C9orf72

TPN-101 had lowering effects on key biomarkers of neurodegeneration and neuroinflammation, including neurofilament light chain (NfL) and interleukin 6 (IL-6) Treatment with TPN-101 also showed clinical benefits on the Revised ALS Functional Rating Scale (ALSFRS-R) and Vital Capacity, key clinical outcome measures for ALS SAN DIEGO, Oct. 9, 2024 /PRNewswire/ -- Transposon Therapeutics, a biotechnology company developing a platform of novel, orally administered therapies for the treatment of neurodegenerative and aging-related diseases, including Alzheimer's disease, today announced that results from its Phase 2 study of TPN-101 in patients with amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) related to hexanucleotide repeat expansion in the C9orf72 gene (C9orf72-related ALS/FTD) have been accepted for both oral and poster presentation at the 2024 Annual Northeastern Amyotrophic Lateral Sclerosis Consortium (NEALS) Meeting. The hybrid meeting will take place October 21-24, 2024, in Clearwater, Florida, and virtually. "Given the effects of TPN-101 on key biomarkers of neurodegeneration and neuroinflammation, including NfL and IL-6, and clinical outcome measures of disease progression and respiratory function in patients with C9orf72-related ALS, we are very pleased these data were accepted for presentation at NEALS," said Andrew Satlin, M.D., Chief Medical Officer at Transposon. "Based on these promising results, we are advancing TPN-101 into a Phase 3 registration study for the treatment of C9orf72-related ALS, while also continuing to develop TPN-101 for other neurodegenerative diseases." Oral presentation details The poster will also be on view during Poster Session 2 on Wednesday, October 23, 2024, from 4:00 to 6:00 pm EDT. For more information, please visit the 2024 Annual NEALS Meeting website. About the Phase 2 Study in C9orf72-related ALS/FTD The Phase 2 study in patients with C9orf72-related ALS/FTD was a multi-center, randomized, double-blind, placebo-controlled parallel-group, two-arm study with an open-label treatment period. Participants (n=42) were randomized 3:2 to receive daily doses of 400 mg of TPN-101 or placebo. The study included a six-week screening period, a 24-week double-blind treatment period, a 24-week open-label treatment period, and a follow-up visit four weeks post-treatment. Further information on the study can be accessed at ClinicalTrials.gov. About TPN-101 TPN-101 specifically inhibits the LINE-1 reverse transcriptase that promotes LINE-1 replication. LINE-1 elements are a class of retrotransposable elements that in humans are uniquely capable of replicating and moving to new locations within the genome. When this process becomes dysregulated, LINE-1 reverse transcriptase drives overproduction of LINE-1 cDNA, triggering innate immune responses that contribute to neurodegenerative, neuroinflammatory, and aging-related disease pathology. About ALS and FTD ALS is a neurodegenerative disease characterized by progressive muscle weakness, and loss of ability to speak, eat, move or breathe. FTD is a progressive frontal/temporal cortex disease associated with behavior and personality changes, emotional problems, and difficulty walking, communicating, or working. A C9orf72 hexanucleotide repeat mutation accounts for 10-15% of both disorders. With onset commonly in middle age or earlier, patients with ALS have a mean survival of two to three years. Patients with FTD have a mean survival of nine years. About Transposon Transposon Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing a platform of novel therapies for the treatment of neurodegenerative and aging-related diseases, including Alzheimer's disease. The company's lead clinical compound, TPN-101, is first-in-class to address LINE-1 reverse transcriptase for treating neurodegenerative and autoimmune diseases. The company also has a discovery platform supporting a deep pipeline of novel therapies to address additional indications. Contact: Rick Orr Transposon Therapeutics, Inc. (858) 535-4821 [email protected] SOURCE Transposon Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Grant to support the in vivo development of first-in-class condensate-modifying drugs (c-mods) targeting the TDP-43 condensatopathy in ALS BOSTON, Aug. 26, 2024 (GLOBE NEWSWIRE) -- Dewpoint Therapeutics Inc., the leading biotechnology company that develops therapeutics by targeting biomolecular condensates, announced today that it was awarded for the second time a Target ALS Foundation grant to validate its leading condensate-modifying compound (c-mod) in a mouse model of slow-progressing amyotrophic lateral sclerosis (ALS). This in-kind grant is a collaboration with Biospective contract research organization. Today, there are no disease-modifying therapeutic options for the ~ 20,000 patients that suffer from ALS in the US. The lack of efficacious drugs is reflected in the poor life expectancy