Nuvation Bio Inc. · NYSE:NUVB
Nuvation Bio — Panacea Acquisition — SPAC Merger (January 2021)
58 slides from Nuvation Bio's SPAC merger presentation, Jan 5, 2021
Slide 1: Nuvation Bio January 2021 Rule 425 filing
JANUARY 2021 Filed by Panacea Acquisition Corp. pursuant to Rule 425 under the Securities Act of 1933 and deemed filed pursuant to Rule 14a-12 under the Securities Exchange Act of 1934 Subject Company: Panacea Acquisition Corp. Commission File No.: 001-39351
Slide 2: Forward Looking Statements and Disclaimers
Forward Looking Statements and Disclaimers Disclaimer: This presentation (“Presentation”) has been prepared to assist interested parties in making their own evaluation with respect to a potential business combination between Nuvation Bio Inc. (“Nuvation Bio”) and Panacea Acquisition Corp. (“Panacea”
Slide 3: Nuvation Bio Analyst Day meeting agenda
Nuvation Bio Overview & Pipeline NUV-422, a CDK 2/4/6 Inhibitor Drug-Drug Conjugate (DDC) Platform NUV-868, a BET Inhibitor NUV-569, a Wee1 Inhibitor NUV-1182, an A2A Adenosine Receptor Inhibitor Manufacturing Intellectual Property Summary Financial Overview Upcoming Milestones & Conclusion Nuvation
Slide 4: Nuvation Bio Overview & Pipeline
Nuvation Bio Overview & Pipeline
Slide 5: Tackling the greatest unmet needs in oncology
Tackling the greatest unmet needs in oncology Experienced biotech leadership team led by David Hung, which successfully developed major oncology drugs including Xtandi ($3.7B in 2019 sales) and Talzenna Broad wholly-owned pipeline with strong IP protection First IND accepted Oct. 2020, 16 months aft
Slide 6: Highly Experienced Management Team & Board
DAN WELCH Former Chairman and CEO, InterMune ROBERT BAZEMORE CEO, Epizyme KIM BLICKENSTAFF Executive Chairman and Director, Tandem Diabetes Care KATE FALBERG Former CFO, Jazz Pharmaceuticals W. ANTHONY VERNON Former CEO, Kraft Foods Group OLEG NODELMAN Founder and Portfolio Manager, EcoR1 MICHELLE D
Slide 7: Deep Pipeline Targeting Multiple Oncology Indications
Nuvation bio’s Deep Pipeline targeting Multiple Oncology Indications Program Product Candidate Potential Indication(s) Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones CDK 2/4/6 NUV-422 High-grade Glioma Brain metastases ER+ mBC mCRPC December 2020 First patient dosed in Phase 1/2 High-gra
Slide 8: NUV-422 | CDK 2/4/6
High-grade Glioma ER+ mBC mCRPC Brain Metastases Dec 2020 First patient dosed 1H22 Initiate Ph1 trial 2H22 Initiate Ph1 trial 4Q22 Initiate Ph1 trial NUV-422 | CDK 2/4/6
Slide 9: CDK2 drives resistance to CDK4/6 inhibitors
Cdk2 drives resistance to cdk4/6 inhibitors Tumors respond to CDK4/6 inhibition by signaling through CDK2, driving resistance Selectively targeting CDK2 in addition to CDK4/6 may prevent or reverse resistance Addressing Resistance CDK4/6 Inhibitors Three approved CDK4/6 inhibitors CDK4/6 class achie
Slide 10: NUV-422 has good drug-like properties
NUV-422 has good drug-like properties 1st Generation CDK 4 CDK 6 CDK 2 2 2 10000 4 2 2470 2 10 504 CDK 1 10000 10000 1627 2nd Generation CDK 4 CDK 6 CDK 2 PF-06873600 2 4 0.3 NUV-422 2 1 7 CDK 1 2 73 Nuv-422 is a Potent inhibitor of CDK2/4/6 that avoids CDK1 Target selectivity Good oral PK Good CYP
