Dyskinesias

- BLA submitted to FDA for Upstaza™ for the treatment of AADC deficiency - - NDA to be submitted mid-year for Translarna™ based on FDA feedback - SOUTH PLAINFIELD, N.J., March 19, 2024 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced the submission of a BLA to the U.S. FDA for Upstaza™ (eladocagene exuparvovec), a gene therapy for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. In addition, based on recent feedback from the FDA, PTC plans to re-submit an NDA for Translarna™ (ataluren) for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD). PTC expects to make the NDA resubmission by mid-year. "We are excited to bring Upstaza one step closer to children in the United States with the highly mortal and fatal disease of AADC deficiency. The data collected to date continue to demonstrate the transformative clinical benefits the gene therapy provides to patients," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "In addition, we look forward to the Translarna NDA resubmission this summer. We know U.S. patients and families have been waiting for an approved therapy that specially targets nmDMD." In addition, the sepiapterin MAA for PKU remains on schedule for submission to the EMA by the end of this month. About Upstaza™ (eladocagene exuparvovec) Upstaza is a one-time gene replacement therapy indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L–amino acid decarboxylase (AADC) deficiency with a severe phenotype. It is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy, containing the human DDC gene.1 It is designed to correct the underlying genetic defect, by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production.2,3 The efficacy and safety profile of Upstaza has been demonstrated across clinical trials and compassionate use programs.1 The first patient was dosed in 2010. In clinical trials, Upstaza demonstrated transformational neurological improvements. The most common side effects were initial insomnia, irritability and dyskinesia. Administration of Upstaza occurs through a stereotactic surgical procedure, a minimally invasive neurosurgical procedure used for the treatment of a number of pediatric and adult neurological disorders. The Upstaza administration procedure is performed by a qualified neurosurgeon in centers specialized in stereotactic neurosurgery. Upstaza has received marketing authorization in Europe, Great Britain and Israel. About aromatic L-amino acid decarboxylase (AADC) deficiency AADC deficiency is a fatal, rare genetic disorder that typically causes severe disability and suffering from the first months of life, affecting every aspect of life – physical, mental and behavioral. The suffering of children with AADC deficiency may be exacerbated by: episodes of distressing seizure-like oculogyric crises causing the eyes to roll up in the head, frequent vomiting, behavioral problems, and difficulty sleeping. The lives of affected children are severely impacted and shortened. Ongoing physical, occupational and speech therapy, and interventions, including surgery, also are often required to manage potentially life-threatening complications such as infections, severe feeding and breathing problems. About Translarna™ (ataluren) Translarna (ataluren), discovered and developed by PTC Therapeutics, is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in Duchenne. Translarna, the tradename of ataluren, is licensed in multiple countries for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) in ambulatory patients aged 2 years and older. Ataluren is an investigational new drug in the United States. About Duchenne Muscular Dystrophy (Duchenne) Primarily affecting males, Duchenne is a rare and fatal genetic disorder that results in progressive muscle weakness from early childhood and leads to premature death in the mid-20's due to heart and respiratory failure. It is a progressive muscle disorder caused by the lack of functional dystrophin protein. Dystrophin is critical to the structural stability of all muscles, including skeletal, diaphragm, and heart muscles. Patients with Duchenne can lose the ability to walk (loss of ambulation) as early as 10 years old, followed by loss of the use of their arms. Duchenne patients subsequently experience life-threatening lung complications, requiring the need for ventilation support, and heart complications in their late teens and 20s. