Orphan Drugs Manufacturers & Companies

1. The mission is to develop life-changing therapies in ophthalmology, rare diseases, and neurology through controlling the complement cascade, a key component of the immune system.

2. A focus is on the C3 protein, targeting C3 as an important factor in the complement system in order to prevent the overactivity of the whole cascade causing cell damage.

3. FDA-approved drugs:

• Syfovre in 2023 treated geographic atrophy (GA).

• Empaveli in 2021 was the first FDA-approved drug for paroxysmal nocturnal hemoglobinuria (PNH), aimed at preventing red blood cell destruction.

4. Clinical Trials under: Phase 2 and 3 for rare diseases

• Amyotrophic Lateral Sclerosis (ALS)

• Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

• Complement 3 Glomerulopathy (C3G)

• Coronary Artery Disease (CAD)

• Post-Hematopoietic Stem Cell Transplantation Thrombotic Microangiopathy (HSCT-TMA)

1. Company Overview: A biopharmaceutical entity under Sumitomo Biopharma Limited engaged in rare diseases and patient-centered innovation.

2. Research areas: T-cell biology; regenerative medicine; excessive serotonin signaling reduction; and regulating lung inflammation.

3. FDA-approved Drug(s): RETHYMIC; treatment of congenital athymia, a disease in which children are born without a thymus and thereby suffer numerous infections.

4. Current Research: Developing new treatments for rare respiratory diseases; phase 2 study on pulmonary arterial hypertension (PAH). 

1.IgA nephropathy (IgAN) treatment:

• Filspari is the first non-immunosuppressant therapy approved by the FDA.

• Blocks both endothelin-1 and angiotensin II receptors to reduce protein in urine and curtail progression of kidney disease.

• Ongoing phase III PROTECT trial to investigate the long-term benefits.

2. Company Focus: Developing therapeutics for rare diseases:

• Alagille Syndrome (ALGS)

• Homocystinuria (HCU)

• Bile Acid Synthesis Disorders (BASD)

• Cystinuria & Peroxisomal Biogenesis Disorder (PBD-ZSD)

• Cerebrotendinous Xanthomatosis (CTX) & Focal Segmental Glomerulosclerosis (FSGS)

3. Pipeline:

• Currently-at-phase 3 study for FSGS and CTX

• Phase 2 study for HCU

• Preclinical for ALGS 

1. Charcot-Marie-Tooth (CMT) is a progressive peripheral neuropathy that affects 1: 2,500 individuals.

2. CMT1A is the most common variant, and no treatment is yet available.

3. Pharnext's Research:

• PXT3003 is a potential therapy for CMT1A, currently in Phase 3 (PREMIER trial).

• Targeting PMP22 overexpression-an underlying cause in CMT1A.

• 387 patients recruited as of May 2022 across 52 centers worldwide.

• Topline results are expected in Q4 2023. 

Antibody Treatments of the Next Generation 

• Creating innovative antibody therapies for diseases for which there are no disease-modifying therapies.

• Studies naturally occurring antibodies in resistant individuals to create new therapies.

• Received a £1.7M ($2M) Innovate UK grant to accelerate Huntington's disease research.

• Huntington's disease is a rare and inherited neurodegenerative disorder, with no cure or treatment to slow progression. 

• It develops treatment for hard-to-treat tumors that act on various survival mechanisms with one single-agent drug.

• IOA-244 (Phase I/II) with the objective to treating solid and blood cancers like uveal melanoma.

• IOA-289 (Phase 1b) and IOA-237 (preclinical).

• IOA-244 inhibits PI3Kδ, a key pathway in cancer signaling.

• Orphan Drug designation granted (FDA; January), because of promising clinical data for uveal melanoma. 

1. Operation of a 220,000-square-foot Gene Therapy Center in New Jersey for research and manufacturing.

2. Upstaza–First gene therapy for AADC deficiency, approved by the European Commission in 2022.

3. Translarna–Approved by NICE for Duchenne Muscular Dystrophy (DMD).

4. Ongoing clinical trials:

• APHENITY (phase 3): Sepiapterin for PKU.

• MIT-E (phase 2/3): Vatiquinone in mitochondrial disease seizures.

• MOVE-FA (phase 3): Vatiquinone in Friedreich ataxia.

1. Gene therapy presents possible cures for rare diseases since 80% of them are being caused either by a single-gene defect.

2. Rocket Pharmaceuticals is developing genetic therapies for life-threatening pediatric rare diseases.

3. Use AAV & lentiviral (LV) vectors to precisely target genetic mutations in affected cells.

4. RP-A501 (AAV-based) has received FDA regenerative medicine designation for Danon disease, a fatal genetic heart and muscle disorder.

5. RP-L201 (Phase 2) is being developed for LAD-I, a rare immunodeficiency disorder that causes severe infections. 

1. Using AAV vectors, whose size limitation is 4.7 kb, they develop next-generation gene therapies.

2. They have engineered split inteins for non-therapeutic splicing of proteins.

3. Raised Series A funding of €50 million ($52.7 million) to further advanced research.

4. The lead candidate is designed to treat Stargardt disease, a rare genetic retinal disorder caused by ABCA4 gene mutations.

5. Due to the large size of ABCA4 (6.8 kb), above the maximum size for AAV vectors, SpliceBio aims to use its Protein Splicing platform to develop a treatment. 

1. Tim Walbert, the CEO of the firm, is afflicted with an exceptional inflammation disease and stands out on the road toward new drug development.

2. The focus is on rare, autoimmune, and severe inflammatory diseases.

3. Key medicines in its portfolio:

• Actimmune- Part of the treatment for chronic granulomatous disease (CGD).

• Buphenyl & Ravicti- Treat urea cycle disorders.

• Krystexxa- Treats gout.

• Procysbi- Used for nephropathic cystinosis.

• Tepezza- Reduces eye bulging and double vision in thyroid eye disease.

• Uplizna-Treats neuromyelitis optica spectrum disorder (NMOSD).