Gemphire Therapeutics (GEMP)

Initiating Coverage
January 4, 2017
Gemphire Therapeutics (GEMP)
Initiation Report
LifeSci Investment Abstract
Analysts
2018 – Launch Phase III programs.
Gemphire Therapeutics (NasdaqGM: GEMP) is a clinical stage biotechnology company
■
focused on the development of compounds for the treatment of diseases that
affect cardiovascular and metabolic systems. The Company’s lead drug candidate is
gemcabene, which is currently being developed for the treatment of various forms of
dyslipidemia. Gemphire has ongoing clinical trials for gemcabene in homozygous familial
hypercholesterolemia (HoFH) and hypercholesterolemia, and also plans to initiate a study in
severe hypertriglyceridemia (SHTG) in the near future. Primary endpoints for the dyslipidemia
trials all focus on lipid lowering, and topline results from these studies are expected in 2017.
Due to gemcabene’s mechanism of action, this asset also has potential to treat liver indications
such as NASH, which Gemphire may pursue in the future.
Market Data
Key Points of Discussion
■ Gemcabene is Being Developed for a Range of Dyslipidemia Disorders. Gemcabene
is an oral, once-daily tablet being developed as an adjunctive lipid-lowering therapy for the
treatment of high-risk patients with various dyslipidemia disorders. Dyslipidemia refers to
abnormal levels of blood lipids, such as low-density lipoprotein cholesterol (LDL-C) and
triglycerides (TG), which are risk factors for cardiovascular disease, stroke, and pancreatitis.
Gemcabene is a first-in-class compound that functions through two mechanisms of action:
reduced hepatic production of cholesterol and triglycerides, and enhanced clearance of
very low-density lipoprotein (VLDL). Three Phase II clinical trials have been completed
to date that have established proof-of-concept, as gemcabene has demonstrated its ability
to reduce various blood lipids.
■ Ongoing Gemcabene Trials. Gemphire has two ongoing Phase IIb clinical trials with
gemcabene for the treatment of dyslipidemia indications. One study, called COBALT-1,
is assessing gemcabene for the treatment of homozygous familial hypercholesterolemia
(HoFH). The second trial, called ROYAL-1, is focused on gemcabene for patients
with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular
disease (ASCVD). The Company also plans to initiate a third Phase IIb study for
severe hypertriglyceridemia (SHTG), which will be called INDIGO-1. Interim data from
COBALT-1 are expected in the first quarter of 2017 and data from ROYAL-1 and
INDIGO-1 are expected in the second half of 2017.
*Pro forma
Financials
Expected Upcoming Milestones
■ Q1 2017 – Interim data from the Phase IIb COBALT-1 study for HoFH are expected.
■ Q2 2017 – Topline data from COBALT-1 are expected.
■ H2 2017 – Topline data from the Phase IIb ROYAL-1 study for HeFH/ASCVD are
expected.
■ H2 2017 – Topline data from the Phase IIb INDIGO-1 study for SHTG are expected.
■ H1 2018 – Hold end of Phase II meetings with FDA.
Jerry Isaacson, Ph.D. (AC)
(646) 597-6991
jisaacson@lifescicapital.com
Patrick Dolezal, M.S.
(212) 915-2579
pdolezal@lifescicapital.com
Price $7.89
Market Cap (M) $73
EV (M) $45
Shares Outstanding (M) 9.3
Fully Diluted Shares (M) 11.6
Avg Daily Vol 13,590
52-week Range: $7.25 - $13.98
Cash (M)* $24.0
Net Cash/Share $2.57
Annualized Cash Burn (M) $18.0
Years of Cash Left 1.3
Debt (M) $0.0
Short Interest (M) 0.01
Short Interest (% of Float) 0.2%
FY Dec 2014A 2015A 2016A
EPS Q1 NA NA NA
Q2 NA NA (0.42)A
Q3 NA NA (0.56)A
Q4 NA NA NA
FY NA NA NA
For analyst certification and disclosures please see page 35
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January 4, 2017
§ Biomarker Data Validate the Primary Endpoints of Ongoing Trials. All of Gemphire’s ongoing trials utilize
one of two biomarkers as their primary endpoint, plasma levels of LDL-C or TG. Gemcabene has previously
demonstrated its ability to lower each of these lipids in various Phase II clinical trials. One study was a Phase II
clinical trial with gemcabene for the treatment of hypercholesterolemia as an adjunct to stable statin therapy. 66
patients were randomized 1:1:1 to receive 300 or 900 mg gemcabene, or placebo for 8 weeks. The primary endpoint
was met, as patients receiving 300 and 900 mg gemcabene achieved LDL-C reductions of 23.4% (p=0.005) and
27.7% (p

January 4, 2017
§ Competing Company Esperion Mimics Gemphire’s Regulatory Strategy, Validating Approach. Esperion is
developing ETC-1002, or bempedoic acid, to treat patients with hypercholesterolemia that is not controlled by use
of lipid-lowering therapies. The company has initiated four Phase III studies with ETC-1002 in various dyslipidemia
populations and also plans to begin a cardiovascular outcomes trial (CVOT), all of which are to be included in
regulatory filings to the FDA and EMA. Notably, three of these studies utilize LDL-C lowering as their primary
endpoint. This strategy was unveiled on October 13 th , 2016, concurrently with results from a Phase II study in
patients with hypercholesterolemia on any statin at any dose. After 8 weeks, patients treated with bempedoic acid
had LDL-C reductions of 22% as compared to baseline (p=0.0028). The inclusion of patients on any statin at any
dose in Esperion’s Phase III program represents a significant departure from their prior strategy to pursue approval
for the treatment of statin-intolerant patients. The change, in addition to the use of LDL-C as a primary endpoint,
makes Esperion’s regulatory approach quite similar to that of Gemphire and comes in light of an ongoing dialogue
that the company has had with the FDA, serving as a point of validation for Gemphire’s strategy.
§ Gemcabene Has a Complementary Mechanism of Action to Approved Therapies. Gemcabene’s mechanism
of action involves reducing the production of cholesterol and triglycerides, while also enhancing the clearance of
very low-density lipoprotein (VLDL). Importantly, this mechanism does not require LDL receptor activity, which
makes the drug particularly well suited for the large group of dyslipidemia patients who do not have LDL receptor
expression or carry non-functional receptors. In contrast, statins and PCSK9 inhibitors both act through
mechanisms that involve the LDL receptor, which is problematic for HoFH and HeFH patients who carry
mutations that render the receptors non-functional. Even those patients with residual LDL receptor activity tend to
inadequately respond to statin therapy. 1 Although these agents do have a beneficial effect for some, many patients
require combination therapy with other lipid lowering agents in order to reach target LDL­C levels. For this reason,
it is mechanistically logical to combine these therapies with gemcabene.
Gemcabene also has a different mechanism than recently approved oral therapies Juxtapid and Kynamro. For example,
Juxtapid is an oral inhibitor of the microsomal triglyceride transport protein (MTP), and Kynamro is an anti­sense
oligonucleotide inhibitor that blocks the synthesis of ApoB100. Both of these therapies cause the accumulation of
fat in the liver and carry boxed warnings for potential liver toxicity. Considering that gemcabene reduces production
of cholesterol and triglycerides in the liver, the mechanisms of these compounds are well differentiated.
§ Unmet Need for Dyslipidemia Patients Remains despite New Therapies. Four new drugs have recently been
approved for reducing LDL-C for some of the dyslipidemia populations that Gemphire is targeting: Aegerion’s
(NasdaqGS: QLTI) Juxtapid (lomitapide), Ionis (NasdaqGS: IONS) and Kastle Therapeutics’ Kynamro (mipomersen),
Amgen’s (NasdaqGS: AMGN) Repatha (evolocumab), and Sanofi (NYSE: SNY) and Regeneron’s (NasdaqGS:
REGN) Praluent (alirocumab). While these relatively new drugs offer additional treatment options for patients with
various dyslipidemias, a large unmet medical need remains. Even with an aggressive combination of available
therapies, subjects with HoFH generally have LDL­C levels substantially above the treatment target of 70 mg/dL.
Furthermore, significant safety risks are associated with Juxtapid and Kynamro treatment, evidenced by their boxed
warnings related to hepatotoxicity concerns. Gemcabene has potential to mitigate these risks while providing
patients with similar or improved reductions in LDL-C.
1 Raal, F.J. et al., 1997. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolemia. Atherosclerosis, 135,
pp244-256.
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January 4, 2017
§ Late Stage Therapies in Development for Dyslipidemia Unlikely to Impact Current Treatment Landscape.
Two notable programs currently in late stage development are Merck’s (NYSE: MRK) anacetrapib and Ionis’s
volanesorsen, but these programs are unlikely to alter the treatment landscape in our view. Anacetrapib is a CETP
inhibitor that has been shown to reduce LDL-C levels, but reductions in lipid levels have not translated into better
cardiovascular outcomes for the CETP inhibitor drug class. Examples of failed CVOTs for CETP inhibitors include
Eli Lilly’s (NYSE: LLY) evacetrapib, Pfizer’s (NYSE: PFE) torcetrapib, and DalCor Pharmaceuticals’ dalecetrapib.
These findings leave us skeptical that CEPT inhibitors are capable of reducing cardiovascular events.
Volanesorsen is an antisense therapy that reduces apoC-III protein production, with the intent of lowering TG
levels. Despite solid efficacy in clinical trials to date, several safety issues have surfaced in similar compounds. For
example, Arrowhead’s (NasdaqGS: ARWR) ARC-520 was recently put on clinical hold due to deaths of primates in
a toxicology study and has since caused them to abandon their three lead programs. Also, Alnylam (NasdaqGS:
ALNY) stopped a late stage clinical trial with revusiran for the treatment of ATTR amyloidosis with cardiomyopathy
due to a higher number of deaths in the treatment arm. Although we discourage speculating on the future potential
of volanesorsen purely based on these events, the safety risks involved with developing antisense compounds are
significant. Volanesorsen is being developed for the treatment of hypertriglyceridemia, familial chylomicronemia
syndrome (FCS), and familial partial lipodystrophy (FPL), and has potential to affect the SHTG treatment landscape,
but is unlikely to affect the treatment of HoFH, HeFH, and ASCVD.
Financial Discussion
Third Quarter 2016 Financials. On November 2 nd , Gemphire announced results for the third quarter of 2016 and
provided a corporate update. General and administrative expenses for the third quarter of 2016 were $1.5 million,
up from $1 million for the same period of 2015. Research and development expenses for the third quarter of 2016
were $1.9 million, as compared to $1.4 million in for the same period of 2015. Net loss attributable to common
shareholders for the third quarter of 2016 was $3.9 million or $0.56 per share, as compared to a net loss of $2.7
million or $0.87 per share for the same period of 2015. Gemphire is expecting increases in operating expenses over
the next several quarters due to costs associated with the clinical development of gemcabene. As of September 30 th ,
2016, Gemphire reported cash and cash equivalents of $28.4 million. The Company has guided that this cash should
be sufficient to fund operations through the three planned Phase IIb clinical trials and end of Phase II meetings with
the FDA in the first half of 2018.
