Palatin Technologies, Inc. · AMEX:PTN
Palatin Technologies — Investor Day (May 2021)
66 slides from Palatin Technologies's investor day presentation, May 21, 2021
Slide 1: Melanocortin Agonists for Ocular Diseases
Melanocortin Agonists for Ocular Diseases May 21, 2021
Slide 2: Agenda
Agenda Introduction Speakers Corporate update Introduction to the Melanocortin System Andrew W. Taylor, Ph.D. Palatin Melanocortin Overview John H. Dodd, Ph.D. Dry Eye Disease & PL9643 Phase 2 Data Eric Donnenfeld, MD Melody 1: PL9643 Phase 3 Clinical Trial George Ousler Retinopathy Preclinical data
Slide 3: Introduction to Speakers
Introduction to Speakers Guest Speakers Andrew W. Taylor, Ph.D. Associate Dean of Research & Professor of Ophthalmology Boston University School of Medicine Eric Donnenfeld, MD Clinical Professor of Ophthalmology New York University School of Medicine George Ousler Senior Vice President Anterior Seg
Slide 4: Development Programs
Development Programs Clinical Pipeline Melanocortin Receptor Programs Pre-clinical Phase 1 Phase 2 Phase 3 NDA Submission FDA Approval Status/Next Steps FDA Approval 6/21/2019. Licensees: Vyleesi® (bremelanotide) Fosun (China, Taiwan, HK, Macau) and Kwangdong (S. Korea) Seeking Hypoactive Sexual Des
Slide 5: FDA Approved Vyleesi®
FDA Approved Vyleesi® Helping Premenopausal Women with Hypoactive Sexual Desire Disorder (HSDD) Improvements to Commercial Infrastructure - Renegotiated supply agreements - Realigned Specialty Pharmacies - Added KnippeRx - Improved PA process - Streamlined HCP and patient experience - Changed Teleme
Slide 6: Financial Snapshot
Financial Snapshot Financial Highlights as of March 31, 2021 Cash and Cash Equivalents $68.6 million Working Capital $69.4 million No Debt Summary Capitalization as of March 31, 2021 Common Shares and Equivalents Common Stock 230.1 million shares Preferred 0.1 million shares Warrants 12.6 million sh
Slide 7: What are Melanocortins?
What are Melanocortins? Investor Day May 21, 2021
Slide 8: Melanocortin Neuropeptides
Melanocortin Neuropeptides Pro-opiomelanocortin Prohormone convertase 1 Pro-ACTH ßLPH Prohormone convertase 2 Carboxypeptidase Peptidylglycine α-amidating monooxygenase N-POC JP ACTHC γLPH ßEND N-acetyltransferase γMSH ACTH1-17 CLIP ßMSH αMSH ACTH SYSMEHFRWGKPVGKKRRPVKVYPNGADDESAEAFPLEF Hypothalamus
Slide 9: Melanocortin Receptors
Melanocortin Receptors MC1r MC2r • α-MSH = ACTH > ß-MSH > γ-MSH • ACTH only • Skin, Melanocytes, Keratinocytes, Endothelial cells, Mucosal cells, Adipocytes, Chondrocytes, Osteoblasts, Macrophages, Monocytes, Dendritic cells, Mast cells, Neutrophils, T cells, B cells MC3r MC4r MC5r • γ-MSH > ACTH =
Slide 10: Activity of Melanocortins
Activity of Melanocortins • Pigmentation • Stimulation of melanogenesis and the modulation of proliferation of melanocytes and melanoma cells • MC1r is a major determinant of mammalian pigmentation • Metabolism • Complement of leptin in the endocrine circuit, regulating bodyweight, food intake, and
Slide 11: Melanocortins and Immunobiology
Melanocortins and Immunobiology • Suppression of endotoxin induced-inflammation (monocytes and neutrophils) • Suppression of CHS • Induction of MC1r expression and α-MSH production in macrophages (self-sustaining regulatory loop) • Induction of suppressor APC • Suppresses phagosome maturation (alter
Slide 12: Effects of Glucocorticoids and α-MSH on the Eye
Effects of Glucocorticoids and ⍺-MSH on the Eye Glucocorticoid α-MSH Immune effects • Suppresses proinflammatory signals • Suppresses proinflammatory signals • Suppresses immune cell activity • Promotes production of anti-inflammatory cytokines • Induces suppressor antigen-presenting cells • Induces
Slide 13: What Role do Melanocortins Have in Ocular Immunobiology?
What Role do Melanocortins Have in Ocular Immunobiology?
Slide 14: What Is Ocular Immune Privilege?
What Is Ocular Immune Privilege? • The result of integrated biological systems (neural, immune, and visual) that exist within a blood-barrier with no direct lymphatic drainage • A tissue site that affords prolonged allograft survival • An evolutionary adaptation of an organ that needs to minimize th
Slide 15: Why Study Immune Privilege?
Why Study Immune Privilege? Understanding the mechanisms of ocular immune privilege provides us with insight into what is necessary to have a healthy ocular microenvironment, along with potential biomarkers of health and therapeutic efficacy, and to identify new, well-tolerated molecules for ocular
Slide 16: Active Mechanisms—Soluble Factors
Active Mechanisms—Soluble Factors Factor Activity TGFß2 Suppresses activation of T cells, NK cells, MØ, promotes tolerance-inducing APCs α-MSH • Converts IFN-producing T cells into regulators • Inhibits PMN activation, works with NPY to induce suppressor MØ • Antagonizes LPS, IL-1, TNF-mediated infl
Slide 17: Active Mechanisms—Membrane-Bound Factors
Active Mechanisms—Membrane-Bound Factors Factor Activity Fas Ligand Induces apoptosis in T cells and neutrophils CD86 Inhibits T cell activation DAF Inhibits complement cascade Galectin-1 Inhibits T cell activation MHC Class 1b Inhibits NK and CTL killing TRAIL Induces apoptosis in MØ and neutrophil
Slide 18: Role of Melanocortin Receptors and α-MSH in Ocular Immune Privilege
Role of Melanocortin Receptors and a-MSH in Ocular Immune Privilege MC5r α-MSH NPY LPS α-MSH Th1 cells MØ Suppressor Macrophages A CGRP g SOM MC1r, MC3r MC5r Alternatively Activated Ag Primed T APC cell α-MSH Th1 cells VIP α-MSH SOM α-MSH MC1r, Primed T MC5r CD25+CD4+ Treg cell MC5r α-MSH cell 18 Cl
Slide 19: Effects of α-MSH Treatment on EAU
Effects of a-MSH Treatment on EAU Effects of a-MSH Treatment on EAU 4 3 EAU Score 2 1 EAU + Vehicle EAU + αMSH 0 1 2 3 4 5 6 7 8 9 10 11 12 19 Treatment
Slide 20: Retinal Histology of α-MSH treated EAU
Retinal Histology of a-MSH treated EAU Healthy Untreated a-MSH 20
Slide 21: Drug Targets in Uveitis
Drug Targets in Uveitis ustekinumab Monocyte IL-12 IL-6 Infliximab Adalimumab Macrophage / Th17 Golimumab Microglial cells Th17 Certolizumab Th1 TNFa Etanercept TNFa TNFa IL-6 IL-6 ROS VEGF IL-1β TNFa IL-1β VEGF EC RPE Tocilizumab Bevacizumab Ranibizumab Photoreceptor Blood-Barrier Leakage Inflammat
Slide 22: α-MSH Targets in Uveitis
a-MSH Targets in Uveitis Ocular Microenvironment Becomes Immunosuppressive? a-MSH Monocyte IL-12 IL-6 a-MSH Macrophage / Th17 Microglial cells Th17 Th1 TNFa TNFa TNFa Suppressor APC IL-6 IL-6 ROS Counter-Conversion VEGF IL-1β TNFa IL-1β VEGF EC RPE Treg Photoreceptor Reestablished Suppression Surviv
Slide 23: α-MSH Targets in the Diseased Ocular Microenvironment
a-MSH Targets in the Diseased Ocular Microenvironment a-MSH Monocyte IL-12 MC5r MC1r MC3r MC5r IL-6 a-MSH Macrophage / Th17 Microglial cells Th17 Th1 TNFa TNFa Suppressor APC TNFa IL-6 IL-6 ROS Counter-Conversion VEGF IL-1β IL-1β VEGF TNFa EC RPE Treg MC1r Photoreceptor Reestablished Suppression Sur
Slide 24: Conclusions
Conclusions • a-MSH peptides are highly effective in suppressing EAU • Stimulating the melanocortin receptors is not just an antagonism of pro-inflammatory signals but a change in cellular behavior (contrast with steroids and biologics) • The melanocortin induction of regulatory immunity could be a
Slide 25: Investor's Day
Investor's Day & PALATIN May 21, 2021
Slide 26: Key to Success – The Right Compounds for the Right Indications
Key to Success – The Right Compounds for the Right Indications Melanocortin System Commercially Inflammatory Disease Successful Product Potential ? ● The most acceptable route of administration ● Optimal potency/selectivity/efficacy ● Excellent safety profile ● Clear advantage over existing/future t
Slide 27: Two Compounds – Ulcerative Colitis and Dry Eye Disease
Two Compounds – Ulcerative Colitis and Dry Eye Disease PL8177 OCD (oral, colon delivery) PL9643 (topical drops) • Selective MC1r agonist for Ulcerative • Pan Melanocortin agonist for Dry Eye Colitis Disease • Oral route of administration • Topical drops • Local site of action – no systemic • Local s
