Driven by Science Inspired by Hope - Corporate Highlights October | 2019 - cloudfront.net
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Forward-Looking Statements This presentation may include forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. Such forward-looking statements are subject to significant risks and uncertainties that are subject to change based on various factors (many of which are beyond Cerecor’s control), which could cause actual results to differ from the forward-looking statements. Such statements may include, without limitation, statements with respect to Cerecor’s plans, objectives, projections, expectations and intentions and other statements identified by words such as “projects,” “may,” “will,” “could,” “would,” “should,” “continue,” “seeks,” “aims,” “predicts,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential,” or similar expressions (including their use in the negative), or by discussions of future matters such as: our 2019 outlook; the development of product candidates; timing and success of trial results and regulatory review (including as it may be impacted by government shut- downs); potential attributes and benefits of product candidates; the expansion of Cerecor’s drug portfolio; and other statements that are not historical. These statements are based upon the current beliefs and expectations of Cerecor’s management but are subject to significant risks and uncertainties, including: reliance on and the need to attract, integrate and retain key personnel; drug development costs, timing and other risks; Cerecor’s cash position and the potential need for it to raise additional capital; risks associated with acquisitions, including the need to quickly and successfully integrate acquired assets and personnel; and those other risks detailed in Cerecor’s filings with the Securities and Exchange Commission. Actual results may differ from those set forth in the forward-looking statements. Except as required by applicable law, Cerecor expressly disclaims any obligations or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Cerecor’s expectations with respect thereto or any change in events, conditions or circumstances on which any statement is based. 2|
Overview 1 Cerecor Transformation 2 Cerecor Today 3 Orphan & Neurological Pipeline 4 Financial Highlights 5 Strategic Growth Plans and Outlook 3|
The New Cerecor Creating Near-Term Shareholder Value • 3 Completed Phase I Trials CERC-800s 505(b)(2) 3 Clinical-Stage programs for CDGS • Proof-of-Concept Fast-to-Market Biotech Programs • NDA submissions in in patients next 12 to 18 months • 2 Fast-Track Designations CERC-800s granted Novel 3 RPDD from FDA • CERC-301 in OH • Market value Neurological PRV-eligible • CERC-406 in PD Pipeline Programs approximately $300M ($80 to $130M)* RPDD = Rare Pediatric Disease Designation 4| Last 5 individual PRV’s sold between $80M and $130M; 2017 thru 2019
Management Team Extensive Experience in Development and Commercialization 30+ years industry experience 20+ years industry experience • President and CEO of Chelsea • V.P. Global CMC & Development, Sucampo Therapeutics Pharmaceuticals Dr. Simon • Chief Business and Strategy Officer, Dr. Pericles • CSO, Pharming Group Pedder Proprietary Products at Athenex Calias • Sr. Director Rare CNS Diseases and Device • Vice President of Oncology Pharma Lead, Shire plc Executive Business at Hoffmann-LaRoche Chief • Sr. Director Drug Delivery and Chemistry, Chairman of the Scientific Officer • Franchise Head of Hepatitis at Eyetech Pharmaceuticals Board & Head of R&D Hoffmann-LaRoche • Ph.D., Tufts University, Bioorganic • Faculty Department of Pharmacology Chemistry College of Medicine, University of Saskatchewan 20+ years industry experience 25+ years industry experience • Vice President of Finance, Sucampo • Sr. Vice President | Principal Pharmaceuticals The NSCI Group Joseph • Senior Director of Accounting, Qiagen James A. • General Manager Specialty Miller • Chief Financial Officer, Eppendorf 5Prime Harrell Pharmaceuticals, Covidien • Certified Public Accountant Chief • Vice President Marketing Pediatric Chief Infectious Disease, MedImmune Commercial Financial Officer Officer • Sr. Director Marketing IMIDs, Centocor a J&J Company • Product Manager & Hospital Specialist, ATOD Rhone Poulenc Rorer 5|
