Olatec Therapeutics’ Post

Regeneron has queued a first-in-human, Phase 1/2 study of REGN10597, an anti-PD-1-IL2RA-IL2 immunocytokine, in patients with advanced solid organ malignancies. The study will enroll an estimated 150 participants and has as estimated start date in September 2024. https://lnkd.in/eYGUkYer A poster from 2023 AACR describes REGN10597 as a PD-1-targeted, receptor-masked IL-2 immunocytokine with attenuated systemic IL-2 activity but maintained capacity to engage endogenous IL-2Rα on PD-1+ T cells. https://lnkd.in/ewQ7867R

Regeneron's REGN10597 and Roche's Dual-Binding Antibody (DBA), acquired through Good Therapeutics, depart from the old dogma of IL-2 therapy. Old Dogma of IL-2: The conventional approach differentiated between 'non-alpha IL-2' and wild-type IL-2 or IL-2Rα-biased agonists. The primary reason for using 'non-alpha IL-2' was to avoid activating regulatory T cells. However, studies have shown that Treg activation is generally limited to peripheral tissues, even when using IL-2 with alpha bias. Minimizing the activation of tumor-infiltrating Tregs can mitigate side effects like vascular leak syndrome caused by systemic IL-2 exposure. Innovent Biologics's IBI363 wtIL-2 or IL-2 with alpha bias promotes IL-2 activation via the CD25 receptor. Tumor-infiltrating T cells expressing CD25 and PD-1 are crucial in killing cancer cells within the tumor microenvironment. Therefore, CD25-mediated IL-2 activation through wtIL-2 or IL-2 with alpha bias can enhance the activation of T cells in the tumor microenvironment, potentially boosting antitumor effects. Ref: https://lnkd.in/d7Jpy3cN Regeneron's Patent Insight: "CD122-directed IL-2 molecules are designed to expand NK and CD8+ T preferentially cells over Tregs, primarily in the blood and spleen, but to a much lesser extent in tumors. In contrast, wild-type IL-2 preferentially expands CD8+ T cells within the tumor but not in peripheral tissues." Patent: https://lnkd.in/dbcCBNq2 AACR23: https://lnkd.in/dxsSWxpR Roche's Dual-Binding Antibody Approach: The Dual-Binding Antibody consists of a sensor and an effector. When the sensor domain of the antibody binds to PD-1-expressing cells, it undergoes a conformational change that activates IL-2. This mechanism ensures that IL-2 is specifically activated in the tumor microenvironment, enhancing the antitumor immune response and minimizing systemic side effects. Ref: https://lnkd.in/dgRXn84F

The MASTER-2 and MIDAS trials are some of the more interesting myeloma trials that use an MRD-guided approach.  MASTER-2 has a primary completion date of December 2026.  Transplant eligible patients receive Dara-VRD for 6 cycles, and then get tested for MRD. MRD negative patients can be randomized to skip transplant, and MRD positive patients can be randomized to receive teclistamab + darzalex after transplant.  The MIDAS trial has a primary completion date of December 2024. In this trial, transplant eligible patients receive Isa-KRD for 6 cycles, and then get tested for MRD.  While this study also randomizes MRD negative patients to skip transplant, it randomizes MRD positive patients to either single or tandem ASCT, followed by isatuximab/iberdomide maintenance.  I find the MIDAS trial more intriguing for two reasons.  First, it doesn't use CD-38 directed maintenance in MRD negative patients, while MASTER-2 does. We know from CASSIOPEIA that patients may not need that maintenance.  Second, the role of tandem ASCT has always been controversial, with 20-30% drop out rates in clinical trials.  The role of tandem ASCT in this era of novel therapy has not been established, and this may be one of the first trials to answer this question.  Since the primary completion date is this year, perhaps we will see something at ASH.  #kyprolis #darzalex #sarclisa #velcade #multiplemyeloma https://lnkd.in/e7HybwuU https://lnkd.in/eQaK27mZ

🌐 Latest Alzheimer's Disease Drug Development in Clinical Trials 🌐 The 2024 Alzheimer's Disease Drug Development Pipeline report highlights significant progress and challenges in the field. Authored by Dr. Jeffrey Cummings and published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, the report notes 164 active trials and 127 unique treatments. Bases on this review paper, it shows key findings include:76% of the treatments are disease-modifying, aiming to slow memory decline. 34% are biological therapies administered intravenously.12% are cognitive enhancers.13% target behavioral symptoms like agitation.31% are repurposed drugs initially developed for other diseases. For a detailed read, you can access the full report here or learn more from the following link. https://lnkd.in/g9KESpYN In addition, I have highlighted the current ongoing studies that are recruiting subjects. Over 20 trials are actively running and enrolling subjects. https://lnkd.in/gWSPq8JH #ClinicalTrials #CRO #Alzheimer #CNRRrsearch #씨엔알리서치 #임상시험 #알츠하이머

#Healthcareconsultant 💡 Clinical Trial Matching Solutions: How to increase recruitment capabilities? Matching solutions in clinical trials are crucial for boosting recruitment efforts. To provide actionable matches, these solutions blend patient characteristics, trial eligibility criteria, site identifiers, and operational status. Data interoperability and standards play a significant role in enhancing matching transactions. The intricacies of protocols, as seen in clinicaltrials.gov listings, underscore the challenges medical oncologists face in recommending suitable trials. Imagine streamlining the process with a single click to match multiple eligibility criteria for any specific trial. Inclusion and exclusion criteria often feature intricate language and interconnected concepts. Simplifying this through a matching solution can revolutionize clinical trial recruitment, making it more efficient and effective. In essence, matching is the key to simplifying clinical trial recruitment, offering a seamless solution for both patients and healthcare professionals. To read more follow the link: https://lnkd.in/g7-3q53Y #ClinicalTrials #RecruitmentSolutions #HealthcareInnovation #Oncology #PrecisionOncology #ClinicaltrialMatching #OneClickaway #AIyourway #ComingSoon

