1. No category

Palatin Technologies
January 2015
Carl Spana, Ph.D.
President & CEO
Stephen T. Wills, CPA/MST
CFO / COO
Forward Looking Statements
The statements in this presentation that relate to future plans, events or performance are forward-looking statements,
which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended. Such
forward-looking statements involve significant risks and uncertainties, and actual results, events and performance may
differ materially from those expressed or implied in this presentation. We have based these forward-looking statements
largely on our current expectations and projections about future events and financial trends that we believe may affect our
financial condition, results of operations, business strategy and financial needs. These forward-looking statements include,
but are not limited to, statements concerning the following: (i) estimates of our expenses, future revenue, capital
requirements; (ii) our ability to obtain additional financing on terms acceptable to us, or at all; (iii) our ability to advance
product candidates into, and successfully complete, clinical trials; (iv) the initiation, timing, progress and results of future
preclinical studies and clinical trials, and our research and development programs; (v) the timing or likelihood of
regulatory filings and approvals; (vi) our expectations regarding the results and the timing of results in our Phase 3
clinical trials of bremelanotide for female sexual dysfunction (FSD); (vii) our expectation regarding the timing of our
regulatory submissions for approval of bremelanotide for FSD in the United States and Europe; (viii) the potential for
commercialization of bremelanotide for FSD and other product candidates, if approved, by us; (ix) our expectations
regarding the potential market size and market acceptance for bremelanotide for FSD and our other product candidates, if
approved for commercial use; (x) our ability to compete with other products and technologies similar to our product
candidates; (xi) the ability of our third party collaborators to timely carry out their duties under their agreements with us
in; (xii) the ability of our contract manufactures to perform their manufacturing activities for us in compliance with
applicable regulations; (xiii) our ability to recognize the potential value of our licensing arrangements with third parties;
(xiv) the potential to achieve revenues from the sale of our product candidates; (xv) our ability to maintain product
liability insurance at a reasonable cost or in sufficient amounts, if at all; (xvi) the retention of key management, employees
and third-party contractors; (xvii) the scope of protection we are able to establish and maintain for intellectual property
rights covering our product candidates and technology; (xviii) our compliance with federal and state laws and regulations;
(xix) the timing and costs associated with obtaining regulatory approval for our product candidates; (xx) the impact of
legislative or regulatory healthcare reforms in the United States; and (xxi) other risks disclosed in our SEC filings. The
forward-looking statements in this presentation do not constitute guarantees of future performance. We undertake no
obligation to publicly update these forward-looking statements to reflect events or circumstances that occur after the date
of this presentation.
2
Company Profile
Palatin Technologies, Inc. (NYSE MKT: PTN) is a
biopharmaceutical company developing targeted, receptorspecific peptide therapeutics for the treatment of diseases
with significant unmet medical need and commercial
potential.
3
Palatin Technologies Value Proposition




Palatin Technologies, Inc. is a biopharmaceutical company developing targeted, receptor-specific
peptide therapeutics for the treatment of diseases with significant unmet medical need and
commercial potential
Lead product: Bremelanotide (BMT) for the treatment of Female Sexual Dysfunction (FSD)
◦ Unmet medical need with multi-billion dollar market opportunity
◦ Enrolling patients in North American (NA) Phase 3 pivotal trials
◦ Gedeon Richter European development and marketing partner
PL-3994 targeting Natriuretic Receptor A for cardiovascular and pulmonary indications
◦ Upregulation of the natriuretic peptide (NP) system is a validated target for improving treatment
outcomes in heart failure
◦ Phase 1 studies complete; Phase 2 ready
Melanocortin receptor-1 (MC1r) agonist peptide program
◦ Efficacy demonstrated in multiple preclinical animal models

