5-HT1F receptor

The comprehensive cancer center’s experts will spotlight scientific data on how dietary choices, psychosocial support, massage therapy and mind-body calming practices can improve outcomes and the quality of life of people touched by cancer LOS ANGELES--(BUSINESS WIRE)--Researchers from City of Hope ® , one of the largest and most advanced cancer research and treatment organizations in the United States, ranked among the nation’s top 5 cancer centers by U.S. News & World Report and a national leader in providing cancer patients with best-in-class, integrated supportive care programs, will present new data on integrative oncology research and clinical trials at the 21st International Conference of the Society for Integrative Oncology taking place Oct. 25 to 27. Integrative oncology is a patient-centered field of cancer care that combines conventional cancer treatments with complementary, evidence-based therapies to improve outcomes and quality of life. The hybrid conference hosted by City of Hope in Costa Mesa, California, will include more than 170 oral and poster abstracts evaluating supplements and herbal therapies, traditional medicine such as acupuncture, lifestyle choices like diet and exercise, mind-body practices, and use of artificial intelligence and machine learning in integrative oncology. “City of Hope and other experts will share the best science that’s occurring in the field of integrative oncology, which aims to optimize health, quality of life and clinical outcomes,” said Richard T. Lee , M.D., Cherng Family Director’s Chair for the Center for Integrative Oncology at City of Hope, medical director of supportive and integrative medicine at City of Hope Orange County and co-chair of the SIO conference. “City of Hope is leading a national effort to make evidence-based integrative oncology a routine and interwoven part of optimal cancer care and survivorship. City of Hope is bringing together leaders in the field to create the most holistic approach to cancer care.” A $100 million gift from Panda Express Co-CEOs Andrew and Peggy Cherng has enabled City of Hope to lead efforts to accelerate research, therapeutic development and clinical trials for the advancement of evidence-based integrative oncology practices so that cancer patients nationwide and their doctors have access to safe, proven approaches. Some of the leading-edge data City of Hope will present include the following oral abstracts. Massage therapy during infusion lessens the side effects of chemotherapy in a pilot study Presentation time and location: Saturday, Oct. 26 in the Plaza Ballroom from 3 to 4:15 p.m. Christy DiCristofano, a City of Hope massage therapist, led a pilot study assessing the therapeutic effects of massage on cancer patients. The research team surveyed 232 individuals who collectively received 500 hand and/or foot massages while undergoing an infusion. They found that massage therapy is a beneficial additional treatment for symptoms induced by chemotherapy. The therapy had no reported side effects and proved useful in managing symptoms, such as anxiety, pain, shortness of breath, nausea and neuropathy, which is marked by shooting pain, numbness or tingling. Further research is needed to comprehensively evaluate the benefits of this intervention during infusion. Increasing white button mushroom intake could slow the progression of prostate cancer Presentation time and location: Sunday, Oct. 27 in the Lido Room from 10:45 a.m. to noon Bidirectional translational research led by Xiaoqiang Wang, M.D., Ph.D., City of Hope staff scientist, and Shiuan Chen , Ph.D., professor and chair of City of Hope’s Department of Cancer Biology and Molecular Medicine and the Lester M. and Irene C. Finkelstein Chair in Biology, revealed that consuming white button mushrooms can alter androgen levels and boost anti-cancer immunity. The comprehensive research included preclinical experiments, mouse models and prostate cancer patients participating in an ongoing phase 2 clinical trial. The physician-scientists collected blood samples from both mouse models and humans, analyzing myeloid-derived suppressor cells that are responsible for squelching immune responses and assisting tumor growth. They found that consuming white button mushrooms enhances anti-tumor immunity and slows prostate cancer progression. They expect to learn more once the phase 2 clinical trial is completed. Can intermittent fasting decrease the side effects of radiotherapy and enhance its efficacy? Presentation time and location: Friday, Oct. 25 in the Mesa Verde Room from 2:30 to 3:45 p.m. Several clinical and preclinical studies suggest that time-restricted eating, more commonly called intermittent fasting, may enhance anti-tumor response, decrease side effects and improve quality of life during systemic therapy. Ziyi Huang, M.D., City of Hope research fellow, and Yun Rose Li , M.D., Ph.D., assistant professor of radiation oncology at City of Hope, are leading an ongoing randomized phase 2 trial testing whether patients with pelvic malignancies who practice time-restricted eating could experience reduced levels of radiotherapy-induced side effects and enhanced radiotherapy efficacy. The time-restricted eating group are asked to fast for 12 to 14 hours on radiotherapy days. Researchers collect diet logs, stool, urine and blood samples alongside patient- and clinician-reported toxicities. Thus far, the results are encouraging and support the tolerability and feasibility of