Leukodystrophy, Globoid Cell

Designation grants access to enter the Innovative Licensing and Access Pathway (ILAP) Five patients treated with FBX-101 show positive safety and efficacy results, including significant improvements in motor function Forge’s CMO, Dr. Maria Escolar, to present updated FBX-101 clinical data during the Advanced Therapies 2024 conference in London March 19-20 Designation provides opportunities for further global acceptance of Forge’s manufacturing process and facility through additional reviews and inspections COLUMBUS, Ohio--(BUSINESS WIRE)-- Forge Biologics, a member of Ajinomoto Bio-Pharma Services and a leading manufacturer of genetic medicines, today announced that the Medicines and Healthcare Products Regulatory Agency (MHRA), the healthcare regulatory body of the United Kingdom (UK), granted Innovation Passport designation to the Company’s novel AAV gene therapy program, FBX-101, to enter the Innovative Licensing and Access Pathway (ILAP). FBX-101 was created for the treatment of patients with Krabbe disease, a rare neurodegenerative disease that is usually fatal in untreated patients by age two. The ILAP is intended to accelerate regulatory and market access interactions in the UK. Maria Escolar, M.D., Forge’s Chief Medical Officer, will discuss the significance of achieving this regulatory designation and present a poster on updated data from REKLAIM, an early phase clinical trial for FBX-101, during the Advanced Therapies 2024 conference being held in London, March 19-20, 2024. “Considering the rapid progression of Krabbe disease in young patients and the positive results we’ve observed in the REKLAIM trial, we are pleased to receive the Innovation Passport designation which will enable Forge to further accelerate the clinical development of FBX-101,” stated Dr. Escolar. “ILAP was created to provide access to tools to decrease the time to market and facilitate patient access to medicines in the UK for life-threatening or seriously debilitating conditions.” The REKLAIM clinical trial is evaluating the safety and efficacy of FBX-101 in patients with infantile and late infantile Krabbe disease. Children assessed in REKLAIM have received intravenous FBX-101 in addition to the current standard of care, hematopoietic stem cell transplantation (HSCT). Clinical data demonstrate that FBX 101 has been well tolerated and has an excellent safety pro the treatment of five patients. Results show improvements in motor function in all patients, the most meaningful clinical outcome for this disease. FBX-101 has been granted Orphan Drug Designation and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA), allowing Forge to advance and expedite the development of FBX-101 as the leading worldwide gene therapy for patients with Krabbe disease. In the US, the FDA has granted FBX-101 Fast Track Designation, Orphan Drug Designation, and Rare Pediatric Disease Designation. ILAP is intended to accelerate regulatory and market access interactions in the UK for patient populations with significant need, leading to accelerated patient access to novel therapies. It also provides access to a range of UK development services and tools, including frequent MHRA interactions, accelerated Marketing Authorization Application (MAA) assessment, a Target Development Profile, expanded licensing routes, and more, creating a roadmap for advancement of therapies through regulatory approval. Regulatory review by the MHRA through ILAP provides opportunities for further global acceptance of Forge’s manufacturing process and facility though additional reviews and inspections, including Compliance Readiness Inspections that provide custom and pragmatic supervisory and licensing inspections specific to the GMP guidelines. Through this designation Forge has expanded global regulatory experience to include interactions with the MHRA in the UK. This access to global health authority resources will enable an added level of assurance to clients utilizing Forge’s CDMO services with integrated regulatory support. About Krabbe Disease Krabbe disease is a rare neurodegenerative disease affecting about 1-2.5 in 100,000 people in the US. Krabbe disease is caused by autosomal recessive mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine. Without functional GALC, psychosine accumulates to toxic levels in cells, specifically in cells insulating the nerves in the brain and peripheral nervous system, causing rapid demyelination. Krabbe disease initially manifests in young patients as irritability, developmental delay, and progressive muscle weakness. Symptoms rapidly advance to difficulty swallowing, breathing, and regression of neurodevelopment followed by seizures, vision and hearing loss. Infantile Krabbe disease (0-12 months of age at onset) usually leads to death in untreated patients by two years of age. Late Infantile patients (12-36 months of age at onset) usually die by the age of six. The current standard of care, hematopoietic stem cell transplantation (HSCT), has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes. However, HSCT does not correct the peripheral neuropathy that is progressive as the patient grows, leading to loss of gross motor skills and eventually death. About FBX-101 FBX-101 was developed to treat children with Krabbe disease. FBX-101 is an adeno-associated viral serotype rh10 (AAVrh10) gene therapy that is delivered intravenously after HSCT infusion. The vector delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system and has shown to functionally correct the central and peripheral neuropathy, improve myelination and gross motor function, and significantly prolong lifespan in animal models. This approach also has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies and extend the duration of gene transfer. About the REKLAIM Trial REKLAIM is a nonblinded, non-randomized, early phase dose escalation clinical trial currently enrolling children with asymptomatic infantile and symptomatic late infantile Krabbe disease to investigate the safety and efficacy of a single intravenous infusion of FBX-101 administered more than 21 days after HSCT, the current standard of care. Data from extensive natural history subjects will be used to compare as the control group. More information on the REKLAIM trial can be found online at . About Forge Biologics Forge Biologics, a member of Ajinomoto Bio-Pharma Services, is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company, enabling access to life-changing gene therapies by bringing them from concept to reality. Forge’s 200,000 square foot facility, the Hearth, is headquartered in Columbus, Ohio, and houses 20 custom-designed cGMP suites with 200,000L of manufacturing capacity. Forge’s end-to-end, scalable plasmid and AAV manufacturing services include research-grade manufacturing, process and analytical development, cGMP manufacturing, fill and finish, and integrated regulatory support to help accelerate the timelines of transformative medicines for patients with genetic diseases. To learn more, visit .

