N-Acetyl-L-Leucine for GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease)

Parent Study Inclusion Criteria

Individuals who meet all of the following criteria are eligible to participate in the
study:

1. Written informed consent signed by the patient and/or their legal representative/
parent

2. Male or female aged ≥6 years in Europe OR ≥18 years in the United States with a
confirmed diagnosis of GM2 Gangliosidosis ( i.e., clinical features and positive
genetic test GM2-gangliosidosis caused by β-hexosaminidase deficiency resulting from
mutations in the HEXA or HEXB genes) at the time of signing informed consent.

3. Females of childbearing potential, defined as a premenopausal female capable of
becoming pregnant, will be included if they are either sexually inactive (sexually
abstinent for 14 days prior to the first dose continuing through 28 days after the
last dose) or using one of the following highly effective contraceptives (i.e.
results in <1% failure rate when used consistently and correctly) 14 days prior to
the first dose continuing through 28 days after the last dose:

1. intrauterine device (IUD);

2. surgical sterilization of the partner (vasectomy for 6 months minimum);

3. combined (estrogen or progestogen containing) hormonal contraception associated
with the inhibition of ovulation (either oral, intravaginal, or transdermal);

4. progestogen-only hormonal contraception associated with the inhibition of
ovulation (either oral, injectable, or implantable);

5. intrauterine hormone-releasing system (IUS);

6. bilateral tubal occlusion.

4. Females of non-childbearing potential must have undergone one of the following
sterilization procedures at least 6 months prior to the first dose:

1. hysteroscopic sterilization;

2. bilateral tubal ligation or bilateral salpingectomy;

3. hysterectomy;

4. bilateral oophorectomy;

OR

be postmenopausal with amenorrhea for at least 1 year prior to the first dose and
follicle stimulating hormone (FSH) serum levels consistent with postmenopausal
status. FSH analysis for postmenopausal women will be done at screening. FSH levels
should be in the postmenopausal range as determined by the central laboratory.

5. Non-vasectomized male patient agrees to use a condom with spermicide or abstain from
sexual intercourse during the study until 90 days beyond the last dose of study
medication and the female partner agrees to comply with inclusion criteria 3 or 4.
For a vasectomized male who has had his vasectomy 6 months or more prior to study
start, it is required that they use a condom during sexual intercourse. A male who
has been vasectomized less than 6 months prior to study start must follow the same
restrictions as a non-vasectomized male.

6. If male, the patient agrees not to donate sperm from the first dose until 90 days
after dosing.

7. Patients must fall within:

a) A Scale for the Assessment and Rating of Ataxia (SARA) score of 5 ≤ X ≤ 33 points
(out of 40) AND i. Within the 2-7 range (out of 0-8 range) of the Gait subtest of
the SARA scale OR ii. Be able to perform the 9 Hole Peg Test with Dominant Hand
(9HPT-D) (SCAFI subtest) in 20 ≤ X ≤150 seconds.

8. Weight ≥15 kg at screening.

9. Patients are willing to disclose their existing medications/therapies for (the
symptoms) of GM2 Gangliosidosis, including those on the prohibited medication list.
Non-prohibited medications/therapies (e.g. concomitant speech therapy, and
physiotherapy) are permitted provided:

1. The Investigator does not believe the medication/therapy will interfere with
the study protocol/results

2. Patients have been on a stable dose/duration and type of therapy for at least 6
weeks before Visit 1 (Baseline 1)

3. Patients are willing to maintain a stable dose/do not change their therapy
throughout the duration of the study.

10. An understanding of the implications of study participation, provided in the written
patient information and informed consent by patients or their legal
representative/parent, and demonstrates a willingness to comply with instructions
and attend required study visits (for children this criterion will also be assessed
in parents or appointed guardians).

Parent Study Exclusion Criteria

Individuals who meet any of the following criteria are not eligible to participate in the
study:

1. Asymptomatic patients

2. Patient has clinical features of Tay-Sachs or Sandhoff disease, but a completely
negative result on a previous genetic test for GM2 Gangliosidosis caused by
β-hexosaminidase deficiency resulting from mutations in the HEXA or HEXB genes

3. Patients who have any of the following:

1. Chronic diarrhea;

2. Unexplained visual loss;

3. Malignancies;

4. Insulin-dependent diabetes mellitus.

5. Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or
derivatives.

6. History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose,
sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan,
dimethicone, methylparaben, and potassium sorbate).

4. Simultaneous participation in another clinical study or participation in any
clinical study involving administration of an investigational medicinal product
(IMP; 'study drug') within 6 weeks prior to Visit 1.

5. Patients with a physical or psychiatric condition which, at the investigator's
discretion, may put the patient at risk, may confound the study results, or may
interfere with the patient's participation in the clinical study.

6. Known clinically-significant (at the discretion of the investigator) laboratories in
hematology, coagulation, clinical chemistry, or urinalysis, including, but not
limited to:

1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper
limit of normal (ULN);

2. Total bilirubin >1.5x ULN, unless Gilbert's syndrome is present in which case
total bilirubin >2x ULN.

7. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol.

8. Current or planned pregnancy or women who are breastfeeding.

9. Patients with severe vision or hearing impairment (that is not corrected by glasses
or hearing aids) that, at the investigator's discretion, interferes with their
ability to perform study assessments.

10. Patients who have been diagnosed with arthritis or other musculoskeletal disorders
affecting joints, muscles, ligaments, and/or nerves that by themselves affects
patient's mobility and, at the investigator's discretion, interferes with their
ability to perform study assessments.

11. Patients unwilling and/or not able to undergo a 6-week washout period from any of
the following prohibited medication prior to Visit 1 (Baseline 1) and remain without
prohibited medication through Visit 6.

1. Aminopyridines (including sustained-release form);

2. N-Acetyl-DL-Leucine (e.g. Tanganil®);

3. N-Acetyl-L-Leucine (prohibited if not provided as IMP);

4. Riluzole;

5. Gabapentin;

6. Varenicline;

7. Chlorzoxazone;

8. Sulfasalazine;

9. Rosuvastatin.

Extension Phase Inclusion Criteria

1. Completed Visit 6 of the IB1001-202 Parent Study

2. The Principal Investigator determines further treatment with IB1001 to be in the
patient's best interest

3. Written informed consent signed by the patient and/or their legal
representative/parent/ impartial witness for participation in the Extension Phase

4. Patients are willing to continue to remain without the following prohibited
medication from Visit 6 throughout the duration of the Extension Phase:

Aminopyridines (including sustained-release form); b) N-Acetyl-DL-Leucine (e.g.
Tanganil®); c) N-Acetyl-L-Leucine (prohibited if not provided as IMP); d) Riluzole; e)
Gabapentin; f) Varenicline; g) Chlorzoxazone; h) Sulfasalazine; i) Rosuvastatin.