bFGF

TOKYO--( BUSINESS WIRE )--RIBOMIC, Inc. (TOKYO:4591), a clinical-stage pharmaceutical company specializing in aptamer therapeutics, has been conducting a Phase IIa clinical trial of umedaptanib pegol (anti-FGF2 aptamer) in pediatric patients (5-14 years old) with achondroplasia (ACH), and today announces that the administration of the low-dose (0.3 mg/kg) subcutaneous injection (once a week) group (cohort 1 Note 1 ) has been completed and demonstrated a positive impact of the test drug on the patient growth rate. In cohort 1, six subjects completed the study, and of the five subjects excluding one subject who withdrew from the study due to interrupting medication, the height growth rate increased by +4.6 cm, +3.3 cm/year compared to before the administration of the test drug (observational study Note 2 ) in two subjects. These results show that the test drug has a significant therapeutic effect compared to the average height growth rate of +1.7 cm/year for Voxzogo ® (vosoritide, manufactured by BioMarin, administered subcutaneously daily) Note 3 , which is currently approved as an ACH treatment. Three patients were unresponsive to the test drug at the low dose. Five of these subjects have been moved on to a long-term low-dose (0.3 mg/kg) administration study, and the efficacy and safety of the test drug will continue to be evaluated. In addition, enrollment of seven patients has been completed for the high-dose (0.6 mg/kg) subcutaneous administration (once every two weeks) study (cohort 2 Note 4 ), and administration has started in four of these patients. The results of cohort 2 study are expected to be announced in September 2025. There have been no safety concerns in the ongoing Phase IIa clinical trials, including this case. The fact that a significant increase in growth rate was confirmed in two out of five patients after low-dose, once-weekly subcutaneous administration is a good news for pediatric patients with ACH, as it provides a new treatment option for ACH. We are considering further increasing the dose and extending the dosing interval to establish an even better treatment regimen. There are no changes to the full-year earnings forecast for the fiscal year ending March 2025, which was revised on August 9, 2024. Note 1 In this study group, low-dose (0.3 mg/kg) subcutaneous injections are administered once every two weeks for eight weeks (a total of four times), and after confirming safety and tolerability, the administration interval is changed to once a week for 26 weeks (a total of 34 weeks of administration). Note 2 The aim of this study is to obtain clinical baseline data, including height growth, in pediatric patients with ACH, and to compare this data with that obtained in the ongoing Phase IIa clinical trial, in order to evaluate the efficacy and safety of the drug, and to select appropriate subjects for the Phase IIa clinical trial (observation period: 26 weeks in total). Note 3 https://clinicaltrials.gov/study/NCT03197766?tab=results Note 4 In this group, the high dose (0.6 mg/kg) is administered subcutaneously once every four weeks for eight weeks (a total of two times), and after confirming safety and tolerability, the dosing interval is changed to once every two weeks and the drug is administered for 26 weeks (a total of 34 weeks). Please see the following for a summary of Phase IIa study in Japan. Phase IIa observational study: https://trialsearch.who.int/Trial2.aspx?TrialID=JPRN-jRCT2031220113 Phase IIa clinical study: https://trialsearch.who.int/Trial2.aspx?TrialID=JPRN-jRCT2031220291 Phase IIa extension study: https://trialsearch.who.int/Trial2.aspx?TrialID=JPRN-jRCT2031220338 ABOUT umedaptanib pegol umedaptanib pegol is a novel oligonucleotide-based aptamer formerly designated RBM-007, with potent anti-FGF2 (fibroblast growth factor 2) activity and is expected to be a fundamental treatment that directly targets the pathogenic mechanism of achondroplasia. The drug has demonstrated clinical POC in exudative age-related macular degeneration. ABOUT Achondroplasia Achondroplasia is disease in which a genetic mutation of the fibroblast growth factor receptor type 3 (FGFR3) causes FGFR3 to be activated, resulting in an excessive influx of FGF signals that inhibit the normal growth of cartilage and other tissues, causing short stature with limb shortening and other symptoms. It is a rare disease with an incidence of 1 in 25,000 newborns and is considered intractable. The development of effective new drugs is required. ABOUT RIBOMIC RIBOMIC is a clinical-stage biopharmaceutical company specializing in the discovery and development of aptamer therapeutics, a type of nucleic acid medicine with great potential for the development of next-generation drugs. The RiboART system, the company’s core drug discovery platform, can be used to discovery many types of aptamer drugs. RIBOMIC is dedicated to the discovery and development of drugs targeting the broad field of unmet medical needs, which includes eye disease, rare childhood disease of short stature, and many other diseases. Please visit the RIBOMIC website for more information. https://www.ribomic.com/eng/ Forward-Looking Statements This announcement contains forward-looking statements relating to current plans, estimates, strategies, belief and the future performance of Company. These statements are based on Company’s current expectations in light of the information and assumptions currently available so that Company does not promise the realization and these expectations may differ materially from those discussed in the forward-looking statements. These factors include, but not limited to, i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, ii) currency exchange rate fluctuations, iii) claims and concerns on the product safety and efficacy, iv) completion and News Release discontinuation of clinical trials, v) infringement of Company’s intellectual property rights by third parties. Information on pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice. "RIBOMIC," "RiboART system" and the RIBOMIC logo are registered trademarks or trademarks of RIBOMIC Inc. in various jurisdictions.