intermittent fasting during pelvic radiotherapy, especially among patients with prostate cancer. Enrollment in the trial is expected to be completed in spring 2025. Nurses can videoconference cancer patients to provide supportive care and improve quality of life Presentation time and location: Saturday, Oct. 26 in the Plaza Ballroom from 3 to 4:15 p.m. Psychosocial support services can be limited in small urban and rural areas. Up to 70% of patients with advanced cancer experience elevated levels of fear of cancer progression characterized by intrusive thoughts, distress and difficulty making future plans. Anne Reb , Ph.D. N.P., assistant professor of nursing research and education at City of Hope, and Betty Ferrell , Ph.D., M.S.N., CHPN, City of Hope director and professor of nursing research and education, led a pilot study to assess the feasibility and preliminary effects of a nurse-guided videoconferencing intervention to manage fear of cancer progression levels in patients with Stage 3 or 4 gynecologic or lung cancer. Some 82% of the 30 study participants completed all five nurse-led videoconferencing sessions and reported using the tools the nurses introduced like attention training and detached mindfulness to focus, connect with what is most important to them and gain control over daily life stressors. The intervention showed improvement in fear and other quality-of-life outcomes. Feasibility and acceptability was established in this small sample size and suggestions for improvement were established. The potential risk of drug interactions with cannabis use Presentation time and location: Saturday, Oct. 26 in the Plaza Ballroom from 11:30 a.m. to 12:45 p.m. In one of the first studies to assess cannabis-related drug interactions in patients receiving cancer treatment, Elyssa Kim, B.S., former City of Hope research assistant, and Richard T. Lee , M.D., City of Hope clinical professor of supportive and integrative medicine, found that a significant proportion of cannabis users are at risk of moderate to major potential medication interactions. Of the 313 participants, 61 were actively using a form of cannabis to address insomnia (46%), pain (41%) and mood (39%). The most common medications whose effectiveness could be compromised due to cannabis use were noted to be medications for pain or inflammation (acetaminophen, dexamethasone), anti-nausea (ondansetron) and even chemotherapy (paclitaxel, doxorubicin). Researchers say that more states are legalizing cannabis and more cancer patients turn to cannabis to alleviate cancer symptoms, but we need more data on the therapeutic effects and pitfalls of cannabis use during cancer treatment. A mix of mindfulness meditation, gentle exercise and spirituality is linked to improved emotional well-being among breast cancer survivors Presentation time and location: Saturday, Oct. 26 in the Lido Room from 11:30 a.m. to 12:45 p.m. Breast cancer survivors often report experiencing anxiety, depression, poor sleep and cognitive impairment. Frank Munoz, a City of Hope chaplain, conducted a pilot study of meditative movement effects on this patient population, taking blood samples to measure serotonin-related (HTR1F and SLC6A4) and mood/cognitive function-related (BDNF, IL6 and IL1b) gene expression levels. The intervention resulted in a biological change in scores of anxiety, depression, sleep quality and cognitive function. This small study, which demonstrated changes in gene expression, suggests that meditative movement such as tai chi and meditation may help breast cancer survivors recover from persistent mental and emotional symptoms. About City of Hope City of Hope’s mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the U.S., and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines , as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHope™ . For more information about City of Hope, follow us on Facebook , X , YouTube , Instagram and LinkedIn . Contacts Zen Logsdon 626-409-9367 zlogsdon@coh.org

Organon becomes the sole distributor and promoter of Emgality® (galcanezumab) and RAYVOW™ (lasmiditan) in Europe, building on strong commercial expertise in central nervous system disorders Expands Organon’s European product portfolio in a condition that primarily affects womeni JERSEY CITY, N.J.--(BUSINESS WIRE)-- Organon (NYSE: OGN), a global healthcare company with a focus on women’s health, announced an agreement with Eli Lilly and Company (Lilly) to become the sole distributor and promoter for the migraine medicines Emgality® (galcanezumab) and RAYVOW™ (lasmiditan) in Europe.1 Emgality, a humanized monoclonal antibody calcitonin gene-related peptide (CGRP) antagonist, is indicated for the prophylaxis of migraine in adults who have at least four migraine days per month. RAYVOW is a first-in-class serotonin 5-HT1F receptor agonist approved for the acute treatment of the headache phase of migraine attacks, with or without aura in adults. “This commercialization agreement aligns seamlessly with Organon’s suite of central nervous system treatments in our Established Brands portfolio and, most importantly, it further bolsters our offerings to women, who are disproportionately impacted by migraine,” said Kevin Ali, Organon CEO. “Our strong commercial expertise and proven track record in this therapeutic area will help enable us to bring these important treatments to more patients across Europe who need them." ______________________ 1 `RAYVOW™ is marketed and distributed in the United States