Issuer Free Writing Prospectus Dated June 7, 2013
(to the Preliminary Prospectus dated June 5, 2013)
Filed Pursuant to Rule 433
Relating to Registration Statement on Form S-1
Registration No. 333-188870
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Corporate overview
June 2013
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This presentation includes forward-looking statements about our business prospects, financial position, and development of MST-188 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 MST-188; and other risks and uncertainties more fully described in our press releases and our filings with the SEC, including the prospectus included in our registration statement on Form S-1 (File No. 333-188870).
We caution you not to place undue reliance on any of these forward-looking statements, which speak onlyas of the dateof thispresentation. We donot intend toupdateany 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.
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corporate overview
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Developing MST-188 for “microcirculatory insufficiency”
Platform technology targeting multiple indications
Initially focused on rare/orphan diseases
Sickle Cell Disease (SCD)
Acute Limb Ischemia (ALI)
Currently enrolling subjects in a pivotal phase 3 study in SCD
Most clinically-advanced new molecular entity in development for SCD
Planned expansion into larger markets
Resuscitation Following Major Hemorrhage
Acute Decompensated Heart Failure
Transfusion (Storage Lesion)
Acute Ischemic Cerebrovascular Infarction (Stroke)
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Drug Product: Formulated as a clear, citrate-buffered solution
Large polymer (8,500 Daltons) manufactured by
CMC: chemical synthesis and proprietary purification process
Administration: ~12-48 hour IV infusion in acute-care settings
(hospital, ICU, specialized out-patient)
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Hydrophobic core binds to hydrophobic domains in circulation (e.g., damaged cell membranes, acute phase reactant proteins)
No Affinity for Healthy Cell Membranes
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Single mechanism with numerous effects addresses multiple pathophysiologic processes
Preclinical Phase 1 Phase 2 Phase 3 2013
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Sickle Cell Disease
(orphan)
Acute Limb Ischemia
(orphan)
Resuscitation of Shock
following Major Trauma*
Acute Decompensated
Heart Failure
Transfusion
(storage lesion)
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Contingent on U.S. government funding/other collaborator |
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Sickle Cell Disease
(vaso-occlusive crisis)
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An inherited genetic disorder and orphan disease
90,000 to 100,000 people with SCD in the U.S.‡
Characterized by severe deformation (i.e., “sickling”) of red blood cells
Sickled cells cannot navigate the microcirculation
Presents as recurring episodes of extreme pain (“crisis”)
Episodes typically last 4 to 5 days, but may last a week or longer
Patients “suffer at home” until pain requires IV analgesia (hospital visit)
Significant unmet need
Average death: ~40 years old
Standard of care; hydration and pain meds
~100,000 hospitalizations/year for crisis
No approved agents to shorten duration or severity of crisis
Substantial recent interest from Big Pharma
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Pfizer: $395 million* for phase 2 investigational drug (Oct 2011)
Novartis: $650 million* for phase 2 investigational drug (Sep 2012)
Vaso-occlusion: RBCs cannot traverse occlusion to
deliver oxygen to tissue (ischemia/infarction)
MST-188: rheologic activity reduces RBC aggregation,
improves RBC deformability, lowers viscosity
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Improvement in microvascular blood flow in SCD patients in crisis following treatment with MST-188
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Improvement in various endpoints in SCD patients in crisis following treatment with MST-188*
Duration of Crisis
Duration of Hospitalization Total Analgesic Use Parenteral Analgesic Use
Subjects who received ? 24h infusion (n=45)
MST-188* Placebo Improvement
60 hours 88 hours 32% shorter
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days 7 days 2 days shorter |
49mg 169mg 71% less
40mg 150mg 73% less
Source: Blood, September 1, 1997 – Vol 90, No. 5
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1st generation (non-purified) formulation |
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Reduction in duration of hospitalization in SCD patients with acute chest syndrome (n=41) following treatment with MST-188*
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Improvement in duration of crisis in SCD patients following treatment with MST-188
Source: JAMA, November 17, 2001 – Vol 286, No. 17
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Completed Phase 3 Study in SCD
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All treated patients (n=249) 51.6% 36.6% 0.02
Patients <16 years old (n=73) 62.2% 27.8% 0.01
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Lessons Learned
Prior Phase 3 was the first large interventional study in SCD
Simplify endpoint to minimize protocol violations and missing (“left- censored”) data
Follow subjects until hospital discharge to avoid truncated (“right- censored”) data
Avoid subjective endpoints, which increase variability
Standardize pain management practices across study sites
Increase homogeneity in terms of cumulative disease burden (chronic pain)
Control duration of crisis (“suffering at home”) prior to randomization
Limit SCD genotypes
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Study design
Randomized, two-arm, double-blind, placebo-controlled
388 patients ages 8-17 from ~40 centers in the U.S. and ~30 centers outside the U.S.
