NXERA PHARMA CO., LTD. Demonstrates changes in brain activity, therapeutic window and M1 receptorselectivity
Tokyo, Japan -10 February 2016: Sosei Group Corporation ("Sosei"; TSE Mothers Index: 4565) today reports that Heptares Therapeutics ("Heptares"), the wholly-owned subsidiary of Sosei Group Corporation, announces positive findings from its Phase 1b clinical studywith HTL9936. HTL9936 is the first selective muscarinic M1 receptoragonist, designed using Heptares StaR® technology, which has entered clinical development as a new treatment for cognitive impairment in patients with dementia and schizophrenia.
Thesepositive results provide strong evidence of a therapeutic window for the selective M1 agonist mechanism in general, and for progression of HTL9936 and similar molecules as medicines to treat cognitive disorders.
The Phase 1b precision medicine study involved 28 healthy elderly subjects who received different doses of HTL9936 and was designed to test the effect of drug on measures of brain activity while simultaneously monitoring side effects.
In the study, HTL9936 exhibited robust and statistically significant changes in brain electrical activity measured using multiple electroencephalography (EEG) biomarkers relevant to cognition, including effects on the P300 evoked response potential (p=0.0052). These pro- cognitive effects were seen at low doses and low blood concentrations that were safe and well tolerated.
M1 receptor selectivity was also confirmed across the dose range studied through the absence of gastrointestinal side-effects (such as diarrhoea and vomiting) typically attributed to the stimulation of M2 and M3 receptors. Such side effects are dose-limiting in standard-of- care acetylcholinesterase inhibitors, which likely work through non-selective muscarinic receptor stimulation.
Heptares is also developing a second patentably distinct M1 agonist, HTL18318, which is in Phase 1 and for which results are expected later this year. Phase 2 studies in dementia and schizophrenia patients are expected to commence in late 2016.
"The results from this Phase 1b study reinforce our earlier findings from clinical and preclinical studies, providing compelling evidence to support the therapeutic potential of Heptares' selective M1 agonists for improving cognitive function in patients with dementia and schizophrenia," commented Tim Tasker, Chief Medical Officer of Heptares. "We are excited by these findings and look forward to progressing the M1 programme into patient studies later this year."
Malcolm Weir, Heptares CEO, added: "We are greatly encouraged by these findings from our lead M1 agonist programme. We have generated a diverse portfolio of selective agonists
that includes not only M1 but M4 agonists for treating psychosis in schizophrenia and Alzheimer's disease patients, and dual M1/M4 agonists for both psychosis and cognitive impairment in these patients; we expect these to reach the clinic from early 2017 onwards. We believe this is a programme with the potential to deliver medicines of immense clinical and commercial significance."
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Enquiries: Sosei Group Corporation | |
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Harumi BANSE, Investor Relations | Kathryn LYDON, Corporate Communications |
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About M1 ReceptorAgonism
Direct M1 receptor agonism is a highly validated mechanism of action for improving cognitive function (memory and thinking) in patients with progressive dementia. By stimulatingdirectly the pro-cognitive M1 receptorson nerve cells in the brain, M1 agonists substitute for the diminishing levels of the neurotransmitter (acetylcholine) in patients that normally act on these receptors. Previous attempts lacked selectivity and were discontinued dueto M2 and M3 mediated side effects.
By contrast, HTL9936 and HTL18318 are small molecules designed using the Company's proprietary structure-based platform (StaR® technology) and are highly selective for M1 over M2 and M3, therefore offering the prospect of a therapeutic window between enhanced cognitive activity and side-effects.
Schizophrenia is a severe psychiatric illness leading to disturbances of thought. 'Positive symptoms' include hallucinations and delusions are linked to changes in dopamine levels and are treated with current antipsychotics. However, these are poorly tolerated due to side effects such as weight gain. There are estimated to be over 21 million people
with schizophrenia worldwide. In addition, 30-50% of AD patients can suffer from severe behavioral symptoms including psychosis, agitation and hallucinations as the disease progresses. Therapies including cholinesterase inhibitors are most commonly used but these have only moderate and transient benefit and the dose is limited by side effects. There is currently no cure.
*Sources: World Health Organization, Alzheimer's Disease International, National Institute of Mental Health, Lewy Body Dementia Association.
Heptares is a clinical-stage company creating transformative medicines targeting G protein-coupled receptors (GPCRs), a superfamily of 375 receptors linked to a wide range of human diseases. Heptares proprietary structure-based drug design technology enables us to engineer drugs for highly validated, yet historically undruggable or challenging, GPCRs. Using this approach, we have built an exciting pipeline of new medicines with the potential to transform the treatment of Alzheimer's disease, schizophrenia, migraine, addiction, metabolic disease, and other indications.
We have advanced our lead assets - the first-in-class selective muscarinic M1 receptor agonists - from the earliest stages of discovery into clinical development for treating cognitive impairment/dementia in Alzheimer's disease and schizophrenia. Preliminary clinicalresults confirm the exquisite selectivity of these compounds for the M1 receptor over other subtypes in human subjects, reinforcing preclinical findings. Other proprietary and partnered candidates across multiple indications are progressing towards the clinic.
We have also entered partnerships for our novel candidates and technologies with leading pharmaceutical and biotechnology companies, including Pfizer, AstraZeneca, MedImmune, MorphoSys and Teva.
Heptares is a wholly owned subsidiary of Sosei Group Corporation. For more information, please visit www.heptares.com and www.sosei.com.
HEPTARES is a registered trademark in the EU, Switzerland, US and Japan; StaR® is a registered trademark in the EU and Japan.
Sosei is a biopharmaceutical company originating from Japan but with global presence. Sosei's primary business model is based on identifying novel and/or differentiated product assets or technology platforms and, through supporting these in preclinical and clinical development and establishing commercial partnerships, advancing new medicines to patients worldwide.
For more information about Sosei, please visit www.sosei.com.
For further information about Sosei, please visit www.sosei.com/en.
This press release contains forward-looking statements, including statements about the discovery, development and commercialisation of products. Various risks may cause Sosei's actual results to differ materially from those expressed or implied by the forward-
looking statements, including: adverse results in clinical development programmes; failure to obtain patent protection for inventions; commercial limitations imposed by patents owned or controlled by third parties; dependence upon strategic alliance partners to develop and commercialise products and services; difficulties or delays in obtaining regulatory approvals to market products and services resulting from development efforts; the requirement for substantial funding to conduct research and development and to expand commercialisation activities; and product initiatives by competitors. As a result of these factors, prospective investors are cautioned not to rely on any forward-looking statements. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Sosei Group Corporation issued this content on 10 February 2016 and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on 10 February 2016 06:48:02 UTC
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