Hereditary Sensory and Motor Neuropathy

CHESHIRE, UK I April 28, 2025 I BlackfinBio Ltd, a clinical stage gene therapy company focused on the development of treatments for rare neurological diseases, announces today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for a Phase 1/2 clinical trial of its novel adeno-associated virus (AAV) gene therapy, BFB-101, in children with Hereditary Spastic Paraplegia, Type 47 (SPG47). The trial will be conducted in the U.S. at Boston Children’s Hospital and is expected to commence recruiting by the end of 2025. The FDA has granted an orphan drug designation (ODD) and rare pediatric disease designation (RPDD) to BFB-101 for the treatment of SPG47. SPG47 is a rare, autosomal-recessive, neurological disorder characterised by progressive lower-limb spasticity, developmental delays and intellectual disability in children. It is caused by deleterious changes in the AP4B1 gene. Currently, there is no cure or effective treatment available for this devastating condition. BFB-101 has been designed specifically to address the underlying genetic cause of SPG47 by delivering a functional copy of the AP4B1 gene, with the goal of halting or reversing disease progression. Preclinical results with BFB-101 have demonstrated promising activity and safety (1). The Phase 1/2 clinical trial is a single-center open-label study with a primary objective to assess the safety and efficacy of a single injection into the cerebrospinal fluid at the base of the brainstem near the spinal cord, termed an ‘ICM’ administration. This type of delivery generally allows for rapid and efficient delivery of agents to the central nervous system. BFB-101 will be administered by ICM in up to five children with AP4B1-associated SPG47. The secondary objectives will aim to evaluate the impact of BFB-101 on motor function, development and health-related quality of life. “The FDA’s clearance of the BFB-101 IND is an important milestone for our rare neurological disease program and the company. We look forward to initiating enrollment in the U.S. later this year and are working closely with the investigator team at Boston Children’s Hospital to evaluate the therapeutic utility of this gene therapy in children with SPG47,” said Peter Nolan, Founder and Chief Executive Officer of BlackfinBio Ltd. “We are proud to be leading this important clinical trial at Boston Children’s Hospital, bringing forward a precision medicine approach for children affected by SPG47. As clinicians, we see firsthand the impact of this disorder and the urgency for effective treatments. BFB-101 represents a promising gene therapy candidate, and this trial is a critical step toward delivering meaningful change for patients and families affected by AP-4-associated hereditary spastic paraplegia and related conditions,” said Dr. Darius Ebrahimi-Fakhari, M.D., Ph.D., Boston Children’s Hospital (Principal Investigator). “Having overseen this therapeutic innovation from discovery stage, it is a huge source of excitement to reach this important IND milestone. Given the incredibly high unmet need for children with this devastating condition, we are on a mission at BlackfinBio to transform treatment options for these young lives and make a real impact to the lives of their families,” added Professor Mimoun Azzouz, Founder and Chief Scientific Officer of BlackfinBio Ltd. Reference: (1): Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47 Disclosure Statement: Dr. Darius Ebrahimi-Fakhari has consulted for BlackfinBio. About BFB-101 BFB-101 aims to address the underlying genetic cause of Hereditary Spastic Paraplegia, Type 47 (SPG47) by delivering a functional copy of the AP4B1 gene, with the goal of halting or reversing disease progression. It is administered via the brain as a single lifetime dose and has shown potential in restoring AP-4 function in vitro and improving motor function in AP4B1 mutant mice. BFB-101 was originally developed by Professor Mimoun Azzouz at the University of Sheffield with the support of Cure AP-4 ( https://cureap4.org ), LifeArc ( www.lifearc.org ). This project has also received partial funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 945473 to support AAV9 capsid synthesis for immune response study. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The FDA has granted an orphan drug designation (ODD) and rare pediatric disease designation (RPDD) to BFB-101 for the treatment of SPG47. About BlackfinBio Ltd BlackfinBio is a clinical stage gene therapy company focused on the development of treatments for rare neurological diseases. The pipeline comprises BFB-101, a clinical stage AP4B1 replacement AAV gene therapy for spastic paraplegia 47 – an ultra-rare genetic neurological disease for which no treatment currently exists. BFB-201 is a preclinical stage gene therapy to treat several rare dopamine deficiency disorders. For more information, please visit https://blackfin.bio and follow us on LinkedIn . SOURCE: BlackfinBio