◦ IND enabling studies complete – first in humans study targeted for 1H2015
Melanocortin receptor-4 (MC4r) obesity/diabetes collaboration with AstraZeneca
◦ Clinical proof of principle established
◦ AstraZeneca responsible for clinical development and costs
– Next steps with collaboration under review
– ~$145M in potential milestones plus royalties
4
Pipeline Overview
Preclinical
Phase 1
Phase 2
Phase 3
Melanocortin Receptor Programs
Bremelanotide for Female Sexual Dysfunction
MC4r Agonist
AstraZeneca Collaboration
Obesity, Metabolic Syndrome & Diabetes
MC4r Agonist
Next Generation Peptide
Female Sexual Dysfunction & Erectile Dysfunction
PL-8177 MC1r Agonist
Inflammatory & Dermatologic Diseases
Natriuretic Peptide Receptor Programs
PL-3994 for Cardiovascular Indications
PL-3994 for Pulmonary Indications
5
Female Sexual
Dysfunction Program
Female Sexual Dysfunction Overview




Female Sexual Dysfunction (FSD) is defined as persistent or recurring
problems during one or more of the stages of sexual response with associated
distress
FSD has a significant impact on patient self-image, relationships and general
well-being
>60 million premenopausal women in US1
◦ 22% reported a sexual problem2
◦ 11% were distressed by their sexual problems2
–
One-third sought formal care2
Market size – U.S.
◦ Presenting premenopausal women ~2.0 million2
◦ Annual sales anticipated to be ~$1.3 billion by 20203
References:
1)
US Census 2010
2)
PRESIDE Study - Shifren JL et al. Sexual Problems and Distress in United States Women: Prevalence and
Correlates. Obstet Gynecol 2008; 112:970-8.
3)
Estimates from EvaluatePharma
7
Approaches to Treating FSD

Low dose transdermal testosterone in surgically menopausal Hypoactive Sexual
Desire Disorder (HSDD) patients.
◦ Intrinsa testosterone patch successful Phase 3 program
–
Failure to approve based on long term use safety risks of cancer and cardiovascular adverse
events
◦ LibiGel testosterone gel failed in Phase 3
–

Flibanserin is a serotonin 5-HT1A agonist, 5-HT2A antagonist that requires chronic
dosing in premenopausal women with HSDD
◦
Failed to meet co-primary endpoint of daily change of desire
–
◦
Negative advisory panel
2 NDA review cycles and formal dispute resolution
–

Failure based upon placebo response that was equivalent to LibiGel
FDA requires additional safety studies
Bremelanotide MC4r agonist enrolling patients in Phase 3 NA pivotal trials
8
Bremelanotide Profile






Novel mechanism of action activating endogenous melanocortin hormone pathways
involved in sexual arousal response
Evaluated in 31 clinical studies (n = 2300) showing efficacy in both FSD and erectile
dysfunction
Phase 2B trial showed a statistically significant and clinically meaningful effect
◦ Met both primary and secondary endpoints
Phase 3 NA pivotal trials enrolling patients - follows FDA design guidance
On-demand use with rapid onset of activity and well-tolerated
Proven manufacturing capabilities
◦ Drug API – manufactured by Lonza at commercial scale
◦ Ypsomed Group – autoinjector
◦ Catalent – fill, finish and packaging
9
Phase 2B FSD Clinical Trial


Dose ranging 16 week at-home placebo-controlled study
◦ Subcutaneous dosing: placebo and 0.75 mg, 1.25 mg and 1.75 mg bremelanotide
◦ Enrollment: 395 patients
Validated patient reported outcome (PRO) endpoints
◦ Increase in Satisfying Sexual Events (SSEs)
–
As measured by event log
◦ Female Sexual Function Index (FSFI)
–
19-item questionnaire measuring improvement in arousal, desire and overall sexual function
◦ Female Sexual Distress Scale-DAO (FSDS-DAO)
–


15-item questionnaire that measures personal distress associated with FSD
Objectives
◦ Evaluate safety and efficacy in premenopausal patients with HSDD, female sexual arousal
disorder (FSAD) and FSAD/HSDD
Multiple presentations and publications of Phase 2B data.
10
Phase 2B FSD Clinical Data


