Vivoryon Therapeutics AG enters myeloid immune checkpoint drug discovery, and collaborates with the University of Kiel to select cancer therapy candidates from its QPCTL inhibitor portfolio

HALLE (SAALE), Germany, 27 June 2019 – Vivoryon Therapeutics AG, (Euronext Amsterdam: currently PBD, to be changed to VVY, ISIN: DE0007921835) announced today that they have entered into a research collaboration with University Medical Center Schleswig-Holstein, Campus Kiel, to discover and develop first-in-class therapeutics in cancer immunotherapy. Professor Thomas Valerius and his group will qualify Vivoryon’s broad portfolio of small molecule QPCTL inhibitors for their use as modulators of the CD47/SIRP-alpha myeloid immune checkpoint. These inhibitors, some of which have already been clinically tested, originated from the Company’s Alzheimer’s disease drug development program which remains to be a core focus for Vivoryon Therapeutics. Besides, these inhibitors also offer interesting therapeutic options in immuno-oncology.

Recently published and internal research has shown that the Glutaminyl-peptide cyclotransferase-like (QPCTL) enzyme is a powerful therapeutic target to silence the “do not eat me” signal provided by the interaction of CD47 (expressed on cancer cells), with the protein SIRP-alpha (expressed on macrophages and other myeloid cells). Tumor immunotherapy that targets this interaction is a current focus of innovation in cancer drug development. Combining a therapeutic tumor-targeted antibody of choice with the inhibition of the CD47/SIRP-alpha interaction is expected to lead to significant therapeutic improvements. By possessing the broadest portfolio of small molecule QPCTL inhibitors and the clinically most advanced compounds in that field, Vivoryon Therapeutics is uniquely positioned. QPCTL inhibitors are expected to have considerable therapeutic advantages compared to antibody approaches that are currently explored in clinical studies to silence the CD47/SIRP-alpha interactions.

Dr. Michael Schaeffer, CBO of Vivoryon Therapeutics said: “We are very pleased to partner with the University Medical Center Schleswig-Holstein, who is -like us- truly dedicated to accelerating innovative cures for cancer. Professor Valerius is a renowned expert in the field of myeloid effector cells in immunotherapy. This collaboration allows us to engage multiple targets and fully exploit our unique patent position. Undoubtedly, we are now entering into one of the most exciting fields of current drug development.”

Within this collaboration Vivoryon Therapeutics will fund focused research with the clear goal of further qualifying its QPCTL inhibitors in cellular cancer models. Vivoryon’s highly active compounds will be tested individually and in combination with therapeutic antibodies.

Prof. Dr. Thomas Valerius, Senior Physician at the Department of Internal Medicine II – Hematology, Oncology of the University Hospital Schleswig-Holstein, added: “Our partnership with Vivoryon Therapeutics fits well with our goal of advancing early-stage therapeutic innovation. We are delighted that we are working on some of the most exciting compounds in myeloid checkpoint inhibition today and are convinced that these molecules could lead to significant improvements in cancer immunotherapy.”

The development partners confirm that the cooperation has no effect on sales transactions of the University Medical Center Schleswig-Holstein – in particular procurement processes – and there are no expectations in this connection.

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For more information, please contact:

Vivoryon Therapeutics AG
Dr. Ulrich Dauer, CEO
Email: contact@vivoryon.com

Universitätsklinikum Schleswig-Holstein, Campus Kiel
Medizinische Klinik II, Sektion für Stammzell- und Immuntherapie
Prof. Dr. med. Thomas Valerius
Email: t.valerius@med2.uni-kiel.de

MC Services AG
Anne Hennecke, Susanne Kutter
Tel: +49 (0) 211 529 252 27
Email: vivoryon@mc-services.eu

Notes to Editors:

About Vivoryon Therapeutics AG

Headquartered in Halle (Saale), Germany, Vivoryon Therapeutics AG, formerly Probiodrug AG (Euronext Amsterdam: currently PBD, to be changed to VVY) is a precision intervention company with an advanced candidate in clinical development focused on bringing first-in-class therapies to patients suffering from age-related diseases. The company has a successful track record in bringing drugs targeted to post-translational modifying enzymes to the market. Current projects are focusing on the two isoenzymes of Glutaminyl cyclase, QPCT and QPCTL. QPCT is the crucial enzyme for the generation of highly neurotoxic pyroglutamate species of Abeta. Its inhibition by Vivoryon’s lead molecule PQ912, has successfully completed a Phase 2a (SAPHIR) study and the Company has initiated a Phase 2b core program for the treatment of Alzheimer’s disease (AD). QPCTL has been identified as a potential target in cancer therapy. Blocking the enzymatic function of QPTCL by small molecule inhibitors is a novel therapeutic approach to silence the CD47/SIRP-alpha signal in cancer immunotherapy. Vivoryon Therapeutics has a unique and exceptionally strong patent position on QPCT and QPCTL inhibitors.

www.vivoryon.com

About PQ912

PQ912, is a first in class, highly specific and potent inhibitor of Glutaminyl-peptide cyclotransferase protein (QPCT), the enzyme that catalyzes the formation of highly neurotoxic pGlu species. 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 resulting in >90% target occupancy in the spinal fluid. In June 2017, Vivoryon Therpeutics announced promising top-line data of the Phase 2a SAPHIR trial of PQ912 and presented the study results at CTAD 2017. Results strongly support that pGlu species of Abeta are especially neurotoxic and correlate with AD disease progression. The SAPHIR study provides important guidance on how to move forward with 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. Today, 50 million people are estimated to live with dementia worldwide, and this number is projected to triple to more than 152 million by 2050. Dementia also has a huge economic impact. Alzheimer’s has an estimated, global societal cost of US$ 1 trillion, and it will become 2 trillion-dollar disease by 2030. (World Alzheimer Report 2018).

Glutaminyl-peptide cyclotransferase-like protein (QPCTL)

Glutaminyl-peptide cyclotransferase-like protein (QPCTL) is a posttranslational modifying enzyme that is responsible for the pyroglutamate formation on CD47 – a crucial receptor protein in the immune response to cancer. QPCTL is an isoenzyme of QPCT and can be inhibited by Vivoryon’s lead candidate small molecule PQ912 and other compounds protected under Vivoryon’s patents.

Cancer immune checkpoint inhibitors

Checkpoint inhibitor therapy is a novel kind of cancer immunotherapy. This therapy targets key regulators of the immune system that stimulate or inhibit its actions, which tumors commonly use to protect themselves from attacks by the immune system. QPCTL inhibitor therapy can silence inhibitory cancer checkpoints and thereby restore beneficial immune system functions.

University Hospital Schleswig-Holstein (UKSH)

The University Hospital Schleswig-Holstein (UKSH) is one of the largest medical centers in Europe, with locations in Kiel and Lübeck. The unique selling point of university medicine is the interplay between patient care, research and teaching with the effect that scientific findings flow directly into patient care (translation). Together with the medical faculty of the Christian-Albrechts-University Kiel and the senate-exchange medicine of the University of Lübeck, the UKSH faces the challenges of the medicine of the 21^st century.

The UKSH, as the only maximum care hospital in the northernmost state, guarantees individualized diagnostics and therapy for 500,000 people – one in six inhabitants – every year and provides one quarter of all hospital services. The 85 clinics and institutes offer the entire spectrum of modern medicine – especially for patients requiring highly differentiated diagnostics and therapy as well as emergency care around the clock.

The UKSH generates a balance sheet total of approx. 1.4 billion euros and is the largest public employer with approx. 14,200 employees from 120 nations as well as an important training company play an important role in the health economy of Northern Germany.

www.uksh.de

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 Vivoryon Therapeutics 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.