Hypophosphatasia

Trial will evaluate ilofotase alfa as a treatment to prevent renal damage in at-risk patients following open heart surgery Ilofotase alfa’s clinical record of renal protective effects supports therapeutic potential in underserved and high-need indication UTRECHT, The Netherlands--(BUSINESS WIRE)-- AM-Pharma B.V. today announced that the first patients have been treated in a Phase 2 clinical study evaluating the company’s proprietary recombinant alkaline phosphatase, ilofotase alfa, as a preventive treatment for cardiac surgery-associated renal damage (CSA-RD). With over 2 million open heart surgeries1 performed worldwide every year, CSA-RD represents a critical surgical complication for which there is no specific pharmacological therapy. CSA-RD is defined as the long-term loss of renal function in cardiac surgery patients and arises from acute kidney injury (AKI) immediately following the surgery. CSA-AKI occurs in approximately 1 out of 3 patients undergoing open heart surgery and is the predominant risk factor for death post-surgery, with 2-5% of patients requiring renal replacement therapy as a result. Ilofotase alfa has a proven safety and tolerability pro a strong record of renal protective effects as observed in previous clinical studies. Notably, prior Phase 2 and Phase 3 trials with ilofotase alfa demonstrated significant improvements in Major Adverse Kidney Events by day 90 (MAKE90) in sepsis-associated AKI. As recently reported in a publication2 on the REVIVAL Phase 3 trial, MAKE90 events were reduced to 57.2% of patients in the ilofotase alfa group compared to 64.7% in the placebo group. “Previous clinical trials showed ilofotase alfa had significant reno-protective effects in sepsis-associated AKI patients. Given the role of AKI in long-term renal impairment in cardiac surgery patients, ilofotase alfa preventative treatment could have substantial clinical benefits on renal function and potentially save lives,” said Peter Pickkers, MD, PhD, Principal Investigator in the Phase 2 study and Professor of Experimental Intensive Care Medicine at Radboud University Nijmegen Medical Centre, The Netherlands. The multicenter, double-blind, randomized, placebo-controlled Phase 2 trial will evaluate the efficacy and safety of ilofotase alfa as a preventive treatment in 150 patients scheduled for cardiac surgery and at risk for CSA-RD. Treatment will be administered intravenously before and after surgery, with a follow-up period of 60 days. The primary endpoint will be the ratio between pre- and post-surgery creatinine levels. Important exploratory endpoints will be the incidence of Major Adverse Kidney Events (MAKE) and the incidence and severity of AKI post-surgery. The trial is planned to end in Q4 2024 with a data readout expected in early 2025. Ilofotase alfa was recently evaluated in a Phase 1b pilot study as enzyme replacement therapy in hypophosphatasia (HPP) patients. “With the initiation of the Phase 2 trial in CSA-RD following the positive results from the Phase 1b study in HPP we have achieved important progress toward establishing ilofotase alfa’s potential through our updated clinical development strategy. We are confident in our new trajectory and remain committed to delivering a therapeutic solution for patients in these two severe, high-need conditions,” said Juliane Bernholz, PhD, Chief Executive Officer of AM-Pharma. “The clinical centers we are working with show great enthusiasm for our approach with ilofotase alfa and we look forward to the data readout.” About ilofotase alfa Ilofotase alfa is a proprietary recombinant alkaline phosphatase, constructed from two human isoforms of alkaline phosphatase, that has been shown to be stable and highly active in multiple clinical trials. The recombinant enzyme displays exquisite activity towards dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), ATP, ADP and other extracellular substrates that drive acute inflammation, coagulation and microvascular ischemia found in kidney following sepsis or ischemia-induced damage. Research has shown that ATP dephosphorylation has a double effect in protecting against kidney injury. When the pro-inflammatory ATP is dephosphorylated, the resulting adenosine further reduces inflammation through the activation of the immunosuppressive adenosine A2a receptor pathway. In hypophosphatasia, ilofotase alfa addresses elevated levels of pyridoxal-5′-phosphate (PLP), inorganic pyrophosphates (PPi), two disease-related biomarkers that are related to bone mineralization and pain sensation, for example. About cardiac surgery-associated renal damage (CSA-RD) CSA-RD is a clinical complication that arises from acute kidney injury (AKI) following open heart surgery performed with the use of a cardiopulmonary bypass (CPB) pump. Apart from sepsis, this type of surgery is the most frequent cause of AKI. CSA-AKI occurs in about 1 in 3 patients undergoing this surgical procedure.3 Pre-operative and intra-operative measures can be taken to reduce the risk of AKI, and post-operative management