03 Mar 5 Companies Bringing Innovation to the Fabry Disease Treatment Market
Fabry Disease also known as angiokeratoma corporis diffusum or alpha-galactosidase A deficiency, is an inherited disorder characterized by the buildup of globotriaosylceramide, a type of fat in the body’s cells and results in numerous disorders such as acroparesthesias (burning, tingling, or prickling sensation in extremities), angiokeratomas (small, dark spots on the skin), hypohidrosis (reduced perspiration), corneal opacity or corneal verticillata tinnitus and hearing loss. In severe cases the disease can lead to progressive kidney damage, stroke and cardiac arrest.
According to the National Institute of Health, an estimated 1 in 40,000 to 60,000 males are affected by this disorder. This disease is primarily caused by a mutation in the GLA gene, which hinders the breakdown of globotriaosylceramide, thereby causing their buildup in the cell lining of blood vessels of the skin, kidneys, heart and nervous system. The condition is inherited through an X-linked pattern.
The disease is diagnosed through genetic testing and new born screening. The treatment for this disease uses a multi-disciplinary treatment approach that targets abnormal substrate accumulation and aims to prevent organ damage. At present enzyme replacement therapy is the recommended course of treatment, in which synthetic enzyme created through recombinant DNA are administered intravenously. Fabrazyme by Sanofi (NASDAQ: SNY) Genzyme is the only is the FDA approved ERT treatment in the U.S.
According to a report by Grandview Research the global Fabry Disease treatment market is expected to reach USD 3.12 billion by 2025, growing at a CAGR of 9.6%. The growth in the market will be driven by introduction of novel therapies such as substrate reduction therapies, enzyme replacement and chaperone treatments. We take a look at few companies at the forefront of innovation in this area.
Resverlogix Corp (OTCPINK: RVXCF)
Market Cap: $201.27M; Current Share Price: 0.95 USD
Data by YCharts
Apabetalon((RVX-208),the Company’s lead drug candidate, is a first-in-class, small molecule selective BET (bromodomain and extra-terminal) inhibitor which plays a crucial role as an epigenetic mechanism that helps regulate disease-causing genes. The Company has received an approval from Health Canada to initiate a clinical trial to study the safety, efficacy and tolerability of Apabetalon in patients with Fabry Disease.
The open-label, exploratory study will be for a period of 16 weeks and will have two cohorts namely patient with Fabry disease who are undergoing Enzyme replacement therapy and Patients with Fabry not receiving any ERT. While the primary objective is to evaluate its safety and tolerability, the secondary objective will evaluate its impact on key biomarkers such as alkaline phosphatase (ALP), high-sensitivity C-reactive protein (hs-CRP), and other well-known markers of chronic kidney disease and CVD as per the Company. In addition the Company is also engaged in an ex vivo study of apabetalone treated blood, obtained from a patient with Fabry Disease.
Apabetalone offers an improvement over traditional approaches to tackling disease-causing factors, by inhibiting bromodomain and extraterminal domain (BET) proteins, thereby positively impacting multiple processes that cause diseases. The candidate also has the ability to normalize dysregulated epigenetics, which are at the core of many life-threatening diseases.
The Company has forged strategic partnerships with Companies such as Shenzhen Hepalink Pharmaceutical Co. (002399.SZ), for application of apabetalone (RVX-208) in high-risk cardiovascular disease patients with diabetes and CKD. Furthermore it has also entered into a partnership with Medison Pharma Ltd , for exclusive rights to distribute and market apabetalone in Israel.
4D Molecular Therapeutics Inc (Private)
4D Molecular’s lead product candidate for treatment of Fabry and other lysosomal storage disorders is 4D-310, which uses a proprietary vector design for efficient delivery to relevant tissues with minimal toxicity and resistance to pre-existing antibodies. The Company has completed a pre-IND discussion with the FDA and will initiate a phase 1/2 clinical trial for the H2,2020. The discussion was on the basis of an IND-enabling pharmacology and Good Laboratory Practices (GLP) toxicology and biodistribution study that was initiated in 2019.
The primary endpoints for the clinical study are will be changes in biomarkers such as cardiac MRI (to assess substrate build up and cardiomyopathy), blood levels of AGA and the substrate Gb3, and organ function as per the Company.
Furthermore the company’s pipeline consists of candidates such as 4D-710 for the treatment of Cystic Fibrosis, a candidate for treatment of Duchenne Muscular Dystrophy and 4D-125 and 4D-110 intended for the treatment of ophthalmological conditions.
4D’s transformative “Therapeutic Vector Evolution” discovery platform facilitates the creation of optimized biopharmaceutical grade customized AAV vectors that can target specific disease tissue. This offers improvement over conventional AAV capsid vectors that do not target any specific tissue in the body, resulting in inefficiency and toxicity. The Company has developed 37 AAV capsid libraries that have more than one billion novel variants, thereby allowing the Company a choice of over 100 million more vectors than conventional AAV gene therapy products.
The Company has entered into a strategic partnership with Roche (OTCQX: RHHBY) for development of targeted and proprietary AAV vectors for use in ophthalmology indications. In addition, it is collaborating with UniQure (NASDAQ: QURE) through an exclusive, worldwide license for developing and commercializing pre-selected AAV capsid variants for central nervous system and the liver. 4D also has an agreement with AstraZeneca (NYSE: AZN) for delivery of certain genes to the lung for treatment of specific lung disorders.
Moderna, Inc. (NASDAQ: MRNA)
Market Cap: $10.11B; Current Share Price: 27.56 USD
Data by YCharts
The Company uses its proprietary mRNA platform to discover and create novel solutions across indications such as prophylactic vaccine development, personalized cancer vaccine, intra-tumoral immune-oncology and localized regenerative medicine to name a few. Moderna has developed a unique mRNA sequence that codes for a protein, and encompasses knowledge of mRNA biology, chemistry, formulation & delivery, bioinformatics and protein engineering to address unmet needs in critical areas.
