Temporomandibular Joint Dysfunction Syndrome

Temporomandibular joint (TMJ) osteoarthritis is a degenerative, debilitating and progressive disease, the second most common musculoskeletal condition affecting five to 12% of the population globallyTMJ causes pain and stiffness in the jaw, making it difficult to chewTMJ osteoarthritis currently has no long-term effective treatments Ness-Ziona, Israel, April 03, 2025 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company” or “Enlivex”), a clinical-stage macrophage reprogramming immunotherapy company, today announced that the first patient has been dosed in an investigator-initiated Phase I trial to evaluate the safety, tolerability and initial efficacy of Allocetra™ for injection into the temporomandibular joint (TMJ) in patients suffering from TMJ osteoarthritis. The study will be conducted by the Rheumatology Unit at Sheba Medical Center in collaboration with the Department of Oral and Maxillofacial Surgery at Sheba Medical Center. Notably, Sheba Medical Center was recently ranked among the top 10 hospitals in the world by Newsweek. Dr. Einat Galamidi, CMO of Enlivex, commented, “This study will provide a preliminary evaluation of the safety and potential effect of AllocetraTM for the treatment of TMJ osteoarthritis, which affects a joint that is critical for daily function. We are pleased to report that the injection of AllocteraTM into the first patient’s TMJ was successfully completed with no complications.” The trial currently plans to recruit six patients who have insufficiently responded to conventional therapies for TMJ osteoarthritis. The trial’s primary safety endpoint will measure the frequency and severity of adverse events and serious adverse events, and efficacy endpoints will assess changes from baseline in TMJ pain, joint functionality, and other disease parameters for up to 12 months following administration of Allocetra™. ABOUT ALLOCETRA™ Allocetra™ is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra™ has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as “unmet medical needs,” as a stand-alone therapy or in combination with leading therapeutic agents. ABOUT TEMPOROMANDIBULAR JOINT (TMJ) OSTEOARTHRITIS TMJ disorders are the second most common musculoskeletal condition affecting five to 12% of the population globally, with an annual health cost estimated at $4 billion1. Osteoarthritis of the TMJ is the most common form of arthritis in the TMJ, causing pain and stiffness in the jaw. It may become difficult to chew. TMJ osteoarthritis is a degenerative disease of the joint, which culminates in the progressive destruction of all soft and hard tissue components of the TMJ. For patients who present in early adulthood with severe clinical symptoms and catastrophic radiographic changes, there are significant implications for management, including the potential need for early total joint replacement. There are currently no effective long-term treatments for this disease2. ABOUT ENLIVEX Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening conditions. For more information, visit http://www.enlivex.com. Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “would,” “could,” “intends,” “estimates,” “suggests,” “has the potential to” and other words of similar meaning, including statements regarding expected cash balances, expected clinical trial results, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRATM programs. All such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivex’s business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRATM product line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivex’s filings with the Securities and Exchange Commission, including in the Company’s most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law. ENLIVEX CONTACT Shachar Shlosberger, CFOEnlivex Therapeutics, Ltd.shachar@enlivexpharm.com INVESTOR RELATIONS CONTACT Dave Gentry, CEORedChip Companies Inc.1-407-644-4256ENLV@redchip.com ____________________________________1 Bianchi et al., Sci Rep 2020 2 Delpachitra et al., British Journal of Oral and Maxillofacial Surgery 60 (2022)

The homologous-use application validated by Dr. Ryan Robinson and NP Rachel Reynolds sets a precedent for non-surgical allograft application. PENSACOLA, Fla., Oct. 26, 2023 /PRNewswire/ -- Regenative Labs (Regenative), a leading HCT/P manufacturer, announces the publication of a case study demonstrating new care advancements using its Wharton's Jelly allografts in the supplementation of Temporomandibular Joint (TMJ) defects. The case study titled "Single-Center Retrospective Study of Flowable Umbilical Cord Tissue Allograft Application in Temporomandibular Joint Defects: An Investigative Study," was published by Walsh Medical Media and can be accessed in its entirety here. Board-certified sleep medicine and craniofacial pain specialists Dr. Ryan Robinson and NP Rachel Reynolds of The Pain and Sleep Therapy Center presented a novel case series studying the application of Wharton's Jelly, an umbilical cord connective tissue, to the structural tissue defect of the temporomandibular joint. This