strategies may also help mitigate further damage.4 However, there is currently no pharmacological therapy to prevent AKI, and the kidney injury can result in long-term renal impairment and the need for renal replacement therapy (RRT) such as dialysis. Notably, mortality can be up to 50% in CSA-AKI patients who require RRT post-operatively. About AM-Pharma AM-Pharma strives to develop medicines for patients confronted with severe medical conditions. Our proprietary asset, ilofotase alfa, is being developed for the treatment of patients with acute kidney injury (AKI) and has been granted FDA fast-track status. We also develop ilofotase alfa in the severe rare disease hypophosphatasia where ilofotase alfa has orphan drug status in the US and EU. With approximately 1,000 subjects evaluated to date in clinical trials, ilofotase alfa has a proven safety pro a demonstrated kidney benefit. We are a dedicated team driven to bring treatment options to severely ill patients, their families and acute care professionals. Find out more about us online at: . 1 2 Pickkers P et al., Intensive Care Med., 2024 3 Andújar A et al., Front. Nephrol., 2023 4 Ostermann M et al., J Clin Med., 2021 View source version on businesswire.com: Contacts Investors: Juliane Bernholz, Chief Executive Officer j.bernholz@am-pharma.com Media: Trophic Communications Gretchen Schweitzer or Priscillia Perrin +31 6 52 33 15 79 am-pharma@trophic.eu Source: AM-Pharma View this news release online at:

NEW HAVEN, Conn.--( BUSINESS WIRE )--Rallybio Corporation (Nasdaq: RLYB), a clinical-stage biotechnology company committed to identifying and accelerating the development of life-transforming therapies for patients with severe and rare diseases, today provided an update on recent accomplishments and announced expected 2024 milestones. The Company will present these updates at the 42 nd Annual J.P. Morgan Health Care Conference in San Francisco, California on Wednesday, January 10, 2024, at 8:15 a.m. PT (11:15 a.m. ET). “Over the past twelve months we made significant progress towards building a broad and sustainable pipeline of transformative therapeutics for rare diseases with severe unmet needs,” said Stephen Uden, M.D., Chief Executive Officer of Rallybio. “In 2023, we announced encouraging Phase 1 results for our lead program, RLYB212, for the prevention of fetal and neonatal alloimmune thrombocytopenia, as well as for RLYB116, our C5 inhibitor. In parallel, we completed critical work on our earlier stage pipeline programs while carefully managing our expenses.” Dr. Uden continued, “We are committed to building on this momentum in 2024. We remain on track to initiate a Phase 2 study for RLYB212 in the second half of 2024 to confirm the dose regimen for RLYB212 in pregnant women at higher risk for FNAIT. Furthermore, we believe RLYB116 is a promising drug candidate that has the potential to address an unmet need for patients by delivering a more convenient once-a-week self-administered therapy, and our earlier stage programs are expected to reach important milestones in 2024. We are also pleased that through careful management of our cash, our current cash runway guidance has been extended into the third quarter of 2025. We expect to have additional updates to our plans and cash runway before the end of the first quarter.” Recent Portfolio Milestones and Expected Upcoming Milestones Maternal Fetal Blood Disorders Rallybio expects to provide an update on Phase 2 discussions with the European Medicines Agency (EMA) for RLYB212, a novel human monoclonal anti-HPA-1a antibody in development for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT), in the first half of 2024. Rallybio expects to initiate its Phase 2 dose confirmation study for RLYB212 in the second half of 2024. The study is designed to confirm the dose regimen for RLYB212 in pregnant women at higher risk for FNAIT, prior to initiation of a Phase 3 registrational study. In addition, Rallybio continues to advance its FNAIT natural history alloimmunization study. The FNAIT natural history study is a non-interventional study designed to provide a contemporary dataset for HPA-1a alloimmunization frequency in a racially and ethnically diverse population that can serve as a control arm for the planned single-arm Phase 3 registrational study. In addition, the natural history study is intended to establish the operational framework for the Phase 2 study and future Phase 3 registrational study. Screening for the natural history study is expected to continue simultaneously with execution of the Phase 2 study. Data from both studies will be used for the end of Phase 2 regulatory discussions with the U.S. Food and Drug Administration and the EMA to support design and initiation of the Phase 3 registrational study. The natural history study has screened more than 7,600 women to date and the Company expects to provide an update on screening for 2024 in the first quarter. Complement Dysregulation In December 2023, Rallybio announced preliminary Phase 1 multiple ascending dose data for