July 31, 2024
SanBio Co., Ltd.
SanBio Obtains Marketing Approval for “AKUUGO🄬🄬 Suspension for Intracranial
Implantation” (INN: Vandefitemcel) as a Therapeutic Agent for Improving Chronic
Motor Paralysis From Traumatic Brain Injury (TBI)- World’s First Therapeutic Agent for Regenerating Brain -SanBio Co., Ltd. (head office: Tokyo, representative director & CEO: Keita Mori) hereby
announces that today on July 31 2024, it obtained conditional and time-limited marketing
approval for the human somatic stem cell-processed product “AKUUGO🄬🄬 suspension for
intracranial implantation” (INN: vandefitemcel; hereafter, “AKUUGO🄬🄬”) in Japan, for theindication of improving chronic motor paralysis resulting from traumatic brain injury.
Traumatic brain injury (TBI) is caused by a strong external force, such as from a traffic
accident or a fall, applied to the head, damaging the brain tissue within the skull. The
manifestation and timing of symptoms of TBI vary widely among patients, and dependingon the affected area of the brain, patients may experience aftereffects such as motor
dysfunction or higher brain dysfunction. Studies suggest that destroyed or damaged brain
tissues do not regenerate naturally, and patients who enter the chronic phase of TBI anddevelop motor paralysis face lifelong impacts on their daily and social lives, indicating that
there is a significant unmet medical need.
AKUUGO🄬🄬 has been shown to be effective in improving chronic motor paralysis associatedwith TBI, and is the world’s first and only allogeneic cell therapeutic agent* approved for thisindication. AKUUGO🄬🄬 is also a world first in that it facilitates the regeneration of brain, andits approval for practical clinical use marks a significant milestone. AKUUGO🄬🄬 is an
allogeneic cell product manufactured by culturing bone marrow-derived mesenchymal
stem cells collected from healthy donors and transiently transfecting the human Notch-1
intracellular domain gene into the cultured cells to enhance their ability to regenerate nerve
cells. The transplantation of AKUUGO🄬🄬 into damaged nerve tissues in the brain isexpected to trigger the release of FGF-2 (a type of protein) and other substances, which
in turn will promote the natural regenerative ability of damaged nerve cells and induce
proliferation and differentiation of nerve cells. The results of basic research have also
shown that AKUUGO🄬🄬 has protective effects on nerve cells, induces angiogenesis, anddemonstrates immunomodulating effects.
Mori Keita CEO of SanBio commented as follows.
“We are extremely pleased to announce that we have obtained conditional and timelimited approval for AKUUGO🄬🄬 after 24 years in operation, enabling us to provide itas a new treatment option for TBI patients in Japan. AKUUGO🄬🄬, which is directly
administered to the brain, represents an innovative and crucial choice for patientswith chronic motor paralysis associated with TBI. Through AKUUGO🄬🄬, we hope tobring hope to the lives of as many TBI patients as possible.”

