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SANGUINATE For the Treatment of Sickle Cell Disease

SANGUINATE For the Treatment of Sickle Cell Disease. February, 2017. Sickle Cell Disease.

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SANGUINATE For the Treatment of Sickle Cell Disease

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  1. SANGUINATE For the Treatment of Sickle Cell Disease February, 2017

  2. Sickle Cell Disease • Sickle cell disease (SCD) is a genetic disease characterized by a change in the Hb composition (HbSS). Under low oxygen conditions, HbSS polymerizes, no longer carries oxygen, and forces the red cell membrane into the characteristic sickle shape. • This results in constant anemia, hemolysis, inflammation and microvascular blockage resulting in pain and organ damage. • Individuals with SCD experience lifelong complications (comorbidities) including anemia, infections, stroke, tissue damage, organ failure, intense painful episodes, and premature death. • There is a need for a therapeutic that will “unsickle” the deoxygenated RBCs and deliver oxygen downstream of blocked blood vessels.

  3. SANGUINATE™ • SANGUINATETM is an IV therapeutic with multiple properties designed to treat hypoxia caused by an ischemic or anemic event • Therapeutic properties: • Reverses the effects of vascular ischemia by reducing inflammation and vasoconstriction • Improves perfusion and oxygenation of hypoxic tissue • Does not bind NO2 • Does not form metHb in vivo • Acts as a potent colloid • Stable for 2 years at 2-25C

  4. SANGUINATE™ What is it? Hemoglobin Molecule

  5. SANGUINATE™ • Orphan Drug designation for treating the “comorbidities” of sickle cell disease • 5 INDs and over 47 eINDs approved by FDA • 220+ people treated to date • Scientific presentations/publications at international hematology and oncology meetings • Preclinical proof of MOA: multiple mechanisms of action

  6. SANGUINATE:Anti-inflammatory Effects on LPS-Challenged SCD Whole Blood Inflammatory Cytokine RNA Inflammatory Cell Surface Protein SANGUINATE pre-treatment of normal and SCD whole blood decreases inflammatory cytokine RNA and protein levels Buontempo FSCDR 2015

  7. In Vitro Effect Of SANGUINATE Treatment On Sickle Cell Morphology

  8. Unsickling Effect

  9. A In Vitro Effect Of SANGUINATE Treatment On Sickle Cell Morphology From In Vitro And Patient Blood Samples Panel A. RBCs from SCD patient volunteers were deoxygenated and then treated with either placebo (PBS) or SANGUINATE for 2 hours. RBCs were then fixed and subjected to imaging flow cytometry. Panel B. SCD patients with VOC were administered either SANGUINATE or placebo (saline). Whole blood was collected in Cytochex tubes to preserve RBC morphology prior to infusion, time of patient discharge and 72 hours post-infusion. Samples were shipped to Prolong for imaging cytometry and shape analysis. . Pre-Treatment Placebo SANGUINATE B Patient 1 RBC Circularity 2 3 Discharge Pre-Infusion 72 hours Symmetry

  10. Summary of SCD patients treated with SANGINATE ACS= Acute Chest Syndrome BNAO= Blood is not an option BMT= Bone Marrow Transplant GI=Gastrointestinal SCD= Sickle Cell Disease TTP= Thrombotic Thrombocytopenic Purpura VOC= Vaso-occlusive crisis

  11. Current Clinical Development Programs in SCD • Phase 2 VOC B. Hospital setting – recruiting patients • Phase 2 VOC A. Ambulatory setting – recruiting patients • Phase 2 SCD leg ulcer study – enrollment complete; data under analysis

  12. VOC A Study – Ambulatory Setting in the USA • Randomized (2:1 ratio), placebo-controlled, single dose in ambulatory settings (ie. infusion clinics, ED) • 24 adult patients; 5 patients have been enrolled and completed the study • Clinical sites • Blood samples are being collected (prior to infusion, at time of discharge and 72-hours post discharge) to assess the impact of SANGUINATE on RBC morphology and inflammatory markers.

  13. VOC A – Preliminary Observations by PI • Five (5) patients randomized into study; 4 treated with SANGUINATE; 1 with saline. • Patients treated with SANGUINATE reported reduction in their pain levels as assessed by pain score index • One patient had complete resolution of pain prior to completing 2hr infusion with SANGUINATE

  14. SCD Leg Ulcer Study • Escalating, repeated-dose, open-label, Phase 2 study to test SANGUINATE at 320 mg/kg (8 mL/kg – approx 1 unit) in subjects suffering from leg ulceration associated with SCD • Patients received once-weekly doses for either 4 or 6 weeks • Safety, efficacy and quality of life were assessed • There were no clinically meaningful changes in laboratory values, ECG intervals, physical examinations, or concomitant medications. Drug was generally well tolerated • Slight decreases in total Venous Clinical Severity Score at most time points, indicating slight improvement in vascular status • Data under analysis

  15. Future Clinical Plans in SCD • Efficacy trial in planning phase for ambulatory setting • Other proposed SCD comorbidities under consideration • stuttering priapism • acute chest syndrome • hyperhemolysis • splenic sequestration

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