Figure 1. Micrographs of spinal cord motoneurons showing SOD1-immunoreactive inclusions.
Image credit: Forsberg, et. al. 2010 under CC BY license

Drugs in Development Database

The Drugs in Development Database provides information about ALS drugs in development by biotechnology and pharmaceutical companies. It covers drugs in preclinical testing, as well as those that are currently in clinical development or were in the past. In addition, it includes information about select drugs in development for other neurodegenerative or neuromuscular diseases with a mechanistic link to ALS.

We hope this will provide a valuable source of information, and a resource for researchers in academia and industry to identify opportunities to collaborate on translational research in ALS.

We will continue to update the database with additional information and references, and will be implementing an improved search function soon! Please let us know of companies or drugs that that we should add to the list at alsresearchforum@prize4life.org.

 


Click a column header to sort alphabetically by that column. Click a drug name to see details.

Drug Name ▾CompanyTypeMechanism TypeConditionStatus for ALS in the U.S.
123C4

123C4

(Click title to open drug details in a new window.)
Company: Iron Horse Therapeutics
Location: US-California
Website: http://www.coipharma.com/portfolio/
Drug Type: Small molecule
Conditions: ALS
Mechanism Type: Axon regeneration
Mechanism: 123C4 may help facilitate the repair of damaged motor neuronal axons by blocking EphA4-mediated signaling. The drug, which acts as an EphA4 agonist, may remove EphA4 from motor neuron surfaces by receptor-mediated endocytosis.
U.S. Status for ALS: Preclinical
Commercial Information: The drug is licensed from the University of California Riverside. It is based on a study from the laboratory of Maurizio Pellecchia.
R&D Status: The drug is now being optimized and is at the preclinical stage.

References:
[1] Potent and Selective EphA4 Agonists for the Treatment of ALS. Wu, B. et al. Cell Chemical Biology. Published online February 9, 2017.
ALS Research Forum Reference: http://www.alsresearchforum.org/scientists-select-potent-agonists-to-target-epha4-in-als/
Iron Horse TherapeuticsSmall moleculeAxon regenerationALSPreclinical
3K3A-APC

3K3A-APC

(Click title to open drug details in a new window.)
Company: ZZ Biotech
Location: US-Texas
Website: http://www.zzbiotech.com
Drug Type: Protein Biologic
Conditions: ALS, stroke, sepsis
Mechanism Type: Neuroprotection
Mechanism: 3K3A-APC is a recombinant Activated Protein C (APC), a protease with anticoagulant and cytoprotective properties for the aging and damaged brain. The drug crosses the blood-brain-barrier. The drug is being developed for stroke and other neurodegenerative disorders. Preclinical studies in SOD1 ALS mouse models have shown that 3K3-APC treatment increases lifespan by 13% and disease duration by 28% compared to saline treated control. The drug is no longer being actively developed for ALS.
U.S. Status for ALS: Inactive
Commercial Information: The company was founded based on discoveries from the laboratory of Prof. Berislav Zlokovic, MD, PhD, of the Keck School of Medicine at University of Southern California, Los Angeles, CA. The last company update was in 2014.
R&D Status: A Phase II study will evaluate safety, tolerability and activity of ZZ Biotech’s 3K3A-APC when given after tissue plasminogen activator, or tPA, in patients who have experienced moderately severe ischemic stroke. There is currently no disclosed program ongoing in ALS.

References:
[1] ZZ Biotech Announces Phase 2 Trial with 3K3A-APC in Stroke; Funds Will Be Provided by NIH and Broadview Ventures. B3C Newswire, 22 Apr 2014. Accessed 11 Mar 2016 from http://www.b3cnewswire.com/201404221062/zz-biotech-announces-phase-2-trial-with-3k3a-apc-in-stroke-funds-will-be-provided-by-nih-and-broadview-ventures.html.
[2] Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Winkler, EA et al. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):E1035-42.
[3] Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells. Zhong, Z et al. J Clin Invest. 2009 Nov 2; 119(11): 3437–3449.

Last updated March 11th, 2016
ZZ BiotechProtein BiologicNeuroprotectionALSInactive
ACE-031

ACE-031

(Click title to open drug details in a new window.)
Company: Shire
Location: US-Massachusetts
Website: http://www.shire.com
Drug Type: Protein Biologic
Conditions: ALS, Duchenne muscular dystrophy
Mechanism Type: Improving muscle function
Mechanism: ACE-031 is a monoclonal antibody that binds and inhibits myostatin. It acts as a decoy receptor for myostatin and other proteins that limit muscle growth. Myostatin blockage has been considered as a therapeutic approach for ALS by improving muscle size and strength.
U.S. Status for ALS: Discontinued
Commercial Information: The programs was conducted in collaboration with Acceleron Pharma and was terminated in 2013.
R&D Status: In May 2013 the Shire and Acceleron Pharma terminated a Phase II trial of ACE-031 in subject with Duchenne muscular dystrophy based on preliminary safety data.

References:
[1] Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis. Holzbaur, EL et al. Neurobiol Dis. 2006 Sep;23(3):697-707.
[2] Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy. ClinicalTrials.gov, 31 Jan 2013. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT01099761.
[3] UPDATE: ACE-031 clinical trials in Duchenne MD Wahl, M. Quest Magazine Online, 2 May 2013. Accessed 9 Mar 2016 from http://quest.mda.org/news/update-ace-031-clinical-trials-duchenne-md.

Last updated March 11th, 2016
ShireProtein BiologicImproving muscle functionALSDiscontinued
AMX0035

AMX0035

(Click title to open drug details in a new window.)
Company: Amylyx Pharmaceuticals
Location: US-Massachusetts
Website: http://www.amylyx.com
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's disease, Parkinson's disease.
Mechanism Type: Neuroprotection
Mechanism: AMX0035 a proprietary combination of two drugs, TUDCA and sodium phenylbutyrate, that acts by reducing cell death and neuronal inflammation in response to oxidative insult.
U.S. Status for ALS: Phase II
Commercial Information: AMX0035 is a proprietary combination of two drugs that contains tauroursodeoxycholic acid and sodium phenylbutyrate.
R&D Status: The phase II clinical trial launched in June 2017.

References:
[1] Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis. Elia, AE et al. Eur J Neurol. 2016 Jan;23(1):45-52.
[2] Phase 2 study of sodium phenylbutyrate in ALS. Cudkowicz, ME et al. Amyotroph Lateral Scler. 2009 Apr;10(2):99-106.
[3] AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS) (CENTAUR) Clinicaltrials.gov, June 19, 2017.

Last updated June 22nd, 2017
Amylyx PharmaceuticalsSmall MoleculeNeuroprotectionALSPhase II
AT-1501 (anti-CD40L)

AT-1501 (anti-CD40L)

(Click title to open drug details in a new window.)
Company: Anelixis Therapeutics
Location: US - Massachusetts
Website: http://www.anelixistherapeutics.com/
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: Immunomodulation
Mechanism: The blocking antibody to CD40L is designed to modulate the immune response associated with disease progression in ALS.
U.S. Status for ALS: Preclinical
Commercial Information: Anelixis Therapeutics is a virtual biotechnology company that is the for-profit subsidiary of ALSTDI. Anelixis has in-licensed the rights to develop the CD40L antibody as a novel candidate therapy for ALS.
R&D Status: Preclinical

References:
[1] CD40L. Anelixis Therapeutics, 2016. Accessed 28 Dec 2015 from http://www.anelixistherapeutics.com/CD40Ligand.aspx.

Last updated December 28th, 2015
Anelixis TherapeuticsProtein BiologicImmunomodulationALSPreclinical
Anavex 2-73

Anavex 2-73

(Click title to open drug details in a new window.)
Company: Anavex Life Sciences Corp.
Location: US - New York
Website: http://www.anavex.com/index.html
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, oncology
Mechanism Type: Sigma-1 receptor agonist, muscarinic receptor agonist, neuroprotection
Mechanism: ANAVEX 2-73, is a sigma-1 and muscarinic receptor agonist for treating Alzheimer's disease and various cancers. The sigma-1 receptors are chaperone proteins localized to the endoplasmic reticulum (ER), and function in pathways that effect ER stress. The sigma-1 receptors have been implicated in several neurodegenerative diseases, including ALS.
U.S. Status for ALS: Preclinical
R&D Status: The drug is currently being tested in Phase IIa clinical trials, alone and in combination with donepezil (Anavex-Plus), for Alzheimer's disease. It is in preclinical development for ALS.

References:
[1] Anavex Encouraged By Scientific Data Confirming Sigma-1 Receptor Agonist Extends Survival in ALS (Lou Gehrig's Disease). GlobeNewswire, 10 Mar 2014. Accessed 3 Mar 2016 from https://globenewswire.com/news-release/2014/03/10/616981/10071871/en/Anavex-Encouraged-By-Scientific-Data-Confirming-Sigma-1-Receptor-Agonist-Extends-Survival-in-ALS-Lou-Gehrig-s-Disease.html.
[2] Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS) Mavlyutov, TA et al. J Pharmacol Sci. 2015 Jan;127(1):10-6.

Last updated March 3rd, 2016
Anavex Life Sciences Corp.Small MoleculeSigma-1 receptor agonist, muscarinic receptor agonist, neuroprotectionALSPreclinical
Arimoclomol (Orph-001)

Arimoclomol (Orph-001)

(Click title to open drug details in a new window.)
Company: Orphazyme
Location: Denmark
Website: http://www.orphazyme.com
Drug Type: Protein Biologic
Conditions: SOD1 ALS
Mechanism Type: Protein misfolding modulator
Mechanism: Orph-001 is a recombinant version of human 70-kDa heat shock protein (Hsp70), a chaperone protein that plays a role in folding of newly translated proteins and refolding or clearance of misfolded proteins. The drug is being developed for lysosomal storage diseases, but the mechanism of action suggests it would be of potential interest in ALS.
U.S. Status for ALS: Phase II/III
Commercial Information: In May 2011, Orphazyme acquired CytRx's molecular chaperone technology including the drug candidate arimoclomol, which is in clinical development for ALS.
R&D Status: The phase II/III clinical trial of arimoclomol in ALS has recently been completed. The results were presented at the International Symposium on ALS/MND in Dublin, Ireland in December 2016.

References:
[1] Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis. Cudkowicz, ME et al. Muscle Nerve. 2008 Jul;38(1):837-44.
[2] Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1 mouse model of ALS. Kalmar, B et al. J Neurochem. 2008 Oct;107(2):339-50.
[3] Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Kieran, D et al. Nat Med. 2004 Apr;10(4):402-5.
ALS Research Forum Reference: http://www.alsresearchforum.org/can-the-heat-shock-response-rescue-muscles-and-motor-neurons/

Last updated June 21st, 2017
OrphazymeProtein BiologicProtein misfolding modulatorSOD1 ALSPhase II/III
AstroRx

AstroRx

(Click title to open drug details in a new window.)
Company: Kadimastem
Location: Israel
Website: http://www.kadimastem.com
Drug Type: Stem Cell Therapy
Conditions: ALS, diabetes mellitus
Mechanism Type: Neuroprotection
Mechanism: AstroRx are human embryonic stem cell-derived astrocyte precursor cells, which are delivered via intrathecal transplantation. The introduction of functional astrocyte precursor cells has the potential to regulate glutamatergic signaling, which is impaired in ALS patients. Transplantation of astrocytes derived from stem cells into mutant SOD1 rats increases survival.
U.S. Status for ALS: Preclinical
Commercial Information: Kadimastem is developing a framework for clinical trials in ALS in consultation with the FDA, and is planning an IND submission for 2016. The company was founded based on patented technologies developing in the laboratory ofProf. Michel Revel (developer of the multiple sclerosis blockbuster drug, Rebif, and Kadimastem's Chief scientific Officer).
R&D Status: Kadimastem is developing a framework for clinical trials in ALS in consultation with the FDA, and is planning an IND submission for 2016.

References:
[1] Kadimastem. Regenerative Medicine - Neurodegenerative Diseases. Kadimastem, n.d. Accessed 9 Mar 2016 from http://www.kadimastem.com/regenerative-medicine/18/neurodegenerative-diseases.
[2] Kadimastem Reached Agreements with the FDA Regarding the Framework of the Clinical Trials in Humans for the Treatment of ALS. BusinessWire, 10 Dec 2015. Accessed 9 Mar 2016 from http://www.businesswire.com/news/home/20151210005420/en/Kadimastem-Reached-Agreements-FDA-Framework-Clinical-Trials.

Last updated March 9th, 2017
KadimastemStem Cell TherapyNeuroprotectionALSPreclinical
BHV-0223

BHV-0223

(Click title to open drug details in a new window.)
Company: Biohaven Phamaceuticals
Website: http://biohavenpharma.com/
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's Disease, Ataxia, Anxiety disorders, Affective disorders, Dementia, Dystonia, Rett Syndrome, Tinnitus
Mechanism Type: Glutamate Excitotoxicity Blocker
Mechanism: BHV-0223 is a new form of riluzole that is easier to swallow. The drug, like riluzole, aims to protect motor neurons from further damage by reducing glutamate release from axon terminals.
U.S. Status for ALS: IND
R&D Status: A bioequivalence study is planned to launch in 2017.

References:
[1] Biohaven Announces Orphan Drug Designation Request Granted For BHV-0223 in the Treatment of Amyotrophic Lateral Sclerosis PR Newswire. December 9, 2016
Biohaven PhamaceuticalsSmall MoleculeGlutamate Excitotoxicity BlockerALSIND
BHV-4157 (FC-4157)

BHV-4157 (FC-4157)

(Click title to open drug details in a new window.)
Company: Biohaven Pharmaceuticals
Location: US-Connecticut
Website: http://biohavenpharma.com/
Drug Type: Protein Biologic
Conditions: Spinocerebellar Ataxia
Mechanism Type: Glutamate Excitotoxicity Blocker
Mechanism: BHV-4157 is a glutamate modulator that aims to protect neurons by reducing glutamate excitotoxicity.
U.S. Status for ALS: N/A
Commercial Information: Biohaven acquired the worldwide intellectual property rights from ALS Biopharma to a portfolio of over 300 prodrugs hat are glutamate modulators including BHV-4157. ALS Biopharma is affiliated with the Pennsylvania Drug Discovery Institute (www.padrugdiscovery.org) at the Pennsylvania Biotechnology Center of Bucks County in Doylestown, PA (www.pabiotechbc.org).
R&D Status: BHV-4157 is currently being evaluated at phase II/III as a potential treatment for Spinocerebellar Ataxia.

References:
[1] Trial in Adult Subjects With Spinocerebellar Ataxia Clinical trials.gov, 15 June 2017.
[2] Biohaven Receives FDA IND Approval for BHV-4157. Biohaven Pharmaceuticals, 5 July 2016. Accessed 29 June 2017 from http://biohavenpharma.com/biohaven-receives-fda-investigational-new-drug-application-ind-approval-for-bhv-4157/

Last updated June 29th, 2017
Biohaven PharmaceuticalsProtein BiologicGlutamate Excitotoxicity BlockerSpinocerebellar AtaxiaN/A
BIIB067 (Isis-SOD1Rx)

BIIB067 (Isis-SOD1Rx)

(Click title to open drug details in a new window.)
Company: Biogen
Location: US-Massachusetts
Website: http://www.biogen.com
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: SOD1-Lowering Therapy
Mechanism: IONIS-SOD1Rx is a generation 2.0 antisense drug specifically designed to inhibit production of mutant superoxide dismutase (SOD1). SOD1 mutations account for approximately 20% of familial ALS cases.
U.S. Status for ALS: Phase I
Commercial Information: This program is a collaboration between Biogen and IONIS Pharmaceuticals (formerly ISIS).
R&D Status: A Phase I clinical trial is recruiting participants as of Feb 2016. The clinical trial aims to determine the safety, tolerability and pharmacokinetics of SOD1RX in people with ALS. The study also aims to evaluate CSF SOD1 levels as a marker of target engagement to facilitate the development of SOD1-reducing therapies (Winer et al., 2013). Study completion is expected in July 2018.