as REYVOW Migraine is the third most common disease worldwidei causing recurrent moderate-to-severe headaches, often accompanied by other debilitating symptoms, including nausea, vomiting, and sensitivity to light and soundii that can negatively interrupt an individual’s daily living including family life, career, education, relationships, and earningsiii. The disease is three times more common in women than in men and is one of the leading causes of disability in women.iv “Lilly is committed to helping people living with migraine, a debilitating neurological disease,” said Ilya Yuffa, executive vice president of Eli Lilly and Company and president of Lilly International. “We are confident this collaboration with Organon will help even more people throughout Europe gain access to our innovative migraine treatments.” Under the terms of the agreement, Organon will become the sole distributor and promoter of Emgality and RAYVOW in Europe. Lilly will remain the marketing authorization holder and will manufacture the products for sale. Total consideration to be paid to Lilly includes an upfront payment of $50 million and sales-based milestone payments. The transaction is expected to close in Q1 2024 upon completion of review with relevant country-specific authorities. About Emgality® Emgality is a monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP) and was approved by the European Medicines Agency (EMA) in November 2018. Indications and Usage in EU: Therapeutic indications: Emgality is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month. Posology and method of administration: Emgality should be initiated by physicians experienced in the diagnosis and treatment of migraine. Posology: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose. Patients should be instructed to inject a missed dose as soon as possible and then resume monthly dosing. The treatment benefit should be assessed within 3 months after initiation of treatment. Any further decision to continue treatment should be taken on an individual patient basis. Evaluation of the need to continue treatment is recommended regularly thereafter. Method of administration: Subcutaneous use. A patient may self-inject galcanezumab by following the Instructions for Use. Galcanezumab is to be injected subcutaneously in the abdomen, thigh, back of the upper arm, or in the gluteal region. After training, patients may self-inject galcanezumab if a healthcare professional determines that it is appropriate. Comprehensive instructions for administration are given in the Package Leaflet. About RAYVOW™ (lasmiditan) RAYVOW is an oral treatment that binds to 5-HT1F receptors with high affinity and is approved by the EMA for the acute treatment of the headache phase of migraine attacks, with or without aura in adults. Its therapeutic effects in the treatment of migraine are presumably mediated by agonist effects at the 5-HT1F receptor; however, the precise mechanism is unknown. RAYVOW is not indicated for preventive treatment of migraine. RAYVOW can be prescribed to patients in oral doses of 50 mg, 100 mg, and 200 mg as needed. No more than 200 mg should be taken in 24 hours. Indications and Usage in EU: RAYVOW is indicated for the acute treatment of the headache phase of migraine attacks, with or without aura in adults. Posology and method of administration: Posology: In general, recommended initial dose in adults is 100 mg lasmiditan for acute treatment of migraine attacks. If necessary, the dose can be increased to 200 mg for greater efficacy or can be decreased to 50 mg for greater tolerability. If the migraine headache recurs within 24 hours of an initial response after taking 50 mg or 100 mg lasmiditan, a second dose of the same strength may be taken. The second dose should not be taken within 2 hours of the initial dose. No more than 200 mg should be taken in 24 hours. If a patient does not respond to the first dose, it is unlikely that a second dose will be of benefit in the same attack. Lasmiditan may be taken with or without food. Method of administration: Oral use. About Organon Organon is a global healthcare company formed to focus on improving the health of women throughout their lives. Organon offers more than 60 medicines and products in women’s health in addition to a growing biosimilars business and a large franchise of established medicines across a range of therapeutic areas. Organon’s existing products produce strong cash flows that support investments in innovation and future growth opportunities in women’s health and biosimilars. In addition, Organon is pursuing opportunities to collaborate with biopharmaceutical innovators looking to commercialize their products by leveraging its scale and presence in fast growing international markets. Organon has a global footprint with significant scale and geographic reach, world-class commercial capabilities, and approximately 10,000 employees with headquarters located in Jersey City, New Jersey. For more information, visit and connect with us on LinkedIn, Instagram, X (formally known as Twitter) and Facebook. Cautionary Note Regarding Forward-Looking Statements Some statements and disclosures in this news release are “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that do not relate solely to historical or current facts and can be identified by the use of words such as “potential,” "may," “expects,” “intends,” “anticipates,” “plans,” “believes,” “seeks,” “estimates,” “will,” or words of similar meaning. These