Transforming Cerecor to Deliver Shareholder Value Three Expected Orphan Disease Product Launches Within the Next Three Years a Neurological Pipeline in Markets of Substantial Size and Unmet Need 2017 2018 2019 2016 CERC-301 misses primary Acquisition Acquisition Pipeline Progression endpoint in Phase II TRx Pharma Avadel (AVDL) CERC-301 IP extended to 2035, in Major (Zylera) Pediatric assets positive Phase I PoC in nOH Depressive Disorder CERC-800s receive ODD CERC-801 & 802 receive FTD, completed Phase I in HVs Out-license Acquisition Asset Divestiture CERC- 501 licensed to Ichorion CERC-611 out-licensed to Janssen Rare Disease Pipeline ES Therapeutics Pediatric Commercial Pipeline Progression Portfolio sold for > $43M in total value CERC-301 re-purposed in Orthostatic Hypotension CERC-800s receive RPDD 6|
Recent Transaction Strengthens Balance Sheet Sale of Pediatric Portfolio Extends Financial Runway and Provides Non-Dilutive Financing for R&D Cerecor Transaction Highlights • Overall deal valued in excess of $43M – Composite of $17M in cash and preferred stock ($4.5M in cash & 12.5M of AYTU stock) • Assumption of Cerecor’s outstanding payment obligations payable to Deerfield CSF, LLC (“Deerfield Note”) and other liabilities in excess of $15 million • Elimination of existing royalty obligations & various commercial accruals of $11 million • The Pediatric Portfolio includes the following five product lines: Aciphex® Sprinkle™, Cefaclor for Oral Suspension, Karbinal® ER, Flexichamber™, Poly-Vi-Flor® and Tri-Vi-Flor™ • Estimated annual expense reduction of $7 to $9 million associated with Commercial Sales organization transfer to AYTU • Company to fund its portfolio of development assets focusing on near-term value drivers; including NDA submissions for CERC-800s and the expansion of the CERC-301 program 7|
Cerecor Today Focused on Advancing Emerging Clinical & Early-stage Pipeline to Critical Value Inflection Points Pediatric Orphan Disease Pipeline Neurological Pipeline • Substrate replacement therapies for Inborn • Novel mechanisms-of-action with clinical Errors of Metabolism (IEMs) proof-of-concept and opportunity for strong clinical differentiation • Three 505(b)(2) programs granted ODD and RPDD (PRV eligible) • Completed Phase I program demonstrating robust and sustained BP effect in patients • Expedited path(s) to NDA with three suffering from neurogenic Orthostatic anticipated NDA filings in 2021 & 2022 Hypotension (nOH) • Two completed Phase I programs with Fast • Expanding clinical development in OH Track Designation (FTD) adjacencies of Diabetic OH (DOH) and • CDG FIRST retrospective study ongoing Intradialytic Hypotension (IDH) • Neurological markets with large commercial opportunity & significant unmet needs 8|
Emerging Clinical & Early-Stage Pipeline Mechanism Lead Program Development Stage of Action Indication D-Galactose CERC-801 PGM1-CDG Phase 1 Complete 505(b)(2) replacement Metabolic Disorders D-Mannose CERC-802 MPI-CDG Phase 1 Complete 505(b)(2) replacement L-Fucose CERC-803 SLC35C1-CDG IND-Enabling 505(b)(2) replacement Nucleoside DGUOK CERC-913 Pre-Clinical replacement Deficiency NMDA receptor Orthostatic CERC-301 Neurology Phase 1 Complete in nOH Disorders antagonist Hypotension CNS-targeted Parkinson’s CERC-406 Pre-Clinical COMT inhibitor Disease Denotes Pediatric Program and Expedited 505(b)(2) Approval Pathway Denotes Pediatric Program Denotes Neurology Program 9|