References:
[1] Single and Multiple Dose Study of BIIB067 (Isis-SOD1Rx) in Adults With Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov, 1 Feb 2016. Accessed 9 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02623699.
[2] SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense oligonucleotide therapy. Winer, L. et al. JAMA Neurol. 2013 Feb;70(2):201-7.
[3] An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Miller, TM et al. Lancet Neurol. 2013 May;12(5):435-42.
ALS Research Forum Reference: http://www.alsresearchforum.org/paper-alert-antisense-oligonucleotide-therapy-safe-for-als/

Last updated June 21st, 2017
BiogenGene TherapySOD1-Lowering TherapyALSPhase I
Biglycan (TVN-102)

Biglycan (TVN-102)

(Click title to open drug details in a new window.)
Company: Tivorsan Pharmaceuticals
Location: US-Rhode Island
Website: http://www.tivorsan.com
Drug Type: Protein Biologic
Conditions: ALS, Duchenne muscular dystrophy (DMD)
Mechanism Type: NMJ stabilization
Mechanism: Recombinant biglycan (TVN-102) aims to stabilize neuromuscular junctions by increasing MuSK activation. The approach is based on previous studies which found that biglycan stabilizes these synapses in part, by regulating the localization and levels of MuSK at motor nerve terminals (Amenta et al., 2012).
U.S. Status for ALS: Preclinical
Commercial Information: Tivorsan's lead candidate, TVN-102, is based on preclinical studies from Brown University's Justin Fallon, Ph.D., scientific founder of Tivorsan which found that biglycan stabilizes neuromuscular junctions.
R&D Status: Preclinical studies in a SOD1 mouse model of ALS is planned. A phase I clinical trial of TVN-102 in DMD is expected to launch in 2017.

References:
[1] Biglycan is an extracellular MuSK binding protein important for synapse stability. Amenta, AR et al. J Neurosci. 2012 Feb 15;32(7):2324-34.
[2] Tivorsan Pharmaceuticals Closes Private Placement. Business Wire, 5 Feb 2016. Accessed 11 Mar 2016 from http://www.businesswire.com/news/home/20160205005030/en/Tivorsan-Pharmaceuticals-Closes-Private-Placement.
ALS Research Forum Reference: http://www.alsresearchforum.org/a-new-als-therapeutic-strategy-sets-sail-in-hopes-to-stabilize-nmjs/

Last updated June 22nd, 2017
Tivorsan PharmaceuticalsProtein BiologicNMJ stabilizationALSPreclinical
CAT-4001

CAT-4001

(Click title to open drug details in a new window.)
Company: Catabasis Pharmaceuticals
Location: US-Massachusetts
Website: http://www.catabasispharma.com
Drug Type: Small Molecule
Conditions: ALS, Friedriech's ataxia
Mechanism Type: Anitoxidant, Immunomodulator
Mechanism: CAT-4001 is a modulator of Nrf2, a basic leucine zipper protein that regulates oxidative stress and inflammation, and NFkB, a regulator of inflammatory pathways. CAT-4001 is a linked conjugate of monomethyl fumarate and DHA designed to modulate these two pathways. Studies in cellular assays and animal models have shown that the conjugate is more effective than either compound alone, in combinations in inconjugated form.
U.S. Status for ALS: Preclinical
R&D Status: Preclinical studies and IND-enabling studies are ongoing for ALS and Friedreich's ataxia. The company anticipates starting a Phase I trial in 2017.

References:
[1] Catabasis. Pipeline - CAT-4001. Catabasis, 2016. Accessed 9 Mar 2016 from http://www.catabasis.com/scitech-pipeline.php.

Last updated March 9th, 2016
Catabasis PharmaceuticalsSmall MoleculeAnitoxidant, ImmunomodulatorALSPreclinical
CDNF

CDNF

(Click title to open drug details in a new window.)
Company: Herantis
Location: Finland
Website: http://www.herantis.com/
Drug Type: Protein Biologic
Conditions: ALS, Parkinson's disease
Mechanism Type: Neuroprotection
Mechanism: Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF), a CDNF paralog represent a novel family of neurotrophic factors. The rationale for testing CDNF in ALS is supported by evidence that enhancing support from other neutrophic factors is beneficial in ALS mouse models. In preliminary unpublished studies, a single dose of CDNF improved survival in ALS mouse models. In non-human primate studies, CDNF has shown neuroprotective and regenerative capacity for dopamine-generating cells. Signals of efficacy are also seen in non-motor symptoms based on preclinical data.
U.S. Status for ALS: Preclinical
R&D Status: Preclinical

References:
[1] Herantis Pharma Plc. HORN International, n.d. Accessed 9 Mar 2016 from http://hornonline.com/herantis-pharma-plc/.
[2] Novel CDNF/MANF Family of Neurotrophic Factors. Lindholm P, Saarma M. Dev Neurobiol. 2010 Apr;70(5):360-71.
[3] Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease. Garea-Rodriguez, E et al. PLoS One. 2016 Feb 22;11(2):e0149776.

Last updated February 3rd, 2016
HerantisProtein BiologicNeuroprotectionALSPreclinical
CNS10-NPC-GDNF

CNS10-NPC-GDNF

(Click title to open drug details in a new window.)
Company: Svendsen Lab
Location: Cedar-Sinai Medical Center Los Angeles, CA
Drug Type: Stem Cell Therapy
Conditions: ALS
Mechanism Type: Neuroprotection
Mechanism: CNS10-NPC-GDNF are genetically engineered human neural progenitor cells that secrete GDNF. The approach aims to use stem cells to deliver GDNF into the CNS in hopes to promote motor neuron survival.
U.S. Status for ALS: Phase I

References:
[1] CNS10-NPC-GDNF for the Treatment of ALS. Clinicaltrials.gov, May 25, 2017.
[2] Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats. Neuroreport. 2014 Apr 16;25(6):367-72.
ALS Research Forum Reference: http://www.alsresearchforum.org/to-evaluate-stem-cell-therapies-think-unilaterally/
Svendsen LabStem Cell TherapyNeuroprotectionALSPhase I
Ceftriaxone

Ceftriaxone

(Click title to open drug details in a new window.)
Company: Roche Pharmaceuticals
Location: Switzerland
Website: http://www.roche.com
Drug Type: Small Molecule
Conditions: ALS, Spinal Muscular Atrophy
Mechanism Type: Glutamate Excitotoxicity Blocker
Mechanism: Ceftriaxone is a cephalosporin antibiotic that protects neurons from glutamate excitotoxicity by increasing the expression of the astrocytic excitatory amino acid transporters (EAAT2, or Glt-1). In this fashion, the drug has potential to protect from glutamate mediated excitotoxicity.
U.S. Status for ALS: Discontinued
R&D Status: Ceftriaxone is an FDA approved antibiotic. It was under development as a potential ALS therapy. However, in August 2012 the Phase III ALS clinical trial of the antibiotic ceftriaxone was discontinued due to lack of statistically significant effect on disease progression in ALS.

References:
[1] Design and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis. Berry, JD et al. PLoS One. 2013 Apr 17;8(4):e61177.
[2] Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial. Cudkowicz, ME et al. Lancet Neurol. 2014 Nov;13(11):1083-91.
ALS Research Forum Reference: http://www.alsresearchforum.org/als-clinical-trials-new-hope-in-wake-of-big-phase-3-setbacks/

Last updated June 21st, 2017
Roche PharmaceuticalsSmall MoleculeGlutamate Excitotoxicity BlockerALSDiscontinued
Copaxone (Glatiramer Acetate)

Copaxone (Glatiramer Acetate)

(Click title to open drug details in a new window.)
Company: Teva Pharmaceutical Industries
Location: Israel
Website: http://www.tevapharm.com
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: Immunomodulation
Mechanism: Copaxone is a synthetic protein composed of four amino acids found in myelin basic protein (MBP). The drug simulates MBP, and prevents damage to myelin caused by T-cells.
U.S. Status for ALS: Discontinued
R&D Status: A Phase II trial in ALS testing Copaxone injections in ALS patients was completed in 2009 and no impact on disease progression was observed. The program was discontinued. The drug is FDA approved for relapsing remitting multiple sclerosis.

References:
[1] Clinical Trial of Glatiramer Acetate in Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov, 29 Aug 2013. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT00326625.
[2] Glatiramer acetate has no impact on disease progression in ALS at 40 mg/day: a double- blind, randomized, multicentre, placebo-controlled trial. Meininger, V et al. Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):378-83.

Last updated March 11th, 2016
Teva Pharmaceutical IndustriesProtein BiologicImmunomodulationALSDiscontinued
Cu(II)ATSM

Cu(II)ATSM

(Click title to open drug details in a new window.)
Company: ProCypra Therapeutics
Location: US-California
Website: http://www.colmeddev.com/procypra/
Drug Type: Small Molecule
Conditions: ALS, Parkinson's disease
Mechanism Type: SOD1 Metalation
Mechanism: Cu(II)ATSM is a bisthiosemicarbazone which selectively delivers copper to cells with impaired mitochondrial electron transport chains, a characteristic of ALS and many other neurodegenerative diseases. In both SOD1 mouse models of ALS and in ALS patients, scientists have found alterations in copper homeostasis, providing a rationale for testing this candidate in ALS. In a series of publications in mouse models of ALS, Cu(II)ATSM improved motor function and prolonged survival.
U.S. Status for ALS: Phase I
Commercial Information: ProCypra is a subsidiary of Collaborative Medicinal Development (CMD). CMD licensed commercial rights to the Cu(II)ATSM technology from the University of Melbourne Australia. The company is founded based on work from Kevin Barnham, Paul Donnelly and Anthony White at the University of Melbourne, as well as Peter Crouch, who led the studies in ALS.
R&D Status: A phase I trial of Cu(II)ATSM in ALS is currently recruiting in Australia. Radiolabeled Copper 64-ATSM is also in clinical testing in the U.S. as a hypoxia imaging agent at low doses.

References:
[1] CuATSM efficacy is independently replicated in a SOD1 mouse model of ALS while unmetallated ATSM therapy fails to reveal benefits. Vieira, FG et al. IBRO Reports 2017 Jun; 2:47-53
[2] Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis. Roberts, BR et al. J Neurosci. 2014 Jun 4;34(23):8021-31.
ALS Research Forum Reference: http://www.alsresearchforum.org/copper-to-the-rescue-in-als-mice/

Last updated June 29th, 2017
ProCypra TherapeuticsSmall MoleculeSOD1 MetalationALSPhase I
Cutamesine

Cutamesine

(Click title to open drug details in a new window.)
Company: M’s Science Corporation
Location: Japan
Website: http://www.m-sci.com/e/
Drug Type: Small Molecule
Conditions: ALS, depression, stroke
Mechanism Type: Sigma-1 receptor (S1R) agonist.
Mechanism: Cutamesine is a highly selective sigma-1 receptor (S1R) agonist, which is being developed for ALS. S1R mutations are associated with juvenile ALS, and mouse studies suggest S1R agonists may have therapeutic benefit in ALS.
U.S. Status for ALS: N/A
R&D Status: A Phase I clinical trial in ALS was completed in Japan and the EU. A Phase II trial was completed in stroke in Japan and the EU.

References:
[1] Pipeline. M's Science Corporation, 2015. Accessed 9 March, 2016 from http://www.m-sci.com/e/pipeline/cutamesine.html
[2] A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Al-Saif, A et al. Ann Neurol. 2011 Dec;70(6):913-9.
[3] Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS). Mavlyutov, TA et al. J Pharmacol Sci. 2015 Jan; 127(1): 10–16.
[4] Phase II trial of the Sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke. Urfer, R et al. Stroke. 2014 Nov;45(11):3304-10.

Last updated March 9th, 2016
M’s Science CorporationSmall MoleculeSigma-1 receptor (S1R) agonist.ALSN/A
Dexpramipexole

Dexpramipexole

(Click title to open drug details in a new window.)
Company: Biogen
Location: US-Massachusetts
Website: http://www.biogen.com
Drug Type: Small Molecule
Conditions: ALS, multiple sclerosis, Alzheimer's disease, spinal muscular atrophy
Mechanism Type: Mitochondrial bioenergetics modulator
Mechanism: The compound is a small molecule modulator of mitochondrial bioenergetics.
U.S. Status for ALS: Discontinued
Commercial Information: Following positive outcomes in a Phase II clinical trial in ALS sponsored by Knopp Biosciences, the compound was licensed to Biogen-Idec (now Biogen) from Knopp Biosciences. The Phase III clinical trial was sponsored by Knopp in collaboration with Biogen, but the drug did not show efficacy on any of the outcome measures examined.
R&D Status: Discontinued by Biogen. A Phase III trial of dexpramipexole that enrolled 943 patients was completed in 2012, and the compound did not show efficacy on any of the endpoints assessed. The primary outcome measure assessed was a joint rank analysis of both survival and function. The Phase III extension study in collaboration with Biogen was terminated based on these results. Knopp is still developing the drug for other indications including hypereosinophilic syndromes.

References:
[1] Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial. Cudkowicz, ME et al. Lancet Neurol. 2013 Nov;12(11):1059-67.
[2] Biogen Idec Reports Top-Line Results from Phase 3 Trial Investigating Dexpramipexole in People with Amyotrophic Lateral Sclerosis (ALS). BusinessWire, 3 Jan 2013. Accessed 9 Mar 2016 from http://www.businesswire.com/news/home/20130103005609/en/Biogen-Idec-Reports-Top-Line-Results-Phase-3.
[3] Phase 3 Extension Study of Dexpramipexole in ALS (ENVISION). ClinicalTrials.gov, 24 Nov 2014. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT01622088.
[4] A post hoc analysis of subgroup outcomes and creatinine in the phase III clinical trial (EMPOWER) of dexpramipexole in ALS. Bozik, ME et al. Amyotroph Lateral Scler Frontotemporal Degener. 2014 Sep;15(5-6):406-13.
ALS Research Forum Reference: http://www.alsresearchforum.org/als-clinical-trials-new-hope-in-wake-of-big-phase-3-setbacks/

Last updated February 1st, 2016
BiogenSmall MoleculeMitochondrial bioenergetics modulatorALSDiscontinued
E0302

E0302

(Click title to open drug details in a new window.)
Company: Eisai Company, Ltd.
Location: Japan
Website: http://www.eisai.com
Drug Type: Small Molecule
Conditions: ALS
Mechanism Type: Neuroprotection
Mechanism: E0302 (mecobalamin) is a coenzyme form of vitamin B(12), and acts as an important cofactor in the activities of B(12)-dependent methyltransferases. It is approve and marketed as a treatment for peripheral neuropathies in Japan. The mechanism of action in unknown, but some studies suggest that it is neuroprotective and leads to axonal regeneration.
U.S. Status for ALS: N/A
R&D Status: A Phase II/III clinical trial of ultra high dose of mecobalamin (E0302) in ALS was completed in July 2014, and a long term study is ongoing. In May 2015, Eisai submitted a new drug application for E0302 for ALS in Japan, but the NDA was withdrawn in March 2016 following a meeting with the Japanese regulatory agency, the Pharmaceuticals and Medical Devices Agency (PMDA), due to insufficient evidence for approval. The drug is approved and marketed in Japan for peripheral neuropathies and other conditions. In the United States, mecobalamin can be purchased over the counter at formulations of lower doses (up to 2500 microgram, while it is being tested at 25 mg and 50mg doses) but clinical testing for ALS is not ongoing.