homologous use application validated by Robinson and Reynolds sets a precedent for non-surgical allograft application. "We've seen a decrease in terms of healing time for patients when we've compared it to other types of injections that we've used previously for patients with temporomandibular joint dysfunction (TMD). We've also seen improvement in outcomes for patients who've been utilizing Wharton's Jelly in conjunction with other types of modalities that we've used for these patients," shared NP Rachel Reynolds. Nearly 10 million patients suffer from TMD in the United States each year. These patients often experience symptoms ranging from joint arthralgia, displacement, degenerative arthritis, limited and painful mouth opening, painful subluxation of the joint, joint clicking, and referred pain to the periauricular area or head and neck muscles. Although there are many treatments for TMD, therapy specific to degenerative pathology of the TMJ disc itself is limited in scope and therapeutic effect. Standard treatment includes simply resting the jaw muscles and avoiding use, massage, physical therapy, medication management, and, when all else fails, surgery. The rising annual number of surgeries and high out-of-pocket costs for patients, overall treatment costs ranging from 5,000-50,000 USD, are enough to implement conservative protocols alternative to invasive surgical repair of the TMJ. "Today, we see many physicians who are wary about treating TMJ and often revert to standard surgical treatments. Showing the outcomes that we have for patients will hopefully help to bolster more physicians to join us in using more conservative treatments. Our patients deserve more options," concluded Reynolds. The five patients in this case series presented with chronic refractory TMD, specifically from severe degeneration of the structural tissues within the joint, and had failed standard-of-care practices for at least three months. After one application of Regenative's Wharton's Jelly allograft, the patient's pain improved by an average of 75% after 90 days. "A few years ago, we started using PRF (platelet-rich fibrin) therapy in the jaw joint, and we thought that was revolutionary. We have seen amazing results; however, the protocol involves additional technology like a centrifuge and consists of multiple rounds of injections to get the desired outcome. It also subjectively eliminates some patients from treatment who are opposed to blood draws on themselves. With Wharton's Jelly, there is only one injection, which makes the application much easier, more convenient, and less invasive to the patient. What's most exciting is the results we are seeing! We're seeing much better patient outcomes than any other modality we've ever treated. We're really excited to continue the use of Wharton's Jelly in our Pain and Sleep clinic, and it soon becoming a routine standard for our patients who can benefit," shared Dr. Ryan Robinson. To advance the necessary research and fill the need for non-surgical alternatives, Regenative has been tracking data in its comprehensive retrospective data repository in which physicians across specialties submit patient data as they track patient outcomes up to 120 days after the patient receives an application of Regenative's products, like its Wharton's Jelly allografts. Regenative has collected data from clinics nationwide on Wharton's Jelly homologous-use applications around the body. Still, very few have documented data on the jaw joint, and Regenative is excited to highlight this unique procedure in the first of many publications on regenerative orthodontic medicine. "Given the high incidence rate and few effective treatment options for defects in the Temporomandibular Joint, this study aims to provide a new, promising alternative intervention for patients who have failed all other standard-of-care treatments. This is just one of many homologous-use applications in regenerative medicine to improve patient outcomes," shared Regenative Labs CEO Tyler Barrett. Barrett and his team hope to enlist physicians to take part in studies regarding uncovered uses. Physicians will have their outcomes highlighted, furthering the understanding of regenerative medicine and uncovering new applications for this groundbreaking field of medicine. "We're doing the research at Regenative, and the results are very promising. We are calling on all physicians across the country to engage with us to advance the field of regenerative medicine," Barrett concluded. Contact Regenative to get your practice involved today. Read the full case study here. About Regenative Labs: Regenative Labs produces regenerative medicine products to address the root cause of a patient's conditions using Wharton's Jelly innovations rather than masking the pain with other treatments. Regenative Labs works closely with scientists, physicians, hospitals, and surgery centers to constantly monitor and improve patient progress and outcomes for new product development. Formed by veteran industry professionals familiar with the daily challenges of innovations in healthcare, the