TOKYO, Oct. 1, 2024 /PRNewswire/ -- PeptiGrowth Inc. (Headquarters: Chiyoda-ku, Tokyo; President: Jiro Sugimoto) has successfully developed a novel synthetic peptide called "FGF2 alternative peptide (FGFR1c agonist)", which has equivalent function to recombinant FGF2 (Fibroblast Growth Factor 2, basic FGF (bFGF)). This product will be on the market at the beginning of October 2024. Development of Synthetic Peptide Growth Factors by PeptiGrowth Continue Reading Conceptual Diagram of the Mechanism of Action of PG-011 Proliferation of human MSCs by PG-011 and observations of cell morphology of iPSCs after 3 passages of culturing in the presence of PG-011 or FGFs, as well as the measurement of undifferentiated markers on Day 7 at P3. Traditional growth factors and cytokines used in regenerative medicine and cell therapy manufacturing face several quality issues, including lot-to-lot variability, potential contamination with biological impurities, low stability, and high costs. PeptiGrowth has focused on developing a series of synthetic peptides that address these challenges while maintaining functionality equivalent to conventional growth factors and cytokines. Their peptides are completely chemically synthesized and free from animal components, enabling the formulation of xeno-free and chemically defined cell culture media. About FGF2 alternative peptide (FGFR1c agonist) [Product code: PG-011] The FGF2 Alternative Peptide ( PG-011) is a dimeric peptide composed of cyclic peptides that bind to human FGFR1c. PG-011 exhibits agonist activity toward FGFR1c by binding to it, thereby activating signaling pathways in various cell types. PeptiGrowth has confirmed that PG-011 promotes the proliferation of human mesenchymal stem cells (MSCs) at approximately one-third the concentration of FGF2 when compared on a ng/mL basis. Additionally, in collaboration with the CiRA Foundation, they evaluated PG-011's ability to maintain the undifferentiated state of human iPSCs. Three iPSC lines were cultured for 7 days in media containing either 100 ng/mL (~5.9 nM) of FGF2 or the same molar concentration (equivalent to ~30 ng/mL) of PG-011, followed by three passages. Afterward, cell morphology observations and undifferentiated marker measurements were conducted. Following three passages, iPSCs cultured in both PG-011 and FGF2 exhibited nearly identical morphology. Furthermore, analysis of undifferentiated markers (SSEA4 and TRA-1-60) indicated that iPSCs cultured with PG-011 displayed a similar positivity rate to those cultured with FGF2. Cell proliferation rates during the culture period were also equivalent under both conditions. These results suggest that PG-011 has the ability to maintain iPSCs in an undifferentiated state, comparable to FGF2. Recombinant FGF2 is known for its low stability, as it degrades and loses activity easily under culture conditions. This necessitates higher concentrations and frequent medium changes, significantly increasing production costs and workload. PeptiGrowth has confirmed that PG-011 maintained its full activity even after 4 days of incubation at 37°C, whereas FGF2's activity significantly declined under the same conditions, demonstrating the superior stability of PG-011. Moreover, they assessed the reactivity of PG-011 with bovine cells, as FGF2 is a key growth factor in cultivated meat production. PG-011 efficiently promoted the proliferation of bovine muscle satellite cells, suggesting that PG-011 may demonstrate cross-reactivity across various cell types, including those of non-human origin, making it a promising candidate for use in cultivated meat production. PG-011 provides cell proliferation and undifferentiated state maintenance comparable to FGF2 but with superior stability, reducing both usage costs and workload. It also shows excellent proliferation activity in both human and bovine cells, making it a compelling choice for regenerative medicine and cultivated meat production. Product Overview Product name: FGF2 alternative peptide (FGFR1c agonist) Product code: PG-011 Product form: Lyophilized Storage conditions: -20°C or less Purity: ≥95% by HPLC Molecular weight: 5127.81(Acetate) Size: 10 µg, 50 μg (volume per glass vial)*This product can be provided with an Animal Component Free (ACF) certificate. *This product is for testing and research use only (RUO). *There is a possibility that the specifications can change. Purchase Our Product If you would like to purchase our products, please contact us using the information below. For customers who would like to purchase GMP compliant products as well as the above PG products in bulk scale, please contact us using the information below. Development of other peptides from PeptiGrowth We have developed alternative peptides targeting numerous growth factors and cytokines. To date, we have launched 11 products and plan to launch several additional growth factor alternative peptides targeting PDGF-AA, KGF, and IL-15 between late 2024 and mid- 2025. Details will be updated on our website () . If you are interested, please contact us using the following contact information. Contacts for inquiries or additional information: PeptiGrowth Inc. E-mail: [email protected] TEL：+81-70-4503-1497 Photo - Photo - Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– 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