Initial Public Offering. Gemphire began trading on the Nasdaq as of August 5 th , 2016, after the completion of an
initial public offering. The Company issued a total of 3,000,000 shares of common stock priced to the public at $10
per share, translating to gross proceeds to Gemphire of $30 million.
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January 4, 2017
Table of Contents
Company Description .................................................................................................................................................................... 6
Gemcabene: A Novel Oral Treatment for the Treatment of Dyslipidemia .......................................................................... 6
Mechanism of Action ................................................................................................................................................................ 7
Preclinical Studies ...................................................................................................................................................................... 8
Safety ........................................................................................................................................................................................... 9
Dyslipidemia .................................................................................................................................................................................. 10
Atherosclerotic Cardiovascular Disease (ASCVD) ............................................................................................................ 11
Heterozygous Familial Hypercholesterolemia (HeFH) ..................................................................................................... 12
Homozygous Familial Hypercholesterolemia (HoFH)...................................................................................................... 12
Severe Hypertriglyceridemia (SHTG) .................................................................................................................................. 13
Pharmacological Treatments for Dyslipidemia ................................................................................................................... 13
Dyslipidemia Market Information ............................................................................................................................................. 16
Epidemiology ........................................................................................................................................................................... 16
Market Size ............................................................................................................................................................................... 16
Commercialization Strategy for Gemcabene ............................................................................................................................ 18
Clinical Data Discussion .............................................................................................................................................................. 18
Phase II Study with Gemcabene for Patients with Hypercholesterolemia (Trial 1027-018) ....................................... 19
Phase II Study with Gemcabene for Patients with Low HDL-C and High TG (Trial 1027-004) ............................. 21
COBALT-1, a Phase IIb Trial for Patients with HoFH ................................................................................................... 23
ROYAL-1, a Phase IIb Trial for Patients with Hypercholesterolemia ........................................................................... 23
INDIGO-1, a Phase IIb Trial for Patient with Severe Hypertriglyceridemia ................................................................ 24
Other Drugs in Development .................................................................................................................................................... 24
Competitive Landscape ............................................................................................................................................................... 27
Gemcabene for the Treatment of Non-Alcoholic Steatohepatitis (NASH) ....................................................................... 29
Intellectual Property ..................................................................................................................................................................... 29
Management Team ....................................................................................................................................................................... 30
Risk to an Investment .................................................................................................................................................................. 34
Analyst Certification ..................................................................................................................................................................... 35
Disclosures ..................................................................................................................................................................................... 35
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January 4, 2017
Company Description
Gemphire Therapeutics is a clinical stage biotechnology company focused on the development of compounds for
the treatment of diseases that affect cardiovascular and metabolic systems. The Company was founded in 2011 upon
the licensing of lead asset gemcabene from Pfizer (NYSE: PFE), and in the third quarter of 2016 completed a $30
million initial public offering to fund several clinical trials for this product. Gemcabene is a first-in-class, oral, oncedaily
tablet with a mechanism of action that has broad therapeutic effects, giving it potential to treat a variety of
indications. Gemphire is currently studying this compound in patients with various dyslipidemias, or blood lipid
disorders, that are at high risk for cardiovascular disease or pancreatitis despite standard of care treatment, as well as
non-alcoholic steatohepatitis (NASH).
The Company has ongoing clinical trials for gemcabene in homozygous familial hypercholesterolemia (HoFH) and
hypercholesterolemia, and also plans to initiate a study in severe hypertriglyceridemia (SHTG) in the near future.
Primary endpoints for the dyslipidemia trials all focus on lipid lowering, and topline results from these studies are
expected in 2017. Due to the mechanism of action of gemcabene, this asset also has potential to treat liver
indications such as NASH, which Gemphire may pursue in the future. The Company’s pipeline, along with key
milestones, is presented in Figure 1.
Figure 1. Gemphire Pipeline
Phase I Phase II Phase IIb
Milestones
Gemcabene
HoFH: COBALT-1 trial
Data expected: H1 2017
Hypercholesterolemia – HeFH & ASCVD: ROYAL-1 trial
Data expected: H2 2017
SHTG: INDIGO-1 trial
Data expected: H2 2017
Source: LifeSci Capital
Gemcabene: A Novel Oral Treatment for the Treatment of Dyslipidemia
Gemcabene is an oral, once-daily tablet being developed as an adjunctive lipid-lowering therapy for the treatment of
high-risk patients with various dyslipidemia disorders. Dyslipidemia refers to abnormal levels of blood lipids, such as
low-density lipoproteins (LDL) and triglycerides (TG), which are risk factors for cardiovascular disease, stroke, and
pancreatitis. Gemcabene is a first-in-class compound that functions through two mechanisms of action: reduced
hepatic production of cholesterol and triglycerides, and enhanced clearance of very low-density lipoprotein (VLDL).
Three Phase II clinical trials have been completed to date that established proof-of-concept in dyslipidemia
indications.
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January 4, 2017
Phase II hypercholesterolemia studies have demonstrated the ability of gemcabene to reduce levels of low-density
lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), apolipoprotein B (apoB), C-reactive
protein (CRP), non-high-density lipoprotein cholesterol (non-HDL-C), and very low-density lipoprotein (VLDL-C).
Gemphire has two ongoing Phase IIb clinical trials with gemcabene for the treatment of various dyslipidemia
indications. One study is assessing gemcabene for the treatment of homozygous familial hypercholesterolemia
(HoFH), called COBALT-1. The second is focused on gemcabene for patients with heterozygous familial
hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD), which is called the ROYAL-1
trial. The Company also plans to initiate a third Phase IIb study for severe hypertriglyceridemia (SHTG), which will
be the INDIGO-1 trial. Interim data from COBALT-1 are expected in the first quarter of 2017 and data from
ROYAL-1 and INDIGO-1 are expected in the second half of 2017.
Mechanism of Action. Gemphire is targeting patients who have dyslipidemia indications characterized by high
levels of LDL-C, a well-validated risk factor that has a positive correlation with cardiovascular events. 2 The
Company is also studying gemcabene in patients with very high TG levels, which is a risk factor for acute
pancreatitis and ASCVD. 3, 4 This product has potential in these indications due to its novel, dual mechanism of
action that results in broad lipid-lowering activity of LDL-C, TG, VLDL, high-sensitivity c-reactive protein (hsCRP),
as well as increases in the healthy blood lipid HDL-C.
Gemcabene is designed to reduce production of cholesterol and triglycerides, while also enhancing the clearance of
very low-density lipoprotein (VLDL), as detailed in Figure 2. Treatment with gemcabene reduces levels of
messenger RNA (mRNA) that codes for apolipoprotein C-III (apoC-III). ApoC-III reduces the clearance of VLDL
and in turn lowers plasma LDL-C, as VLDL is converted to LDL-C in the bloodstream. In addition, the reduction
of apoC-III also reduces hepatic uptake of VLDL by remnant receptors.
2 Stein, E. et al., 2016. Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients.
Journal of Clinical Lipidology, 10(5), pp1212-1222.
3 Ewald, N. et al., 2009. Severe hypertriglyceridemia and pancreatitis: presentation and management. Current Opinion in Lipidology,
20(6), pp497-504.
4 Esther, M. et al., 2008. Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. Clinical Science, 114(10),
pp611-624.
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January 4, 2017
Gemcabene Novel Mechanism of Action
Figure 2. Gemcabene Mechanism of Action and Chemical Structure
Acetyl-CoA
2. Production Mechanism
Cholesterol Pathway
Triglyceride Pathway
2B
Gemcabene
reduces
production of
cholesterol in
the pathway
Acetoacetyl-CoA
HMG-CoA
Acetyl-CoA
carboxylase (ACC)*
Malonyl-CoA
2A
Gemcabene
reduces
production of
triglycerides in
the pathway
LDL
Gemcabene Molecule
• Plasma half life of 32 to 41 hours
• Liver is target organ
• Gemcabene is the active compound
• Renal elimination
Mevalonate
Fatty-acyl-CoA
TG
*Potential molecular targets are in italics
Cholesterol
Results in
reduction
of lipids
Triglycerides
1
ApoC–III*
VLDL
ApoC–III
VLDL
ApoE
ApoE
VLDL Remnant
1. Clearance Mechanism
Gemcabene clears
VLDL efficiently due to
a reduction in ApoC-III
LDL
Results in
reduction of
LDL
15
Source: Company Presentation
Preclinical Studies
Several preclinical studies have been performed to assess the mechanism of action, toxicity, and efficacy of
gemcabene. Below we highlight an efficacy study that sought to determine the impact of gemcabene treatment on
low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels in a commonly used mouse model of
HoFH. This study is informative for the ongoing COBALT-1 Phase IIb clinical trial in this indication.
Gemcabene and Atorvastatin Alone and Combination in LDL-C Receptor Deficient Mice. This study tested
the effects of gemcabene and/or Lipitor (atorvastatin) in the treatment of LDL-C receptor deficient mice on a chow
or cholesterol-enriched diet. Baseline TC and LDL-C levels were assessed and mice received one of three treatment
regimens for 14 days: 60 mg/kg/day gemcabene as monotherapy, 60 mg/kg/day atorvastatin as monotherapy, or
both treatments in combination. Following treatment, TC and LDL-C levels were measured again and the percent
change from baseline is presented in Figure 3. Baseline TC and LDL-C levels were 329 mg/dL and 246 mg/dL,
respectively.
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January 4, 2017
Figure 3. Preclinical Effects of Gemcabene and Atorvastatin on LDL-C and Total Cholesterol
0
Atorvastatin 60 mg/kg/day Gemcabene 60 mg/kg/day
Atorvastatin + Gemcabene
60 mg/kg/day
Percent Change Relative to Control
-0.1
-0.2
-0.3
-0.4
-0.5
-0.6
-0.7
-0.8
-21% -22%
Total Cholesterol
-47%
LDL-C
-55%
-58%
-72%
Source: Bisgaier, C. et al., 2015.
Mice treated with gemcabene alone had meaningful reductions in both TC and LDL-C as compared to controls.
These reductions are numerically greater than those achieved in mice treated with atorvastatin alone. Notably, mice
treated with both drugs in combination showed the greatest reductions in TC and LDL-C levels. These data speak
to the mechanism of action of gemcabene, which appears to be distinct from that of atorvastatin and may be
independent of LDL-C receptor expression. In light of these findings, investigators speculated that gemcabene may
be exerting this effect by reducing VLDL production, as opposed to acting through the LDL-C receptor.
Therapies that can reduce LDL-C levels in patients with little or no LDL-C receptor expression, as is the case in
HoFH and HeFH patients, is extremely important because the LDL-C lowering effects of statins and PCSK9
inhibitors involve these receptors. These data are a major point of validation for the potential of gemcabene in
HoFH patients.
