NM-3086

---Single therapy for multiple forms of Age-Related Macular Degeneration (AMD) NM3086 is a highly potent Alternative Pathway (AP) blocker that does not affect the Classical Pathway (CP).Dysfunction of the Complement Alternative Pathway is a critical factor in disease onset and progression in Wet-AMD, Dry-AMD, and Geographic Atrophy (GA).The lead drug candidate NM3086 prevented hemorrhage, fibrosis, and neovascularization in a 28-day disease model in rhesus monkeys.The specificity and functional ability of NM3086 are an upgrade over other drugs approved by the FDA for the treatment of GA.NovelMed is seeking to license the Anti-Properdin program to advance the development of NM3086 for Wet-AMA, Dry-AMD, GA, and rare ocular diseases. CLEVELAND, March 06, 2023 (GLOBE NEWSWIRE) -- NovelMed Therapeutics announced today that NM3086, the lead clinical asset in its Properdin-associated Alternative Pathway (AP) program, demonstrated favorable efficacy in an animal model of neovascular age-related macular degeneration (AMD) in rhesus monkeys. This animal model is characterized not only by the abnormal growth of new blood vessels behind the retina, as shown in Figure 1, but also by retinal fibrosis and vascular hemorrhage, which are the critical characteristics of Wet-AMD, Dry-AMD, and GA. While it is difficult to extrapolate the visual acuity score in animals, the damage prevented by NM3086 in this model suggests the drug's efficacy in treating the disease. Figure 1: Fluoresceine angiogram data from three animals treated with NM3086 (bottom) and three that received placebo control. The picture shows reduced hemorrhage and neovascularization (Left) and Fibrosis (Right) in the drug-treated animals. Scientists of Charles River Laboratories established a preclinical Choroidal Neovascularization (CNV) efficacy model in rhesus monkeys. This study administered NM3086 (1.2 mg/eye ) intravitreally to monkeys before creating nine laser-induced retinal lesions. Following a two-week observation period, choroidal neovascularization (formation of new blood vessels), retinal fibrosis (scar tissue), and hemorrhage (vascular leakage) were quantified against a placebo control. NM3086 resulted in a significant decrease in the extent of all three damage markers. "This All-in-One approach in ophthalmic space is a significant achievement for treating multiple ocular chronic ailments with a single therapy," states Dr. Bansal of NovelMed Therapeutics. About Complement-Mediated Ocular DisordersAMD is of two main types: "Wet" and "Dry." In the Wet form, abnormal blood vessels (choroidal neovascularization or CNV) grow under the retina and macula. These new blood vessels then bleed or leak fluid which causes the macula to bulge and distort central vision, resulting in rapid and severe vision loss. Approximately 10% of the total AMD cases have new blood vessels and leakage interactions, categorized as Wet-AMD. The Dry form (non-neovascular AMD) does not involve fluids from blood vessels; cases of this form are known as geographic atrophy (GA). GA is a chronic, progressive deterioration of the macula that affects ~1.45 million people in the United States and over 8 million people worldwide. The incidence of GA is expected to rise as the age-related disease burden of developed countries increases. The AP activation is essential to AMD pathogenesis of both types. It is well-accepted that excessive activation of the AP is a significant cause of the illness in both Wet- and Dry-AMD, including GA. Preventing tissue damage and excessive inflammation requires complete shutdown of the Alternative Pathway. A therapy that can prevent excessive activation of the AP would prove to be a blockbuster treatment for Wet AMD, Dry AMD, and GA. About NM3086NM3086 selectively binds Properdin and blocks the AP activation. As a result, the formation of C3 and C5 convertases is blocked. In general, the C3 convertase converts C3 to C3a and C3b, while the C5 convertase converts C5 to C5a and C5b. C3a and C5a are potent inflammation-causing agents which activate a variety of cells. Activated cells release pro-inflammatory molecules such as tumor necrosis factor alfa (TNFα), vascular endothelial growth factor (VEGF) and other cytokines. The C5b molecule converts into a membrane attack complex (MAC) which damages cells and tissues. This cycle repeats itself until the entire tissue is damaged and gone. This vicious cycle produces excessive levels of pro-inflammatory cytokines such as TNF and VEGF, typically elevated in ocular diseases. The VEGF is known to promote the growth of new blood vessels and makes the blood vessels leaky in Wet-AMD. Anti- VEGF drugs (Lucentis and Eyelea) stop the development of these new blood vessels. These drugs prevent the loss of central vision in Wet AMD, Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR). As an investigational drug, NM3086 has been extensively studied in various in vitro and in vivo disease models, which prove that the drug: a) blocks AP-driven cellular lysis, TNF production, and VEGF production, and b) prevents neovascularization, scar formation, hemorrhage, and inflammation in animal models. Treatment with NM3086 is specific to the AP while preserving the regular activity of the classical Pathway (CP). Collectively, selective blockade of the AP without impacting the CP will allow