Red-Cell Aplasia, Pure

ROSAH syndrome is caused by mutations in the ALPK1 gene. Credit: Gorodenkoff via Shutterstock. Drug Farm has been granted a rare paediatric disease (RPD) designation from the US Food and Drug Administration (FDA) for DF-003 to treat retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache (ROSAH) syndrome. DF-003 is an alpha-kinase 1 (ALPK1) indicated for the treatment of the rare autosomal dominant disorder ROSAH syndrome. The condition is caused by mutations in the ALPK1 gene, characterised by the symptoms listed in its name. ROSAH syndrome currently has no approved treatments. Drug Farm received FDA clearance of its investigational new drug (IND) application to initiate Phase I studies for the candidate in June 2023, after pre-clinical studies in ROSAH syndrome transgenic mouse models showed significant activity and favourable drug-like properties. If a new drug application for DF-003 is approved by the FDA, the company may be eligible to receive a priority review voucher (PRV) that can be redeemed to receive for any later marketing application. The double-blind, placebo-controlled Phase I trial (NCT05997641) is evaluating the safety, tolerability, and pharmacokinetics of DF-003 on 96 healthy subjects.  The study is expected to conclude in Q1 2025. The company has other candidates in the pipeline, including another ALPK1 agonist DF-006, which is under investigation in the third part of a Phase I study for the treatment of chronic hepatitis B infection. The trial is assessing the levels of DF-006 and its related compounds in the blood following doses of the formulation. In May 2023, Drug Farm generated $27m in a Series C funding round led by Betta Capital. The company, which has offices in both the US and China, also raised $56m in February 2021 in a Series A lead by BVCF. In the announcement accompanying the designation, Drug Farm’s chief medical officer Jeysen Yogaratnam said: “Obtaining Rare Pediatric Disease Designation recognizes the serious and debilitating complications of this rare disease and upholds our goal to provide DF-003 as the first targeted drug for potential treatment in patients afflicted with ROSAH syndrome.”

GUILFORD, Conn.--( BUSINESS WIRE )-- Drug Farm , a clinical-stage biopharmaceutical company announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) Designation for the company’s alpha-kinase 1 (ALPK1) inhibitor, DF-003, to treat patients with ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache) Syndrome. DF-003 is currently being evaluated in a Phase 1 trial ( NCT05997641 ) to assess safety and pharmacokinetics in normal healthy volunteers. “Pediatric patients living with ROSAH Syndrome face a significant unmet need with limited options to treat vision loss,” said Jeysen Yogaratnam, Chief Medical Officer, Drug Farm. “Obtaining Rare Pediatric Disease Designation recognizes the serious and debilitating complications of this rare disease and upholds our goal to provide DF-003 as the first targeted drug for potential treatment in patients afflicted with ROSAH Syndrome.” About Rare Pediatric Disease Designation Rare Pediatric Disease (RPD) Designation is granted by the FDA for serious or life-threatening diseases which affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If a New Drug Application (NDA) for DF-003 to treat ROSAH Syndrome is approved by the FDA, Drug Farm may be eligible to receive a Priority Review Voucher (PRV) that can be redeemed to receive a priority review for any subsequent marketing application or may be sold or transferred. The FDA has implemented this program to encourage development of new drugs for treatment of rare pediatric diseases. About ROSAH Syndrome ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache) Syndrome is a rare, autosomal dominant autoinflammatory disease named according to the characteristic symptoms exhibited by affected patients (1, 2). The disease is caused by a genetic gain-of-function mutation in ALPK1. The most common presenting symptom is a progressive decline in visual acuity that typically begins before 20 years of age, with ophthalmologic examination often revealing optic disc elevation, uveitis, and retinal nerve degeneration (2, 3). Most ROSAH patients also exhibit inflammatory features such as non-infectious low-grade fevers, arthralgia, headaches, and persistently elevated levels of inflammatory cytokines including tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-1β (3). Tantravahi SK, et al. An inherited disorder with splenomegaly, cytopenias, and vision loss. Am J Med Genet A. 2012;158(3):475-81. Williams LB, et al. ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. Genet Med. 2019;21(9):2103-15. Kozycki CT, et al. Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome. Ann Rheum Dis. 2022;81(10):1453-64. About DF-003 DF-003 is a first-in-class drug developed by Drug Farm that inhibits the activity of ALPK1 and variants of ALPK1 that have a gain-of-function mutation and cause ROSAH Syndrome. DF-003 currently is in a Phase 1 clinical trial (NCT05997641) in normal healthy volunteers. About Drug Farm Drug Farm is a private biotechnology Company developing innovative treatments targeting innate immunity for hepatitis B, heart and kidney diseases, and ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache) syndrome. Drug Farm's unique IDInVivo platform combines breakthrough technologies in genetics and AI to discover new treatments. IDInVivo technology allows the direct assessment of gene targets in living animals with intact immune systems. Using the IDInVivo platform, Drug Farm has identified novel innate immunity pathways and targets and is now rapidly advancing multiple first-in-class drug candidates into clinical development. For more information please visit: https://www.drug-farm.com

ROCKVILLE, Md. & EDMONTON, Alberta--(BUSINESS WIRE)-- Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the Company) today announced that the Company’s collaboration partner, Otsuka Pharmaceutical Ltd., filed a new drug application (NDA) for voclosporin for the treatment of lupus nephritis (LN) with the Japanese Ministry of Health, Labour, and Welfare for the manufacture and sale in Japan of voclosporin, a second-generation oral calcineurin inhibitor for the treatment of lupus nephritis (LN). LN is a complication of the autoimmune disease systemic lupus erythematosus (SLE) that seriously impacts the kidneys. In January 2021, the U.S. Food and Drug Administration (FDA) approved voclosporin in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active LN and it is currently available in the U.S. under the brand name LUPKYNIS®. Aurinia and Otsuka entered a collaboration and licensing agreement in December 2020 for the development and commercialization of voclosporin for the treatment of LN in the EU, Japan, the United Kingdom, Russia, Switzerland, Norway, Belarus, Iceland, Liechtenstein, and Ukraine. As part of the agreement, Aurinia is eligible to receive a payment of $10 million upon approval in Japan along with low double-digit royalties on net sales once launched. “Lupus nephritis is a serious, complex condition associated with SLE, that can benefit from advanced therapies that focus toward the treatment goal of kidney preservation,” said Peter Greenleaf, President, and Chief Executive Officer of Aurinia Pharmaceuticals. “We look forward to continuing to work with Otsuka to expand availability to voclosporin and provide patients and physicians access to this new therapy that addresses a significant unmet need in lupus nephritis.” About Lupus Nephritis LN is a serious manifestation of SLE, a chronic and complex autoimmune disease. About 200,000-300,000 people live with SLE in the U.S. and about one-third of these people are diagnosed with lupus nephritis at the time of their SLE diagnosis. About 50 percent of all people with SLE may develop lupus nephritis. If poorly controlled, LN can lead to permanent and irreversible tissue damage within the kidney. Black and Asian individuals with SLE are four times more likely to develop LN and individuals of Hispanic ancestry are approximately twice as likely to develop the disease when compared with Caucasian individuals. Black and Hispanic individuals with SLE also tend to develop LN earlier and have poorer outcomes when compared to Caucasian individuals. About LUPKYNIS LUPKYNIS® is the first U.S. FDA- and EC-approved oral medicine for the treatment of adult patients with active LN. LUPKYNIS is a novel, structurally modified calcineurin inhibitor (CNI) with a dual mechanism of action, acting as an immunosuppressant through inhibition of T cell activation and cytokine production and promoting podocyte stability in the kidney. The recommended starting dose of LUPKYNIS is three capsules twice