Probiodrug reports full year 2018 financial results

• Conference call and webcast (in English) at 3:00 pm CET (10:00 am EDT)
• NIH grant of 15million USD received
• PQ912 Phase 2b core program prepared

HALLE (SAALE), Germany, 28 March 2019 Probiodrug AG (Euronext Amsterdam: PBD), a clinical stage biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer’s disease (AD), today announced its financial results for the twelve-month period ending December 31, 2018, prepared in accordance with German GAAP (“HGB”) and on a voluntary basis, in accordance with IFRS as endorsed by the European Union. The Financial Statements are available on the company website (www.probiodrug.de/investors/reports-and-presentations/).

KEY HIGHLIGHTS

• PQ912 Phase 2b core program prepared
• Publication of new results of PQ912 pharmacology in peer reviewed journal
• Annual Shareholders’ Meeting held on June 21, 2018
• Expenditures and corresponding cash position in line with management expectations
• Cash and cash equivalents of EUR 3.8 million as of December 31, 2018 to provide, according to present projections, a cash reach through 3^rd quarter of 2019

POST PERIOD HIGHLIGHTS

In March 2019 Probiodrug announced a funding of the National Institutes of Health (NIH) of total 15 million USD over four years.

The grant was awarded by the National Institute on Aging, part of the NIH, for the project “A Seamless Phase 2A-B Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of PQ912 in Patients with Early Alzheimer’s Disease”. The funding is under award number R01AG061146 to the University of California, San Diego. Probiodrug is the sponsor of the U.S. study led by study principal investigator Howard Feldman, MD, Director of the ADCS, a national consortium of clinical sites, based at the University of California, San Diego.

Commenting on the 2018 results, Dr. Ulrich Dauer, Chief Executive Officer of Probiodrug, said:

“The overarching theme of the biopharma industry in 2018 can be expressed as a year of change. However, change is the catalyst of growth. Probiodrug followed the industry trend and experienced a change itself. The reorganization of the management team has allowed us to focus on the future funding of the company, while continuing the important work initiated by our predecessors – entering into the next stage of development for our lead candidate PQ912 and our company as a whole.”

FINANCIAL PERFORMANCE

Key Figures (according to IFRS)

Details of the Financial Results (according to IFRS)

Net loss

The operating loss improved to EUR 7,698k (2017: EUR 9,961k), mainly due to lower research and development expenses amounting to EUR 4,836k (2018: EUR 7,454k). General and administrative expenses amounted to EUR 2,891k (2017: EUR 2,511k). The net loss is slightly better than last year at EUR 7,737k (2017: EUR 8,009k) as 2017 included income from a tax gain in the amont of EUR 1,102k.

All expenditures are in line with the projections of Probiodrug.

Equity

The equity amounts to EUR 1,230k (2017: EUR 8,923k), leading to an equity ratio of 30.4%. In 2018, the share capital was unchanged at EUR 8,208k.

Cash

The cash flow used in investing activities showed proceeds from the expiration of a pension liabilities insurance in the amount of EUR 460k (2017: EUR 459k) and costs in intangible assets and equipment in the amount of EUR 16k (2017: EUR 8k). Cash and cash equivalents at year end 2018 were EUR 3,783k (2017: EUR 10,291k).

Noncurrent/ current liabilities

The noncurrent liabilities in the amount of EUR 1,854k (2017: EUR 1,171k) represent the net commitment (defined benefit liability) of the pension commitments (defined benefit obligations) of EUR 1,644k (2017: EUR 1,619k). The current liabilities increased and amount to EUR 964k (2017: EUR 668k) as at December 31, 2018. The trade payables amounting to EUR 772k (2017: EUR 344k) result from the ordinary course of business. They have a remaining term of up to one year.

NEW THERAPEUTIC APPROACH

Pipeline update

Probiodrug`s therapeutic approach targets pyroglutamate-Abeta (pGlu-Abeta, also called N3pG Abeta) as a therapeutic strategy to fight Alzheimer’s disease (AD). This modified Abeta is considered to be linked with disease initiation and progression by seeding the formation of soluble neurotoxic amyloid oligomers. Probiodrug is developing proprietary product candidates to target toxic pGlu‑Abeta via two modes of action: by (i) inhibiting the production of pGlu-Abeta; and (ii) clearing existing pGlu-Abeta from the brain.

Probiodrug’s innovative approach is based on the development of specific inhibitors for the enzyme Glutaminyl Cyclase (QC), which is instrumental in the creation of pGlu-Abeta. In addition, the Company is developing a monoclonal antibody targeting pGlu-Abeta to enhance its clearance.

To date, Probiodrug’s pipeline consists of a small molecule inhibitor of the QC-enzyme, PQ912, and a monoclonal antibody, PBD-C06, targeting pGlu-Abeta.

PQ912

PQ912 is a first-in-class inhibitor of the QC enzyme that plays a central role in the formation of synaptotoxic pGlu-Abeta oligomers. Probiodrug reported in 2017 on the first clinical study with PQ912 in subjects with biomarker-proven AD. The aim of “SAPHIR”, a Phase 2a study, was to determine the maximal tolerated dose, target occupancy and treatment-related pharmacodynamic effects. The exploratory efficacy readouts selected were tailored to the patient population with early AD. The therapeutic approach focuses on synaptic dysfunction as captured by various measures such as electroencephalography (EEG), synaptic biomarkers and sensitive cognitive tests.

PQ912 treatment resulted in a significant reduction in QC activity, which resulted in an average target occupancy of > 90%. A significant reduction of theta power in the EEG frequency analysis and a significant improvement in the One Back test of our Neuropsychological Test Battery was observed. The exploratory biomarker readouts, neurogranin for synaptic toxicity and YKL-40 as a marker of inflammation, appear to be sensitive enough to serve as efficacy markers in the next Phase 2b study.

