Herlev Hospital

Ionis Pharmaceuticals is looking to extend the reach of Tryngolza (olezarsen) beyond its initial approval for an ultra-rare genetic lipid disorder, as new Phase III trial data suggest its drug could become the first treatment option for a much larger patient group. On Tuesday, the company reported that an 80-mg monthly dose of the RNA-targeted medicine lowered fasting triglyceride levels by 72% in the CORE study and 55% in the CORE2 study, compared to placebo, in patients with severe hypertriglyceridaemia (sHTG). A 50-mg dose produced placebo-adjusted reductions of 63% and 49%, respectively. Both studies, which together enrolled a total of 1063 participants, required patients to remain on standard lipid-lowering therapy throughout the trial period.The trials also met their secondary endpoint, showing a substantial decline in acute pancreatitis events. Across both trials, pooled data indicated that Tryngolza reduced such events by 85% versus placebo over 12 months, the first therapy to do so, according to Sam Tsimikas, Ionis' head of global cardiovascular development"Despite current standard of care and lifestyle changes, people with sHTG — who could have triglyceride levels reaching into the thousands — remain vulnerable to unpredictable and life-threatening acute pancreatitis attacks," Tsimikas said. Participants were randomised to receive Tryngolza or placebo every four weeks via subcutaneous injection for a year. Adverse events were generally mild, with injection site reactions being the most common side effect. Year-end filing Ionis intends to file a supplemental new drug application with the FDA by year-end, with detailed trial data slated for presentation at an upcoming medical conference. The readout could position Ionis to expand beyond the narrow market it entered last December, when the FDA approved Tryngolza for familial chylomicronaemia syndrome (FCS), a rare subtype of sHTG. While FCS represents only about 3000 US patients, sHTG affects some 3 million people in the country, including more than a million who are considered high risk. In an interview with FirstWord last year, CEO Brett Monia said that "having first-mover advantage just solidifies our leadership in this space," as the company looks to tackle other forms of sHTG. For more, see – ViewPoints: Though Tryngolza faces modest FCS market, nod offers foot in door to larger opportunity.

Data from the cutaneous T-cell lymphoma (CTCL) cohort demonstrate promising clinical activity that correlates with strong immune activation One complete response (CR), three partial responses (PR), and four stable diseases (SD) achieved as of Feb 2025 in eight evaluable patients Study currently enrolling patients for signal-seeking. Dose optimization phase to follow Lund, Sweden – May 14, 2025 – BioInvent International AB (“BioInvent”) (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, today announced that additional data from the ongoing Phase 2a dose expansion study of BI-1808 monotherapy in Cutaneous T-cell Lymphoma (CTCL) will be presented in a poster at the European Hematology Association (EHA) 2025 congress to take place June 12-15 in Milan, Italy. The submitted abstract data from the CTCL cohort include results from ten patients treated with BI-1808 with eight deemed evaluable. As of the cut-off date February 20, 2025, one patient had achieved a complete response (CR), three achieved partial response (PR), and four demonstrated stable disease (SD). The treatment was well tolerated with primarily mild to moderate adverse events with no grade 3 or higher events reported. Notably, immune activation was observed in the early weeks of treatment, specifically depletion of regulatory T cells and an influx of CD8+ T cells into the skin, suggesting that BI-1808 effectively stimulates the targeted response in CTCL. The upcoming poster presentation will include more detailed and recent data, including findings in patients with PTCL (Peripheral T-cell lymphoma). “We look forward to presenting these positive data at EHA, which illustrate BI-1808’s potential as an immunomodulatory treatment for CTCL patients, said Martin Welschof, Chief Executive Officer of BioInvent. “The emerging clinical responses, along with immune activation reflect the meaningful biological activity of BI-1808 and support further development in hematologic malignancies and solid tumor settings. We believe that BI-1808 could become a novel treatment option for CTCL patients, where innovative approaches are urgently needed – a belief further supported by the recent Fast Track and Orphan Drug Designation granted by the FDA.” Details of the presentation are below: Title: Robust Single Agent Activity of BI-1808, a Tumor Necrosis Factor Receptor 2 (TNFR2) Blocker/Depleter, in Cutaneous T Cell Lymphoma (CTCL) PatientsSession Date and Time: June 13, 2025, 6:30-7:30 pm CESTSession Title: Poster Session 1Lead Author: Stefan K. Barta, University of Pennsylvania Hospital, Philadelphia, PA, USAAbstract Number: PF961 The poster will be posted to the Scientific Publications section of the company website after the e-poster disclosure (https://www.bioinvent.com/en/our-science/scientific-publications) on June 12 at 9:00 am CEST. The safety and preliminary efficacy of BI-1808 monotherapy are currently being evaluated in Part A of the ongoing Phase 2a (NCT04752826) study in patients with T-cell lymphomas, including CTCL. The trial is expected to enroll 20 patients at a signal-seeking dose, after which a dose optimization phase will be initiated. About BI-1808The anti-TNFR2 antibody BI-1808 is part of BioInvent’s tumor-associated regulatory T cells (Treg)-targeting program. TNFR2 is particularly upregulated on Tregs of the tumor microenvironment and has been shown to be important for tumor expansion and survival, representing a new and promising target for cancer immunotherapy. BI-1808 is a first-in-class drug candidate in clinical development for the treatment of solid tumors and blood cancer. BI-1808 has shown single agent activity and excellent tolerability in an ongoing Phase 2a study and signs of efficacy and favorable safety profile in combination with pembrolizumab in the ongoing Part B of the Phase 1/2a study (ASCO 2024). About BioInventBioInvent International AB (Nasdaq Stockholm: BINV) is a clinical-stage biotech company that discovers and develops novel and first-in-class immuno-modulatory antibodies for cancer therapy, with currently five drug candidates in six ongoing clinical programs in Phase 1/2 trials for the treatment of hematological cancer and solid tumors. The Company's validated, proprietary F.I.R.S.T™ technology platform identifies both targets and the antibodies that bind to them, generating many promising new immune-modulatory candidates to fuel the Company's own clinical development pipeline and providing licensing and partnering opportunities. The Company generates revenues from research collaborations and license agreements with multiple top-tier pharmaceutical companies, as well as from producing antibodies for third parties in the Company's fully integrated manufacturing unit. More information is available at www.bioinvent.com. For further information, please contact:Cecilia Hofvander, VP Investor RelationsPhone: +46 (0)46 286 85 50Email: cecilia.hofvander@bioinvent.comBioInvent International AB (publ)Co. Reg. No.: 556537-7263Visiting address: Ideongatan 1Mailing address: 223 70 LUNDPhone: +46 (0)46 286 85 50www.bioinvent.com The press release contains statements about the future, consisting of subjective assumptions and forecasts for future scenarios. Predictions for the future only apply as the date they are made and are, by their very nature, in the same way as research and development work in the biotech segment, associated with risk and uncertainty. With this in mind, the actual outcome may deviate significantly from the scenarios described in this press release.