References:
[1] Eisai Submits New Drug Application for Mecobalamin Ultra-High Dose Preparation as Treatment for Amyotrophic Lateral Sclerosis in Japan. JCN Newswire, 27 May 2015. Accessed 9 Mar 2016 from http://en.acnnewswire.com/press-release/english/22659/eisai-submits-new-drug-application-for-mecobalamin-ultra-high-dose-preparation-as-treatment-for-amyotrophic-lateral-sclerosis-in-japan.
[2] Eisai Withdraws new drug application for mecoblamain ultra-high dose prepation as treatment for amyotrophic lateral sclerosis. Eisai, 22 Mar 2016. Accessed 28 Mar 2016 from http://www.eisai.com/news/news201615.html
[3] A Long-Term Study in Patients With Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov, 26 Feb 2016. Accessed 9 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT00445172
[4] Methylcobalamin facilitates collateral sprouting of donor axons and innervation of recipient muscle in end-to-side neurorrhaphy in rats. Liao, WC et al. PLoS One. 2013 Sep 30;8(9):e76302.

Last updated March 29th, 2016
Eisai Company, Ltd.Small MoleculeNeuroprotectionALSN/A
EVT302

EVT302

(Click title to open drug details in a new window.)
Company: Evotec
Location: Germany
Website: http://www.evotec.com
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's disease
Mechanism Type: Anitoxidant
Mechanism: EV302 is an inhibitor of monoamine oxidase B, an enzyme that breaks down dopamine, and contributes to production of free radicals and oxidative stress conditions.
U.S. Status for ALS: Preclinical
Commercial Information: The compound was originally licensed to Evotec by Roche in 2006, but in 2011, the two companies entered into an exclusive license agreement to co-develop it for Alzheimer's disease (AD). In July 2015, the companies announced that a Phase IIb trial in AD had failed. Evotec established a collaboration with the Harvard Stem Cell Institute scientists Dr. Kevin Eggan and Dr. Lee Rubin in 2013 to identify drugs that slow motor neuron degeneration in ALS, in a program called
R&D Status: The company announced in 2015 that the drug failed in a Phase IIb clinical trial in Alzheimer's disease.

References:
[1] Roche forced to concede another flop for Alzheimer's program. Carroll, J. FierceBiotech, 1 Jul 2015. Accessed 11 Mar 2016 from http://www.fiercebiotech.com/story/roche-forced-concede-another-flop-alzheimers-program/2015-07-01.
[2] Evotec and Harvard Stem Cell Institute form CureMN collaboration to advance ALS research. Evotec, 12 Sep 2013. Accessed 9 Mar 2016 from https://www.evotec.com/article/en/Press-releases/Evotec-and-Harvard-Stem-Cell-Institute-form-CureMN-collaboration-to-advance-ALS-research/2435.
[3]

Last updated March 9th, 2016
EvotecSmall MoleculeAnitoxidantALSPreclinical
Edaravone

Edaravone

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Company: Mitsubishi Tanabe Pharma Corporation
Location: Japan
Website: http://www.mt-pharma.co.jp
Drug Type: Small Molecule
Conditions: ALS, stroke
Mechanism Type: Anitoxidant
Mechanism: Edaravone is a free radical scavenger, which functions as an antioxidant by neutralizing peroxyl radicals and peroxynitrite. In mouse models of ALS, edaravone reduced motor neuron loss and functional decline. The drug is thought to help protect motor neurons in ALS by reducing oxidative stress.
U.S. Status for ALS: FDA Approved
R&D Status: Edaravone is approved for the treatment of ALS in the US, Japan and South Korea.

References:
[1] Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Abe, K et al. Lancet Neurol. 2017 May 15. pii: S1474-4422(17)30115-1.
[2] Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice. Abe, K et al. Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):610-7.
ALS Research Forum Reference: http://www.alsresearchforum.org/fda-approves-edaravone-as-a-treatment-for-als-2/

Last updated June 9th, 2017
Mitsubishi Tanabe Pharma CorporationSmall MoleculeAnitoxidantALSFDA Approved
Elamipretide (MTP-131)

Elamipretide (MTP-131)

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Company: Stealth BioTherapeutics
Location: US-Massachusetts
Website: http://www.stealthbt.com/
Drug Type: Small Molecule
Conditions: skeletal muscular disorders, mitochondrial myopathy
Mechanism Type: Mitochondrial bioenergetics
Mechanism: Elamipretide targets cardiolipin, a lipid residing in the mitochondrial inner membrane, which is critical to maintaining mitochondrial function and cellular energy supply. Bendavia has been shown to promote energy production and reduce the production of excess of reactive oxygen species. This drug could have potential applications in neurodegenerative diseases, including ALS.
U.S. Status for ALS: Preclinical
R&D Status: A Phase II trial testing the impact of Bendavia on skeletal muscle function in the eldery is currently recruiting.

References:
[1] A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia) on Skeletal Muscle Function in Elderly (SPITM-201). ClinicalTrials.gov, 30 Jul 2015. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02245620.

Last updated March 11th, 2016
Stealth BioTherapeuticsSmall MoleculeMitochondrial bioenergeticsSkeletal muscular disordersPreclinical
FRM-0334

FRM-0334

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Company: Forum Pharmaceuticals (formerly EnVivo Pharmaceuticals)
Location: US-Massachusetts
Website: http://www.forumpharma.com
Drug Type: Small Molecule
Conditions: FTD
Mechanism Type: HDAC inhibitor
Mechanism: FRM-0334 is a brain penetrant histone deacetylase (HDAC) inhibitor. FRM-0334 increases transcription of the granulin gene and is being developed as a therapy for frontotemporal dementia (FTD) due to mutations in the granulin gene, known as FTD-GRN. FRM-0334 has been shown to increase progranulin expression in rodents and in cells derived from patients carrying granulin mutations.
U.S. Status for ALS: N/A
Commercial Information: The company was formerly named EnVivo Pharmaceuticals.
R&D Status: Forum Pharma initiated a Phase II trial in FTD. As of May 2015, the study was recruiting participants.

References:
[1] HDAC Program. Forum Pharmaceuticals, 2015. Accessed 9 Mar 2016 from http://www.forumpharma.com/innovation-pipeline/hdac-program/.
[2] Study to Assess the Safety, Tolerability, and Pharmacodynamic (PD) Effects of FRM-0334 in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation. ClinicalTrials.gov, 6 May 2015. Accessed 9 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02149160.

Last updated March 9th, 2016
Forum Pharmaceuticals (formerly EnVivo Pharmaceuticals)Small MoleculeHDAC inhibitorFTDN/A
Fingolimod (Gilenya)

Fingolimod (Gilenya)

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Company: ALS Therapy Development Institute
Location: US-Massachusetts
Website: http://www.als.net
Drug Type: Small molecule
Conditions: ALS
Mechanism Type: Immunomodulation
Mechanism: TDI-132 (aka: fingolimod/ Novartis' drug Gilenya) is an agonist of the sphigosine 1 phosphate receptor.It blocks T-cell infiltration into the CNS by reducing their circulation in the blood and retaining them in the lymph nodes. The drug is being developed to reduce neuroinflammation associated with disease progression in ALS.
U.S. Status for ALS: Inactive
Commercial Information: For full details of the ALS TDI pipeline click here: http://www.alstdi.org/als-research/.
R&D Status: Gilenya is approved for treating relapsin-remitting forms of multiple sclerosis.

References:
[1] Fingolimod (Gilenya, TDI 132). ALS Therapy Development Institute, 2016. Accessed 9 Mar 2016 from http://www.alstdi.org/als-research/als-topics/gilenya/.

Last updated March 9th, 2016
ALS Therapy Development InstituteSmall moleculeImmunomodulationALSInactive
GDC-0134

GDC-0134

(Click title to open drug details in a new window.)
Company: Genentech
Location: US-California
Website: http://www.gene.com
Drug Type: Unknown
Conditions: ALS
Mechanism Type: Glutamate Excitotoxicity Blocker
Mechanism: GDC-0134 is an inhibitor of the dual leucine zipper kinase (DLK). It aims to promote survival of motor neurons in ALS by reducing glutamate-mediated excitotoxicity.
U.S. Status for ALS: Phase I
R&D Status: A Phase I clinical trial trial of safety and pharmacokinetics of GDC-0134 in ALS opened in 2016.

References:
[1] Dual leucine zipper kinase is required for excitotoxicity-induced neuronal degeneration. Pozniak, CD et al. J Exp Med. 2013 Nov 18;210(12):2553-67.
[2] A Single-Ascending-Dose Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Patients With Amyotrophic Lateral Sclerosis. ClinicalTrials.gov, 1 Feb 2016. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02655614.

Last updated March 11th, 2016
GenentechUnknownGlutamate Excitotoxicity BlockerALSPhase I
GM604

GM604

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Company: Genervon Biopharmaceuticals
Location: US-California
Website: http://www.genervon.com/
Drug Type: Protein Biologic
Conditions: ALS, stroke, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosis
Mechanism Type: Neuroprotection
Mechanism: GM604 is based on motorneuronotrophic factor (MNTF), a fetally expressed six amino acid endogenous neurotrophin that exhibits neuroprotective, anti-apoptotic, anti-oxidative and anti-inflammatory effects. It acts by modulating 8 or more key pathways that are disrupted in ALS. In animal studies, GM604 prolonged survival and delayed disease onset. Results from a Phase II trial in 12 patients suggest that GM604 is well tolerated and may have therapeutic benefit that merits further studies in larger cohorts.
U.S. Status for ALS: Phase IIA
Commercial Information: GM604 was the subject of a large campaign from the ALS patient and caregiver community to accelerate approval of this therapy for ALS, but many scientists in the ALS research community expressed the need for further validation of the results in larger patient cohorts over longer periods of time.
R&D Status: The drug was granted Orphan Drug and Fast Track Designation by the U.S. FDA. A Phase II clinical trials in ALS that enrolled 12 patients was completed in 2014. The data was reported in company press releases but not in peer-reviewed publications. The company reported improvements in both clinical measurements, such as a reduction in slope of ALSFRS-R as compared to historical controls, and biomarker measurements. GM604 was reported to reduce aggregation of TDP-43 protein, with a mean percent reduction of 34% in the treated group as compared to a 6% reduction in the placebo group.

References:
[1] Genervon. Therapeutic Applications ALS. Genervon, 2016. Accessed 9 Mar 2016 from http://www.genervon.com/genervon/science_development.php.
[2] Genervon GM604 Reduced TDP-43 Protein Aggregates to Homeostasis Normal Range and thus Slowed Down Heterogeneous ALS Progression. Genervon, 22 Sep 2015. Accessed 11 Mar 2016 from http://www.genervon.com/genervon/PR20150922.php.
[3] Genervon Announces ALS and PD Phase 2a Trial Results Businesswire, 19 Oct 2014. Accessed 11 Mar 2016 from http://www.businesswire.com/news/home/20141019005074/en/Genervon-Announces-ALS-PD-Phase-2a-Trial.
[4] Experimental ALS Drug Triggers Social Media Hype, But Doctors Say Facts about GM604 Are Slim. Fitzgerald, Susan. Neurology Today, 2 Jul 2015 Vol.15(13):20–22. Accessed 9 Mar 2016 from http://journals.lww.com/neurotodayonline/Fulltext/2015/07020/Experimental_ALS_Drug_Triggers_Social_Media_Hype,.8.aspx.

Last updated March 9th, 2017
Genervon BiopharmaceuticalsProtein BiologicNeuroprotectionALSPhase IIA
Gnx4728

Gnx4728

(Click title to open drug details in a new window.)
Company: Congenia
Location: Italy
Website: http://www.congenia.it/
Drug Type: Small Molecule
Conditions: ALS
Mechanism Type: Regulator of mitochondrial permability
Mechanism: Gnx4728 is an inhibitor of the mitochondrial Permeability Transition Pore (mPTP). Increases in mitochondrial permeability are associated with mitochondrial swelling and rupturing, calcium release and release of apoptotic factors. Congenia is collaborating with academic researchers on testing their proprietary inhibitor Gnx4728 in mouse models of ALS.
U.S. Status for ALS: Preclinical
Commercial Information: Congenia is a biotechnology compay owned by Genextra.
R&D Status: Preclinical

References:
[1] GNX-4728, a novel small molecule drug inhibitor of mitochondrial permeability transition, is therapeutic in a mouse model of amyotrophic lateral sclerosis. Martin, LJ et al. Front Cell Neurosci. 2014 Dec 19; 8:433.

Last updated March 9th, 2016
CongeniaSmall MoleculeRegulator of mitochondrial permabilityALSPreclinical
HSF1

HSF1

(Click title to open drug details in a new window.)
Company: Chaperone Therapeutics
Location: US-North Carolina
Website: http://www.chaperonetherapeutics.com
Drug Type: Small Molecule
Conditions: ALS, Huntington's disease, hearing loss, glycogen storage disease
Mechanism Type: Protein misfolding modulator
Mechanism: Chaperone Therapeutics is developing therapies HSF1, a key modulator of protein folding and stress response pathways.
U.S. Status for ALS: Preclinical
Commercial Information: In August 2015, Chaperone Therapeutics and ALS TDI announced a partnership to develop therapies for ALS.
R&D Status: Preclinical

References:
[1] Chaperone Therapeutics and ALS Therapy Development Institute Enter into Research Partnership. ChaperoneTherapeutics, 10 Aug 2015. Accessed 9 Mar 2016 from http://www.chaperonetherapeutics.com/wp-content/uploads/2015/08/Chaperone-Therapeutics-and-ALS-TDI-press-release.pdf.

Last updated March 9th, 2016
Chaperone TherapeuticsSmall MoleculeProtein misfolding modulatorALSPreclinical
IMS-088

IMS-088

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Company: ImStar Therapeutics
Location: Canada
Website: http://www.imstartx.com/
Drug Type: Small Molecule
Conditions: ALS
Mechanism Type: SOD1 protein misfolding and aggregation
Mechanism: IMS-088 is a novel compound derived from withaferin A, a natural compound isolated from the leaves of the winter cherry plant, with improved pharmacological properties for a therapeutic drug. Studies in the SOD1 mouse model of ALS have shown that presymptomatic treatment with withaferin A prolongs survival in this model and reduces misfolded SOD1 levels.
U.S. Status for ALS: Preclinical
Commercial Information: The company was co-founded by Dr. Jean-Pierre Julien from Laval University. The last update from the company was in January 2014.
R&D Status: Preclinical

References:
[1] ImStar Therapeutics. Pipeline. ImStar Therapeutics, n.d. Accessed 9 Mar 2016 from http://imstartx.com/pipeline.html

Last updated March 9th, 2017
ImStar TherapeuticsSmall MoleculeSOD1 protein misfolding and aggregationALSPreclinical
IPL344

IPL344

(Click title to open drug details in a new window.)
Company: Immunity Pharma
Location: Israel
Website: http://www.immunitypharma.com/
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: Anti-apoptotic
Mechanism: IPL344 is an activator of the Akt pathway, a key signaling pathway in cell survival and repair.In mutant SOD1 mouse models of ALS, IPL344 delayed disease progression and prolonged survival.
U.S. Status for ALS: Preclinical
Commercial Information: Immunity Pharma's drug candidates were originally discovered laboratory of Prof. Irun R. Cohen at the Weizmann Institute of Science in Rehovot, Israel. The last update from the company was in 2012, and it is unclear whether this program is active.
R&D Status: Preclinical

References:
[1] Immunity Pharma - Pipeline. Immunity Pharma, n.d. Accessed 9 Mar 2016 from http://www.immunitypharma.com/company/.

