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Probiodrug positioning its pGlu-Abeta Antibody in the field of Abeta antibodies
Published: 08 May 2018

Probiodrug positioning its pGlu-Abeta Antibody in the field of Abeta antibodies

Probiodrug co-authored a review paper entitled
"Passive Abeta Immunotherapy: Current Achievements and Future Perspectives "

HALLE (SAALE), Germany, 08 May 2018 Probiodrug AG (Euronext Amsterdam: PBD), a clinical stage biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), today announced that results from its preclinical candidate antibody PBD-06 were reviewed : Schilling, S., Rahfeld, J.-U., Lues, I. and Lemere, C.A. in Molecules and can be found here:

The review article is authored by researchers from the Fraunhofer-Institute for Cell Therapy and Immunology, Germany, the Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, USA and Probiodrug AG, Germany. It is part of a special issue dedicated to the 25th anniversary of the amyloid cascade hypothesis, the leading hypothesis of the pathology of the  Alzheimer's disease (AD). The review highlights the current development status of monoclonal antibodies in advanced clinical development for the treatment of AD. A special emphasis is put  on current limitations of immunotherapy of AD and recent strategies to overcome these issues by tailoring the specificity and effector function of the antibodies. Probiodrug's strategy to target pGlu-Abeta, a highly aggregatable and neurotoxic form of amyloid peptide specific for AD, is comprehensively reviewed as well as the status of preclinical pGlu-Abeta antibody developments. PBD-C06 is PBD's humanized and deimmunized anti-pGlu-Abeta monoclonal antibody currently in CMC development. The molecule was selected based on an optimal pharmacological  profile.

Dr. Stephan Schilling  from the Fraunhofer Institute for Cell Therapy and Immunology IZI comments: "The review provides an overview on current strategies to improve immunotherapeutics for the treatment of AD. Among those, especially the targeting of posttranslationally modified amyloid peptides such as pGlu-Abeta offers several advantages for a treatment with low risk of side effects."  Dr. Schilling is a group leader at Fraunhofer IZI and serves together with Dr. Hutter-Paier (QPS Austria) as a guest editor of the special issue.

Dr. Inge Lues, Chief Development Officer of Probiodrug added: "The review highlights the differentiating factors of anti-pGlu3-Abeta immunontherapy over other monoclonal antibodies, providing a comprehensive overview on the mode of action of our development candidate  PBD-C06."

Probiodrug is progressing two complementary strategies for tackling pGlu-Abeta with two candidates in development: PQ912, a small molecule inhibitor of Glutaminyl Cyclase, now in Phase 2, and PBD-C06, a pGlu-Abeta-specific monoclonal antibody in preclinical stage.


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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 (AD). Probiodrug has identified a new therapeutic concept linked to disease initiation and progression. The approaches are targeting a key neuro/synaptotoxic component of the pathology, pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy. Its lead product, PQ912, has successfully completed a Phase 2a (SAPHIR) study. The company's pipeline also includes PBD-C06, an anti-pGlu-Abeta-specific monoclonal antibody, in preclinical development. Probiodrug has medical use and composition of matter patents related to the inhibition of QC and anti-pGlu-Abeta-specific monoclonal antibodies, and has, in the Company's view, a leading position in this field of research.

Founded in 1997 by Hans-Ulrich Demuth and Konrad Glund, 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. Today, Probiodrug aims to become a leading company in the development of AD treatments and to thereby provide a better life for Alzheimer's disease patients.

About PBD-C06
PBD-C06 is a monoclonal antibody, currently in preclinical stage. PBD-C06 targets pGlu-Abeta, aiming to selectively clear the brain of pGlu-Abeta while leaving non-toxic forms of Abeta untouched. PBD C06 has been successfully humanized and also de-immunized to avoid detection by the patient's endogenous immune system. For the first time for an anti-pGlu-Abeta approach, PBD-C06 has not only shown the ability to reduce Abeta/plaques but also to significantly improve cognitive deficits in aged Alzheimer's mice. Moreover, no evidence was found of increased microhemorrhages after treatment with PBD-C06.

About PQ912
Probiodrug's lead product candidate, PQ912, is a highly specific and potent inhibitor of Glutaminyl Cyclase (QC), the enzyme catalyzing the formation of synaptotoxic pGlu-Abeta. PQ912 has shown therapeutic effects in AD animal models. A Phase-1 study in  healthy young and elderly volunteers revealed a dose dependent exposure  and showed good safety and tolerability up to the highest dose  with >90% target occupancy in the spinal fluid. In June 2017, Probiodrug announced top-line data of the Phase-2a SAPHIR trial of PQ912 and presented the study results at CTAD 2017. The positive effects seen on secondary exploratory efficacy markers strongly support (a) the hypothesis of pGlu-Abeta being synaptotoxic and (b) the therapeutic concept pursued by Probiodrug. The study revealed a positive benefit risk ratio of PQ912 and provides important guidance how to move forward in the development of PQ912 as a disease-modifying drug for AD. Altogether, the results make the program highly attractive for further development; the company has initiated the preparation of a Phase 2b core program.

About Alzheimer's disease
Alzheimer's disease is a neurological disorder, which is the most common form of dementia, and ultimately leads to death. Today, 47 million people live with dementia worldwide, and this number is projected to treble to more than 131 million by 2050, as the global population ages. Dementia also has a huge economic impact. Alzheimer's 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.