90% power to show 16h benefit versus standard of care
Primary endpoint
Duration of crisis
Time from randomization to last dose of parenteral opioid
Secondary endpoints
Re-hospitalization rate (for vaso-occlusive crisis) within 14 days
Acute chest syndrome within 120 hours of randomization
First Active Site: March 2013
Expected enrollment completion and data read-out: 2015
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1248 (Prior Study) EPIC (Ongoing)
Primary Endpoint Duration of crisis Duration of crisis
Assessment tool Pain score plus Last dose parenteral opioid
Total analgesic use; 14-day rehospitalization
Secondary endpoint Length of rate; Acute chest
hospitalization syndromes
No. Patients 350 (255 actual) 388
Patient age 8-65 8-17
No. Centers 40 US 40 US + 30 ex-US
Power (alpha) 80% (0.05) 90% (0.05)
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Potential Competition in SCD
Drug
Sponsor
GMI-1070 Glycomimetics
(Phase 2) (Pfizer)
Sel-G1 Selexys
(Phase 1) (Novartis)
Prasugrel Lilly (Daiichi)
(Phase 3)
LentiGlobin® bluebird bio
(Phase 1/2)
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Challenges
Only blocks selectins; other adhesion molecules not affected
Subjectivity of pain scores
Variability inherent in hospital discharge as endpoint
MOA targets only 1 aspect of multi-factorial SCD pathophysiology; blocks P-selectin, one of many CAMs
Early stage, no efficacy data (phase 1 was in healthy subjects)
MOA targets only 1 aspect of multi-factorialulti SCD pathophysiology
Modest benefit (trend) observed in phase 2, and only in secondary endpoints, not in primary endpoint
Risk of hemorrhage
Early stage (phase 1/2 in beta-thalassemia to start July 2013)
Regulation of expression control and insertion location
Historical challenges related to gene therapy
Acute Limb Ischemia
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A progressive circulatory problem in which obstructed arteries reduce blood flow to tissue
Thrombolytic agents (tPA) used to treat acute complications
Significant morbidity and mortality
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 larger markets
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Animals randomized to tPA (duteplase) (n = 10) or tPA + MST-188* (n = 10)
Source: Data on file
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1st generation (non-purified) formulation |
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Generate Clinical Proof-of-Concept Data
Biomarkers
Clinical outcomes
Protocol under development
Study Concept
Design: dose-finding, randomized, double-blind, active-controlled
Population: Rutherford Class 2A / 2B and catheter-directed thrombolysis
Arms: tPA vs. tPA + MST-188
Sample Size: 60 subjects
Timing
Initiation: late 2013/early 2014
Enrollment: ~15 months
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Multiple Barriers to Entry
Marketing 3/4 SCD: orphan drug designation in U.S. and EU
Exclusivity 3/4 ALI: will seek orphan drug designation in U.S. and EU
3/4 Filed applications cover:
ƒ proprietary purification process
Patents ƒ methods of using poloxamers
ƒ use of poloxamers in combination therapy
3/4 Additional applications in-process
3/4 Macromolecules difficult to characterize (“biosimilars”)
Trade 3/4 Non-patented / non-published manufacturing steps
Secrets 3/4 Proprietary specifications (in-take; in-process; release)
3/4 Evaluating proprietary analytical standards / bioassays
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Cash/investments at 3/31/13: ~$32.0 million
Market capitalization: ~$33 million*
46.3 million shares outstanding
ƒ Warrants for 16.5 million shares (10.6m @ $1.10; 5.9m @ $3.04‡)
Average daily volume (3 mo): ~215,500*
No debt
Opportunities for U.S. government funding
Evaluating ex-U.S. partnerships to fund U.S. development
Weighted average exercise price * As of May 31, 2013
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2013 Activities
Event Timing
Initiate tQT/QTc Study Completed
Secure Orphan Designation for MST-188 for SCD in EU Completed
Activate First Site in Phase 3 Study Completed
File New Patent Applications Completed
Request “Rare Pediatric Disease” Designation for SCD Completed
Dose First Subject in Phase 3 Study Completed
Report data from tQT/QTc Study Q3
Submit Applications for U.S. Government Funding for Phase Q3
2 Study in Resuscitation of Shock following Major Trauma
Request Orphan Designation for MST-188 for ALI in U.S. Q3
Initiate Nonclinical Proof-of-Concept Study in Heart Failure Q3
Open First Ex-U.S. Clinical Site in Phase 3 Study Q4
Initiate mBF Sub-Study Q4
Initiate Phase 2 Study in ALI Q4 ‘13/Q1 ‘14
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3/4Brian Culley, M.A., M.B.A.—Chief Executive Officer
3/4Patrick L. Keran, J.D. – President and Chief Operating Officer
3/4Santosh Vetticaden, M.D., Ph.D.—Chief Medical Officer
3/4Brandi Roberts, CPA, M.B.A.—Chief Financial Officer
3/4R. Martin Emanuele, Ph.D., M.B.A.—Senior VP, Development
3/4Gregory D. Gorgas, M.B.A. – Senior VP, Commercialization
Board of Directors & Affiliations
3/4Jack Lief – Chairman—Arena, Cephalon, Abbott
3/4Ted Love – Director—Onyx, Nuvelo, Theravance, Genentech
