Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study of Autologous MSC-NTF Cells in Patients With ALS

The MSC-NTF cell therapy (NurOwn™) is based on transplantation of autologous bone marrow
derived mesenchymal stromal cells (MSC), which are enriched from the patients' own bone
marrow, propagated ex vivo and induced to secrete NTFs. The autologous MSC-NTF cells are
back-transplanted into the ALS patient into the sites of damage, the spinal cord and the
muscles.

NTFs are potent survival factors for embryonic, neonatal, and adult neurons and are
considered potential therapeutic candidates for ALS. Delivery of appropriate NTFs to the
immediate environment of afflicted neurons in ALS patients is expected to improve their
survival and thus slow down disease progression and alleviate symptoms.

Previous open-label clinical trials have shown that MSC-NTF cells treatment was well
tolerated and appears to be generally safe. Some initials indications of clinical benefit
were also observed in some patients.

This multi-center, randomized, double blind, placebo controlled study will evaluate the
safety and efficacy of a single combined intramuscular and intrathecal administration of
MSC-NTF cells in early-stage ALS patients. Patients will be followed for approximately three
months before transplantation with their autologous MSC-NTF cells or placebo. During this
period of time, patient bone-marrow will be harvested and mesenchymal stromal cells will be
isolated and expanded. Following treatment patients will be followed for a total of six
months at monthly visits.

Inclusion Criteria

1. Males and females ages 18 to 75 years old, inclusive.

2. ALS diagnosed as possible, laboratory-supported probable, probable, or definite as
defined by revised El Escorial criteria.

3. Disease onset, as defined by first reported occurrence of symptomatic weakness,
spasticity, or bulbar symptoms, of more than 12 months and less than or equal to 24
months.

4. Current disease symptoms must include limb weakness.

5. ALSFRS-R ≥30 at the Screening Visit.

6. Upright slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and
age at the Screening Visit.

7. Subjects must be taking a stable dose of riluzole for at least 30 days prior to
enrolment or not be on riluzole, and not have been on it for at least 30 days prior to
enrolment (riluzole-naïve subjects are permitted in the study).

8. Capable of providing informed consent and willing and able to follow study procedures,
including willingness to undergo lumbar puncture.

9. Geographic accessibility to the study site and willingness and ability to comply with
follow-up.

10. Women of child-bearing potential must agree not to become pregnant for the duration of
the study. Women must be willing to consistently use two forms of contraceptive
therapy throughout the course of the trial, and undergo a pregnancy test one week
before bone marrow aspiration. Men must be willing to consistently use two forms of
contraceptive if their partners are of child-bearing age.

11. Citizen or permanent resident of the United States.

Exclusion Criteria:

1. Prior stem cell therapy of any kind.

2. Inability to lie flat for the duration of intrathecal cell transplantation and/or bone
marrow biopsy, or inability to tolerate study procedures for any other reason.

3. History of autoimmune disease (excluding thyroid disease) myelodysplastic or
myeloproliferative disorder, leukemia or lymphoma, whole body irradiation, hip
fracture, or severe scoliosis.

4. Any unstable clinically significant medical condition other than ALS (e.g., within six
months of baseline, had myocardial infarction, angina pectoris, and/or congestive
heart failure), treatment with anticoagulants that, in the opinion of the
investigator, would compromise the safety of patients.

5. Any history of malignancy including any malignancy affecting the central nervous
system and melanoma, within the previous 5 years, with the exception of localized skin
cancers (with no evidence of metastasis, significant invasion, or re-occurrence within
three years of baseline).

6. Serum AST or ALT value >3.0 times the upper normal limit.

7. Serum creatinine value >2.0 times the upper normal limit.

8. Positive test for Hepatitis B, Hepatitis C, HIV.

9. Current use of immunosuppressant medication or use of such medication within 4 weeks
of Screening visit (Visit 1).

10. Any history of acquired or inherited immune deficiency syndrome.

11. Exposure to any other experimental agent (off-label use or investigational) or
participation in a clinical trial within 30 days prior to Screening Visit (Visit 1).

12. Use of non-invasive ventilation (NIV), diaphragm pacing system or invasive ventilation
(tracheostomy).

13. Any history of either substance abuse within the past year, or unstable psychiatric
disease according to PI judgment.

14. Placement or usage of feeding tube.

15. Pregnant women or women currently breastfeeding.