Probiodrug announces publication of initial PQ912 clinical data demonstrating inhibition of glutaminyl cyclase

  • PQ912 is currently in Phase 2a studies in Alzheimer's disease patients

HALLE/SAALE, Germany, 15 December 2015 - Probiodrug AG (Euronext Amsterdam: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), today announced that data from an extensive phase 1 study with PQ912, its lead glutaminyl cyclase (QC) inhibitor for the treatment of AD, have been published in Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 1, Issue 3, Pages 182-195. PQ912 is a first-in-class competitive inhibitor of glutaminyl cyclase, essential for the formation of pyroglutamate-Amyloid-beta (pGlu-Abeta). PGlu-Abeta seeds Abeta oligomers which, due to their hypertoxicity, are regarded as the key culprits behind AD.

In the published data, over 200 young and elderly healthy volunteers were included in a single-and multiple-ascending dose design. PQ912 was found to be safe and well tolerated; the maximum tolerated dose was not reached. The study also evaluated pharmacokinetic parameters of the compound as well as the extent of QC inhibition in the cerebral spinal fluid (CSF), which is a measure for QC-inhibition in the brain. Based on the data obtained in CSF, the dose dependent target inhibition could be reliably determined and was used for dose selection in the current phase 2a trial. The study was conducted with Covance in Switzerland and the UK.

Dr Inge Lues, Chief Development Officer at Probiodrug and first author of the paper, said: "This is ground-breaking data as for the first time a compound targeting glutaminyl cyclase (QC) enzyme inhibition has been assessed in man for the inhibition of pyroglutamate-amyloid-beta (pGlu-Abeta) formation and thus potentially the treatment of AD. The primary objective of our ongoing phase 2a study (SAPHIR) is to evaluate the safety of PQ912 in the AD patient population. Exploratory read-outs are also included to investigate the hypotheses that inhibition of QC interferes with AD pathology. Beside sensitive cognitive measures to capture acute cognitive improvement, we are also measuring by means of EEG and functional MRI any effects on synaptic plasticity and neuronal connectivity, the physiological basis of memory and learning. In addition, we will introduce a set of biomarkers closely related to the concept, Abeta Oligomer- and pE-Abeta levels in CSF to learn about their potential as AD biomarkers."

Dr Konrad Glund, CEO of Probiodrug and co-author, added: "The publication of the phase 1 results in a peer reviewed journal marks an important milestone for Probiodrug. The company has progressed the project from the discovery of QC as the enzyme responsible for modifying truncated Abeta into pGlu-Abeta to the current stage. The resulting data provide the basis for testing the attractive hypothesis of inhibiting QC as a treatment for AD in patients, which we are currently evaluating in our phase 2a study. This concept of preventing the formation of pGlu-Abeta via QC inhibition as a treatment for AD addresses exclusively toxic Abeta species, and is unique and differentiated to any other Abeta focused therapeutic concept."

The article "A phase 1 study to evaluate the safety and pharmacokinetics of PQ912, a glutaminyl cyclase inhibitor, in healthy subjects; Lues, Inge et al, Alzheimer's & Dementia: Translational Research & Clinical Interventions [Volume 1, Issue 3, Pages 182-195], can be found here: http://dx.doi.org/10.1016/j.trci.2015.08.002.

For more information, please contact:
Probiodrug
Dr Konrad Glund, CEO
Email: contact@probiodrug.de

Hume Brophy
Supriya Mathur, Eva Haas, Alexia Faure
Tel: +44 (0) 203 440 5657
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, 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.
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, 44 million people worldwide currently live with the condition and this number is expected to almost double by 2030 and to more than triple by 2050 to over 132 million. Alzheimer's also has an estimated, global societal cost of over $600 billion (World Alzheimer Report 2014).

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.