Safety. Relative to most Phase II assets, gemcabene has a robust dataset regarding its use in humans. Gemcabene
has been studied in 18 clinical trials that cumulatively enrolled 1,272 patients. Through these studies, participants
received single doses of up to 1,500 mg and were treated for up to 12 weeks. 10 volunteers experienced serious
adverse events (SAE) overall, but none were determined to be related to gemcabene use. There were small mean
increases in serum creatinine and blood urea nitrogen levels in some trials, and these effects were reversed after
treatment was stopped. ALT and AST levels were similar between gemcabene and placebo groups. Though
increases in creatinine and blood urea nitrogen levels represent potential excretion concerns, the events seem to be
rare and greater clinical detail is required prior to drawing any meaningful conclusions. Overall, there are no major
safety concerns to date and the profile of gemcabene supports continued development in human clinical trials.
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January 4, 2017
Two Phase I pharmacokinetic studies were conducted to determine whether gemcabene has drug-drug interactions
when used in combination with high-dose statins. The results of these trials are presented in Figure 4, which
assessed gemcabene use with Zocor (simvastatin, left) and atorvastatin (right).
Figure 4. High Dose Statin Exposure in Combination with Gemcabene
Atorvastatin Concentration, ng/mL
30
25
20
15
10
5
0
Atorvastatin 80 mg
Atorvastatin 80 mg + GEM 300 mg
Atorvastatin 80 mg + GEM 900 mg
0 4 8 12 16 20 24
Time (Hr)
Active HMG-CoA Reductase Inhibitor
Concentration, ng equivalents/mL
35
30
25
20
15
10
5
0
Simvastatin 80 mg
Simvastatin 80 mg + GEM 900 mg
0 4 8 12 16 20 24
Time (Hr)
Source: Company Presentation
Concentrations of active HMG-CoA reductase inhibitors, or statins, do not appear to be appreciably different in
patients receiving 80 mg simvastatin and 900 mg gemcabene as compared to simvastatin alone. Concentrations of
atorvastatin are almost identical between 80 mg atorvastatin alone and in combination with 300 or 900 mg
gemcabene. Taken together, these findings greatly de-risk any potential safety risks of gemcabene when used in
combination with statins.
Dyslipidemia
Dyslipidemia is the presence of abnormal levels of lipids, primarily cholesterols, circulating in the blood stream. Less
than half of US adults maintain normal total blood cholesterol (TC) levels, which are defined as less than 200
mg/dL. Approximately 31 million US adults have TC greater than or equal to 240 mg/dL, which is defined as
dyslipidemia/hypercholesterolemia and is a risk factor for cardiovascular disease and stroke. 5 TC is a cumulative
measure of blood lipid levels, including low-density lipoproteins (LDL), 20% of triglyceride (TG) levels and highdensity
lipoproteins (HDL).
LDL, TG, and HDL are the primary biological markers used to assess dyslipidemias, and are frequently used as
surrogate endpoints in trials for lipid disorders. Gemphire is assessing gemcabene for its ability to modify blood lipid
levels in the following dyslipidemia disorders: non-familial hypercholesterolemia and mixed dyslipidemia (ASCVD),
heterozygous familial hypercholesterolemia (HeFH), homozygous familial hypercholesterolemia (HoFH), and severe
hypertriglyceridemia (SHTG). A summary of the characteristics of these dyslipidemia indications is highlighted in
Figure 5.
5 Mozaffarian, D. et al., 2015. Heart Disease and Stroke Statistics—2016 Update, A Report from the American Heart
Association. Circulation, 134(12), pp1-323.
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January 4, 2017
Figure 5. Summary of Dyslipidemia Indications
Affected Lipids
Diagnostic Criteria
Treatment Goal
ASCVD HeFH HoFH SHTG
LDL-C, in some
cases TG
LDL-C > 70 mg/dL
& CV events; TG >
150 mg/dL
Lower LDL-C &
TG, Raise HDL-C
LDL-C LDL-C TG
LDL-C > 190
mg/dL
LDL-C > 500
mg/dL
TG 500-2000
mg/dL
Lower LDL-C Lower LDL-C Lower TG
Atherosclerotic Cardiovascular Disease (ASCVD)
Source: LifeSci Capital
Atherosclerotic cardiovascular disease (ASCVD) develops as a result of the build up of cholesterol-rich plaques,
causing arteries to narrow and harden. 6 As the condition of the arteries worsens over time, cardiovascular events can
precipitate, such as stroke or heart attack. Risk factors for ASCVD include high TC and LDL-C, diabetes, smoking,
high blood pressure, or low HDL-C. Clinical ASCVD refers to patients who have had cardiovascular events in the
past combined with LDL-C levels above the target of 70 mg/dL. Some of these patients also have triglyceride levels
above the target of 150 mg/dL, which is called mixed dyslipidemia. Cardiovascular events/diseases that qualify
clinical ASCVD include the following:
§ Coronary artery disease
o Acute coronary syndrome
o History of myocardial infarction
o Stable or unstable angina
o History of coronary revascularization
§ Stroke or transient ischemic attack (TIA)
§ Peripheral arterial disease, with history of revascularization
Testing blood lipid levels provides physicians supportive data for diagnosis of ASCVD, which is performed with a
blood lipid panel. If additional diagnostic criteria are desired, physicians can assess lifetime heart attack and stroke
risk, coronary artery calcium score, high-sensitivity c-reactive protein levels, and ankle brachial index. Treatment of
non-familial dyslipidemia focuses on reducing LDL-C levels, while in mixed dyslipidemia reducing TG levels and
increasing HDL-C levels are also goals.
Other lifestyle changes can also be implemented, including: weight control, exercise, and a low-fat diet rich in fruit,
vegetables, and whole grains can help modulate the relevant lipid levels. However these changes can be difficult for
patients to adhere to and usually are not adequate. Standard of care medications to reduce LDL-C are statins and
6Guideline for Treating Blood Cholesterol to Reduce Cardiovascular Risk. American College of Cardiology. Available at:
https://www.cardiosmart.org/Heart-Conditions/Guidelines/Cholesterol. Accessed November 15, 2016.
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January 4, 2017
additional therapies can be added if necessary, including: ezetimibe, bile acid sequestrants, and niacin. Patients
requiring TG reduction may also take fibrates.
Heterozygous Familial Hypercholesterolemia (HeFH)
Heterozygous familial hypercholesterolemia (HeFH) is a genetic lipid disorder that affects roughly 1 in every 500
people. 7 The disorder is usually caused by a heterozygous loss of function mutation to the low-density lipoprotein
(LDL) receptor gene, which produces a protein responsible for removing LDL cholesterol (LDL-C) from the
blood. 8 Patients with HeFH have LDL-C levels greater than 190 mg/dL, which can lead to early cardiovascular
disease, myocardial infarction, or stroke. Due to the asymptomatic nature of the disease prior to a cardiovascular
event or appearance of cholesterol deposits called xanthomas, just 10% of patients with HeFH are properly
diagnosed. Patients with a family history of heart disease or high cholesterol should have lipid panels performed to
test for high LDL-C levels that could be a result of HeFH.
The goal of HeFH treatment is to lower LDL-C to the normal range. This includes lifestyle modifications such as
weight control, exercise, smoking cessation, and a low-fat diet rich in fruit, vegetables, and whole grains, though
these changes typically are not sufficient. Standard of care medications include statins and additional therapies can
be added if necessary, including: ezetimibe, bile acid sequestrants, and niacin.
Homozygous Familial Hypercholesterolemia (HoFH)
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder that affects approximately 1 in
every 1 million individuals worldwide. 9 The disorder is usually caused by homozygous mutations leading to loss of
function in the low-density lipoprotein (LDL) receptor gene, which produces a protein responsible for removing
LDL cholesterol (LDL-C) from the blood. 10 LDL­C levels are around 100 mg/dL in healthy individuals. Patients
with HoFH may present with levels that exceed 500 mg/dL. These patients quickly develop atherosclerosis, which
increases the risk of a serious or fatal cardiac event very early in life. Many HoFH patients experience heart attack or
stroke before the age of 20, and the average age of death is approximately 40.
The current standard of care is lipid apheresis combined with high dose statins. However, this procedure is not
universally available and most patients do not achieve optimal LDL levels with these therapies. Aegerion’s
(NasdaqGS: QLTI) Juxtapid (lomitapide) and Sanofi’s (NasdaqGS: SNY) Kynamro (mipomersen) have recently been
approved for the treatment of HoFH in the US. Both labels carry boxed warnings due to liver toxicity, and patients
must undergo monthly liver function testing. Amgen’s (NasdaqGS: AMGN) Repatha (evolocumab) was also recently
approved for HoFH as an adjunct to statin therapy, and belongs to a novel class of cholesterol-lowering therapies
called PCSK9 inhibitors.
7 Raal, F. et al., 2012. Low-Density Lipoprotein Cholesterol-Lowering Effects of AMG 145, a Monoclonal Antibody to
Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia.
Circulation, 126(20), pp2408-2417.
8 Brown, M.S. and Goldstein, J.L., 1986. A receptor-mediated pathway for cholesterol homeostasis. Science, 232(4746), pp34-47.
9 Bruckert, E., 2014. Recommendation for the management of patients with homozygous familial hypercholesterolaemia:
Overview of a new European Atherosclerosis Society consensus statement. Atherosclerosis, 15, pp26-32.
10 Brown, M.S. and Goldstein, J.L., 1986. A receptor-mediated pathway for cholesterol homeostasis. Science, 232(4746), pp34-47.
Page 12

January 4, 2017
Repatha blocks LDL receptor recycling so that the receptors remain available on the surface of hepatocytes and
remove circulating cholesterol. However, not all HoFH patients have sufficient LDL receptor function to benefit
from Repatha. This is in stark contrast to the mechanism of action of gemcabene, which does not require LDL
receptor activity. Gemphire is developing gemcabene as a more convenient, less expensive, and more broadly
applicable treatment for the reduction of LDL-C in patients with HoFH.
Severe Hypertriglyceridemia (SHTG)
Severe hypertriglyceridemia (SHTG) is defined by plasma triglyceride levels between 500-2000 mg/dL and is
associated with coronary artery disease and pancreatitis. 11 Triglycerides are primarily derived from dietary fat or are
produced by the liver, and levels predominantly become elevated secondary to conditions such as diabetes, obesity,
carbohydrate-rich diet, hypothyroidism, hepatitis, and use of alcohol or certain drugs. 12 SHTG is diagnosed via lipid
panel at fasting TG levels, utilizing the following criteria in Figure 6:
Figure 6. Diagnostic Criteria for Severity of Hypertriglyceridemia
Severity
Normal
Mild hypertriglyceridemia
Moderate hypertriglyceridemia
Severe hypertriglyceridemia
Very severe hypertriglyceridemia
Triglyceride Level
< 150 mg/dL
150-199 mg/dL
200-499 mg/dL
500-2000 mg/dL
> 2000 mg/dL
Source: Christian, J.B. et al., 2011
First line treatment for SHTG involves lifestyle modifications such as weight control, exercise, and diet
modifications that restrict fat to 10-15% of total energy intake with reductions in saturated, unsaturated, and trans
fats. Pharmacologic treatments are typically used as an adjunct to lifestyle modifications, first alone and then in
combination if needed. Standard of care pharmacologic treatment for SHTG is with fibrates, which can reduce
plasma TG levels by as much as 50%. Second-line therapies include statins and niacin. In the case of a medical
emergency such as hypertriglyceridemic pancreatitis, lipid apheresis may be performed.
