Familial Paroxysmal Dystonia

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.

Advancing leading pipeline of six disclosed programs across AAV cardiovascular and LV hematology portfolios; all milestones remain on track for 2024 Expanding commercial capabilities to support launch of LV portfolio beginning with KRESLADI™ (marnetegragene autotemcel) for severe LAD-I; PDUFA date of June 30, 2024 Cash, cash equivalents and investments of approximately $407.5M; expected operational runway into 2026 CRANBURY, N.J.--(BUSINESS WIRE)-- Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of genetic therapies for rare disorders with high unmet need, today reported financial and operational results for the fourth quarter and year ended December 31, 2023. “I am pleased with the strong results Rocket delivered in 2023, as we closed another successful year of progress across all six disclosed gene therapy programs spanning our AAV cardiovascular and LV hematology portfolios,” said Gaurav Shah, M.D., Chief Executive Officer, Rocket Pharma. “We are well poised to make further strides in 2024, notably expanding our commercial and operational capabilities to support the anticipated launch of KRESLADI™ (marnetegragene autotemcel) for severe LAD-I, representing Rocket’s first step in making our gene therapies available to patients who need them most. At the same time, we are laser focused on regulatory filings in Fanconi Anemia and continuing to advance our clinical programs in Danon Disease, PKP2-ACM and PKD in the year ahead. As we close the quarter, Rocket continues to solidify our industry leadership in gene therapy across multiple therapeutic areas and platforms as we seek to meet the needs of patients living with rare and devastating diseases.” Recent Pipeline and Operational Updates Milestones remain on track for 2024 across pipeline of adeno-associated virus (AAV) cardiovascular and lentiviral (LV) vector hematology portfolios. The Marketing Authorisation Application (MAA) and Biologics License Application (BLA) for Fanconi Anemia remain on track for filing with the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA), respectively, in the first half of 2024. Rocket is also progressing its Phase 2 pivotal study of RP-A501 for Danon Disease, Phase 2 pivotal study of RP-L301 for Pyruvate Kinase Deficiency (PKD), Phase 1 study of RP-A601 for PKP2-arrhythmogenic cardiomyopathy (ACM), and IND-enabling studies for BAG3-associated dilated cardiomyopathy (DCM). KRESLADI™ for severe Leukocyte Adhesion Deficiency-I (LAD-I) on track for PDUFA date of June 30, 2024. Based on the positive top-line efficacy and safety data from the global Phase 1/2 study and high unmet need in patients with severe LAD-I, the FDA accepted the BLA and granted Priority Review for KRESLADI™. On February 13, 2024, Rocket announced the FDA extended the Priority Review period by three months, to June 30, 2024, to allow additional time to review clarifying Chemistry, Manufacturing, and Controls (CMC) information submitted by Rocket in response to FDA information requests. The FDA further confirmed that an advisory committee meeting is not needed. In support of its first product launch, Rocket continues to expand its commercial and operational infrastructure, including Qualified Treatment Center initiation, channel strategy, disease education, and payer engagement. Published data from preclinical study of RP-A601 in PKP2-ACM. “AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans” was published in Circulation: Genomic and Precision Medicine. Results from the study demonstrated the potential of RP-A601 as a gene therapy for patients with PKP2-ACM. Bolstered commercial and operational expertise of Board of Directors with appointment of R. Keith Woods. Mr. Woods is a seasoned executive with more than 30 years of experience spanning commercialization, global operations, business strategy and supply chain. He recently served as Chief Operating Officer of argenx, where he led its global commercial organization, including marketing, market access, medical affairs, program management, and supply chain, during the company’s successful transition to commercial stage. Mr. Woods launched Vyvgart, a treatment for a rare autoimmune condition that causes muscle weakness, generating more than $1 billion in sales. Upcoming Investor Conferences Cowen’s 44th Annual Health Care Conference: March 5, 2024 Leerink Partners Global Biopharma Conference: March 12, 2024 Needham 23rd Annual Virtual Healthcare Conference: April 9, 2024 Fourth Quarter and Full Year 2023 Financial Results Cash position. Cash, cash equivalents and investments as of December 31, 2023, were $407.5 million. R&D expenses. Research and development expenses were $41.7 million and $186.3 million for the three and twelve months ended December 31, 2023, respectively, compared to $50.0 million and $165.6 million for the three and twelve months ended December 31, 2022, respectively. The increase in R&D expenses for the twelve months ended December 31, 2023, was primarily driven by increased compensation and benefits expense of $16.9 million due to increased R&D headcount, increased clinical trial costs of $14.5 million, and increased non-cash stock compensation expense of $5.0 million, offset by a decrease in manufacturing and development costs of $17.0 million. G&A expenses. General and administrative expenses were $21.5 million and $73.3 million for the three and twelve months ended December 31, 2023, respectively, compared to $19.0 million and $58.8 million for the three and twelve months ended December 31, 2022, respectively. The increase in G&A expenses for the twelve months ended December 31, 2023, was primarily driven by increases in commercial preparation expenses which consists of commercial strategy, medical affairs, market development and pricing analysis of $8.4 million and increased non-cash stock compensation expense of $3.4 million. Net loss. Net loss was $59.7 million and $245.6 million or $0.64 and $2.92 per share (basic and diluted) for the three and twelve months ended December 31, 2023, compared to $66.7 million and $221.9 million or $0.92 and $3.26 per share (basic and diluted) for the three and twelve months ended December 31, 2022. Shares outstanding. 