patients to maintain host defense mechanisms responsible for preventing infections. "NM3086 is expected to be therapeutically effective across a broad range of rare and common complement-mediated disorders including ocular (Wet AMD, Dry AMD, and GA), inflammatory, renal, and hematological," states Dr. Rekha Bansal, Founder, and Chief Executive Officer of NovelMed Therapeutics. About NovelMed NovelMed is a clinical-stage biopharmaceutical company focused on developing novel biologics for treating a broad range of complement-mediated diseases caused by the activation of the Alternative Pathway. NovelMed is the first Company to have invented and validated an Anti-Bb antibody, an Anti-Properdin antibody, and an Anti-C3b antibody that selectively blocks the AP without inhibiting the classical Pathway. NovelMed has completed a Phase I trial for one of its lead product candidates (NCT05642546) and is currently evaluating this product in clinical trials for a) Paroxysmal Nocturnal Hemoglobinuria (PNH - NCT05646524, NCT05646563, NCT05731050), b) Atypical Hemolytic Uremic Syndrome (aHUS - NCT05684159), and c) Complement Glomerulopathy (C3G - NCT05647811). Irrespective of the target protein of the AP, a drug that expresses the best safety and efficacy profile for patients will be finalized for approval. NovelMed has recently selected lead albumin-linked antibodies designed to have an increased half-life in humans. NovelMed is a leader in developing AP-targeting therapies to resolve debilitating common and rare complement-mediated and complement-associated diseases. In addition to Anti-Properdin, the Company is advancing the development of Anti-Bb and Anti-C3b monoclonal antibodies that selectively block activation of the AP in a search for the best-in-class molecule with high potency and an extended half-life. As Dr. Bansal states: "NovelMed is committed to leveraging creativity and compassion to deliver game-changing therapies to patients." NovelMed seeks licensing, partnership, and acquisition opportunities to drive NM3086 through further development and approval in multiple rare disease indications. For more information or to contact NovelMed, please visit www.novelmed.com and contact us at bd@novelmed.com. Communication Teambd@novelmed.comTel: (216) 440 2696 NovelMed is on LinkedIn! Sign up to follow @NovelMed at https://www.linkedin.com/company/www.novelmedlinkedin.com. References NovelMed's Complement Alternative Pathway Specific Anti-Bb Antibody (NM8074) for Rare Diseases Achieves a Major Milestone. NovelMed. January 31, 2022.NovelMed Announces Interim Positive Results from Its Phase I Clinical Trial of NM8074, a Bb Complement Alternative Pathway Blocker Antibody. NovelMed. February 21, 2022.Returning to complement – can NovelMed's next-gen antibody outperform Ultomiris? NovelMed. April 22, 2022.Alternative Pathway Blocker Anti-Bb Antibody (NM8074) Receives US FDA Clearance to Start Efficacy Trial in C3 Glomerulopathy (C3G) Patients. NovelMed. August 15, 2022.Anti-Properdin Antibody (NM3086) Reduced Hemolysis, LDH, and Free Hemoglobin in an Animal Model of Paroxysmal Nocturnal Hemoglobinuria (PNH) -- a Rare Disease. NovelMed. December 12, 2022.NovelMed reports topline data with Anti-Properdin antibody NM-3086 in a rabbit model of PNH. NovelMed. December 13, 2022Anti-Bb Antibody (NM8074) Receives US FDA Clearance to Start Clinical Trial in Naïve aHUS Patients (Rare Disease). January 30, 2023.Study of NM8074 in Soliris-Treated Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT 05731050).Study of Efficacy and Safety of NM8074 in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (NCT 05646524).Study of NM8074 in Adult PNH Patients With Inadequate Response to Soliris (NCT 05646563).Study of NM8074 in Patients With aHUS With Evidence of Ongoing Thrombotic Microangiopathy (NCT 05684159).Study of NM8074 in Adult C3 Glomerulopathy Patients (NCT 05647811).First-in-Human (FIH) Clinical Study of NM8074 in Healthy Adult Volunteers (NCT05642546). A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/f70c3b84-1cc6-4e65-8156-d8d60f573716

-- FDA Clears Initiation of Efficacy Trial in aHUS (Atypical Hemolytic Uremic Syndrome) Patients An Efficacy Trial in Adult aHUS Patients Who Are Naïve to Complement Inhibitor Therapy (NCT05684159) Phase I trial in healthy volunteers shows that NM8074 completely blocks the alternative pathway (AP) without blocking the classical pathway (CP), an important advantage over other complement blockers already approved by the FDA NM8074 is expected to provide the selectivity and the specificity required for complete remission of thrombotic microangiopathy which remains as an unmet need in patients with aHUS Given the role of the AP in multiple complement-mediated rare diseases, NM8074 has the potential to treat not only aHUS but several other complement-mediated diseases including ocular, inflammatory, renal, neurological and hematological CLEVELAND, Jan. 30, 2023 (GLOBE NEWSWIRE) -- NovelMed 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 aHUS in coming months. NovelMed is advancing its anti-Bb antibody (NM8074) to treat patients with evidence of treatment-related resistance or complement-mediated relapses in aHUS, a rare disease with unmet need. NovelMed is a clinical-stage biopharma company focused on the development of humanized monoclonal antibody treatments