Analysis of the primary and key secondary endpoints of 327 pre-menopausal patients
shows clinically meaningful and statistically significant effects for bremelanotide vs.
placebo. Pre-specified analysis was of pooled 1.25 mg & 1.75 mg doses vs. placebo.
Primary endpoint improvement in the number of satisfying sexual events (SSE)
◦
◦

◦
FSFI-total score mean change
FSDS-DAO-total score mean change
3.55 vs. 1.88 (p=0.0017)
-11.1 vs. -6.8 (p=0.036)
SSE improvement from baseline
FSFI-total score mean change
FSDS-DAO-total score mean change
1.8 to 2.6 (p=0.021)
4.4 vs. 1.88 (p=0.0021)
-13.1 vs. -6.8 (p=0.0005)
1.75 mg dose analysis also demonstrated clinically meaningful and statistical significance
◦
◦
◦

1.6 to 2.4 (50% increase) (p=0.018)
1.7 to 1.9 (12% increase)
Key secondary endpoints
◦

Bremelanotide mean change from baseline
Placebo mean change from baseline
0.75 mg dose analysis demonstrated a response that was not significantly different from
placebo
11
Phase 2B FSD Clinical Data
*
0.7
0.6
0.5
0.4
0.3
0.2
0.1
FSFI Total Score
4.0
3.5
3.0
*
2.5
2.0
1.5
1.0
* P<0.05
** P<0.01
*** P<0.001
0.0
Placebo 0.75 mg 1.25 mg 1.75 mg
Placebo 0.75 mg 1.25 mg 1.75 mg
-2.0
-4.0
-6.0
-8.0
-10.0
-12.0
0.5
Placebo 0.75 mg 1.25 mg 1.75 mg
0.0
**
4.5
Mean Change From Baseline
Mean Change From Baseline
0.8
0.0
5.0
SSE
Mean Change From Baseline
0.9
-14.0
*
FSDS-DAO
Total Score
***
12
Phase 2B FSD Clinical Data





395 premenopausal FSD patients were randomized to receive drug or placebo
26 patients met the predefined blood pressure withdrawal criteria and were evenly
distributed among placebo and active arms of the study
Drug treated subjects had ~2 mm Hg change in blood pressure, predominately during
the first 4 hours of dosing
No significant adverse events attributed to bremelanotide occurred during the study
Most common adverse events on drug were nausea, flushing, headache and emesis
◦ <3% discontinued due to adverse events
13
Phase 3 NA Pivotal Program

Key Points
◦
◦
◦
◦
◦
◦
Patient population – HSDD & HSDD with decreased arousal
24 week treatment evaluation period
Co-primary endpoints – SSE and FSFI Desire subdomain (28 day recall)
Key secondary endpoint – FSDS-R (revised) question #13
1.75 mg versus placebo
Cardio-Renal Division
–
–
Intra-nasal Definitive QTc study is acceptable for NDA submission
Proposed blood pressure monitoring is acceptable (standard blood pressure cuff)
◦ Carcinogenicity and reproductive toxicity studies acceptable for NDA submission
◦ No outstanding CMC issues

Phase 3 clinical program
◦ 2 pivotal trials (~1100) in North America (primarily US) – Commenced 4Q2014
◦ 1 pivotal trial in Europe (~900) – Commencing in 2H2015
◦ Open label Study (~600) extension of pivotal trials
14
Phase 2B Analyzed for Phase 3 Patient Population & Endpoints
SSE
0.8
0.7
0.6
FSFI-Desire
P=0.03
P=0.001
0.3
-1
0.2
Placebo 1.25mg 1.75mg
0
-0.25
-0.75
0.4
0.2
0
-0.5
0.6
0.4
0
1
0.8
0.5
0.1
1.2
FSDS-Q13
Placebo 1.25mg 1.75mg
-1.25
P=0.008
Placebo 1.25mg 1.75mg
Phase 2B data from patients diagnosed with HSDD and HSDD with FSAD (the proposed
Phase 3 patient population) were analyzed using proposed Phase 3 endpoints of total
SSEs, the FSFI desire subdomain and FSDS-R question 13. The 1.75 mg dose was
statistically and clinically significant for all three endpoints.
15
Corporate Partnering