daily with no requirement for serum drug monitoring. Dose modifications can be made based on Aurinia’s proprietary personalized eGFR-based dosing protocol. Boxed Warning, warnings, and precautions for LUPKYNIS are consistent with those of other CNI-immunosuppressive treatments. About Aurinia Aurinia Pharmaceuticals is a fully integrated biopharmaceutical company focused on delivering therapies to treat targeted patient populations with a high unmet medical need that are impacted by autoimmune, kidney and rare diseases. In January 2021, the Company introduced LUPKYNIS® (voclosporin), the first FDA-approved oral therapy dedicated for the treatment of adult patients with active lupus nephritis. The Company’s head office is in Edmonton, Alberta, its U.S. commercial office is in Rockville, Maryland. The Company focuses its development efforts globally. INDICATION AND IMPORTANT SAFETY INFORMATION INDICATIONS LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active LN. Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation. IMPORTANT SAFETY INFORMATION BOXED WARNINGS: MALIGNANCIES AND SERIOUS INFECTIONS Increased risk for developing malignancies and serious infections with LUPKYNIS or other immunosuppressants that may lead to hospitalization or death. CONTRAINDICATIONS LUPKYNIS is contraindicated in patients taking strong CYP3A4 inhibitors because of the increased risk of acute and/or chronic nephrotoxicity, and in patients who have had a serious/severe hypersensitivity reaction to LUPKYNIS or its excipients. WARNINGS AND PRECAUTIONS Lymphoma and Other Malignancies: Immunosuppressants, including LUPKYNIS, increase the risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to increasing doses and duration of immunosuppression rather than to the use of any specific agent. Serious Infections: Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections (including opportunistic infections), which may lead to serious, including fatal, outcomes. Nephrotoxicity: LUPKYNIS, like other CNIs, may cause acute and/or chronic nephrotoxicity. The risk is increased when CNIs are concomitantly administered with drugs associated with nephrotoxicity. Hypertension: Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy. Neurotoxicity: LUPKYNIS, like other CNIs, may cause a spectrum of neurotoxicities: severe include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremor, paresthesia, headache, and changes in mental status and/or motor and sensory functions. Hyperkalemia: Hyperkalemia, which may be serious and require treatment, has been reported with CNIs, including LUPKYNIS. Concomitant use of agents associated with hyperkalemia may increase the risk for hyperkalemia. QTc Prolongation: LUPKYNIS prolongs the QTc interval in a dose-dependent manner when dosed higher than the recommended lupus nephritis therapeutic dose. The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation. Immunizations: Avoid the use of live attenuated vaccines during treatment with LUPKYNIS. Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS. Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another CNI immunosuppressant. If PRCA is diagnosed, consider discontinuation of LUPKYNIS. Drug-Drug Interactions: Avoid co-administration of LUPKYNIS and strong CYP3A4 inhibitors or with strong or moderate CYP3A4 inducers. Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors. Reduce dosage of certain P-gp substrates with narrow therapeutic windows when co-administered. ADVERSE REACTIONS The most common adverse reactions (>3%) were glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain upper, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite. SPECIFIC POPULATIONS Pregnancy/Lactation: May cause fetal harm. Advise not to breastfeed. Renal Impairment: Not recommended in patients with baseline eGFR ≤45 mL/min/1.73 m2 unless benefit exceeds risk. Severe renal impairment: Reduce LUPKYNIS dose. Mild and Moderate Hepatic Impairment: Reduce LUPKYNIS dose. Severe hepatic impairment: Avoid LUPKYNIS use. Please see Prescribing Information, including Boxed Warning, and Medication Guide for LUPKYNIS. View source version on businesswire.com: Contacts Aurinia Investor Contact: ir@auriniapharma.com Aurinia Media Inquiries: Andrea Christopher Corporate Communications Director, Aurinia achristopher@auriniapharma.com Source: Aurinia Pharmaceuticals Inc. View this news release online at: