ABSTRACT Our lead drug candidate is being developed as a disease modifying, potent and efficacious treatment for paroxysmal nocturnal hemoglobinuria (PNH), an “orphan disease”, and is anticipated to be far superior to the current monotherapy Soliris (Eculizumab) treatment. Soliris blocks both the classical (CP) and the alternative (AP) pathways of complement, and is used in treatment of PNH, atypical uremic syndrome (aHUS), neuromyelitis optica (NMO), and myasthenia gravis (MG). The FDA approved Soliris in 2007 despite its possessing two troubling properties: a) uncontrolled extravascular hemolysis (EVH) that causes incurable anemia and b) vulnerability to secondary infections due to blockade of the classical pathway (CP) which is required for host defense, despite vaccination against such ailments as meningitis. Because there is no other treatment for PNH currently approved by the FDA, use of Soliris continues to increase yearly. Our clinical candidate is a selective inhibitor of the AP and does not block the CP. By mechanistically blocking the upstream AP specifically, the two issues deficient during Soliris treatment can be addressed. Our lead drug: a) blocks AP-mediated C3b formation and deposition on erythrocytes and therefore prevents EVH, and b) does not block the CP, which is required for host defense against pathogens and infection. Further to this, potential success of this drug in effectively treating PNH is supported by the following characteristics: a) high affinity binding, b) high potency of AP inhibition, c) inhibition of AP-mediated lactate dehydrogenase (LDH) release, d) lack of CP inhibition, e) successful toxicology studies, and f) completion of a successful phase I clinical. A streamlined cGMP manufacturing process has been established, and guarantees robust production of the quality material for treatment. Given this unique mechanism of action, we believe that this drug will provide benefits in diseases where specific blockade of proximal AP is required. Preliminary data from the recently completed phase I trial in 48 healthy volunteers suggests that the drug candidate completely blocks the AP at 1mg/kg, and does not block the CP at any of the doses tested, confirming the beneficial therapeutic potency of this monoclonal antibody. Furthermore, administration of the lead drug did not require loading doses and was deemed safe in humans with no reported severe adverse events. This ensures that administration of this drug is patient friendly. Results from this phase I trial are supported by multiple in vitro and ex vivo studies on normal human serum and blood, and serum from naïve and Soliris treated PNH patients. This submission outlines a proposed phase II PNH clinical study to examine the effects and benefits of NovelMed's lead drug in PNH naïve patients, compared to use as an add-on to Soliris treated PNH subjects. Dosing of our clinical candidate is proposed at a single dose of 10 mg/kg administered every 4 weeks for 3 mont...