Pipeline Provides Strategic Optionality World-Wide Estimated Patient Populations Clinical 240M Develop Internally & Proof-of-Concept 185M Commercialize Independently OH >65 Toward Strategic Partnership Orphan Pediatric Diseases Larger CNS Indications 50M Diabetic OH 1.9M 2.9M SCI OH 1.7M 500 500 nOH 250 50 655k IDH CERC-801 CERC-802 CERC-803 CERC-913 CERC-301 CERC-406 PGM1-CDG MPI-CDG SLC35C1-CDG DGUOK Orthostatic Parkinson’s Deficiency Hypotension Disease 10| IDH = Intra-Dialytic Hypotension; nOH = Neurogenic Orthostatic Hypotension; SCI = Spinal Cord Injury; DM = Diabetes Mellitus
R&D Milestones Multiple Potential Value-Generating Inflection Points Over Next 12 to 18 Months Program Target Indication Upcoming Milestone FDA Meeting Request YE19 CERC-801* PGM1-CDG Targeted NDA Submission 2021 Metabolic Disorders FDA Meeting Request 1H20 CERC-802* MPI-CDG Targeted NDA Submission 2021 IND Filing 2020 CERC-803* SLC35C1-CDG Targeted NDA Submission 2022 Initiate Proof-of-Concept in CERC-301 Orthostatic Hypotension Additional Indication(s) YE19 Neurology Disorders Initiate Phase II 2020 CERC-406 Parkinson’s Disease IND Filing 2020 11| *505(b)(2) Pathway
Pediatric Orphan Disease Portfolio CERC-800s CERC-913
Congenital Disorders of Glycosylation (CDG) Genetic Diseases that Result in Impaired Glycoprotein Production and Function, but are Treatable with Substrate Replacement Therapy Glycosylation is essential for protein Factor XI structure & function, particularly for Thrombin circulating proteins and enzymes such Liver enzymes as hormones and coagulation factors Hemoglobin Some CDG patients lack the ability to effectively utilize monosaccharide Normal Glycosylation 3 Pattern substrates for glycoprotein synthesis due to a single enzyme defect Substrate replacement with monosaccharides can compensate for Substrate replacement 2 w/ oral monosaccharides enzyme deficiencies Treatment with oral monosaccharides results in improvement in serum biomarkers of glycosylation, which can correlate with clinical benefit Glycosylation Deficiency 1 due to CDG 13|
CERC-800s Substrate Replacement Therapies for CDGs Monogenic Disorders Resulting in Glycoprotein Defects with Broad Clinical Spectrum, Including Life-threatening Complications Multi-system disease manifestation in PGM1-CDG CERC-801 D-Galactose leads to significant improvement in key clinical symptoms Life-threatening gastrointestinal disorder in MPI-CDG CERC-802 D-Mannose rapidly resolves hematological & intestinal abnormalities Immunodeficiency with CNS impairment in SLC35C1-CDG CERC-803 L-Fucose normalizes cell counts & reduces infection risk Ultra-orphan IEMs with Serious and Life-threatening Medical Needs • Symptoms evidenced by serum •
CERC-800s Substrate Replacement Therapies for CDGs Oral, Small Molecule, Naturally Occurring Monosaccharides Used as Standards-of-care for CDGs • Rapid onset of action • Safe and well-tolerated • Symptoms return upon treatment withdrawal D-Galactose D-Mannose L-Fucose Eligibility CERC-801 CERC-802 CERC-803 505(b)(2) NDA Pathway ✓ ✓ ✓ NCE 5-yrs Exclusivity ✓ ✓ ✓ FDA ODD 7-yrs Exclusivity ✓ ✓ ✓ EMA ODD 10-yrs Exclusivity ✓ ✓ ✓ Priority Review Voucher ✓ ✓ ✓ 15|
The Value of a Priority Review Voucher Recent PRV Sales with Purchase Amount (in millions) The Mean purchase price over the past 5 years has been $140M $200 The Median purchase price over the past 5 years has been $125M $125 $130 $125 $130 $110 $105 $81 $80 2016 2016 2017 2017 2017 2017 2018 2018 2019 16| Reference: https://priorityreviewvoucher.org/ downloaded April 24, 2019
