE TARGETS PARP Inhibitory Warhead AR Targeting Small Molecule Fuse Binding Domains NUV-1156 is a novel drug-drug conjugate that targets AR and PARP AR
Slide 42: NUV-1156 targets high 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, Uterine Endometrium Androgen Receptor Expression Leve
Slide 43: NUV-1156 kills resistant prostate cancer cells
NUV-1156 DDC potently kills prostate cancer cells resistant to current standards of care Cell Proliferation IC50 (nM) >30,000 7844 6152 NUV-1156 (PARP-AR DDC) 201 +
Slide 44: NUV-1156 more potent in prostate cancer cells than gut cells
NUV-1156 is >100-fold more potent at inhibiting cell growth in prostate cancer 22RV1 cells than in IEC6 gut epithelial cells Approved PARP inhibitors have high rates of GI toxicity
Slide 45: NUV-1156 kills HR-deficient and HR-proficient cells
Unlike current PARP inhibitors, NUV-1156 kills HR-Deficient and HR-proficient cancer cell lines with equally high potency NUV-1156 >$7B IN 2025 PROJECTED SALES HR-DEFICIENT 1/3 OF HR-DEPENDENT TUMORS HR-PROFICIENT 2/3 OF HR-DEPENDENT TUMORS
Slide 46: ER expression limited to female sex organs
ER protein expression is limited to female sex organs; Low ER expression in sites of PARP-related toxicity like bone marrow and GI tract Bone Marrow Duodenum Small Intestines Colon Smooth Muscle Fallopian Tube Breast Vagina Cervix, Uterine Endometrium Estrogen Receptor Expression Level Low ER expres
Slide 47: NUV-1176 ER-targeted DDC 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
Slide 48: NUV-1511 suppresses prostate and breast cancer growth
NUV-1511, a DDC derivative of a widely used chemo agent, suppresses prostate and breast cancer growth in xenografts 48 Prostate Cancer CDX Tumor Volume ER+ Breast Cancer CDX Tumor Volume
Slide 49: Adenosine Antagonist
Adenosine Antagonist Advanced Solid Tumors with IO Clinical Candidate Selection by Year End 2022
Slide 50: NUV-1182, an A2A adenosine receptor inhibitor
NUV-1182, an A2A adenosine receptor inhibitor, boosts immune function and may enhance the efficacy of IO-targeted therapies NUV-1182 targets the A2A adenosine receptor A2A adenosine receptor plays multiple critical roles in human physiology and pathophysiology including anti-cancer immunity Accumula
Slide 51: A2A inhibitors increase checkpoint inhibitor activity in melanoma model
Nuvation A2A inhibitors increase the anti-tumor activity of immune checkpoint inhibitors in an in vivo melanoma xenograft model
Slide 52: Upcoming Milestones & Summary
Upcoming Milestones & Summary
Slide 53: Broad wholly-owned pipeline
Broad wholly-owned pipeline leveraging and improving upon validated drug mechanisms heading into multiple clinical trials/indications Program Product Candidate Potential Indication(s) Current Stage Anticipated Milestones Program Product Candidate Potential Indication(s) Potential Indication(s) Precl
Slide 54: Upcoming catalysts across multiple programs
Upcoming catalysts across multiple programs 1H22 2H22 2023 CDK2/4/6 Initiate Phase 1b combo study in HR+ aBC Initiate Phase 1b combo study in mCRPC Phase 1 Dose Escalation Data Phase 2 Mono Initiation for rGB, HR+ aBC, & mCRPC Present First Efficacy Data from High-grade Glioma trial BET Phase 1 Init
Slide 55: Committed team tackling unmet needs in oncology
Committed team tackling the greatest unmet needs in oncology Broad Wholly-Owned Pipeline 3 INDs cleared for NUV-422, a CDK2/4/6 inhibitor, with ongoing studies in brain, breast and prostate cancer NUV-868, a BD2 selective BET inhibitor, entering the clinic for solid tumors Nuv-569, a selective Wee1