Continued momentum in upliFT-D trial of PBFT02 for the treatment of patients with frontotemporal dementia (FTD) with granulin mutations (GRN) with clinical trial site expansion into Europe and seven global sites now activatedPursuing new indications for PBFT02, including adult neurodegenerative diseases FTD-C9orf72, amyotrophic lateral sclerosis (ALS) and Alzheimer’s diseaseEnded 2023 with robust balance sheet sufficient to deliver meaningful clinical data; with cash runway into Q4 2025 PHILADELPHIA, March 04, 2024 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on improving the lives of patients with neurodegenerative diseases, today reported financial results for the fourth quarter and year ended December 31, 2023 and provided recent business highlights. "In 2023, we achieved a significant milestone by announcing encouraging data from three patients in Cohort 1 of our FTD-GRN program. This data showcased the ability of PBFT02 to raise CSF progranulin to supraphysiologic levels, even at the lowest dose, Dose 1, and positions PBFT02 as a potential best-in-class treatment for FTD-GRN. Our global upliFT-D study continues to see strong momentum, and we're excited to announce the activation of our first clinical trial site in Europe to further bolster recruitment efforts. We are on track to complete dosing for Cohort 1 patients in the first half of this year and share 6-month additional safety and biomarker data from Cohort 1 in the second half of 2024," said Will Chou, M.D., president and chief executive officer of Passage Bio. "Buoyed by this promising data and additional evidence supporting progranulin's role in neurodegeneration, we are optimistic about expanding the application of PBFT02 beyond FTD-GRN and into new indications with significant unmet needs, including FTD-C9orf72, ALS, and Alzheimer's disease. We eagerly anticipate a catalyst-rich 2024, supported by our robust balance sheet, bringing us closer to improving patient outcomes across neurodegenerative diseases." Recent Highlights Sustained momentum in global Phase 1/2 upliFT-D clinical trial evaluating PBFT02 for frontotemporal dementia (FTD) with granulin mutations (GRN), marked by the activation of two new trial sites and expansion into Europe: Initial data from the first three patients in Cohort 1 demonstrated elevated CSF progranulin levels to supraphysiologic levels at the lowest tested dose, Dose 1, up to six months post-treatment (n=1). Additionally, Dose 1 of PBFT02 continued to be generally well-tolerated in patients who received an enhanced steroid regimen for immunosuppression. In the first half of 2024, the company expects to complete dosing for Cohort 1 patients and report 6-month safety and biomarker data in the second half of 2024. Following the positive data, multiple GRN+ patients have been identified and are being evaluated for eligibility across seven clinical trial sites in Brazil, Canada, the United States and Europe.Expansion of PBFT02 into additional adult neurodegenerative indications: In response to the promising initial data for PBFT02 in FTD-GRN and evidence supporting progranulin’s role in neurodegeneration, the company is currently evaluating the therapeutic potential of PBFT02 in additional indications, including FTD-C9orf72, ALS, and Alzheimer’s disease. The company is preparing for regulatory discussions and expects to obtain regulatory feedback on the clinical pathway to treating FTD-C9orf72 and ALS patients with PBFT02 in 2H 2024.Robust balance sheet to support operations: The company’s decision to focus resources on the exploration of PBFT02 in additional indications, while simultaneously pursuing potential out-licensing opportunities for clinical-stage pediatric programs in GM1 gangliosidosis, Krabbe disease and metachromatic leukodystrophy, provides sufficient cash runway into Q4 2025 to execute through critical value-inflecting milestones. Appointed Kathleen Borthwick as Chief Financial Officer, effective March 1, 2024: Ms. Borthwick previously served as the company’s Senior Vice President, Finance and Interim CFO and brings 25 years of pharmaceutical and biotech strategic financial leadership experience. Anticipated Upcoming Milestones: FTD-GRN Initiate dosing for Cohort 2 FTD-GRN patients in 1H 2024Report 6-month safety and biomarker data from Cohort 1 patients in 2H 2024Announce 12-month follow-up data from Cohort 1 patients in 1H 2025Report initial safety and biomarker data from Cohort 2 patients in 1H 2025 FTD-C9orf72 and ALS Obtain regulatory feedback on the pathway to treating FTD-C9orf72 and ALS patients with PBFT02 in 2H 2024 Fourth Quarter and Full-Year 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $114.3 