forward-looking statements include, but are not limited to, statements about the expected timing for the completion of the transaction between Organon and Eli Lilly and Company, Organon’s ability to obtain required licenses and commercialize Emgality® and RAYVOW™ in Europe during the expected timeframe, and the expected benefits of the commercialization agreement. Such statements are based on Organon’s current plans and expectations and are subject to a number of risks and uncertainties that could cause its plans and expectations, including actual results, to differ materially from the forward-looking statements. Risks and uncertainties include, but are not limited to, the timing and impact of any required regulatory reviews or approvals, any failure to satisfy the conditions to closing the commercialization transaction, an inability of Organon to fully execute on its commercialization plans for Emgality® and RAYVOW™ and/or an inability to obtain required licenses to commercialize such assets, efficacy, safety, or other quality concerns with respect to marketed products, including market actions such as recalls, withdrawals, or declining sales; general industry conditions and competition; the impact of pharmaceutical industry regulation and health care legislation and trends toward health care cost containment; new products and patents attained by competitors; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; difficulties developing and sustaining relationships with commercial counterparties; dependence on the effectiveness of patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. Organon undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Organon’s filings with the Securities and Exchange Commission ("SEC"), including Organon’s Annual Report on Form 10-K for the year ended December 31, 2022 and subsequent SEC filings, available at the SEC’s Internet site ( ). ______________________ i American Brain Foundation, Migraine overview, available: Migraine - American Brain Foundation [last accessed: November 2023] ii National Institute of Neurological Disorders and Stroke, Migraine, available: Migraine | National Institute of Neurological Disorders and Stroke (nih.gov) [last accessed: November 2023] iii Buse DC. et al. Life With Migraine: Effects on Relationships, Career, and Finances From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, Headache: The Journal of Head and Face Pain, 2019;59:1286-1299 doi: 10.1111/head.13613 iv Pavlović JM. The impact of midlife on migraine in women: summary of current views. Womens Midlife Health. 2020;6(1):11. doi:10.1186/s40695-020-00059-8

Neurologists have had relatively few tools at their disposal to help migraine patients, but the treatment landscape has evolved considerably in recent years, according to Alexander Feoktistov, a neurologist at the Synergy Integrative Headache Center in Chicago. “I’ve been in this field of headache medicine for probably over 20 years now, and I’ve never been as excited to work in this field as in the past few years,” he said. The most recent article in a two-part interview with Dr. Feoktistov discusses both drug and device treatments for migraine headaches, which affect roughly 1 billion people globally. How has the migraine treatment landscape evolved in recent years? Feoktistov: It has been unprecedented. It’s like a small revolution in the headache medicine field in the past three years. So the first CGRP monoclonal antibody, which was erenumab-aooe, came out in May of 2018. And since that time, we’ve had three other CGRP monoclonal antibodies come out. We’ve had two gepants come out as acute treatments. We’ve had a 5-HT1F receptor agonist come out known as Lasmiditan. And now, one of those gepants, as of last week, was approved for prophylactic use. It’s unbelievable, but we have never experienced this type of development of new medications specifically developed for migraine treatment. If you think about it, migraine is a pretty ancient condition. Hippocrates described migraines in his papers with great detail. We’re talking about thousands of years of migraine history, yet 2018 was the first year we had a drug specifically developed for migraines. Before the first CGRP monoclonal antibody, everything else we used for migraine treatment was developed to treat something else, whether it was a seizure disorder, high blood pressure or depression. We sort of borrowed those medications from other fields. But CGRP is the first dedicated class of drugs for migraine alone. The landscape is changing. What about the device landscape for migraines? Feoktistov: We also have this relatively novel field of headache medicine called noninvasive neuromodulation that’s also evolved pretty intensely over the past several years. We now have four FDA-cleared devices for migraine treatment either acutely or prophylactically. Those are the noninvasive nerve stimulators that utilize different mechanisms of action. They all work very differently in showing promising results as far as offering our patients non-pharmacological/non-medicinal options to treat headaches. The most commonly used treatment now is called Cefaly, which is a brand name. It’s a supraorbital/supratrochlear nerve stimulator. It is a relatively small device that a patient puts on their forehead between the eyebrows. Patients put a sticky electrode on the skin and then attach the device to it. After the press of a button, it electrically stimulates those supraorbital and supratrochlear nerves that innervate the