Last updated March 9th, 2017
Immunity PharmaProtein BiologicAnti-apoptoticALSPreclinical
Ibudilast (MN-166

Ibudilast (MN-166

(Click title to open drug details in a new window.)
Company: MediciNova
Location: US-California
Website: http://www.medicinova.com
Drug Type: Small Molecule
Conditions: ALS, multiple sclerosis, neuropathic pain, addiction
Mechanism Type: Immunomodulation
Mechanism: Ibudilast is an orally bioavailable, centrally acting phosphodiesterase inhibitor that attenuates glial cell activation, at least in part, by reducing the effect of proinflammatory factors. MN-166 may minimize the production of pro-inflammatory cytokines.
U.S. Status for ALS: Phase II
R&D Status: In 2014, MedicinNova received FDA approval to begin a Phase II trial of MN-166 in ALS. The study is ongoing. In 2015, the FDA approved a new clinical protocol to add on a biomarker study component using a novel imaging technology, and to assess the effect of MN-166 on this biomarker.

References:
[1] Ibudilast (MN-166) in Subjects With Amyotrophic Lateral Sclerosis (ALS) (IBU-ALS-1201). ClinicalTrials.gov, 23 Sep 2015. Accessed 9 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02238626.
[2] FDA Approves a New Clinical Protocol to Evaluate the Effects of MN-166 (ibudilast) on a Biomarker of ALS; MediciNova Plans to Initiate a Clinical Trial with MGH (Massachusetts General Hospital). MarketWatch, 9 Nov 2015. Accessed 9 Mar 2016 from http://www.marketwatch.com/story/fda-approves-a-new-clinical-protocol-to-evaluate-the-effects-of-mn-166-ibudilast-on-a-biomarker-of-als-medicinova-plans-to-initiate-a-clinical-trial-with-mgh-massachusetts-general-hospital-2015-11-09.
ALS Research Forum Reference: http://www.alsresearchforum.org/new-als-clinical-trial-to-start-for-medicinovas-ibudilast/

Last updated June 21st, 2017
MediciNovaSmall MoleculeImmunomodulationALSPhase II
LMTX

LMTX

(Click title to open drug details in a new window.)
Company: TauRx Therapeutics
Location: Singapore
Website: http://www.taurx.com
Drug Type: Small Molecule
Conditions: Alzheimer's disease, bvFTD
Mechanism Type: Protein misfolding
Mechanism: LMTX reduces levels of aggregated or misfolded Tau proteins. The active ingredient, methyltionininium, also targets aggregation of synuclein, TDP-43 and huntingtin.
U.S. Status for ALS: Preclinical
R&D Status: LMTX is in being tested in Phase III trials for mild and moderate Alzheimer's disease and behavioral variant frontotemporal dementia. Phase I trials in Parkinson's disease are also ongoing.

References:
[1] Cellular Models of Aggregation-dependent Template-directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer Disease. Harrington, CR et al. J Biol Chem. 2015 Apr 24;290(17):10862-75.
[2] TauRx Completes US$135m Financing Round to Support Phase 3 Clinical Trials Program in Alzheimer's and Frontotemporal Dementia. PR Newswire, 8 Oct 2015. Accessed 11 March 2016 from http://www.prnewswire.com/news-releases/taurx-completes-us135m-financing-round-to-support-phase-3-clinical-trials-program-in-alzheimers-and-frontotemporal-dementia-531217421.html.
[3] Open-Label Study of TRx0237 in Subjects With Alzheimer's Disease or Behavioral Variant Frontotemporal Dementia (bvFTD). ClinicalTrials.gov, 17 Sep 2014. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02245568.

Last updated March 11th, 2016
TauRx TherapeuticsSmall MoleculeProtein misfoldingAlzheimer's diseasePreclinical
MANF (AMRS001)

MANF (AMRS001)

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Company: Amarantus Therapeutics
Location: US-California
Website: http://www.amarantustherapeutics.com
Drug Type: Protein Biologic, Diagnostic
Conditions: Parkinson's Disease, Retinitis Pigmentosa
Mechanism Type: Neurotrophic support, anti-apoptotic
Mechanism: Mesencephalic astrocyte-derived neurotrophic factor (MANF), is a highly potent growth factor exhibiting anti-apoptotic effects. The company is also developing the Lymphocyte Proliferation Test (LymPro Test) as a diagnostic blood test for Alzheimer's disease and is under evaluation for traumatic brain injury and chronic traumatic encephalopathy.
U.S. Status for ALS: Preclinical
Commercial Information: Amarantus acquired DioGenix in 2015, thereby expanding is pipeline of diagnostic tests focused on neuroinflammation in neurological diseases, including ALS.
R&D Status: Preclinical

References:
[1] Amarantus Announces Acquisition of Specialized Neuro-Diagnostics Company, DioGenix. Amarantus, 12 Jan 2015. Accessed 11 Mar 2016 from http://www.amarantus.com/news/press-releases/detail/1874/amarantus-announces-acquisition-of-specialized.

Last updated March 9th, 2016
Amarantus TherapeuticsProtein Biologic
Diagnostic
Neurotrophic support, anti-apoptoticParkinson's DiseasePreclinical
MC116

MC116

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Company: M’s Science Corporation
Location: Japan
Website: http://www.m-sci.com/e/
Drug Type: Small Molecule
Conditions: Parkinson's disease
Mechanism Type: Sigma-1 receptor (S1R) agonist.
Mechanism: MC116 is a sigma-1 receptor (S1R) agonist, which is being developed for Parkinson's disease. These is a potentially interesting compound for ALS, since S1R mutations are associated with juvenile ALS, and mouse studies suggest S1R agonists may have therapeutic benefit in ALS.
U.S. Status for ALS: N/A
R&D Status: N/A

References:
[1] M's Science Corporation. Pipeline. Pipeline. M's Science Corporation, 2015. Accessed 9 Mar 2016 from http://www.m-sci.com/e/pipeline/cutamesine.html
[2] A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Al-Saif, A et al. Ann Neurol. 2011 Dec;70(6):913-9.
[3] Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS). Mavlyutov, TA et al. J Pharmacol Sci. 2015 Jan; 127(1): 10–16.
[4] Phase II trial of the Sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke.

Last updated March 9th, 2016
M’s Science CorporationSmall MoleculeSigma-1 receptor (S1R) agonist.Parkinson's diseaseN/A
MRG-107

MRG-107

(Click title to open drug details in a new window.)
Company: miRagen Therapeutics
Location: US-Colorado
Website: http://www.miragentherapeutics.com
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: Immunomodulation
Mechanism: MRG-107 is an oligonucleotide drug that target miR-155, a microRNA that is elevated in the spinal cord of patients with ALS, and in ALS mouse models. It is key player in neuroinflammation and immune regulation, and is a therapeutic target of interest in ALS.
U.S. Status for ALS: Preclinical
R&D Status: MRG-107 is at the stage of investigational new drug (IND)-enabling studies in ALS.

References:
[1] miRagen Therapeutics - Pipeline. miRagen Therapeutics, 2016. Accessed 11 Mar 2016 from http://miragentherapeutics.com/pipeline/.
[2] Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Butovsky, O et al. Ann Neurol. 2015 Jan; 77(1): 75–99.
[3] Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice. Koval, ED et al. Hum Mol Genet. 2013 Oct 15;22(20):4127-35.
ALS Research Forum Reference: http://www.alsresearchforum.org/miragen-advances-anti-mir-155-therapy-with-alsa-grant/

Last updated March 11th, 2017
miRagen TherapeuticsGene TherapyImmunomodulationALSPreclinical
Masitinib

Masitinib

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Company: AB Science
Location: France
Website: http://www.ab-science.com/
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's disease, multiple sclerosis, stroke, cancer, rheumatoid arthritis
Mechanism Type: Immunomodulation
Mechanism: Masitinib is thought to reduce inflammation in ALS by blocking microgliosis, at least in the spinal cord. (Trias et al., 2016). The drug may also help protect peripheral motor neurons in ALS by inhibiting the infiltration of macrophages and mast cells. Masitinib is an enzymatic inhibitor which blocks tyrosine kinases including CSF1R, c-Kit and PDGFRα/β.
U.S. Status for ALS: Phase III
Commercial Information: France discontinued evaluation of this drug as a potential therapy for non-fatal conditions in 2015 due to severe adverse side effects observed in clinical studies.
R&D Status: A second Phase III clinical trial of masitinib in combination with riluzole is planned. Locations will include the U.S, Canada and Europe. The drug is currently being considered for conditional marketing approval in Europe. This decision could be made as early as the end of 2017.

References:
[1] Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. Trias, E. J Neuroinflammation. 2016 Jul 11;13(1):177.
[2] France Banned AB Science Drug Studies Because of Side Effects. Benoit, A. Bloomberg Business, 8 Jul 2015. Accessed 11 Mar 2016 from http://www.bloomberg.com/news/articles/2015-07-08/france-banned-ab-science-drug-studies-because-of-side-effects.
[3] The Objective is to Compare the Efficacy and Safety of Masitinib in Combination With Riluzole in the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov. 27 Oct 2015. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02588677?term=Masitinib&rank=12.
ALS Research Forum Reference: http://www.alsresearchforum.org/the-phase-iii-results-for-masitinib-are-now-in-but-experts-remain-divided/

Last updated June 9th, 2017
AB ScienceSmall MoleculeImmunomodulationALSPhase III
Mexitil (Mexiletine)

Mexitil (Mexiletine)

(Click title to open drug details in a new window.)
Company: Boehringer Ingelheim
Website: https://www.boehringer-ingelheim.com
Drug Type: Small Molecule
Conditions: ALS, Heart Arrhythmia, Muscle Cramps, Neuropathic Pain
Mechanism Type: Neuronal hyperexcitability
Mechanism: Mexiletine is a sodium channel blocker that may reduce neuronal hyperexcitability by reducing sodium ion influx (the persistent sodium current).
U.S. Status for ALS: Phase II
R&D Status: A phase II study is currently recruiting. The study aims to determine whether mexiletine may slow progression of ALS, and/or reduce muscle cramps and twitching in the disease.

References:
[1] A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression. Neurology. 2016 Apr 19;86(16):1474-81.
ALS Research Forum Reference: http://www.alsresearchforum.org/mexiletine-alleviates-key-source-of-muscle-pain-in-als/
Boehringer IngelheimSmall MoleculeNeuronal hyperexcitabilityALSPhase II
MoNuDin

MoNuDin

(Click title to open drug details in a new window.)
Company: Oxford Biomedica
Location: United Kingdom
Website: http://www.oxfordbiomedica.co.uk/
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: Neuroprotection
Mechanism: MoNuDin is a lentiviral vector technology for delivering vascular endothelial growth factor (VEGF) to motor neurons for the treatment of ALS
U.S. Status for ALS: Preclinical
Commercial Information: The program is being conducted in collaboration with VIB/University of Leuven and is being funded by the UK Motor Neurone Disease Association
R&D Status: Preclinical

References:
[1] MoNuDin. Oxford BiomMedica, 2016. Accessed 11 Mar 2016 from http://www.oxfordbiomedica.co.uk/monudin-r/.
[2] VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Azzouz, M et al. Nature. 2004 May 27;429(6990):413-7.

Last updated March 11th, 2016
Oxford BiomedicaGene TherapyNeuroprotectionALSPreclinical
NI-204

NI-204

(Click title to open drug details in a new window.)
Company: Neurimmune Therapeutics
Location: Switzerland
Website: http://www.neurimmune.com
Drug Type: Protein Biologic
Conditions: ALS, frontotemporal dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease
Mechanism Type: SOD1 aggregation modulator
Mechanism: NI-204 is a human-derived monoclonal antibody, which targets superoxide dismutase (SOD1) and prevents accumulation of SOD1 aggregates.
U.S. Status for ALS: Preclinical
Commercial Information: This project is being conducted in collaboration with ALS TDI.
R&D Status: Preclinical

References:
[1] Neurimmune NI-204 / TDI 200. ALS Therapy Development Institute, 2016. Neurimmune NI-204 / TDI 200. Accessed 11 Mar 016 from http://www.alstdi.org/als-research/als-topics/tdi-200/.

Last updated March 11th, 2016
Neurimmune TherapeuticsProtein BiologicSOD1 aggregation modulatorALSPreclinical
NI-205

NI-205

(Click title to open drug details in a new window.)
Company: Neurimmune Therapeutics
Location: Switzerland
Website: http://www.neurimmune.com
Drug Type: Protein Biologic
Conditions: ALS, frontotemporal dementia, Alzheimer's disease
Mechanism Type: TDP-43 aggregation modulator
Mechanism: NI-205 is a human-derived monoclonal antibody that targets TDP-43. Pathological cytoplasmic aggregates of TDP-43 are a hallmark of ALS and ALS/frontotemporal dementia, and mutations in the gene are associated with both diseases.
U.S. Status for ALS: Preclinical
Commercial Information: This asset is being developed in partnership with BIogen.
R&D Status: Preclinical

References:
[1] Neurimmune - Product Pipeline. Neurimmune. Product Pipeline. Accessed 11 Mar 2016 from http://www.neurimmune.com/products/product-pipeline.html
[2] NeurImmune allies with Biogen. European Biotechnology. NeurImmune allies with Biogen. 2 Jun 2011. Accessed 11 Mar 2016 from http://www.european-biotechnology-news.com/nc/news/messages-archive/archive-switzerland/browse/9/article/neurimmune-allies-with-biogen.html.

Last updated March 11th, 2016
Neurimmune TherapeuticsProtein BiologicTDP-43 aggregation modulatorALSPreclinical
NI-308

NI-308

(Click title to open drug details in a new window.)
Company: Neurimmune Therapeutics
Location: Switzerland
Website: http://www.neurimmune.com
Drug Type: Protein Biologic
Conditions: ALS, frontotemporal dementia
Mechanism Type: Unspecified
Mechanism: NI-308 is a human-derived monoclonal antibody that targets an undisclosed target for ALS/frontotemporal dementia.
U.S. Status for ALS: Preclinical
R&D Status: Preclinical

References:
[1] Neurimmune. Product Pipeline. Neurimmune, 2016. Accessed 11 Mar 2016 from http://www.neurimmune.com/products/product-pipeline.html
[2] NeurImmune allies with Biogen. European Biotechnology. 2 Jun 2011. Accessed 11 Mar 2016 from http://www.european-biotechnology-news.com/nc/news/messages-archive/archive-switzerland/browse/9/article/neurimmune-allies-with-biogen.html

Last updated March 11th, 2016
Neurimmune TherapeuticsProtein BiologicUnspecifiedALSPreclinical
NP001

NP001

(Click title to open drug details in a new window.)
Company: Neuraltus Pharmaceuticals
Location: US-California
Website: http://www.neuraltus.com
Drug Type: Small Molecule
Conditions: ALS, Parkinson's disease, Alzheimer's disease, frontotemporal dementia, ataxis-telangiectasia
Mechanism Type: Immunomodulation
Mechanism: NP001 is a small molecule regulator of macrophage activation. It is thought to restore macrophages to their neuroprotective state and reduce inflammation seen in ALS. Treatment of ALS mouse models with NP001 extended survival. In the Phase IIa safety study, administration of a high dose of NP001 (2mg/kg) over a 6 month period was associated with a slowing of disease progression in 27% of patients, approximately 2.5 times greater than the percentage in patients on placebo (10%).
U.S. Status for ALS: Phase II
Commercial Information: The confirmatory Phase II study of NP001 in ALS is ongoing. It is being directed by Robert Miller, M.D., Director of the Forbes Norris MDA/ALS Research Center at California Pacific Medical Center in San Francisco, CA.
R&D Status: A Phase II study was completed in 2012. A confirmatory Phase II study is ongoing. Neuraltus is establishing a managed access program for ALS patients in Europe.

