8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 12, 2015

 

 

Mast Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-32157   84-1318182

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

 

12390 El Camino Real, Suite 150,

San Diego, California

  92130
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code: (858) 552-0866

Not Applicable

Former name or former address, if changed since last report

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

 

 


Item 8.01. Other Events.

The information attached as Exhibit 99.1 to this report relating to Mast Therapeutics, Inc. (the “Company”) and its development programs may be presented from time to time by the Company at various investor and analyst meetings, including on January 12, 2015 at the 2015 Biotech Showcase Conference.

 

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

The list of exhibits called for by this Item is incorporated by reference to the Exhibit Index immediately following the signature page of this report.

By filing this report, including the information contained in Exhibit 99.1 attached hereto, the Company makes no admission as to the materiality of any information in this report. The information contained in Exhibit 99.1 hereto is summary information that is intended to be considered in the context of the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”), including its Annual Report on Form 10-K filed on March 26, 2014, Quarterly Report on Form 10-Q filed on October 31, 2014, and other public announcements that the Company makes, by press release or otherwise, from time to time. The Company undertakes no duty or obligation to publicly update or revise the information contained in this report, although it may do so from time to time as it believes is appropriate. Any such updating may be made through the filing of other reports or documents with the SEC, through press releases, or through other public disclosure.

Forward-Looking Statements

Mast Therapeutics cautions you that statements included in this report, including in Exhibit 99.1 attached hereto, that are not a description of historical facts are forward-looking statements that are based on the Company’s current expectations and assumptions. Such forward-looking statements include, but are not limited to, statements regarding the Company’s development, regulatory and commercialization strategies and plans for its product candidates, including vepoloxamer (MST-188) in sickle cell disease, occlusive arterial disease, heart failure, and AIR001 in heart failure with preserved ejection fraction, as well as the timing of activities related to those plans, including commencement and completion of clinical and nonclinical studies. Among the factors that could cause or contribute to material differences between the Company’s actual results and the expectations indicated by the forward-looking statements are risks and uncertainties that include, but are not limited to: the uncertainty of outcomes in ongoing and future studies of its product candidates and the risk that its product candidates may not demonstrate adequate safety, efficacy or tolerability in one or more such studies, including vepoloxamer in the ongoing EPIC study and phase 2 study in acute lower limb ischemia; delays in the commencement or completion of clinical studies, including the EPIC study, the phase 2 study of vepoloxamer in acute limb ischemia, the planned phase 2 study of vepoloxamer in heart failure and the phase 2a studies of AIR001, including as a result of difficulties in obtaining regulatory agency agreement on clinical development plans or clinical study design, opening trial sites, enrolling study subjects, manufacturing sufficient quantities of clinical trial material, completing manufacturing process development activities, being subject to a “clinical hold,” and/or suspension or termination of a clinical study, including due to patient safety concerns or lack of funding; the potential for institutional review boards or the FDA or other regulatory agencies to require additional nonclinical or clinical studies prior to initiation of planned clinical study of a product candidate; the risk that, even if clinical studies are successful, the FDA or another regulatory agency may determine they are not sufficient to support a new drug application; the potential that even if clinical studies of a product candidate in one indication are successful, clinical studies in another indication may not be successful; the Company’s reliance on contract research organizations (CROs), contract manufacturing organizations (CMOs), and other third parties to assist in the conduct of important aspects of development of its product candidates, including clinical studies, manufacturing, and regulatory activities for its product candidates and that such third parties may


fail to perform as expected; the Company’s ability to obtain additional funding on a timely basis or on acceptable terms, or at all; the potential for the Company to delay, reduce or discontinue current and/or planned development activities, including clinical studies, partner its product candidates at inopportune times or pursue less expensive but higher-risk and/or lower return development paths if it is unable to raise sufficient additional capital as needed; the risk that the FDA and regulatory agencies outside of the U.S. do not grant marketing approval of a product candidate, on a timely basis, or at all; the risk that, even if the Company successfully develops a product candidate in one or more indications, it may not realize commercial success with its products and may never generate revenue sufficient to achieve profitability; the risk that the Company is not able to adequately protect its intellectual property rights and prevent competitors from duplicating or developing equivalent versions of its product candidates; and other risks and uncertainties more fully described in the Company’s periodic filings with the SEC and press releases.