90,282,267 shares of common stock were outstanding as of December 31, 2023. Financial Guidance Cash position. As of December 31, 2023, Rocket had cash, cash equivalents and investments of $407.5 million. Rocket expects such resources will be sufficient to fund its operations into 2026, including producing AAV cGMP batches at the Company’s Cranbury, N.J. R&D and manufacturing facility and continued development of its six clinical and/or preclinical programs. About Rocket Pharmaceuticals, Inc. Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare disorders. Rocket’s innovative multi-platform approach allows us to design the optimal gene therapy for each indication, creating potentially transformative options that enable people living with devastating rare diseases to experience long and full lives. Rocket’s lentiviral (LV) vector-based gene therapies target hematologic diseases and consist of late-stage programs for Fanconi Anemia, a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD), a monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Our adeno-associated virus (AAV)-based cardiovascular portfolio includes a late-stage program for Danon Disease, a devastating heart failure condition resulting in thickening of the heart, an early-stage program in clinical trials for PKP2-arrhythmogenic cardiomyopathy (ACM), a life-threatening heart failure disease causing ventricular arrhythmias and sudden cardiac death, and a pre-clinical program targeting BAG3-associated dilated cardiomyopathy (DCM), a heart failure condition that causes enlarged ventricles. For more information about Rocket, please visit and follow us on LinkedIn, YouTube and X. Rocket Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements concerning Rocket’s future expectations, plans and prospects that involve risks and uncertainties, as well as assumptions that, if they do not materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. All statements other than statements of historical facts contained in this release are forward-looking statements. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. These forward-looking statements include, but are not limited to, statements concerning Rocket’s expectations regarding the safety and effectiveness of product candidates that Rocket is developing to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Danon Disease (DD) and other diseases, the expected timing and data readouts of Rocket’s ongoing and planned clinical trials, the expected timing and outcome of Rocket’s regulatory interactions and planned submissions, Rocket’s plans for the advancement of its DD program, including its planned pivotal trial, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, Rocket’s ability to establish key collaborations and vendor relationships for its product candidates, Rocket’s ability to develop sales and marketing capabilities or enter into agreements with third parties to sell and market its product candidates and Rocket’s ability to expand its pipeline to target additional indications that are compatible with its gene therapy technologies. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, unexpected expenditures, Rocket’s competitors’ activities, including decisions as to the timing of competing product launches, pricing and discounting, Rocket’s ability to develop, acquire and advance product candidates into, enroll a sufficient number of patients into, and successfully complete, clinical studies, Rocket’s ability to acquire additional businesses, form strategic alliances or create joint ventures and its ability to realize the benefit of such acquisitions, alliances or joint ventures, Rocket’s ability to obtain and enforce patents to protect its product candidates, and its ability to successfully defend against unforeseen third-party infringement claims, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket’s Annual Report on Form 10-K for the year ended December 31, 2022, filed February 28, 2023 with the SEC and subsequent filings with the SEC including our Quarterly Reports on Form 10-Q. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 Operating expenses: Research and development $ 41,744 $ 50,037 $ 186,342 $ 165,570 General and administrative 21,535 19,044 73,317 58,773 Total operating expenses 63,279 69,081 259,659 224,343 Loss from operations (63,279 ) (69,081 ) (259,659 ) (224,343 ) Research and development incentives - 500 - 500 Interest expense (470 ) (467 ) (1,875 ) (1,862 ) Interest and other income, net 814 1,245 5,288 3,889 Accretion of discount and amortization of premium on investments, net 3,275 1,081 10,651 (47 ) Net loss $ (59,660 ) $ (66,722 ) $ (245,595 ) $ (221,863 ) Net loss per share - basic and diluted $ (0.64 ) $ (0.92 ) $ (2.92 ) $ (3.26 ) Weighted-average common shares outstanding - basic and diluted 93,336,541 72,889,548 84,009,004 68,148,925 December 31, December 31, 2023 2022 Cash, cash equivalents, and investments $ 407,495 $ 399,670 Total assets 566,341 551,807 Total liabilities 73,767 62,121 Total stockholders' equity 492,574 489,686

It's official: The ketogenic diet proved to be effective at controlling polycystic kidney disease (PKD) in the first randomized controlled clinical trial of ketogenic metabolic therapy for PKD. It's official: The ketogenic diet proved to be effective at controlling polycystic kidney disease (PKD) in the first randomized controlled clinical trial of ketogenic metabolic therapy for PKD. "I'm really happy about these clinical trial results," said UC Santa Barbara biologist Thomas Weimbs, whose lab was part of an international collaboration to investigate the effect of the fasting response known as ketosis on the cysts that are the hallmark of the disease. "We now have the first evidence in humans that the cysts really don't like to be in ketosis and that they don't seem to grow." The researchers' study is published in the journal Cell Reports Medicine. Nurture over nature For PKD patients, these findings represent an opportunity