million as of December 31, 2023, as compared to $189.6 million as of December 31, 2022. The company expects current cash, cash equivalents and marketable securities to fund operations into Q4 2025.Research and Development (R&D) Expenses: R&D expenses were $12.1 million for the quarter ended December 31, 2023, and $61.4 million for the year ended December 31, 2023, compared to $17.7 million and $86.1 million for the same quarter and year ended in 2022, respectively.General and Administrative (G&A) Expenses: G&A expenses were $6.3 million for the quarter ended December 31, 2023, and $41.6 million for the year ended December 31, 2023, compared to $10.6 million and $49.3 million for the same quarter and year ended in 2022, respectively.Net Loss: Net loss was $16.8 million, or $0.30 per basic and diluted share, for the quarter ended December 31, 2023 and $102.1 million, or $1.86 per basic and diluted share, for the year ended December 31, 2023, compared to a net loss of $27.1 million, or $0.50 per basic and diluted share, for the quarter ended December 31, 2022 and $136.1 million, or $2.50 per basic and diluted share, for the year ended December 31, 2022. About Passage Bio Passage Bio (Nasdaq: PASG) is a clinical stage genetic medicines company on a mission to improve the lives of patients with neurodegenerative diseases. Our primary focus is the development and advancement of cutting-edge, one-time therapies designed to target the underlying pathology of these conditions. Passage Bio’s lead product candidate, PBFT02, seeks to treat neurodegenerative conditions, including frontotemporal dementia, by elevating progranulin levels to restore lysosomal function and slow disease progression. To learn more about Passage Bio and our steadfast commitment to protecting patients and families against loss in neurodegenerative conditions, please visit: www.passagebio.com. Forward-Looking StatementsThis press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including the progress of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; our expectations about potential out-licensing opportunities related to PBGM01, PBKR03 and PBML04; and the ability of our product candidates to treat their respective target CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Passage Bio, Inc.Balance Sheets December 31,(in thousands, except share and per share data) 2023 2022Assets Current assets: Cash and cash equivalents $21,709 $34,601 Marketable securities 92,585 155,009 Prepaid expenses and other current assets 923 926 Prepaid research and development 2,742 6,508 Total current assets 117,959 197,044 Property and equipment, net 15,295 22,515 Right of use assets - operating leases 16,858 19,723 Other assets 433 4,267 Total assets $150,545 $243,549 Liabilities and stockholders’ equity Current liabilities: Accounts payable $1,298 $4,065 Accrued expenses and other current liabilities 11,670 11,011 Operating lease liabilities 3,373 3,275 Total current liabilities 16,341 18,351 Operating lease liabilities – noncurrent 22,921 23,832 Total liabilities 39,262 42,183 Stockholders’ equity: Preferred stock, $0.0001 par value: 10,000,000 shares authorized; no shares issued and outstanding at both December 31, 2023 and December 31, 2022 — — Common stock, $0.0001 par value: 300,000,000 shares authorized; 54,944,130 shares issued and outstanding at December 31, 2023 and 54,614,690 shares issued and outstanding at December 31, 2022 5 5 Additional paid‑in capital 705,789 694,733 Accumulated other comprehensive income (loss) (43) (966)Accumulated deficit (594,468) (492,406)Total stockholders’ equity 111,283 201,366 Total liabilities and stockholders’ equity $150,545 $243,549 Passage Bio, Inc.Statements of Operations and Comprehensive Loss Year Ended December 31,(in thousands, except share and per share data) 2023 2022Operating expenses: Research and development $61,419 $86,053 Acquired in‑process research and development — 3,000 General and administrative 41,580 49,341 Impairment of long-lived assets 5,390 — Loss from operations (108,389) (138,394)Other income (expense), net 6,327 2,269 Net loss $(102,062) $(136,125)Per share information: Net loss per share of common stock, basic and diluted $(1.86) $(2.50)Weighted average common shares outstanding, basic and diluted 54,743,490 54,429,023 Comprehensive loss: Net loss $(102,062) $(136,125)Unrealized gain (loss) on marketable securities 923 (553)Comprehensive loss $(101,139) $(136,678) For further information, please contact: Investors:Stuart HendersonPassage Bio267.866.0114shenderson@passagebio.com Media:Mike BeyerSam Brown Inc. Healthcare Communications312.961.2502MikeBeyer@sambrown.com