Slide 11: Abemaciclib CDK2 potency and breast cancer trial results
(1) Abemaciclib inhibits CDK2 approximately 5x more potently than palbociclib Abemaciclib’s greater potency against CDK2 may explain the discordant results in the recently reported adjuvant breast cancer trials Cdk2 activity may explain the discordant results in breast cancer trials between first-ge
Slide 12: Abemaciclib improved PFS in newly diagnosed GBM
Abemaciclib (a potent inhibitor of CDK4/6 and a weak inhibitor of CDK2) demonstrated an improvement of progression-free survival (PFS) in newly diagnosed GBM patients in Phase 21 More than 60% of GBM patients exhibit alteration of CDKN2 which regulates CDK2, CDK4, CDK6 2 PFS was significantly longer
Slide 13: Loss of p16 and p21 activates CDK2/4/6
With loss of p16 and p21 (via loss of p14) CDK2/4/6 is activated p14 and p16 are products of the CDKN2A gene CDKN2a deletion (driving CDk 2/4/6) and CDK2 specifically drives growth of Primary high-grade gliomas CDKN2A Gene CDKN2A Deletion is Associated With Worse Survival CDK2 Expression Is Associat
Slide 14: NUV-422 superior to temozolomide in glioblastoma xenograft
NUV-422 is superior to standard of care temozolomide in in vivo xenograft model of glioblastoma multiforme Tumor Volume Vehicle Temozolomide 1 mg/kg NUV-422 10 mg/kg QD NUV-422 30 mg/kg QD NUV-422 60 mg/kg QD NUV-422 60 mg/kg QOD
Slide 15: NUV-422 achieves high concentrations in the brain
NUV-422 achieves High concentrations in the brain Dose (mg/kg) Brain Conc (nM) Plasma Conc (nM) Brain / Plasma Ratio 30 4096 375 11 100 5827 506 12 NUV-422 Concentration Six Hours Post Dose (Rat) ~12X Higher Exposure in Brain vs Plasma
Slide 16: NUV-422-02 seamless Phase 1/2 trial design
Ph2 Dose Expansion in CDKN2A Deleted Patients Ph1 Dose-Escalation in Unselected Population Select RP2D Cohort…. n Cohort 4 Cohort 3 Cohort 2 Cohort 1, 25 mg QD Expansion Cohort 1 CDKN2A deleted relapsed/refractory high-grade glioma (up to 40 pts) with measurable disease OBJECTIVES Safety and Tolerab
Slide 17: NUV-422 active in cell lines of cancers metastasizing to brain
Tumor Types with Brain Mets Breast Colon NSCLC Melanoma CDKN Deleted Solid Tumors (e.g., pancreas) Potent, low nanomolar IC50s seen in cell lines of cancers that commonly metastasize to brain Cell Proliferation (IC50 nM) Beyond primary brain tumors, NUV-422 is active in multiple cell lines of cancer
Slide 18: CDK inhibitors dominate the ER+ breast treatment landscape
Cdk inhibitors dominate THE er+ breast treatment landscape $8B Surgery & Radiation Adjuvant Therapy 1L Metastatic 2L+ Metastatic Salvage Tx Hospice $25B ~500K Patients Annually $4B Positive Ph3 Data from MONARCH-E trial for abemaciclib at ESMO20 suggests role for CDK4/6 inhibitors in adjuvant ER+ br
Slide 19: NUV-422 superior to fulvestrant in ER+ breast cancer xenograft
NUV-422 is Superior to standard of care Fulvestrant in in vivo Xenograft model of ER+ metastatic breast cancer Tumor Volume
Slide 20: Deep tumor reductions in enzalutamide-resistant prostate xenograft
Complete Responses 0% 0% 10% 40% Tumor Volume (Day 39) NUV-422 causes Deep tumor reductions in an Enzalutamide-Resistant Patient-derived prostate cancer xenograft Model
Slide 21: Drug-Drug Conjugate (DDC) Platform
