05 Nov 5 Companies making headway in the Amyotrophic lateral sclerosis (ALS) Disease Space
Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s disease is a progressive neurodegenerative disease, characterized by the atrophy of nerve cells in brain and spinal cord, leading to hardening and scarring in the affected region. As the disease progresses, patients gradually lose the functioning of muscles, including those that control speech, movement and breathing. The disease manifests in two forms, sporadic and familial, with 90 to 95 percent of all cases in the U.S being Sporadic. Familial or the inherited form of the disease constitutes the other 5 to 10 percent.
According to information made available by the ALS association, there are over 16,500 Americans afflicted by this illness and nearly 5000 new cases are diagnosed each year. The life expectancy after diagnosis is merely 2 to 5 years, with an estimated $250,000 being spent on out-of-pocket treatment costs. The Global ALS treatment market is expected to be worth over USD 3.6 billion by 2026, growing at a CAGR of 21.6 percent, from USD 0.75 billion in 2018, according to a report by Data Bridge Market Research.
We take a look at five companies that are using extensive research and development to create novel therapeutics which can address the large unmet need in this area.
Medicinova (NASDAQ: MNOV)
Market Cap: $360.38M; Current Share Price: 8.22 USD
Data by YCharts
MediciNova’s therapeutic focus is on developing novel small molecules for the treatment of neurological, respiratory and fibrotic diseases. To this end, the Company is pursuing strategic alliances with North American, European and Japanese pharmaceutical companies, to develop a diverse yet robust pipeline of candidates that have a strong patent portfolio and commercial potential.
The Company, which develops small molecule therapeutics, has received notice of allowances for grant of new patents for MN-166 (ibudilast) for the treatment of amyotrophic lateral sclerosis (ALS) from the Canadian Intellectual Property Office. MN-166 (ibudilast), a small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor, can inhibit pro-inflammatory cytokines and promotes neurotrophic factors.
In preclinical and clinical studies, the drug has demonstrated the ability to offer anti-neuroinflammatory and neuroprotective actions, which is useful in treating a wide range of conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), substance abuse/addiction and glioblastoma (GBM).
The Company’s pipeline consists of candidates for the treatment of acute exacerbations of asthma and COPD, progressive multiple sclerosis, methamphetamine addiction, neuropathic pain, asthma, interstitial cystitis, and solid tumor cancers. MN-001, its lead candidate for the treatment of ALS, was licensed from Kyorin Pharmaceutical Co., Ltd. (Tokyo) in 2002. Additionally, the Company licensed the MN-029 from Angiogene Pharmaceuticals Ltd. (Oxford, UK) the same year. MediciNova also acquired MN-221 from Kissei Pharmaceutical Co., Ltd. (Matsumoto City, Japan), MN-305 and MN-246 from Mitsubishi Pharma Corp. (Osaka) and MN-166 from Kyorin Pharmaceutical Co., Ltd. (Tokyo) in 2004.
The Company is engaged in developing MN-001 for liver fibrosis (NASH and others) and Pulmonary Fibrosis. In the area of neurological diseases, its targets are progressive multiple sclerosis, ALS and Methamphetamine addiction. In addition, it is also trying to address the unmet need in acute exacerbations of asthma through MN-221.
MediciNova has research collaboration with National Cerebral and Cardiovascular disease Research Centre in Japan for the development of MN-001. The Company has a strong intellectual property rights portfolio, with extensive protection for its candidates under clinical development.
AZtherapies ( Private)
This privately held biotechnological company’s focus is on developing innovative treatment solutions, for Central nervous system (CNS) related disorders such as ALS, Alzheimer’s (AD) and ischemic stroke, which exhibit characteristics of neurodegeneration and neuroinflammation. The Company’s AZT-101 has demonstrated delayed disease onset and progress in preclinical studies, with reduced motor deficits, significantly spared lumbar spinal cord motor neurons and reduced pro-inflammatory cytokine/chemokine levels in the spinal cord and plasma as per the Company. The Company is planning to file for an approval with the FDA and commence clinical development in the first half of 2020.
The Company’s ALZT-OP1 is a multi-action combination drug targeted at halting the disease progression of Alzheimer’s. The company under a Special Protocol Assessment with the FDA is currently enrolling patients in the Cognite Trial, a Phase III clinical study, which will allow the company to use the 505(b) (2) accelerated pathway for approval.
ALZT-OP1, its lead product candidate for halting the progression in Alzheimer’s in its initial stages, is built on the basis of the technology it licensed from Harvard Medical School and Massachusetts General Hospital. It not only inhibits neurotoxic amyloid-beta protein aggregation but also inhibits neuroinflammatory responses that trigger nerve death and progressive brain damage.
Additionally the company is also developing M1 (ALZT-QoL) a reversible acetylcholine esterase inhibitor for patients with moderate to severe Alzheimer’s. In its quest to be a comprehensive care provider for Alzheimer’s it is developing a single dose disposable inhalation device named AZHALER-D and a patch named ALZT-Patch for improving patient compliance.
The company has a robust Intellectual property rights portfolio with 9 patents granted covering the method of imaging, therapeutic applications of cromolyn derivatives, treatment of Amyloid plaques caused by Alzheimer’s diseases to name a few. AZTherapies recently acquired Smith Therapeutics, a private biopharmaceutical company, developing therapeutics targeting neuroinflammation to treat neurodegenerative disease, using its a proprietary research platform that uses engineered immunosuppressive T regulatory (Treg) cells with Chimeric Antigen Receptors (CARs) targeting brain glial cells.