References:
[1] Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis. Lunetta, C. et al. JAMA Neurol. 2017 Jun 1;74(6):660-667.
[2] Randomized phase 2 trial of NP001-a novel immune regulator: Safety and early efficacy in ALS. Miller, RG et al. Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9;2(3):e100.
[3] Differential effects on innate versus adaptive immune responses by WF10. Giese, T. et al. Cell Immunol. 2004 Jun;229(2):149-58.
ALS Research Forum Reference: http://www.alsresearchforum.org/clinicians-c-potential-in-the-emerging-als-prognostic-serum-biomarker-crp/

Last updated June 21st, 2017
Neuraltus PharmaceuticalsSmall MoleculeImmunomodulationALSPhase II
NPT088

NPT088

(Click title to open drug details in a new window.)
Company: Proclara Biosciences
Location: US-Massachusetts
Website: http://www.proclarabio.com
Drug Type: Protein Biologic
Conditions: Alzheimer's disease, Parkinson's disease
Mechanism Type: Protein misfolding modulator
Mechanism: The company's technology revolved around the General Amyloid Interaction Motif (GAIM) technology that simultaneously targets multiple misfolded proteins or amyloids. The GAIM technology are able to both prevent the formation of new toxic protein aggregates and also clear existing aggregates in the form of both soluble oligomers and insoluble fibers, such as plaques and tangles. NPT088 is the GAIM motif fused to a portion of a human antibody, which can be easily administered to patients. This mechanism of action suggest that the GAIM technology could also be beneficial in ALS.
U.S. Status for ALS: N/A
R&D Status: Preclinical

References:
[1] Neurophage. Our Science, Papers and Posters. Neurophage, 2015. Accessed 11 Mar 2016 from http://neurophage.com/science/papers-posters/.
[2] Hunting For Brain Plaques, Neurophage Turns to a Virus. Fidler, B. Xconomy, 31 Jan 2016. Accessed 11 Mar 2016 from http://www.xconomy.com/boston/2014/01/31/hunting-for-brain-plaques-neurophage-turns-to-a-virus/.

Last updated February 28th, 2017
Proclara BiosciencesProtein BiologicProtein misfolding modulatorAlzheimer's diseaseN/A
NSI-566

NSI-566

(Click title to open drug details in a new window.)
Company: NeuralStem
Location: US-Maryland
Website: http://www.neuralstem.com
Drug Type: Stem Cell Therapy
Conditions: ALS, spinal cord injury
Mechanism Type: Neuroprotection
Mechanism: NSI-566 are human spinal cord stem cell (HSSCs) that are administered into the gray matter of the spinal cord. In mouse models of ALS, NSI-566 cells expressed neutrophic factors and established synaptic connections with motor neurons. The cells are intended to provide neuroprotection to motor neurons in ALS patients.
U.S. Status for ALS: Phase II
R&D Status: An open-label phase II clinical trial in ALS was completed in 2015. The trial found that stem cell transplantation was safe in people with ALS. The approach, however, did not slow progression of the disease according to a comparison to 3 historical control groups.

References:
[1] Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials. Glass, JD. et al. Neurology. 2016 Jul 26;87(4):392-400.
[2] Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I trial, cervical microinjection, and final surgical safety outcomes. Riley, J et al. Neurosurgery. 2014 Jan;74(1):77-87.
[3] Human neural stem cell grafts in the spinal cord of SOD1 transgenic rats: differentiation and structural integration into the segmental motor circuitry. Xu, L et al. J Comp Neurol. 2009 Jun 1;514(4):297-309.
ALS Research Forum Reference: http://www.alsresearchforum.org/stem-cell-treatment-reported-safe-following-als-clinical-trial/

Last updated June 21st, 2017
NeuralStemStem Cell TherapyNeuroprotectionALSPhase II
NT-K0-003

NT-K0-003

(Click title to open drug details in a new window.)
Company: Neurotec Pharma
Location: Spain
Website: http://www.neurotec-pharma.com
Drug Type: Small Molecule
Conditions: ALS, multiple sclerosis, stroke
Mechanism Type: Neuroprotection, anti-inflammatory
Mechanism: NT-K0-003 is a small molecule modulator of microglial activity that confer neuroprotection and anti-inflammatory effects. Based on published patents owned by the company, this compound may be diazoxide, a potassium channel activator, or a pharmaceutically accepted salt of diazoxide.
U.S. Status for ALS: Preclinical
R&D Status: A Phase II study of NT-KO-001 for multiple sclerosis was completed in 2014.

References:
[1] Diazoxide For Use In The Treatment Of Amyotrophic Lateral Sclerosis (ALS). FreePatentsOnline, 6 June 2013. Accessed 11 March, 2016 from http://www.freepatentsonline.com/y2013/0143873.html
[2] A Phase IIa Study of NT-KO-003 for Multiple Sclerosis ClinicalTrials.gov, 14 March, 2014. Accessed 11 March 2016 from https://clinicaltrials.gov/ct2/show/NCT01428726

Last updated March 11th, 2017
Neurotec PharmaSmall MoleculeNeuroprotection, anti-inflammatoryALSPreclinical
Neurostem

Neurostem

(Click title to open drug details in a new window.)
Company: Medipost
Location: South Korea
Website: http://www.medi-post.com
Drug Type: Stem Cell Therapy
Conditions: ALS, Alzheimer's disease, stroke
Mechanism Type: Anti-apoptotic, anti-inflammatory, reduction of oxidative stress
Mechanism: The Neurostem therapy consists of mesenchymal stem cells derived from allogeneic umbilical cord blood that are believed to confer therapeutic benefit by inducing the release of therapeutic proteins (i.e.: anti-apoptotic, anti-inflammatory and anti-oxidative stress) from endogenous cells through paracrine actions. The treatment is first being developed to treat Alzheimer's type dementia, but the company aims to also apply it to ALS and stroke.
U.S. Status for ALS: N/A
R&D Status: Medipost is currently conducting a Phase I/II trial of Neurostem for Alzheimer's disease in Korea.

References:
[1] Stem Cell Products - Neurostem. Medipost America, 2015. Accessed 11 Mar 2016 from http://medipostamerica.com/stem-cell-products-overview/adult-stem-cell-drugs/neurostem/.
[2] Safety and Exploratory Efficacy Study of NEUROSTEM Versus Placebo in Patients With Alzheimer's Disease. ClinicalTrials.gov, 6 Jan 2016. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02054208.

Last updated March 11th, 2017
MedipostStem Cell TherapyAnti-apoptotic, anti-inflammatory, reduction of oxidative stressALSN/A
Noscapine

Noscapine

(Click title to open drug details in a new window.)
Company: KineMed
Location: US-California
Website: http://www.kinemed.com
Drug Type: Small Molecule
Conditions: ALS, Parkinson's disease, diabetic neuropathy
Mechanism Type: Microtubule stability modulator
Mechanism: Kinemed is developing noscapine and new analogues for neurodegenerative diseases and fibrotic diseases. Noscapine regulates abnormal microtubule (MT) dynamics, and reverses MT-mediated neuronal transport defects. The company has developed a proprietary technology for assessing MT turnover that is being developed as a biomarker in several neurodegenerative diseases, including ALS.
U.S. Status for ALS: Preclinical
R&D Status: Preclinical

References:
[1] KineMed Receives U.S. Patent Allowance for Noscapine to Treat ALS, Parkinson’s Disease, and Diabetic Neuropathy. BioSpace, 4 Sep 2014. Accessed 9 Mar 2016 from http://www.biospace.com/News/kinemed-inc-receives-u-s-patent-allowance-for/345325.
[2] Kinemed. Neurodegenerative Diseases. Kinemed, n.d. Accessed 9 Mar 2016 from http://www.kinemed.com/Corporate/Core-Areas/Neuro.aspx.

Last updated March 9th, 2017
KineMedSmall MoleculeMicrotubule stability modulatorALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: Aestus Therapeutics
Location: US-New Jersey
Website: http://www.aestustherapeutics.com
Drug Type: Small Molecule
Conditions: ALS, neuropathic pain, epilepsy, schizophrenia
Mechanism Type: Computational analysis, drug repurposing
Mechanism: Targets undisclosed. Aestus Therapeutics developed a proprietary genomic data mining technique to identify well-studied biological pathways that may be implicated in neurological diseases. They then select relevant drug candidates that have already been tested in clinical trials as potential drug candidates for these novel indications.
U.S. Status for ALS: Preclinical
Commercial Information: They company is collaborating with ALS TDI on their ALS program, and in Sept 2011 both announced expansion of the collaboration. No further updates have been made publicly. Aestus was co-founded in 2005 by Dr. Tage Honore and Dr. Lillian Chang. The most recent updates on the company activitiy were in 2011.
R&D Status: Preclinical

References:
[1] ALS Therapy Development Institute and Aestus Therapeutics expand collaboration on development of novel ALS therapies. PRNewsire, 19 Sep 2011. Accessed 27 Dec 2015 from http://www.prnewswire.com/news-releases/als-therapy-development-institute-and-aestus-therapeutics-inc-expand-collaboration-on-development-of-novel-als-therapies-130108413.html.

Last updated February 3rd, 2016
Aestus TherapeuticsSmall MoleculeComputational analysis, drug repurposingALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: Anelixis Therapeutics
Location: US - Massachusetts
Website: http://www.anelixistherapeutics.com/
Drug Type: Small Molecule
Conditions: ALS
Mechanism Type: SOD1 protein aggregation modulator
Mechanism: The company is aiming to identify small molecules that bind the misfolded SOD1 dimer and stabilize it, thereby preventing aggregation and seeding of protein misfolding in wild-type SOD1. Efforts are focused on medicinal chemistry followed by in vivo and in vitro optimization to identify compounds optimized for human testing.
U.S. Status for ALS: Preclinical
Commercial Information: Anelixis Therapeutics is a virtual biotechnology company that is the for-profit subsidiary of ALSTDI.
R&D Status: Preclinical

References:
[1] SOD1 Program. Anelixis Therapeutics, 2016. Accessed 28 Dec 2015 from http://www.anelixistherapeutics.com/SOD1Program.aspx.

Last updated December 28th, 2015
Anelixis TherapeuticsSmall MoleculeSOD1 protein aggregation modulatorALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: Aquinnah Pharmaceuticals
Location: US-Massachusetts
Website: http://www.aquinnahpharma.com/
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's disease
Mechanism Type: TDP-43 protein aggregation
Mechanism: Drugs that disaggregate and prevent formation of TDP-43 positive, RNA stress granules.
U.S. Status for ALS: Preclinical
Commercial Information: Co-founded by Dr. Benjamin Wolozin from Boston University.
R&D Status: Preclinical

References:
[1] Aquinnah Pharmaceuticals Receives $5 Million Investment from Takeda Pharmaceuticals To Advance New Therapies in ALS. PR Newswire, 21 Dec 2015. Accessed 28 Dec 2015 from http://www.prnewswire.com/news-releases/aquinnah-pharmaceuticals-receives-5-million-investment-from-takeda-pharmaceuticals-to-advance-new-therapies-in-als-300195607.html.

Last updated December 28th, 2015
Aquinnah PharmaceuticalsSmall MoleculeTDP-43 protein aggregationALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: Denali Therapeutics
Location: US-California
Website: http://www.denalitherapeutics.com/
Drug Type: Unspecified
Conditions: ALS, Alzheimer's disease, Parkinson's disease
Mechanism Type: Unspecified target. Modifiers of intracellular trafficking pathways, inflammation, axon degeneration and synapse elimination.
Mechanism: The company is leveraging new discoveries on genetics of neurodegenerative diseases to identify promising new therapeutic targets and therapies for neurodegenerative disease, with a focus on targets belonging to intracellular trafficking pathways, inflammation, axon degeneration and synapse elimination.
U.S. Status for ALS: Preclinical
Commercial Information: Denali was founded with a record-setting $217M Series A financing. The company was founded by Marc Tessier-Lavigne, currently President of Rockefeller University and Professor and Head of the Laboratory of Brain Development and Repair and formerly Head of Research at Genentech, Ryan Watts, previously Director of the Department of Neuroscience at Genentech, and Alexander Schuth, formerly Director and Head Technology and Diagnostics Partnering at Genentech. In March 2016, Denali announced a partnership with ALS TDI to investigate potential new endpoints for clinical trials in ALS using data generated through the ALS TDI precision medicine initiative.
R&D Status: Preclinical

References:
[1] Denali Therapeutics. FierceBiotech's 2015 Fierce 15. FierceBiotech, 27 Sep 2015. Accessed 9 Mar 2016 from http://www.fiercebiotech.com/special-reports/denali-therapeutics-2015-fierce-15.
[2] ALS Therapy Development Institute to Explore New Clinical Trial Endpoints with Denali Therapeutics. ALS Therapy Development Institute, 28 Mar 2016. Accessed 29 Mar 2016 from http://www.als.net/news/als-therapy-development-institute-to-explore-new-clinical-trial-endpoints-with-denali-therapeutics/.

Last updated March 28th, 2016
Denali TherapeuticsUnspecifiedUnspecified target. Modifiers of intracellular trafficking pathways, inflammation, axon degeneration and synapse elimination.ALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: ProMIS Neurosciences
Location: Canada
Website: http://www.promisneurosciences.com/
Drug Type: Vaccine, Protein Biologic
Conditions: ALS, Alzheimer's disease
Mechanism Type: SOD1 aggregation inhibitor
Mechanism: ProMIS is developing therapeutic approaches for immunization against disease-specific epitopes (DSE) of misfolded or aggregated mutant superoxide dismutase-1 (SOD-1). The company uses a dual approach of passive immunization with anti-SOD1 monoclonal antibodies, in combination with activate immunization with an anti-SOD1 vaccine to produce antibodies in the patient's body. The vaccine is expected to eliminate the misfolded protein, while sparing wild-type SOD-1.
U.S. Status for ALS: Preclinical
Commercial Information: The company changed its name from Amorfix Life Sciences to ProMIS Neurosciences in July, 2015. The company is based around research from the laboratory of scientist Dr. Neil Cashman, Professor of Medicine at the University of British Columbia
R&D Status: Preclinical

References:
[1] Promis Neurosciences. Promis Neurosciences, 2016. http://promisneurosciences.com/company/. Accessed 9 Mar 2016.

