Acidaemia

Genespire’s GENE202 was developed using the company’s Immune Shielded Lentiviral Vector (ISLV) platform that allows a patient’s liver to produce the therapy throughout its lifetime. Image credit: jack8 / Shutterstock. Italian biotech Genspire is set to launch a Phase I/II clinical trial of its lead gene therapy, GENE202, as a treatment for a group of rare, inherited diseases – methylmalonic acidemia. The company will be able to fund the trial after it received €46.6m ($52.1m) in a Series B financing round. The financing will also help to fund discovery and preclinical work for other gene therapy candidates. Investors included European investment firms such as Sofinnova Partners, XGEN Venture and CDP Venture Capital. Genspire is a spinout from Milan-based San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), and has previously raised €16m in Series A financing in 2020. Methylmalonic acidaemia is a group of rare genetic disorders where an individual is unable to metabolise proteins and fats properly. This results in high levels of acid in the blood (acidaemia) and body tissues. Methylmalonic acidaemia often manifests within the first few months of life and its severity can vary from mild disease to life-threatening. According to the US National Organization for Rare Disorders (NORD), methylmalonic acidaemia usually affects 1 in 50,000 to 1 in 100,000 live births. The disease is usually managed through dietary modifications to limit certain proteins and fats. See Also: Biologic API Manufacturing Companies (Protein and Peptide) in Contract Manufacturing for the Pharmaceutical Industry Bavarian Nordic gains US contract for additional mpox vaccine GENE202 is an off-the-shelf, one time gene therapy developed using the company’s Immune Shielded Lentiviral Vector (ISLV) platform. ISLV-based therapies are designed to allow a patient’s liver to produce the therapy throughout its lifetime. Gene therapies are a growing area of interest , with multiple gene therapies gaining approval from the US Food and Drug Administration (FDA) in recent years. In recent months, multiple companies have entered the gene therapy market by acquiring or merging with specialist companies and pipelines. Last year, Alexion AstraZeneca Rare Disease signed a definitive agreement, acquiring and licensing Pfizer ’s early-stage gene therapy portfolio for rare diseases . The deal included a $1bn payment along with net sale royalties from the acquired therapies. Despite the recent interest, the uptake of gene therapies is limited due to their high price tags . Furthermore, not all gene therapies make it to market, especially for rare diseases, as their high cost and limited commercial market can deter companies from investing. In some cases, academic institutes and non-profit organisations have ‘rescued’ these gene therapy programmes. Another therapy in development for methylmalonic acidaemia is Moderna ’s mRNA therapy, mRNA-3705. The therapy is being investigated in the Phase I/II Landmark study (NCT04899310) as a treatment for a specific type of methylmalonic acidaemia, one due to CoA mutase (MUT) deficiency. In June 2024, mRNA-3705 was included in a Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot programme by the US Food and Drug Administration (FDA). The START programme is aimed at expediting the development of novel drugs and biological products for rare diseases. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

NEW YORK--( BUSINESS WIRE )--Cayuga Biotech, a company that develops drugs that harness the body’s innate ability to heal and stop bleeding, today presented preclinical data on its first generation, first-in-class, polyphosphate (polyP)-based therapy designed to address life-threatening hemorrhage. The results demonstrated that the infused polyP-SNP (silica nanoparticle) complex was able to overcome conditions known to be associated with poor survival after injury with hemorrhage, known as the “lethal triad”—hemodilution, acidemia, and hypothermia. These data were presented as a poster presentation at the Military Health System Research Symposium in Kissimmee, FL. “Bleeding is the leading cause of preventable death after traumatic injury in the battlefield, in large part due to the difficulty in treating non-compressible hemorrhage, such as from penetrating injury,” said Charles Pollack, MD, emergency medicine physician at the University of Mississippi and previously, Regimental Surgeon, 4 th Marines, US Navy Medical Corps. “These data are exciting because this novel polyP-SNP complex can overcome some of the most challenging clinical conditions to help restore the ability to clot.” Data presented in the “Technologies for the Treatment of Battlefield Hemorrhage and Management of Vascular Dysfunction” session demonstrated normalized thrombin generation and clotting under extreme hemodilute conditions in which normal plasma failed. Improved coagulation was also observed under severe acidotic and hypothermic conditions. As an injected drug that is inert in healthy tissue, the polyP-SNP complex travels via the bloodstream to any site of bleeding and acts to accelerate the clotting response without driving excess clotting, a problem that has limited development for other injectable drugs to treat hemorrhage. Poster Session 1: “A synthetic short-chain polyphosphate (polyP) complexed with silica nanoparticle (SNP), corrects coagulopathy under hemodilute, hypothermic, or acidotic conditions” About Hemorrhage Nearly 2 million people globally per year die of hemorrhage, the majority of which is preventable. The top causes of preventable death by hemorrhage are non-compressible hemorrhage sites (such as internal bleeding and from penetrating injury) and delays in hemostatic control neither of which are adequately addressed by today’s current care model. Due to the nature of non-compressible hemorrhage sites, the complexity of clinical intervention is time consuming and delays in treatment often lead to patient death. About Cayuga Biotech, Inc. Cayuga is developing novel biomimetic therapies leveraging inorganic polyphosphate, a polymer that modulates the healing response. The company has an optimized polyP-SNP complex in late preclinical development for the treatment of acute major hemorrhage, a discovery-stage novel composition for the treatment of inherited bleeding disorders, as well as a portfolio of early-stage programs focused across the healing continuum. To learn more, please visit www.CayugaBiotech.com .

