Transcript GLMD - Wsimg.com

Investor Presentation
May / June 2015
Forward Looking Statement
This presentation contains forward-looking statements about our expectations, beliefs or intentions regarding, among other things, our product
development efforts, business, financial condition, results of operations, strategies or prospects. In addition, from time to time, we or our
representatives have made or may make forward-looking statements, orally or in writing. Forward-looking statements can be identified by the
use of forward-looking words such as “believe,” “expect,” “intend,” “plan,” “may,” “should” or “anticipate” or their negatives or other variations
of these words or other comparable words or by the fact that these statements do not relate strictly to historical or current matters. These
forward-looking statements may be included in, but are not limited to, this presentation, various filings made by us with the SEC, press
releases or oral statements made by or with the approval of one of our authorized executive officers. Forward-looking statements relate to
anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters
that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause our actual results to differ
materially from any future results expressed or implied by the forward-looking statements. Many factors could cause our actual activities or
results to differ materially from the activities and results anticipated in forward-looking statements, including, but not limited to, the factors
summarized below.
These factors include, but are not limited to, the following: FDA approval of, or other regulatory action with respect to aramchol; the
commercial launch and future sales of aramchol or any other future products or product candidates; our ability to achieve favorable pricing for
aramchol; our expectations regarding the commercial market of NASH in patients who also suffer from obesity and insulin resistance; thirdparty payor reimbursement for aramchol; our estimates regarding anticipated capital requirements and our needs for additional financing;
patient market size and market adoption of aramchol by physicians and patients; the timing, cost or other aspects of the commercial launch
of aramchol; the timing and cost of Phase IIb and Phase III trials for aramchol or whether such trials will be conducted at all; completion and
receiving favorable results of Phase IIb and Phase III trials for aramchol; the development and approval of the use of aramchol for additional
indications or in combination therapy; and our expectations regarding licensing, acquisitions and strategic operations.
These statements are only current predictions and are subject to known and unknown risks, uncertainties and other factors that may cause our
or our industry’s actual results, levels of activity, performance or achievements to be materially different from those anticipated by the forwardlooking statements. Given these uncertainties, you should not rely upon forward-looking statements as predictions of future events.
All forward-looking statements attributable to us or persons acting on our behalf included in, but not limited to, this presentation speak only as
of the date hereof and are expressly qualified in their entirety by the foregoing. We undertake no obligations to update or revise forwardlooking statements to reflect events or circumstances that arise after the date made or to reflect the occurrence of unanticipated events. In
evaluating forward-looking statements, you should consider these risks and uncertainties.
The Short Story
Focused Strategy,
Broad Vision
Aramchol addresses a significant, and growing unmet need
in the U.S., EU & RoW – Non-alcoholic steatohepatitis
(NASH) and liver diseases
Novel Technology
First in a new class of drug candidates with favorable safety
profile and Proof-of-Concept as demonstrated in Phase I &
IIa clinical trials
Significant Market
Opportunity
~10% population in U.S. & EU-5 nations has NASH;
prevalence expected to rise in parallel with obesity and
diabetes. No approved drugs
Strong Track
Record of
Execution
Completed pre-clinical and 4 clinical trials (Phase Ia/Ib, PK
Food effect & Phase IIa … on time and under budget)
Compelling
Valuation
GLMD still trades significantly below other Phase IIb
comparable companies despite relatively strong YTD 2015
price performance
May 2015
1
Focused on Near- and Mid-Term Milestones
Obtained IND
Received
NASH fast
track
designation
2H14
Initiate
randomization in
ARREST Study in
US, Europe,
LatAm and Israel
Initiation of
Phase II PoC
clinical trial(s) in
new
indication(s)
2015
Began
enrollment
ARREST Study
Expansion of the
Study to the US
Release of preclinical data for
combination
therapy
May 2015
1H16
Release
interim
ARREST Study
results
2
Recent Developments
Update on ARamchol for the REsolution of
STeatohepatitis (ARREST) Study
• Commenced screening in all 14 sites in Israel
• Screening process to randomization is usually ~6 weeks
– European sites (France, Italy, Germany): ~29 sites; regulatory and IRB
approval expected in April; sites recruiting by May
– LatAm (Mexico, Chile, Peru, Columbia): ~16 sites; regulatory and IRB
approval expected in April; sites recruiting by May
• Expanded ARREST Study to include patient recruitment in the U.S.