Last updated March 9th, 2016
ProMIS NeurosciencesVaccine
Protein Biologic
SOD1 aggregation inhibitorALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: Verge Genomics
Location: US-California
Website: http://www.vergegenomics.com/
Drug Type:
Conditions: ALS, Alzheimer's disease, Parkinson's disease
Mechanism Type: Computational analysis
Mechanism: Verge Genomics is applying network algorithms to large-scale gene expression data to map out clusters of co-regulated genes implicated in neurodegenerative diseases, including in ALS. They then examine publicly-available information to identify FDA-approved drugs that can be tested to affect the gene clusters of interest.
U.S. Status for ALS: Preclinical
Commercial Information: The company was launched out of the YCombinator accelerator program by Alice Zhang and Jason Chen, both from the University of California, Los Angeles - Caltech MD/PhD program.
R&D Status: Preclinical

References:
[1] Verge Genomics Wants To Cure Neurodegenerative Diseases Through Advanced Algorithms. Crook, J. TechCruch, 21 Jul 2015. Accessed 11 Mar 2016 from http://techcrunch.com/2015/07/21/verge-genomics-wants-to-cure-neurodegenerative-diseases-through-advanced-algorithms/.
[2] A multiancestral genome-wide exome array study of Alzheimer disease, frontotemporal dementia, and progressive supranuclear palsy. Chen, JA et al. JAMA Neurol. 2015 Apr;72(4):414-22.

Last updated March 11th, 2016
Verge GenomicsComputational analysisALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: Yumanity Therapeutics
Location: US-Massachusetts
Website: http://www.yumanity.com
Drug Type: Small Molecule
Conditions: ALS, Parkinson's disease, Alzheimer's disease
Mechanism Type: Protein misfolding regulators
Mechanism: Yumanity’s innovative new approach to drug discovery and development concentrates on reversing the cellular phenotypes and disease pathologies caused by protein misfolding. Yumanity's discovery platform combines high-throughput screening in yeast cells with a human neural platform composed of induced pluripotent stem cells from patients, which allows for iterative and parallel analysis of results in both systems. In addition, the company has a drug-target identification platform that leverages yeast genetics and analysis of protein networks to identify drug targets. The company's lead candidate is for Parkinson's disease.
U.S. Status for ALS: Preclinical
Commercial Information: Formed in 2014 by former CEO of Onyx Pharmaceuticals, Tony Coles, MD, and protein folding science pioneer, Prof. Susan Lindquist, PhD, from Massachusetts Institute of Technology in Cambridge, MA.
R&D Status: Preclinical

References:
[1] From yeast to patient neurons and back again: powerful new discovery platform. Tardiff, DF et al. Mov Disord. 2014 Sep;29(10):1231-40.

Last updated March 11th, 2016
Yumanity TherapeuticsSmall MoleculeProtein misfolding regulatorsALSPreclinical
Not Disclosed

Not Disclosed

(Click title to open drug details in a new window.)
Company: miCure Therapeutics
Location: Israel
Website: http://www.micurerx.com
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: MicroRNA therapeutics
Mechanism: miCure Therapeutics is developing microRNA-based therapeutics for CNS disorders. The company is pursuing an approach to treat ALS by restoring microRNA expression to their endogenous levels.
U.S. Status for ALS: Preclinical
Commercial Information: The company was founded based on technologies developed by Prof. Alon Chen and Dr. Eran Hornstein of the Weizmann Institute of Science in Rehovot, Israel.
R&D Status: Preclinical

References:
[1] miCure Therapeutics Areas of Focus. miCure Therapeutics, 2013. Accessed 11 Mar 2016 from http://www.micurerx.com/#!-areas-of-focus/caob

Last updated March 11th, 2017
miCure TherapeuticsGene TherapyMicroRNA therapeuticsALSPreclinical
Not Disclosed (RIPK1 Inhibitor)

Not Disclosed (RIPK1 Inhibitor)

(Click title to open drug details in a new window.)
Company: Denali Therapeutics
Website: http://www.denalitherapeutics.com
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's Disease
Mechanism Type: Neuroprotection
Mechanism: An RIPK1 kinase inhibitor. This drug aims to protect motor neurons by blocking necroptosis, which may destroy motor neurons in ALS.
U.S. Status for ALS: Preclinical
Commercial Information: This drug is licensed from Harvard University. It is based on the work of Junying Yuan at Harvard Medical School.
R&D Status: A phase I clinical trial of healthy volunteers is planned in Europe.

References:
[1] Ito, Y. et al. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science. 2016 Aug 5;353(6299):603-8.
ALS Research Forum Reference: http://www.alsresearchforum.org/targeting-ripk1-may-increase-granularity-in-ftd/
Denali TherapeuticsSmall MoleculeNeuroprotectionALSPreclinical
Nuedexta

Nuedexta

(Click title to open drug details in a new window.)
Company: Avanir Pharmaceuticals
Location: US-California
Website: http://www.avanir.com
Drug Type: Small Molecule
Conditions: ALS, pseudobulbar affect
Mechanism Type: Sigma-1 receptor, NMDA receptor
Mechanism: Nuedexta is Avanir's first-in-class dual action drugs, which acts on both sigma-1 receptors and NMDA receptors. The precise mechanism of action is not known. Nuedexta diminishes the unpredictable emotional episodes of pseudobulbar affect (PBA) according to clinical studies (Schoedel et al., 2014).
U.S. Status for ALS: FDA Approved
Commercial Information: The active ingredient of Nuedexta is dextromethorphan. The drug is stabilized through a formulation which contains quinidine sulfate.
R&D Status: The drug is FDA-approved for treating pseudobulbar affect (emotionality) which can occur in many neurological disorders including ALS and FTD. More recently, however, the drug has been shown to help some patients with ALS speak, swallow and reduce salivation (Smith et al., 2017).

References:
[1] Enhanced Bulbar Function in Amyotrophic Lateral Sclerosis: The Nuedexta Treatment Trial. Smith, R. et al. Neurotherapeutics. 2017 Jan 9.
[2] Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect. Schoedel, KA et al. Neuropsychiatr Dis Treat. 2014 Jun 26;10:1161-74.
[3] Clinical Trial Nuedexta in Subjects With ALS. ClinicalTrials.gov, 18 Feb 2015. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT01806857.
ALS Research Forum Reference: http://www.alsresearchforum.org/help-for-speech-swallowing-and-salivation-problems-in-als/

Last updated June 21st, 2017
Avanir PharmaceuticalsSmall MoleculeSigma-1 receptor, NMDA receptorALSFDA Approved
NurOwn

NurOwn

(Click title to open drug details in a new window.)
Company: BrainStorm Cell Therapeutics
Location: Israel
Website: http://www.brainstorm-cell.com/
Drug Type: Stem Cell Therapy
Conditions: ALS, multiple sclerosis, Parkinson's disease, Huntington's disease.
Mechanism Type: Neuroprotection
Mechanism: NurOwn is a platform containing autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a possible treatment for patients with ALS.
U.S. Status for ALS: Phase II
R&D Status: Phase II studies for ALS have been completed in Israel and the United States. Other neurological diseases are in preclinical phase.

References:
[1] Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. Petrou P et al. JAMA Neurol. 2016 Mar;73(3):337-44.
[2] Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS (NurOwn). ClinicalTrials.gov, 13 Jan 2016. Accessed 9 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02017912.

Last updated June 29th, 2017
BrainStorm Cell TherapeuticsStem Cell TherapyNeuroprotectionALSPhase II
Olesoxime

Olesoxime

(Click title to open drug details in a new window.)
Company: Roche Pharmaceuticals
Location: Switzerland
Website: http://www.roche.com
Drug Type: Small Molecule
Conditions: ALS, Spinal Muscular Atrophy
Mechanism Type: Mitochondrial function modulator, neuroprotection
Mechanism: Olesoxime is a cholesterol-oxime compound that targets and preserves mitochondrial integrity and function under conditions of cellular stress by modulating the mitochondrial permeability transition pore, and as a result promotes the function and survival of neurons and other cell types under disease-relevant stress conditions. The compound improved muscle function and reduced astrogliosis and microglial activation in preclinical studies in SOD1 ALS mouse models, but failed Phase III trials in ALS.
U.S. Status for ALS: Discontinued
Commercial Information: The company Trophos was developing olesoxime for ALS, but it failed to show a statistically significant effect in a Phase III clinical trial in ALS in Europe, so the company discontinued development of the compound for ALS. This asset was aquired by Roche from Trophos in early 2015.
R&D Status: A Phase III, double-blind, placebo-controlled clinical trial of olexosime as add-on therapy to riluzole in 512 people with ALS over 18 months conducted in Europe failed to yield a clinically significant improvement in the 18 month survival rate (Lenglet et al., 2014). The company has shifted it focus for this drug to spinal muscular atrophy (SMA) and a Phase II clinical trial to evaluate long term safety, tolerability and effectiveness of olesoxime is ongoing. Trophos was granted orphan drug designation for olesoxime by the US FDA.

References:
[1] Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS) (MITOTARGET) ClinicalTrials.gov, 27 Mar 2012. Accessed 16 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT00868166.
[2] A Study to Evaluate Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy. ClinicalTrials.gov, 1 Mar 2016. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02628743.
[3] A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis. Lenglet, T. et al. Eur J Neurol. 2014 Mar;21(3):529-36.
[4] Olesoxime delays muscle denervation, astrogliosis, microglial activation and motoneuron death in an ALS mouse model. Sunyach, C et al. Neuropharmacology. 2012 Jun;62(7):2346-52.
ALS Research Forum Reference: http://www.alsresearchforum.org/news-brief-als-drug-olesoxime-fails-in-phase-3-trial/

Last updated June 21st, 2017
Roche PharmaceuticalsSmall MoleculeMitochondrial function modulator, neuroprotectionALSDiscontinued
OptiKira - Unspecifed

OptiKira - Unspecifed

(Click title to open drug details in a new window.)
Company: OptiKira
Location: US-California
Website: http://www.optikira.com
Drug Type: Small Molecule
Conditions: ALS, diabetes, retinites pigementosa
Mechanism Type: Unfolded protein response regulator
Mechanism: OptiKira's technology platform targets cell death linked to unfolded or misfolded proteins. OptiKira is developing inhibitors of the unfolded protein response, specifically of inositol-requiring enzyme-1a (IRE1a), a key activation step in the unfolded protein response (UPR). The technology has applications for ALS, although the company's current focus is diabetes and retinitis pigementosa.
U.S. Status for ALS: Preclinical
Commercial Information: OptiKira was launched in 2015 by BioMotiv, the mission-driven accelerator associated with The Harrington Project for Discovery and Development. The technologies licensed by the company were developed in the laboratories of Scott Oakes and Feroz Papa at the University of California San Francisco and Bradley Backes (UCSF) and Dustin Maly (University of Washington).
R&D Status: Preclinical

References:
[1] OptiKira, a New Biotech Start-up, Created to Develop Drugs to Prevent Cell Death Caused by the Unfolded Protein Response. PR Newswire, 2 Feb 2015. Accessed 11 Mar 2016 from http://www.prnewswire.com/news-releases/optikira-a-new-biotech-start-up-created-to-develop-drugs-to-prevent-cell-death-caused-by-the-unfolded-protein-response-300028909.html.

Last updated March 11th, 2017
OptiKiraSmall MoleculeUnfolded protein response regulatorALSPreclinical
Ozanezumab

Ozanezumab

(Click title to open drug details in a new window.)
Company: GlaxoSmithKline, GSK
Location: United Kingdom
Website: http://www.gsk.com
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: Axon regeneration
Mechanism: Ozanezumab (GSK 1223249) is a neurite outgrowth inhibitor (NOGO-A) monoclonal antibody. The rationale for testing ozanezumab in ALS is supported by evidence that NOGO is overexpressed in skeletal muscle of ALS patients, and inhibiting its expression may promote axonal sprouting of new neurites.
U.S. Status for ALS: Discontinued
R&D Status: As Phase II trial in ALS was completed. Primary endpoints were joint rank analysis of function via ALSFRS, and survival. The results indicated a non-significant difference in the joint rank score in favor of placebo (difference -30, P =.120), and all secondary efficacy endpoints supported this finding.

References:
[1] Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial. Meininger, V et al. Lancet Neurol. 2017 Mar;16(3):208-216.
[2] Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis. ClinicalTrials.gov, 9 Jul 2015. Accessed 9 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT01753076.

Last updated June 21st, 2017
GlaxoSmithKline, GSKProtein BiologicAxon regenerationALSDiscontinued
Q-cells

Q-cells

(Click title to open drug details in a new window.)
Company: Q Therapeutics
Location: US-Utah
Website: http://www.qthera.com/
Drug Type: Stem Cell Therapy
Conditions: ALS, transverse myelitis, multiple scleorsis, spinal cord injury
Mechanism Type: Neuroprotection
Mechanism: Q-cells are purified human glial-restricted progenitors derived from human fetal neural tissue. In rats overexpressing mutant superoxide dismutase (SOD1), transplanted glial-restricted precursors prolong lifespan, reduce microgliosis, improve motor neuron survival and attenuate decline in motor and respiratory function. In SOD1 mice, transplantation did not attenuate motor neuron death or improve survival, however, the glial-restricted progenitors survived and differentiated into astrocytes in the spinal cord.
U.S. Status for ALS: Phase I/IIa
Commercial Information: Q Therapeutics has exclusive worldwide rights to the Q-Cells product through a license from University of Utah Research Foundation and through internally-developed intellectual property.
R&D Status: Q-cells were granted FDA orphan drug designation in 2014 for ALS. A Phase I/II clinical trial in ALS is listed but not yet open for recruitment.

References:
[1] Study to Investigate the Safety of the Transplantation (by Injection) of Human Glial Restricted Progenitor Cells (hGRPs; Q-Cells) Into Subjects With Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov, 18 Jun 2015. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02478450.
[2] Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Lepore, AC et al. Nat Neurosci. 2008 Nov;11(11):1294-301.
[3] Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS. Lepore, AC et al. PLoS One. 2011;6(10):e25968.
ALS Research Forum Reference: http://www.alsresearchforum.org/q-therapeutics-gains-fda-clearance-to-initiate-clinical-trials-in-als/

Last updated June 21st, 2017
Q TherapeuticsStem Cell TherapyNeuroprotectionALSPhase I/IIa
RDC5

RDC5

(Click title to open drug details in a new window.)
Company: Chronos Therapeutics
Location: United Kingdom
Website: http://www.chronostherapeutics.com
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's disease, Parkinson's disease, Huntington's disease
Mechanism Type: Autophagy regulator
Mechanism: RDC5 increases autophagy and protein turnover in cells. Additional activated pathways include repair of DNA damage, as reducing oxidative stress. Chronos has tested RDC5 in both a C. elegan SOD1 model and in SOD1 and TDP-43 mouse models. RDC5 was protective in the C. elegans model, showing a decreased toxicity and a decrease in the level of toxic protein aggregates.
U.S. Status for ALS: N/A
R&D Status: A Phase I clinical trial was completed in healthy volunteers.

References:
[1] A Phase 1 Study of the Pharmacokinetics of RDC5 in Healthy Volunteers. ClinicalTrials.gov, 11 Mar 2014. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02016742.

Last updated March 9th, 2016
Chronos TherapeuticsSmall MoleculeAutophagy regulatorALSN/A
RNS60

RNS60

(Click title to open drug details in a new window.)
Company: Revalesio Corporation
Location: US-Washington
Website: http://www.revalesio.com
Drug Type: Nanoparticle, Small Molecule
Conditions: ALS
Mechanism Type: Immunomodulation, Neuroprotection
Mechanism: RNS60 is an aqueous fluid composed of oxygen and saline that has been electrokinetically altered using Revalesio's patented technology to create charge-stabilized nanostructures. RNS60 modulates the PI3K-Akt pathway, a central pathway responsible for multiple cellular functions including cellular protection from apoptosis, and suppression of inflammation. RNS60 has also been shown to possitively affect mitochondrial bioenergetics.
U.S. Status for ALS: Phase I, Phase II
R&D Status: RNS60 was well tolerated in three phase I clinical trials, one after intravenous administration and two after inhalation. A Phase II study in ALS has opened for enrollment.