External heart rate monitoring, the most common method of monitoring the fetus, may leave signs of fetal hypoxia undetected if the maternal pulse rate is not simultaneously monitored. The risk is that the fetal heart rate is masked by the maternal pulse, with fetal distress going unnoticed. Cardiotocography (CTG) refers to the electronic recording of the fetal heart rate and uterine contractions. Fetal heart rate recorded through the mother's abdomen is the most commonly used fetal monitoring method during childbirth. Now, a research team from the University of Helsinki and Helsinki University Hospital (HUS) has found that external fetal heart rate monitoring without simultaneous maternal pulse recording is associated with both an increased risk of neonatal encephalopathy and acidemia in fetal umbilical artery blood, i.e., critically low pH and base excess concentrations. Acidemia increases the need for newborn resuscitation and the length of intensive care. The study, published in the esteemed American Journal of Obstetrics and Gynecology, analysed almost 214,000 spontaneous full-term births in HUS maternity hospitals between 2005 and 2023. The study included the largest CTG dataset ever published. The study demonstrated that a newborn monitored during labour with external fetal heart rate monitoring alone had a 1.6-fold risk of neonatal encephalopathy and a 2.3-fold risk of severe umbilical cord blood acidemia compared to those monitored with an internal electrode attached to the skin of the fetal head (internal monitoring) or by concurrent external fetal heart rate monitoring and maternal pulse recording. "Especially during the second stage of labour, when mothers tend to display increased heart rate while pushing, fetuses more commonly exhibit heart rate decelerations. Consequently, the fetal heart rate can be quite easily mixed with the maternal pulse, in which case abnormal fetal heart rate tracing, indicating fetal hypoxia, may go unnoticed by professionals," says Researcher Mikko Tarvonen, describing the challenges of external CTG monitoring. In the majority of the labours in the study (38%), solely external monitoring was used. Internal monitoring was the second most common method (33%), followed by external monitoring simultaneously with maternal pulse recording (29%). Years of safer practice at HUS The world's largest organisations of obstetricians and midwives recommend in their fetal monitoring guidelines that external fetal heart rate monitoring be used as the primary CTG registration method. However, the new study indicates that, without simultaneous maternal pulse recording, this method is a significant risk factor predisposing the fetus to labour-related hypoxia and its long-term neurological effects. "Based on our results, this tragedy can be effectively prevented by combining maternal pulse recording with fetal heart rate monitoring. This method allows professionals to be sure of whose heart rate they are monitoring," says Tarvonen. In 2019 HUS adopted a new protocol emphasising the necessity of recording maternal heart rate alongside fetal heart rate during childbirth. "Practices have long varied at Finnish maternity hospitals, but training and research evidence have resulted in a shift in attitudes and thus the increased use in recent years of maternal pulse monitoring," Tarvonen notes. The present study demonstrated that, based on the incidence of neonatal encephalopathy, external fetal heart rate monitoring combined with maternal heart rate recording is equally as safe as internal fetal monitoring. However, internal monitoring was the most accurate way of assessing fetal wellbeing. Its use was associated with the lowest incidence of hypoxia-related neonatal outcomes. The incidence of both neonatal encephalopathy and severe umbilical artery blood acidemia has decreased significantly in the HUS region during the study's 18-year follow-up period. "This trend is exceptional even by international standards," Tarvonen points out. Facts: Monitoring the wellbeing of the unborn child through cardiotocography (CTG)