Notch-1

– World’s First Therapeutic Agent for Regenerating Brain – TOKYO, Japan I July 31, 2024 I SanBio Co., Ltd. (TOKYO:4592) (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 the indication 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 depending on 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 and develop 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 associated with TBI, and is the world’s first and only allogeneic cell therapeutic agent* approved for this indication. AKUUGO ® is also a world first in that it facilitates the regeneration of brain, and its 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 is expected 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, and demonstrates immunomodulating effects. Mori Keita CEO of SanBio commented as follows. “We are extremely pleased to announce that we have obtained conditional and time-limited 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 patients with chronic motor paralysis associated with TBI. Through AKUUGO ® , we hope to bring 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 of Neurology 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 extent of the damage determine the duration and severity of symptoms, as well as aftereffects. Rehabilitation in the acute phase is effective in restoring a certain level of motor function; however, because damaged brain cells do not regenerate, there has been no effective treatment for chronic motor deficit and other aftereffects of traumatic 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 of AKUUGO ® 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 paralysis resulting 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 else in the world, brings us closer to achieving our goal of supporting patients with central nervous system disorders, especially brain disorders, around the world who still suffer from the lack of effective treatment options.“ Reference Product Overview *About allogeneic cell transplantation Regenerative medicine therapies can be classified into autologous and allogeneic cell therapies. 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 cell transplantation, 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 the estimated global prevalence of chronic impairment secondary to TBI was 55.5 million cases* 1 . Overall, TBI and long-term motor deficits secondary to TBI significantly impair a person’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 disabilities* 2 , and it is estimated that 3.17 million people are living with long-term disabilities secondary to TBI* 3 . There are about 60,000* 4 TBI patients 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 by modifying and culturing mesenchymal stem cells derived from the bone marrow aspirate of healthy adults. The transplantation of AKUUGO ® into damaged nerve tissues in the brain is expected 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 conditional and time-limited approval was based on the results of SanBio’s global Phase 2 clinical trial. The primary endpoint of the trial—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 of Neurology. We are pushing forward with R&D targeting multiple indications, including chronic effects 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. Going forward, 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 1 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 from traumatic 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 external causes (intracranial injuries)” in Patient Survey 2020, the Ministry of Health, Labour and Welfare 5 The number of patients under “T905 After effects of intracranial injury” in Patient Survey 2020, the Ministry of Health, Labour and Welfare SOURCE: SanBio

SAN DIEGO--(BUSINESS WIRE)-- DermTech International (NASDAQ: DMTK) (DermTech or the Company), a leader in precision dermatology enabled by a non-invasive skin genomics technology, today announced the presentation of two research abstracts at the 2024 American Academy of Dermatology (AAD) Annual Meeting, taking place March 8th-12th in San Diego, California. The first research abstract, “Non-invasive gene expression analyses to rule out melanoma in patients with Fitzpatrick skin types IV-VI” will be presented March 9th at 8:45am PT by Maral K. Skelsey, MD, lead author and Clinical Professor of Dermatology at Georgetown University’s Medical School. In this research, the negative predictive value (NPV) for both Fitzpatrick skin type group I-III and Fitzpatrick skin type group IV-VI was greater than 99%, and the 95% confidence interval indicated that there was no significant difference between the skin phototype groups. “This real-world clinical study demonstrates that the DMT can help clinicians improve outcomes for cutaneous melanomas in patients of all skin types,” commented Dr. Skelsey. “This is especially important because ruling out melanoma in individuals with Fitzpatrick IV-VI skin types can be particularly challenging.” The second research abstract titled, “Skin cancer risk is increased by somatic mutations detected noninvasively in healthy-appearing sun-exposed skin” will be presented March 9th at 10:05am PT by lead author John Whitaker, Ph.D., Senior Director of Bioinformatics at DermTech. The research found that somatic mutations in healthy-appearing sun-exposed skin indicate an increased risk for skin cancer. Furthermore, these mutations capture skin cancer risk information that is not accounted for by other risk factors. A complete description of this research has been accepted for publication in the Journal of Investigative Dermatology and will be published on March 19th: ( (24)00176-3/fulltext) This research study used non-invasively sampled DNA from healthy-appearing skin, in a reference cohort of 1,038 individuals, to measure the occurrence of somatic mutations at skin cancer-associated hotspots located within TP53 and NOTCH1. The number of detected mutations was combined with clinical variables known to be associated with skin cancer risk to create a skin cancer risk model (DNA-Skin Cancer Assessment of Risk, DNA-SCAR). DNA-SCAR’s risk calculation was validated by comparison to the U.S. population and was trained to predict personal history of skin cancer from age, family history, skin tone and mutation count. About DermTech DermTech is a leading genomics company in dermatology and is creating a new category of medicine, precision dermatology, enabled by its non-invasive skin genomics technology. DermTech’s mission is to improve the lives of millions by providing non-invasive precision dermatology solutions that enable individualized care. DermTech provides genomic analysis of skin samples collected using its Smart StickersTM. DermTech develops and markets products that facilitate the assessment of melanoma. For additional information, please visit DermTech. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. The expectations, estimates, and projections of DermTech may differ from its actual results and consequently, you should not rely on these forward-looking statements as predictions of future events. Words such as “expect,” “estimate,” “project,” “budget,” “forecast,” ”aim,” “runway,” "outlook," “anticipate,” “intend,” “plan,” “strive," “may,” “will,” “sustain,” “could,” “should,” “believe,” “predict,” “potential,” “continue,” and similar expressions are intended to identify such forward-looking statements. These forward-looking statements include, without limitation, expectations and evaluations with respect to: the performance, patient benefits, cost- effectiveness, commercialization and adoption of DermTech’s products and the market opportunity for these products; expectations regarding DermTech’s potential growth, scale, patient reach, financial outlook, including its cash runway and future financial performance DermTech’s ability to increase its test volume, revenue and the proportion of reimbursed billable tests and control or reduce cost, expenses and cash burn, including as a result of DermTech’s recent restructuring actions; and expectations regarding agreements with or reimbursement or cash collection patterns from government payers (including Medicare) or commercial payers and related billing practices or number of covered lives. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from the expected results. Most of these factors are outside of the control of DermTech and are difficult to predict. Factors that may cause such differences include, but are not limited to: (1) the outcome of any legal proceedings that may be instituted against DermTech; (2) DermTech’s ability to obtain additional capital when and as needed or on acceptable terms; (3) the existence of favorable or unfavorable clinical guidelines for DermTech’s tests; (4) the reimbursement of DermTech’s tests by government payers (including Medicare) and commercial payers; (5) the ability of patients or healthcare providers to obtain coverage of or sufficient reimbursement for DermTech’s products; (6) DermTech’s ability to grow, manage growth and retain its key employees and maintain or improve its operating efficiency and reduce operating expenses; (7) changes in applicable laws or regulations; (8) the market adoption and demand for DermTech’s products and services together with the possibility that DermTech may be adversely affected by other economic, business, and/or competitive factors; (9) DermTech’s ability to continue as a going concern and (10) other risks and uncertainties included in the “Risk Factors” section of the most recent Annual Report on Form 10-K filed by DermTech with the Securities and Exchange Commission (the “SEC”), and other documents filed or to be filed by DermTech with the SEC, including subsequently filed reports. DermTech cautions that the foregoing list of factors is not exclusive. You should not place undue reliance upon any forward- looking statements, which speak only as of the date made. DermTech does not undertake or accept any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based.