– Professor Vlad Ratziu serves as our global Principal Investigator, and
Professor Rohit Loomba is U.S. Principal Investigator
– Revised IND submitted; enrollment to begin in June
– Expect 30-40% of patients to be recruited in the U.S.; 12-14 sites
– Hired full-time, US-based team, including VP Clinical Operations to execute
strategy
May 2015
3
ARREST Study
Design:
• Multicenter, randomized, double-blind, placebo-controlled, dose ranging
study
Participants:
• Biopsy-diagnosed NASH patients with obesity and insulin resistance
Doses:
• Placebo (62 patients)
• 400 mg (89 patients)
• 600 mg (89 patients)
Treatment
Plan:
• 12 months treatment (once-daily tablet) and 3 months of follow-up
• Interim analysis planned on first 120 patients completing 6 months of
treatment (1H16). Top-line results in 2H16
Number of
Subjects (Est.):
• 240 patients
• ~80 sites in U.S., Europe, Latin America and Israel
Primary
Endpoint:
• Statistically significant reduction in liver fat content measured by NMRS
Secondary
Endpoints:
• Resolution of NASH as measured by biopsy
• Improvement of liver and metabolic markers
May 2015
4
FDA/AASLD Joint Workshop – NASH Guidance
• January’s manuscript acknowledges – for the first
time –the approvability of “early stage disease” (prefibrotic NASH), which represents 80% of all NASH
patients
• Acceptance of accelerated approval pathway:
– Surrogate marker as the endpoint (liver biopsy); reversal of
steatohepatitis
– No worsening of fibrosis
– Likely post-approval “hard clinical outcomes” (liver-related
mortality, cirrhosis and hepatocellular cancer)
May 2015
5
NASH
The Continuum of Liver Disease
In Galmed’s studies to date, aramchol has been shown to:
1. Reduce liver fat
2. Improve metabolic parameters
3. Prevent liver & cardiovascular
complications
May 2015
6
Non-Alcoholic Steatohepatitis (NASH)
NASH
NAFLD
Healthy Liver
•
•
Prominent retention and
deposits of fat (steatosis)
Associated with insulin
resistance and metabolic
syndrome (obesity, type II
diabetes and high blood
pressure)
•
Notable ballooned
hepatocytes, an elevated
immune response and
collagen deposition
indicative of fibrosis
Source: Nature Reviews – Hebbard, L. & George, J. (2010) Animal models of nonalcoholic fatty liver disease Nat. Rev.
Gastroenterol. Hepatol. doi:10.1038/nrgastro.2010.191
May 2015
7
Addressable Market (US + EU-5)
Adult Population (441m)
NAFLD (167m)
NASH (45m)
Diagnosed (5.5m)
Treated (1.6m)
Source: Deutsche Bank by 2025
May 2015
8
Current Therapies on the Market
There are NO Approved Medications for NASH
NASH is predicted to become the leading indication for liver transplant within the next few years
May 2015
9
Science Rationale &
Clinical Data
Aramchol
• Novel
• First-in-Class
• Potentially disease modifying
• Orally administered
• Favorable safety and tolerability
parameters
• Synthetic conjugate of Cholic (bile) acid
and Arachidic (fatty) acid
May 2015
10
A Visible Reduction in Lipid Deposits & Ballooning
Fatty Liver
Treated with Aramchol
Fatty Liver
Gilat et. al., HEPATOLOGY, Vol. 38, No. 2, 2003
Rodents in this study were treated with aramchol for ten weeks
March 2015
11
Intervention to Reduce Body and Liver Fat Results in
the Improvement in NASH
• 5-7% reduction in body weight (exercise/diet) has shown
to reverse NASH
• Surgically-induced weight loss (laparoscopic gastric
bypass) significantly improves NASH, as well as metabolic
syndrome (within 15 +/- 9 months with p < 0.001)**
–
–
–
–
Significant improvement in liver steatosis (from 88%  8%)
Noticeable improvement in inflammation (from 23%  2%)
Marked improvement in fibrosis (from 31%  13%)
Inflammation and fibrosis resolved in 37% and 20%, respectively,
corresponding to improvement of 82%
** Mattar et. al.; based on research sponsored by the University of Pittsburgh and the Cleveland Clinic; Annals of Surgery,
Volume 242
May 2015
12
Differentiation through Mechanism-of-Action: (1)
Partial Inhibition of SCD1
P < 0.05
35
31
Fatty Acid Ratio*
30
25
20
15
10
12
7
5
Redular Diet
High Fat Diet +
Placebo
High Fat Diet +
Aramchol 150
* Mice at 4-weeks; fatty acid ratio is a reliable marker of SCD activity
May 2015
13
Phase IIa : Statistically Significant Reduction in Liver
Fat Content
May 2015
14
Phase IIa: Marked Improvement in Adiponectin
Levels
May 2015
15
Phase IIa: Discernable Improvement in Endothelial
Function
May 2015
16
Phase IIa: Favorable Safety Profile
• No significant changes in LDL and total cholesterol levels
• No severe drug-related adverse events (AEs) during 3-month treatment
period and subsequent recovery period
May 2015
17
Summary of Safety Data
Study
Chronic
Toxicology
(non-clinical)
Phase I
Phase IIa
N
Summary of Safety Results
No AEs and minimal toxicity following single doses (750 mg/kg);
repeat dose studies in rats up to 6-months (1000 mg/kg) and in
dogs up to 9-months (1500 mg/kg); reproductive studies in rats
(1000 mg/kg) and rabbits (750 mg/kg). NOAEL determined at
highest dose tested for all studies; didn’t reach MTD
Single doses of aramchol from 30 mg to 900 mg and repeated
41 dose of 100 mg, 300 mg were found to be safe and well tolerated
in healthy male subjects
No severe AEs during the 3-month treatment period. Mild AE in 6
57 patients were mild or moderate and transient, and did not differ
between the placebo and treated groups
All doses of aramchol were safe and well tolerated.