3/4David Ramsay – Director—Halozyme, Lathian, Valeant
3/4Lewis Shuster – Director—Kemia, Life Technologies, Pharmacopeia
3/4Brian Culley—CEO & Director—iTherx, Neurocrine, UC San Diego
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Balanced Platform Pipeline
Mitigates corporate-level development risk
Multiple partnering opportunities
Multi-Stage Development Strategy
Initial focus on rare diseases; expand into larger markets
Late-Stage Program in Sickle Cell Disease
Only company with new drug in phase 3 development
Increasing trend for Big Pharma deal-making
Non-Dilutive Financing Opportunities
U.S. government funding
Ex-U.S. partnerships to fund U.S. development
Attractive Valuation
Market capitalization: ~$33 million*
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Additional Slides
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Corporate Evolution
Appoint new CEO and COO
Raise ~$60 million
2010
2011
2012
2013
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Theradex
30 year collaboration with National Cancer Institute
Experience with pediatric trials, minority populations, and sickle cell disease trials, including phase 3
Pierre-Fabre Medicament
Manufacturing active ingredient in MST-188
Second largest independent pharmaceutical group in France
Supercritical Fluids Division has expertise and specialized facilities for purification of products via supercritical extraction
Patheon
Formulation, fill and finish of MST-188
A leading global provider of manufacturing services
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MST-188: generally well-tolerated
Transient elevations in liver function tests, return to baseline during follow-up
Evaluated in 6 clinical studies*
255-subject phase 3 randomized, controlled study in sickle cell disease
~250 subjects* exposed to active drug
Thorough QT/QTc Study
Standard design to assess cardiac repolarization (QT interval)
Initiated: Jan 2013
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Numbers include only subjects exposed to 2nd generation (purified) formulation. |
Over 2,250 additional subjects exposed to 1st generation (non-purified) formulation.
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Four-period, four-way cross-over, placebo- and positive- controlled, double-blind randomized trial in 60 healthy volunteers
Subjects receive each of four treatments:
ƒ Placebo (saline) ƒ MST-188 therapeutic dose
ƒ Positive control ƒ MST-188 supra-therapeutic dose
Primary objective: evaluate the effect of MST-188 on cardiac ventricular repolarization (specifically the QT interval)
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Preclinical
Phase I
Phase II
MST 188
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Effect of IV blocking agents on RBC adhesion following topical LPS
Poloxamer 188 is as effective as targeted agents
Source: Microcirculatory Effects Of Blocking Cell Adhesion Molecules In Transgenic Sickle Cell Mice, Dr. L.L. Hsu
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MST-188* studied in 5 controlled models of hemorrhagic shock / resuscitation by 4 different investigator groups
Consistently improved survival (reproducibility across studies)
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Resuscitation (2011) (DARPA-funded) MST-188 Control pValue
(n=7) (n=16)
Median Survival Time (min) 161 55.8 0.0186
(95% CI) (80—180) (36.5—86)
Shock (2009) MST-188 + Hextend p Value
Hextend
Survival time from onset of hemorrhage
(min) 589±99 289±37 0.002
(n=10/arm)
Source: Resuscitation 82 (2011) 1453-1459, SHOCK, Vol 32, No. 4, pp. 442-450, 2009
*Some studies evaluated 1st generation (non-purified) formulation
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Resuscitation of Shock following Major Trauma Planned Phase 2 Study & Funding
Generate Clinical Proof-of-Concept Data
Study Protocol (complete)
Design: dose-ranging, randomized, double-blind, controlled
Population: admitted to ICU for resuscitation following major torso trauma
Arms: standard resuscitation protocol (SRP) vs SRP + MST-188
Sample Size: 60 subjects
Enrollment: 18—24 months
Collaboration with University of Florida
A leader in clinical research and trauma care
U.S. Government Funding
MST-188 prior recipient of funding (DARPA)
Preparing / submitting new applications
Timeline: 9—12 months
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Contact Info:
Brian M. Culley Chief Executive Officer culley@mastthera.com
Brandi Roberts
Chief Financial Officer
broberts@mastthera.com
12390 El Camino Real, Ste. 150 San Diego, CA 92130 Ph: (858)-768-6325
Mast Therapeutics, Inc. has filed a registration statement (Registration No. 333- 188870, including a prospectus) under the Securities Act of 1933, as amended, with the Securities and Exchange Commission for the offering to which this communication relates. Before you invest, you should read the prospectus in that registration statement for more complete information about the Company and the Offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the prospectus may be obtained from Piper Jaffray & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, via telephone at 800-747-3924 or email at prospectus@pjc.com.