forehead. Those are the major sensory nerves from the trigeminal nerve, the main sensory nerve in the head and face area. That’s the nerve that gets actively involved and activated during the migraine attack. So patients apply the stimulation. And depending on the type of stimulation and the duration, it could be used prophylactically or acutely. So, acutely a patient would apply one-hour-long stimulation with migraine onset. Prophylactically, a patient would apply 20 minutes of stimulation every single day, regardless of whether they have a headache or not. This stimulation can cause the sensation of pins and needles in the forehead. It is something patients will have to get used to. But it was FDA cleared many years ago, and, in November of 2020, it became over the counter. It no longer requires a prescription. The second device that we’ve been using extensively with a lot of research behind it is a so-called noninvasive vagus nerve stimulation device. The brand name is GammaCore Sapphire. This device is a handheld device that patients hold in their hand. They apply stimulation to the side of their neck right below the jaw. They apply proprietary stimulation to the vagus nerve fibers located next to the carotid artery. Once that patient finds the vagus nerve, they apply this device to that area. They continue stimulation for just literally a couple of minutes with migraine or cluster headache onset. Patients can then use the stimulation regularly as well for prophylactic use for either migraine or cluster headaches. It has been FDA cleared to be used for migraine and cluster headache treatment — acutely and prophylactically. In February of this year, it received an extended indication to treat adolescent migraine as well. And its mechanism of action is sophisticated. Multiple human clinical trials were done that were placebo-controlled and randomized. They found GammaCore to be very effective and very well tolerated by patients. Its mechanism of action is unique. It changes certain neurotransmitter levels. It impacts so-called cortical spreading depression, which is a neurophysiological phenomenon involved in migraine aura development. It’s not a painful stimulation. Patients feel a little bit of tingling. Finally, the other device that we’ve had a lot of success with is called Nerivio. This device is made in Israel. It is an example of remote or conditioned pain modulation. It’s almost like an armband applied above the elbow and below the shoulder. This device is connected wirelessly to a smartphone, and then patients turn on the device using the smartphone app to start the stimulation. As they continue the stimulation for about 45 minutes, patients can regulate the intensity, which should be pretty intense. It should not be painful, but it should be very noticeable. Patients use it for about 45 minutes. This device is approved only as an acute treatment. Patients use it at the onset of a migraine attack. It’s supposed to abort the migraine attack. Studies have looked into the overall patient satisfaction when patients use Nerivio stimulation instead of standard-of-care oral medication treatment of migraine. Patients frequently were more satisfied with the electronic stimulation than the oral tablets. There are some reports of neurologists having a high prevalence of migraines. A 2018 study in Brain Behavior reported that between 27.6% and 48.6% of neurologists have migraine headaches. What’s your take on that? Feoktistov: If a neurologist is familiar with migraines, it’s very hard to misdiagnose. They would literally feel it and know what is going on. Sometimes patients can’t verbalize or describe some of their symptoms. Certainly, if a neurologist experiences a migraine attack and knows what a migraine attack feels like and looks like, it’s probably much easier to diagnose. How often do you see patients whose migraines are non-responsive to treatment? Feoktistov: It’s a prevalent theme, unfortunately. Migraine can present differently in some patients. They have different clinical symptoms sometimes. In some patients, nausea is very prevalent. And in other patients, nausea is minimal, if it is present at all. In some patients migraine, develops very rapidly. It takes several hours for the migraine to start from a level zero and go to a more severe stage in other patients. It could take half of the day for some patients. All of these factors and just patient susceptibility and tolerability of the medications influence the overall treatment efficacy. Maybe 50% of the time, you have to go back and revisit with the patient and adjust the medication or switch them to something else. I wouldn’t say that we’re expecting that, but it’s something that we encounter very frequently. Plus, migraine is a very multifactorial condition. There are many different factors and even pathophysiological mechanisms that could be involved in some patients, and therefore, their responses might be different. We know that this chemical called calcitonin gene-related peptide (CGRP) has been studied and investigated aggressively over about 20 years. We now have several medications targeting CGRP. But as important as it is, it may not be as important in every patient with migraine. There might be other mechanisms involved in some patients. That may require a different treatment or a new treatment. So, yes, we frequently see patients who need to have either medication adjusted or even try something completely different, just looking at different patterns.