You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date they are made. Mast Therapeutics does not intend to revise or update any forward-looking statement set forth in this report to reflect events or circumstances arising after the date hereof, except as may be required by law. This caution is made under the safe harbor provisions of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended.


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

  Mast Therapeutics, Inc.
January 12, 2015   By:  

/s/ Brandi L. Roberts

  Name:   Brandi L. Roberts
  Title:  

Chief Financial Officer and

Senior Vice President


Exhibit Index

 

Exhibit

No.

  

Description

99.1    Mast Therapeutics, Inc. corporate presentation, January 12, 2015
EX-99.1
NYSE MKT: MSTX
2015 Biotech Showcase Conference
Brian M. Culley, CEO
January 12, 2015
Exhibit 99.1


NYSE MKT:  MSTX
2
Forward-Looking Statements
This presentation includes forward-looking statements about our business prospects, financial
position, and development of MST-188 and AIR001 for therapeutic use in humans. Any
statement that is not a statement of historical fact should be considered a forward-looking
statement. Because forward-looking statements relate to the future, they are subject to inherent
risks, uncertainties and changes in circumstances that are difficult to predict.  Actual events or
performance may differ materially from our expectations indicated by these forward-looking
statements due to a number of factors, including, but not limited to, results of our pending and
future clinical studies, the timeline for clinical and manufacturing activities and regulatory
approval; our dependency on third parties to conduct our clinical studies and manufacture our
clinical trial material; our ability to raise additional capital, as needed; our ability to establish
and protect proprietary rights related to our product candidates; and other risks and
uncertainties more fully described in our press releases and our filings with the SEC, including
our annual report on Form 10-K filed with the SEC on March 26, 2014.
We caution you not to place undue reliance on any of these forward-looking statements, which
speak only as of the date of this presentation. We do not intend to update any forward-looking
statement included in this presentation to reflect events or circumstances arising after the date
of the presentation, except as may be required by law.


NYSE MKT:  MSTX
Developing vepoloxamer to improve blood flow and cell
membrane integrity
Sickle Cell Disease (SCD) –
Phase 3 enrolling (>33% complete)
Acute Limb Ischemia (ALI) –
Phase 2 enrolling
Acute Heart Failure (ADHF) –
Phase 2 initiation 2Q’15
Developing AIR001 to improve cardiovascular hemodynamics and
exercise tolerance
Heart Failure with Preserved Ejection Fraction (HFpEF) –
Phase 2a
3
Corporate Overview


NYSE MKT:  MSTX
4
Vepoloxamer
(Purified Poloxamer 188
)


NYSE MKT:  MSTX
API Structure:
CMC:
Large, synthesized polymer with extraction process to
remove undesirable (toxic) components.
Composition of matter claims pending.
Administration:
IV infusion
ADME:
Rapidly and predominantly cleared by kidneys (4-8h)
Ether linkages cannot be cleaved; no drug metabolites
5
Vepoloxamer Overview
HO –
(CH
2
CH
2
O)
79
(CH
2
CHO)
30
(CH
2
CH
2
O)
79
H
CH
3
|
5


NYSE MKT:  MSTX
Core of molecule adheres to hydrophobic domains on cell surface,
such as damaged membranes and adhesive proteins.
6
Vepoloxamer Mechanism of Action
No Affinity for Healthy Cell Membranes…
But Adheres to Damaged Cell Membranes


NYSE MKT:  MSTX
7
Vepoloxamer Pharmacodynamics
Vepoloxamer
Hemorheologic
Inhibits cell adhesion,
reduces aggregation;
improves flow.
Cytoprotective
Seals membranes,
restores integrity (e.g.
gives cells time to heal).
Simple biophysical mechanism improves flow and membrane integrity.


