TRKA

STOCKHOLM, SWEDEN / ACCESSWIRE / January 29, 2024 / AlzeCure Pharma (STO:ALZCUR)(FRA:AC6) AlzeCure Pharma AB (publ) (FN STO: ALZCUR, a pharmaceutical company that develops a broad portfolio of small molecule candidate drugs for diseases affecting the central nervous system, with projects in both Alzheimer's disease and pain, today announced that the company has selected a TrkA-NAM drug candidate, ACD137, and started the preclinical development phase with the compound. "AlzeCure's unique TrkA-NAM substances have extremely selective effects so that optimal pain-relieving effect is achievable without inducing side effects. As the TrkA-NAM substances are small molecules, they can be taken in tablet form, which makes it easier for the patient but also contributes to a more cost-effective treatment," said Pontus Forsell, Head of Discovery and Research at AlzeCure. ACD137 is being developed within the TrkA-NAM project in AlzeCure's Painless platform, with the aim of developing a new pain-relieving drug for the treatment of osteoarthritis and other severe pain conditions. In the project, a drug candidate has now been selected to proceed into the preclinical development program, which includes safety and tolerability studies, as well as formulation work and stability testing. ACD137 blocks NGF-mediated signaling via TrkA receptors, a biological mechanism with strong genetic, preclinical and clinical validation for its role in pain. AlzeCure has already demonstrated that TrkA-NAM substances have a potent analgesic effect in preclinical pain models. Studies also show that they have a substantial anti-inflammatory effect, something that can enhance the analgesic effects in clinical contexts and open up further areas of use. Furthermore, effects have been seen on relevant biomarkers for inflammation and pain. "We are very pleased to have now selected a promising drug candidate and started the preclinical development phase with ACD137. There is great interest from the pharmaceutical industry in this target mechanism, and the fact that we have such a potent and selective substance is a decisive advantage, as several big pharma companies have tried to develop TrkA-NAM assets. In indications such as knee osteoarthritis, there are also large medical needs and a growing patient group," said Martin Jönsson, CEO of AlzeCure. For more information, please contact Martin Jönsson, CEO Tel: +46 707 86 94 43 martin.jonsson@alzecurepharma.com About AlzeCure Pharma AB (publ) AlzeCure® is a Swedish pharmaceutical company that develops new innovative drug therapies for the treatment of severe diseases and conditions that affect the central nervous system, such as Alzheimer's disease and pain - indications for which currently available treatment is very limited. The company is listed on Nasdaq First North Premier Growth Market and is developing several parallel drug candidates based on three research platforms: NeuroRestore®, Alzstatin® and Painless. NeuroRestore consists of two symptomatic drug candidates where the unique mechanism of action allows for multiple indications, including Alzheimer's disease, as well as cognitive disorders associated with traumatic brain injury, sleep apnea and Parkinson's disease, as well as for depression treatment. The Alzstatin platform focuses on developing disease-modifying and preventive drug candidates for early treatment of Alzheimer's disease and comprises two drug candidates. Painless is the company's research platform in the field of pain and contains two projects: ACD440, which is a drug candidate in the clinical development phase for the treatment of neuropathic pain, and TrkA-NAM, which targets severe pain in conditions such as osteoarthritis. AlzeCure aims to pursue its own projects through preclinical research and development through an early clinical phase, and is continually working on business development to find suitable outlicensing solutions, alternatively partnership, with other pharmaceutical companies. FNCA Sweden AB is the company's Certified Adviser. For more information, please visit . About TrkA-NAM The TrkA-NAM project, which is in research phase, is focused on the treatment of pain. The target mechanism, NGF / TrkA signaling, is well-validated both preclinically and clinically and provides a promising alternative to new analgesics without the side effects and addiction problems observed with opioids. For the TrkA-NAM drug project, we have leveraged our knowledge concerning the underlying biology for the NeuroRestore platform in order to develop new compounds that focus on providing pain relief in conditions associated with severe pain. The goal of the project is to develop a small-molecule TrkA-negative allosteric modulator for the treatment of osteoarthritis pain and other severe pain disorders. The global osteoarthritis market is expected to reach USD 11.0 billion by 2025, from USD 7.3 billion in 2020. Growth in this market is driven by factors such as the increasing occurrence of osteoarthritis, the growing aging population, and an increase in the number of sports injuries. Over 240 million people worldwide suffer from painful and activity-limiting osteoarthritis of the hip or knee. Many patients experience insufficient pain relief or side effects with current treatment, which today usually consist of NSAIDs or opiates and there is a great need for more effective and better tolerated drugs in this field. Image Attachments Martin Jönsson CEO And Pontus Forsell Head Of D&R AlzeCure Pharma Attachments AlzeCure selects drug candidate and enters next phase of development with TrkA-NAM ACD137 against severe pain SOURCE: AlzeCure Pharma View the original press release on accesswire.com

A newly developed PET imaging agent has been found to be effective in identifying medullary thyroid cancer (MTC) in preclinical and clinical studies. The results of the studies indicate that the PET imaging agent may be a promising theranostic candidate for clinical use. A newly developed PET imaging agent has been found to be effective in identifying medullary thyroid cancer (MTC) in preclinical and clinical studies, according to research published in the January issue of The Journal of Nuclear Medicine. The results of the studies indicate that the PET imaging agent may be a promising theranostic candidate for clinical use. MTC is one of the rarest forms of thyroid cancer and accounts for approximately three percent of all cases. Since MTC originates from different cells than most thyroid cancers, different imaging and therapy targets are needed for these patients. "The cholecystokinin-2 receptor (CCK-2R) is overexpressed on most MTC cells and various compounds targeting CCK-2R have been developed over the past several years. Most of these compounds, however, have low metabolic stability, which is not ideal for radioligand therapy," noted Thomas Günther, PhD, pharmaceutical radiochemist at Stanford University in Stanford, California. "With a simplistic design modification to tackle instability issues, our team created multiple theranostic agents and sought to evaluate their effectiveness." In the study, three compounds (DOTA-CCK-66, DOTA-CCK 66.2, and DOTA-MGS5 external reference]) were each labeled separately with 64Cu, 67Ga, and 177Lu. CCK-2R affinity of each of the radiolabeled compounds was examined on MTC cells. All three compounds exhibited a high affinity, however, due to the more favorable in vitro properties overall of DOTA-CCK-66, DOTA-CCK-66.2 was excluded from further studies. Next, in vivo stability, biodistribution, imaging, and competition studies were performed on mice bearing a CCK-2R-expressing tumor. 68Ga-DOTA-CCK-66 was selected for proof-of-concept PET/CT application based on its overall in vitro and in vivo properties. Two MTC patients then underwent 68Ga-DOTA-CCK-66 PET/CT. The compound was well tolerated, showed a favorable biodistribution, and demonstrated high accumulation of activity in tumors. "Due to increased in vivo stability, our compound reveals favorable tumor uptake as well as an improved activity clearance from off-target tissues. This could result in enhanced lesion detection in PET imaging and additionally enable targeted MTC radioligand therapy," said Constantin Lapa, MD, director of nuclear medicine at University Hospital Augsburg, in Augsburg, Germany. Günther and Lapa added, "A significant outcome of our work is the notion that it is possible to optimize pharmacokinetics by chemical design. Analyzing weaknesses of existing compounds and then systematically addressing those to improve imaging and treatment is crucial for future clinical translation." This research was published online in November 2023. The authors of "Preclinical Evaluation of Minigastrin Analogs and Proof-of-Concept [68Ga]Ga-DOTA-CCK-66 PET/CT in 2 Patients with Medullary Thyroid Cancer" include Thomas Günther, Nadine Holzleitner, Roswitha Beck, and Hans-Jürgen Wester, Department of Chemistry, Chair of Pharmaceutical Radiochemistry, TUM School of Natural Sciences, Technical University of Munich, Garching, Germany; and Oliver Viering, Georgine Wienand, Alexander Dierks, Christian H. Pfob, Ralph A. Bundschuh, Malte Kircher, and Constantin Lapa, Nuclear Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany.

In collaboration with leading cancer centers, research results to be presented from four studies across a breadth of breast tumor types and genomic alterations demonstrating Caris' impact on precision medicine IRVING, Texas, Dec. 4, 2023 /PRNewswire/ -- Caris Life Sciences®(Caris), the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI, today announced that the company and collaborators within the Caris Precision Oncology Alliance™ (POA) will collectively present findings at the San Antonio Breast Cancer Symposium (SABCS) that illustrate the potential impact of molecular profiling on the treatment of breast cancer. The findings demonstrate the power of Caris' comprehensive clinico-genomic database that enables novel insights into cancer that could have profound effects on a patient's diagnosis, prognosis, care plan, and response to treatment. SABCS is being held December 5-9, 2023 (Booth #1433) in San Antonio, Texas. Continue Reading "The San Antonio Breast Cancer Symposium continues to be the premiere conference for breast cancer research," said George W. Sledge, Jr., MD, Executive Vice President and Chief Medical Officer of Caris. "As part of our continuing commitment to the breast cancer community, Caris is proud to share important clinical/translational research created with our academic partners on important breast cancer questions." The research findings demonstrate the power of Caris' comprehensive clinico-genomic database Post this Presentations and posters from Caris include: Milan Radovich, PhD, Senior Vice President and Chief Scientific Officer of Caris, will participate in a Concurrent Educational Session entitled "Genomics for Clinical Research and Cancer Care" from 3:10 – 5:00 p.m. CT on Thursday, December 7 in the Stars at Night Ballroom 1-2. Dr. Radovich will deliver a presentation on "Emerging approaches to targeting pathways using precision medicine in breast cancer" from 3:10 – 3:40 p.m. before participating in a panel discussion from 4:40 – 5:00 p.m. "Precision oncology in breast cancer is rapidly evolving with the recent approval of several targeted therapies that rely on the detection of molecular biomarkers to inform selection. On the horizon are