European rights licensed to Gedeon Richter (August 2014)
◦ European pharmaceutical company with a focus on female healthcare
- $1.6B in 2013 sales - $500M in female healthcare
◦ EMA/ CHMP guidance on the EU Phase 3 program received
◦ Jointly working on EU Phase 3 clinical development program
- Estimated start 2H2015
◦ Financial Terms
- $9.8M total upfront
- $3.0M milestone triggered on start of US Phase 3 clinical trial program
-
4Q2014 – to be received 1Q2015
- $25M in regulatory milestones / $75M in sales milestones

- Low double-digit royalties
Pursuing discussions with potential partners for US and non-EU rights
16
Key Points FDA Public Meeting on FSD

On October 27 & 28, 2014 the FDA held a Patient-Focused Drug Development
Public Meeting and Scientific Workshop on Female Sexual Dysfunction
◦ FSD is an underserved, unmet medical need that distresses patients and is in need of
multiple treatment options
◦ FDA will work with Sponsors to address this need
◦ FSFI is a well validated PRO instrument and is the appropriate end point for Phase 3
registration trials
◦ 28 day recall period is an appropriate time period for measuring desire for both
intermittently and chronically taken drugs for FSD
17
Bremelanotide NA & EU Program Timelines
 NA (primarily U.S.)
◦
◦
◦
◦
◦
Phase 3 pivotal trials enrolling patients
Complete Phase 3 enrollment
Phase 3 trials topline results
FDA NDA submission
FDA action
 EU
◦
◦
◦
◦
EMA/CHMP guidance - completed
Commence Phase 3 trial
EU submission
EU action
4Q2014
2H2015
Mid-2016
4Q2016
4Q2017
1H2014
2H2015
2H2017
2H2018
18
Natriuretic Peptide
Receptor Program
Natriuretic Peptide System
Prohormone
CNP
BNP
ANP
Neuropeptide hormone system
plays an important role in the regulation
of cardiovascular homeostasis
Corin processing
GTP
•
•
•
•
•
•
PKG
Physiological Effects
Neutral endopeptidase (neprilysin)
And the NP-C receptor downregulate
the NP system through removal of
active ANP, BNP and CNP
Downregulate renin-angiotensin-aldosterone system
Suppression of cardiac hypertrophy & remodeling
Stimulation of diuresis & natriuresis
Increased myocardial perfusion
Vasodilation & decreased blood pressure
Bronchodilation
20
Paradigm Shift in HF: Upregulation of NP System





LCZ696 (Novartis compound) – combined ARB & neprilysin inhibitor
◦ Inhibits angiotensin function and upregulates endogenous natriuretic peptides
Phase 3 trial in heart failure (HF) patients with reduced ejection fraction compared
LCZ696 to ACEi (enalapril) control
◦ LCZ696 significantly reduced rate of death from CV causes (20% reduction)
◦ LCZ696 significantly reduced hospitalization for HF (21% reduction)
◦ LCZ696 significantly improved HF symptoms
LCZ696 clearly demonstrated that upregulation of the NP system in combination with
angiotensin inhibition is superior to ACEi alone
LCZ696 provides validation of the NP system as a target for improving outcomes in
treating HF patients
LCZ696 revenue projections – analysts estimate $5B-$10B in annual sales
21
Overview Palatin Natriuretic Peptide Program


Design and develop commercial candidates selective for NPR-A, NPR-B, NPR-C &
NPR-A/B
PL-3994 lead product candidate
◦
◦
◦
◦