References:
[1] A Pilot Study of RNS60 in Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov, 30 Dec 2015. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02525471.
[2] A physically-modified saline suppresses neuronal apoptosis, attenuates tau phosphorylation and protects memory in an animal model of Alzheimer's disease. Modi KK, Jana A, Ghosh S, Watson R, Pahan K. PLoS One. 2014;9(8):e103606.

Last updated March 11th, 2016
Revalesio CorporationNanoparticle
Small Molecule
Immunomodulation, NeuroprotectionALSPhase I, Phase II
Retigabine

Retigabine

(Click title to open drug details in a new window.)
Company: GlaxoSmithKline, GSK
Drug Type: Small Molecule
Conditions: ALS, Epilepsy
Mechanism Type: Neuronal hyperexcitability
Mechanism: Retigabine is a Kv7 potassium channel activator that may reduce neuronal hyperexcitability by helping neurons return to the resting state upon firing.
U.S. Status for ALS: Phase II
Commercial Information: The drug is no longer commercially available after June 30, 2017.
R&D Status: The phase 2 clinical trial of retigabine in ALS is ongoing. The study aims to determine the safety and tolerability of retigabine in people with ALS. The study also plans to determine whether retigabine reduces motor neuron hyperexcitability in people with the disease.

References:
[1] Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Wainger, BJ et al., Cell Rep. 2014 Apr 10;7(1):1-11.
ALS Research Forum Reference: http://www.alsresearchforum.org/a-key-ion-channel-may-slack-off-in-als/
GlaxoSmithKline, GSKSmall MoleculeNeuronal hyperexcitabilityALSPhase II
rhVEGF165

rhVEGF165

(Click title to open drug details in a new window.)
Company: NeuroNova
Location: Sweden
Website: http://www.neuronova.com
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: Neuroprotection
Mechanism: sNN0029 is a formulation of vascular endothelial growth factor (VEGF) protein that is suitable for administration into the central nervous system. The drug will be delivered via intracerebroventricular infusion. Multiple studies have shown that VEGF expression is impaired in ALS, and that VEGF treatment ameliorates disease in ALS mouse models.
U.S. Status for ALS: Discontinued
Commercial Information: Neuronova was acquired by Newron Pharmaceuticals in 2012.
R&D Status: The company announced initiation of a Phase II study in ALS, but the studies have been terminated, due to issues with development and supples of the infusion system and lack of favorable benefit risk ratio based on review of interim data.

References:
[1] Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Storkebaum, E et al. Nat Neurosci. 2005 Jan;8(1):85-92.
[2] An Open Label, Safety and Tolerability Continuation Study of Intracerebroventricular Administration of sNN0029 to Patients With Amyotrophic Lateral Sclerosis. ClinicalTrials.gov, 26 Jan 2016. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT01384162.
ALS Research Forum Reference: http://www.alsresearchforum.org/newron-pharmaceuticals-embarking-on-phase-ii-clinical-trial-for-vegf-therapy-in-als/

Last updated June 21st, 2017
NeuroNovaProtein BiologicNeuroprotectionALSDiscontinued
RhinoCyte Cells

RhinoCyte Cells

(Click title to open drug details in a new window.)
Company: RhinoCyte
Location: US-Kentucky
Website: http://www.rhinocyte.com/
Drug Type: Stem Cell Therapy
Conditions: ALS, Parkinson's disease, multiple sclerosis, spinal cord injury.
Mechanism Type: Unspecified
Mechanism: RhinoCyte develops therapies based on autologous adult olfactory-derived neural progenitor stem cells (RhinoCytes). It is unclear whether this program is active.
U.S. Status for ALS: Preclinical
Commercial Information: The company was founded in partnership with MetaCyte Business Lab, LLC.
R&D Status: Preclinical. RhinoCyte Cells were granted Orphan Drug Designation for use in treatment of ALS in 2009.

References:
[1] RhinoCyte - Our Research. RhinoCyte, 2016. Accessed 11 Mar 2016 from http://www.rhinocyte.com/.
[2] Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery. Xiao M et al. Neurobiol Dis. 2007 May;26:363-374.

Last updated March 11th, 2016
RhinoCyteStem Cell TherapyUnspecifiedALSPreclinical
Riluzole (Rilutek)

Riluzole (Rilutek)

(Click title to open drug details in a new window.)
Company: Covis Pharma
Location: Switzerland, US-North Carolina
Website: http://www.covispharma.com.
Drug Type: small molecule
Conditions: ALS, Alzheimer's disease, Parkinson's disease, Huntington's disease
Mechanism Type: Glutamate Excitotoxicity Blocker
Mechanism: Riluzole is a benzothiazole. Its mechanism of action is unknown, but its pharmacological properties include inhibition of glutamate release, inactivation of voltage-dependent sodium channels, modulation of signaling pathways activated by neurotransmitter binding to excitatory amino acid receptors (EAAT2).
U.S. Status for ALS: FDA Approved
Commercial Information: Covis Pharma Sarl acquired the commercial rights to Rilutek from Sanofi-aventis in the U.S. in 2013.
R&D Status: Riluzole is the first FDA approved disease-modifying therapy for ALS. The effect on survival is moderate, and the drug prolongs survival by an estimated 2-6 months. It is in Phase II clinical trials for Alzheimer's disease, and has been discontinued for Parkinson's and Huntington's diseases due to lack of effect.

References:
[1] Rilutek (riluzole). Sanofi-aventis, 2008. Accessed 11 Mar 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020599s011s012lbl.pdf.
[2] Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lacomblez, L et al. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet. 1996 May 25;347(9013):1425-31.
[3] A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. Bensimon, G et al. N Engl J Med. 1994 Mar 3;330(9):585-91.
[4] Riluzole in mild Alzheimer's disease. ClinicalTrials.gov, 2 Mar 2016. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT01703117.
[5] Riluzole in Huntington's disease: a 3-year, randomized controlled study. Landwehrmeyer GB et al. Ann Neurol. 2007 Sep;62(3):262-72.
[6] Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Bensimon G et al. Brain. 2009 Jan;132(Pt 1):156-71.

Last updated March 11th, 2017
Covis Pharmasmall moleculeGlutamate Excitotoxicity BlockerALSFDA Approved
SB-509

SB-509

(Click title to open drug details in a new window.)
Company: Sangamo Biosciences
Location: US-California
Website: http://www.sangamo.com
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: Neuroprotection
Mechanism: SB-509 is an injectable formulation of a plasmid encoding a zinc finger DNA-binding protein transcription factor designed to upregulate the expression of the gene encoding vascular endothelial growth factor (VEGF-A).
U.S. Status for ALS: Discontinued
Commercial Information: Sangamo acquired Ceregene in 2013;
R&D Status: In 2010, Sangamo Biosciences completed a Phase II clinical trial to evaluate their drug, SB-509, in subjects with ALS. The company does not appear to have plans for further developing this drug for ALS.

References:
[1] Clinical Trial of SB-509 in Subjects With Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov, 30 Oct 2012. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT00748501.

Last updated March 11th, 2016
Sangamo BiosciencesGene TherapyNeuroprotectionALSDiscontinued
SB618

SB618

(Click title to open drug details in a new window.)
Company: SanBio
Location: US-California
Website: http://www.san-bio.com
Drug Type: Stem Cell Therapy
Conditions: multiple sclerosis, spinal cord injury
Mechanism Type: Myelination
Mechanism: SB618 is a stem cell therapy based on genetic manipulation of autologous bone marrow stromal cells. SB618 is being developed for the treatment of disorders that have myelin sheath degeneration, including multiple sclerosis and spinal cord injury.
U.S. Status for ALS: N/A
R&D Status: Preclinical

References:
[1] SanBio Product Pipeline. SanBio, 2016. Accessed 11 Mar 016 from http://www.san-bio.com/product/.

Last updated March 11th, 2016
SanBioStem Cell TherapyMyelinationMultiple sclerosisN/A
SB623

SB623

(Click title to open drug details in a new window.)
Company: SanBio
Location: US-California
Website: http://www.san-bio.com
Drug Type: Stem Cell Therapy
Conditions: stroke, traumatic brain injury, retinal diseases, Parkinson's disease, spinal cord injury
Mechanism Type: Neural regeneration
Mechanism: SB623 is a stem cell therapy based on genetic manipulation of autologous bone marrow stromal cells. SB623 reverses neural damage by stimulating the natural regenerative process. In preclinical studies, SB623 restored function to neurons that were damaged by Parkinson's disease, stroke or spinal cord injury. The company has suggested that SB623 might hold potential for other diseases, such as ALS and Huntington's disease.
U.S. Status for ALS: N/A
R&D Status: A Phase II clinical trial is recruiting for patients with chronic motor deficits from ischemic stroke. A Phase II clinical trial to evaluate safety and efficacy in traumatic brain injury is also ongoing.

References:
[1] A Study of Modified Stem Cells in Traumatic Brain Injury (TBI) (STEMTRA). I Study of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke (ACTIsSIMA). ClinicalTrials.gov, 4 Mar 2016. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02416492.

Last updated March 11th, 2016
SanBioStem Cell TherapyNeural regenerationStrokeN/A
SF0034

SF0034

(Click title to open drug details in a new window.)
Company: SciFluor
Location: US-Massachusetts
Website: http://scifluor.com/our-approach/our-approach-fluoro.php
Drug Type: Small Molecule
Conditions: ALS, Epilepsy, Tinnitus
Mechanism Type: Neuronal hyperexcitability - Retigabine derivative
Mechanism: SF0034 is a KCNQ2/3-specific channel activator that aims to reduce neuronal hyperexcitability by enabling neurons to return to the resting state upon firing. The drug is a fluorinated-derivative of the FDA-approved epilepsy drug retigabine.
U.S. Status for ALS: Preclinical
Commercial Information: Researchers in the laboratory of Thanos Tzounopoulos at the University of Pittsburgh in Pennsylvania developed SF0034 in hopes to improve the safety and selectivity, and thereby reduce the side effects of retigabine.

References:
[1] Potent KCNQ2/3-Specific Channel Activator Suppresses In Vivo Epileptic Activity and Prevents the Development of Tinnitus Kalappa, BI et al. Journal of Neuroscience. 10 June 2015, 35 (23) 8829-8842.
SciFluorSmall MoleculeNeuronal hyperexcitability - Retigabine derivativeALSPreclinical
SR-3306

SR-3306

(Click title to open drug details in a new window.)
Company: Opko Health
Location: USA-Florida
Website: http://www.opko.com
Drug Type: Small Molecule
Conditions: Parkinson's disease
Mechanism Type: MAPK inhibitor, neuroprotection, anti-apoptotic
Mechanism: SR3306 is an orally bioavailable, aminopyrimidine inhibitor of c-Jun N-terminal kinases (JNKs), a class of mitogen-activated protein kinases (MAPK) that respond to conditions of stress and regulate neuronal survival. The compound has demonstrated oral bioavailability and CNS penetration in animal models, as well as efficacy in two animal models of Parkinson's disease. The mechanism of action is potentially relevant to ALS due to a evidence for link between JNK activation and TDP-43 toxicity.
U.S. Status for ALS: N/A
Commercial Information: Opko is developing SR3306 under an exclusive license from the Scripps Research Institute, and preclinical testing is being conducted in Philip LoGrasso's laboratory at the Scripps Research Institute in Jupiter, FL.
R&D Status: N/A

References:
[1] JNK Inhibition Protects Dopamine Neurons and Provides Behavioral Improvement in a Rat 6-Hydroxydopamine Model of Parkinson’s Disease. Crocker, C et al. ACS Chem Neurosci. 2011 Apr 20;2(4):207-212.
[2] The JNK/c-Jun signaling axis contributes to the TDP-43-induced cell death. Suzuki, H, Matsuoka, M. Mol Cell Biochem. 2013 Jan;372(1-2):241-8.

Last updated March 11th, 2017
Opko HealthSmall MoleculeMAPK inhibitor, neuroprotection, anti-apoptoticParkinson's diseaseN/A
SUN11031

SUN11031

(Click title to open drug details in a new window.)
Company: Daiichi Sanyo, Inc
Location: US-New Jersey
Website: http://www.dsi.com/home
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: Promoting appetite (Cachexia)
Mechanism: SUN11031 is a peptide hormone that is a ghrelin receptor agonist (it is a synthetic form of ghrelin). In preclinical studies in the SOD1 models of ALS, ghrelin attenuated disease progression through orexigenic effects (promoting appetite), as well as by preventing muscle wasting and weight loss via non-oregigenic effects.
U.S. Status for ALS: Inactive
Commercial Information: In 2015, Asubio Pharmaceuticals merged with Daiichi Sanyo's US subsidiary. Previously, in 2013, Asubio Pharmaceuticals presented preclinical studies on the beneficial effects of ghrelin receptor agonist in ALS mouse models. The program appears to have been discontinued.
R&D Status: A Phase II study in Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD) was completed.

References:
[1] Ghrelin attenuates disease progression in a mouse model of amyotrophic lateral sclerosis. Matsuo, T et al. F1000Posters 2014, 5:29 (poster). Accessed 28 Dec 2015 from http://f1000research.com/posters/1094908.
[2] SUN11031 in Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD). ClinicalTrials.gov, 19 Oct 2015. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT00698828.

Last updated December 28th, 2015
Daiichi Sanyo, IncProtein BiologicPromoting appetite (Cachexia)ALSInactive
SUN13837

SUN13837

(Click title to open drug details in a new window.)
Company: Daiichi Sanyo, Inc
Location: US-New Jersey
Website: http://www.dsi.com/home
Drug Type: Small Molecule
Conditions: spinal cord injury
Mechanism Type: Neuroprotection
Mechanism: SUN13837 acts by a similar mechanism to basic fibroblast growth factor (bFGF), and binds the FGF receptor. In preclinical studies, it was shown to promote axonal regrowth and exert neuroprotective effects again glutamate excitotoxicity. SUN13837 is a highly lipid soluble small molecule that can be administered through peripheral intravenous injection.
U.S. Status for ALS: N/A
Commercial Information: In 2015, Asubio Pharmaceuticals merged with Daiichi Sanyo's US subsidiary.
R&D Status: A phase II study in spinal cord injury was completed. A phase II study in stroke was withdrawn prior to enrollment (due to business considerations).

References:
[1] Daiichi Sankyo's U.S. Subsidiary Merges with Asubio Pharma. Genetic Engineering & Biotechnology News, 1 Apr 2015. Accessed 3 Mar 2016 from http://www.genengnews.com/gen-news-highlights/daiichi-sankyo-s-u-s-subsidiary-merges-with-asubio-pharma/81251099/.
[2] Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of SUN13837 Injection in Adult Subjects With Acute Spinal Cord Injury (ASCI). ClinicalTrials.gov, 19 Oct 2015. Accessed 3 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT01502631/.

Last updated January 1st, 1970
Daiichi Sanyo, IncSmall MoleculeNeuroprotectionSpinal cord injuryN/A
TANA

TANA

(Click title to open drug details in a new window.)
Company: ImStar Therapeutics
Location: Canada
Website: http://www.imstartx.com/
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: TDP-43 aggregation modulator
Mechanism: ImStar is developing small molecules and single chain variable domain antibodies targeting TAR DNA binding protein 43 (TDP-43) and TDP-43-associated nuclear factor-kB (NFkB) activation (TANA). TDP-43 abnormally accumulates ad aggregates in the cytoplasm of the vast majority of ALS patients. In addition, recent studies have shown that TDP-43 activates NFkB, and may increase inflammation via this pathway.
U.S. Status for ALS: Preclinical
Commercial Information: The company was co-founded by Dr. Jean-Pierre Julien from Laval University. The last update from the company was in January 2014.
R&D Status: Preclinical

References:
[1] ImStar Therapeutics. Pipeline. ImStar Therapeutics, n.d. Pipeline. Accessed 9 Mar 2016 from http://imstartx.com/pipeline.html.
[2] Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kappaB-mediated pathogenic pathways. Swarup, V et al. J Exp Med. 2011 No 21;208(12):2429-47.