Slide 28: MC1r Selective PL8177 OCD Properties
MC1r Selective PL8177 OCD Properties Superior potency and stability to the endogenous ligand – a-MSH Potency • Cellular in vitro assays demonstrate 640 times more potency (14 picomolar) than the endogenous ligand • a-MSH in human cells – allows practical dosing levels Selectivity • Inactive at MC2r,
Slide 29: Pan Melanocortin Agonist PL9643 Properties
Pan Melanocortin Agonist PL9643 Properties Superior potency and stability to the endogenous ligand – a-MSH Potency Stability • More potent in cellular in vitro functional assays • Cyclic peptide structure inhibits proteolysis and compared to a-MSH (EC50, nanomolar, nM) degradation, significantly mor
Slide 30: Back of the Eye Research Progress – PL9654
Back of the Eye Research Progress – PL9654 • Palatin melanocortins have been evaluated in several animal models of retinal disease. We have observed effects equal to anti-VEGF therapy • Progress is being made on identifying the formulation and route of administration for advancement into development
Slide 31: Summary: PL8177 and PL9643
Summary PL8177 PL9643 Oral route of administration, high Topical administration, high potency, potency, no systemic exposure, no systemic exposure, excellent extreme selectivity, and excellent pre-clinical efficacy, rapid onset of preclinical efficacy result in a product action and no tolerability i
Slide 32: Dry Eye Disease
Dry Eye Disease May 21, 2021 Eric Donnenfeld, MD
Slide 33: What Is Dry Eye Disease?
What Is Dry Eye Disease? • Dry eye is extremely common and is often underdiagnosed1 • Dry eye can negatively impact vision quality and can cause blurred vision, fluctuating vision, reduced contrast sensitivity, and increased glare2-4 • Quality of life and daily activities can be greatly impacted by
Slide 34: Background
Background • Dry eye disease • Multifactorial inflammatory and aqueous tear deficient disorder affecting the cornea and conjunctiva1,2 • Characterized by ocular irritation and potential visual impairment1,2 • Existing dry eye therapies are often regarded as inadequate by many physicians and patients
Slide 35: Prevalence of Dry Eye Disease
Prevalence of Dry Eye Disease Salisbury Study Melbourne Study Beaver Dam Study WHS Study 14.4% 5.5% 14.4% 6.7% However, the percentage of individuals who experience signs and symptoms of dry eye at one time or another due to environmental factors is 100%. 35
Slide 36: DED Is One of the Most Common Eye Diseases in the United States
DED Is One of the Most Common Eye Diseases in the United States1 29 million = 1 out of every American 7 Adults2,3,a AMERICAN ADULTS suffer from symptoms of DED2,3,a a Aged 25 to 84 years. 1. Schaumberg DA et al. Am J Ophthalmol. 2003;136(2):318-326. 2. Paulsen AJ et al. Am J Ophthalmol. 2014;157(4):
Slide 37: DED Deserves Increased Attention
DED Deserves Increased Attention Symptoms of DED • 30% of patients who seek treatment from an ophthalmologist and are among the most 40% from an optometrist have symptoms consistent with DED2 common complaints1 – Reduce work productivity3,4 DED may impair patients’ ability to – Impair the ability to
Slide 38: Phase 2 Study Evaluating PL9643 Compared to Placebo in Dry Eye
A Phase 2, Multi-center, Randomized, Double- Masked, Placebo-Controlled Study Evaluating the Efficacy and Safety of PL9643 Ophthalmic Solution Compared to Placebo in Subjects with Dry Eye
Slide 39: Study Design
Study Design 12-week Phase 2, multicenter, 1:1 randomized, double-masked, placebo-controlled study Primary Screening Randomization analysis Week –2 0 2 4 6 8 10 12 Placebo 1 µg/mL PL9643 ophthalmic solution 3 times daily run-in N=160 Placebo/Vehicle ophthalmic solution 3 times daily Visit CAE® CAE®
Slide 40: Co-Primary Endpoints & Patient Population
Co-Primary Endpoints & Patient Population • Co-primary endpoints measured as change from baseline to Week 12: • Sign: Inferior corneal fluorescein staining • Symptom: Ocular discomfort • Overall intent-to-treat (ITT) population (N = 160) • Patients with mild, moderate, or severe dry eye disease • No