Pharmacological Treatments for Dyslipidemia
Standard of care pharmacological treatments for ASVCD, HeFH, and HoFH are drugs belonging to the statin drug
class, and other therapies that lower LDL-C levels may be added if patients are unable to reach target lipid levels.
However, the FDA recently withdrew approval for combination use of fibrate or niacin as adjunct to statin therapy,
likely greatly limiting their use in these indications considering statins are first-line therapies. These therapies largely
work by increasing activity of the LDL receptor, which is problematic for patients who carry mutations that render
the receptors non-functional, as is the case for HeFH and HoFH. Even those patients with residual LDL receptor
11 Ewald, N. et al., 2012. Treatment options for severe hypertriglyceridemia (SHTG): the role of apheresis. Clinical Research in
Cardiology Supplements, 7(1), pp31-35.
12 Kota, S.K. et al., 2012. Hypertriglyceridemia-induced recurrent acute pancreatitis: A case-based review. Indian Journal of
Endocrinology and Metabolism, 16(1), pp141-143.
Page 13

January 4, 2017
activity tend to inadequately respond to these therapies. 13 Four new drugs have recently been approved for reducing
LDL-C for some of these dyslipidemia populations: Aegerion’s (NasdaqGS: QLTI) Juxtapid (lomitapide), Ionis
Pharmaceuticals’ (NasdaqGS: IONS) Kynamro (mipomersen), Amgen’s (NasdaqGS: AMGN) Repatha (evolocumab),
and Sanofi/Regeneron’s (NYSE: SNY, NasdaqGS: REGN) Praluent (alirocumab). They are discussed in more detail
below. A summary of lipid lowering therapies and their respective indications, all of which are being targeted by
gemcabene, are presented in Figure 7.
Figure 7. Lipid Lowering Treatments and Indications
Drug Class Mechanism of Action ASCVD HeFH/HoFH SHTG
Statin
HMG-CoA reductase
inhibitor
✓* ✓* ✓
Fibrate PPAR agonist ✓*
Niacin
Niacin receptor
agonist
✓
✓
PCSK9 PCSK9 inhibitor ✓ ✓
Omega-3 fatty acid
ethyl esters
Acyl CoA inhibitor
✓
Other Drugs:
Ezetimibe
Lomitapide
Mipomersen
*denotes first-line therapy
PCSK9 Inhibitors
✓
Source: LifeSci Capital
✓
✓ (HoFH)
✓ (HoFH)
The two drugs most recently approved for dyslipidemia are in a novel class of compounds called PCSK9 inhibitors
that have generated a significant amount of excitement in the space. These compounds function by blocking
PCSK9, which ultimately reduces LDL receptor degradation and thus increases receptor availability to bind
circulating LDL. This combination therapy only has potential to be effective in HeFH or HoFH patients with
residual LDL receptor activity. The approved PCSK9 inhibitors are Amgen’s (NasdaqGS: AMGN) Repatha
(evolocumab) and Sanofi/Regeneron’s (NYSE: SNY, NasdaqGS: REGN) Praluent (alirocumab).
Both therapies received approval by showing reductions in LDL-C, a surrogate endpoint for risk of cardiovascular
events. The uptake of these products has been rather anemic to date, which is likely greatly due to pricing in excess
of $14,000 but may also be due to the lack of proven reductions in the risk of cardiovascular events. This may
change depending on results from ongoing cardiovascular outcomes trials (CVOT) for each compound, which have
potential to solidify the drug class in the dyslipidemia treatment landscape and further validate LDL-C as a surrogate
endpoint for future studies.
13 Raal, F.J. et al., 1997. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolemia. Atherosclerosis, 135,
pp244-256.
Page 14

January 4, 2017
Repatha (evolocumab) - Amgen. Repatha received FDA approval on August 27 th , 2015 following a positive
Advisory Committee vote. This drug received a slightly broader label than class-competitor Praluent, as it is indicated
as an adjunct to maximally tolerated statin therapy for patients with ASCVD, HeFH, or HoFH that require
additional LDL-C lowering. For ASCVD patients on maximum-dose statin therapy, the mean reduction in LDL-C
for those taking Repatha compared to placebo at 12 weeks was 71% (p

January 4, 2017
Dyslipidemia Market Information
Epidemiology. Approximately 13.1% or 31 million US adults have TC greater than or equal to 240 mg/dL, which
is defined as dyslipidemia/hypercholesterolemia and is a risk factor for cardiovascular disease and stroke. 17 This is
largely driven by LDL-C, one of the components of TC, as roughly 71 million US adults have elevated levels of this
deleterious type of cholesterol. 18 Out of these patients, just 34 million receive LDL-C lowering therapies for their
condition and 23 million have reached their target levels for LDL-C. The large disparity between treated patients and
those achieving their LDL-C targets points to the unmet need of this population, despite a rising number of patients
receiving therapy.
From 2005 to 2008 the proportion of individuals with high LDL-C receiving treatment was approximately 48%, as
compared to 28% of patients receiving therapy between 1999 and 2002. 19 This trend has potential to continue in the
future, especially considering a recent move by the American College of Cardiology and American Heart Association
(ACC/AHA) to broaden the eligibility criteria for statin use. The change could result in an additional 45 million US
adults being recommended for treatment. Beyond these relatively direct modes of market expansion, there are also
more general macroeconomic trends that signal growth of the dyslipidemia populations in the future.
Trends that could drive expansion of the dyslipidemia markets in the US include the ongoing obesity epidemic and
aging population. The prevalence of obesity has continued to rise in the US over the past several decades, with
approximately 36.5% of the population currently considered obese. 20 Obesity also becomes more prevalent with age,
affecting 40% of people between 40-59 years of age and 37% of people above 60, as compared to 32% between 20-
39 years of age. Considering that obesity is a major risk factor for cardiovascular disease, it’s not surprising that high
LDL-C also disproportionately affects middle-aged and elderly individuals.
The number of individuals affected by dyslipidemia is likely to increase, considering that these disorders
disproportionately affect elderly individuals and that the US population is aging. The number of Americans aged 65
years or greater is expected to grow to from 43 million in 2012, to 56 million in 2020 and 73 million in 2030. 21
Continued growth in the dyslipidemia market seems likely when considering the demography of these disorders, the
high prevalence of obesity and elevated lipid levels, along with an aging US population.
Market Size. Dyslipidemias affect a large and growing number of individuals, and despite available therapies a void
remains in the treatment landscape that has created a substantial market opportunity. In order to help patients who
are not being served by current treatments and address this unmet need, Gemphire is developing gemcabene for the
treatment of HoFH, HeFH, SHTG, and ASCVD. Figure 8 highlights the patient populations for the various lipid
disorders that the Company is targeting, which is based on the following assumptions:
17 Mozaffarian, D. et al., 2015. Heart Disease and Stroke Statistics—2016 Update, A Report from the American Heart
Association. Circulation, 134(12), pp1-323.
18 Kuklina, et al., 2011. Vital Signs: Prevalence, Treatment, and Control of High Levels of Low-Density Lipoprotein Cholesterol
- United States, 1999-2002 and 2005-2008. Morbidity and Mortality Weekly Report, 60(4), pp109-14.
19 Centers for Disease Control and Prevention (CDC). Vital signs: prevalence, treatment, and control of high levels of lowdensity
lipoprotein cholesterol: United States, 1999-2002 and 2005-2008. MMWR Morbidity and Mortality Weekly Report, 60(4),
pp109-14.
20 Ogden, C.L. et al., 2015. Prevalence of Obesity Among Adults and Youth: United States, 2011-2014. National Center for Health
Statistics, 219, pp1-7.
21 Ortman, J.M. et al., 2014. An Aging Nation: The Older Population in the United States. United States Census Bureau, pp1-28.
Page 16

January 4, 2017
§ Prevalence/Incidence – The prevalence of homozygous familial hypercholesterolemia (HoFH) is
assumed to be 1 per 1,000,000 individuals. 22 The prevalence of heterozygous familial hypercholesterolemia
(HeFH) is assumed to be 200 per 100,000 individuals. 23 The prevalence of severe hypertriglyceridemia
(SHTG) is assumed to be 1,700 per 100,000 individuals. 24 The prevalence of atherosclerotic cardiovascular
disease (ASCVD) is assumed to be 2,100 per 100,000 individuals. 25
§ US Population – We assume that there are 321 million people in the US, and of those approximately 246
million are adults.
Figure 8. US Target Populations for Gemcabene
Disease
Affected US Individuals
Homozygous familial hypercholesterolemia (HoFH) ~320
Heterozygous familial hypercholesterolemia (HeFH)
640k
Severe hypertriglyceridemia (SHTG) 4.2M
Atherosclerotic cardiovascular disease (ASCVD) 6.8M
Total target population 11.6M
Source: LifeSci Capital
Gemphire is targeting several indications that are associated with abnormal blood lipid levels. The largest
constituents of the addressable market are ASCVD and SHTG, which represent a total of 11 million patients in the
US. The company is also assessing gemcabene in HoFH and HeFH, which affect a combined 640,000 patients. As a
whole, Gemphire is initially targeting a market of 11.6 million patients with gemcabene for the treatment of
dyslipidemias. Despite the large number of patients affected by these ailments, many are not well served by existing
therapies. As such, gemcabene has robust sales potential in the US markets as determined in our analysis, which is
presented in Figure 9. The following assumptions were used in this analysis:
§ Pricing – We assume the wholesale acquisition cost (WAC) of gemcabene is $3000 annually.
§ Target Population – We assume the number of patients affected by each indication is consistent with our
analysis in Figure 8.
§ Penetrance Rates – Our base case scenario assumes penetrance rates of: 40% for HoFH due to disease
severity and market competition, 5% for HeFH due to low rates of diagnosis and disease severity, 7% for
SHTG due to penetrance of other treatments in this population, and 7% for ASCVD due the penetrance of
other treatments in this population and the high proportion of patients taking statins but not reaching LDL-
C targets.
22 Bruckert, E., 2014. Recommendation for the management of patients with homozygous familial hypercholesterolaemia:
Overview of a new European Atherosclerosis Society consensus statement. Atherosclerosis, 15, pp26-32.
23 Raal, F. et al., 2012. Low-Density Lipoprotein Cholesterol-Lowering Effects of AMG145, a Monoclonal Antibody to
Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia.
Circulation, 126(20), pp2408-2417.
