• Phase I Clinical Trial in healthy subjects shows that NM3086 was safe and well tolerated at all doses (0.1 to 20 mg/kg) in six cohorts.

• Total AP inhibition was achieved through all cohorts and the duration of alternative pathway (AP) inhibition occurred in a dose-dependent manner. Correspondingly, the classical pathway (CP) remained unaffected, suggesting that NM3086 selectively blocks the AP while maintaining the host defense.
  

• NM3086 blocked the deposition of C3b via AP, a marker of extravascular hemolysis (EVH). The duration of AP-C3b inhibition followed the AP inhibition profile very closely in a dose dependent manner.
  

• NM3086 did not block the deposition of C3b via the CP, a marker of opsonization. There was no suppression of CP driven C3b activity across all cohorts.
  

• Results suggest that NM3086 has the potential to selectively inhibit both intravascular hemolysis (IVH) and EVH via the AP while maintaining the CP required for bacterial clearance and opsonization in Paroxysmal Nocturnal Hemoglobinuria (PNH) and other hemolytic disorders.
  

CLEVELAND, June 05, 2023 (GLOBE NEWSWIRE) -- NovelMed Therapeutics, Inc. announced today topline results from First-in-Human Phase I clinical trial of its complement blocker monoclonal anti-Properdin antibody, known as NM3086. The trial was a randomized, double-blind, placebo-controlled, single ascending dose study designed to assess safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and immunogenicity (ADA) of NM3086 in healthy volunteers.

NM3086 was administered as a single dose (ranging from 0.1 to 20 mg/kg) and the study was followed for up to 90 days. The drug was safe and well tolerated in all doses. Assays of the alternative pathway (AP), classical pathway (CP), extravascular hemolysis (EVH), and opsonization were performed. AP activation, AP-driven C3b formation and deposition were inhibited in a dose dependent manner with the highest dose of 20 mg/kg blocking AP for more than 6 weeks. Sustained targeted inhibition of the AP, without blocking the CP, is a critical aspect of NM3086 that distinguishes itself from other FDA approved anti-complement drugs.

These results from Phase I trial are consistent with our in vitro studies conducted on PNH serum and in naïve and Soliris-Treated PNH sera. Early success in Phase I studies marks the first clinical milestone towards the development of NM3086 as a safe AP blocker for anemia in PNH and other complement-mediated disorders.

NM3086 selectively binds the critical protein ‘properdin” of the AP responsible in part for amplification of the AP, a major advantage of NM3086 over other FDA approved complement blockers. “This is the first clinical study to demonstrate that selective blockade of the AP can be safely achieved by neutralizing Properdin, a critical protein in the AP cascade,” said Rekha Bansal, Ph.D., Chief Executive Officer of NovelMed.

Because NM3086 selectively blocks AP-mediated C3b and MAC formation, it is therefore expected to treat both extra- and intra- vascular hemolysis in PNH patients. NM3086 blocks the formation of C3a/C3b, C5a/C5b, and MAC which are responsible for overall pathology of complement-mediated disorders including PNH. “Our drug, NM3086, is expected to treat disorders mediated via (Factors B, D and P), C3a, C3aR, C5a, C5aR, and MAC. Instead of targeting each one individually, our molecule would target all of them by blocking the initiation step of the AP,” says Dr. Bansal. NovelMed is moving this molecule in multiple indications as a result.

“We continue to be impressed by the data from in vitro and clinical trial studies, which confirm the potential of NM3086 to outperform other drug candidates in the complement space,” says Robert Bard, VP Regulatory Affairs.

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. PNH is a rare, chronic, and serious complement-mediated blood disorder with a significant unmet need despite treatment with anti-C5 therapies, as a large proportion of people with PNH remain anemic, fatigued, and dependent on blood transfusions.

About NM3086

NM3086 is an anti-P humanized monoclonal antibody that binds properdin with high affinity. NM3086 blocks 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 NM3086 also blocks the production 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.  

NM3086 is suitable for use in multiple disease indications e.g., complement-mediated hemolytic disorders, renal disorders, ocular disorders, neurological disorders, dermatological disorders, and inflammation. Currently available complement inhibitors indiscriminately block both the alternative and the classical complement pathways, where in the latter is required for clearing infectious microorganisms. NM3086 is expected to control hemolysis, C3b deposition, and LDH release, all while sustaining patient host defense against infections. Given its unique mechanism of action, NM3086 is expected to function as a superior therapeutic to currently FDA approved treatment options possibly without the Black-Box warning.

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-Properdin 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.

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, dermatology, and neurology. For more information, please visit www.NovelMed.com.

Seeking Funds to Advance the Development of NM3086 for Rare Disease Platform

PNH is a rare disease characterized by intravascular and extravascular hemolysis, higher LDH values, and lower hemoglobin values. In PNH patients currently treated with C5 blockers, approximately 36% of these patients still require more than one transfusion per year. In addition, almost all patients were found to be positive for opsonization markers while nearly 70% continued to have low hemoglobin levels despite treatment. NM3086 on the other hand is expected to fully control AP related disease progression in PNH patients.

NovelMed is currently seeking licensing, partnership, and acquisition opportunities to drive NM3086 through further development and approval in multiple rare disease indications. For more information, please visit www.NovelMed.com/news

Contact:

Robert Bard
NovelMed Business Development Team
bd@novelmed.com
(216) 440 2696