Data from Krabbe patients treated with hematopoietic stem cell transplantation (HSCT) and FBX-101 gene therapy in clinical trials continue to demonstrate safety and efficacy post-FBX-101 systemic administration Five patients have received FBX-101, all of whom were identified by newborn screening CEO Timothy J. Miller, Ph.D., is slated to comment during the public meeting of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) to reinforce the importance of the addition of Krabbe Newborn Screening to the national Recommended Newborn Screening Panel (RUSP) on Tuesday, January 30, 2024 Dr. Maria Escolar, Chief Medical Officer, will present updated FBX-101 clinical data as a late-breaking oral presentation on Friday, February 9, 2024, during the 10:30 a.m. ET session at the WORLD Symposium in San Diego, California COLUMBUS, Ohio--(BUSINESS WIRE)-- Forge Biologics (Forge), a member of Ajinomoto Bio-Pharma Services and a leading manufacturer of genetic medicines, announced a clinical update today on five patients with Krabbe disease that have received FBX-101, an AAV gene therapy, after hematopoietic stem cell transplantation (HSCT). Timothy J. Miller, Ph.D., CEO and President of Forge Biologics, will provide comments during the open period at the public meeting of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) on Tuesday, January 30, 2024, in support of adding Krabbe disease to the Recommended Uniform Screening Panel (RUSP). Krabbe disease is caused by mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine, associated with myelination of the nervous system. Without functional GALC, psychosine accumulates to toxic levels in cells, damaging cells that myelinate and insulate the nerves in the brain and peripheral nervous system, causing rapid demyelination and eventual death. Infantile Krabbe patients, often not diagnosed until after significant disease manifestations have occurred, typically die by the age of two if not treated by HSCT before symptoms are observed. Previously published data have demonstrated that patients with Krabbe treated with HSCT demonstrate increased lifespan and stabilization of neurodegenerative disease in the central nervous system. FBX-101, an investigational adeno-associated viral (AAV) gene therapy, has been designed to address the peripheral nerve disease not corrected by HSCT. Data recently presented at the European Society for Gene and Cell Therapy (ESGCT) demonstrated that FBX-101 provided to Krabbe patients identified through newborn screening who also received HSCT demonstrated increased GALC expression, reduced psychosine levels, normalized motor function, and corrected brain white matter growth. “Inclusion of Krabbe disease on the RUSP would extend Krabbe Newborn Screening to eight additional states, based on RUSP alignment legislation, ensuring that nearly 70% of all newborns in the United States are screened for this devastasting disease,” said Dr. Miller. “That would mean the potential of identifying dozens of babies every year, based on published incidence, who could receive the opportunity of life-saving treatments such as transplant and newly developing treatments like gene therapy.” The responsibility of the committee members of the ACHDNC is to provide the Secretary of Health and Human Services with recommendations, advice, and information to enhance, expand, or improve the ability of the Secretary to reduce mortality and morbidity from heritable disorders—such as Krabbe disease—in newborns and children. In early 2023, Krabbe disease came up for the second time (previously in 2010) to the ACHDNC for a vote to be added to the RUSP—a vote which ended in a tie of seven members voting approve, and seven members voting not to approve, something that had never happened before and has been a focus of multiple advocacy group efforts requesting a re-vote. As a result, after a year of patient and foundation advocacy, Krabbe disease is again being voted on for potential inclusion on the RUSP. “For infantile Krabbe patients, the alternative of not being able to receive a treatment such as a transplant is 100% chance of death,” said Lesa Brackbill, Director of Advocacy at Leukodystrophy Newborn Screening Action Network (LDNBS), whose daughter Victoria died from Krabbe disease in 2016. “The risk-to-benefit approach of identifying patients as early as possible in their genetic disease to help provide their children any relief, justifies the addition of Krabbe to the RUSP. Newborn screening for Krabbe will help enhance the efforts of all parents, industry partners, and treatment providers’ ceaseless search for cures.” Additionally, Maria Escolar, M.D., Chief Medical