Karyopharm Therapeutics Inc (NASDAQ:KPTI) a clinical-stage pharmaceutical company, today reported that its SINE™ nuclear transport compounds are being evaluated for the treatment of Amyotrophic Lateral Sclerosis (ALS) and that preclinical data abstracts will be presented at two upcoming neuroscience meetings. A recent publication appearing in the journal Nature confirmed that nuclear transport is disrupted in a common mutation found in ALS. Given the tremendous unmet need for new treatments for ALS, Karyopharm is advancing its oral SINE™ compound KPT-350 for this indication. While Karyopharm’s primary clinical focus is in advancing its lead SINE™ compound oral selinexor for human cancer, other SINE™ compounds have already shown beneficial pharmacological effects in several neurodegenerative and anti-inflammatory preclinical models, including multiple sclerosis, systemic lupus and traumatic brain injury.

The Nature publication entitled “The C9orf72 repeat expansion disrupts nucleocytoplasmic transport” reported that C9orf72, the most common cause of familial and sporadic ALS and Frontotemporal Degeneration, results in problems with nuclear protein trafficking that affect neural function and survival. The mutation causes the affected cells to create long strands of repeating RNA, thus blocking critical pathways for nuclear transport of proteins. A first set of experiments using a fruit fly model of human ALS to screen for candidates that block brain cell death in a living organism identified a protein RanGAP, a key regulator of nucleocytoplasmic transport, that acts as a potent suppressor of neurodegeneration. Consistent with the interaction of RanGAP with XPO1 (exportin 1), the studies further showed that suppressing nuclear export of proteins also suppresses neurodegeneration. The results were validated in human stem cell derived motor neurons and autopsied brains.

In a second set of experiments, using fly and human stem cells, the addition of antisense oligonucleotides targeting C9orf72 or small molecule inhibitors of XPO1 including one of Karyopharm’s SINE™ compounds, restored proper protein nuclear localization. Importantly, this effect was sufficient to suppress neurodegeneration. This study supports the premise that nucleocytoplasmic transport defects may be a fundamental pathway for ALS that is amenable to pharmacotherapeutic intervention. The results from this publication will also be presented at the Society for Neuroscience (SfN) meeting in Chicago on October 19, 2015 by Thomas E. Lloyd, MD, Ph.D. of Johns Hopkins University.

“This valuable research reinforces that modulation of nucleocytoplasmic transport presents a potential therapeutic strategy for neurodegenerative diseases such as ALS,” said Sharon Shacham, PhD, President and Chief Scientific Officer of Karyopharm. “More broadly, this work extends earlier findings in multiple sclerosis, traumatic brain injury, and auto-inflammatory disorders, further validating the vast therapeutic applicability of Karyopharm’s SINE™ compounds across a broad spectrum of diseases.”

In addition to the above presentation, Karyopharm’s other collaborators will be presenting abstracts on the neuroprotective effects of SINE™ compounds at two upcoming neuroscience meetings this fall. Sami Barmada, MD, Ph.D. from the University of Michigan will be presenting an abstract entitled “Selective inhibition of nuclear export in amyotrophic lateral sclerosis and frontotemporal dementia” at the upcoming American Neurological Association (ANA) Meeting in Chicago on September 26, 2015 from 9:35am-11:35am. Hilary Archbold, also from the University of Michigan, will be presenting an abstract entitled “The role of nuclear export in TDP-43-mediated neurodegeneration” at the Society for Neuroscience (SfN) meeting in Chicago from October 18, 2015 from 4:00pm-5:00pm.

Karyopharm’s SINE compound research efforts in ALS are being supported entirely by collaborator grant funding. The ALS Therapy Alliance is funding the in vitro research of Karyopharm’s collaborator Sami Barmada, MD, Ph.D. of the University of Michigan until 2016. The goal of that grant is to investigate the mechanism of neuroprotection by SINE™ compounds and determine if they are protective in human stem cell-derived neurons from patients with ALS and FTD. Another collaborator, Ronald Klein, Ph.D. of Louisiana State University Health Sciences Center, Shreveport has been funded by the ALS Association beginning in July 2015 for two years to evaluate the therapeutic efficacy of KPT-350 in an adult onset ALS model. This in vivo research is expected to confirm whether Karyopharm’s compound can ameliorate the ALS-like disease state in rats induced by gene transfer of cytoplasmic TDP-43, a major disease protein in ALS. (Original Source)

Shares of Karyopharm Therapeutics INC closed yesterday at $14.63. KPTI has a 1-year high of $49.01 and a 1-year low of $11.58. The stock’s 50-day moving average is $17.98 and its 200-day moving average is $25.84.

On the ratings front, Karyopharm Therapeutics has been the subject of a number of recent research reports. In a report released yesterday, J.P. Morgan analyst Cory Kasimov initiated coverage with a Buy rating on KPTI and a price target of $20, which implies an upside of 36.7% from current levels. Separately, on August 12, MLV & Co.’s Arlinda Lee reiterated a Buy rating on the stock and has a price target of $42.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Cory Kasimov and Arlinda Lee have a total average return of 2.8% and -12.0% respectively. Kasimov has a success rate of 43.9% and is ranked #1191 out of 3748 analysts, while Lee has a success rate of 29.6% and is ranked #3677.

Karyopharm Therapeutics Inc. is a clinical-stage pharmaceutical company focused on the discovery, development and subsequent commercialization of drugs directed against nuclear transport targets for the treatment of cancer and other major diseases.