Drug-Drug Conjugate (DDC) Platform DDC1 [PARP-AR] mCRPC DDC2 [PARP-ER] Breast Cancer 2H22 Nominate First DDC Candidate DDC2 [PARP-ER] Ovarian Cancer
Slide 22: DDC platform: advance beyond ADCs
THE Drug-drug conjugate (ddc) platform IS a potentially revolutionary advance beyond adcs Antibody Drug Conjugate Drug-Drug Conjugate Drug-Drug Conjugates Tissue-selective targeting improves therapeutic index vs. untargeted warhead Oral Binds intracellular and cell membrane targets Highly cell perme
Slide 23: DDCs designed to bind two different targets simultaneously
Drug-drug conjugates are designed to bind TWO different targets simultaneously Drug Target X Drug Target Y Drug X Drug Y Drug Target X Drug Target Y Drug X Drug Y Fuse Binding Domains
Slide 24: NUV-1156: DDC targeting AR and PARP
NUV-1156: a novel NUVATION BIO DRUG-DRUG CONJUGATE THAT TARGETs AR AND PARP PARP AR Lynparza Xtandi PARP AR Lynparza Xtandi Fuse Binding Domains Two Separate Drugs / Two Separate Targets PARP Inhibitory Warhead AR Targeting Small Molecule
Slide 25: 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 26: NUV-1156 kills resistant prostate cancer cells
NUV-1156 DDC potently kills prostate cancer cells resistant to current standards of care IC50 (uM) Cell Proliferation IC50 (nM) >30,000 7844 6152 NUV-1156 (PARP-AR DDC) 201 +
Slide 27: NUV-1156 kills HR-deficient and HR-proficient cell lines
Unlike current parp inhibitors, NUV-1156 kills HR-Deficient and hr-proficient cancer cell lines with equally high potency >$7B IN 2025 PROJECTED SALES HR-DEFICIENT (HRD) 1/3 OF TUMORS HR-PROFICIENT (HRP) 2/3 OF TUMORS Prostate cancer TNBC TNBC TNBC NUV-1156
Slide 28: NUV-1156 kills prostate cancer cells but spares healthy colon cells
NUV-1156 KILLS Enzalutamide-resistant prostate cancer (high AR) cells BUT SPARES HEALTHY colon (low ar) cells In VITRO 0.3uM 22RV1 PROSTATE CELLS (CANCER CELLS) IEC-6 RAT GUT EPITHELIAL CELLS (HEALTHY CELLS) APPROVED PARP INHIBITORS HAVE HIGH RATES OF GI TOXICITY (1) Source: Lynparza Label
Slide 29: Prostate cancer market opportunity
~600K Men Annually Surgery & Radiation Androgen Deprivation Tx Combined Androgen Blockade Non-Metastatic CRPC 1L mCRPC R/R mCRPC Salvage Tx / Hospice Erectile Dysfunction Urinary and Fecal Incontinence Invasive Surgical Risk THE Only potentially Curative Procedure for Prostate Cancer currently is Su
Slide 30: Pharmacological prostatectomy vision
NUV-1156 has the potential to kill prostate cancer cells with unprecedented specificity, sparing blood vessels and nerve cells Potentially allows men to avoid surgical prostatectomy/radiation ablation Nuvation bio’s Vision: use prostate specific DDC to achieve a nerve/blood vessel-sparing “pharmacol
Slide 31: 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 gut and marrow Bone Marrow Duodenum Small Intestines Colon Smooth Muscle Fallopian Tube Breast Vagina Cervix, Uterine Endometrium Estrogen Receptor Expression Level Low ER expression in gu
Slide 32: NUV-1176 kills HR-D and HR-P 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 COLON CELLS IEC6 0.3uM ER+ BREAST CANCER CELLS HEALTHY COLON CELLS ER+ Breast cancer ER+, HER2+ Breast cancer ER+ Breast cancer ER+ Breast cancer NUV-1176 HR Deficient HR Proficient
