Savara, Inc. · NASDAQ:SVRA
Savara — Mast Therapeutics — IPO Roadshow (June 2013)
40 slides from Savara's IPO roadshow presentation, Jun 10, 2013
Slide 1: Corporate overview
Corporate overview June 2013
Slide 2: Forward-looking statements
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 stateme
Slide 3: Developing MST-188 for microcirculatory insufficiency
TY | > 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-a
Slide 4: Developing MST-188 for microcirculatory insufficiency
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 molecul
Slide 5: Drug Product: Formulated as a clear, citrate-buffered solution
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)
Slide 6: Hydrophobic core binds to hydrophobic domains in circulation
Hydrophobic core binds to hydrophobic domains in circulation (e.g., damaged cell membranes, acute phase reactant proteins) No Affinity for Healthy Cell Membranes
Slide 7: Single mechanism with numerous effects addresses multiple pathophysiologic processes
Single mechanism with numerous effects addresses multiple pathophysiologic processes Preclinical Phase 1 Phase 2 Phase 3 2013
Slide 8: Sickle Cell Disease and other indications pipeline
Sickle Cell Disease (orphan) Acute Limb Ischemia (orphan) Resuscitation of Shock following Major Trauma* Acute Decompensated Heart Failure Transfusion (storage lesion) * Contingent on U.S. government funding/other collaborator
Slide 9: Sickle Cell Disease
Sickle Cell Disease (vaso-occlusive crisis)
Slide 10: An inherited genetic disorder and orphan disease
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 la
Slide 11: Big Pharma interest in SCD; vaso-occlusion and MST-188
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 def
Slide 12: Improvement in microvascular blood flow in SCD patients in crisis
Improvement in microvascular blood flow in SCD patients in crisis following treatment with MST-188
Slide 13: Improvement in various endpoints in SCD patients in crisis
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 days 7 days
Slide 14: Reduction in hospitalization in SCD patients with acute chest syndrome
Reduction in duration of hospitalization in SCD patients with acute chest syndrome (n=41) following treatment with MST-188*
Slide 15: Improvement in duration of crisis in SCD patients
Improvement in duration of crisis in SCD patients following treatment with MST-188 Source: JAMA, November 17, 2001 – Vol 286, No. 17
Slide 16: Completed Phase 3 Study in SCD
Completed Phase 3 Study in SCD
Slide 17: Prior phase 3 results by patient group
All treated patients (n=249) 51.6% 36.6% 0.02 Patients <16 years old (n=73) 62.2% 27.8% 0.01
Slide 18: Lessons Learned
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 variabil
Slide 19: Study design
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
Slide 20: Prior study versus EPIC (ongoing) comparison
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) 38
Slide 21: Potential Competition in SCD
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) Challenges Only blocks selectins; other adhesion molecules not affected Subjectivity of pain scores Variab
Slide 22: Acute Limb Ischemia: progressive circulatory problem
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
Slide 23: Animals randomized to tPA or tPA + MST-188
Animals randomized to tPA (duteplase) (n = 10) or tPA + MST-188* (n = 10) Source: Data on file * 1st generation (non-purified) formulation
Slide 24: Generate Clinical Proof-of-Concept Data
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
Slide 25: Multiple Barriers to Entry
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 t
Slide 26: Cash, market capitalization and shares outstanding
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
Slide 27: 2013 Activities
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
Slide 28: Management and Board of Directors
3 / 4 Brian Culley, M.A., M.B.A.—Chief Executive Officer 3 / 4 Patrick L. Keran, J.D. – President and Chief Operating Officer 3 / 4 Santosh Vetticaden, M.D., Ph.D.—Chief Medical Officer 3 / 4 Brandi Roberts, CPA, M.B.A.—Chief Financial Officer 3 / 4 R. Martin Emanuele, Ph.D., M.B.A.—Senior VP, Devel
Slide 29: Balanced Platform Pipeline
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 t
Slide 30: Additional Slides
Additional Slides 30
Slide 31: Corporate Evolution
Corporate Evolution Appoint new CEO and COO Raise ~$60 million
Slide 32: Theradex, Pierre-Fabre and Patheon collaborations
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 Supercr
Slide 33: MST-188: generally well-tolerated
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
Slide 34: Thorough QT/QTc study design
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 effe
Slide 35: Preclinical to Phase II development
Preclinical Phase I Phase II MST 188
Slide 36: Effect of IV blocking agents on RBC adhesion
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
Slide 37: MST-188 in hemorrhagic shock / resuscitation models
MST-188* studied in 5 controlled models of hemorrhagic shock / resuscitation by 4 different investigator groups Consistently improved survival (reproducibility across studies)
Slide 38: Resuscitation and shock survival data
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) 14
Slide 39: Resuscitation of Shock following Major Trauma Planned Phase 2 Study & Funding
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 resusci
Slide 40: Contact Info
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, inc