of patients, at 2-5 years post diagnosis. Dewpoint is approaching ALS drug discovery and development from a new angle, by taking advantage of a pathology-driving aberration shared by over 97% of all patients – the wrongful localization of the protein TDP-43 from the nucleus to membrane-less cytoplasmic bodies, called biomolecular condensates. The TDP-43 mislocalization causes loss of TDP-43 splicing function and gain of toxic function caused by aberrant localization of other proteins into the TDP-43 cytoplasmic condensates. Together, these lead to systemic defects and the complex pathophysiology of ALS. Dewpoint’s lead c-mod was discovered through a high-content, high throughput approach that selected compounds that dissolve the aberrant TDP-43 condensates. Repairing the disease-driving aberrant condensate (condensatopathy), also repairs systemic TDP-43 loss of function and restores neuronal health, as well as clinically relevant ALS biomarkers in animal models. The slow-progressing ALS NLS8 mouse model offered by Biospective and Target ALS recapitulates the TDP-43 cytoplasmic mislocalization, neurodegeneration and motor deficit phenotypes experienced by patients. Validation of Dewpoint’s c-mod into the NLS8 model will complement the existing data package, and the ongoing work in a C9orf72 mouse model, supported through another grant awarded by Target ALS, to better understand the efficacy, safety and mechanism of action of this pre-clinical candidate. "Target ALS is thrilled to have the opportunity to help advance Dewpoint's mission to deliver a novel, effective treatment to ALS patients. Their molecule will be one of the first to test a central hypothesis regarding the role of TDP-43 in motor neuron degeneration and may have the potential to treat both sporadic and familial forms of ALS," said Dr. Amy Easton, Senior Director of Scientific Programs at Target ALS. “We are excited to expand our partnership with Target ALS and are appreciative of the foundation’s transformational effort to bring the academic and biotech communities together. This alliance will accelerate the path to the clinic for Dewpoint’s revolutionary TDP-43 condensatopathy-targeted c-mod, which we believe holds great promise for patients,” said Isaac Klein, MD PhD, CSO of Dewpoint Therapeutics. ABOUT CONDENSATES Condensates are membraneless organelles that form dynamically throughout the cell via a process called phase separation. These subcellular compartments organize and concentrate molecules within cells to enable a diversity of key biochemical processes. The dysregulation of biomolecular condensates has been observed in many diseases, including cancer, diabetes, and neurological disorders. Condensate-modifying drugs (c-mods) potentially provide novel therapeutic options for complex diseases and historically undruggable targets. ABOUT DEWPOINT THERAPEUTICS Dewpoint is the leading biotech company in the application of biomolecular condensate biology towards the development of a new generation of therapeutics to address diseases of high unmet need. The realization that a vast range of conditions are regulated by or arise from the dysfunction of condensates has provided new possibilities for modulating the function of high-value targets previously deemed ‘undruggable,' opening unexplored avenues to identify hundreds of novel therapeutic targets. Dewpoint’s proprietary AI/ML-powered state-of-the-art platform underlies a drug discovery pipeline that spans multiple therapeutic areas, including oncology, neurodegenerative, cardiopulmonary, and metabolic diseases. Through collaborations with Bayer, Novo Nordisk and Evotec, Dewpoint pushes the boundaries to accelerate the translation of condensate biology into medicine for patients suffering from difficult to treat diseases. Learn more at Dewpointx.com and follow us on X and LinkedIn. ABOUT TARGET ALS Target ALS is a 501(c)(3) medical research foundation committed to the search for effective treatments for Amyotrophic Lateral Sclerosis (ALS). Founded in 2013 by former New York City deputy mayor Dan Doctoroff — who lost both his father and uncle to ALS and was himself diagnosed in 2021 – Target ALS has transformed ALS research through their landmark Innovation Ecosystem model. The organization has fostered unprecedented collaborations between academia and the pharma and biotech industry, lowered barriers to access for critical research tools, and become a hub of communication and networking for the worldwide scientific community, resulting in the launch of 7 clinical trials and several drug discovery programs over the last decade. Building upon this momentum, Target ALS launched a groundbreaking Seven Pillar Strategy that will expand the breadth and depth of their ecosystem to accelerate ALS drug discovery with the goal of realizing a world where Everyone Lives. For more information and to get involved, visit www.targetals.org. Media contact: media@dewpointx.com Investor contact: Michael Fenn, Ph.D.Head of External Innovation & Investor Relations mfenn@dewpointx.com