24 Christian, J.B. et al., 2011. Prevalence of Severe (500 to 2,000 mg/dl) Hypertriglyceridemia in United States Adults. The
American Journal of Cardiology, 107(6), pp891-897.
25 Lin, I. et al., 2016. Patterns of Statin Use in a Real-World Population of Patients at High Cardiovascular Risk. Journal of
Managed Care & Specialty Pharmacy, 22(6), pp685-98.
Page 17

January 4, 2017
Figure 9. Scenario Analysis of US Sales Potential for Gemcabene
HoFH HeFH SHTG ASCVD Total
Downside 30% 3% 6% 5%
Sales Potential $0.3 M $58 M $753 M $1,020 M $1,831 M
Base 40% 5% 9% 7%
Sales Potential $0.4 M $96 M $1,130 M $1,428 M $2,655 M
Upside 50% 7% 12% 9%
Sales Potential $0.5 M $135 M $1,507 M $1,836 M $3,478 M
Source: LifeSci Capital
If gemcabene receives broad approval across HoFH, HeFH, SHTG, and ASCVD, our base case analysis finds that
sales could eclipse $2.6 billion, with the bulk of revenues being driven by ASCVD ($1.4 billion) and SHTG ($1.1
billion). In an upside case that utilizes more optimistic penetrance rates, annual sales could approach $3.5 billion.
Commercialization Strategy for Gemcabene
Gemphire has already developed a preliminary commercialization strategy for gemcabene that involves both inhouse
commercialization as well as partnerships for certain indications and territories. In the US, the Company will
likely commercialize Gemcabene for the indications of HoFH and SHTG, although they have not excluded the
possibility of co-promoting the drug for SHTG. In contrast, Gemphire currently plans to form partnerships in the
US to market the treatment for HeFH and ASCVD. In all other territories worldwide, the Company plans to seek
commercialization partners for all indications. Gemphire’s preliminary commercialization strategy is outlined in
Figure 10.
Figure 10. Preliminary Commercialization Strategy
HoFH SHTG HeFH ASCVD
US Strategy Internal
Internal or copromotion
Partner Partner
Ex-US Strategy Partner Partner Partner Partner
Source: LifeSci Capital
Clinical Data Discussion
Several clinical trials evaluating gemcabene for the treatment of dyslipidemia have been completed. Proof-ofconcept
was established with gemcabene as a therapy for hypercholesterolemia in a Phase II study, which found that
patients receiving gemcabene achieved significant LDL-C reductions. Gemphire is currently conducting Phase IIb
clinical trials with gemcabene for the treatment of HoFH and hypercholesterolemia, which are called COBALT-1
Page 18

January 4, 2017
and ROYAL-1, respectively. The Company is also planning an additional Phase IIb study for SHTG, called
INDIGO-1, which is expected to begin in the second half of 2016.
All three of these trials utilize surrogate primary endpoints: the lowering of LDL-C levels in COBALT-1 and
ROYAL-1, and the lowering of triglycerides (TG) in INDIGO-1. Data from COBALT-1 are expected in the first
quarter of 2017, and data from ROYAL-1 and INDIGO-1 are expected in the second half of 2017. Figure 11
outlines key clinical trials for gemcabene.
Figure 11. Key Clinical Trials with Gemcabene
Clinical Trial Treatment Population Primary Endpoint
Source: LifeSci Capital
Number of
Patients
Phase I 26 Healthy adults on statins Safety / PK profile 20
Phase I 27 Healthy adults on statins Safety / PK profile 20
Phase II 28
Hypercholesterolemia patients
on statins
LDL-C lowering 66
Phase II 29 Hypertriglyceridemia patients TG lowering 161
Phase II 30
COBALT-1 Phase
IIb 31
ROYAL-1 Phase IIb 32
INDIGO-1 Phase
IIb 33
Hypercholesterolemia patients
on statins
LDL-C lowering 277
Phase II Study with Gemcabene for Patients with Hypercholesterolemia (Trial 1027-018)
Expected
Results
Complete
(2000)
Complete
(2002)
Complete
(2002)
Complete
(2001)
Complete
(2003)
HoFH patients on statins LDL-C lowering 8 H1 2017
HeFH or ASCVD patients on
moderate or high-intensity statins
LDL-C lowering 104 H2 2017
SHTG patients TG lowering 90 H2 2017
Gemphire conducted a Phase II clinical trial with gemcabene for the treatment of hypercholesterolemia to establish
proof-of-concept and assess initial signs of efficacy. This study found that patients treated with gemcabene had
26 https://clinicaltrials.gov/ct2/show/NCT02587390
27 https://clinicaltrials.gov/ct2/show/NCT02587416
28 https://clinicaltrials.gov/ct2/show/NCT02571257
29 https://clinicaltrials.gov/ct2/show/NCT02585869
30 https://clinicaltrials.gov/ct2/show/NCT02591836
31 https://clinicaltrials.gov/ct2/show/NCT02722408
32 https://clinicaltrials.gov/ct2/show/NCT02634151
33 https://clinicaltrials.gov/ct2/show/NCT02944383
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January 4, 2017
significant reductions in LDL-C at both doses tested, supporting the continued development of this compound in
dyslipidemias.
Trial Design. This was a randomized, double-blind, placebo controlled Phase II clinical trial with gemcabene for
the treatment of hypercholesterolemia as an adjunct to stable statin therapy. 34 66 patients were randomized 1:1:1 to
receive 300 or 900 mg gemcabene, or placebo for 56 days. The primary endpoint was mean percent change of LDL-
C levels as compared to baseline after 8 weeks of treatment. Secondary endpoints included mean percent change of
the following lipids as compared to baseline: triglycerides (TG), total cholesterol (TC), apolipoprotein B (apoB), C-
reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), and very low-density lipoprotein (VLDL-C).
Enrolled patients had to be adults with baseline LDL-C levels of at least 130 mg/dL or greater. Important exclusion
criteria were: triglyceride levels greater than 400 mg/dL, creatine phosphokinase levels of at least 3 times the upper
limit of normal (ULN), uncontrolled diabetes mellitus (HbA1c > 10%), renal or hepatic dysfunction, and major
cardiovascular events in prior 30 days.
Trial Results. This study met the primary endpoint of percent change in LDL-C levels as compared to baseline
after 8 weeks of treatment. The mean LDL-C baseline in this study was 150 mg/dL. Patients treated with 300 and
900 mg gemcabene had mean reductions in LDL-C of 23.4% (p=0.005) and 27.7% (p

January 4, 2017
Figure 12. Mean % Change of Key Biomarkers Compared to Baseline
0.0%
LDL-C apoB TC non-HDL-C
-5.0%
-10.0%
-6.2%
-2.8%
-4.8%
-6.9%
-15.0%
-20.0%
-25.0%
-30.0%
-23.4%
*
-27.7%
*
-11.9%
-17.2%
-15.6%
*
-19.9%
*
300 mg gemcabene 900 mg gemcabene placebo
-19.8%
*
-23.9%
*
*Denotes statistical significance (p-value < 0.05)
Source: Company Presentation
Phase II Study with Gemcabene for Patients with Low HDL-C and High TG (Trial 1027-004)
Prior to Gemphire’s acquisition of gemcabene, Pfizer conducted a phase II trial with gemcabene for the treatment
of patients with low levels of HDL-C and normal or elevated levels of TG. This study found that patients treated
with low doses of gemcabene had significantly greater TG reductions from baseline as compared to placebo. The
Company has also reported data from this study showing meaningful reductions in the subset of patients with TG
above 500 mg/dL, providing the Company with rationale to develop gemcabene for SHTG.
Trial Design. This was a randomized, double-blind, placebo controlled Phase II trial with gemcabene for the
treatment of individuals with low HDL-C and either normal or elevated TG. 35 161 patients were randomized to
receive once-daily 150, 300, 600, or 900 mg gemcabene or placebo for 12 weeks. Results were stratified based on TG
levels, and elevated TG was defined as greater than or equal to 200 mg/dL (n = 94). The primary endpoint was the
change in HDL-C levels as compared to baseline as 12 weeks. Secondary endpoints included levels of TG, LDL-C,
and VLDL-C, as well as adverse events and safety. In order to participate, patients were required to have levels of
HDL-C below 35 mg/dL. Some exclusion criteria were: creatine phosphokinase levels greater than 3 times the
upper limit of normal, body mass index greater than 35 kg/m 2 , renal or hepatic dysfunction, and history of major
cardiovascular events.
35 https://clinicaltrials.gov/ct2/show/NCT02585869
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January 4, 2017
Trial Results. The results of this trial for the cohort of patients with TG levels of 200 mg/dL or greater are
presented in Figure 13. 36 This cohort met the primary endpoint at the 150 mg gemcabene dose, showing a 17.6%
increase in HDL-C levels (p

January 4, 2017
COBALT-1, a Phase IIb Trial for Patients with HoFH
Gemphire is currently conducting a Phase IIb clinical trial (COBALT-1) with gemcabene for the treatment of HoFH
as an adjunct to statin therapy. The trial began enrolling patients in mid-2016 and interim data are expected in the
first quarter of 2017, with topline data in the second quarter of 2017.
Trial Design. This is an open-label, dose finding, Phase IIb trial with gemcabene for the treatment of HoFH. 37 8
patients will be enrolled to receive 300, 600, and 900 mg oral doses of gemcabene for four weeks each. For example,
patients will begin receiving therapy at the lowest dosage of 300 mg for four weeks, and subsequently receive doses
of 600 and 900 mg for four weeks each. This doing schedule is used to determine optimal dosing in terms of
efficacy and safety. The primary endpoint of the study is LDL-C levels at 12 weeks as compared to baseline.
Secondary endpoints include levels of TC, TG, apoB, hs-CRP, and nonHDL-C. Eligibility criteria include the
following:
§ LDL-C levels above 130 mg/dL when fasting, and upon initial screening.
§ Clinical diagnosis of HoFH as determined by: genetic testing, a history of LCL-C levels above 500 mg/dL
with xanthoma prior to age 10, or LDL-C levels above 300 mg/dL while taking statins at the MTD. Stable
doses of one or a combination of the following lipid-lowering therapies for four weeks: statins, PCSK9
inhibitors, cholesterol absorption inhibitors, bile acid sequestrants, nicotinic acid.
§ Consistent diet low in fat and cholesterol content.
Important criteria for exclusion are: abnormal liver function including liver disease, TG levels above 400 mg/dL,
renal insufficiency, major cardiovascular events, and cardiac arrhythmia. This trial began enrolling patients in August
of 2016 and interim results are expected in the first quarter of 2017.
ROYAL-1, a Phase IIb Trial for Patients with Hypercholesterolemia
Gemphire has an ongoing Phase IIb clinical trial known as ROYAL-1 with gemcabene for the treatment of patients
with hypercholesterolemia who are currently taking stable doses of high-intensity statin therapy. The Company
announced the enrollment of the first patient in this trial in the fourth quarter of 2016 and data are expected in the
second half of 2017.