for several complement-mediated disorders. NM8074 has recently completed a Phase I trial in healthy volunteers with no safety concerns. Our results show that NM8074 completely blocks the alternative pathway (AP) without blocking the classical pathway (CP) consistent with the laboratory data generated by NovelMed scientists. This is an important advantage over other complement blockers already approved by the FDA or in development. NM8074 blocks the AP-mediated formation of C3b, an important molecule responsible for incurable anemia seen in both Soliris and Ultomiris treated patients. Opsonization controlled by the CP is not affected by NM8074, which is a key factor in targeted AP inhibition of the complement system. “We speculate that patients would not have to take the meningococcal vaccine in the future should the drug prove effective in the upcoming clinical trial of this rare disease” stated Dr. Bansal. "The FDA's clearance of the Phase II clinical trial for aHUS, a rare disease, is an important milestone in the active life of NM8074," said Rekha Bansal, Ph.D., Chief Executive Officer of NovelMed. “Our drug functions by binding Bb at its catalytic site and has no affinity for Factor B. As a result, the drug selectively blocks the alternative pathway (AP) without affecting the CP. Our proposed trial is entitled ‘An Open Label Trial to Evaluate Safety and Efficacy of NM8074 in Adult aHUS Patients Who Are Naïve to Complement Inhibitor Therapy’ (NCT05684159).” The AP plays a key role in controlling anemia, inflammation, and tissue damage in several complement-mediated disorders. “Based on our initial clinical data, it is clear that NM8074 could provide the selectivity and the specificity required for developing a novel biologic for the complete remission of thrombotic microangiopathy in patients with aHUS. Given the role of the AP in multiple complement-mediated rare diseases, NM8074 has the potential to treat not only aHUS but several other complement-mediated diseases as well, where AP is the sole contributor of the pathological outcome,” stated Dr. Bansal. Seeking Funds to Advance the Development of NM8074 for Rare Disease Platform aHUS is a rare disease characterized by exaggerated AP activation and hemolysis. “Because the disease is rare (orphan), its market size is significant,” states the Business Development Team at NovelMed. Hence, NM8074 has the potential to capture a significant portion of this market. NovelMed is currently seeking licensing, partnership, and acquisition opportunities to drive NM8074 through further development and approval in multiple rare disease indications. For more information, please visit . About NM8074 NM8074 is a humanized monoclonal antibody that binds Bb, the catalytic domain of Factor B, and selectively blocks the initiation and propagation of the alternative pathway (AP). Treatment with NM8074 would selectively target the AP while leaving the CP pathway intact. In addition to treating aHUS, NM8074 is expected to benefit patients suffering from a variety of kidney disorders where activation of the AP is the key driver of pathogenesis. Furthermore, NM8074 is expected to be therapeutically effective across a broad range of rare diseases and disorders, including hemolytic PNH (NCT 05646524, NCT05646563), hemolytic aHUS (NCT05684159), renal C3G (NCT05647811), ocular, neurological, and inflammatory disorders. Multiple clinical trials have been registered on 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 block the formation of C3/C5 convertases. NovelMed is currently creating 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 . Business Development Team bd@novelmed.com Tel: (216) 440 2696 NovelMed is on LinkedIn. Sign up to follow @NovelMed at References 1. NovelMed's Complement Alternative Pathway Specific Anti-Bb Antibody (NM8074) for Rare Diseases Achieves a Major Milestone. NovelMed. January 31, 2022. 2. NovelMed Announces Interim Positive Results from Its Phase I Clinical Trial of NM8074, a Bb Complement Alternative Pathway Blocker Antibody. NovelMed. February 21, 2022. 3. Returning to complement – can NovelMed’s next-gen antibody outperform Ultomiris? NovelMed. April 22, 2022. 4. Alternative Pathway Blocker Anti-Bb Antibody (NM8074) Receives US FDA Clearance to Start Efficacy Trial in C3 Glomerulopathy (C3G) Patients. NovelMed. August 15, 2022. 5. Anti-Properdin Antibody (NM3086) Reduced Hemolysis, LDH, and Free Hemoglobin in an Animal Model of Paroxysmal Nocturnal Hemoglobinuria (PNH) -- a Rare Disease. NovelMed. December 12, 2022. 6. NovelMed reports topline data with anti-properdin antibody NM-3086 in rabbit model of PNH. NovelMed. December 13, 2022 7. Study of NM8074 in Patients With aHUS With Evidence of Ongoing Thrombotic Microangiopathy. clinicaltrials.gov; 2022. Accessed January 25, 2023. 8. Study of Efficacy and Safety of NM8074 in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy clinicaltrials.gov; 2022. Accessed January 25, 2023. 9. Study of NM8074 in Adult PNH Patients With Inadequate Response to Soliris clinicaltrials.gov; 2022. Accessed January 25, 2023. 10. Study of NM8074 in Patients With aHUS With Evidence of Ongoing Thrombotic Microangiopathy clinicaltrials.gov; 2022. Accessed January 25, 2023. 11. Study of NM8074 in Adult C3 Glomerulopathy Patients clinicaltrials.gov; 2022. Accessed January 25, 2023.