PK /
No serious AEs. Most of AEs were mild and unrelated to aramchol
66
Food Effect
and all AEs were transient and gave no indication of target organ
toxicity
May 2015
18
NASH Substantially Adds CV Risk to Diabetic
Patients
Diabetic Patients with Nash Have a
2.5x Higher Cardiovascular Risk*
Without
Nash
With
Nash
* Risk factors for CV disease include age to diagnosis, duration of diabetes, gender, blood pressure, presence of diabetic retinopathy and arterial fibrillation, urine
albumin/creatinine ratio, non-density lipoprotein cholesterol, treatment for hypertension and A1C level. N = 310 cross-sectional diabetic patients receiving
outpatient care from March-December 2013. Albai O, Timar, B. European Scientific Journal J. 2013; 9(12):99-111.
May 2015
19
FINANCIALS &
VALUATION
Lean & Clean; Solid Balance Sheet
2014A
(USD in thousands, except share and per share data)
1Qa
2Qa
3Qa
4Qa
Income Statement:
Expenses:
Research and development
$
1,502 $
1,245 $
2,791 $
1,126
$
General and administrative
633
518
399
928
Capital Loss
Subtotal - Operating Expenses
2,135
1,763
3,190
2,054
Financial expenses, net
26
(6)
16
(76)
Operating loss before income taxes
2,161
1,757
3,206
1,978
Taxes on income
NET LOSS
$
2,161 $
1,757 $
3,206 $
1,978
$
Basic and diluted net loss per share
$
0.27
$
Weighted average number of shares outstanding used in
8,004
computing basic and diluted net loss per share (000s)
Balance Sheet:
Assets:
Current Assets:
Cash and cash equivalents
Other accounts receivable
Total current assets
Property and equipment, net
TOTAL ASSETS
39,769 $
94
39,863
18
39,881 $
37,399 $
61
37,460
24
37,484 $
35,342 $
67
35,409
775
36,184 $
31,986
165
32,151
774
32,925
Liabilities and Stockholders' Deficiency
Total current liabilities
1,498
Total long-term liabilities
430
Total stockholders' equity (deficiency)
37,953
TOTAL LIABILITIES AND STOCKHOLDERS'
$ EQUITY
39,881 $
694
442
36,348
37,484 $
2,565
368
33,251
36,184 $
1,118
400
31,407
32,925
Ordinary shares issued and outstanding
$
$
11,100,453
11,100,453
May 2015
11,100,453
11,100,453
$
2013A
Full
Year
7,207 $
7,355
10
14,572
2,912
17,484
1
17,485 $
2.51 $
6,954
2014A
Full
Year
6,664
2,478
9,142
(40)
9,102
1
9,103
0.88
10,324
$
137 $
16
153
13
166 $
31,986
165
32,151
774
32,925
$
1,689
428
(1,951)
166 $
1,118
400
31,407
32,925
9,739
11,100,453
20
20% of Market
Fibrosis
Competitive Landscape
(Cirrhosis; IV Formulation)
(Phase I)
80% of Market
NASH
Phase III Design  ???