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC's ability to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC's mission is to provide access to best-in-class treatments for patients who have little to no treatment options. PTC's strategy is to leverage its strong scientific and clinical expertise and global commercial infrastructure to bring therapies to patients. PTC believes this allows it to maximize value for all its stakeholders. To learn more about PTC, please visit us at and follow us on Facebook, Instagram, LinkedIn and Twitter at @PTCBio. For More Information: Investors: Kylie O'Keefe +1 (908) 300-0691 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statement This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; PTC's strategy, future operations, future financial position, future revenues, projected costs; the extent, timing and financial aspects of our strategic pipeline prioritization and reductions in workforce; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; PTC's ability to use the results of Study 041, a randomized, 18-month, placebo-controlled clinical trial of Translarna for the treatment of nmDMD followed by an 18-month open-label extension, and from its international drug registry study to support a marketing approval for Translarna for the treatment of nmDMD in the United States; whether investigators agree with PTC's interpretation of the results of clinical trials and the totality of clinical data from our trials in Translarna; expectations with respect to Upstaza, including any regulatory submissions and potential approvals, commercialization, manufacturing capabilities, the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligated to make; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Translarna and Upstaza. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. Acronyms: BLA: Biologics License Application DMD: Duchenne Muscular Dystrophy EMA: European Medicines Agency FDA: U.S. Food and Drug Administration MAA: Marketing Authorization Application NDA: New Drug Application PKU: Phenylketonuria References: Tai CH, et al. Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022;30(2):509-518. Chien et al. AGIL-AADC gene therapy results in sustained improvements in motor and developmental milestones through 5 years in children with AADC deficiency. Poster presented at the 48th Annual Meeting of the Child Neurology Society, Charlotte, NC, USA, Oct 23-26, 2019. Chien YH, et al. Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial. Lancet Child Adolesc Health. 2017;1(4):265-273. SOURCE PTC Therapeutics, Inc.

CALGARY, Alberta, March 19, 2024 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANUA WKN: A3UNZ), a late-stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease, is pleased to provide a summary of Company’s achievements in 2023 and objectives planned for 2024. Dr. Allen Davidoff, CEO of XORTX, stated, “2023 marked a year of substantial clinical, technological and regulatory progress, establishing the foundation for the Company’s 2024 goals. Key milestones include: 1/ the grant of U.S. Orphan Drug Designation for the XRx-008 program for Autosomal Dominant Polycystic Kidney Disease (“ADPKD”) that is being developed under the US FDA 505(b)2 rules further de-risking this program; 2/ ongoing discussions with the US FDA have aligned our endpoints and other Phase 3 clinical trial elements to make XORLO™ the Company’s proprietary oxypurinol formulation, eligible for accelerated approval. These key advances on the XRx-008 program during 2023 were made possible by the exceptional efforts of our Board of Directors, employees, consultants, and vendors. We believe the goals set for 2024 will advance our lead program XRx-008 for ADPKD ever closer to conducting a registration clinical trial leading to marketing approval and value creation for XORTX and its shareholders.” In 2023, the Company made steady progress advancing its strategic plan in key areas, including chemistry, formulation, manufacturing, and non-clinical studies using XORLO™ to attenuate polycystic kidney disease (“PKD”) progression in animal models, and topline results from the XRX-OXY-101 bridging clinical study of XORLO™. Each of these milestones permit the next step in the Company’s clinical development plan, being a “registration” clinical trial – XRX-OXY-201 in pursuit of accelerated approval and support of the Company’s lead program XRx-008 program for ADPKD. Synopsis of 2023 Achievements Chemistry and Manufacturing, Clinical and Pre-Clinical Highlights – Produced drug substance for oxypurinol production and produced GMP drug substance; confirmed XORLO™ formulation, produced enhanced bioavailability and produced clinical supply of tablets for clinical trials. Regulatory Submissions to US Food and Drug Administration (“FDA”) and European Medicines Agency (“EMA”) Supporting Clinical Trial Conduct April 21, 2023 – FDA granted Orphan Drug Designation for XRx-008 program for ADKPD, following review of February 1st submission of a comprehensive scientific review package within an Orphan Drug Designation application for XRx-008 for treatment of progressing kidney disease due to ADPKD with the US FDA.May 5, 2023 – FDA confirmed the eligibility of XORLO™ for Accelerated Approval following review of March 14th submission of type D meeting request with US FDA to discuss the clinical development plan (XRX-OXY-201 clinical trial design).August 29, 2023 – XORTX submitted an Orphan Drug Designation