Officer, will present updated FBX-101 clinical data during the 20th Annual WORLD Symposium in San Diego, California, on February 9, 2024 at 10:30 a.m. ET. Dr. Escolar’s late-breaking oral presentation is titled, “REKLAIM, the novel phase 1b clinical trial of FBX-101 (AAVrh10.galc) intravenously administered after UCBT for the treatment of infantile Krabbe disease.” The session will also be available on demand for registered attendees February 14 to March 14, 2024. For more details on the conference, please visit: . “We continue to be encouraged by the safety and efficacy observed in FBX-101 treated patients,” stated Dr. Escolar. “The window of treatment for patients with Krabbe disease is very narrow and newborn screening is a critical step for these babies to benefit from any treatment, but unfortunately newborn screening for this devastating and quickly progressing disease is still only available in a handful of states. Dr. Miller’s comments to the ACHDNC will reflect the urgency physicians have been trying to convey for this patient community.” About Krabbe Disease Krabbe disease is a rare neurodegenerative disease affecting about 1-2.5 in 100,000 people in the U.S. Krabbe disease is caused by autosomal recessive mutations in the galactocerebrosidase (GALC) gene, an enzyme responsible for the breakdown of certain types of sphingolipids, such as psychosine, associated with myelination of the nervous system. Without functional GALC, psychosine accumulates to toxic levels in cells, specifically in cells that make myelin insulating the nerves in the brain and peripheral nervous system, resulting in rapid demyelination. Krabbe disease initially manifests in young patients as irritability, feeding difficulties, increased muscle tone and developmental delay. Symptoms rapidly advance to difficulty breathing, and regression of neurodevelopment followed by seizures, vision and hearing loss. Infantile Krabbe disease (0-12 months of age at onset) usually leads to death in untreated patients by two years of age. Late Infantile patients (12-36 months of age at onset) usually die by the age of six. The current standard of care, hematopoietic stem cell transplantation (HSCT), has been shown to stabilize cognitive decline and significantly improve long-term neurological outcomes when performed prior to symptom onset. However, HSCT does not correct the peripheral neuropathy that is progressive as the patient grows, leading to loss of gross motor skills and eventually death. Early diagnosis is key for treating patients with Krabbe disease before symptoms are evident and significant neurological damage has occurred. Currently, 11 states in the U.S. are conducting newborn screening for Krabbe disease. Infants who screen positive due to insufficient GALC activity undergo psychosine testing and mutation analysis to confirm the diagnosis and determine which infants need immediate treatment because they are at high risk to progress. More details can be found at . About FBX-101 FBX-101 was developed to treat children with Krabbe disease. FBX-101 is an adeno-associated viral serotype rh10 (AAVrh10) gene therapy that is delivered intravenously after HSCT. The vector delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral neuropathy associated with Krabbe, improve myelination and gross motor function, and significantly prolong lifespan in animal models. This is a novel approach that has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies (without transplantation). HSCT has normal GALC and provides an immune system that does not recognize GALC as an antigen. The FDA has granted FBX-101 Fast Track Designation, Orphan Drug Designation, Rare Pediatric Disease Designation, and the EMA has granted FBX-101 Orphan Drug Designation and Priority Medicines (PRIME) designation. FBX-101 investigation use is currently being evaluated for new subjects in the REKLAIM clinical trial (NCT05739643). More information on the REKLAIM trial can be found online at . About Forge Biologics Forge Biologics, a member of Ajinomoto Biopharma Services, is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company enabling access to life-changing gene therapies by bringing them from concept to reality. Forge’s 200,000 square foot facility, the Hearth, is headquartered in Columbus, Ohio, and houses 20 custom-designed cGMP suites. Forge’s end-to-end, scalable plasmid and AAV manufacturing services include research-grade manufacturing, process and analytical development, cGMP manufacturing, fill and finish, and regulatory consulting support to help accelerate the timelines of transformative medicines for patients with genetic diseases. To learn more, visit .