Intestinal Pseudo-Obstruction

LAVAL, QC / ACCESSWIRE / March 6, 2024 / Bausch Health Companies Inc. (NYSE:BHC)(TSX:BHC) and its gastroenterology business, Salix Pharmaceuticals, Ltd., today announced that it is supporting a Phase 2 investigator-initiated study (IIS) of RELISTOR® (methylnaltrexone bromide: MNTX) in patients with resectable head and neck squamous cell carcinoma. An IIS is a study that is proposed, developed, and conducted by a qualified sponsor external to Bausch Health/Salix who assumes full responsibility for the study. The clinical study is being led by Juan P. Cata, M.D. at The University of Texas MD Anderson Cancer Center. The trial is designed to evaluate the potential of treating oral cavity squamous cell carcinoma patients with MNTX. It is a prospective, nonrandomized pilot "proof of concept" study where patients receive subcutaneous MNTX two weeks preoperatively and two weeks postoperatively. "The preclinical data and clinical suggestions point to potential activity against cancer," Robert Israel, M.D., Senior Vice President, Clinical and Medical Affairs, said. "Having Dr. Cata study this drug in head and neck cancer will shed light on how and if this agent could be further developed as a potential treatment option in neoplastic disease." Upon completion of the study, participants will be monitored every 3 months during the first two years. The primary endpoint is the successful administration of MNTX for two weeks preoperatively and postoperatively without interruption due to adverse events. Secondary endpoints include tumor viability, proliferation and apoptosis index, objective response rate, survival rates, and patient-reported outcomes. Identifier: NCT06162377. About RELISTOR RELISTOR® (methylnaltrexone bromide) is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. RELISTOR injection is also indicated for the treatment of OIC in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care. IMPORTANT SAFETY INFORMATION RELISTOR tablets and injection are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation. Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie's syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit pro using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn's disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom. If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their health care provider. Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal. Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. A dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment. A dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child- Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions and dose adjust per Prescribing Information as may be indicated. In the clinical studies, the most common adverse reactions were: OIC in adult patients with chronic non-cancer pain RELISTOR tablets (≥ 2% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (14%), diarrhea (5%), headache (4%), abdominal distention (4%), vomiting (3%), hyperhidrosis (3%), anxiety (2%), muscle spasms (2%), rhinorrhea (2%), and chills (2%). RELISTOR injection (≥ 1% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (21%), nausea (9%), diarrhea (6%), hyperhidrosis (6%), hot flush (3%), tremor (1%), and chills (1%). OIC in adult patients with advanced illness RELISTOR injection (≥ 5% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (29%) flatulence (13%), nausea (12%), dizziness (7%), and diarrhea (6%). To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800- FDA-1088 or Please click here for full Prescribing Information for RELISTOR tablets and RELISTOR injection. About Salix Salix Pharmaceuticals is one of the largest specialty pharmaceutical companies in the world committed to the prevention and treatment of gastrointestinal diseases. For more than 30 years, Salix has licensed, developed and marketed innovative products to improve patients' lives and arm health care providers with life-changing solutions for many chronic and debilitating conditions. Salix currently markets its product line to U.S. health care providers through an expanded sales force that focuses on gastroenterology, hepatology, pain specialists and primary care. Salix is headquartered in Bridgewater, New Jersey. For more information about Salix, visit and connect with us on Twitter and LinkedIn. About Bausch Health Bausch Health Companies Inc. (NYSE:BHC)(TSX:BHC) is a global company whose mission is to improve people's lives with our health care products. We develop, manufacture and market a range of pharmaceutical, medical device and over-the-counter products, primarily in the therapeutic areas of eye health, gastroenterology and dermatology. We are delivering on our commitments as we build an innovative company dedicated to advancing global health. For more information, visit and connect with us on Twitter and LinkedIn. Forward-looking Statements This news release may contain forward-looking statements, which may generally be identified by the use of the words "anticipates," "hopes," "expects," "intends," "plans," "should," "could," "would," "may," "believes," "estimates," "potential," "target," or "continue" and variations or similar expressions. These statements are based upon the current expectations and beliefs of management and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include, but are not limited to, the risks and uncertainties discussed in the Bausch Health most recent annual report on Form 10-K and detailed from time to time in Bausch Health's other filings with the U.S. Securities and Exchange Commission and the Canadian Securities Administrators, which factors are incorporated herein by reference. They also include, but are not limited to, risks and uncertainties caused by or relating to the evolving COVID-19 pandemic, and the fear of that pandemic and its potential effects, the severity, duration, and future impact of which are highly uncertain and cannot be predicted, and which may have a material adverse impact on Bausch Health, including but not limited to its project development timelines, and costs (which may increase). Readers are cautioned not to place undue reliance on any of these forward-looking statements. These forward-looking statements speak only as of the date hereof. ### Investor Contact: Media Contacts: ir@bauschhealth.com Kevin Wiggins (877) 281-6642 (toll-free) corporate.communications@bauschhealth.com (908) 541-3785 SOURCE: Salix Pharmaceuticals View the original press release on accesswire.com

– Initiated a Phase 1 clinical trial of ENTR-601-44 for the potential treatment of Duchenne muscular dystrophy, marking Entrada’s transition to a clinical-stage company – – Expanded the Company’s Duchenne franchise with the selection of its third clinical candidate, ENTR-601-50, for the potential treatment of people living with Duchenne who are exon 50 skipping amenable – – Cash runway expected through 2025 with $354 million in cash, cash equivalents and marketable securities as of September 30, 2023 – BOSTON, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Entrada Therapeutics, Inc. (Nasdaq: TRDA), a biopharmaceutical company aiming to transform the lives of patients by establishing intracellular Endosomal Escape Vehicle (EEV™)-therapeutics as a new class of medicines, today reported financial results for the third quarter ending September 30, 2023, and highlighted recent business updates. “The third quarter marked an important milestone for Entrada, as we transitioned into a clinical-stage company, with the initiation of the Phase 1 clinical trial in healthy volunteers for our lead Duchenne product candidate, ENTR-601-44. Duchenne muscular dystrophy is a relentlessly progressive neurodegenerative disease, and we are committed to bringing forward potential new therapeutic options for people living with Duchenne who have mutations that are amenable to particular exon skipping therapies,” said Dipal Doshi, President and Chief Executive Officer of Entrada Therapeutics. “We are well-positioned to embark upon our next phase of growth, as we further advance our Duchenne franchise and progress indications beyond neuromuscular diseases.” Recent Corporate Highlights In September 2023, Entrada dosed the first participant in its Phase 1 clinical trial evaluating ENTR-601-44 for the potential treatment of individuals with Duchenne muscular dystrophy (DMD) who are exon 44 skipping amenable. The primary objective of Entrada’s Phase 1 clinical trial, which is being conducted in the United Kingdom, is to evaluate the safety and tolerability of a single dose of ENTR-601-44 in healthy male volunteers, with a target enrollment of approximately 40 participants. The trial will also evaluate pharmacokinetics and target engagement, as measured by exon skipping in skeletal muscle. Entrada expects to report data from the Phase 1 clinical trial in the second half of 2024.The Company will provide an update on the clinical hold on its Investigational New Drug (IND) application for ENTR-601-44 with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2023. Entrada announced the selection of a third clinical candidate within its Duchenne franchise, ENTR-601-50, for the potential treatment of people living with Duchenne who are exon 50 skipping amenable. The selection of ENTR-601-50 is based on in vivo preclinical data demonstrating robust exon 50 skipping and dystrophin production across cardiac and skeletal muscle groups. Entrada expects to present these preclinical data in the first half of 2024 and plans to submit a Clinical Trial Application (CTA)/IND submission to initiate clinical development for ENTR-601-50 in 2025. In October 2023, the Company achieved a milestone pursuant to the Vertex Agreement related to preclinical IND-enabling GLP toxicology studies of ENTR-701 that triggered a $17.5 million milestone payment, which the Company expects to receive in the fourth quarter of 2023. In July 2023, Entrada entered into a license agreement to advance the development of ENTR-501 with Pierrepont Therapeutics, Inc., a mitochondrial