Last updated March 9th, 2017
ImStar TherapeuticsProtein BiologicTDP-43 aggregation modulatorALSPreclinical
TDI-846

TDI-846

(Click title to open drug details in a new window.)
Company: ALS Therapy Development Institute
Location: US-Massachusetts
Website: http://www.als.net
Drug Type: Protein Biologic
Conditions: ALS
Mechanism Type: Immunomodulation
Mechanism: TDI-846 (blocking antibody to CD40L) is designed to modulate the immune response associated with disease progression in ALS.
U.S. Status for ALS: Preclinical
Commercial Information: ALSTDI has licensed its CD40L antibody program to Anelixis Therapeutics. ALSTDI is collaborating with Biogen and UCB Pharma on development of a newer version of the anti-CD40L antibody called CDP7657. For full details of the ALS TDI pipeline click here: http://www.alstdi.org/als-research/.
R&D Status: Preclinical

References:
[1] From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis. Lincecum JM et al. Nat Genet. 2010 May;42(5):392-9.
[2] AntiCD40L (TDI28). ALS Therapy Development Institute, 2016. Accessed 9 Mar 2016 from http://www.alstdi.org/als-research/als-topics/anticd40l/.

Last updated March 9th, 2016
ALS Therapy Development InstituteProtein BiologicImmunomodulationALSPreclinical
TW001

TW001

(Click title to open drug details in a new window.)
Company: Treeway
Location: Netherlands
Website: http://www.treeway.nl/
Drug Type: Small Molecule
Conditions: ALS
Mechanism Type: Anitoxidant
Mechanism: TW001 is an oral formulation of the free radical scavenger edaravone. Edaravone, marketed under the name Radicut and Radicava, is approved for the treatment of ALS in Japan and South Korea. But this therapy requires frequent intravenous infusions. TW001 is being developed in hopes to provide an option for people with ALS that is easier and more convenient to administer.
U.S. Status for ALS: Phase I
R&D Status: TW001 was granted orphan drug designation by the FDA and the EMA. In two Phase I studies of TW001 in healthy volunteers and ALS patients, the drugs was safe and well tolerated. A Phase II/III study is planned.

References:
[1] Treeway Announces Positive Data From Two Separate Phase I TW001 Clinical Trials. B3Newswire, 10 Dec 2015. Accessed 21 June 2017.
ALS Research Forum Reference: http://www.alsresearchforum.org/treeways-tw001-shows-promising-results-in-two-clinical-trials-in-als/

Last updated June 21st, 2017
TreewaySmall MoleculeAnitoxidantALSPhase I
TW002

TW002

(Click title to open drug details in a new window.)
Company: Treeway
Location: Netherlands
Website: http://www.treeway.nl/
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: Neuroprotection
Mechanism: TW002 is a gene therapy for ALS, which uses AAV5 vectors to administer glial cell line-derived neurotrophic factor (GDNF) in order to provide neurotrophic support for motor neurons.
U.S. Status for ALS: Preclinical
Commercial Information: Treeway obtained exclusive rights from uniQure to develop AAV5-GDNF for ALS. Treeway is collaborating with the team of Prof. Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute in Los Angeles, CA to advance the development of TW002 for ALS.
R&D Status: Preclinical

References:
[1] Treeway Pipeline. Treeway, 2015. Accessed 11 Mar 2016 from http://www.treeway.nl/pipeline.
[2] Treeway to collaborate on developing AAV5-GDNF gene therapy for amyotrophic lateral sclerosis (ALS). FirstWord Pharma, 8 Dec 2015. Accessed 11 March 2016 from http://www.firstwordpharma.com/node/1338949?tsid=33#axzz42fVwf3bf.
[3] UniQure exclusively licensed this technology to Treeway, and the companies are collaborating on its development for ALS. PR Newswire, 14 Jan 2015. Accessed 11 Mar 2016 from http://www.prnewswire.com/news-releases/treeway-announces-license-and-collaboration-agreement-with-uniqure-to-develop-a-gene-therapy-for-amyotrophic-lateral-sclerosis-als-288529301.html.

Last updated March 11th, 2016
TreewayGene TherapyNeuroprotectionALSPreclinical
TW003

TW003

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Company: Treeway
Location: Netherlands
Website: http://www.treeway.nl/
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: Immunomodulation
Mechanism: TW003 is a vaccine therapy to restore immune balance by targeting the adaptive immune response in ALS. The drug incorporates a patented viral gene delivery platform called SVac. SVac is reported as a safe, highly efficient and nonimmunogenic vector platform.
U.S. Status for ALS: Preclinical
Commercial Information: The project is being conducted in collaboration with Amarna Therapeutics.
R&D Status: Preclinical

References:
[1] Treeway Pipeline. Treeway, 2015. Accessed 11 Mar 2016 from http://www.treeway.nl/pipeline.
[2] Development of ALS therapy by restoring the immune balance. Amarna Therapeutics, 23 Jun 2014. Accessed 11 Mar 2016 from http://www.amarnatherapeutics.com/uploads/Press%20release%20Amarna%20Treeway%20collaboration%20-%20Final.pdf

Last updated March 11th, 2016
TreewayGene TherapyImmunomodulationALSPreclinical
TW004

TW004

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Company: Treeway
Location: Netherlands
Website: http://www.treeway.nl/
Drug Type: Gene Therapy
Conditions: ALS
Mechanism Type: Immunomodulation
Mechanism: TW004 is a combination therapy to restore immune balance.
U.S. Status for ALS: Preclinical
R&D Status: Preclinical

References:
[1] Treeway Pipeline. Treeway, 2015. Accessed 11 Mar 2016 from http://www.treeway.nl/pipeline.

Last updated March 11th, 2016
TreewayGene TherapyImmunomodulationALSPreclinical
Talampanel

Talampanel

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Company: Teva Pharmaceutical Industries
Location: Israel
Website: http://www.tevapharm.com
Drug Type: Small Molecule
Conditions: ALS
Mechanism Type: Glutamate Excitotoxicity Blocker
Mechanism: Talampanel is a selective non-competitive antagonist of AMPA receptors, a type of glutamate receptor. Talampanel was tested as a drug to reduce neuronal death due to glutamate excitotoxicity.
U.S. Status for ALS: Discontinued
R&D Status: A Phase II trial in ALS was completed in 2010, but no efficacy measure reached statistical significance in treated vs. control patients, at two different doses tested. The program was discontinued.

References:
[1] Talampanel for Amyotrophic Lateral Sclerosis (ALS). ClinicalTrials.gov, 20 Oct 2011. Accessed 11 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT00696332.
[2] A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis. Pascuzzi, RM et al. Amyotroph Lateral Scler. 2010 May 3;11(3):266-71.

Last updated March 11th, 2017
Teva Pharmaceutical IndustriesSmall MoleculeGlutamate Excitotoxicity BlockerALSDiscontinued
Tirasemtiv

Tirasemtiv

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Company: Cytokinetics
Location: US-California
Website: http://www.cytokinetics.com
Drug Type: Small Molecule
Conditions: ALS
Mechanism Type: Improving muscle function
Mechanism: Tirasemtiv is a skeletal muscle activator that activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium.
U.S. Status for ALS: Phase III
R&D Status: The company completed a Phase IIb clinical trial in ALS in 2014 with mixed results: no statistically significant difference was detected between ALSFRS-R scores between treated and untreated groups, however, a statistically significant improvement in Slow Vital Capacity (SVC) in treated patients was observed. These findings led to the initiation of a Phase III trial, which is currently ongoing.

References:
[1] A randomized, placebo-controlled, double-blind phase IIb trial evaluating the safety and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis. Shefner, JM et al. Amyotroph Lateral Scler Frontotemporal Degener. Jul-Aug;17(5-6):426-35.
[2] A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Shefner, JM et al. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):574-81.
[3] Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year (VITALITY-ALS). ClinicalTrials.gov, 8 Mar 2016. Accessed 9 Mar 2016 from https://clinicaltrials.gov/ct2/show/NCT02496767.
[4] Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model. Hwee, DT. PLoS One. 2014 May 7;9(5):e96921.

Last updated June 29th, 2017
CytokineticsSmall MoleculeImproving muscle functionALSPhase III
Tocilizumab (Actemra)

Tocilizumab (Actemra)

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Company: Genentech
Website: http://www.gene.com
Drug Type: Protein Biologic
Conditions: ALS, Rheumatoid Arthritis, Polyarticular Juvenile Idiopathic Arthritis (PJIA)
Mechanism Type: Immunomodulation
Mechanism: Tocilizumab may reduce neuroinflammation by lowering levels of the pro-inflammatory cytokine IL-6. The drug, which is a monoclonal antibody, competitively inhibits the binding of interleukin-6 (IL-6) to its receptor.
U.S. Status for ALS: Phase II
R&D Status: A phase II clinical trial is ongoing.

References:
[1] Fiala, M. et al. Tocilizumab infusion therapy normalizes inflammation in sporadic ALS patients. Am J Neurodegener Dis. 2013 Jun 21;2(2):129-39.
GenentechProtein BiologicImmunomodulationALSPhase II
Usp14 inhibitor

Usp14 inhibitor

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Company: Proteostasis
Location: US-Massachusetts
Website: http://www.proteostasis.com/
Drug Type: Small Molecule
Conditions: Alzheimer's disease, Parkinson's disease
Mechanism Type: Protein aggregate clearance
Mechanism: In collaboration with Biogen, the company is developing novel inhibitors of Usp14, a deubiquitinating enzyme, to enhance clearance of aggregation-prone proteins such as alpha synuclein and tau. Inhibition of Usp14 promotes clearance of TDP-43 by retaining ubiquiting chains, suggesting this could be a promising therapeutic approach in ALS. However, Amgen recently reported that the company could not reproduce these published results.
U.S. Status for ALS: N/A
Commercial Information: The Usp14 program is being conducted in partnership with Biogen with technology licensed from Harvard University. The Usp14 technology was originally developed at Harvard Medical School by Professors Daniel Finley, Ph.D., and Randall King, Ph.D., M.D.
R&D Status: Preclinical

References:
[1] Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Lee, BH et al. Nature. 2010;467:179–184.
[2] If you fail to reproduce another scientist’s results, this journal wants to know. Kaiser, J. Science, 4 Feb 2016. Accessed 11 Mar 2016 from http://www.sciencemag.org/news/2016/02/if-you-fail-reproduce-another-scientist-s-results-journal-wants-know.
[3] Proteostasis Therapeutics Announces Collaboration with Biogen Idec for Research, Development and Commercialization of Therapies for Neurodegenerative Diseases. Harvard Office of Technology Development. 27 Feb 2016. Accessed 11 Mar 2016 from http://otd.harvard.edu/news-events/proteostasis-therapeutics-announces-collaboration-with-biogen-idec-for-rese/.

Last updated March 9th, 2016
ProteostasisSmall MoleculeProtein aggregate clearanceAlzheimer's diseaseN/A
VM202

VM202

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Company: ViroMed
Location: Seoul, South Korea
Website: http://viromed.co.kr/main/
Drug Type: Gene Therapy
Conditions: ALS, Diabetic Neuropathy, Diabetic Foot Ulcers, Peripheral Arterial Disease
Mechanism Type: Neuroprotection, Axon Regeneration
Mechanism: VM202 uses a pCK vector to deliver hepatocyte growth factor to muscles. The gene therapy strategy aims to stimulate angiogenesis (to provide neuronal trophic support) and the regeneration of damaged peripheral nerve axons.
U.S. Status for ALS: Phase I/II
Commercial Information: The US subsidiary of ViroMed is known as VM Pharma.

References:
[1] Sufit, RL et al. Open Label Study to Assess the Safety of VM202 in Subjects with Amyotrophic Lateral Sclerosis Amyotroph Lateral Scler Frontotemporal Degener. 2017 Feb 6:1-10.
ALS Research Forum Reference: http://www.alsresearchforum.org/neurotrophic-factors-in-als-a-winning-combination/

Last updated June 21st, 2017
ViroMedGene TherapyNeuroprotection, Axon RegenerationALSPhase I/II
VY-SOD101

VY-SOD101

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Company: Voyager Therapeutics
Location: Cambridge, MA
Website: http://voyagertherapeutics.com/programs.php
Drug Type: Gene Therapy
Conditions: SOD1 ALS
Mechanism Type: RNAi-based inhibition of SOD1 expression
Mechanism: VY-SOD101 is an adeno-associated viral (AAV)-based gene therapy that aims to slow progression of SOD1 ALS by reducing levels of ALS-linked mutant SOD1. SOD1 mutations account for approximately 20% of familial forms of ALS.
U.S. Status for ALS: Preclinical
Commercial Information: ReGenX licensed their Next Generation AAV (NAV) technology to Voyager Therapeutics for ALS and other rare indications. The gene therapy approach was originally developed in the laboratory of Professor James Wilson, M.D., Ph.D. at the University of Pennsylvania Perelman School of Medicine in Philadelphia, PA.
R&D Status: Voyager Therapeutics is targeting an IND filing for VY-SOD101 in late 2017.

References:
[1] Voyager Therapeutics Highlights Programs in Parkinson’s Disease and ALS; Announces Expansion of CNS Pipeline at R&D Day. Globe Newswire. April 29, 2016.
Voyager TherapeuticsGene TherapyRNAi-based inhibition of SOD1 expressionSOD1 ALSPreclinical
XN-001

XN-001

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Company: Xonovo
Location: Israel
Website: http://www.futurx.co.il/
Drug Type: Small Molecule
Conditions: ALS, Alzheimer's disease
Mechanism Type: Neuroprotection, neurotrophic support
Mechanism: XN-001 is a small molecule synthetic derivative of the natural brain metabolite Lanthionine Ketimine (LK). It targets collapsin response mediator protein (CRMP2). XN-001 has shown promising results in mouse models of Alzheimer's disease and ALS.
U.S. Status for ALS: Preclinical
Commercial Information: The technology was licensed from Oklahoma Medical Research Foundation. XoNovo Ltd. was founded by Dr. Rafi Gidron, the founder and chairman of Israel Brain Technologies and by Professor Kenneth Hensley from Toledo University in Ohio. The company is based on Hensley's work on lanthionine ketimine.
R&D Status: Preclinical

References:
[1] Emerging Biological Importance of Central Nervous System Lanthionines. Hensley K. Molecules. 2010;15: 5581-5594.
[2] Novel Alzheimer's disease (AD) drug to be developed by Xonovo Inc. FierceBiotech Research, 15 Oct 2013. Accessed 11 Mar 2016 from http://www.fiercebiotechresearch.com/press-releases/novel-alzheimers-disease-ad-drug-be-developed-xonovo-inc.
[3] J&J, Takeda team up to open Israeli biotech incubator. Shamah, D. Times of Israel, 19 Jan 2015. Accessed 11 Mar 2016 from http://www.timesofisrael.com/jj-takeda-team-up-to-open-israeli-biotech-incubator.

Last updated March 11th, 2016
XonovoSmall MoleculeNeuroprotection, neurotrophic supportALSPreclinical
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