NovelMed Announces Interim Positive Results from Its Phase I Clinical Trial of NM8074, a Bb Complement Alternative Pathway Blocker Antibody

CLEVELAND, Feb. 21, 2022 /PRNewswire/ -- NovelMed Therapeutics, Inc. announced today interim positive results from a First-in-Human Phase I clinical trial of its complement blocker monoclonal anti-Bb antibody, known as NM8074. The trial was a randomized, double-blind, placebo-controlled, single ascending dose study designed to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity (ADA) of NM8074 in healthy volunteers.

Forty healthy subjects were administered NM8074 as a single dose (ranging from 0.3 to 20 mg/kg). Interim data evaluation has demonstrated that NM8074 is safe at all doses and is well tolerated. Assays testing classical pathway (CP) and alternative pathway (AP) function confirm that the drug is specific to the AP and has no effect on the CP, which is critical for host defense. Sustained targeted inhibition of the AP, while leaving the protective CP intact, is a critical aspect of NM8074 that distinguishes itself from other anti-complement drugs. These results further confirm Novelmed's in vitro studies that have evaluated sera from both healthy subjects and patients with paroxysmal nocturnal hemoglobinuria (PNH). Those in vitro studies demonstrated NM8074 targeted specificity for the AP and not the CP. Full analysis of all dose cohorts for completion of the Phase I trial is underway with additional clinical trials gearing up in PNH. Early success in Phase I studies marks the first clinical milestone towards the development of NM8074 as a highly effective and safe therapeutic against complement-mediated inflammation and hemolysis associated with PNH and other complement disorders.

NM8074 selectively binds disease-specific Bb and does not bind Factor B of the AP, which is a major advantage over other complement inhibitors. "This is the first study to demonstrate that selective blockade of Bb can be safely achieved in a clinical study," said Rekha Bansal, Ph.D., Chief Executive Officer of NovelMed. Because NM8074 selectively blocks AP-mediated C3b and MAC formation, it is therefore expected to comprehensively treat the persistent clinical symptoms associated with chronic AP-mediated mechanisms, specifically prevention of red blood cell loss via both extra- and intra- vascular hemolysis in PNH patients, including lactate dehydrogenase (LDH) release. The mechanism of NM8074 is distinct from that of C3 and C5 blockers, treatments currently approved by the FDA. These inhibitors target both the AP and CP complement pathways, thereby introducing deficiencies in this therapeutic approach. "We believe that NM8074 would address the deficiencies associated with current treatments, both approved or in development," says Bansal.

NovelMed is presently filing for initiation of clinical trials designed to assess the safety, and efficacy of NM8074 in patients with PNH.

About Paroxysmal Nocturnal Hemoglobinuria

PNH is a rare blood disorder in which hemolysis and thrombosis, accompanied by impaired bone marrow function, cause debilitating symptoms that adversely affect patient quality of life and can lead to early death. Empaveli™, a C3 blocker has recently been approved by the FDA. Empaveli improves hemoglobin levels as compared to Soliris™ but improvement in LDH levels is not robust. Further, as a pegylated molecule, the long-term effects of this drug in extended treatment of chronic disease are not known. Soliris and its successor, Ultomiris, have been approved for treatment of other complement-mediated diseases, but the current cost of Soliris therapy is nearly $500,000 per year per patient, which severely limits affordability and accessibility to patients worldwide.

About NM8074

NM8074 is an anti-Bb humanized antibody that binds and neutralizes the activity of both C3 and C5 convertases produced by the disease-specific alternative complement pathway. Blocking the formation of these two convertases results in the blockade of both C3b and membrane-attack complex (MAC) formation, thereby preventing lysis of red blood cells via extra- and intra-vascular hemolysis in PNH. Treatment with NM8074 also blocks the production of two potent anaphylatoxins, C3a and C5a, and consequential cellular activation. Overall, NM8074 inhibits the pathology associated with complement over-activation  by mechanistically blocking the formation of: a) anaphylatoxins C3a and C5a, b) C3 and C5 convertases, c) C3b, d) MAC, and e) LDH release. This targeted approach collectively and broadly applies to numerous complement-mediated disorders.

NM8074 is suitable for use in disease indications driven by the dysregulation of the complement system e.g., complement-mediated hemolytic disorders, renal disorders, ocular disorders, neurological disorders, and inflammation. Treatment with selective upstream alternative pathway (AP) inhibitors is a targeted strategy to combat chronic diseases like PNH. Although approved for treatment of a handful of complement-mediated disorders, marketed complement inhibitors indiscriminately block the alternative complement pathway as well as classical complement pathway, which is required for clearing infectious microorganisms. Additionally, C3b formation persists and therefore render patients susceptible to unresolved extravascular hemolysis. Because NM8074 solely targets the disease-specific AP, it is expected to collectively control hemolysis, C3b deposition, and LDH release, all while sustaining patient host defense against infections. Given its unique mechanism of action, NM8074 is expected to function as a superior therapeutic to currently FDA approved treatment options.

About NovelMed

NovelMed is a clinical-stage biopharmaceutical company focused on the development of novel biologics for the treatment of a broad range of complement-mediated diseases. NovelMed is the first company to have invented and validated an anti-Bb antibody to treat chronic complement-mediated and complement-associated disorders. NovelMed is currently evaluating its lead product candidate in clinical trials, with PNH as the first indication and C3G as a second indication.

NovelMed is committed to leveraging creativity and compassion to deliver game-changing therapies to patients. NovelMed is positioning itself as a leader in developing AP-targeted therapies to resolve debilitating diseases in the areas of hematology, ophthalmology, nephrology, and neurology. For more information, please visit www.novelmed.com.

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