TauRx Reports First Phase 3 Results for LMTX(R)

PR65240

ABERDEEN, Scotland and SINGAPORE, July 27, 2016 /PRNewswire=KYODO JBN/ --

     Promising Read-Out for First-Ever Tau Aggregation Inhibitor to Enter Phase

3 Trials

    - LMTX(R) as monotherapy demonstrates significant reductions in disease

progression in mild and moderate Alzheimer's disease

     - Strong results in both cognitive and functional tests supported by brain

scan evidence of slow-down in progression of pathology

     - Study misses co-primary endpoints as LMTX(R) as add-on therapy shows no

beneficial effects

     - Initial analysis from second phase 3 study in patients with mild

Alzheimer's disease confirm positive findings

    TauRx Therapeutics Ltd today announced Phase 3 clinical trial results that

show treatment with LMTX(R), the company's novel tau aggregation inhibitor, had

a marked beneficial effect on key measures of Alzheimer's disease in patients

with mild or moderate forms of the disease.

    (Logo: http://photos.prnewswire.com/prnh/20160727/393315LOGO )

    While the TRx-237-015 study in 891 subjects failed to meet its co-primary

endpoints, clinically meaningful and statistically significant reductions in

the rate of disease progression were observed across three key measures in

patients who were treated with LMTX (R) as their only Alzheimer's disease

medication. These three key measures comprised a cognitive assessment

(ADAS-Cog), a functional assessment (ADCS-ADL) and an assessment of the level

of brain atrophy (lateral ventricular volume, LVV, as measured by MRI). An

abstract of the results will be presented during an open session at the 2016

Alzheimer's Association International Conference (AAIC) in Toronto, Canada this

afternoon by Dr. Serge Gauthier, CM, MD, FRCPC, Director of the Alzheimer's

Disease Research Unit, McGill University, Canada.

    "In a study of this size across a combined mild to moderate patient

population, it is both encouraging to see improvements of this magnitude in the

standard cognitive and functional tests and reassuring to see the supporting

brain scan evidence of a slowing in disease progression during 15 months of

treatment," said Dr. Gauthier, "As a practising clinician I see Alzheimer's

patients, their families and care-givers every day, and continually share their

desperate need for a truly therapeutic product as today we only have

symptomatic treatments available to us. In a field that has been plagued by

consistent failures of novel drug candidates in late-stage clinical trials and

where there has been no practical therapeutic advance for over a decade, I am

excited about the promise of LMTX(R) as a potential new treatment option for

these patients."

    The same efficacy findings were not seen in study patients who took LMTX(R)

in combination with other standard Alzheimer's treatments. Since these patients

formed the substantial majority of those recruited to the trial, the treatment

benefits seen in those taking LMTX(R) as monotherapy could not be seen when all

patients taking LMTX(R) were pooled in the primary analysis model. Although

this prevented the study from achieving an overall statistical significance in

the pooled analysis, the primary analysis model showed a highly significant

effect of treatment in the patients taking LMTX(R) as monotherapy. This

treatment benefit was confirmed in a prespecified supportive analysis of all of

the study's primary and secondary outcomes. This is the first treatment in

which a clinical effect has been supported by evidence in delay of progression

in brain atrophy shown by MRI scans.

    Professor Claude Wischik, Professor of Psychiatric Geratology at Aberdeen

University and co-founder of TauRx said, "The results we have seen in this

study confirm the results we saw in our Phase 2 study, where an earlier version

of the drug was also given as monotherapy. The results we see in those patients

not taking Alzheimer's disease medications show the considerable potential of

LMTX(R) as a monotherapy for both mild and moderate Alzheimer's disease.

Perhaps more importantly, these results support the targeting of the tau tangle

pathology in Alzheimer's disease as being a very promising drug development

pathway.  However, the reason for the observed loss of efficacy of LMTX(R)  

when taken in combination with currently available treatments for Alzheimer's

disease is not as yet understood."

    An initial analysis of data from the second of TauRx's two Phase 3 trials

in Alzheimer's disease, study TRx-237-005 undertaken in 800 patients with the

mild form of the disease, confirms the findings of study TRx-

    237-015 and supports the potential of LMTX(R) as monotherapy.  The results

from this study are expected to be published and presented later in 2016.

    Impact of LMTX(R) Treatment on Key AD Measures

    - The ADAS-cog decline analysis produced highly statistically significant

treatment effects of -6.3 +/-1.4 (p＜.0001) and -5.8 +/-1.4 (p＜.0001) units

after taking 75mg b.i.d or 125mg b.i.d of LMTX(R) as monotherapy respectively,

while the ADCS-ADL decline analysis produced a statistically significant

treatment effect of 6.5 +/-1.8 (p=.0013) and 6.9 +/-1.9 (p=.0007) following

treatment of 75mg b.i.d or 125mg b.i.d of LMTX(R) as monotherapy respectively.

     - LMTX(R) taken as monotherapy also slowed down the rate of progression of

brain atrophy as measured by LVV derived from MRI scans. There was a reduction

in the expansion of the LVV by 38%+/-9% (p=.0023) and 33%+/-9% (p=.0014) for

75mg twice a day and 125mg twice a day, respectively, compared to the control

in these patients.  These reductions in LVV expansion were statistically

significant and confirmed by corresponding increases in the whole brain volumes

in the same patient groups.

     - In those study patients taking LMTX(R) as add-on therapy to current AD

medications, there were no statistically significant differences in ADAS-cog,

ADCS-ADL or LVV measurements between the control, 75mg b.i.d LMTX(R) or 125 mg

b.i.d. LMTX(R) treatment groups. ＜end_indent＞

    About Study TRx-237-015

    Study TRx-237-015, was a randomised double-blind placebo-controlled study

in 891 subjects with mild or moderate Alzheimer's disease that compared

treatment for 15 months with LMTX(R) with placebo. The safety profile of

LMTX(R) in the study was acceptable, with rates of amyloid-related imaging

abnormalities reported similar to placebo arms in recent Phase 3 trials and

with the overall adverse event profile also similar to those typically seen in

Phase 3 studies of novel late-stage Alzheimer's disease treatments. The most

common adverse events occurred in the gastrointestinal and urinary tracts, and

were typically mild in nature and easily controlled.

    Data Presentation Details

    Study TRx-237-015 will be presented at an oral session at AAIC on 27 July

2016, 16:15-17:45.

    Tau aggregation inhibitors

    TauRx's tau aggregation inhibitors (TAIs) have arisen from nearly 30 years

of research. TAIs work by undoing the tau tangles that cause dementia, thereby

slowing and even arresting memory loss[1]. The first-generation TAI, rember(R),

was a patented, highly-purified version of methylene blue, a compound

previously used to treat a variety of conditions.

    About TauRx Therapeutics Ltd

    TauRx Therapeutics Ltd is a member of the TauRx Pharmaceuticals group which

is developing technology spun-out from the University of Aberdeen, Scotland,

and was established in Singapore in 2002 with the aim of developing new

treatments and diagnostics for a range of neurodegenerative diseases. The

company's tau aggregation inhibitor, LMTX(R)  targets aggregates of abnormal

fibres of tau protein that form inside nerve cells in the brain, giving rise to

'tau tangles'. TauRx's headquarters are in Singapore and its primary research

facilities are based in Aberdeen. For more information, please visit:

http://www.taurx.com.

    References

    1) Wischik CM, et al. Tau-aggregation inhibitor therapy for Alzheimer's

disease. Biochem Pharmacol 2014;88:529-39.

    Email: taurxpress@hkstrategies.com

    Website: http://www.taurx.com

SOURCE: TauRx Therapeutics Ltd