application to the EMA for the treatment of ADPKD. Following discussion and guidance from EMA, XORTX will expand data package and resubmit to gain EMA Orphan Drug Designation. Technology and Patent Advancements January 3, 2023 – XORTX submitted a new Provisional Patent Application seeking broadened and lengthened future patent protection, in a patent entitled “Compositions and Methods for Diagnosis, Treatment and Prevention of Kidney Disease.November 2, 2023 – XORTX sponsored study results were presented at American Society of Nephrology (“ASN”) under Session Title: “Genetic Diseases of the Kidneys”, by Dr. Charles Edelstein of the University of Colorado. Results of these studies suggest that management of xanthine oxidase activity in PKD may be more important than previously appreciated and further that previously unrecognized factors related to diet, genetic factors or prescribed drugs that increase uric acid levels could potentially aggravate the progression of PKD. Organizational Highlights In addition to substantial technological advancement, the Company continued to bolster the XORTX team with the following appointments: June 26, 2023 - James Fairbairn was appointed Chief Financial Officer of XORTX Therapeutics. Mr. Fairbairn has more than 20 years of experience with publicly-traded companies. He is a Chartered Professional Accountant, and an Institute-certified Director.December 31, 2023 – Patrick Treanor was appointed as a member of the XORTX Board of Directors. Patrick Treanor is a seasoned pharmaceutical industry executive with over 25 years experience. He is the current Chief Operating Officer of Pathalys Pharma, Inc., a private company specializing in advanced therapeutics for late-stage chronic kidney disease management. Mr. Treanor earned a BS in Management from Bryant University and an MBA from Rensselaer Polytechnic Institute. On November 29, 2023, XORTX returned to NASDAQ compliance following a reverse split to increase share price to greater than $1.00. XRx-008 Program Highlights – Independent Commercial Assessment In support of ongoing pharmaceutical partnership discussions, XORTX initiated an independent commercial assessment of the XRx-008 program for ADPKD with Bluestar BioAdvisors. This evaluation included interviews with 30 Nephrologists and 10 “Payers” with Large national Plans that cover greater than 290 million lives. Outcome of this assessment suggests that the XRx-008 program for ADPKD worldwide peak net sales per year that may exceed $1B, with a total product life estimated to surpass 7 to 10 years.2024 Corporate Objectives March 4, 2024 – XORTX completed an oversubscribed financing of $2.7 million.The Company will provide guidance, in the near future, regarding 2024 Corporate Objectives including announcements regarding clinical and regulatory submissions in support of the XRX-OXY-201 clinical “registration” trial designed to demonstrate the benefit of XORLO™ in slowing the progression of declining filtering capacity in ADPKD. About XORTX Therapeutics Inc. XORTX is a pharmaceutical company with two clinically advanced products in development: 1) our lead, XRx-008 program for ADPKD; and 2) our secondary program in XRx-101 for acute kidney and other acute organ injury associated with Coronavirus / COVID-19 infection. In addition, XRx-225 is a pre-clinical stage program for Type 2 Diabetic Nephropathy. XORTX is working to advance its clinical development stage products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. At XORTX, we are dedicated to developing medications to improve the quality of life and future health of patients. Additional information on XORTX is available at www.xortx.com. For more information, please contact: Allen Davidoff, CEONick Rigopulos, Director of Communicationsadavidoff@xortx.com or +1 403 455 7727nick@alpineequityadv.com or +1 617 901 0785 Neither the TSX Venture Exchange nor Nasdaq has approved or disapproved the contents of this news release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein. Forward Looking Statements This press release contains express or implied forward-looking statements pursuant to U.S. Federal securities laws. These forward-looking statements and their implications are based on the current expectations of the management of XORTX only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as otherwise required by law, XORTX undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. More detailed information about the risks and uncertainties affecting XORTX is contained under the heading “Risk Factors” in XORTX’s Registration Statement on Form F-1 filed with the SEC, which is available on the SEC's website, www.sec.gov (including any documents forming a part thereof or incorporated by reference therein), as well as in our reports, public disclosure documents and other filings with the securities commissions and other regulatory bodies in Canada, which are available on www.sedarplus.ca.