Slide 33: NUV-868 | BET
NUV-868 | BET AML/solid tumors 1H22 Initiate Ph1 trial
Slide 34: BET: Bromodomain and Extra-Terminal motif proteins
BET: BROMODOMAIN AND EXTRA-TERMINAL MOTIF PROTEINS BRD4 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 focu
Slide 35: NUV-868 is a highly selective BD2 inhibitor
NUV-868 is A highly selective bd2 vs BD1 inhibitor BRD4 Affinity BD2 BD1 Selectivity NUV-868 2 2920 1460x ABBV-774 1.05 340 234x CPI-0610 17 85 5x ABBV-075 7 27 3.9x MK-8628 17 26 1.5x INCB-57643 59 81 1.4x BET inhibitors have historically targeted BD1 and BD2 non-selectively, causing GI toxicity an
Slide 36: NUV-868 anti-tumor activity in two AML xenograft models
NUV-868 demonstrates striking anti-tumor activity in two AML xenograft models NUV-868 is highly potent in killing Acute myeloid leukemia (AML) cells in in vivo xenograft Models MV-4-11 Kasumi-1
Slide 37: BD2 selectivity reduces gut toxicity
High selectivity for Bd2 over bd1 significantly reduces the gUT toxicity observed with other bet inhibitors NUV-868 (BD2 Selective) Avoids GI Toxicity ABBV-075 (Dual BD1 / BD2) Vehicle NUV-868 30 mg/kg BID Treatment of mice for 10 days with BD2 selective compound NUV-868 shows no evidence of goblet
Slide 38: NUV-868 deep tumor reductions in prostate xenograft
NUV-868 causes Deep tumor reductions in an Enzalutamide-Resistant Patient-derived prostate cancer xenograft Model Individual Animal Tumor Volume
Slide 39: NUV-569 | WEE1
NUV-569 | WEE1 Pancreatic Cancer/other solid tumors 2H22 Initiate Ph1 trial
Slide 40: WEE1 inhibitors increase efficacy of DNA-damaging therapies
WEE1 Inhibitors increase the efficacy of DNA-damaging therapies by forcing cancers to replicate before they can repair their dna Tumors Activate Their Wee1 Checkpoint Arrest Their Own Replication Giving Them Time to Fix Their Damaged DNA Then Turn Off Their Own Wee1 TUMOR GROWTH Wee1 Inhibitor TUMOR
Slide 41: Promise of existing WEE1 inhibitors limited by tolerability
Ovarian Cancer(1) Uterine Serous Carcinoma(2) Pancreatic Cancer(3) Combo with carboplatin Phase 2 (n): 24 (21 evaluable) ORR: 43% Monotherapy Phase 2 (n): 27 (21 evaluable) ORR: 30% Combo with gemcitabine Phase 2 (n): 34 Median OS of 21.7 months(4) The Promise of Existing WEE1 Inhibitors is limited
Slide 42: PLK1 may be responsible for gut and bone marrow toxicity
PLK1 is a ubiquitous cell kinase that may be responsible for gut and bone marrow toxicity NUV-569 is highly potent against Wee1 but avoids PLK1 unlike AZD1775 10X reduced potency on rat gut epithelial cells (IEC6), relative to AZD1775, suggests these new compounds have significantly improved tolerab
Slide 43: NUV-569 synergy with gemcitabine and radiation
NUV-569 shows strong synergy with standard-of-care gemcitabine and radiation In-vivo xenograft tumor models ongoing In addition to pancreatic cancer, we are also evaluating NUV-569 in breast, ovarian and endometrial cancer NUV-569 significantly increases In Vitro Killing of pancreatic cancer cells b
Slide 44: NUV-1182 | A2A receptor
NUV-1182 | A2A receptor Solid Tumors in Combo with IO 4Q22 Initiate Phase 1 trial
Slide 45: NUV-1182 targets the A2A adenosine receptor
