Testing the Safety and Preliminary Efficacy of the New Drug ORY-2001 in Mild to Moderate Alzheimer's Disease

This phase IIa study is a double-blind, randomized, parallel-group and multicenter study with
a placebo-controlled 24-week treatment period followed by a no placebo-controlled 24-week
extension period.

It is planned to randomise 25 patients. In the double-blind placebo-controlled treatment
period, all patients will be randomized between two doses of ORY-2001 and placebo. In the
double-blind no placebo-controlled extension period, patients in the placebo arm will be
re-allocated in one of the two different dose levels of ORY-2001. Randomization will be
stratified by cognitive impairment severity.

An independent Data Monitoring Committee (DMC) will review un-blinded safety data throughout
the study.

Inclusion Criteria:

- Probable Alzheimer's Disease (AD) diagnosed according to National Institute of
Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and
Related Disorders Association (NINCDS-ADRDA) criteria

- MMSE score at Screening and Baseline Visits of at least 16 and not greater than 26

- Evidence of the AD pathophysiological process indicated by decreased levels of amyloid
antigen binding (AB) and increased levels of total Tau protein or phospho-Tau protein
in cerebrospinal fluid (CSF)

- Outpatient consulting a general practitioner, or a
psychiatrist/neurologist/geriatrician

- Knowledgeable and reliable close relative/caregiver who will accompany the patient to
all clinic visits during the study

- Daily treatment with the same acetylcholinesterase inhibitor on a stable dose

- Fertile male and female must use highly effective contraception, from the Screening
Visit until 90 days after last dose.

- Signed informed consent by patient (or legal representative, if applicable) and a
close relative/caregiver prior to the initiation of any study specific procedure

Exclusion Criteria:

- Failure to perform screening or baseline examinations

- Hospitalization or change of concomitant medication 1 month prior to Screening visit
or during Screening Period

- Clinical, laboratory or neuroimaging findings consistent with:

1. Other primary degenerative dementia;

2. Other neurodegenerative condition;

3. Cerebrovascular disease;

4. Other central nervous system diseases;

- A current Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of major depression,
schizophrenia or bipolar disorder

- Positive results for tuberculosis, human immunodeficiency virus (HIV), hepatitis C or
hepatitis B (hepatitis B surface antigen [HbsAg]) serology at the Screening Visit

- Clinically significant, advanced or unstable disease that may interfere with
evaluation.

- Disability that may prevent the patients from completing all study requirements.

- Chronic drug intake of forbidden concomitant medication.

- Treatment with anti-amyloid beta or anti-Tau protein monoclonal antibodies or other
disease modifying strategies within three months or five half-lives, whichever is
longer, prior to the Screening Visit

- Treatment with an active vaccine targeting amyloid beta or Tau protein

- Suspected or known drug or alcohol abuse

- Metallic implants or any other cause precluding the performance of brain MRI

- Enrolment in another investigational study or intake of investigational drug within
the previous 3 months since the last dose

- Suicide attempt within the last year or significant risk of suicide (in the opinion of
the investigator, defined as a "yes" to suicidal ideation questions 4 or 5, or
answering "yes" to suicidal behavior on the Columbia-Suicide Severity Rating Scale
within the past 12 months)

- Any condition that in the opinion of the investigator makes the patient unsuitable for
inclusion in the study