NYSE MKT:  MSTX
Vepoloxamer
Clinical Development
8
Preclinical
Phase 1
Phase 2
Phase 3
2015
Sickle Cell Disease
(orphan)
Acute Limb Ischemia
(orphan)
Acute Heart Failure
Enrolling
Planned initiation: 2Q 2015
Enrolling


NYSE MKT:  MSTX
9
Sickle Cell Disease


A chronic, genetic disorder and rare (orphan) disease
Hallmark of disease is a “vaso-occlusive crisis”
Significant unmet need
Vaso-occlusion is associated with early death
10
Overview of Sickle Cell Disease
Affects 90,000 to 100,000 people in the U.S.
Characterized by severe deformation (i.e., “sickling”) of red blood cells
Indescribably painful condition
Leading cause of hospitalization
No approved agents
to shorten duration or severity of crisis
Standard of care (hydration and analgesics) unchanged for >10 years
Obstructed blood flow -> hypoxia -> tissue death -> organ failure
Average age at death; 42 years (males), 48 years (females)
NYSE MKT:  MSTX


NYSE MKT:  MSTX
11
Vepoloxamer:
Vaso-Occlusion:
Role of Vepoloxamer in Sickle Cell Disease
Adhesion
of
poorly-deformable,
“sticky”
cells
to
endothelium
Entrapment of rigid, sickled cells and vessel obstruction results in ischemia and infarction
Reduces aggregation and adhesion of cells to endothelium (anti-inflammatory)
Improves RBC deformability, lowers viscosity, restores flow (rheology), and reduces
reperfusion injury (cytoprotection)


NYSE MKT:  MSTX
Lung pathology was compared in transgenic mice pretreated with either vepoloxamer
(400
mg/kg)
or
saline
and
subject
to
hypoxia
(5%
O
2
).
(Asakura,
et
al.)
Vepoloxamer Reduced Organ Pathology
in Transgenic Sickle Mice
12
0
20
40
60
80
100
Lung Pathology
Vepoloxamer
Control


NYSE MKT:  MSTX
Transgenic mice pretreated with either vepoloxamer (400 mg/kg) or saline, subject to
hypoxia
(5%
O
2
),
and
monitored
for
survival.
(Asakura,
et
al.)
Vepoloxamer Increased Survival in
Transgenic Sickle Mice
13
0
20
40
60
80
100
0
10
20
30
40
50
60
Survival of Transgenic Sickle Mice
Post
exposure
to
5%
0
2
(60 -
100% ß
S
-Globin)
Vepoloxamer
Control
Time (min)


NYSE MKT:  MSTX
Vepoloxamer
Placebo
Before Infusion
(Crisis Baseline)
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2-Hours                          7-Hours                        
After Loading
Infusion
After Loading
Infusion
Source: J. Investig. Med. 2004;52(6):402-6
(p = 0.00003)
14
Vepoloxamer improved microvascular blood flow in SCD patients in
crisis
Vepoloxamer Improves Blood Flow
Red cell velocity (mm/s)
measured by video
microscopy in nine
sickle cell patients with
vaso-occlusive crisis.


NYSE MKT:  MSTX
Phase 2 Study
Source: Blood,
September
1,
1997
Vol
90,
No. 5
* Vepoloxamer is purified poloxamer 188
15
Subjects Who Received Full Dose
±
Poloxamer 188*
(n=18)
Placebo
(n=13)
p
value
±±
Duration of Crisis
44 hours
80 hours
0.025
Duration of Hospitalization
5 days
7 days
0.111
Total Analgesic Use
34mg
145mg
0.045
Parenteral Analgesic Use
27mg
133mg
0.022
±
Excludes patients who had drug administration errors or incomplete pain assessments (16), who withdrew consent (2) and who withdrew because of injection
site
pain
after
15
minutes
of
infusion.
Subjects
were
excluded
equally
(n=9)
between
poloxamer
188
and
placebo. 
±±
Proportional hazards model adjusted for baseline pain. 
Randomized, double-blind, placebo-controlled, multi-center study in SCD
patients hospitalized for crisis
Significantly improved important efficacy parameters


NYSE MKT:  MSTX
Source: JAMA, November 17, 2001 –
Vol 286, No. 17
16
Randomized, double-blind, placebo-
controlled, multi-center study of    
vepoloxamer in 350 patients with SCD.
Time-to-event analysis showed
consistent trend in support of earlier
crisis resolution.
However, prior sponsor ended
enrollment at only 255 patients
due to
capital constraints, lowering statistical
power, and,
The observation period was specified
to be only 168 hours,
observation of any late-treatment
differences (e.g. “right censoring”).
Phase 3 Study
p = 0.09
All Treated Patients
(n=249)
Hours After Randomization
Children (<16 years)
(n=73)
p = 0.007
Vepoloxamer
Vepoloxamer
eliminating