NUV-1182 is focused on targeting the A2A adenosine receptor, which plays multiple critical roles in human physiology and pathophysiology including anti-cancer immunity. Accumulation of adenosine in the tumor microenvironment may be a critical factor in limiting the activity of currently available im
Slide 46: NUV-1182 potent and selective A2A inhibitor
NUV-1182 is a potent and selective A2a vs A1 adenosine receptor inhibitor IC50 (nM) AZD4635 CPI444 AB928 NUV-121 NUV-191 NUV-1182 A2A binding 20 7.1 2.4 2.4 1.4 2.9 A1 binding 366 118 16 21 9.4 234 A2A Selectivity (A2A/A1) 18 16 7 9 7 81 A2A cAMP (400 nM NECA) 1614 1007 70 607 311 441 PPB Hu/Mu (A2a
Slide 47: NUV-1182 PK profile and blood-brain barrier
Brain to plasma ratios are 0.02 to 0.2, demonstrating that NUV-1182 does not effectively cross the blood-brain barrier NUV-1182 currently being tested in several syngeneic tumor models, with tumor volume and tumor infiltrating immune cell profiling and mechanism of action studies NUV-1182 has an att
Slide 48: NUV-1182 increases checkpoint inhibitor activity in melanoma model
NUV-1182 increases the anti-tumor activity of immune checkpoint inhibitors in an in vivo melanoma xenograft model Melanoma CDX Model B16F10 Vehicle Anti-PD1 Anti-PDL1 NUV-1182 NUV-1182 + anti-PD1 NUV-1182 + anti-PDL1
Slide 49: Manufacturing
Manufacturing
Slide 50: Manufacturing Strategy
MANUFACTURING Strategy All Manufacturing and Supply Chain are Outsourced Allows for greater flexibility in production planning and execution More efficient infrastructure, eliminates capital investment Our focus is on rapid development and concurrent execution A Diverse Array of Specialized 3rd part
Slide 51: Intellectual Property
Intellectual Property
Slide 52: Patent Families by Program
Patent Families by Program CDK Program 4 patent families with normal expiration 2039-2040 1 case published DDC Program 3 patent families with normal expiration 2039-2040 2 cases published BET Program 5 patent families with normal expiration 2039-2041 1 case published WEE1 Program 8 patent families w
Slide 53: Financial Overview
Financial Overview
Slide 54: Nuvation Bio financing history
Nuvation Bio was founded on March 20, 2018 by Dr. David Hung $275M raised in June 2019 in a Series A from high profile, experienced investors including Fidelity, Baupost, Omega, EcoR1, Altitude, Citadel, Boxer, etc. Merger with Panacea (EcoR1 sponsored SPAC) and $500M in concurrent financing announc
Slide 55: Upcoming Milestones & Summary
Upcoming Milestones & Summary
Slide 56: Upcoming Catalysts Across Multiple Programs
Upcoming Catalysts ACROSS MULTIPLE PROGRAMS CONFIDENTIAL 4Q20 1H21 2H21 1H22 2H22 1H23 Dosed first patient in Ph1 High-grade Glioma trial Initiate Ph1 in Brain metastases Initiate Ph1 in ER+ mBC Initiate Ph1 in mCRPC Present PFS Data from Ph1 High-grade Glioma trial CDK2/4/6 BET WEE1 A2A Submit IND
Slide 57: Broad wholly-owned pipeline with strong IP protection
Broad wholly-owned pipeline with strong IP protection Up to 5 INDs in 6 years Multiple drug lead candidates addressing large markets with blockbuster drug sales potential Leveraging and improving upon validated drug mechanisms Focused on best-in-class drug candidate profiles vs. competitors Experien
Slide 58: Nuvation Bio
So y . . ae Nuvation Bio aVE y JANUARY 2021