Enrolled first FTD-GRN patient in Cohort 2 in upliFT-D trial Plan to present updated safety and biomarker data from Cohort 1 FTD-GRN patients treated with PBFT02 at 14th International Conference on Frontotemporal Dementias (ISFTD2024) in September 2024 Achieved alignment with Food and Drug Administration (FDA) on the company's proposed clinical development plans to expand the upliFT-D trial to assess PBFT02 in FTD patients with C9orf72 gene mutations Completed out-licensing of pediatric lysosomal storage disease programs to GEMMA Biotherapeutics Strong balance sheet to support continued execution, with cash runway to fund operations extended to the end of Q2 2026 PHILADELPHIA, Aug. 08, 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 second quarter ended June 30, 2024 and provided recent business highlights. “This has been a pivotal quarter for our company, marked by significant momentum in our upliFT-D trial, increased clarity around our strategy to expand PBFT02 into additional adult neurodegenerative indications, and out-licensing of our pediatric lysosomal storage disorder programs,” said Will Chou, M.D., president and chief executive officer of Passage Bio. “The positive recommendation of the IDMC to proceed to Cohort 2 dosing in our upliFT-D trial for FTD-GRN reinforces the well-tolerated safety profile of PBFT02 when combined with our revised immunosuppression regimen, and we are excited to present updated safety and biomarker data from Cohort 1 at the ISFTD2024 conference in Amsterdam this September. We are also pleased the FDA is aligned with our proposed expansion of our upliFT-D trial to include FTD-C9orf72 patients and expect to initiate dosing of these patients in the first half of 2025. The company remains on track to gain regulatory feedback on the pathway to treating ALS patients with PBFT02 in the second half of 2024.” Dr. Chou continued, "Furthermore, we completed the out-licensing of our pediatric lysosomal storage disease programs to GEMMA Biotherapeutics. Dr. Wilson and the entire GEMMABio team are committed to developing these promising therapies for pediatric patients with life-threatening conditions. We look forward to our continued research and collaboration efforts with their team, driving advancements and hope for those affected by neurodegenerative diseases.” Recent Highlights Enrolled first patient in Cohort 2 in upliFT-D trial for FTD-GRN: Following IDMC review of all available Cohort 1 safety data, the first patient in Cohort 2 has been enrolled in the trial; Cohort 2 will consist of three to five FTD-GRN patients to be treated with Dose 1. Dose 1 of PBFT02 continues to be well-tolerated in Cohort 1 patients who received the revised immunosuppression protocol (n=4). Recruitment efforts for subsequent Cohort 2 patients are well underway across seven clinical trial sites in Brazil, Canada, the United States and Europe. Plan to present updated safety and biomarker data from Cohort 1 patients in upliFT-D trial at ISFTD2024: Juan Chavez, M.D., vice president of clinical development at Passage Bio, will deliver updated data from Cohort 1 during an oral presentation, Interim Safety and Biomarker Data From upliFT-D Trial of PBFT02 in FTD with GRN Mutations, on Friday, September 20, 2024 at the 14th International Conference on Frontotemporal Dementias (ISFTD2024). Received FDA agreement on the company’s proposed expansion of the ongoing upliFT-D trial to treat FTD-C9orf72 patients with PBFT02: Substantial preclinical evidence, coupled with available safety and robust progranulin (PGRN) expression data from the first cohort of FTD-GRN patients treated with PBFT02, supported FDA alignment on the proposed trial expansion. The company intends to amend the protocol for the ongoing upliFT-D study to introduce a new population of FTD-C9orf72 patients and expects to initiate dosing of FTD-C9orf72 patients in 1H 2025. Completed out-licensing of pediatric lysosomal storage disease programs to GEMMA Biotherapeutics: Under the terms of the transaction, the company will receive initial payments of $10 million for the purchase of clinical product supply and up to an additional $10 million contingent on completion of certain GEMMABio business milestones. The company is also eligible to receive up to an additional $114 million in development and commercial milestones, as well as future royalties. GEMMA Biotherapeutics, a newly formed company co-founded by James M. Wilson, M.D., Ph.D., received an exclusive, worldwide license to PBGM01 for the treatment of GM1 gangliosidosis, PBKR03 for the treatment of Krabbe disease, and PBML04 for the treatment of metachromatic leukodystrophy. GEMMA Biotherapeutics is responsible for all future development of, and any remaining financial obligations owed to the University of Pennsylvania for