Trial Design. This is a randomized, double-blind, placebo controlled Phase IIb trial with gemcabene for the
treatment of hypercholesterolemia patients that are currently taking stable doses of moderate or high-intensity statin
therapy. 38 This trial will randomize 104 patients 1:1 to receive 600 mg gemcabene or placebo, for 12 weeks. The
primary endpoint is the lowering of LDL-C levels at 12 weeks as compared to baseline. Secondary endpoints include
levels of TC, TG, apoB, hs-CRP, and nonHDL-C. Eligibility criteria include the following:
§ LDL-C levels above 100 mg/dL when fasting, and upon initial screening.
§ Stable statin usage alone or in combination with ezetimibe (10 mg).
§ Consistent diet low in fat and cholesterol content.
37 https://clinicaltrials.gov/ct2/show/NCT02722408
38 https://clinicaltrials.gov/ct2/show/NCT02634151
Page 23

January 4, 2017
Some criteria for exclusion are: abnormal liver function including liver disease, TG levels above 400 mg/dL, renal
insufficiency, major cardiovascular events, and cardiac arrhythmia. The first patient was enrolled in this trial in the
fourth quarter of 2016 and results are expected in the second half of 2017.
INDIGO-1, a Phase IIb Trial for Patient with Severe Hypertriglyceridemia
Gemphire is planning a Phase IIb clinical trial called INDIGO-1 with gemcabene for the treatment of patients with
SHTG. The Company plans to initiate this trial imminently and data are expected in the second half of 2017.
Trial Design. This will be a randomized, double-blind, placebo controlled Phase IIb trial with gemcabene for the
treatment of SHTG. 39 This trial will randomize 90-120 SHTG patients 1:1 to receive 300, 600 mg gemcabene or
placebo for 12 weeks. The primary endpoint is the lowering of TG levels at 12 weeks as compared to baseline.
Secondary endpoints include levels of TC, TG, apoB, hs-CRP, and nonHDL-C. Eligibility criteria include the
following:
§ Mean TG levels within the range of 500-1500 mg/dL while fasting.
§ Consistent diet low in fat and cholesterol content.
Participants will be excluded per the following criteria: history of pancreatitis within 6 previous months, prior
bariatric surgery, abnormal liver function including liver disease, renal insufficiency, major cardiovascular events, and
cardiac arrhythmia. The Company expects to initiate this trial in the near term and results are expected in the second
half of 2017.
Other Drugs in Development
Due to the large proportion of people who are unable to control their dyslipidemia disorders with current treatment
options, there is strong patient and physician interest in novel treatment options. Furthermore, the aging of the US
population and the ongoing obesity epidemic stand to potentially increase the number of patients seeking
dyslipidemia treatments in years to come. This is particularly true for individuals affected by HoFH, as many of
these patients remain unable to meet LDL-C goals despite use of statins, ezetimibe, mipomersen, and PCSK9
inhibitors. The large and growing market opportunity to treat dyslipidemia disorders has attracted substantial interest
over the past several years. Drugs in Phase II and Phase III development for the treatment of various dyslipidemia
disorders are presented in Figure 14, and more detailed descriptions of select programs are included below.
39 https://clinicaltrials.gov/ct2/show/NCT02944383
Page 24

January 4, 2017
Figure 14. Phase II and III Compounds in Development for Dyslipidemia Indications
Drug
Company
Mechanism /
Class
Phase
Indications
Anacetrapib Merck (NYSE: MRK) CETP inhibitor III 40 HeFH
ETC-1002
Esperion Therapeutics
Hypercholesterolemia, ASCVD,
ACL inhibitor III
(NasdaqGM: ESPR)
HeFH
Valsartan/Rosuvastatin EMS (private)
Angiotensin II
agonist / HMG
CoA reductase
III Hypertension and Dyslipidemia
inhibitor
Volanesorsen
Ionis Pharmaceuticals
(NasdaqGS: IONS)
ApoC-III inhibitor III 42,43 FCS, FPL
Apabetalone
Resverlogix (Toronto:
RVX)
BET inhibitor III ASCVD
Gemcabene
Gemphire
(NasdaqGM: GEMP)
Apo-C III inhibitor II ASCVD, HeFH, HoFH, SHTG
PCSK9si
CaPre
Evinacumab
VK2809
AMG899
The Medicines
Company (NasdaqGS:
MDCO)
Acasti Pharma
(NasdaqCM: ACST)
Regeneron
(NasdaqGS: REGN)
Viking Therapeutics
(NasdaqCM: VKTX)
Amgen (NasdaqGS:
AMGN)
PCSK9 synthesis
inhibitor
Omega-3
phospholipid
II
II
ASCVD
SHTG
ANGPTL3 inhibitor II HoFH, severe hyperlipidemia
Thyroid hormone
receptor beta (TRβ)
agonist
II
Hypercholesterolemia, NAFLD,
X-ALD
CETP inhibitor II Dyslipidemia
Source: LifeSci Capital
Anacetrapib – Merck (NYSE: MRK). Anacetrapib is an inhibitor of cholesteryl ester transfer protein (CETP), a
protein responsible for exchanging cholesteryl esters from HDL for triglycerides from very low-density lipoproteins
(VLDL) or LDL. Merck is developing anacetrapib as an LDL-C lowering agent for the treatment various
dyslipidemia indications. The company most recently conducted a Phase III trial with anacetrapib for the treatment
of HeFH, which met the primary endpoint of LDL-C reduction at 52 weeks (p

January 4, 2017
There are several examples of failed cardiovascular outcomes trials (CVOT) for CETP inhibitors, including trials for
Eli Lilly’s (NYSE: LLY) evacetrapib, Pfizer’s (NYSE: PFE) torcetrapib, and DalCor Pharmaceuticals’ (private)
dalecetrapib which was licensed from Roche (Swiss: ROG.VX). Based on these results, the CETP inhibitor drug
class simply may not be capable of reducing cardiovascular events. The negative results found broadly across this
drug class provide reason to believe that Merck’s ongoing Phase III REVEAL trial 44 will not meet the primary
endpoint of reduction in cardiovascular events. A caveat to the comparison is that clinical trials should not be
directly compared to each other due to potential differences in trial design. This trial is a CVOT for patients with
established vascular disease receiving anacetrapib or placebo, and results expected in the first quarter of 2017.
ETC-1002 – Esperion (NasdaqGM: ESPR). ETC-1002, also known as bempedoic acid, is designed to inhibit an
enzyme critical for cholesterol and fatty acid synthesis in the liver, ultimately reducing plasma LDL-C levels.
Esperion is developing ETC-1002 to treat patients with hypercholesterolemia that is not controlled by use of lipidlowering
therapies. A brief description of the company’s three planned Phase III trials are below:
§ 1002-046 – This is a 24-week Phase III trial with bempedoic acid assessing LDL-C lowering at 12 weeks for
patients with or without ASCVD who have hypercholesterolemia that is not adequately controlled by
current lipid-modifying therapies. This trial is expected to enroll 300 statin intolerant patients and begin in
2016.
§ 1002-047 – Participants will be enrolled into this 52-week Phase III study to assess bempedoic acid LDL-C
lowering at 12 weeks for patients with ASCVD or HeFH who have hypercholesterolemia that is not
adequately controlled by current lipid-modifying therapies. This trial is expected to enroll 750 patients and
begin in 2016.
§ 1002-048 – This is a 12-week Phase III trial with bempedoic acid assessing LDL-C lowering at 12 weeks in
patients with or without ASCVD as an adjunct to ezetimibe. It is expected to enroll 225 patients and begin
in 2016.
§ CLEAR Harmony (1002-040) – Participants will be randomized into this 52-week Phase III safety study
for patients with ASCVD and/or HeFH who have hypercholesterolemia that is not adequately controlled
by current lipid-modifying therapies. 45 The company has initiated this trial and expects to enroll 1,950
patients, with top-line results expected in mid-2018.
In addition to these trials, Esperion also plans to initiate a Phase III CVOT in the near-term. These trials are all
designed to be included in regulatory filings to the FDA and EMA, which the company expects to occur in the first
half of 2019. This strategy was unveiled on October 13 th , 2016, concurrently with results from a Phase II study in
patients with hypercholesterolemia on any statin at any dose. After 8 weeks, patients treated with bempedoic acid
had LDL-C reductions of 22% as compared to baseline (p=0.0028). The inclusion of patients on any statin at any
dose in Esperion’s Phase III program represents a significant departure from their prior strategy to pursue approval
for the treatment of statin-intolerant patients. The change makes Esperion’s regulatory approach quite similar to that
of Gemphire and comes in light of an ongoing dialogue that the company has had with the FDA, serving as a point
of validation for Gemphire’s strategy.
Volanesorsen (ISIS-APOCIII RX) – Ionis Pharmaceuticals (NasdaqGS: IONS). Volanesorsen is an antisense
therapy that reduces apoC-III protein production with the intent of lowering TG levels. Ionis Pharmaceuticals’
44 https://clinicaltrials.gov/ct2/show/NCT01252953
45 https://clinicaltrials.gov/ct2/show/NCT02666664
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January 4, 2017
wholly owned subsidiary, Akcea Therapeutics, is developing volanesorsen for the treatment of orphan
hypertriglyceridemia diseases, specifically familial chylomicronemia syndrome (FCS) and familial partial
lipodystrophy (FPL). Results from a randomized, placebo controlled, double-blind Phase II trial with ISIS-
APOCIII RX for the treatment of patients with very high to severely high triglyceride levels (440-2,000 mg/dL) were
generally positive. Patients receiving ISIS-APOCIII RX had mean TG reductions of 71% and apoC-III reductions of
80%, as compared to baseline. Akcea is currently conducting two randomized, double-blind, placebo controlled
Phase III trials with volanesorsen for FCS (APPROACH) 46 and FPL (BROADEN) 47 , both of which are assessing
percent change in fasting triglyceride levels after three months of treatment. The company plans to report topline
data from APPROACH in 2017.
Competitive Landscape
Unmet Need for Dyslipidemia Patients Remains Despite New Therapies. Four new drugs have recently been
approved for reducing LDL-C for some of the dyslipidemia populations that Gemphire is targeting: Aegerion’s
Juxtapid (lomitapide), Ionis and Aegerion’s Kynamro (mipomersen), Amgen’s Repatha (evolocumab), and Sanofi /
Regeneron’s Praluent (alirocumab). While these relatively new drugs offer additional treatment options for patients
with various dyslipidemias, there remains a large unmet medical need. Even with an aggressive combination of
available therapies, subjects with HoFH generally have LDL­C levels substantially above the treatment target of 70
mg/dL. Furthermore, serious safety risks are associated with Juxtapid and Kynamro treatment, evidenced by their
boxed warnings related to hepatotoxicity concerns. Gemcabene has potential to mitigate these risks while providing
patients with similar or improved reductions in LDL-C.