CDG FIRST: Cerecor-Initiated Retrospective Study in CDG Retrospective Chart Reviews & Registry Data Have Been Successfully Used to Minimize or Obviate Prospective Clinical Studies Developer Therapeutic (Indication) Pivotal Study Strategy Retrospective case series summary (13/23 patients Carbaglu with complete data) & 3 patients treated (NAGS Deficiency) prospectively (2010) Case report form from retrospective chart review of Cholbam patients in open-label, single-arm Expanded Access (Bile Acid Disorders) Protocol (2015) Retrospective case reports from a multicenter chart ProVay Blue review in addition to cases found in published (Acquired Methemoglobinemia) literature (2016) Expanded label (from 10 mutations to 33) based on Kalydeco registry data & mechanistic information from lab (Cystic Fibrosis) studies (2017) Reference to survival data from an international Lumizyme registry of infantile-onset disease demonstrating (Pompe Disease) mortality benefit (2010) CDG Connect Patient Insights Network (PIN) https://connect.invitae.com/org/cdg 17|
CDG FIRST Global Site Selection & Recruitment Multi-center, International, Non-interventional, Retrospective Study of CDG Patients to Collect Natural History and Treatment-related Data North America Europe Cerecor plans to leverage data from CDG FIRST Trial and other sponsor-initiated studies to accelerate development and approval under the 505(b)(2) pathway, with our targeted NDA filing for CERC-801 in 2021 CDG Connect Patient Insights Network (PIN) https://connect.invitae.com/org/cdg 18|
Key CERC-800s Milestones Multiple Potential Value-Generating Inflection Points Over Next 12 to 18 Months • Type B Meetings with FDA to clarify path to NDA – Briefing package expected to include data collected under CDG FIRST – Determine if pivotal study requirement and/or design Program Target Indication Upcoming Milestone • Type B Meeting 2020 CERC-801 PGM1-CDG • BTD Request 2020 (D-Galactose) • NDA Submission 2021 505(b)(2) NCEs • Type B Meeting 2020 CERC-802 MPI-CDG • BTD Request 2020 (D-Mannose) • NDA Submission 2021 • IND Filing 2020 CERC-803 SLC35C1-CDG • BTD Request 2020 (L-Fucose) • NDA Submission 2022 19| BTD = Break Through Therapy Designation
Deoxyguanosine Kinase (DGUOK) Deficiency Ultra-rare, Inborn Error of Metabolism Due to Loss-of-function Mutations in DGUOK • Inability to produce deoxyguanosine monophosphate (dGMP) results in depletion of mitochondrial DNA (mtDNA), leading to organ dysfunction • Most frequently mutated gene in patients with early hepatocerebral mtDNA depletion syndrome; estimated prevalence of 1 in 500,000 • Severe depletion (>90%) of mtDNA relative to healthy individuals • Two forms: neonatal multisystem disorder that presents in early infancy and isolated hepatic disorder that presents later in infancy or childhood • Liver involvement is the most prominent feature, leading to liver cirrhosis and causing early-onset liver failure • Liver transplant can benefit patients with isolated hepatic disease, but less so for patients with moderate to severe neurological symptoms • 5-Year Overall Survival
CERC-913 dGMP ProTide for DGUOK Deficiency Overcome Key Limitations of Direct Substrate Replacement • The ProTide nucleotide offers plasma stability, improved permeability and intracellular activation dGMP Unstable in Plasma Poor Permeability Phenotypic Rescue CERC-913 Stable in Plasma Good Permeability 21|
Neurological Disorders CERC-301 CERC-406
Orthostatic Hypotension (OH) Autonomic Nervous System Fails to Regulate Vasoconstriction Due to Underlying Neurological Disease Rapid and Significant (20mm Hg) Drop in Systolic Blood Pressure (SBP) Induced by Postural Change • Increased risk of falls or injury, leading to decreased quality of life • Estimated approximately 300k patients in U.S. and 1.5mm WW Two FDA-Approved Therapies, Northera® (droxidopa) & Midodrine Northera® Midodrine • Norepinephrine pro-drug acting upon • Vasoconstrictor / Hypertensive Agent adrenergic receptors • α-adrenergic receptor agonist producing an increase • Effectiveness beyond 2 weeks of treatment in vascular tone and elevation of blood pressure has not been established • Pro-drug with half-life ~25 minutes • High rate (>1/3) of non-responders • Dosing Q6 to Q8 Daily • Estimated 40K TRx Annually in the US Jun’19-Jul’18 • Estimated 1.6M TRx Annually in the US Jun’19-Jul’18 • Estimated Gross $349M Jun19-Jul’18 • Estimated Gross $457M in Annual Sales Jun’19-Jul’18 CERC-301 (Formerly Known as MK-0657) • Established safety profile in ~400 patients and healthy volunteers • Several studies demonstrated rapid and sustained increase in SBP without an increase in heart rate 23|