The approval of AKUUGO🄬🄬 was based on the results of the global Phase 2 clinical trial
SanBio conducted in Japan and the United States. Dr. Nobuhito Saito, Professor ofNeurology at the University of Tokyo led the clinical trial, commented as follows.
“Traumatic brain injury can affect various areas of the brain, and the site and extentof the damage determine the duration and severity of symptoms, as well asaftereffects. Rehabilitation in the acute phase is effective in restoring a certain levelof motor function; however, because damaged brain cells do not regenerate, there
has been no effective treatment for chronic motor deficit and other aftereffects oftraumatic brain injury. The approval of AKUUGO🄬🄬 may provide a new treatment
option for patients suffering from the chronic aftereffects of traumatic brain injury,
and I look forward to seeing further progress in research and analysis.”
Dr. David O. Okonkwo, Professor of neurological surgery and director of the Neurotrauma
Clinical Trials Center at University of Pittsburg commented as follows.
“Patients with chronic traumatic brain injury experience lifelong disability affecting
quality of life, particularly those with motor deficits. Living with traumatic brain injury
also places burdens on the caregivers who support them. The approval ofAKUUGO🄬🄬 is a breakthrough and opens a new chapter in the treatment of motor
deficits in chronic traumatic brain injury.”.
Dr. Hideyuki Okano, a Keio University professor and SanBio’s founding scientist who has
supported the Company over many years, commented as follows.
“For more than 20 years, SanBio has conducted R&D in the field of brain
regenerative medicine. I’m pleased that AKUUGO🄬🄬 has been approved for treating
chronic motor paralysisresulting from traumatic brain injury, the first such treatment
to be approved in the world, and thrilled to offer the product as a new treatment option
to patients in Japan. The approval of AKUUGO🄬🄬 in Japan, ahead of anywhere elsein the world, brings us closer to achieving our goal of supporting patients with central
nervous system disorders, especially brain disorders, around the world who stillsuffer from the lack of effective treatment options. “Product Overview
Brand name

Generic nameIndications andeffects
Dosage andadministration

Reference
AKUUGO🄬🄬 Suspension for Intracranial Implantation
Vandefitemcel
Improvement of chronic motor paralysis associated with traumaticbrain injury
For adults, implant 5 x106 live human (allogeneic) bone marrowderived mesenchymal stem cells (300μL of cell suspension) toperilesional brain tissues via stereotactic brain surgery using thededicated delivery device set.
Implant the cells into the perilesional area through threetrajectories via a burr hole made in the skull. To each trajectory,
inject 100μL of the cell suspension, depositing 20μL of the solution
each across a total of five sites placed at 5–6mm intervals from thedeepest site. The rate of implantation should be approximately
10μL/min. Follow the steps below for implantation.

Date of marketing
approval

1. Bef ore starting the procedure, attach the guide & stop and stylet-equipped
inserter f rom the dedicated delivery device set to the head f ixation device f orinvasive neurosurgery.
2. Thaw the cell suspension f or intracranial implantation, wash it with the dedicatedpreparation solution, and adjust the concentration of the cell suspension to 1.67 x
106 cells/100μL using the dedicated preparation solution. Cleanse the micro-syringe
f ixed with the cannula f rom the dedicated delivery device set with the dedicatedpreparation solution bef ore f illing it with the prepared cell suspension.

July 31, 2024

Product image

Vial containing cell suspension for
intracranial implantation

Dry shipper

Hard case and dry shipper fortransportation

Dedicated preparation solution

Outer package for dedicated preparation
solution

Dedicated delivery device set
Outer package for dedicated delivery
device set[Condition of approval]
1. Considering the limited manufacturing record for the Product, the Company shall promptly collectinformation on the Product’s quality based on a pre-determined plan, and evaluate and report on theequivalence/homogeneity, in terms of quality, of the investigational product (clinical trials product) and theProduct intended for commercial distribution. Based on the evaluation results, the Company shall apply
for a partial change of approved matters. It shall not ship the Product until the partial change application
has been approved.
2. The Company must ensure that the Product is used in medical facilities fully equipped to handle
emergencies, by physicians who possess sufficient knowledge and experience in the diagnosis andtreatment of traumatic brain injury and stereotactic brain surgery techniques. The physicians must also
have sufficient knowledge of the clinical trial results and adverse events of the Product.
3. Until the Company re-applies for marketing approval for the Product prior to the expiration of theconditional and time-limited approval, the Company must conduct post-marketing evaluation of all cases
where the Product is used.
4. Until the Company re-applies for marketing approval for the Product prior to the expiration of theconditional and time-limited approval, the Company must collect information on the biologicalcharacteristics reflecting the mechanisms of action of the Product and take necessary measures, such asimproving its quality control strategy.

