Pharmiweb ChannelsAll | PharmaCo | Clinical Research | R&D/BioTech | Sales/Mktg | Healthcare | Recruitment | Pharmacy | Medical Comms

Pharmiweb.com RSS Feed Pharmiweb.com RSS Feeds

Pharmiweb.com RSS Feed PharmiWeb Candidate Blog

Pharmiweb.com RSS Feed PharmiWeb Client Blog

Advertising

Press Release

Amyloid-beta (Abeta) aggregate-clearing by the murine anti-pyroglutamate-3 Abeta IgG2a monoclonal antibody PBD-C06 with and without a complement mutation in an Alzheimer's mouse model

Probiodrug
Posted on: 16 Nov 16

Amyloid-beta (Abeta) aggregate-clearing by the murine anti-pyroglutamate-3 Abeta IgG2a monoclonal antibody PBD-C06 with and without a complement mutation in an Alzheimer's mouse model

HALLE (SAALE), Germany, 16 November 2016 - Probiodrug AG (Euronext Amsterdam: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), announced today the first results of a preclinical study in an AD mouse model with the pyroglutamate-3 Abeta (pGlu3-Abeta)-specific antibody mPBD-C06, comparing versions with and without a mutation eliminating complement activation which will be presented as a poster at the Society for Neuroscience (SfN) meeting on 16 November 2016 in San Diego, CA.

Data were generated in collaboration with Cynthia Lemere of Brigham and Women's Hospital, Harvard Medical School, and QPS, Graz, Austria.

Previously, Lemere's team showed that the mouse IgG2a variant of the anti-pGlu3-Abeta monoclonal antibody was more effective at clearing Abeta aggregates and rescued behavioral deficits compared to the mouse IgG1 version (SfN 2015). In the present study,  the effect of eliminating the antibody's ability to activate complement (CDC) on the efficiency to reduce Abeta plaques was investigated and it was found that both variants - with and without CDC - reduced pGlu3-Abeta  as well as general Abeta to the same extent - without inducing microhemorrhages. Thus, avoiding complement activation did not impact the capacity of mPBD-C06 to eliminate pGlu3-Abeta aggregates. In addition, microglial activation was assessed in vivo by 18 F-GE180 TSPO microPET imaging at baseline and following a single injection of the pGlu3-Abeta antibody variants. In contrast to the IgG2a variant, which showed enhanced whole brain uptake of 18 F-GE180 in AD mice, the antibody lacking CDC did not alter the TSPO signal after injection.

In summary, the data demonstrate for the first time, that microglial activation, analyzed by TSPO microPET, can be reduced by CDC inactivation without impairing the potency of the antibody to clear amyloid deposits. Further studies are underway to better understand the clearance mechanisms for each of these anti-pGlu3 Abeta antibodies.

Inge Lues, Chief Development Officer of Probiodrug, commented: "These data are very exciting as they demonstrate efficient Abeta clearance without potential side- or dose-limiting effects of inducing inflammation."

Cynthia Lemere, PhD, scientist at Brigham and Women's Hospital, added: "Although further investigation is needed, these early data suggest that the novel CDC-mutant anti-pGlu3 Abeta antibody may improve efficacy and safety as an AD immunotherapy." Lemere is currently the recipient of pre-clinical sponsored research from Probiodrug AG.

###

For more information please contact:

Probiodrug
Dr Konrad Glund, CEO
Email: contact@probiodrug.de

Hume Brophy
Mary Clark, Supriya Mathur, Eva Haas
Tel: +44 (0) 207 862 6475
Email: probiodrug@humebrophy.com

The Trout Group
Tricia Truehart
Tel: +1 646 378-2953
Email: ttruehart@troutgroup.com

Notes to Editors:

About Probiodrug AG
Headquartered in Halle (Saale), Germany, Probiodrug AG (Euronext Amsterdam: PBD) is a biopharmaceutical company focused on the development of new therapeutic products for the treatment of Alzheimer's disease.
Founded in 1997, the company successfully developed a novel therapeutic concept for diabetes - the DP4 inhibitors - which provided the basis for a novel class of antidiabetics - the gliptins. Its core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes involved in the modification of proteins and peptides, which play a central role in pathological conditions.

Today Probiodrug's aim is to become a leading company in the development of Alzheimer's disease treatments and to thereby provide a better life for Alzheimer's disease patients. It has identified a new therapeutic concept linked to disease initiation and progression. The development approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy to fight Alzheimer's disease. The Company has medical use and composition of matter patents related to the inhibition of Glutaminyl Cyclase (QC) and anti-pGlu-Abeta- specific monoclonal antibodies, providing it, in the Company's view, with a leading position in this field of research.

Probiodrug's lead product candidate, PQ912, is a highly specific and potent inhibitor of Glutaminyl Cyclase (QC), which has shown therapeutic effects in Alzheimer's animal models. PQ912 is currently in a Phase 2a study, the SAPHIR trial. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 has shown to be safe and well tolerated and also revealed high QC-inhibition.
www.probiodrug.de

About Alzheimer's disease
Alzheimer's disease is a neurological disorder, which is the most common form of dementia, and ultimately leads to death. Because Alzheimer's disease cannot be cured and is degenerative, the affected patients must increasingly rely on others for assistance. . Today, 47 million people live with dementia worldwide, and this number is projected to treble to more than 131 million by 2050, as populations age. Dementia also has a huge economic impact. Alzheimer's also has an estimated, global societal cost of US$ 818 billion, and it will become a trillion dollar disease by 2018. (World Alzheimer Report 2016).

Forward Looking Statements
Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgment of Probiodrug AG as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.



This announcement is distributed by NASDAQ OMX Corporate Solutions on behalf of NASDAQ OMX Corporate Solutions clients.

The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.

Source: Probiodrug via GlobeNewswire
HUG#2057252
GlobeNewswire
globenewswire.com

Last updated on: 17/11/2016

Advertising
Share | | |
Site Map | Privacy & Security | Cookies | Terms and Conditions

PharmiWeb.com is Europe's leading industry-sponsored portal for the Pharmaceutical sector, providing the latest jobs, news, features and events listings.
The information provided on PharmiWeb.com is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her physician.