(Pre-Clinical)
Phase IIa
or Earlier
Phase IIb
Ongoing
May 2015
Phase IIb
Complete
21
Comparable Company Analysis
(All figures in millions, unless otherwise noted)
Company
Ticker
Conatus
CNAT
Galectin
GALT
Genfit PA
GNFTF
Intercept
Current:
Share Price
Franchise
Value
Cash
YTD
2015
2014
52-Week 52-Week
High
Low
47%
53%
-20%
9%
-52%
8%
2.75
65
45%
55%
-21%
-57%
-83%
5%
43.45
1,041
8%
92%
4%
N/A
-45%
102%
ICPT
263.50
6,340
12%
88%
69%
128%
-25%
105%
La Jolla
LJPC
20.26
308
14%
86%
10%
131%
-19%
228%
Tobira
RGDO
13.44
50
N/A
N/A
1377%
-81%
-80%
87%
Average
1,319
25%
75%
237%
26%
-50%
89%
Median
210
14%
86%
7%
9%
-48%
94%
92
33%
67%
43%
-57%
-39%
81%
5,070.03
7%
13%
-1%
24%
796.11
13%
28%
-3%
47%
1,255.66
4%
4%
-2%
21%
GLMD
NASDAQ Composite
^IXIC
NASDAQ Health Care
^IXHC
Russell 2000 Index
^RUT
$
5.62 $
Market
Value
Share Price Appreciation:
111
Galmed
$
Per Share (%):
8.30 $
Market data as of 5/19/15; financial data based on Google Finance and company reports;
2013 share price appreciation for GLMD based on IPO price of $13.50 on 3/13/14.
$13.50
Imputed GLMD Price PS Based on
Cash PS of Peer Median = ~$20
May 2015
22
Mergers & Acquisitions … Gaining Steam
May 2015
23
Increased Visibility with the Investment Community
May 2015
24
In Closing – The Galmed Opportunity
Major strides in shifting the ARREST study into 5 th gear
Aramchol remains highly differentiated with a strong safety
profile, and MoA that addresses the underlying cause of NASH
Material macro advancements in NASH space – potentially the
largest disease with no approved drugs – including (a) FDA
guidance, (b) first Phase III protocol approved by FDA/EMA
Drastically increasing visibility through enhanced and proactive
IR strategy, and incremental, high-quality research coverage
Valuation arbitrage creates opportunity
May 2015
25
Thank you!
Josh Blacher, CFO
551 Fifth Avenue, New York, NY 10176
T: +1.646.780.7605 | M: +972.52.770.2655
[email protected]
Please visit www.galmedpharma.com for more information
BACK-UP
SLIDES
Leadership
• Allen Baharaff – President & Chief Executive Officer
– Founded Galmed and advanced the Company to current stage of development
– BSc from London School of Economics; LLB, MA from Cambridge University
• Maya Halpern, MD, MA – Chief Medical Officer
– Extensive experience in conducting clinical trials, and medical aspects of drug marketing
– Previously Medical Director at Teva Pharmaceuticals
– MD from Hadassah Medical School; MA in Health Admin. from Ben Gurion University
• Josh Blacher – Chief Financial Officer
– Previously Director of Business Development at Teva Pharmaceuticals and LifeWatch
– Key positions in investment management and strategic advisory at DB, MS and Lehman
– MBA in Finance from Columbia Business School
• George Tonelli – Vice President, Clinical Operations
– Previously planned and managed multiple diabetes trials at MannKind culminating in FDA approval of
Afrezza® Inhalable Insulin
• Maureen Graham, PhD – Vice President, Regulatory Affairs
– 25+ years experience including (GSK, Merck, IVAX and Amgen)
• Antony Appleyard, PhD – Vice President, Drug Development
– 15+ years of experience in R&D, formulation, and manufacturing
May 2015
The Variation in Endpoints
ARREST
(Galmed)
FLINT
(Intercept)
Golden
(Genfit)
Enrollment
240
283
275
Primary Endpoint
Statistically significant
reduction in liver fat
content measured by
NMRS
2-point decrease in NAS
and no worsening of
fibrosis
“Reversing histological
steatohepatitis without
worsening of fibrosis”
Disappearance of
ballooning*
“Pattern of injury,”
independent of lesion
scores
Elimination of either
steatosis or
inflammation or
ballooning
No increase in fibrosis
score
Allow increase in fibrosis
score: Baseline F0/F1
patients can increase to
F2 and still meet
endpoint
“NASH Resolution”
“No Worsening of
Fibrosis”
No increase in fibrosis
score
* Ballooning, which is only histological feature correlated with fibrosis, occurs when the liver cell dies due to accumulation of fat; same
endpoint by Novo Nordisk (Victoza in the Lean Study, which is Phase IIa with 52 patients).
Cholesterol efflux (%of total)
Differentiation through Mechanism-of-Action: (2)
Cholesterol Efflux
7
6
5
4
3
2
1
0
0
1
2
3
Aramchol (µg/mL)
4
• “An important factor in the etiology of atherosclerosis is the process of deranged
•
transport of excess cholesterol from peripheral cells to the liver followed by its
secretion into bile.
Activity of ABCA1 in the liver is considered to be a major factor in the control of
this process.”
May 2015
Change in Flow-Mediated Dilation (mm Hg)
Phase IIa Results: Aramchol Shown to Improve
Important Metabolic Parameters
May 2015