Slide 41: LS Mean Change from Baseline: Fluorescein Staining
Differences between PL9643 and placebo (least squares mean change from baseline) in fluorescein staining in the Moderate-to-Severe Subgroup – observed data only Total Corneal Total Total Sum (inferior + Conjunctival (corneal + superior + (temporal + conjunctival) central) nasal) Nasal Temporal Infer
Slide 42: LS Mean Change from Baseline: Lissamine Green Staining
Differences between PL9643 and placebo (least squares mean change from baseline) in Lissamine™ green staining in the Moderate-to-Severe Subgroup – observed data only Total Corneal Total Total Sum (inferior + Conjunctival (corneal + superior + (temporal + conjunctival) central) nasal) Temporal Nasal
Slide 43: Conjunctival Redness and Tear Film Break-up Time
Differences between PL9643 and placebo (least squares mean change from baseline) in conjunctival redness and tear film break-up time in the Moderate-to-Severe Subgroup – observed data only Conjunctival Redness Tear Film Break-up Time 0.00 0.45 * 0.40 -0.05 0.35 0.30 LS Mean Chnage LS Mean Change fro
Slide 44: Co-Primary Endpoint: Ocular Discomfort Scale
Co-Primary Endpoint (Single Question Scale): Differences between PL9643 and placebo (least squares mean change from baseline) in Ora Calibra® Ocular Discomfort Scale* scores in the Moderate-to-Severe Subgroup – observed data only Ora Calibra® Ocular Discomfort Scale For ocular discomfort, PL9643 dem
Slide 45: Secondary Endpoint: 5-Question Scale
Secondary Endpoint (5-Question Scale): Differences between PL9643 and placebo (least squares mean change from baseline) in the Ora Calibra® Ocular Discomfort and 4-Symptom Questionnaire† scores in the Moderate-to-Severe Subgroup subgroup – observed data only Ocular Burning PL9643 demonstrated discom
Slide 46: Components of the Visual Analog Scale
Differences between PL9643 and placebo (least squares mean change from baseline) in components of the visual analog scale* in the Moderate-to-Severe Subgroup – observed data only After 2 weeks, and also at Burning/ Foreign body Eye Eye stinging Itching sensation discomfort dryness Photophobia Pain 1
Slide 47: AEs by Severity and Relation to Treatment: Safety
Table 1. AEs by severity and relation to treatment Event Mild Moderate Severe Total PL9643 13 3 0 16 Non-ocular 12 3 0 15 Safety Not related 10 3 0 13 • No treatment-related Possibly related 1 0 0 1 serious AEs or ocular AEs Unlikely related 1 0 0 1 were observed, and no Ocular 1 0 0 1 subjects rece
Slide 48: Conclusions
Conclusions • In subjects with moderate or severe dry eye disease, PL9643 ophthalmic solution led to benefits in signs and symptoms by the first evaluation at 2 weeks, which were maintained for the 12-week study duration • PL9643 was well tolerated, with no treatment-related ocular AEs and a safety
Slide 49: A Novel Approach to Dry Eye Disease
A Novel Approach to Dry Eye Disease • The melanocortin pathway provides a novel way to treat inflammatory conditions like dry eye disease by activating endogenous melanocortin receptors • The efficacy of PL9643 as demonstrated in the phase 2 clinical trial presented here shows promise for treating b
Slide 50: The Advantages for Patients
The Advantages for Patients • PL9643 is potent when compared to other treatments (eg, Restasis®); therefore, a smaller concentration was effective in treating DED signs and symptoms • Patients experienced no stinging or ocular discomfort due to these drops, potentially leading to improved patient co
Slide 51: Thank You
THANK YOU &Y PALATIN
Slide 52: PL9643-301 (MELODY-1) Study Overview
PL9643-301 (MELODY-1) Study Overview: Efficacy and Safety of the Melanocortin Agonist PL9643 in Subjects With Moderate and Severe Dry Eye Disease May 21, 2021
Slide 53: Study Design
Study Design • Multicenter, randomized, vehicle-controlled, double-masked, adaptive design Ph 3 study • Evaluate the efficacy and safety of PL9643 in up to 320 adults with moderate or severe dry eye disease defined as: • Disease duration ≥ 5 years prior to screening • Inferior corneal staining score
Slide 54: Phase 3 Study Design and Primary Endpoints