to control a genetic disease that leads to a progressive condition, causing pain and robbing them of their quality of life, and often resulting in the need for dialysis and kidney transplantation as the cysts destroy the kidneys' ability to effectively filter and remove waste from the body. "If you have PKD, the dogma is that it's a genetic disease," Weimbs said. "And no matter what you do, you progress toward kidney failure and diet doesn't make any difference, which unfortunately most patients are told to this day." This prevailing belief was what the Weimbs Lab and colleagues from various research institutions in Germany set out to challenge with their trial. Sixty-six PKD patients were recruited by the German research team headed by research physician Dr. Roman Müller of the University of Cologne and randomly split into three groups: a control group that received routine PKD counseling, another group that underwent a three-day water fast every month and a third group that observed a low-carbohydrate, high-fat ketogenic diet. The patients were followed closely with blood draws and MRI scans. At the end of the three-month trial period, the researchers found that while the control group experienced the expected growth in the size of their kidneys, the ketogenic diet patients' kidneys stopped growing and appeared to show a tendency to shrink somewhat, though the researchers pointed out that the shrinkage over the 90-day trial period failed to meet statistical significance. The most striking evidence came in the form of measurably improved kidney function in the ketogenic diet patients which was statistically significant. "To everyone's great surprise, kidney function actually improved with the ketogenic diet," said Wiembs. It's not something one would expect, he added, if PKD was truly something that could only get worse over time. "And that was a hard outcome of statistical significance." Kidney function was measured by the concentration of a protein called cystatin C -- higher-than-normal concentrations of this protein in the blood indicate a faltering filtration system, a symptom that worsened in the control group. The ketogenic diet was rated as "highly feasible" by the patients during the study, indicating a strong motivation and ability to control their condition via diet choices alone. "Doctors often assume that their patients cannot adhere to a diet anyway, so they don't even try. Clearly, this is not true. People with PKD are highly motivated to do something about their condition," he said. Different kinds of keto There is no one ketogenic diet to fit all, however, according to Weimbs. To get the best out of their diet, PKD patients should consult with their physicians and nutritionists as they shift away from the usual carbohydrate and sugar-laden standard diets that are pervasive in industrialized societies. "A keto diet just means very low carbs," he pointed out. There are many mainstream applications of this diet which is popular for weight loss. Though a popular version of the ketogenic diet is heavy on meat, that may not be the best option for all people with kidney disease. More plant-focused ketogenic diets are also available such as the Ren.Nu diet that was developed by Weimbs in collaboration with renal dietitians specifically for people with PKD and has been available to the public for two years. More Trials to Come These results represent a significant milestone for the Weimbs Lab, which has for more than two decades been researching the cell mechanisms that underlie PKD and other renal diseases. A chance discovery made by researchers in the lab -- kidney cysts had dramatically shrunk in mouse models that had undergone caloric restriction -- led them to pursue the idea that the fasting response known as ketosis might have some impact on the growth of the apparently glucose-dependent cysts. However as any scientist knows, one needs solid evidence to back up any claims of medical benefit for humans. You need clinical trials. "If you make a discovery in animals, but you don't check it in actual people, you'll never quite know if it's going to be meaningful," Weimbs said. "There's always going to be the doubt, and people are going to say animal experiments don't always translate to humans." Money to fund these trials became a challenge, thanks to the prevailing notion that PKD was unrelenting because of its genetic origin. "And, of course, it's always hard to find funding for diet interventions, because nobody wants to fund diets; they want to fund drug research," Weimbs added. Drug companies, which fund most clinical trials, have no interest in a diet, he added. However, Weimbs, together with Dr. Müller, was able to garner additional funding from the PKD Foundation to conduct the clinical trial in Germany. "Dr. Müller was able to supplement this with some other funding he had, and we essentially designed this trial together based on the animal results," Weimbs said. "But really the entire trial was run by his team, so they deserve all the credit and they did a fantastic job. They did everything despite the challenges of COVID." With these results, Weimbs and his team are looking ahead to further clinical trials slated to start in the coming year, one in Toronto and the other in Tokyo, to assess the efficacy of a medical food they developed specifically to assist PKD patients in reaching ketosis. Called KetoCitra and available through the Weimbs Lab's spinoff company Santa Barbara Nutrients, it's a formulation of the ketone beta-hydroxy-butyrate (BHB) that is generated during fasting, without the other ingredients and fillers that may be present in drugstore versions of BHB. The studies will involve more people -- 80 in Toronto and 200 in Tokyo -- and follow patients for a year. These trials will investigate the efficacy of the Ren.Nu plant-focused ketogenic diet in conjunction with KetoCitra. "We want to investigate the longer-term effects," Weimbs said. "If this trend of kidney volume change we saw in the three-month study holds true, we would expect to see a larger and statistically significant difference there as well.