Gemcabene Has a Complementary Mechanism of Action to Approved Therapies. Gemcabene’s mechanism
of action involves reducing the production of cholesterol and triglycerides, while also enhancing the clearance of
very low-density lipoprotein (VLDL). Importantly, this mechanism does not require LDL receptor activity, which
makes the drug particularly well suited for patients who do not have LDL receptor expression or carry nonfunctional
receptors. In contrast, statins and PCSK9 inhibitors both act through mechanisms that involve the LDL
receptor, which is problematic for HoFH and HeFH patients who carry mutations that render the receptors nonfunctional.
Even those patients with residual LDL receptor activity tend to inadequately respond to statin therapy. 48
Although these agents do have a beneficial effect for some, many patients require combination therapy with other
lipid lowering agents in order to reach target LDL­C levels. For this reason, it is mechanistically logical to combine
these therapies with gemcabene.
Gemcabene also has a different mechanism than recently approved oral therapies Juxtapid and Kynamro. For example,
Juxtapid is an oral inhibitor of the microsomal triglyceride transport protein (MTP), and Kynamro is an anti­sense
oligonucleotide inhibitor that blocks the synthesis of ApoB100. Both of these therapies cause the accumulation of
fat in the liver and carry boxed warnings for potential liver toxicity. Considering that gemcabene reduces production
of cholesterol and triglycerides in the liver, the mechanisms of these compounds well differentiated.
46 https://clinicaltrials.gov/ct2/show/NCT02211209
47 https://clinicaltrials.gov/ct2/show/NCT02527343
48 Raal, F.J. et al., 1997. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolemia. Atherosclerosis, 135,
pp244-256.
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January 4, 2017
Gemcabene Likely to Be Priced Competitively. One of the major pitfalls of the novel treatments approved for
the treatment of dyslipidemia disorders is their excessive pricing. For example, Kynamro costs $176,000 per year,
while Juxtapid has an annual price tag of $295,000. Although these therapies are exclusively approved for HoFH, an
orphan indication, the cost is likely prohibitive to payers that may otherwise consider reimbursement for off-label
usage in broader indications like HeFH and ASCVD. Repatha and Praluent have also had poor uptake, in part due to
high pricing, as both of these therapies cost more than $14,000 per patient annually. The lack of data on
cardiovascular outcomes has also put a damper on market uptake, despite these therapies being approved for
treatment in the large HeFH and ASCVD markets.
Gemphire has guided that pricing of gemcabene will likely cost $3,000 for wholesale acquisition annually, similar to
pricing of branded statins. With such a competitive price point, if gemcabene is able to achieve a clinical impact
similar to other branded treatments, the cost-benefit analysis of treating with gemcabene will be very favorable.
Aging Population and Increasing Prevalence of Metabolic Diseases to Drive Dyslipidemia Market Growth.
Macroeconomic trends including the ongoing obesity epidemic and aging US population could drive expansion of
the dyslipidemia markets. The prevalence of obesity has continued to rise in the US over the past several decades,
with approximately 36.5% of the population currently affected by this disorder. Obesity is also more prevalent in
older individuals, affecting 40% of people between 40-59 years of age and 37% of people above 60, as compared to
32% between 20-39 years of age. Similarly, the number of US people aged 65 years or greater is expected to grow to
from 43 million in 2012, to 56 million in 2020 and 73 million in 2030. Continued growth in the dyslipidemia market
seems likely when considering is primarily affects older individuals, the high prevalence of obesity, and the aging US
population.
Late Stage Therapies in Development for Dyslipidemia Unlikely to Impact Current Treatment Landscape.
Two notable programs currently in late stage development are Merck’s anacetrapib and Ionis’ volanesorsen, but
these programs are unlikely to alter the treatment landscape in our view. Anacetrapib is a CETP inhibitor that has
been shown to reduce LDL-C levels, but reductions in lipid levels have not translated into better cardiovascular
outcomes for the CETP inhibitor drug class. Examples of failed CVOTs for CETP inhibitors include Eli Lilly’s
evacetrapib, Pfizer’s torcetrapib, and DalCor Pharmaceuticals’ dalecetrapib. The findings leave us skeptical that
CEPT inhibitors are capable of reducing cardiovascular events.
Volanesorsen is an antisense therapy that reduces apoC-III protein production, with the intent of lowering TG
levels. Despite solid efficacy in clinical trials to date, several safety issues have surfaced in similar compounds. For
example, Arrowhead’s (NasdaqGS: ARWR) ARC-520 was recently put on clinical hold due to deaths of primates in
an ongoing toxicology study and has since caused them to abandon their three lead programs. Also, Alnylam
(NasdaqGS: ALNY) stopped a late stage clinical trial with revusiran for the treatment of ATTR amyloidosis with
cardiomyopathy due to a higher number of deaths in the treatment arm. Although we discourage speculating on the
future potential of volanesorsen purely based on these events, the safety risks involved with developing antisense
compounds are significant. Beyond these potential risks, volanesorsen is being developed for the treatment of
hypertriglyceridemia, familial chylomicronemia syndrome (FCS), and familial partial lipodystrophy (FPL), and has
potential to affect the SHTG treatment landscape, but is unlikely to affect the treatment of HoFH, HeFH, and
ASCVD.
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January 4, 2017
Gemcabene for the Treatment of Non-Alcoholic Steatohepatitis (NASH)
Non-alcoholic fatty liver disease (NAFLD) is a broad-spectrum condition in which excess fat accumulates in the
liver. As the name suggests, hepatic fat accumulation in NAFLD is not due to alcohol use, but rather to a multitude
of other pathologic processes. The clinical progression of NAFLD is still very similar to that of alcoholic liver
disease, beginning with mild inflammation in the earliest stages and progressing to cirrhosis and eventually hepatic
failure in the more advanced stages. Non-alcoholic steatohepatitis (NASH) is the middle stage of NAFLD, where
inflammation is present that can lead to fibrosis and scarring. Despite prevalence as high as 30% in developed
countries, the current best intervention for NAFLD is lifestyle modification, and patients are often noncompliant.
There are no FDA-approved therapies for NAFLD or NASH, making it difficult to accurately assess the market.
However, independent estimates of the off-label market for NASH in the United States and Europe suggest the
annual market is approaching $250 million. Other sources have reported that off-label sales of therapies used for
NASH were approximately $615 million in 2010, including sales of vitamin E, metformin, and statins. Considering
the substantial market for drugs being used off-label in this indication, an efficacious product approved for NASH
would likely surpass sales of these therapies and expand the overall market significantly.
Gemphire may pursue the development of gemcabene for the treatment of NASH due to the strong mechanistic
rationale for the compound to target the pathology of this disease. Gemcabene use has been shown to reduce levels
of serum LDL-C, TG, hsCRP, and ApoB in human clinical trials, and its mechanism of action has been validated
through preclinical models as well. Studies in rat hepatocytes and apoB100-only mice with gemcabene have
demonstrated decreases in the synthesis of cholesterol and triglycerides as compared to vehicle, while treatment is
also associated with VLDL reductions in rats. Considering the ability of this compound to lower blood lipid levels
by reducing synthesis of these compounds while also reducing inflammation (hsCRP), it is logical to develop
gemcabene for the treatment of a disorder characterized by excess fat accumulation and inflammation of the liver.
The Company is actively considering strategic partnerships for the development of gemcabene for the treatment of
NASH.
Intellectual Property
Gemphire’s patent estate includes a total of 28 issued patents and an additional 24 patents pending for gemcabene.
These include original patents in-licensed from Pfizer regarding gemcabene formulation, as well as several patents
that have been filed in the prior 5 years as a result of clinical development work. The latter include method of use
patents for acute pancreatitis as a result of SHTG, reduction of CV risk as an adjunct to statin therapy, mixed
dyslipidemia, and NASH. Gemphire has also filed patents for fixed-dose combination formulations of gemcabene as
well as manufacturing. We note the absence of a composition of matter patent for gemcabene, although the drug is
eligible for 5 years of marketing exclusivity as a New Chemical Entity (NCE) and may receive up to 7 years of
exclusivity if approved for HoFH due to Orphan Drug Exclusivity (ODE). A summary of the Company’s patent
estate is presented in Figure 15.
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January 4, 2017
Figure 15. Gemphire’s Patent Estate
Total US
Total Ex-US
Issued 4 24
Pending 9 15
Source: LifeSci Capital
Management Team
Mina Sooch, M.B.A.
President and Chief Executive Officer
Mina Sooch, MBA, serves as the President and Chief Executive Officer of Gemphire Therapeutics. Prior to joining
the Company, she served from 2012 to 2014 as the CEO of ProNAi (NASDAQ:DNAI), a clinical-stage oncology
company, and a board director from its founding in 2004 through 2014. At ProNAi, Ms. Sooch pioneered a new
drug modality, DNAi, led the execution of Phase I and II trials on PNT2258 (a novel bcl2 targeted drug candidate)
and raised over $70M in Series C and D financing from top tier institutional investors. The last round of $60M was
the largest VC financing ever in Michigan’s history. Prior to her operating role, she has spent over a decade in life
sciences venture capital through founding of Apjohn Ventures and also as EIR at Northcoast Technology Investors.
As a VC, she led the sourcing and evaluation of deals across therapeutic areas, the investment terms and syndication,
the governance, the follow-on financings totaling over $300M, and the exits of several life sciences companies. Also,
she co-founded three start-ups (Afmedica, ProNAi, and Nephrion/Cytopherx). Notable exits from the Apjohn
portfolio include the acquisition of ZyStor by BioMarin (NASDAQ:BMRN) in 2010, the acquisition of Afmedica by
Angiotech Pharmaceuticals in 2005, and the product acquisition from Ikano by Upsher-Smith in 2010. Ms. Sooch
has served on over 10 private, public, and VC industry boards including ProNAi, ZyStor, Asterand, Cytopherx,
Svelte, Wolverine Venture Fund, and Michigan Venture Capital Association. Earlier in her career from 1993-2000,
she served as global account manager at Monitor Group, a top tier global strategy consulting firm based in Boston.
In 1995, she worked on the multi-billion Pharmacia & Upjohn merger. Mina received a MBA from Harvard
Business School in 1993. She graduated summa cum laude and commencement speaker from Wayne State
University in 1989 with a B.S. in Chemical Engineering.
Jeff Mathiesen
Chief Financial Officer
Jeff Mathiesen serves as the Chief Financial Officer of Gemphire Therapeutics. Prior to joining the Company, he
served as CFO of Sunshine Heart, Inc., leading the medical device company through its transition from the
Australian capital markets to the U.S., which included a successful IPO and equity financings totaling approximately
$100 million. Mr. Mathiesen has more than 20 years of experience as Chief Financial Officer (CFO) of publicly
traded companies, including two successful initial public offerings (IPOs). His experience encompasses a variety of
highly competitive, technology based industries in organizations with global reach and includes several M&A
transactions, divestitures, organizational development and equity and debt financing. He began his career at Deloitte.