*

About allogeneic cell transplantation

Regenerative medicine therapies can be classified into autologous and allogeneic celltherapies. In autologous cell transplantation, the patient’s own cells are harvested and used,
but cell processing procedures are time-consuming and labor-intensive. In allogeneic celltransplantation, on the other hand, cells are collected from a donor and cultured in large
quantities. Since allogeneic cell medicines can be mass produced, they can treat a large
number of patients.
About Traumatic Brain Injury
Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide.
The estimated global incidence of acute TBI during 2016 was 27 million cases, and theestimated global prevalence of chronic impairment secondary to TBI was 55.5 million
cases1.Overall, TBI and long-term motor deficits secondary to TBI significantly impair aperson’s self-care, employability, and quality of life, and are major burdens on healthcare
systems worldwide. In the United States, approximately 43% of surviving hospitalized
persons with TBI experience long-term disabilities2, and it is estimated that 3.17 million
people are living with long-term disabilities secondary to TBI3. There are about 60,000*4 TBIpatients in Japan, and of which, 20%*5 are estimated to suffer from aftereffects of the injury.
About "AKUUGO🄬🄬 suspension for intracranial implantation”
AKUUGO🄬🄬 suspension for intracranial implantation(INN: vandefitemcel) is a human(allogeneic) bone marrow-derived modified mesenchymal stem cell that is produced bymodifying and culturing mesenchymal stem cells derived from the bone marrow aspirate ofhealthy adults. The transplantation of AKUUGO🄬🄬 into damaged nerve tissues in the brain isexpected to trigger the release of FGF-2 (a type of protein) and other substances, which inturn will promote the natural regenerative ability of damaged nerve cells and induce
proliferation and differentiation of nerve cells. The conditional and time-limited approval wasbased on the results of SanBio’s global Phase 2 clinical trial. The primary endpoint of thetrial—mean change from baseline in Fugle-Meyer Motor Scale (FMMS) score at 24 weeks
after treatment—was met, with the AKUUGO🄬🄬-treated group reporting 8.3-point improvement
versus 2.3 for the control group, demonstrating a statistically significant difference. The final
analysis of the study was presented at the annual meeting of American Academy ofNeurology. We are pushing forward with R&D targeting multiple indications, including chroniceffects associated with chronic cerebral infarction.
About SanBio Group (SanBio Co., Ltd. and SanBio, Inc.)
SanBio is engaged in the regenerative cell business—we research, develop, manufacture,and sell regenerative cell medicines. In July 2024, under the Sakigake Designation Program,
we obtained conditional and time-limited approval for our mainstay product AKUUGO🄬🄬 for
the indication of improving chronic motor deficit resulting from traumatic brain injury. Goingforward, we will continue focusing our R&D efforts on central nervous system disorders withsignificant unmet medical needs that cannot be addressed by existing medicine or drugs.
The Company is headquartered in Tokyo, Japan and Oakland, California, and additional
information about SanBio Group is available at https://sanbio.com/en/<References>

James SL, et al. “Global, regional, and national burden of traumatic brain injury and spinal
cord injury, 1990- 2016: a systematic analysis for the Global Burden of Disease Study 2016.”
Lancet Neurol 2019;18:56-87.
2 Selassie AW, et al. “Incidence of long-term disability following traumatic brain injury
hospitalization, U.S.”, 2003. J Head Trauma Rehabil 2008;23:123-31
3 Zaloshnja E, Miller T, Langlois JA, Selassie AW. Prevalence of long-term disability fromtraumatic brain injury in the civilian population of the United States, 2005. J Head Trauma
Rehabil. 2008 Nov-Dec;23(6):394-400.
4 The number of patients under “19 Injury, poisoning, and other consequences of externalcauses (intracranial injuries)” in Patient Survey 2020, the Ministry of Health, Labour andWelfare
5 The number of patients under “T905 After effects of intracranial injury” in Patient Survey
2020, the Ministry of Health, Labour and Welfare
1For more information, contact:
SanBio Co., Ltd.
Management Administration
Email: info@sanbio.com