PL-3994 is potent NPR-A agonist
◦
◦
◦
◦


Selective NPR-A agonist
Increased metabolic stability
Once daily subcutaneous (SC) patient administration
Phase 2 ready drug development candidate
2 Phase 1 studies – healthy and controlled hypertensive subjects
Placebo and escalating doses of PL-3994 delivered SC
Well tolerated - no adverse or severe adverse events
Met key pharmacology endpoints
– ↓SBP, ↑diuresis, ↑natriuresis, ↑cGMP plasma levels
Pharmacokinetics and duration of pharmacology support chronic use
Active discussions with potential partners for US and ROW rights
22
Daily PL-3994 Significantly Reduces Cardiac Remodeling
Heart Weight /Body Weight
Attenuation of RAAS Activation
following 6 weeks of treatment
* p < 0.05
42
14
7
-7
*
2000
1000
0
42
(P
L3
99
4)
2K
1C
(s
al
in
e)
)
2K
1C
(P
L3
99
4
Sh
am
Sh
am
(s
a
lin
e)
0.0
20000
14
0.2
2K1C (saline)
2K1C (PL3994)
40000
7
* p < 0.05
0.4
*
60000
-7
HW/BW
*
*
Plasma aldosterone
(pg/ml)
80000
0.6
Time (days)
The “2 Kidney, 1 Clip” rat model causes renovascular hypertension and cardiac
hypertrophy. Treatment with PL-3994 reduces both excess production of
aldosterone and cardiac hypertrophy.
23
Opportunities for Treating Heart Failure



Heart Failure with Preserved
Ejection Fraction (HF-PEF)

◦ High unmet need; no approved
treatment options
Heart Failure with Reduced Ejection
Fraction (HF-REF)
Patients with corin and/or reduced
active NP expression
◦ High unmet medical need; poor
response to current therapies
◦ Restore normal NP function

Phase 2A multiple dose study in HF
patients
◦ HF-PEF, HF-REF & corin deficient patients
◦ Evaluate safety, symptom relief and cardiac
imaging, LVEF
◦ Targeted start 1H2015; data anticipated
2H2015
Phase 2 proof-of-principle study
◦ 3-6 month treatment
◦ Evaluate safety, cardiac function, effects on
remodeling, symptom improvement and
hospital admission
◦ Targeted start 2H2015; data anticipated
2H2016
24
Melanocortin Receptor-1 Agonists
Inflammation and Dermatologic
Indications
MC1r Agonist Anti-Inflammatory Program

Goal: design and develop selective MC1r agonists for treating a variety of inflammatory
and autoimmune indications
◦ Inflammatory indications: inflammatory bowel disease, nephritis (inflammation of the kidneys)
and rheumatoid arthritis
◦ Ocular indications: uveitis and dry eye
◦ Dermatologic indications: vitiligo and erythropoietic protoporphyria
◦ Rational design and synthesis of selective MC1r agonists
◦ Excellent metabolic stability (> 2 hour in vivo half life)
◦ MC1r agonism functions to resolve pro-inflammatory responses

Lead pre-clinical candidate PL-8177 selective MC1r agonist
◦
◦
◦
◦
Demonstrated efficacy in multiple preclinical models: EAU, IBD and nephritis
Preclinical toxicology and CMC activities to support IND filing completed
First-in-human clinical trial targeted start 1H2015
Actively exploring collaboration or licensing transactions for specific market areas
26
TNF-α Inhibition via MC1r Agonists
Results
pmole/mL TNFa
3000
Dose – mg/kg SC
2000
1000
10
1
77
@
@
L8
1
P
L8
1
77
@
P
P
L8
1
76
76
L8
1
P
10
1
@
5
@
ex
a
D
V
eh
ic
le
0
Preclinical mouse model TNF-α stimulated by LPS administration with
dexamethasone as positive control
27
PL-8177 Experimental Autoimmune Uveitis
Untreated EAU mice
PL-8177 Low Dose Treated EAU mice
PL-8177 High Dose Treated EAU mice
α-MSH Treated EAU mice
EAU Clinical Score
4
3
2
*
1
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Day
Days of injections
* P = 0.0001 by Anova
◦ MC1r agonism has significant effects in reversing uveitis
◦ Conducted in collaboration with Dr. A. Taylor at Boston University School of Medicine
28
Melanocortin Receptor-4 Agonist
Obesity & Diabetes
Melanocortins and Obesity Overview
Hypothalamus
arcuate nucleus
POMC
Peripheral Signals
Leptin
Grelin
GLP-1
Insulin
CCK
MC4r
Brainstem & Cortex
signals
Down stream effects on
food intake, weight
and energy expenditure
AGRP
•
•
•
•
Stimulates MC4r – decrease in food intake & weight loss
Inhibits MC4r – increase in food intake & weight gain
MC4r mutations most prevalent form of monogenetic obesity in humans
MC4r loss of function – hyperphagic, obese increased growth & hyperinsulinemia
MC4r agonist BMT reduces food intake and weight loss in obesity clinical studies
Currently approved obesity treatments require functional MC4r pathway
30
MC4r Obesity & Diabetes Program