NEW YORK, March 19, 2024 /PRNewswire/ -- Seelos Therapeutics, Inc. (Nasdaq: SEEL) ("Seelos"), a clinical-stage biopharmaceutical company focused on the development of therapies for central nervous system disorders and rare diseases, today provided an update on top-line data of the Phase 2/3 HEALEY ALS Platform trial. This study was performed in collaboration with The Sean M. Healey and AMG Center, which is viewed as an influential force in ALS research and in caring for the ALS community. Their unique and innovative approach continues to be a benefit to the ALS community and its contributions have helped bring the last two FDA approved therapies for ALS to market. We plan to request a meeting with the FDA to discuss potential next steps for the program The study was designed to evaluate SLS-005 (IV trehalose), a low molecular weight disaccharide that stabilizes misfolded proteins and activates autophagy, in decreasing the slope of the ALS Functional Rating Scale (ALSFRS-R) and separation from placebo in Function and Mortality in an all-comers population of Persons with ALS (PALS). While the study did not meet statistical significance in the primary and secondary endpoint in the Full Analysis Set (FAS)2, by showing a 13% improvement in Function and Mortality with an 88% success probability (versus the pre-specified 98%), it showed a potential signal of efficacy in a pre-specified subgroup (ERF)1. In the pre-specified subgroup of PALS treated with SLS-005, without RELYVRIO®, the top-line data favored SLS-005 versus placebo in efficacy measures in the Efficacy RELYVRIO® Free (ERF)1 data set (n=130), including: a 22% improvement in slope of change in ALSFRS-R assessment adjusted for mortality, with an 89% success probability, at 24 weeks the rate of decline in ALSFRS-R slope (points per month) also favored the SLS-005 treatment group versus placebo over 6 months (-0.80 and -1.07 points per month, respectively) a 25% slowing of Slow Vital Capacity (SVC) decline versus placebo (-11.5% for SLS-005 and -15.4% for placebo) at 24 weeks Additional analysis and information from these data accessible here. "The HEALEY platform is designed to detect signals of efficacy and we believe the observed signal and success probability is competitive to other recently FDA-approved therapies for ALS which also failed to achieve statistical significance when measured for function and mortality on similar primary and efficacy endpoints," said Raj Mehra Ph.D., Chairman and Chief Executive Officer of Seelos. "We plan to request a meeting with the FDA to discuss potential next steps for the program and will continue our potential partner discussions." Seelos has not yet received the full dataset and upon receiving it in the near future, Seelos plans to run additional analyses, including biomarkers of neurodegeneration, neurofilament light chain (NfL), exploratory efficacy results, subgroups and post-hoc analyses. SLS-005 was generally well-tolerated and comparable to placebo in safety. There was an imbalance of deaths/death equivalents observed in the study, with more events seen in the SLS-005 group compared to placebo, all were considered unrelated to the study drug. Populations – ERF1, FAS2 and ERO3: Seelos received top-line results for Regimen E (RGE). This included a Full Analysis Set (FAS), an Efficacy Regimen Only (ERO) population and an Efficacy RELYVRIO® Free (ERF) population. FAS includes shared placebo from all regimens, including RGE (n=204) and the RGE SLS-005 participants (n=120). The Efficacy Regimen Only (ERO) population includes 120 RGE SLS-005 and 41 RGE placebo participants. 31 participants in the ERO population received RELYVRIO® during the SLS-005 RGE study, thus confounding results from this population. The ERF analyses exclude participants who initiated RELYVRIO® during the study. ERF represents the participants who followed the protocol as envisioned (n=130, i.e., the ERF population comprises 81% of ERO/RGE participants). About SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion) SLS-005 is a low molecular weight disaccharide (0.342 kDa) that crosses the blood brain barrier and is thought to stabilize proteins and activate autophagy through the activation of Transcription Factor EB (TFEB), a key factor in lysosomal and autophagy gene expression. The activation of TFEB is an emerging therapeutic target for a number of diseases with pathologic accumulation of storage material. In animal models of several diseases associated with abnormal cellular protein aggregation or storage of pathologic material, SLS-005 has been shown to reduce aggregation of misfolded proteins and reduce accumulation of pathologic material. SLS-005 has previously received Orphan Drug Designation for the treatment of ALS from the U.S. Food and Drug Administration and from