5-HT1F receptor

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.

Looking to make a splash in sickle cell, Forma Therapeutics presented new data they hope can improve their shot at an eventual FDA OK. As part of an ongoing Phase I study, Forma said its FT-4202 program showed enough hemoglobin increases to support the doses selected in the upcoming Phase II/III trial, which is currently enrolling. Data from two cohorts illustrated 10 of 14 patients taking the once-daily therapy saw a hemoglobin increase of at least 1 g/dL from baseline over the two-week treatment period. The results support “the evaluation of safety and efficacy at an upper range of 400 mg in our Phase II/III trial,” CMO Patrick Kelly said in a statement. Forma’s data come from cohorts measuring a 300 mg dose and a 600 mg dose. In the Phase I study, six of seven individuals in the 300 mg arm saw the appropriate hemoglobin increase, while four of seven taking a 600 mg dose reached the threshold. The Watertown, MA-based biotech is continuing to evaluate the benefit of FT-4202 beyond 14 days of treatment as part of an ongoing open-label extension. That program is measuring 400 mg doses in patients taking the experimental drug for 12 weeks. Data from Tuesday’s higher cohort remain blinded, but Forma noted an initial analysis suggests a similar safety profile to the 300 mg dose. Additionally, there were no dose-limiting or treatment-related side effects, Forma said. FT-4202 is taking a different approach to sickle cell disease than those seen from Novartis and Global Blood Therapeutics, which saw their drugs approved in the last couple of years. While their competitors attempt to relieve the disease’s worst symptoms or complications, Forma says its program modifies the course and underlying biology of the disease without affecting the genome. It activates an enzyme called pyruvate kinase-R that is supposed to help prevent sickling and help hemoglobin bind to oxygen. Forma’s program also differs from companies that are attempting to offer a cure for sickle cell disease through gene therapies, such as bluebird bio , Editas and Vertex/CRISPR Therapeutics . Perceptive’s China play has a new partner and some new cash. LianBio has teamed up with Tarsus Pharmaceuticals to develop a therapy for eye irritation caused by Demodex mites, a common ectoparasite found on humans. The agreement calls for a $15 million upfront payment to Tarsus, with the pharma being eligible for up to $185 million in milestones. In exchange, LianBio will gain exclusive rights to commercialize the treatment in China, Hong Kong, Macau and Taiwan. The therapy in question is called TP-03, a 0.25% lotilaner ophthalmic solution designed to eradicate mites that have infested the eyelid margin. Tarsus says it has completed four Phase II trials of TP-03 in Demodex blepharitis, all of which met their respective endpoints with no significant side effects popping up. “With more than 100 million estimated Demodex blepharitis and Meibomian Gland Disease patients in China…we’ve selected TP-03 to anchor LianBio’s ophthalmology portfolio,” LianBio chairman Konstantin Poukalov said in a statement. Perceptive launched LianBio as its first in-house startup last August, following up two months later with a $310 million raise. Among a host of other marquee VCs, the syndicate also included Pfizer, which in November chipped in another $70 million to co-develop pipeline programs. The migraine competition between AbbVie and Biohaven continues, as the FDA accepted Abbvie’s NDA for preventative treatment for atogepant on Tuesday. The FDA is likely to make its decision in the late third quarter of 2021, AbbVie said. Atogepant was developed specifically for the prevention of migraines. As part of its pitch, AbbVie tested atogepant in about 2,500 patients with four to 14 migraine days per month. The data come from at least three clinical studies, a Phase III trial, a Phase IIb/III study and a Phase III long-term safety study. AbbVie has another migraine drug in Ubrelvy, which approved for the treatment of acute migraines with or without aura back in 2019. The migraine space has seen hefty competition in recent years. Ubrelvy, also known as ubrogepant, has gone up against Biohaven’s rimegepant, sold as Nurtec. Both drugs are oral CGRP receptor antagonists, with Nurtec publishing its most recent Phase III data back in December. Nurtec is looking to add migraine prevention to its label. Eli Lilly also has a migraine drug on the market in Reyvow, approved in October 2019, but it targets the 5-HT1F receptor. About four and a half years since debuting with an $18 million startup round, Fortis Therapeutics has returned to the venture well. The San Diego-based biotech pulled in a new $40 million Series A on Monday, as it looks to continue development of an antibody drug conjugate against CD46. The program, called FOR46, binds a specific conformational epitope of CD46, Fortis says. CD46 acts as part of the body’s immune defense system and appears to be specific to tumor cells, the company added. Fortis says it’s completed single patient cohorts and is now enrolling an expansion cohort for the treatment of relapsed or refractory multiple myeloma. Existing investors such as Avalon, Bregua, Lilly Asia Ventures, Osage University Partners, and Vivo Capital all participated. New investors also joined in — the Myeloma Investment Fund, and Fulcrum 2020. DNA sequencing biotech Oxford Nanopore is prepping an IPO — for the London stock exchange. The company sent investors a notice Tuesday morning stating its intent to go public, but did not disclose further details. Oxford Nanopore’s move will likely be seen as a big win for UK Prime Minister Boris Johnson’s government, Bloomberg News reported , as it looks to attract life sciences investment in a post-Brexit climate. Johnson reportedly met with the biotech last December in an effort to convince them to list in London. The biotech, spun out of Oxford University, boasts “scalable” DNA and RNA sequencing tech that can range from bench-top devices to pocket-sized machines. It had previously been privately valued at almost $2 billion. Correction: An earlier version this piece incorrectly referred to AbbVie’s Ubrelvy migraine drug as atogepant. It is ubrogepant.