Goal: design and develop selective for MC4r agonists for treating obesity, diabetes
and related metabolic syndrome
◦ High selectivity for MC4r with limited off-target effect
◦ None of the toxicities associated with small molecules
Lead compound PL-8905
◦
◦
◦
◦
High selectivity of MC4r over MC1r (>100x functional)
Minimal effect on blood pressure, limited CNS penetration
Chemical/metabolic stability (>2 hour in vivo half life)
Preclinical studies in animal models:
Body weight change from Day 0
Body Weight Change (g)

10
5
0
1
3
2
-5
Day
4
5
Vehicle
PL-8905 0.3 mg/kg
PL-8905 1 mg/kg
PL-8905 3 mg/kg
-10
-15
31
AstraZeneca Obesity Collaboration

Exclusive global licensing and research collaboration
◦ $10M upfront and $10M milestones received
◦ $145M in additional potential milestones
◦ Royalties on sales of approved products

Clinical proof-of-concept studies for MC4r mechanism have been completed
◦ Primary objectives met: significant decrease in food intake and weight loss

Drug Candidates under development/review
◦ AZD2820 (initial clinical candidate) development halted during Phase 1 program for
compound-specific safety concern
◦ Program next steps and drug candidate evaluation under review by AstraZeneca
32
Palatin Potential Near-Term Development Milestones

Bremelanotide for Female Sexual Dysfunction
◦
◦
◦
◦
◦

Commence Phase 3 pivotal trials in NA
Complete Phase 3 enrollment in NA
Commence Phase 3 pivotal trial in EU
NA Phase 3 pivotal trial results
Corporate collaborations – US (ongoing discussions)
PL-3994 for Cardiovascular/Pulmonary Indications
◦ Commence Phase 2A clinical trial in HF patients
- Subject to funding


4Q2014 
2H2015
2H2015
Mid-2016
1H2015
◦ Corporate collaboration target
1H2015
◦ First-in-human clinical trial
◦ Corporate collaboration target
1H2015
1H2015
◦ Clinical candidate selection
◦ Phase 1 clinical trial
1H2015
2H2015
MC1r Inflammation/Dermatologic Indications
AstraZeneca MC4r development obesity/diabetes program
33
Financial Snapshot
Financial Highlights as of September 30, 2014
Cash & Equivalents
Total Debt
Common Stock
Preferred
Warrants
Options
RSU’s
Fully Diluted Shares
$17.8 million1
Summary of Capitalization as of January 2015
$0.01
Common Equivalent2
41.5 million shares
0.1 million shares
116.7 million shares3
4.2 million shares
0.8 million shares
163.3 million shares
1) Does not include December 2014 financing of $20 million in equity consisting of common shares and pre-funded warrants (see 3 below) at $0.75
per share, and $10 million in venture debt financing.
2) Rounded to the nearest hundred thousand shares.
3) Includes “pre-funded” Series A and Series B warrants to purchase 32.0 million and 35.5 million shares of common stock, respectively, at a $0.01
per share exercise price ($0.49 per warrant received by Palatin with July 2012 financing) and Series C warrants to purchase 24.9 million shares of
common stock at a $0.01 per share exercise price ($0.74 per warrant received by Palatin with December 2014 financing).
34
Thank You