Mainstay Medical Announces Coverage Recommendation from the International Society for the Advancement of Spine Surgery (ISASS) for ReActiv8

Mainstay Medical Holdings plc today announced that the International Society for the Advancement of Spine Surgery (ISASS) has issued recommendations and coverage criteria for the use of restorative neurostimulation for the treatment of chronic mechanical low back pain associated with multifidus muscle dysfunction. ReActiv8® restorative neurostimulation is the only therapy approved in the United States, Europe and Australia for this indication.

The Statement, which affirms ISASS’ support for coverage by payers of implantable restorative neurostimulation in appropriately selected patients, was published in the December issue of the International Journal of Spine Surgery and can be accessed here: https://www.ijssurgery.com/content/early/2025/12/10/8833.

The Statement reflects the growing body of clinical evidence supporting the use of ReActiv8, as well as recent developments in diagnostic coding and reimbursement pathways since ISASS’ 2023 Statement on Restorative Neurostimulation for Chronic Mechanical Low Back Pain Resulting from Neuromuscular Instability. Key updates include: published five-year results from the pivotal randomized clinical trial; published one-year results from a second randomized clinical trial demonstrating ReActiv8’s superiority over standard of care; evidence from multiple real-world studies; the introduction of the new ICD-10 code M62.85: dysfunction of the multifidus muscles, lumbar region; and payer trends, including the recent establishment by Anthem Blue Cross Blue Shield of favorable coverage for ReActiv8.

“ISASS has a well-established history of supporting evidence-based technologies for patients with spine disease. The evidence for restorative neurostimulation - reactivating the multifidus muscle that drives mechanical low back pain - demonstrates meaningful improvements in pain, disability, and quality of life,” said Morgan P. Lorio, MD, ISASS Past President and Chair Emeritus, Coding & Reimbursement Task Force. “With new Level I data, the dedicated ICD-10 code, recent payer decisions, and the well-established clinical and economic significance of multifidus dysfunction, ISASS supports broader coverage and appropriate clinical adoption of restorative neurostimulation to improve outcomes and reduce the healthcare burden in this defined disease state.”

“We are pleased that ISASS has taken the lead by reviewing the totality of evidence, recognizing that ReActiv8 can benefit patients and payers,” stated Jason Hannon, Chief Executive Officer of Mainstay Medical. “We look forward to discussing our robust clinical and real-world evidence with health plans, with the goal of providing access to ReActiv8 for more patients seeking durable solutions for their mechanical chronic low back pain.”

MMI Wins FDA Clearance and Completes First U.S. Clinical Use of Robotic Microsurgical Dissection Instruments with Symani

First U.S. Patient Treated with NanoWrist Dissection Instruments, Marking Early Clinical Adoption and Portfolio Growth

JACKSONVILLE, FL — December 9, 2025 — MMI (Medical Microinstruments, Inc.), a robotics company dedicated to expanding treatment options and improving outcomes for patients with complex conditions, today announced that it received U.S. Food and Drug Administration 510(k) clearance for its NanoWrist® Scissors and Forceps indicated for soft tissue dissection. This clearance enables delicate tissue manipulation and dissection in robotic microsurgery, expanding the role of the Symani® Surgical System beyond anastomosis to include additional critical steps in complex surgery.

The first U.S. clinical use of the cleared instruments was recently completed at Tampa General Hospital (TGH), home to an established microsurgical robotics program. The lymphovenous bypass (LVB) procedure, leveraging the full capabilities of Symani, represents the world’s first fully robotic-assisted microsurgical operation from initial incision to skin closure.

Dr. Nicholas J. Panetta, MD, FACS, Chair of the Department of Plastic Surgery at the University of South Florida Morsani College of Medicine and Chief of the Plastic Surgery Institute at TGH, specializes in microvascular reconstructive plastic surgery. For the surgery, Symani and the NanoWrist Instrument Portfolio were utilized to complete a specialized microsurgical technique that redirects tiny lymphatic vessels to nearby veins, helping relieve swelling by restoring fluid drainage. He accessed the surgical site and prepared the lymphatic vessels and veins using the NanoWrist Scissors and Forceps for delicate tissue handling, precise dissection, and vessel preparation. The bypass was then performed with the NanoWrist SuperMicro Needle Holder Suture Cut and SuperMicro Dilator. All instruments in the portfolio offer seven degrees of freedom, delivering precise robotic capabilities and the full benefits of Symani’s motion scaling and tremor reduction features.