NYSE MKT:  MSTX
Randomized, Double-Blind, Placebo-Controlled, Multicenter
Primary Efficacy Assessment
Secondary Efficacy Assessments
Power
Open-label extension
17
EPIC: Pivotal Phase 3 Study Design
388 patients
Standard of care +/-
vepoloxamer
Duration of crisis (transition off IV analgesia)
No assessment of subjective pain scores
Re-hospitalization for crisis within 14 days
Occurrence of acute chest syndrome
85% power to detect a 24-hour difference (p=0.01)
90% power to detect a 16-hour difference (p=0.05)
Expands safety database with repeat exposures to vepoloxamer
Will enroll patients who have completed treatment on EPIC


NYSE MKT:  MSTX
Enrollment on-track. Top-line data expected Q1 2016.
Most Advanced New Drug in SCD
Positive Factors for Regulatory Decision-Making
18
EPIC Success Factors
~70 sites opened, >50 within the U.S.
>33% enrolled as of Jan 6.
Potential to be first approved drug to treat an ongoing vaso-occlusive crisis
Substantial
head
start
versus
other
new
drugs
in
development
for
SCD
Significant unmet need
Fast Track designation
Orphan Drug designation
Healthcare disparity
FDA declaration of SCD as an “agency priority”


NYSE MKT:  MSTX
19
Acute Limb Ischemia
(Vepoloxamer In Combination with Thrombolytics)


A progressive circulatory problem in which obstructed arteries reduce
blood flow
to tissues
20
Acute Ischemic Cerebrovascular Infarction
(stroke)
Acute Myocardial Infarction
(heart attack)
Peripheral Arterial Disease
Intermittent Claudication
Critical Limb Ischemia
Acute Limb Ischemia
Development Strategy:
Develop
initially
in
ALI
Expand
into
other
AD
markets
Overview of Occlusive Arterial Disease
Thrombolytic agents (tPA) are used to treat acute complications
Significant morbidity and mortality
NYSE MKT:  MSTX


NYSE MKT:  MSTX
21
Improved t-PA Effectiveness
Animals
randomized
to
t-PA
(n
=
10)
or
t-PA
+
poloxamer
188*
(n
=
10) 
Control (t-PA)
Poloxamer 188*
Source: Data on file
* Vepoloxamer is purified poloxamer 188


NYSE MKT:  MSTX
22
Synergy with Thrombolytics
in Heart Attack
Source: Circulation 1996; 94: 298-307
*Vepoloxamer is purified poloxamer 188
Parameter
Poloxamer 188*
Control
Difference
p
Value
N=114
Myocardial
Infarct Size
(median)
16%
26%
38% reduction
0.031
Myocardial
Salvage (median)
13%
4%
125% increase
0.033
Ejection Fraction
(median)
52%
46%
13%
improvement
0.020
Incidence of
Reinfarction
1%
13%
92% reduction
0.016


NYSE MKT:  MSTX
23
Clinical Proof-of-Concept Study
Biomarkers
Clinical outcomes
Study Design
Randomized, double-blind, and active-controlled (t-PA)
t-PA +/-
low or high dose vepoloxamer
60 subjects (20 per arm)
Timing
Completion of enrollment anticipated 2H 2016
ALI data can be supportive of clinical development in stroke
Embolic stroke preclinical studies initiated
Phase 2 Study in ALI


NYSE MKT:  MSTX
24
Heart Failure


NYSE MKT:  MSTX
Overview of Heart Failure
25
Chronic condition characterized by decreasing heart function
Heart cannot pump enough blood to meet the body’s needs
Significant Unmet Medical Need
Leading healthcare cost in U.S. and Europe
Substantial and Growing Market Opportunity
> 5 million individuals with heart failure in the U.S.
Acute Decompensation
Each decompensation event contributes to worsening heart failure
and damage to
vital organs, decreasing survival probability following the next
event
Vepoloxamer
Membrane-sealant activity may restore weakened cardiac cell membranes,
minimizing calcium overload injury
Durable effect may indicate a direct
improvement in cardiac function