company provides non-addictive, non-invasive options for patients. Regenative Labs' expert product research and development team complies with FDA guidelines of minimal manipulation for homologous use. The company adheres to AATB and FDA guidelines. Learn more at Regenative's website: About Dr. Ryan Robinson: Dr. Robinson is Delaware's first and only doctor triple-boarded in Craniofacial Pain and Dental Sleep Medicine. After many years of treating the airway in his general dental practice, Dr. Robinson decided to open up a specialty practice to address the needs of the community. This new practice, called The Pain and Sleep Therapy Center of Delaware Valley, focuses on finding the origin of the problem as opposed to treating it with medications and "band-aid" fixes that have become so routine in today's medical system. Learn more at Pain and Sleep Therapy Center's website: About Rachel Reynolds: Rachel is a Family Nurse Practitioner (FNP) who joined the Pain and Sleep team in July 2021. Originally, Rachel is from upstate New York, where she completed her Bachelor of Nursing and Master of Nursing at Binghamton University. Prior to completing her Master's, Rachel worked in Neurology as a registered nurse, focusing on patients who dealt with chronic pain and headaches. Upon moving to Delaware, Rachel completed a fellowship in Primary Care with Christiana Care. During her fellowship, she identified her passion for comprehensive patient care, which resulted in her devotion to identifying the root cause of her patient's issues. Upon identifying a need for nutritional guidance for our patient population, Rachel acquired a certification in nutrition from the University of Stanford. Rachel is also completing a second master's degree program in Psychiatry at this time to better assist patients and provide a more comprehensive scope of practice. Learn more at Pain and Sleep Therapy Center's website: SOURCE Regenative Labs

The CGRP receptor, also known as the calcitonin gene-related peptide receptor, plays a crucial role in the human body. It is a G-protein coupled receptor found in various tissues, including the central and peripheral nervous systems. Activation of the CGRP receptor by the neuropeptide CGRP leads to vasodilation, modulation of pain transmission, and regulation of inflammatory responses. This receptor has gained significant attention in the pharmaceutical industry due to its involvement in migraine pathophysiology. Targeting the CGRP receptor has emerged as a promising therapeutic approach for the treatment of migraines, leading to the development of CGRP receptor antagonists as potential medications. CGRP Competitive LandscapeAccording to Patsnap Synapse, as of 27 Sep 2023, there are a total of 17 CGRP receptor drugs worldwide, from 39 organizations, covering 22 indications, and conducting 171 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the target CGRP receptor in the pharmaceutical industry reveals that Pfizer Inc., Amgen, Inc., and Novartis AG are the companies growing fastest under this target. Migraine disorders have the highest number of approved drugs, followed by acute migraine, nasal polyps, and chronic sinusitis. Small molecule drugs and monoclonal antibodies are progressing most rapidly under this target. The United States, European Union, and Japan are the countries/locations with the highest development phases. China has also shown progress in the development of drugs targeting the CGRP receptor. The competitive landscape for the target CGRP receptor is intense, with a focus on developing innovative drugs and potential competition from biosimilars. Future development in this area will require further research and analysis to stay competitive in the pharmaceutical industry. Recently approved for market CGRP antagonist: Rimegepant SulfateRimegepant Sulfate is a small molecule drug that targets the CGRP receptor. It has been developed by Biohaven Ltd., a pharmaceutical company specializing in biomedicine. The drug has received approval for use in the treatment of various conditions related to the nervous system, mouth and tooth diseases, skin and musculoskeletal diseases, immune system diseases, infectious diseases, respiratory diseases, and otorhinolaryngologic diseases. The active indications for Rimegepant Sulfate include migraine disorders, chronic sinusitis, nasal polyps, acute migraine, plaque psoriasis, trigeminal neuralgia, and temporomandibular joint dysfunction syndrome. This indicates that the drug has a broad range of potential applications in the field of biomedicine. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Rimegepant Sulfate has achieved the highest phase of development, which is approval, on a global scale. It received its first approval in the United States in February 2020. This suggests that the drug has undergone rigorous testing and evaluation to ensure its safety and efficacy. In China, Rimegepant Sulfate is currently in the NDA/BLA phase, indicating that it is undergoing the process of seeking approval in the country. Overall, Rimegepant Sulfate is a promising drug in the field of biomedicine. Its small molecule structure and targeting of the CGRP receptor make it a potentially effective treatment for various conditions. With its approval in the United States and ongoing efforts for approval in China, the drug has the potential to provide relief to patients suffering from migraine disorders, chronic sinusitis, nasal polyps, and other related conditions. The diverse therapeutic areas it covers further highlight its potential impact in the pharmaceutical industry. As an expert in the pharmaceutical industry, it would be beneficial to closely monitor the progress of Rimegepant Sulfate and its potential impact on patient care and treatment outcomes. UbrogepantUbrogepant is a small molecule drug that targets the CGRP receptor and is primarily used in the treatment of migraine disorders. It falls under the therapeutic area of nervous system diseases. The drug was first approved in the United States in December 2019 and is currently in the highest phase of development, which is the approved stage. Ubrogepant is developed by Merck Sharp & Dohme Corp., a renowned pharmaceutical organization. As a small molecule drug, it is designed to interact with the CGRP receptor, which plays a crucial role in migraine pathophysiology. By targeting this receptor, ubrogepant aims to alleviate the symptoms associated with migraine disorders. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Migraine disorders are a prevalent neurological condition characterized by recurrent headaches, often accompanied by other symptoms such as nausea, vomiting, and sensitivity to light and sound. The approval of ubrogepant provides a new treatment option for individuals suffering from migraines, offering potential relief and improved quality of life. And this approval allows healthcare professionals to prescribe ubrogepant to patients, providing them with a much-needed alternative to existing treatments. The development and approval of ubrogepant highlight the continuous efforts in the pharmaceutical industry to address unmet medical needs and improve patient outcomes. By specifically targeting the CGRP receptor, ubrogepant offers a targeted approach to migraine treatment, potentially minimizing side effects and enhancing therapeutic efficacy. In conclusion, ubrogepant is a small molecule drug developed by Merck Sharp & Dohme Corp. that targets the CGRP receptor for the treatment of migraine disorders. Its approval in the United States in December 2019 signifies its safety and efficacy in alleviating migraine symptoms. This development represents a significant advancement in the field of biomedicine, providing healthcare professionals with a new treatment option to improve the lives of individuals suffering from migraines. The earliest approved CGRP receptor antagonist for market launch: Erenumab Erenumab (Genetical Recombination) is a monoclonal antibody drug that targets the CGRP receptor. It is primarily used in the treatment of various nervous system diseases, mouth and tooth diseases, as well as skin and musculoskeletal diseases. The active indications for this drug include migraine disorders, temporomandibular joint dysfunction syndrome, and headaches. The drug was developed by Amgen, Inc., a renowned pharmaceutical company. It has received approval for use in the highest phase globally. The first approval for Erenumab (Genetical Recombination) was granted in May 2018 in the United States. As a monoclonal antibody, Erenumab (Genetical Recombination) works by targeting the CGRP receptor. CGRP, or calcitonin gene-related peptide, is a neuropeptide involved in the transmission of pain signals. By blocking the CGRP receptor, this drug aims to reduce the frequency and severity of migraines, alleviate symptoms associated with temporomandibular joint dysfunction syndrome, and provide relief from headaches. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. The approval of Erenumab (Genetical Recombination) marks a significant advancement in the treatment of these conditions. Migraine disorders, in particular, affect a substantial portion of the population and can significantly impact the quality of life for those affected. The introduction of a targeted therapy like Erenumab (Genetical Recombination) offers new hope for patients who have previously struggled to find effective treatment options. The approval of this drug in the global markets highlights its potential to address the unmet medical needs of patients worldwide. The fact that it has reached the highest phase of approval indicates that it has undergone rigorous testing and demonstrated its safety and efficacy. In summary, Erenumab (Genetical Recombination) is a monoclonal antibody drug developed by Amgen, Inc. It targets the CGRP receptor and is approved for the treatment of various nervous system diseases, mouth and tooth diseases, and skin and musculoskeletal diseases. Its active indications include migraine disorders, temporomandibular joint dysfunction syndrome, and headaches. The drug has received approval in the United States and China, marking a significant advancement in the field of biomedicine.