More than 10 urgent visits to the bathroom a day due to diarrhea can make it virtually impossible to lead a normal life. But new research can help doctors diagnose bile acid diarrhea and find the right treatment. Most people have at some point in their life suffered an intestinal infection or food poisoning forcing them to stay close to the bathroom. It is very uncomfortable. Most of the time, though, it passes quickly. But around 60,000-100,000 Danes suffer from a form of chronic diarrhea called bile acid malabsorption or bile acid diarrhea. It is a chronic condition characterised by frequent and sudden diarrhea more than 10 times a day. Even though the disease is not life-threatening, it can seriously affect the patient's everyday life, especially their social life, and be extremely disabling. "You have to rush to the bathroom several times a day. Therefore, keeping a job or maintaining social relations can be difficult, and a lot of people isolate themselves. The disease controls their life," says Professor Jesper Bøje Andersen from the Biotech Research & Innovation Centre. He and his research group and clinical cooperation partners at Herlev and Gentofte Hospital headed by Professor and Consultant Doctor Filip Krag Knop are responsible for a new study, which provides new ways of diagnosing bile acid diarrhea and identifying the most effective treatment for the individual patient. "A lot of people with chronic diarrhea don't realise that they suffer from bile acid diarrhea and what has caused it. This is a result of lack of knowledge among healthcare workers and the relatively complex and expensive -- and for the patient difficult -- process of diagnosing the disease," says Filip Krag Knop. Jesper Bøje Andersen adds: "We have developed a new concept which may be used to diagnose the disease based on a simple blood sample. Today, diagnostics involves radiopharmaceuticals, which means that there is a radiation risk. The process is not necessarily dangerous, but unpleasant and arduous, and not all countries in the world support the method, including the US." The new method means that doctors should be able to determine whether the patient has bile acid diarrhea based on a simple blood sample. They focus on molecules known as metabolites in the blood. "A blood sample contains lots of different metabolites. Right now we are able to identify almost 1,300 different metabolites, and around a handful of these can be used to diagnose bile acid diarrhea. The metabolites of bile acid diarrhea patients form a particular pattern that makes them recognisable," says Jesper Bøje Andersen. Which treatment? The researchers analysed blood samples from 50 patients and they quickly realised that the samples -- and patients -- could be divided into two groups. "First, we did not understand why. All the blood samples had been taken before treatment, typically at the time of diagnosis," says Jesper Bøje Andersen. The patients then participated in a randomised clinical study at the Center for Clinical Metabolic Research at Herlev and Gentofte Hospital. Here the doctors studied the effect of two different treatments: the conventional treatment involving bile acid sequestrant colesevelam and a new treatment involving liraglutide, which is normally used to treat type 2 diabetes and severe overweight. "What is interesting is that the metabolites in the patients' blood divided them into two groups: one that responds well to colesevelam and one that responds well to liraglutide. This suggests that we should be able to say which treatment is the most effective by analysing the patient's blood at the time of diagnosis," says Jesper Bøje Andersen. The clinical study showed that colesevelam treatment eased the bile acid diarrhea symptoms of 50 per cent of the patients, while liraglutide treatment eased the symptoms of 77 per cent of the patients. Jesper Bøje Andersen, Filip Krag Knop and their research groups hope the new study will benefit the 60,000-100,000 Danes who suffer from bile acid diarrhea. The majority of cases of bile acid diarrhea is diagnosed at a very late stage or never diagnosed at all. "Around 40 per cent of the patients suffer from this condition for up to five years before it is diagnosed. Of course, this may be because they do not realise that it is a disease and that it can be treated. But it may also be because chronic diarrhea is a tabooed disease," says Filip Krag Knop.