The Platform offers great flexibility and wide applicability; by changing the sequence of the genetic code it can combine different mRNA sequences for different proteins in a single mRNA medicine. It has a drug design studio, which can develop mRNA within a very short period of time, using a proprietary Sequence Designer module, bioinformatics algorithms and its modular synthesis robotics, making it a pioneering Digital Biotech Company™.
The Company is developing a treatment for Fabry disease as part of its systemic secreted therapeutics modality, besides developing therapeutics for methylmalonic acidemia (MMA), propionic acidemia (PA), glycogen storage disorder Type 1a (GSD1a) and phenylketonuria (PKU) through its systemic intracellular therapeutics modality. mRNA-3630 is currently undergoing pre-clinical evaluation and the Company intends to file for an IND soon.
Moderna is also developing mRNA-3704 for the treatment of Methylmalonic Acidemia, which is currently undergoing a phase 1/2 open label study to evaluate its safety and efficacy. The Company uses its proprietary mRNA platform to discover and create novel solutions across indications such as prophylactic vaccine development, personalized cancer vaccine, intra-tumoral immune-oncology and localized regenerative medicine to name a few. Moderna is developing an mRNA vaccine for the treatment of the novel coronavirus (2019-nCoV), in collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI) and the National Institutes of Health (NIH). Additionally the Company has had six positive Phase 1 clinical readouts in its prophylactic vaccines modality and moved two additional programs into development.
The Company has built a robust and diverse network of strategic collaborations with pharmaceutical and biotechnology organisation, in addition to government entities and research organisations to leverage its mRNA platform for drug discovery and development. Some of its collaborations are with AstraZeneca, Merck (NYSE: MRK), Vertex (NASDAQ: VRTX), BARDA, DARPA and Bill and Melinda gates foundation.
Pharming Group (OTCPINK: PHGUF)
Market Cap: $751.54M; Current Share Price: 1.35 USD
Data by YCharts
Pharming’s proprietary patented Transgenic Production Technology Platform (TPTP) offers a highly scalable production GMP validated methodology for the development of recombinant human proteins. The Company has been able to generate complex therapeutic proteins, using its transgenesis method, which does not trigger the body’s immune system to launch a defense against the new protein. The platform is capable of high-quality, large-scale and easy upscale-able production.
Furthermore using its technology platform the Company is evaluating protein replacement products for treatment of Pompe and Fabry disease. The aim is to create a new recombinant treatment with improved better immunogenicity, safety and efficacy that can overcome the limitations of existing treatment options. Pharming already markets RUCONEST, a recombinant human C1 esterase inhibitor for the treatment of hereditary angioedema (HAE) and is targeting the development of a recombinant human C1 esterase inhibitor (rhC1INH) for the treatment of preeclampsia contrast induced nephropathy (CIN) and other indications.
In August 2019, the Company entered into a development and licensing collaboration with Novartis (NYSE: NVS) for the development and commercialization of CDZ173, a small molecule phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor, indicated for the treatment of patients with Activated Phosphoinositide 3-kinase Delta Syndrome (“APDS”). Pharming has developed its proprietary technology platform in partnership with The Shanghai Institute of Pharmaceutical Industry (SIPI), a Sinopharm Company. It has a robust intellectual property rights portfolio covering the technology for the production of recombinant proteins from the milk of transgenic animals.
Sangamo Therapeutics, (NASDAQ: SGMO)
Market Cap: $985.47M; Current Share Price: 8.56 USD
Data by YCharts
The Company is leveraging its expertise in gene therapy, genome editing and gene regulation technologies to deliver adeno associated virus (AAV) and mRNA platforms based therapeutics for the treatment of inherited metabolic diseases, CNS, Oncology, hematology and immunology applications. Its zinc finger nuclease technology is the gold standard for genomic therapies when it comes to three critical criterions of specificity, precision, and efficiency. It is currently developing ZFN 2.0 platform, touted to be the next-generation ZFN construct, which is 20 times more active than current options and has the potential to develop genomic therapies for a broad range of monogenic diseases.
The Company’s lead candidate for the treatment of Fabry Disease is ST-920, which uses its proprietary AAV Gene therapy. In preclinical animal model studies, the AAV-mediated delivery of hGLA cDNA constructs resulted in expression of high levels of glycosylated α-Gal A in the liver and reduction in substrates Gb3 and lyso-Gb3 in tissues within 2 months of administration.
Its lead product candidate for the treatment of Beta-Thalassemia is ST-400, a gene-edited cell therapy based on its ZFN genome editing technology, which can be used to alter antilogous hematopoietic stem cells (HSCs) using fetal hemoglobin to produce functional red blood cells. The Company has tied-up with Sanofi for the development of this product candidate.
In addition its pipeline consists of product candidates for the treatment of Inherited Metabolic diseases, Hematology and CNS diseases such as MPS, Fabry Disease, Hemophilia, Sickle Cell Disease, Tauopathies, Huntington’s Disease to name a few. It has entered into strategic collaborations with numerous companies such as Kite, a Gilead company for engineered cell therapies for oncology, with Pfizer Inc., for gene therapy programs for Hemophilia A, with Bioverativ for hemoglobinopathies, including beta thalassemia and sickle cell disease and Shire International GmbH to develop therapeutics for Huntington’s disease.
The Company has entered into a partnership with Biogen (NASDAQ: BIIB) to develop its Alzheimers and Parkinson’s programs. It has also signed an option agreement with Brammer Bio, a gene therapy contract development and manufacturing organization, to gain access to large-scale, commercial-grade AAV manufacturing.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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