A Study of Modified Stem Cells in Traumatic Brain Injury (TBI)

SB623 cells are adult bone-marrow-derived cells that are transiently transfected with a
plasmid construct encoding the intracellular domain of human Notch-1. These cells produce
trophic factors that protect neurons in models of ischemic insult. In a rat contusion model
of TBI, implantation of SB623 around the area of the injury resulted in significant
improvement of motor function. Further, safety evaluation of animal models implanted with
SB623 cells have shown no adverse effects and no SB623-related clinical, laboratory, or
histological abnormalities were found. A 2-year Phase 1/2A dose escalation study
(NCT01287936) of SB623 stereotactically implanted into the brains of patients with chronic
motor deficits due to ischemic stroke has completed.The study has shown
statistically-significant improvements in motor function in each of three scales: the
European Stroke Scale (ESS), the National Institute of Health Stroke Scale (NIHSS) and the
Fugl-Meyer scale. The study showed no serious adverse events likely attributed to SB623, and
only minor adverse events mostly grade 1 or 2 (with one grade 3) that were unrelated,
unlikely related, or possibly related to SB623. No dose-limiting toxicities were observed.

Inclusion Criteria:

- Documented history of TBI, with correlated MRI or CT

- At least 12 months post-TBI

- Focal cerebral injury able to be identified on MRI (+/- concomitant diffuse axonal
injury)

- Neurological motor deficit substantially due to focal cerebral injury observed on MRI

- GOS-E score of 3-6 (i.e. moderate or severe disability)

- Require Motricity Index 10-81 (UE Scale) and/or 10-78 (LE Scale)

- Able and willing to undergo computed tomography (CT) and magnetic resonance imaging
(MRI)

- Subjects must be willing to participate in study related exercises to the extent
possible

- Able to undergo all planned neurological assessments

Exclusion Criteria:

- History or presence of any other major neurological disease

- Any seizures in the prior 3 months

- The presence of contracture at any joints that would interfere with interpretation of
any of the neurological assessments (e.g. contracture preventing the detection of any
increase in the range of motion or ability to perform a task)

- Other neurologic, neuromuscular or orthopedic disease that limits motor function

- Clincially significant finding on MRI of brain not related to TBI

- Known presence of any malignancy except squamous or basal cell carcinoma of the skin

- History of CNS malignancy

- Positive findings on tests for occult malignancy, unless a non-malignant etiology is
confirmed

- Uncontrolled systemic illness, including, but not limited to: hypertension (systolic
>150 mm Hg or diastolic >95 mm Hg); diabetes; renal, hepatic, or cardiac failure

- Uncontrolled major psychiatric illness, including depression symptoms (CESD-R Scale of
≥16)

- Unexplained abnormal preoperative test values (blood tests, electrocardiogram [ECG],
chest X-ray); x-ray evidence of infection; uncontrolled atrial fibrillation or
uncontrolled congestive heart failure

- Presence of craniectomy (without bone flap replacement) or other contraindication to
stereotactic surgery

- Participation in any other investigational trial within 4 weeks of initial screening
or within 7 weeks of study entry

- Botulinum toxin injection, phenol injection, intrathecal baclofen, or any other
interventional treatments for spasticity (except bracing and splinting) 16 weeks priot
to the Baseline visit.

- Ongoing use of other non-traditional drugs

- Substance use disorder (per DSM-V criteria, including drug or alcohol)

- Contraindications to head CT or MRI

- Pregnant or lactating

- Female patients of childbearing potential unwilling to use an adequate birth control
method during the 12 months of the study