the licensed programs. Entered into research, collaboration, and license agreement with GEMMA Biotherapeutics: Following a restructuring of the company’s original agreement with the University of Pennsylvania’s Gene Therapy Program, a research, collaboration, and license agreement with GEMMA Biotherapeutics was finalized. The partnership will focus on continued execution of preclinical studies in Huntington's disease, and the company will retain rights to future options in the CNS field, ensuring continued strategic growth and innovation in these critical areas. Anticipated Upcoming Milestones: FTD-GRN Report updated safety and biomarker data from Cohort 1 patients at ISFTD2024 in September 2024Report 12-month Cohort 1 and interim Cohort 2 data in 1H 2025Seek regulatory feedback on pivotal trial design in 2H 2025 FTD-C9orf72 and ALS Obtain regulatory feedback on the pathway to treating amyotrophic lateral sclerosis (ALS) patients with PBFT02 in 2H 2024Initiate dosing of FTD-C9orf72 patients in 1H 2025 Second Quarter 2024 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $91.8 million as of June 30, 2024, as compared to $151.5 million as of June 30, 2023. The company expects current cash, cash equivalents and marketable securities, together with the initial payments from our out-licensing agreements with Gemma Biotherapeutics, to fund operations to the end of Q2 2026.Research and Development (R&D) Expenses: R&D expenses were $10.4 million for the quarter ended June 30, 2024, as compared to $17.3 million for the quarter ended June 30, 2023.General and Administrative (G&A) Expenses: G&A expenses were $6.5 million for the quarter ended June 30, 2024, as compared to $8.1 million for the quarter ended June 30, 2023.Net Loss: Net loss was $16.0 million, or $0.26 per basic and diluted share, for the quarter ended June 30, 2024, as compared to a net loss of $23.9 million, or $0.44 per basic and diluted share, for the quarter ended June 30, 2023. 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 Statements This 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 initiation of dosing of FTD-C9orf72 patients, feedback from regulatory authorities, the progress of clinical studies and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our ability to receive milestone payments from our partners; our expectations about cash runway; 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 (Unaudited) (in thousands, except share and per share data) June 30, 2024 December 31, 2023Assets Current assets: Cash and cash equivalents $24,770 $21,709 Marketable securities 67,003 92,585 Prepaid expenses and other current assets 1,397 923 Prepaid research and development 1,830 2,742 Total current assets 95,000 117,959 Property and equipment, net 13,054 15,295 Right of use assets - operating leases 16,822 16,858 Other assets 516 433 Total assets $125,392 $150,545 Liabilities and stockholders’ equity Current liabilities: Accounts payable $621 $1,298 Accrued expenses and other current liabilities 8,063 11,670 Operating lease liabilities 3,701 3,373 Total current liabilities 12,385 16,341 Operating lease liabilities - noncurrent 22,450 22,921 Total liabilities 34,835 39,262 Stockholders’ equity: Preferred stock, $0.0001 par value: 10,000,000 shares authorized; no shares issued and outstanding at both June 30, 2024 and December 31, 2023 — — Common stock, $0.0001 par value: 300,000,000 shares authorized; 61,754,786 shares issued and outstanding at June 30, 2024 and 54,944,130 shares issued and outstanding at December 31, 2023 6 5 Additional paid‑in capital 717,788 705,789 Accumulated other comprehensive income (loss) (67) (43)Accumulated deficit (627,170) (594,468)Total stockholders’ equity 90,557 111,283 Total liabilities and stockholders’ equity $125,392 $150,545 Passage Bio, Inc. Statements of Operations and Comprehensive Loss (Unaudited) Three Months Ended June 30, Six Months Ended June 30, (in thousands, except share and per share data) 2024 2023 2024 2023Operating expenses: Research and development $10,430 $17,324 $21,965 $34,160 General and administrative 6,510 8,064 13,025 27,111 Impairment of long-lived assets 438 — 438 — Loss from operations (17,378) (25,388) (35,428) (61,271)Other income (expense), net 1,387 1,532 2,726 3,077 Net loss $(15,991) $(23,856) $(32,702) $(58,194)Per share information: Net loss per share of common stock, basic and diluted $(0.26) $(0.44) $(0.55) $(1.06)Weighted average common shares outstanding, basic and diluted 61,682,475 54,683,817 58,989,007 54,651,488 Comprehensive loss: Net loss $(15,991) $(23,856) $(32,702) $(58,194)Unrealized gain (loss) on marketable securities 2 87 (24) 626 Comprehensive loss $(15,989) $(23,769) $(32,726) $(57,568) For further information, please contact: Investors: Stuart Henderson Passage Bio 267.866.0114 shenderson@passagebio.com Media: Mike Beyer Sam Brown Inc. Healthcare Communications 312.961.2502 MikeBeyer@sambrown.com