NYSE MKT:  MSTX
In heart failure, elevated wall tension impairs lipid flow and
membrane repair.  This results in calcium influx and cardiac
troponin leak.
Vepoloxamer re-seals membranes and reduces membrane
tensions, enabling lipid flow and facilitating membrane repair,
thus reducing cardiac troponin and calcium overload damage.
Heart Failure Development Rationale


NYSE MKT:  MSTX
Non-clinical Model of Heart Failure
27
A single, 2h infusion improved hemodynamic parameters (LVEF, CO)
and biomarkers correlated with clinical outcomes (troponin, NT-proBNP)
A potentially novel mechanism, compatible with existing treatments
Planning to initiate Phase 2 in acute decompensated HF in Q2 2015
Source: data on-file


NYSE MKT:  MSTX
28
AIR001
(sodium nitrite) inhalation solution


NYSE MKT:  MSTX
AIR001 is nitrite for intermittent inhalation (via nebulizer)
AIR001 is being developed for Heart Failure with Preserved
Ejection Fraction (HFpEF)
29
AIR001
Beneficial effects include dilation of blood vessels and
reduced inflammation
Positive hemodynamic effects; reductions observed in:
Responsible for ~50% of heart failure hospitalizations
80% develop Pulmonary Hypertension
Leads to shortness of breath, dizziness, fainting, leg swelling,
etc.
No approved medications
pulmonary vascular resistance
pulmonary capillary wedge pressure
right atrial pressure


NYSE MKT:  MSTX
Three Phase 1 studies:
Established MTD and safe dose level
Confirmed conversion of nitrite to nitric oxide (NO)
Acute improvements in hypoxia-induced pulmonary hypertension
No drug-drug interaction with sildenafil
One Phase 2 study:
Safety data in 124 healthy volunteers and patients with
various forms of pulmonary hypertension (well-tolerated)
30
AIR001 Clinical Data
Well-tolerated, with no treatment-related serious adverse events
All doses showed improvement in median pulmonary vascular resistance
(PVR) & median distances obtained in the 6-minute walk test
Methemoglobin levels remained normal (< 1.5%)


NYSE MKT:  MSTX
Supporting three institution-sponsored Phase 2a studies to:
Preliminary data anticipated 2H 2015
If positive, conduct Phase 2b proof-of-concept
31
AIR001 Clinical Development Plan
Evaluate acute hemodynamic effects of AIR001
Evaluate acute effects versus placebo on maximum oxygen consumption and
exercise hemodynamics
Evaluate inhaled versus intravenous administration of nitrite and safety of
multiple doses of AIR001


NYSE MKT:  MSTX
32
Upcoming News & Events
Initiate dosing in Phase 2a studies of AIR001
Q1 ’15
Initiate enrollment in EPIC extension study (repeat exposure) (EPIC-E)
1H ’15
Report data from nonclinical study of vepoloxamer in embolic stroke
Q2 ’15
Initiate enrollment in Phase 2 study of vepoloxamer in heart failure
Q2 ’15
Complete enrollment in EPIC study
Q4 ’15
Report data from Phase 2a study of AIR001 in HFpEF
2H ’15
Report
interim
safety
from
Phase
2
study
of
vepoloxamer
in
heart
failure
2H ’15
Report EPIC study top-line data
Q1 ’16
Complete enrollment in Phase 2 study of vepoloxamer in ALI
2H ’16


NYSE MKT:  MSTX
Cash/investments at 12/31/14: $57 million
Market capitalization: ~$94 million*
Shares outstanding: ~159 million*
Average daily volume (3 mo): ~1 million*
No debt
33
* As of January 5, 2015
MSTX Financial Overview


NYSE MKT:  MSTX
A Leader in Areas of Significant Unmet Need (Vepoloxamer)
AIR001
Multiple clinical readouts anticipated within 15 months
34
Mast Investment Summary
Phase 2 program in heart failure with preserved ejection fraction
Multiple phase 2a studies planned/ongoing
Sickle cell: Phase 3 top-line
Heart failure: Phase 2 (interim safety data)
HFpEF: Phase 2a studies
Sickle Cell Disease: Most advanced new drug in development
Arterial Disease: Ongoing Phase 2 in ALI with opportunity in stroke
Heart Failure: Phase 2 study to begin Q2 2015