RLYB116. Preliminary results showed that a 100 mg low volume once-a-week dose of subcutaneously administered RLYB116 achieved sustained mean reductions in free C5 of greater than 93%. In addition, RLYB116 administered as a 100 mg once-a-week dose was observed to be generally well tolerated with injection site reaction as the most common adverse event (AE) in the cohort, occurring in 60% of the participants in the cohort. All AEs with the 100 mg weekly dose were mild in severity. While the data support advancement of RLYB116 for patients with certain complement-mediated diseases, including generalized myasthenia gravis (gMG), the Company is prioritizing near-term investments in RLYB116 manufacturing and expects that additional manufacturing work will improve tolerability at higher doses with a low injection volume and infrequent subcutaneous administration. The Company believes such enhancements will enable higher exposure to RLYB116 and potentially increase C5 reduction, which can result in treating a broader range of complement-mediated diseases, including paroxysmal nocturnal hemoglobinuria and antiphospholipid syndrome. Rallybio expects to complete this manufacturing work and provide an update on the development plan for RLYB116 in the second half of 2024. Rallybio, together with its partner EyePoint Pharmaceuticals, Inc., continue to evaluate sustained delivery of Rallybio’s inhibitor of C5 using EyePoint’s proprietary Durasert ® technology for sustained intraocular drug delivery, with the initial focus on geographic atrophy, an advanced form of age-related macular degeneration that leads to irreversible vision loss. Rallybio and EyePoint expect to provide an update on this collaboration in the first half of 2024. Hematological Disorders Rallybio continues to advance preclinical activities for RLYB331, a preclinical, therapeutic monoclonal antibody that inhibits Matriptase-2 (MTP-2), to support the transition of this asset into clinical development. Rallybio expects to report additional animal data from this program in the first half of 2024. Metabolic Disorders Rallybio, together with its partner Exscientia, continues to work toward the selection of a small molecule development candidate to advance into the clinic targeting ENPP1 for the treatment of patients with hypophosphatasia (HPP). Significant progress has been made and proof of mechanism studies are in progress with a leading global HPP expert. Rallybio and Exscientia plan to provide an update on the progress of the program in the second half of 2024. Rallybio, together with its partner AbCellera, are focused on the discovery, development, and commercialization of novel antibody-based therapeutics for rare diseases. The partnership’s first discovery program is focused on identifying a novel treatment for patients with rare metabolic diseases. Financial Update Cash, cash equivalents, and marketable securities were $121.4 million as of September 30, 2023. The Company currently expects its cash runway to extend into the third quarter of 2025. Webcast of Presentation at the 42 nd Annual J.P. Morgan Health Care Conference Rallybio is scheduled to present at the 42 nd Annual J.P. Morgan Health Care Conference on Wednesday, January 10, 2024, at 8:15 a.m. PT (11:15 a.m. ET). A live webcast of the presentation and subsequent question and answer session will be accessible through the Events and Presentations section of Rallybio’s website. An archived replay of the webcast will be available for 30 days following the presentation. About Rallybio Rallybio (NASDAQ: RLYB) is a clinical-stage biotechnology company with a mission to develop and commercialize life-transforming therapies for patients with severe and rare diseases. Rallybio has built a broad pipeline of promising product candidates aimed at addressing diseases with unmet medical need in areas of maternal fetal health, complement dysregulation, hematology, and metabolic disorders. The Company has two clinical stage programs: RLYB212, an anti-HPA-1a antibody for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT) and RLYB116, an inhibitor of complement component 5 (C5), with the potential to treat several diseases of complement dysregulation, as well as additional programs in preclinical development. Rallybio is headquartered in New Haven, Connecticut. For more information, please visit www.rallybio.com and follow us on LinkedIn and Twitter . Forward-Looking Statements This press release contains forward-looking statements that are based on our management’s beliefs and assumptions and on currently available information. All statements, other than statements of historical facts contained in this press release are forward-looking statements. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements concerning the timing of initiation of the Phase 2 dose confirmation study for RLYB212, the progress and number of women screened in the natural history study, whether the results of the natural history study and the planned Phase 2 dose confirmation study will be sufficient to support design and implementation of a Phase 3 registrational study for RLYB212, whether the manufacturing work for RLYB116 will be timely completed or successful, our expectations regarding the usefulness of data from our clinical studies, the timing of reporting results from our collaboration with EyePoint, the timing of reporting results of the animal studies with RLYB331, the timing of providing an update of our joint venture with Exscientia, the likelihood that Rallybio will be successful in developing RLYB212, RLYB116, or any of our other product candidates, and our cash runway. The forward-looking statements in this press release are only predictions and are based largely on management’s current expectations and projections about future events and financial trends that management believes may affect Rallybio’s business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions, including, but not limited to, our ability to successfully initiate and conduct our planned clinical studies, and complete such clinical studies and obtain results on our expected timelines, or at all, whether our cash resources will be sufficient to fund our operating expenses and capital expenditure requirements and whether we will be successful raising additional capital, our ability to enter into strategic partnerships or other arrangements, competition from other biotechnology and pharmaceutical companies, and those risks and uncertainties described in Rallybio’s filings with the U.S. Securities and Exchange Commission (SEC), including Rallybio’s Quarterly Report on Form 10-Q for the period ended September 30, 2023, and subsequent filings with the SEC. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Except as required by applicable law, we are not obligated to publicly update or revise any forward-looking statements contained in this press release, whether as a result of any new information, future events, changed circumstances or otherwise.

When developing new medicines, drugmakers typically try to make treatments that are more effective, durable or safer than whats already available.If theyre lucky, they can hit on something that meets at least one of those goals. Rampart Bioscience, a new biotechnology company eyeing a way to make better DNA-based medicines, is striving to hit all three.Headquartered in La Jolla, California, Rampart emerged from stealth Tuesday with $85 million in new funding to develop its lead program for a rare inherited condition known as hypophosphatasia.The company is led by Louis Breton and Jeffrey Bartlett, a pair of biotech veterans who last oversaw Calimmune, a cell and gene therapy developer that worked to create new treatments for HIV and other diseases. Calimmune was picked up by CSL Behring in 2017 through a $91 million deal.Their latest endeavor was born after a phone call with David Bonita, a partner with the venture capital fund OrbiMed.OrbiMed previously funded another company developing a treatment for infants whose bones and teeth did not mineralize properly, which would later become Alexion Pharmaceuticals enzyme replacement therapy Strensiq. But the drug is used for severe forms of hypophosphatasia, leaving patients with more moderate symptoms without any options approved by the Food and Drug Administration. Breton and Bartlett wondered: Could they do better?Rampart, which takes its name from a word meaning to fortify, hopes to create a treatment that could be more long-lasting and effective for those patients. The severe form of hypophosphatasia affects an estimated 1 in 100,000 babies, but milder cases likely occur more frequently and later in life.Especially for those who have diseases where it impacts their quality of life, helping them fortify their own bodies ... is a great step, Breton said.Genetic medicines have, especially in the last decade, proven they can dramatically benefit patients with certain inherited conditions. Often, though, their effectiveness has been hampered by limitations of delivery. Rampart believes its approach can address both delivery and the issue of re-dosability, which may be necessary as hypophosphatasia progresses, according to the company.There are many groups that have been working for specific rare diseases on genetic therapies that potentially would be a one-and-done. But in the way of looking at what would be optimal for patients, this provides more flexibility for doctors, Breton said. It's not just the availability of options for patients; it provides much more specificity to their symptoms and some of the aspects of their own disease progression.Rampart is also developing an unspecified number of other programs.Since its inception in 2019, the company has raised $125 million in private financing, including a $40 million seed round from OrbiMed. Joining OrbiMed in the Series A round were investors RA Capital Management and HealthCap.We are very much a product company,“ Bartlett said. But Rampart's near-term milestones also include continuing to develop the platform and collect the kind of data we've been fortunate in getting. '