Issued 12,765,958 new sharesPriced at €2.35 per share, representing a 15.44% discount on the 5-day VWAPStrong investor demand, with the offering significantly oversubscribed€15 million anchored by a leading US institutional investorProceeds to fund clinical development and corporate initiatives MADRID and CAMBRIDGE, Mass., April 24, 2025 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, announced today the successful completion of a €30 million capital increase through the issuance of 12,765,958 new shares, priced at €2.35 per share. This pricing reflects a 15.44% discount to the 5-day volume-weighted average price (VWAP) of €2.779 per share prior to April 22, 2025, and a 19.38% discount to the April 22 closing price of €2.915. The offering, which was structured as straight equity with no warrants attached, attracted strong demand and was significantly oversubscribed. A US-based institutional investor anchored the round with a €15 million order, with the remaining demand filled by investors across the US, Europe, and Spain. The capital increase was capped at €30 million by the company’s Board of Directors. Maxim (U.S.), All-Invest (EU/UK), and Singular Bank (Spain) acted as bookrunners. Banco Sabadell, S.A. acted as the Settlement and Technical Pre-financing Agent for the Capital Increase, while Gómez-Acebo & Pombo Abogados, S.L.P. (Spanish law) and Gibson, Dunn & Crutcher LLP (U.S. law) served as legal advisors to the Company, and Loeb & Loeb LLP acted as U.S. legal counsel to Maxim Group LLC. The funds raised will be used to: Advance the clinical development of vafidemstat for the treatment of aggression in CNS disorders such as Borderline Personality Disorder (BPD) and Autism Spectrum Disorder (ASD)Expand ongoing clinical programs in oncology and hematologySupport CMC activities and preparations for Phase IIb-III trials, as well as other regulatory initiativesStrengthen the company's balance sheet to support future partnership or M&A negotiationsCover general administrative expenses and financial obligationsEnhance legal and audit readiness for a potential dual listing on Nasdaq Dr. Carlos Buesa, CEO of Oryzon, commented: “This financing marks a key milestone that enables us to continue progressing our clinical programs with vafidemstat in aggression-related CNS disorders and to further develop our oncology and hematology pipeline. It also reinforces our financial position, supporting strategic conversations with investors and potential partners.” About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About IadademstatIadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU and in a trial sponsored by the U.S. National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI to collaborate on further clinical development of iadademstat in different types of hematologic and solid cancers. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a collaborative Phase II trial with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center. Oryzon is further expanding the clinical development of iadademstat through additional investigator-initiated studies. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. About Vafidemstat Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong, and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE, see Ferrer et al, Psychiatry & Clin Neurosci, 2025, doi.org/10.1111/pcn.13800) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 was observed after 6 and 12 months of treatment, and the pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity was also observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patients. Vafidemstat is currently advancing as a Phase III-ready asset in Borderline Personality disorder (BPD) following completion of the global, randomized, double blind Phase IIb PORTICO trial (final data presented at ECNP-2024). Following receipt of the minutes from the End-of-Phase II meeting with the FDA to discuss PORTICO’s results, the company announced plans to move forward with a Phase III PORTICO-2 trial in agitation/aggression in BPD (FDA submission planned in 1H2025). Vafidemstat is also being investigated in a double-blind, randomized, placebo-controlled Phase IIb trial in negative symptoms of schizophrenia (EVOLUTION trial, recruitment ongoing). The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is evaluating a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This document does not constitute an offer or invitation to purchase or subscribe shares in accordance with the provisions of Regulation (EU) 2017/1129 of the European Parliament and of the Council of 14 June 2017, and/or the restated text of the Securities Market Law, approved by Law 6/2023 of 17 March, and its implementing regulations. Nothing in this document constitutes investment advice. In addition, this document does not constitute an offer of purchase, sale or exchange, nor a request for an offer of purchase, sale or exchange of securities, nor a request for any vote or approval in any jurisdiction. The shares of Oryzon Genomics, S.A. may not be offered or sold in the United States of America except pursuant to an effective registration statement under the Securities Act of 1933 or pursuant to a valid exemption from registration.. Spain Oryzon IR & Media, Europe & US Patricia Cobo/Mario Cordera Emili Torrell Sandya von der Weid Atrevia Chief BD Officer LifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 +41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com svonderweid@lifesciadvisors.com