Phase I Study Design in PD Patients with nOH Opportunity to Efficiently Demonstrate Proof-of-concept in Patients Phase I SAD in PD Patients with nOH Visit 1 Visit 2 Visit 3 Visit 4 Visit 5a Enrollment • 12 active centers in US Arm 1 pbo 8 mg 12 mg 16 mg 20 mg (n = 5) • N = 20 (8, 12, 16 & 20 mg) Arm 2 • Double-blind, randomized, 8 mg pbo 12 mg 16 mg 20 mg Design (n = 5) pbo-controlled • Interim Analysis at 10 patients Arm 3 8 mg 12 mg pbo 16 mg 20 mg (n = 5) • Safety, Tolerability & PK Endpoints • BP measurement Arm 4 8 mg 12 mg 16 mg pbo 20 mg • Symptomatic assessment (n = 5) • 5 visits (7 to 10 days apart), 4 single escalating doses of CERC-301 or placebo • Assess safety, tolerability & pharmacokinetics • Measure BP effects during orthostatic standing test (OST) pre- and post-dose • Symptomatic assessment (OHSA Item #1) at each visit 24| a Randomized 4:1
CERC-301 Improves Blood Pressure Upon Standing 20mg dose results in +29.8mm Hg increase in standing SBP over placebo at 6-hour post- dose during an Orthostatic Sanding Test 20mg vs Placebo pre-dose vs 6-hours post-dose 155 Semi-Supine Standing +29.8 SBP (mm Hg) 135 115 CERC-301 reduces the magnitude of SBP drop following an OST 95 SBP SBP SBP SBP SBP SBP SBP SBP Seated -10 mins -5 mins Imed Prior +1 min +3 min +5 mins Seated Placebo - PD 20 mg - PD Placebo - 6hr 20 mg - 6 Hr 25|
CERC-301 PK Data Consistent and Predictable Pharmacokinetic Profile Across All Doses Studied CERC-301 Plasma Concentrations 450 400 350 300 250 8 mg ng/Ml 200 12 mg 16 mg 150 20 mg 100 50 0 0 0.5 1 2 4 6 -50 Nominal Time in Hours 26|
Positive Phase I Data in nOH Final Phase l Results Depict a Rapid, Robust and Durable Increases in SBP in PD Patients with nOH • All doses demonstrated clinically meaningful increases in SBP over placebo within the 6-hour post-dose timepoints – 20mg dose demonstrated a 15.2 mm Hg increase in SBP from baseline at 1-hour post-dose, which improved to 29.1 mm Hg from baseline at 4 hours – Early and sustained effect may differentiate CERC-301 from existing nOH / OH treatments • All doses tested were safe and well-tolerated with no serious adverse events • Opportunity to develop CERC-301 for additional indications characterized by hypotension (i.e. diabetics, hemodialysis, elderly populations) – Northera® limited to norepinephrine-deficient patient population(s) – CERC-301’s mechanism-of-action is potentially more broadly applicable – Initiate additional proof-of-concept study in OH population(s) by YE19 27|
CERC-301: A Pipeline Within a Product CERC-301’s Differentiated Profile Expands Addressable Patient Population to Additional Diseases Characterized by Low Blood Pressure Neurogenic Orthostatic Diabetic Orthostatic Intradialytic Hypotension Hypotension Hypotension (IDH) Estimated Patient Population Estimated Patient Population Estimated Patient Population 46.2M 3.0M 1.5M 220K 250K 405K US ROW US ROW US ROW Phase I Demonstrated Rapid, Initiating Phase I in Patients Initiating Phase II in Patients Robust & Sustained BP Effect by YE 2019 in 2020 in Patients • Large target addressable markets with limited therapeutic options – Northera® and midodrine act as direct adrenergic agonists with narrow clinical utility, resulting in unmet medical needs – Clinical proof-of-concept throughout 2019 and 2020 will create an opportunity for strategic partnership(s) 28| Population estimates at mean values from the literature