Stealth Bio Therapeutics (NASDAQ: MITO)
Market Cap: $227.08M; Current Share Price: 6.48 USD
Data by YCharts
The Company is exploring the potential of Mitrochondrial therapies to treat diseases that are caused by gene mutations leading to mitrochindrial disorders. The Companies pipeline has candidates addressing areas such as primary (inherited) mitochondrial myopathy (PMM), Leber’s hereditary optic neuropathy, or LHON, Dry age-related macular degeneration, or dry AMD and neurodegenerative indications such as Alzheimer’s and Parkinson’s disease, rare mitochondrial diseases, such as Leigh’s syndrome and Friedreich’s ataxia, and other rare diseases, such as ALS.
SBT-272, its lead candidate for the treatment of ALS, is a mitochondrial targeting investigational molecule, which is likely to advance into Phase 1 first-in-man safety studies by the end of 2019. The candidate has demonstrated dose-dependent delay in the onset of neurological disease, a reduction in systemic markers of neurodegeneration and prolonged lifespan in a mouse model of amyotrophic lateral sclerosis (ALS) in pre-clinical studies, as per a Company statement.
Preclincial studies involving mice models, have shown the efficacy of the drug in increasing the lifespan and reducing circulating plasma levels of neurofilament ( a biomarker of nerve damage) when treated with daily intraperitoneal injections of placebo, 0.5 mg/kg of SBT-272 or 5.0 mg/kg of SBT-272 for up to 10 weeks.
Stealth has recently entered into an agreement for option with Alexion Pharmaceuticals Inc (NASDAQ: ALXN), to co-develop and commercialize elamipretide for mitochondrial disease. Under the terms of the agreement, Alexion has the rights to exercise its option upon the announcement of results from a Phase 3 study in primary mitochondrial myopathy (PMM) being conducted by Stealth. If Alexion chooses to exercise its option, then the Companies will co-develop subcutaneous elamipretide for PMM and Barth syndrome and Leber’s hereditary optic neuropathy (LHON) in the U.S. Alexion will receive exclusive rights to develop and commercialize subcutaneous elamipretide outside the U.S in consideration for $30 million, including an option fee, an equity investment and development funding as per the Company.
CytoKinetics Inc (NASDAQ: CYTK)
Market Cap: $646.64M; Current Share Price: 11.02 USD
Data by YCharts
CytoKinetics is developing therapeutics for the treatment of cardiovascular and neuromuscular diseases that are characterized by impaired muscle function such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) heart failure and hypertrophic cardiomyopathies (HCM). The Company has entered into strategic collaboration with Companies such as Amgen (NASDAQ: AMGN), Royalty Pharma, GSK (NYSE: GSK), AstraZeneca (NYSE: AZN), MyoKardia (NASDAQ: MYOK) and Astellas (OTCPINK: ALPMY) to develop and commercialize its diverse pipeline.
The Company is developing RELDEMESTIV, in collaboration with Astellas. The investigational drug candidate is a fast skeletal muscle troponin activator (FSTA), which can regulate the rate of calcium release from the regulatory troponin complex of fast skeletal muscle fibres.
The Company conducted a Phase 2, double-blind, randomized, dose-ranging, placebo-controlled, parallel group study of reldesemtiv in patients with ALS named FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS). The study had enrolled over 458 patients with ALS in the US, Canada, Europe and Australia and showed lower decline than patients on placebo; however it failed to meet its primary endpoint of change from baseline in slow vital capacity (SVC) after 12 weeks of dosing.
ProMIS Neurosciences (OTCQB: ARFXF)
Market Cap: $41.10M; Current Share Price: 0.1579 USD
Data by YCharts
ProMIS is targeting toxic oligomers, primarily responsible for the development of neurodegenerative diseases, through its proprietary antibody candidates targeting the neurotoxin form of TAR DNA-binding protein 43 (TDP-43), the underlying cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Preclinical studies have shown the ability of ProMIS candidates in being able to bind to the pathogenic, misfolded form of TDP-43 in post-mortem brain tissue from patients with FTD.
The Company uses two proprietary computational discovery technologies namely ProMIS™ and Collective Coordinates, to screen and shortlist novel targets called Disease Specific Epitopes (DSEs) on the molecular surface of toxic oligomers. ProMIS has a robust patent portfolio consisting of over 75 patents issued or pending, for disease specific epitopes (targets) and monoclonal antibodies (mAbs) selectively targeting toxic oligomers, indicated for the treatment of ALS (oligomers of SOD1, TDP43), Alzheimer’s disease (oligomers of amyloid beta), and Parkinson’s disease (oligomers of alpha synuclein).
The Company’s lead candidate PMN310 shows selectivity for the toxic oligomers of amyloid beta (Aβ), without binding to nontoxic forms, and offers a promising therapeutic potential for various neurodegenerative diseases, including ALS, Alzheimer’s and Parkinson’s. The Company has filed for IP for ALS and has generated antibodies that will be used to target the disease, it is currently engaged in validating the Murine monoclonal antibodies (mAb) selectivity to select the best candidates to take into clinical development.
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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