Study Design and Primary Endpoints: 12-week Phase 3, multicenter, 1:1 randomized, double-masked, vehicle-controlled adaptive design study Interim Interim Screening Randomization Assessment #1 Assessment #2 Week –2 0 2 4 6 8 10 12 Placebo run-in 1 µg/mL PL9643 ophthalmic solution 3 times daily N=up t
Slide 55: Additional Endpoints
Additional Endpoints Secondary Endpoints: Signs Secondary Endpoints: Symptoms • Temporal lissamine green staining • Grittiness (Ocular Discomfort & 4-Symptom Questionnaire) • Conjunctival redness • Ocular Discomfort Scale • Nasal lissamine green staining • Foreign Body Sensation (VAS) • Tear film br
Slide 56: PL9643 DED Program Timelines
PL9643 DED Program Timelines 2nd Interim Assessment MELODY-1 DBL MELODY-1 TFLs 1st Interim Assessment MELODY-1 CSR NDA Submission 2021 2021 2022 2023 2023 PL9643-301 MELODY-1 (Efficacy) PL9643-302 MELODY-2 (Efficacy) PL9643-303 MELODY-3 (Safety) 56
Slide 57: Retinopathy Preclinical Data and Clinical Opportunity
Retinopathy Preclinical Data and Clinical Opportunity Investor Day May 21, 2021
Slide 58: Preclinical Proof-of-Concept
Preclinical Proof-of-Concept To validate melanocortin receptors as therapeutic targets for retinal vascular diseases, Palatin’s melanocortin agonist compounds were tested in two relevant animal models 58
Slide 59: Laser-Induced Choroid Neovascularization (CNV) Model
Laser-Induced Choroid Neovascularization (CNV) Model Palatin compounds demonstrated that engaging the melanocortin receptors led to improved outcomes, including: • Decreased CNV leakage grades and area • Reduced neovascularization • Reduced collagen deposition This mouse model recapitulates the main
Slide 60: Diabetic Retinopathy Model
Diabetic Retinopathy Model Melanocortin agonist demonstrated key indicators of improve retinal health, including: • Preserved retinal anatomy • Suppressed pro-inflammatory cytokine to healthy control levels • Increased levels of IL-10, a marker of inflammation resolution Healthy Control Diabetic Unt
Slide 61: Therapeutic Candidate Selection
Therapeutic Candidate Selection Criteria for lead clinical candidate: • High potency at melanocortin receptors 1 and 5 • Demonstrated efficacy in preclinical animal models • Enabling pharmacokinetics • Desirable solubility profile • Straight-forward synthesis path • Excellent IP position PL9654 was
Slide 62: PL9654 in a Mouse CNV Model
PL9654 in a Mouse CNV Model MEAN AREA OF MEAN LEAKAGE AREA MEAN AREA OF FIBROSIS ANGIOGENESIS M M M M M µM 00µ 0µ 00µ 10µ 00µ 10 1 1 54 54 41 54 54 1 65 4 96 96 65 96 96 L L 9 PL L9 P P PL PL P Treatment Groups Treatment Groups Treatment Groups • PL9654 showed therapeutic activity comparable to an a
Slide 63: PL9654 in a Rat Diabetic In-Life Retinopathy Model
PL9654 in a Rat Diabetic In-Life Retinopathy Model CONTRAST VISION PL9654 preserves contrast vision as compared to controls Vehicle 0.05 mg/kg 0.1 mg/kg 0.5 mg/kg A second measure of visual acuity demonstrated similar efficacy to this measurement 63
Slide 64: PL9654 Preserves Contrast Sensitivity in a Rat Diabetic Retinopathy Model
PL9654 Preserves Contrast Sensitivity in a Rat Diabetic Retinopathy Model Final Mean Change in Contrast Sensitivity ✱ ✱✱ ✱✱✱ 6.0 5.5 This prevention of visual function loss 5.0 demonstrates the potential utility of 4.5 4.0 melanocortins in retinal vascular diseases Grating Contrast Threshold-1 (%) 3
Slide 65: PL9654 Delays Cataract Formation and Doesn't Affect Blood Glucose
PL9654 Delays Cataract Formation and Doesn’t Affect Blood Glucose Levels in Rat Diabetic Retinopathy In-Life model CATARACT SCORE BLOOD GLUCOSE LEVELS 4 600 Vehicle 550 PL9654, 0.05mg/kg 500 Blood Glucose (mg/dL) - Day 114 PL9654, 0.1mg/kg 3 450 PL9654, 0.5mg/kg Cataract Score 400 350 2 300 250 200
Slide 66: PL9654 Is Progressing as a Retinopathy Therapeutic Candidate
PL9654 Is Progressing as a Retinopathy Therapeutic Candidate Ongoing Activities • Additional preclinical models and measurements • Genomic and proteomic characterization of treated animal models • Extensive PK • Toxicology studies Determine optimal Route of Administration to maximize value to patien