the European Medicines Agency in the EU. SLS-005 is an investigational treatment and is not currently approved by any health authority for medicinal use. About Amyotrophic Lateral Sclerosis (ALS) According to the National Institute of Neurological Disorders and Stroke, amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken, start to twitch (called fasciculations), and waste away (called atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive, meaning the symptoms get worse over time. The majority of ALS cases (90 percent or more) are considered sporadic. This means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease. Although family members of people with sporadic ALS are at an increased risk for the disease, the overall risk is very low, and most will not develop ALS. Most people with ALS eventually die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease. A 1-point change in the ALSFRS-R score can indicate a meaningful difference in a person's ability to function independently with activities of daily living (ADL's), including eating, bathing, dressing or walking.4 4. FDA Center for Drug Evaluation and Research, Application Number 209176Orig1s000, Office Director Memo, Ellis F. Unger, MD, May 4, 2017. Paganoni S, et al. New Eng J Med. 2020. About Seelos Therapeutics Seelos Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development and advancement of novel therapeutics to address unmet medical needs for the benefit of patients with central nervous system (CNS) disorders and other rare diseases. The Company's robust portfolio includes several late-stage clinical assets targeting indications including Acute Suicidal Ideation and Behavior (ASIB) in Major Depressive Disorder (MDD), amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia (SCA), as well as early-stage programs in Huntington's disease, Alzheimer's disease, and Parkinson's disease. For more information, please visit our website: , the content of which is not incorporated herein by reference. Forward Looking Statements Statements made in this press release, which are not historical in nature, constitute forward-looking statements for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. These statements include, among others, those regarding the Phase 2/3 study of SLS-005, statements regarding the competitiveness of the results to recently approved FDA therapies for ALS, statements regarding any planned meetings and discussions with the FDA, statements regarding The Sean M. Healey and AMG Center's contributions to the ALS community, statements regarding the timing of Seelos's receipt of the full dataset for the trial, statements regarding additional analyses to be run by Seelos and statements regarding SLS-005's prospects and any future analyses that may be conducted. These statements are based on Seelos' current expectations and beliefs and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Risks associated with Seelos' business and plans described herein include, but are not limited to, the risk of not successfully executing its preclinical and clinical studies, not being able to move forward with the development of SLS-005, and not gaining marketing approvals for SLS-005 and/or its other product candidates; the risk that prior clinical results may not be replicated in future studies and trials (including the risk that the results from the prior studies of SLS-005 may not be replicated or may be materially different from the results of the top-line data from the SLS-005 study); the risks that clinical study results may not meet any or all endpoints of a clinical study and that any data generated from such studies may not support a regulatory submission or approval; the risks associated with the implementation of Seelos' business strategy; the risks related to raising capital to fund its development plans and ongoing operations; the risks related to Seelos' current stock price; as well as other factors expressed in Seelos' periodic filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. Although we believe that the expectations reflected in our forward-looking statements are reasonable, we do not know whether our expectations will prove correct. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, even if subsequently made available by us on our website or otherwise. We do not undertake any obligation to update, amend or clarify these forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Contact Information: Anthony Marciano Chief Communications Officer Seelos Therapeutics, Inc. (Nasdaq: SEEL) 300 Park Avenue, 2nd Floor New York, NY 10022 (646) 293-2136 anthony.marciano@seelostx.com Mike Moyer Managing Director LifeSci Advisors, LLC 250 West 55th St., Suite 3401 New York, NY 10019 (617) 308-4306 mmoyer@lifesciadvisors.com Company Codes: NASDAQ-NMS:SEEL