novel genomic and AI based approaches that will further shape the future treatment of this disease," said Dr. Radovich. "This education session at SABCS will highlight advances in new drug modalities and targetable pathways; liquid biopsies and clonal hematopoiesis; emerging evidence on treatment resistance; and the forefront of AI-enabled digital pathology for biomarker detection." A Caris study will be featured in the Concurrent Poster Spotlight Sessions Block 5 in the "PS13 Special Populations: Pregnancy, Male and Geriatric Patients" section on Thursday, December 7, from 5:30 – 6:30 p.m. CT in the Stars at Night Ballroom 3-4. The spotlight poster is titled "Molecular and Immunological Landscape of Sex-Based Differences in Breast Cancer: A Distinct Disease in Men" (Presentation #PS13-09). The study was performed in collaboration with Caris Precision Oncology Alliance™ (POA) members Dana-Farber Cancer Institute and Legorreta Cancer Center at Brown University, as well as others including the Mayo Clinic. In the featured study, the molecular and immunological landscapes of male and female breast cancer were investigated across 10,728 breast cancer samples (male, n=137; female, n=10,591) using Caris' Next-Generation Sequencing (NGS) technology. The results of this analysis indicate that male breast cancer has differential molecular and immune features compared to female breast cancer. A better understanding of these sex-based differences may help inform disease outcomes, provide a rationale for tailored therapeutic approaches, and guide the design of future treatments. "The Caris Precision Oncology Alliance™ continues its contribution to advancing breast cancer research by presenting novel findings on the molecular and immunological features of male breast cancer at this year's SABCS," said Chadi Nabhan, MD, MBA, FACP, Chairman of the POA. "By leveraging Caris' expansive real-world clinico-genomic database, our partner academic institutions are able to uncover new insights into the underpinnings of breast cancer biology leading to better therapeutic interventions." The POA includes 90 cancer centers, academic institutions, research consortia and healthcare systems, including 42 NCI-designated cancer centers, collaborating to advance precision oncology and biomarker-driven research. POA members work together to establish and optimize standards of care for molecular testing through innovative research focused on predictive and prognostic markers that improve the clinical outcomes for cancer patients. Additional Presentations Reveal Potential Impact of Comprehensive Molecular Profiling Caris will present additional data from studies demonstrating the critical role of precision medicine and molecular profiling in the treatment of breast cancer. All presentations will be made available online through Caris' website beginning December 7. Comprehensive Molecular and Immunological Characterization of Invasive Ductal Triple-Negative Breast Cancer (Presentation Number: PO4-24-01) This investigation of the molecular and immune signatures of invasive ductal (ID) triple-negative breast cancer (TNBC) aimed to improve understanding of TNBC biology to facilitate future identification of novel targets for treatment of this heterogenous disease. The results of this retrospective study of more than 13,000 breast cancer samples indicate that ID TNBC is associated with a distinct mutational and immunological profile compared to ID non-TNBC. ID TNBC is also associated with worse overall survival compared to ID non-TNBC. However, ID TNBC patients have improved survival post-pembrolizumab treatment. Comprehensive Characterization of BCL2 Family Genes in Metaplastic Triple Negative Breast Cancer (Presentation Number: PO4-24-02) This study aimed to investigate the expression of BCL2 family genes in metastatic TNBC. Results of this molecular profiling study suggest a strong association between higher expression of PMAIP1 and worse patient survival in this cancer. This association may potentially be attributable to higher immune checkpoint and stem cell-related gene expression, in addition to higher frequency of PD-L1 positivity in PMAIP1-High tumors. Further investigation is needed to prospectively validate PMAIP1 as a potential prognostic biomarker candidate in metaplastic TNBC. Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy (Presentation Number: PO4-24-08) Phyllodes tumors are rare tumors of the breast, a subset of which have considerable malignant potential. This study aimed to identify targetable alterations and enhance understanding of the mutational profiles of malignant phyllodes tumors (MPTs) to potentially enhance treatment options. NGS identified actionable genomic alterations, including an NTRK1 fusion and low HER2 transcriptional expression. These findings highlight the importance of NGS-based profiling, including RNA sequencing, in MPT research to uncover potential targeted treatment options for patients. About Caris Life Sciences Caris Life Sciences® (Caris) is the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms, Caris has created the large-scale, clinico-genomic database and computing capability needed to analyze and unravel the molecular complexity of disease. This convergence of sequencing power, big data and AI technologies provides an unmatched platform to deliver the next-generation of precision medicine tools for early detection, diagnosis, monitoring, therapy selection and drug development. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S., Europe, Asia and other international markets. To learn more, please visit CarisLifeSciences.com. Caris Life Sciences Media Contact: Lisa Burgner [email protected] 214.294.5606 SOURCE Caris Life Sciences