Researchers used various sequencing technologies to explore the molecular characteristics of myeloid/natural killer cell precursor acute leukemia (MNKPL). They observed activation of the NOTCH1 and RUNX3 genes, with lower expression of the BCL11B gene. MNKPL cells were also highly sensitive to a drug called L-asparaginase. Collectively, these qualities make MNKPL distinct from other leukemia types. These insights will assist with more accurate clinical diagnoses and therapeutic development for MNKPL. Leukemia is a common term used to refer to a form of blood cancer. However, there are different types of leukemia depending on the cell type involved. One unique form is myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL). Because of its rarity, there is no consensus on the specific characteristics needed to clinically identify this disease. In a recent article published in Science Advances, a team led by researchers at Tokyo Medical and Dental University (TMDU) used various approaches to better assess the molecular pro drug sensitivity characteristics of MNKPL. MNKPL was only first proposed as a leukemia subtype in 1997. Extramedullary involvement is one of the hallmarks of MNKPL. It is prevalent in East Asian countries. Although the immunological phenotype of MNKPL was explored previously, a full genetic characterization of this cancer type had not been performed. These details would help support more accurate diagnoses for patients, which would lead to more appropriate therapeutic decisions. Therefore, the TMDU group aimed to investigate MNKPL on a single-cell level. "A single-cell exploration of MNKPL would not only help us better understand its clinical and genomic features, but also clarify the specific cellular origin of this disease," says Dr. Akira Nishimura, lead author of the study. The team first used what is known as a multiomics approach to investigate MNKPL patient samples. They used various sequencing technologies to determine if there were any relevant mutations in specific genes, look for expression differences in certain signaling pathways at the RNA level, and examine any unique DNA methylation patterns. "Our results demonstrate that MNKPL has molecular qualities that are distinct from other similar cancers, such as acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia," explains Dr. Masatoshi Takagi, senior author. "Specific hallmarks of MNKPL include activation of the NOTCH1 and RUNX3, as well as lower expression of the BCL11B." Further work at the single-cell level in MNKPL cells showed that NK cells and myeloid cells come from a common progenitor cell type. The researchers also conducted in vitro drug sensitivity assays where they measured MNKPL cell responses to 79 individual anti-cancer drugs. "We observed that MNKPL cells were highly sensitive to a drug called L-asparaginase, which has already shown clinical effectiveness for this disease," says Dr. Nishimura. "Mechanistically, we found that this was from low expression of asparagine synthetase, a quality that was distinct from other similar types of leukemia." Overall, the robust and comprehensive analysis performed in this study provides crucial molecular details for characterizing MNKPL. This work will undoubtedly help clinicians more effectively diagnose MNKPL and choice of therapeutic option. Additionally, this work provides data that will assist with novel therapeutic target identification and drug development in this leukemia.