Mr. Mathiesen also serves as Director and Audit Committee Chair of Sun BioPharma, Inc. a publicly traded
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January 4, 2017
biopharmaceutical company developing therapies for pancreatic diseases. Mr. Mathiesen graduated summa cum
laude from the University of South Dakota with a B.S. degree in Accounting.
Charles Bisgaier, Ph.D.
Chief Scientific Office and Co-Founder
Dr. Bisgaier serves as the Chairman and Chief Scientific Officer of Gemphire Therapeutics. From 1990 to 1998, Dr.
Bisgaier was an Associate Research Fellow in the Department of Vascular and Cardiac Disease at Warner-
Lambert/Parke-Davis. There he participated in the discovery and/or development of gemfibrozil (LOPID®),
atorvastatin (LIPITOR®) and gemcabene (AKA CI-1027 and PD 72953). Subsequently, Dr. Bisgaier co-founded
the first Esperion Therapeutics (1998- 2004), which was then acquired by Pfizer. At Pfizer he then served as the
Senior Director of Pharmacology at the Esperion Division of Pfizer Global Research and Development. Notably, he
was a major influence in the discovery, research and/or development of many small molecules with potential utility
for metabolic syndrome including ETC-1002 (AKA ESP 55016) which was licensed by the new Esperion
(NASDAQ: ESPR) from Pfizer, as well as HDL-therapy product candidates, such as ApoA-I Milano (ETC-216)
which was also licensed by The Medicines Company (NASDAQ: MDCO) from Pfizer. After Pfizer, he served as a
Company Director, Board Member and President of Pipex Pharmaceuticals (2006-2008, currently known as
Synthetic Biologics, NYSE: SYN), a specialty pharmaceutical company focused on developing fibrotic and
neurological disease therapies, that included a treatment for Relapsing Remitting Multiple Sclerosis. Both Pipex
Pharmaceuticals and the first Esperion Therapeutics became public companies through a reverse-merger and an
initial public offering (IPO), respectively during Dr. Bisgaier's tenure. He is also a co-founder of Michigan Life
Therapeutics (predecessor to Gemphire) and Michigan Life Ventures. In addition, he is currently a Board member at
Hygieia, Inc., a company that has developed a novel handheld medical device to assist diabetics to determine
appropriate dosage when self-administering insulin, and a Board member at BioSavita Inc., a company that has
developed a novel platform technology for protein expression in yeast. He also has served as a Board member
(2009-2014) and President and CEO (2010-2011) of ProNAi Therapeutics (NASDAQ: DNAI). Currently, Dr.
Bisgaier is also an Adjunct Associate Professor of Pharmacology at the University of Michigan. He received a B.A.
in Biology from the State University College at Oneonta, NY (1974), and a M.S.(1977) and Ph.D. (1981) in
biochemistry from George Washington University, Washington, D.C. After receiving his doctorate, he studied
lipoprotein metabolism within the Specialized Center of Research (SCOR) for atherosclerosis at Columbia
University College of Physicians and Surgeons, NY.
Lee Golden, M.D.
Chief Medical Officer
Dr. Golden has over 20 years of clinical and industry experience. He has held several roles with increasing
responsibilities within the pharmaceutical industry since beginning his career with Pfizer, Inc. His experience
includes Medical Affairs, Clinical Development and Business Development, for market leading therapeutics within
primary care and orphan indications. At Pfizer, in addition to working on the Global atherosclerosis team and
overseeing several large global cardiovascular trials, he was the US Medical Team Leader during the filing and launch
of several products. After leaving Pfizer, Dr. Golden broadened his experience with responsibility for leading
medical teams in Cardiopulmonary, GI and CNS therapeutic areas. During his time at Actelion he oversaw multiple
products and trials in Pulmonary Arterial Hypertension and was involved with design and oversight of several other
pulmonary related diseases. In his previous role at Eisai Inc. he was the Therapeutic Area Head for Cardiovascular
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January 4, 2017
and Blood Disorders where he was responsible for leading global development teams from discovery through
NDA/MAA approvals.
Dr. Golden was most recently the Therapeutic Area Head for CV, Pulmonary and CNS at Mesoblast, Ltd., a global
regenerative medicine company. His was responsible for overseeing the strategic planning, implementation and
execution from preclinical through registration across multiple indications. He championed regulatory interactions
that led to the first global phase 3 cardiovascular program with allogeneic stem cells in patients with congestive heart
failure.
Dr. Golden earned his MD degree from New York University School of Medicine. After his Internal Medicine
Residency at New York University Medical Center, he completed fellowships in Cardiology, At University of Miami
Health Center, and Interventional Cardiology, at George Washington University Hospital. While at George
Washington University Hospital, Dr. Golden also held the position of Adjunct Instructor.
Seth Reno, M.B.A.
Chief Commercial Officer
Mr. Reno serves as the Chief Commercial Officer of Gemphire Therapeutics and has over 25 years of experience in
the Bio-Pharmaceutical industry. He has extensive experience in building commercial capabilities to successfully
commercialize both small and large molecules across a range of therapeutic areas including the cardiovascular
market. Prior to joining Gemphire, he spent five years at Medimmune building commercial teams and capabilities
that focused on launching complex biologics such as Mylept and Lynparza with orphan designation status into rare
disease markets. As Medimmune’s Head of Commercial Operations he was responsible for leading core business
functions across: Sales Operations, Marketing Operations, Market Research, Fleet Services, Sales Training,
Commercial Insight, Advanced Analytics and Forecasting. Mr. Reno spent ten years at AstraZenca across a number
of roles in Sales, Commercial Operations, Managed Markets and Brand Team. He led the Commercial Insight’s team
for the dyslipidemia franchise, most notably the successful launch of Crestor’s atherosclerosis indication. He also led
the insight work for several mixed dyslipidemia fixed dose combinations in development with industry partners.
Prior to Joining AstraZeneca in 2001, Mr. Reno Spent eleven years at Wyeth in commercial operations and sales
account management successfully building B2B relationships across Federal, Trade, Military and Commercial
accounts. Mr. Reno holds a B.S. in Human Resources from University of Delaware and a MBA from Strayer
University.
Daniela Oniciu, Ph.D.
Vice President, Preclinical R&D and Manufacturing
Dr. Oniciu serves as the VP of Preclinical R&D and Manufacturing of Gemphire Therapeutics. Dr. Oniciu has more
than 30 years of experience in chemical research, with her last sixteen years dedicated to pharmaceutical research and
development in various therapeutic areas including: cardiovascular disease, metabolic disorders and cholesterol
management, neuroprotective drug analogs, prodrugs and chemical delivery systems. Most recently she has focused
on preclinical R&D and CMC related regulatory affairs for pharmaceuticals and fine chemicals that span small
molecules. Prior to that, Dr. Oniciu was appointed as Senior Director of Chemistry at Cerenis Therapeutics Holding
SA, a French biotech dedicated to the development of novel HDL therapies for the treatment of cardiovascular and
metabolic diseases. At Cerenis, Dr. Oniciu participated in the financing of the company with top tier investors,
leading to €92M out of the total of €117M in equity raised by Cerenis. Prior to joining Cerenis, Dr. Oniciu was
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January 4, 2017
Senior Director of Chemical R&D at Esperion Therapeutics Inc., where she was a co-inventor of small molecule
drug candidates including ETC-1002, and served as co-chair of the preclinical research team. Following the
acquisition of Esperion by Pfizer Inc., Dr. Oniciu served as Associate Director of Chemistry at Pfizer. Prior to
joining Esperion in 2001, Dr. Oniciu was co-founder of a custom research organization, Alchem Laboratories
Corporation, one of the first CROs in the United States, specialized in drug design and process development
support for the pharmaceutical industry. In addition, Dr. Oniciu is Courtesy Professor of Chemistry at the
University of Florida at Gainesville since 2004. Dr. Oniciu holds a Ph.D. in organic chemistry from the Polytechnic
University of Bucharest (Romania), and a M.S. in Organic Chemistry and Chemical Engineering from the same
University.
Rebecca Bakker-Arkema
Vice President of Drug and Clinical Development
Rebecca Bakker-Arkema serves as Gemphire’s VP of Drug and Clinical Development. Rebecca has worked in
pharmaceutical development for over 25 years, starting her clinical career as a Clinical Scientist and then Director in
Clinical Development at Warner-Lambert/Parke-Davis. She was primarily involved with the clinical development
program for atorvastatin (LIPITOR®) with responsibility for several studies from Phase 2 through Phase 3b as well
as the Integrated Summary of Safety. Following acquisition by Pfizer Rebecca was Director of Exploratory Clinical
Development responsible for several early stage compounds including gemcabene (AKA CI-1027 and PD 72953).
When Rebecca left Pfizer in 2007 she was the Cardiovascular and Metabolic Disease Translational Medicine Site
Head, overseeing the early development and biomarker work on a portfolio of early stage compounds
cardiovascular/metabolic disease discovered in Ann Arbor. Rebecca has been a consultant over the past 9 years
working for several large companies (Medical Diagnostics, GE Healthcare) as well as several small biotech
companies (Senior Director of Clinical Research at Metabasis Therapeutics, Inc). She was most recently Vice-
President of Clinical Development at AlphaCore Pharma, LCC which was acquired by MedImmune/Astrazeneca in
2012. Rebecca has over 50 publications in peer reviewed journals and scientific presentations, is a Fellow of the
American Heart Association, and is an adjunct Clinical Associate Professor at the University of Michigan School of
Pharmacy. Rebecca earned a pharmacy degree from the University of Kansas School of Pharmacy and a Master’s
degree from the University of Michigan in the School of Public Health. She is a registered Pharmacist in Kansas and
Michigan.
Liz Masson
Vice President, Clinical Operations
Liz Masson serves as the Vice President of Clinical Operations of Gemphire Therapeutics. Prior to that, she held
several progressive management roles in clinical operations, specifically site development, CRO oversight and rescue
work. Responsible for strategic and operational development activities, Liz has a passion for growing and developing
highly engaged teams and assuring the highest standards for program execution. As a clinical entrepreneur, Liz
started Clinical Minds, a specialty consulting firm committed to provide small pharmaceutical and biotechnology
companies relevant and decisive guidance. Liz received her B.A. in Leadership and Organizational Management
from Bay Path College.
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January 4, 2017
Risk to an Investment
We consider an investment in Gemphire to be a high-risk investment. Gemphire is currently in clinical-stage
development and does not have any marketed or approved products. The Company has not entered Phase III
clinical trials for any program. Failure to show convincing results in future pivotal clinical studies or failure to reach
FDA or EMA approval could adversely affect Gemphire’s stock price. Regulatory approval to market and sell a drug
does not guarantee that the drug will penetrate the market, and sales may not meet expectations. As a clinical-stage
company, Gemphire is not profitable and may need to seek additional financing from the public markets, which may
result in dilution of existing shareholder value.
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security or subject company that the research analyst covers in this research, that: (1) all of the views expressed in this report accurately
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analyst(s) in this report.
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