disease-focused company. ENTR-501 is an intracellular thymidine phosphorylase enzyme replacement therapy in development for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is a slowly progressive and fatal, ultra rare disease for which there are no treatment options available. Third Quarter 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $353.6 million as of September 30, 2023, compared to $188.7 million as of December 31, 2022. Entrada anticipates that its cash, cash equivalents and marketable securities as of September 30, 2023, together with Vertex collaboration ongoing research support and the anticipated achievement of certain milestones, will be sufficient to fund the Company's operating expenses and capital expenditure requirements through 2025. Collaboration Revenue: Collaboration revenue was $43.7 million for the third quarter of 2023. There was no collaboration revenue in the third quarter of 2022. Research & Development (R&D) Expenses: R&D expenses were $22.2 million for the third quarter of 2023, compared to $19.0 million for the same period in 2022. This increase was primarily due to the initiation of the ENTR-601-44 Phase 1 clinical trial, additional investment in IND-enabling studies to support future clinical trials and higher personnel costs, including non-cash, stock-based compensation. General & Administrative (G&A) Expenses: G&A expenses were $7.5 million for the third quarter of 2023, compared to $7.0 million for the same period in 2022. This increase was primarily due to higher personnel costs, including non-cash, stock-based compensation, legal costs and other costs to support its ongoing clinical trial and continued research and development activities. Net Income (Loss): Net income was $35.5 million for the third quarter of 2023, compared to a net loss of $(25.1) million for the same period in 2022. About Entrada TherapeuticsEntrada Therapeutics is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines, Endosomal Escape Vehicle (EEV™)-therapeutics, to engage intracellular targets that have long been considered inaccessible and undruggable. The Company’s EEV therapeutics are designed to enable the efficient intracellular delivery of a wide range of therapeutics into a variety of organs and tissues, resulting in an improved therapeutic index. Through its proprietary, highly versatile and modular EEV platform, Entrada is building a robust development portfolio of RNA-, antibody- and enzyme-based programs for the potential treatment of neuromuscular, immunological, ocular and metabolic diseases, among others. The Company’s lead oligonucleotide programs include ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the potential treatment of people living with Duchenne who are exon 44, 45 and 50 skipping amenable, respectively, as well as our partnered candidate ENTR-701 for the potential treatment of myotonic dystrophy type 1 (DM1). For more information about Entrada, please visit our website, www.entradatx.com, and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Entrada’s strategy, future operations, prospects and plans, objectives of management, Entrada’s ability to continue to recruit for and complete a healthy volunteer trial for ENTR-601-44 in the United Kingdom, expectations regarding the timing of data from its Phase 1 trial for ENTR-601-44 in the second half of 2024, express or implied statements regarding the clinical hold on the IND for ENTR-601-44, Entrada’s ability to address the FDA’s concerns regarding its IND for ENTR-601-44, expectations regarding the timing and content of any update expected in the fourth quarter of 2023 concerning the clinical hold on the IND for ENTR-601-44, expectations regarding the therapeutic benefits of ENTR-601-44, expectations regarding the timing of preclinical data results and planned CTA/IND submission for ENTR-601-50, the continued development and advancement of ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the treatment of DMD, ENTR-501 for the treatment of MNGIE, and ENTR-701 for the treatment of DM1, including the IND-enabling studies, expectations regarding the expected timing, progress and success of our collaboration with Vertex, including any future payments we may receive under our collaboration and license agreements, the ability to develop additional therapeutic programs, including further exon skipping programs, the potential therapeutic benefits of its EEV candidates, statements regarding any future payments Entrada may receive under the Vertex Agreement, and the sufficiency of its cash resources through 2025, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Entrada may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities and the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Entrada’s ability to submit and obtain regulatory clearance for IND or equivalent foreign applications and initiate or complete clinical trials; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; whether Entrada’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Entrada’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-K