Phase I Study Design in Diabetic OH Further Assess Durability of BP Effect to Facilitate Phase 2 Study Design OST Performed @ 1, 2, 4 , 6, 12 and 24 Phase I Single Dose Study in Diabetic OH Hours Post-dose Enrollment • N = 10, single center Postural Change • Single 20 mg dose or placebo Supine Standing Design • Double-blind, randomized, -10 -5 0 +1 +3 +5 two-way crossover min min min min min min X X X X X X • Safety (HbA1c monitoring ) • Tolerability & PK Endpoints X = measure systolic/diastolic blood • BP measurement • Symptomatic assessment pressure and heart rate • 2 visits (7 to 10 days apart), single 20mg dose of CERC-301 or placebo • Assess safety, tolerability & pharmacokinetics • Measure BP effects before and after an OST for up to 24 hours post-dose • Symptomatic assessment (OHSA Item #1) at each visit 29| a Randomized 4:1
Phase 2 Study Design in Intradialytic Hypotension Well-defined Clinical Setting Facilitates Recruitment, Shared Opportunity for Hemodialysis (HD) Centers with Expected Study Start in 2020 • Clinical Endpoint: change in the Number of Hypotension-induced Interventions During Hemodialysis (HD) Sessions N = 75 12mg /20mg 301 Group A Randomization End of Study 2-week lead-in baseline 12mg/20mg 301 Group B evaluation period A = dose 1 hour prior to HD B = dose 2 hours prior to HD Placebo Group 4-week treatment period Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 12 Week Study Duration with Hemodialysis 3x / week (18 sessions) 30| a Randomized 4:1
CERC-406 COMT inhibitor for Parkinson’s Disease Highly-Selective with Greater CNS Permeability for Potentially Improved Efficacy • COMT regulates dopamine (levodopa) breakdown via the conversion of dihydroxyphenyl-acetic acid (DOPAC) to homovanillic acid (HVA) 1st Gen COMT Drawbacks / CSF Biomarkers: Inhibitors Marketing Status Single, 100 mg/kg CERC-406 Dose in Rats DOPAC HVA black box warning Tolcapone 300 120 generic 250 100 DOPAC (% of Control) ** HVA (% of Control) peripherally- 200 80 Entacapone restricted 150 60 generic 100 40 ** peripherally- 50 20 Opicapone restricted NDA Filed 7/19 0 0 Veh CERC-406 Veh CERC-406 31|
Key Financial Information
Financial and Investor Information Key Financial Indicators as of October 3, 2019 (Subject to Change) Stock Information Investor Information • Founded January 31, 2011 • 44.1M Shares Outstanding • NASDAQ listed CERC • Analyst Coverage (12 month target price) • IPO – October 16, 2016 – Michael Higgins Ladenburg Thalmann ($9.00) – Jason McCarthy Maxim ($10.00) • Initiated at $6.50 – Ram Selvaraju HC Wainwright ($11.00) – 4M Units @ $6.50 for $26M • Added to Russell 3000 Index July 1, 2019 • Stock Range (52 weeks 10/3/19) – 52 week high $7.66 Financial Information – 52 week low $2.71 • Cash Position June 30, 2019 = ~$10M • Average Volume 80,390 • Ongoing Revenue from Millipred® • Market Cap in excess of $130M – Estimated 2019 Gross Margin of $5–$6M – Provides Strategic Optionality 33|
2019 Growth Plans Recent Events Increase Shareholder Value by Strengthening Balance Sheet to Prioritize Pipeline Development 1 2 3 Advance Accelerate Business Commercial Readiness Pipeline Development Activity Advance CERC-800s to Build commercial footprint for Out-license or partner NDA filings and launch pediatric orphan disease in indications and/or preparation for 2021 launch geographies Provide further clinical proof-of-concept in Increase market knowledge Acquire/in-license adjacencies for CERC-301 and and insights for pricing / complimentary initiate Phase 2 program reimbursement and pipeline assets distribution strategies Advance CERC-406 and CERC- 913 into Phase I studies Develop go-to-market strategy for CERC-800s 34|
Driven by Science Inspired by Hope NASDAQ:CERC www.cerecor.com
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