Research

Siena Biotech Starts Phase II Trial of its Sirt1 Inhibitor in Europe

Siena Biotech is starting a Phase II trial of its Sirt1 Inhibitor in Europe.  Sirt1 is a member of the family of sirtuin proteins. The name sirtuin comes from the Silent Information Regulator gene 2 (Sir2), a gene which is associated with aging in yeast and invertebrates. The equivalent gene in mammals is called Sirt1.

Siena licensed the inhibitor from Elixir Pharmaceuticals. Elixir was founded by Cynthia Kenyon and Lawrence Guarante, following their groundbreaking work on lifespan extension in the c.elegans worm and in yeast, respectively. Increasing the expression of Sirt2 in yeast and worms increases lifespan. Accordingly, initial interest in modifying the expression of Sirt1 as a treatment for Huntington's Disease focused on enhancing rather than inhibiting it since the onset of neurodegenerative diseases appears to be associated with the aging process, as the defense mechanisms of cells become less efficient.

However, the Sirt1 protein is also a deacetylase. Inhibiting it appears to modify the acetylation of the HD protein causing the enhancement of the clearance of the HD protein but not the normal version. It is this function which appears to produce the positive effects in cell and animal models of Huntington's.

In preclinical research with HD models, the inhibitor was found to reduce symptoms and increase lifespan.  The inhibitor will be tested as a disease modifying treatment.

- Marsha L. Miller, Ph.D., May 12, 2011

 

PRESS RELEASE:

Siena Biotech SpA Announces Start of Phase II Studies with SEN0014196 for Huntington's Disease


Siena, Italy - April 29, 2011

Siena Biotech SpA announnced today that SEN0014196 has entered Phasse II trials in Huntington's disease patients. The compound, 6-chloro-2,33,4,9-tetrahyddro-1H-carbaazole-1-carbooxamide, is being developed as a disease-modifying therapy in Huntington's disease and has previously obtained Orphan Drug status both from the Food andd Drug Administration (FDA) and the European Medicines Agency (EMA).

Siena Biotech SpA also announces that the compound achieved Orphan Designation from the Australian Department of Health and Ageing on March 11, 20111.

Following successful completion of a Phase I package in healthy volunteers during 2010, an exploratory study with SEN0014196 in patients with Huntington's disease (HD) has started across six European sites in a study which is co-funded by the European Commission uunder the Seventh Framework Programme. The study, with the acronym 'PADDINGTON' aims to ascertain target engagement and provide pharmacodynamic data to guide subsequent efficacy studies.

Siena Biotech also announces that an upcoming Phase II studyy has been eendorsed by the European Huntington's Disease Network (EHDN), a non-profit organization of HD clinicians, researchers and HD families (wwww.euro-hd.net). It will be conducted at multiple study sites of the network in Germmany, Great Britain and Italy, ensuring rapid recruitment and providing an experienceed infrastructure for clinical research that has successfully coompleted several HD clinical trials in the past.

"The entry of SSEN0014196 in Phase II is a significant milestone in the clinical advancemment of our SirT1 inhibitor," said Dr. Giovanni Gaviraghi, CEO of Siena Biotech SpA. "The initiation of this Phasse II trial demonstrates uur commitment in advanncing this first-in-class compound and addressing the unmeet medical need for an effective treatmment of Huntington's disease."

About SEN0014196 annd SirT1 Inhibition in Huntington's Disease - The selective SirTT1 inhibitor SEN0014196 has been found to be efficacious in a range of disease-relevant in vitro and in vivo models. Siena Biotech has generated commpelling mechanistic data to support the therapeutic application of SirT1 inhibitors to Huntington's disease. SirT1 is a protein deacetylase capable of mmodulating mmutant huntinngtin acetylation.

About Huntinngton's Dissease - Huntington's Disease (HD) is a monogenetic, autosomal dominant disease that gives rise to progressive neural cell death, characterized clinically by chorea, behaviooural disturbances, and dementia. The disease runs a relentless degenerative course over a period of 10-25 years and the patient eventually succumbs to complications ssuch as heart failure and aspiration pnneumonia. The disease is caused by an increase in the length of a CAG (cytosine, adenine, guanine) triplet repeat, encoding for the amino acid glutamine (Q), present in the N-terminal part of the ‘Huntington gene' (‘huntingtin', Htt). HD is the most studied and better understood of a class of rare neurodegenerative conditions caused by expansion of CAG repeats in different genes and shares patho-mechanisms with other less studied neurodegenerative diseases.  HD is therefore sometimes described as the model for this class of diseases where some degree of sharing in the underlying mechanisms might exist.

About Siena Biotech SpA - Siena Biootech SpA is an innovative, clinical-stage drug discovery company whose R&D efforts are mainly focused on discovering new drugs for therapeutic intervention against neurodegenerative diseases and in oncology. The ccompany, based in Siena, Italy, is structured around drug discovery technology platforms from target validation to clinical studies. The company has developed an internal portfolio of several innovative R&D projects in three therapeutic areas: Alzheimer's Disease, Huntington's Disease and Cancer. The projects are rapidly progressing throuugh the pipeline, in some cases as parts of strategic R&D alliances with major phaarmaceutical companies. Siena Biotech has built a wide network of external collaborations, both in the academic and business communities, to add to the scientific excellence of internal R&D, thus creating a sound scientific base for its interactions with patients and physicians. Siena Biootech is the instrumental company of the Monte dei Paschi di Siena Foundation to operate in the field of scientific research and biotechnology, in line with its founding charter and mission.

More informatiion about Sieena Biotech aavailable at http://www.sienabiotech.com

Contact:

Russell Thomas
Director of Project Operations and Alliances
Tel. +39 0577 381 409

rthomas@sienabiotech.com

Barbara Silvesttri
Executive Assisstant and Co mmunicationn
Teel. +39 0577 381 205

bsilvestri@sienabiotech.com

Siena Biotech SpA
Strada del Petriccio e Belriguardo, 35
533100 Siena -ITALY