“Robotics will define the future of microsurgery, especially in lymphedema work where sub-millimeter precision is essential. I have been able to push the limits of microsurgery to treat some of the smallest and most delicate vessels, and the impact Symani is having on our patients has been transformative,” shared Dr. Panetta. “With robotic enabled dissection, I was able to complete a fully robotic LVB, from incision to closure, with unmatched precision, control and improved ergonomics. These tools are unlocking capabilities that extend beyond the limits of the human hand to support the best possible outcomes for patients.”

MMI’s dissection instruments are the world’s first and smallest fully wristed robotic instruments designed specifically for dissection in open microsurgery. The NanoWrist Scissors and Forceps are designed to preserve tissue integrity and reduce vessel trauma to help improve patient outcomes. This level of precision and control is especially critical in complex procedures such as surgical lymphatic repair, perforator-to-perforator reconstruction, and cancer-related head & neck reconstruction.

“As we continue to evolve Symani, the first dissection instruments are a critical step in that mission,” said Mark Toland, CEO of MMI. “The addition of these capabilities to our platform is game-changing in supermicrosurgical procedures where extreme precision for the smallest vessels is essential. We will continue to develop technologies that advance the future of microsurgery with Symani and transform microsurgical care and countless lives worldwide.”

These achievements follow a string of meaningful milestones for MMI and the microsurgical sector this year, including the company’s advancement into neurosurgery, launching the largest U.S. prospective clinical trial in robotic microsurgery, additional expanded technological and digital surgery capabilities, and gaining reimbursement support for select procedures.

For more information about Symani and the dissection instruments, visit www.mmimicro.com.

Lynkuet™ (elinzanetant) approved in the EU for the treatment of moderate to severe vasomotor symptoms associated with menopause or endocrine therapy for breast cancer

Elinzanetant, now approved in the EU under the brand name Lynkuet™ is a dual neurokinin (NK)-targeted therapy (NK-1 and NK-3 receptor antagonist) and the only hormone-free treatment for moderate to severe vasomotor symptoms (VMS; also known as hot flashes) associated with menopause or caused by adjuvant endocrine therapy (AET) related to breast cancer / European approval in these two indications is based on positive results from the OASIS Phase III program, comprising four clinical studies (OASIS-1-4), in which elinzanetant significantly reduced the frequency and severity of moderate to severe VMS in women experiencing menopause or receiving endocrine therapy for breast cancer and demonstrated a favorable safety profile.

The European Commission has granted marketing authorization in the European Union (EU) for elinzanetant, under the brand name Lynkuet™. The compound is approved for the treatment of moderate to severe vasomotor symptoms (VMS; also known as hot flashes) associated with menopause or caused by adjuvant endocrine therapy (AET) related to breast cancer.

“The European approval of Lynkuet™ brings a new option to women whose daily lives are disrupted by vasomotor symptoms,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization, and Member of the Pharmaceutical Leadership Team at Bayer. “We understand how challenging and isolating these symptoms can be, often interfering with daily rhythm, personal productivity, and overall quality of life. Our commitment is to support women with solutions that truly address their needs, helping them feel like them themselves again by supporting health and wellbeing at every stage.”

By 2030, it is estimated that 1.2 billion women globally will be experiencing menopause.1 VMS affect up to 80% of women during the menopausal transition.2 In Europe, approximately 40% of women report moderate to severe VMS,3 highlighting the substantial burden of these symptoms on daily life and overall well-being.

“Menopause symptoms, including hot flashes, can greatly affect women's quality of life,” said Nick Panay, Principal Investigator for OASIS-3, Consultant Gynecologist, Imperial College Healthcare NHS Trust, Professor of Practice, Imperial College London and Immediate Past President of the International Menopause Society. “This approval is an important milestone in the area of menopause care as it expands therapeutic options for women experiencing distressing menopause symptoms with a novel targeted hormone-free treatment and facilitates healthcare professionals to achieve more personalized treatment.”