New “Decision to grant” communications in Europe and JapanMADRID and CAMBRIDGE, Mass., April 21, 2025 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, announced today that the European Patent Office has issued a “Decision to grant” communication for its European patent application EP20712563.4 relating to vafidemstat. The patent, titled “Methods of treating Attention Deficit Hyperactivity Disorder using KDM1A inhibitors such as the compound vafidemstat”, covers the use Oryzon’s LSD1 inhibitor, vafidemstat, currently in clinical development for psychiatric disorders. A “Decision to grant” is a formal communication from a Patent Office indicating that the patent application has met all requirements for issuance as a patent. Once formally granted, this European patent will remain in force until at least 2040, excluding any potential patent term extension. A counterpart patent has already been granted in Japan, and additional applications are pending in other countries. Oryzon also announced that it has received a “Decision to grant” from the Japanese Patent Office for its patent application JP2022-514201, titled “Methods of treating autism spectrum disorder”. This will be the first granted patent in this patent family, with applications pending in other countries. This Japanese patent, once issued, will also remain in force until at least 2040, not including potential term extension. “These new patent allowances in Europe and Japan complement the ample portfolio we’ve already secured for vafidemstat,” said Neus Virgili, Oryzon’s Chief IP Officer. “They further strengthen our global IP position and support the compound’s commercial potential across multiple CNS indications and our competitive position.” Oryzon’s patent porfolio for vafidemstat in CNS also includes two additional patent families:. One covers the treatment of aggression and social withdrawal, with patents already granted or allowed in Europe, Australia, Hong Kong, Korea, Malaysia, the Philippines, and Russia, and patent applications pending in other countries. These patents will remain in force until at least 2038, excluding any potential patent term extensions, which may provide additional years of protection.The second patent family relates to the treatment of borderline personality disorder, with allowed or granted patents in Europe, Japan, Mexico, Russia, Singapore and South Africa, and patent applications pending in additional countries. These patents will remain in force until at least 2040, excluding any potential patent term extensions, which may provide additional years of protection. About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About Vafidemstat Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong, and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE, see Ferrer et al, Psychiatry & Clin Neurosci, 2025, doi.org/10.1111/pcn.13800) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 was observed after 6 and 12 months of treatment, and the pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity was also observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patients. Vafidemstat is currently advancing as a Phase III-ready asset in Borderline Personality disorder (BPD) following completion of the global, randomized, double blind Phase IIb PORTICO trial (final data presented at ECNP-2024). Following receipt of the minutes from the End-of-Phase II meeting with the FDA to discuss PORTICO’s results, the company announced plans to move forward with a Phase III PORTICO-2 trial in agitation/aggression in BPD (FDA submission planned in 1H2025). Vafidemstat is also being investigated in a double-blind, randomized, placebo-controlled Phase IIb trial in negative symptoms of schizophrenia (EVOLUTION trial, recruitment ongoing). The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is evaluating a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This document does not constitute an offer or invitation to purchase or subscribe shares in accordance with the provisions of Regulation (EU) 2017/1129 of the European Parliament and of the Council of 14 June 2017, and/or the restated text of the Securities Market Law, approved by Law 6/2023 of 17 March, and its implementing regulations. Nothing in this document constitutes investment advice. In addition, this document does not constitute an offer of purchase, sale or exchange, nor a request for an offer of purchase, sale or exchange of securities, nor a request for any vote or approval in any jurisdiction. The shares of Oryzon Genomics, S.A. may not be offered or sold in the United States of America except pursuant to an effective registration statement under the Securities Act of 1933 or pursuant to a valid exemption from registration.. Spain Oryzon IR & Media, Europe & USPatricia Cobo/Mario Cordera Emili Torrell Sandya von der Weid Atrevia Chief BD Officer LifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 +41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com svonderweid@lifesciadvisors.com