There was no significant difference between treatments in the number of subjects with (serious) adverse events, although there were slightly more patients with a serious adverse event in the PQ912 group compared to placebo. More subjects treated with PQ912 discontinued treatment due to adverse events, mostly related to gastrointestinal and skin/subcutaneous tissue disorders.

The maximal tolerated dose of PQ912 has been identified and the results support future studies at still lower doses reaching > 50% target occupancy, a longer up-titration phase to potentially induce adaptation and longer treatment periods to confirm the early signals of efficacy as seen in this study.

The study revealed a positive benefit to 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 strategy for the Phase 2b and proof of concept program has been defined and the set-up phase of “SAPHIR 2” in Europe with Professor Philip Scheltens, Director of the Alzheimer Center VU University Medical Center Amsterdam, NL, again as Chairperson has commenced. A second complementary trial is in the planning phase, and will be run by Professor Howard Feldman, Director of ADCS in San Diego, USA.

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. In addition, the antibody was modified to reduce complement activation, which is assumed to be the cause for dose-limiting side effects (micro-bleed and micro-hemorrhage). 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 AD-mice. Moreover, no evidence was found of increased micro-hemorrhages after treatment with PBD-C06.

Publications / Presentations

255th ACS National Meeting & Exposition, New Orleans, USA

In March 2018, Probiodrug presented an oral presentation entitled: “Inhibition of glutaminyl cyclase as a new concept for the treatment of Alzheimer’s disease: PQ912, the first-in-class QC-inhibitor in clinical development for AD”.

Molecules

In May 2018, Probiodrug announced a co-authored review paper entitled ”Passive Abeta Immunotherapy: Current Achievements and Future Perspectives” in a peer-reviewed journal (S. Schilling et al. Molecules May 3, 2018, Molecules 2018, 23, 1068; DOI: 10.3390/molecules23051068).

Alzheimer’s Research & Therapy

In October 2018, the publication entitled: “Safety, tolerability and efficacy of the glutaminyl-cyclase inhibitor PQ912 in Alzheimer’s disease: results of a randomized, double-blind, placebo-controlled Phase 2a Study” (P. Scheltens et al.; Alzheimer’s Research & Therapy October 12, 2018, Alzheimer’s Research & Therapy 2018 10:107; DOI: 10.1186) was published.

Antibody Engineering & Therapeutics 2018, San Diego, USA

In December 2018, Probiodrug presented an oral presentation entitled: “Structural and Functional Analyses and Humanization of an Anti-pyroglutamate-3 Abeta Antibody for Immunotherapy of Alzheimer’s Disease”.

CORPORATE

General Meeting of Shareholders of Probiodrug AG on June 21, 2018

All resolutions proposed by the Company’s Management and Supervisory Board were approved at the meeting with a large majority.

Supervisory Board

The general shareholder meeting on June 21, 2018 re-elected Charlotte Lohmann, Dr. Erich Platzer, Dr. Dinnies von der Osten and Dr. Jörg Neermann. The Supervisory Board then re-elected Dr. Erich Platzer as chairman and Dr. Dinnies von der Osten as vice chairman.

Extraordinary Meeting of Shareholders of Probiodrug AG on December 07, 2018

An Extraordinary General Shareholders’ Meeting was held as required pursuant to section 92 (1) of the German Stock Corporation Act (Aktiengesetz – AktG) following the notice of a loss on October 15, 2018. The announcement was made as soon as the loss was assessed, to the best judgment of the management team, that the Comapany had incurred a loss greater than half of our its share capital.

OUTLOOK

The mid-term focus of Probiodrug’s business activities can be summarised as follows:

• Carrying out the Phase 2b clinical study program for PQ912,
• Continuing the development of PBD-C06,
• Conclusion of one or more industrial partnerships,
• Further scientific analysis of potential second indications for the use of QC inhibitors and
• Further strengthening Probiodrug’s financial resources.

ANNUAL FINANCIAL REPORT 2018

Probiodrug has finalized its financial statements for the year ended December 31, 2018 according to German GAAP (“HGB”) and IFRS. The auditor KPMG has issued an unqualified auditors report for both statements. The reports are available on the company website (https://www.vivoryon.com/investors/reports-and-presentations/).

FINANCIAL CALENDAR

CONFERENCE CALL AND WEBCAST

Probiodrug will host a conference call and webcast open to the public today, March 28 ,2019, at 3:00 pm CET (10:00 am EDT); the presentation will also be available on the company website. The conference will be held in English. A Question & Answer session will follow the presentation of results.

To participate in the conference call, please call one of the following numbers 10 minutes prior to commencement.

A live webcast and slides will be made available at: www.probiodrug.de/investors/

Approximately a day after the call, a slide-synchronized audio replay of the conference will be available on: www.probiodrug.de/investors/reports-and-presentations/

Please dial one of the following access numbers, then enter the PIN Code: 99703460#

###

For more information, please contact:

Probiodrug
Dr. Ulrich Dauer, CEO
Email:  contact@probiodrug.com

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

Notes to Editors:

About Probiodrug AG

Headquartered in Halle (Saale), Germany, Probiodrug AG (Euronext Amsterdam: PBD) is a clinical stage 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 development approaches are targeting a key neuro-/synaptotoxic component of the pathology, pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy. The enzyme Glutaminyl Cyclase (QC) plays a central role in this process.

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.

www.probiodrug.com

About Alzheimer’s disease

Alzheimer’s disease is a neurological disorder, which is the most common form of dementia. Today, 50 million people live with dementia worldwide, and this number is projected to treble 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).

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.