Heartbeats Highlights: *A DUE trial* Fixed-Dose Macitentan/Tadalafil Combo Gets FDA Approval for PAH FDA approved macitentan/tadalafil (Opsynvi) today (03/25/2024) as the first single-tablet combination therapy targeting multiple pathways for pulmonary arterial hypertension (PAH). A study of 187 people in WHO functional class II or III that showed that dual macitentan/tadalafil reduced pulmonary vascular resistance nearly 30% more than macitentan and tadalafil monotherapy by week 16. #Cardiovascular #interventionalCardiology #cardiacImaging #heartfailure

Tirzepatide for Metabolic Dysfunction–Associated Steatohepatitis with Liver Fibrosis..#fattyliver #nash In this phase 2 trial involving participants with MASH and moderate or severe fibrosis, treatment with tirzepatide for 52 weeks was more effective than placebo with respect to resolution of MASH without worsening of fibrosis. Larger and longer trials are needed to further assess the efficacy and safety of tirzepatide for the treatment of MASH. (Funded by Eli Lilly; SYNERGY-NASH ClinicalTrials.gov number, NCT04166773.)

In our latest #study, Annabelle Iken, Maaike Gademan, and I assessed the #quality of #data in Total Knee Arthroplasty trials by identifying inconsistencies, inaccuracies, and missing information and proposed ways to improve the reliability of these clinical trial registries. WHAT IS NEW? Key findings: We identified the following causes of data irregularities in trial registries: inconsistency, inaccuracy, incompleteness, and deficient timeliness. We found significant variations in the data quality depending on the data irregularity, the evaluated variable, and selected response option. What does this add to what was known? We introduced a systematic approach to assess the reliability, consistency, and accuracy of information recorded in CTG and identified significant irregularities.    What is the implication, and what should be changed now? Consider irregularities in recorded trial information when making decisions concerning published articles, treatment protocols, replication, and trial design improvements. Clinical trial sponsors should be mindful of their responsibility to provide accurate trial information to ensure accountability and transparency. ClinicalTrials.gov should prioritize plain language and illustrative examples in response options for broader comprehension.  #EBM Landelijke Registratie Orthopedische Interventies (LROI) #TotalKneeArthroplasty #Knee #TotalKnee #TKA #Research #Trials #qualityofdata #clinicaltrials #clinicaltrialsgov #clinicaltrialregistries #registries Orthopaedie - LUMC Nederlandse Orthopaedische Vereniging (NOV) https://lnkd.in/eWkMpmv3

Psoriasis Awareness Month: Focusing on Patient Needs   Over the past few years, Origins - The Patient Focused Specialists has been honoured to partner with psoriasis patients and organisations around the world to share their opinions and experiences as part of patient focused drug development programmes.   Some highlights have included: • Exploring the challenges of every day life through patient ethnography • Partnering with patients to tell their stories at scientific symposium at European congresses • Comprehension testing of informed consent forms (ICFs) and patient information leaflets (PILs) in preparation for clinical trials • Patient advisory groups to input into clinical trial protocol development • Physician observed patient (POP) sessions to identify misalignment in clinical objectives and patient goals   We would like to thank the wider psoriasis community for their continued collaboration and commitment. #PsoriasisAwarenessMonth #PatientSupport #EmpathyMatters #PatientFocused #Origins #PatientEngagement

From June to November 2020, the company conducted a Phase 1 safety trial of NX210. It enrolled 39 healthy adults in five cohorts, to receive single intravenous doses of 0.4, 1.25, 2.5, 5, or 10 mg/kg, or placebo. According to published results, one-third of participants reported mild adverse events. The most common were dizziness, headache, and sleepiness. NX210 cyclized to NX210c in blood. The peptide was widely distributed and rapidly cleared, with a half-life in plasma of 20 minutes or less. Potential pharmacodynamic effects were reported on EEG, and on plasma tryptophan and homocysteine (Bourdes et al., 2022). In October 2022, the FDA granted NX210c #Orphan Drug Designation for ALS. In December 2022, a multiple-dose Phase 1 trial began enrolling 29 healthy aged volunteers. Thirty participants are to receive 5 or 10 mg/kg NX210c or placebo by 10-minute intravenous infusion three times a week for four weeks. The primary outcome is adverse events; blood and #CSF pharmacokinetic measures serve as secondary outcomes. The study assesses neurologic safety using the Neurocart Battery, as well as 34 blood and 16 CSF biomarkers. Conducted in the #Netherlands, the trial is set to finish in December 2024. In April 2024, the company registered a Phase 2 trial in ALS. To begin in September 2024, it will recruit 80 adult patients. The trial will compare four weeks of thrice-weekly 5 or 10 mg/kg doses to placebo, with a three-month follow-up. The sole outcome listed on clinicaltrials.gov is blood neurofilament light, or the CSF/serum albumin ratio, an indicator of blood-brain barrier integrity. Completion is expected in February #2026.