and in subsequent filings Entrada may make with the SEC. In addition, the forward-looking statements included in this press release represent Entrada’s views as of the date of this press release. Entrada anticipates that subsequent events and developments will cause its views to change. However, while Entrada may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Entrada’s views as of any date subsequent to the date of this press release. ENTRADA THERAPEUTICS, INC.Condensed Consolidated Statements of Operations (Unaudited)(In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Collaboration revenue 43,735 — 87,165 — Operating expenses: Research and development 22,191 18,958 71,593 50,924 General and administrative 7,532 6,978 23,639 20,745 Total operating expenses 29,723 25,936 95,232 71,669 Income (loss) from operations 14,012 (25,936) (8,067) (71,669)Other income: Interest and other income 4,051 799 10,926 1,682 Total other income 4,051 799 10,926 1,682 Income (loss) before benefit from income taxes 18,063 (25,137) 2,859 (69,987)Benefit from income taxes 17,398 — — — Net income (loss) 35,461 (25,137) 2,859 (69,987)Net income (loss) per share, basic$1.07 $(0.80) $0.09 $(2.24)Net income (loss) per share, diluted$1.02 $(0.80) $0.08 $(2.24)Weighted‑average common shares outstanding, basic 33,281,287 31,298,052 32,942,958 31,273,612 Weighted‑average common shares outstanding, diluted 34,775,451 31,298,052 34,289,411 31,273,612 ENTRADA THERAPEUTICS, INC.Condensed Consolidated Balance Sheet Data (Unaudited)(In thousands) September 30,2023 December 31,2022 Cash, cash equivalents and marketable securities$353,578 $188,712Total assets 485,033 252,056Total liabilities 238,370 39,502Total stockholders’ equity 246,663 212,554 Investor and Media ContactKarla MacDonaldChief Corporate Affairs Officerkmacdonald@entradatx.com

Three New RFPs Now Open for Qualified Researchers of AVM, LYS, and MMIHS DANBURY, Conn., Sept. 19, 2023 /PRNewswire/ -- The National Organization for Rare Disorders (NORD®) announced three new grant funding opportunities related to the following rare diseases: Arteriovenous Malformation (AVM), Levy-Yeboa Syndrome (LYS), and Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS). NORD's Research Grants Program provides seed-money grants to qualified investigators for scientific and clinical research into diseases for which there are few other sources of funding. These grants are competitive and international. Continue Reading The National Organization for Rare Disorders (NORD) announces three new research opportunities for AVM, LYS, and MMIHS. Tweet this Photo of a medical researcher looking through a microscope With funding from the Tyler James Abizeid Foundation, NORD is accepting applications for one grant of up to $35,000 US, for scientific and/or clinical research studies related to Arteriovenous Malformation (AVM). Deadline for initial applications is Monday, October 16. View more information and apply here. With funding by the Maxwell Family, NORD is accepting applications for one grant of up to $40,000 US, for scientific and/or clinical research studies related to Levy-Yeboa syndrome (LYS). Deadline for initial applications is Monday, October 16. View more information and apply here. With funding from the MMIHS Foundation, NORD is accepting applications for one grant of $30,000 US for scientific and/or clinical research studies related to megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS). Deadline for initial applications is Monday, October 16. View more information and apply here. Grants will be awarded to qualified researchers to initiate small scientific research studies or clinical trials, the results of which could be used to obtain funding from the NIH, FDA, or other funding agencies, or to attract a corporate sponsor. "Since 1989, NORD's grants have led to the development of two FDA-approved treatments and many peer-reviewed publications. Over 200 grants have been awarded, totaling over $9 million in approved funding. The vision behind these critical study grants is to ultimately lead to new diagnostics, treatments, and cures for rare diseases," said Aliza Fink, Director, Research Programs, NORD. To learn more or submit to the 2023 NORD Research Grants Cycle, visit rarediseases.org/advancing-research/request-for-proposals/ About the National Organization for Rare Disorders (NORD) With a 40-year history of advancing care, treatments and policy, the National Organization for Rare Disorders (NORD) is the leading and longest-standing patient advocacy group for the 25-30 million Americans living with a rare disease. NORD, a 501(c)(3) nonprofit, is dedicated to individuals with rare diseases and the organizations that serve them. NORD, along with its more than 330 patient organization members, is committed to improving the health and well-being of people with rare diseases by driving advances in care, research and policy. For more information, please visit . SOURCE National Organization for Rare Disorders (NORD)