Alternative Pathway Blocker Anti-Bb Antibody (NM8074) Receives US FDA Clearance to Start Efficacy Trial in C3 Glomerulopathy (C3G) Patients

-- FDA Clears Initiation of Efficacy Trial for C3 Glomerulopathy (C3G)

CLEVELAND, OH, USA I August 15, 2022 I NovelMed Therapeutics is a clinical-stage biopharmaceutical company focused on the development of targeted therapies for complement-mediated rare diseases. The Company announced today that the U.S. Food and Drug Administration (FDA) cleared the Company's Investigational drug NM8074 to initiate an Efficacy trial in patients with C3G in the First Quarter of 2023. NM8074 has recently completed a Phase I trial in forty (40) healthy volunteers with no safety concerns. 

"The FDA's decision conveys the unmet clinical need for and importance of NM8074 as a treatment for C3G," stated Rekha Bansal, Ph.D., Chief Executive Officer of NovelMed. "We believe that our drug's novel and well-differentiated mechanism of action is expected to result in a superior safety and efficacy profile compared to those in development for C3G indication"

NM8074 functions by binding Bb and selectively blocking the alternative pathway by neutralizing the activity of C3 convertase and C5 convertase, the two powerful proteases of the alternative pathway (AP). Further, NM8074 also blocks the formation of these proteases by impairing the amplification loop of the AP. Interestingly, NM8074 does not block the classical pathway (CP) which is critical for host defense against infections.

The AP plays a key role in the initiation and propagation of C3b deposition, inflammation, and tissue damage, as evident in complement-mediated diseases including C3G. AP-specific C3 convertase is responsible for the conversion of C3 to C3a/C3b, while AP C5 convertase is responsible for the conversion of C5 to C5a/C5b and Membrane Attack Complex (MAC). As a result, NM8074 would provide the selectivity and the specificity required for developing a novel treatment for C3G, a rare disease. "Given the role of the AP in multiple complement-mediated rare diseases, NM8074 has the potential to treat not only C3G but several other complement-mediated and complement-associated diseases as well," said Dr. Bansal.

C3G is a rare disease collectively characterized by the deposition of C3/C3b on kidney cells, proteinuria, and reduced eGFR. In addition to C3G, other complement-mediated renal diseases include C3-glomerulonephritis (C3GN), dense deposit disease (DDD), membranoproliferative glomerulonephritis (MPGN), and immune complex membranoproliferative glomerulonephritis (IC-MPGN). "Whereas each of these diseases is rare, market size is significant," stated Dr. Bansal. With each potential indication's patient population combined and the price of a complement blocker (Soliris) applied, the annual market size could reach in billions of USD.

In a Phase I placebo-controlled, a double-blind, single-ascending-dose study in healthy patients, NM8074 was shown to be safe while effectively inhibiting the AP in human serum over an extended period of time, indicating that it would be successful in treating C3G as well as other chronic diseases. Given NM8074's effectiveness in selectively blocking the AP, and its ability to maintain the CP and host defense, NM8074 has the potential to capture a significant portion of this market.

About NM8074

NM8074 is a humanized monoclonal antibody that binds Bb with picomolar affinity and exhibits dual specificity. First, NM8074 selectively blocks the AP. Second, it is specific to Bb without binding Factor B, which is present in large amounts. In essence, this protease inhibitor monoclonal antibody blocks the formation of two powerful proteases (C3 and C5 convertases) produced by the activation of the AP. The dual specificity of NM8074 is important in the initiation and propagation of C3b deposition, inflammation, and tissue damage, as evident in complement-mediated and complement-associated chronic rare diseases. Mechanistically, AP-specific C3 convertase is responsible for the conversion of C3 to C3a/C3b, while AP C5 convertase is responsible for the conversion of C5 to C5a/C5b and MAC. Treatment with NM8074 would provide selectivity and specificity to the AP while sustaining the activity of the CP. Therefore, patients will be able to maintain their host defense mechanisms that are critical for the prevention of infections. The investigational drug product, NM8074, has been extensively studied in several AP model systems to demonstrate that it:

a) Blocks AP activation upstream, confirming that NM8074 would prevent C3b deposition in C3G
b) Blocks the formation of two potent anaphylatoxins responsible for acute and chronic inflammatory cascades
c) Blocks the formation of MAC that causes tissue damage
d) Is well differentiated from Soliris®/Ultomiris® and Empaveli® having no effect on CP-mediated host defense against infections

Collectively, the drug is expected to benefit patients suffering from a variety of kidney disorders including C3G, where activation of the AP is the key driver of pathogenesis. Further, NM8074 is expected to be therapeutically effective across a broad range of rare and common AP-mediated diseases, including hemolytic, ocular, neurological, and inflammatory disorders. NM8074 has the potential to treat many complement-mediated and complement-associated illnesses, especially those for which there are inadequate treatment regimens or complete unavailability of treatment.

About NovelMed

As a clinical-stage biopharmaceutical company, we are committed to innovating and developing novel biologics for the treatment of rare (orphan) diseases. Our goal is to develop an alternative pathway specific drug that can treat a multitude of rare diseases and provide patients with low-cost treatment.

NovelMed has created a strong portfolio of intellectual property with broad applications to rare and common diseases. This includes the use of NM8074 as a treatment for a range of complement-mediated disorders related to uncontrolled activation of the AP. As part of its antibody platform, NovelMed's portfolio also includes humanized antibodies to C3b and Factor P (Properdin) that also block the formation of C3/C5 convertases. NovelMed is currently seeking licensing, partnership, and acquisition opportunities to drive its antibody development through Phase III and approval in multiple rare disease indications. For more information, please visit www.NovelMed.com.

SOURCE: Novelmed Therapeutics

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