VMS may also be caused by endocrine therapy, for the treatment or prevention of breast cancer. Breast cancer remains the most common cancer diagnosed in women worldwide, with approximately 70% of cases categorized as hormone-receptor positive (HR+).4,5 Endocrine therapy, an established treatment for women with HR+ breast cancer, can often result in VMS6,7 impacting quality of life and treatment adherence.

“Menopausal symptoms are common side effects of endocrine therapy for breast cancer, frequently leading to treatment discontinuation, which highlights the importance of managing these symptoms in breast cancer care,” said Dr. Fatima Cardoso, Principal Investigator of OASIS-4, from Lisbon, Portugal. “With the approval of this hormone-free therapy, we now have the first approved treatment option for this indication that will help in addressing an important unmet medical need of women and improve their quality of life during this challenging time.”

The approval of elinzanetant in the EU is based on the positive results from the OASIS Phase III clinical development program, comprising OASIS-1, -2, -3 and -4, which met all primary endpoints and key secondary endpoints in all four studies and demonstrated a favorable safety profile. Data have been published in diverse medical journals: OASIS-1 and –2 in August 2024 in The Journal of the American Medical Association (JAMA)8, OASIS-3 in The Journal of the American Medical Association (JAMA) Internal Medicine in September 20259 and OASIS-4 in the New England Journal of Medicine (NEJM) in June 2025.10

About elinzanetant (Lynkuet™)

Elinzanetant is the first dual neurokinin (NK)-targeted therapy, (NK-1 and NK- 3 receptor antagonist), globally developed for the treatment of moderate to severe vasomotor symptoms (VMS; also known as hot flashes) associated with menopause or endocrine therapy (ET) for breast cancer, administered orally once daily. Increasing evidence indicates that hypothalamic neurons called kisspeptin, neurokinin B, and dynorphin (KNDy) neurons, expressing both NK-1 and NK-3 receptors and their ligands Substance P and NKB, play a role in thermoregulation. Declining estrogenic activity due to natural menopause or endocrine therapy leads to hyperactivity of KNDy neurons and dysregulation of the thermoregulatory center, resulting in VMS. NK-1 receptors may also have a role in the cooling response through sweating and peripheral vasodilatation as well as on sleep disturbances.

Elinzanetant is approved under the brand name Lynkuet™ in Australia, Canada, the UK, the U.S., and Switzerland for the treatment of VMS associated with menopause and in the EU for the treatment of moderate to severe VMS associated with menopause or caused by adjuvant endocrine therapy (AET) related to breast cancer. Submissions for marketing authorizations for elinzanetant are also ongoing in other markets around the world.

About the Elinzanetant clinical development program

The Phase III clinical development program of elinzanetant, OASIS, comprises four Phase III studies: OASIS-1, -2, -3 and -4. OASIS-1 and -2 investigated the efficacy and safety of elinzanetant administered orally once daily in women with moderate to severe VMS associated with menopause over 26 weeks and randomized 396 and 400 postmenopausal women between 40 and 65 years across 184 sites in 15 countries. Patients in the elinzanetant arm received a 120 mg dose of elinzanetant once daily for 26 weeks and patients in the control arm received a matching placebo once daily for 12 weeks, followed by elinzanetant 120 mg dose for 14 weeks. OASIS-3 investigated the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause over 52 weeks and randomized 628 postmenopausal women between 40 and 65 years across 83 sites in 9 countries. OASIS-4 is a double-blind, randomized, placebo-controlled multicenter study to investigate the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with endocrine therapy for treatment or prevention of hormone receptor positive (HR+) breast cancer over 52 weeks and optionally for an additional 2 years in women taking endocrine therapy, for treatment of breast cancer. 474 patients at 90 centers in 16 countries (excluding the US) were randomized.

About Menopause

By 2030, the global population of women experiencing menopause is projected to increase to 1.2 billion, with 47 million women entering this phase each year. Menopause is a phase in women’s lives, related to the progressive decline of ovarian function usually occurring in their late 40s or early 50s. Menopause symptoms can also be a consequence of surgical or medical treatment such as breast cancer treatment. The most frequently reported and disruptive menopause symptoms are VMS and sleep disturbances, which can substantially affect a woman’s health, quality of life and work productivity. Addressing disruptive menopause symptoms is key to maintaining functional ability and quality of life which is highly relevant from both a healthcare and socio-economic perspective.

About Women’s Healthcare at Bayer

Women’s Health is in Bayer’s DNA. As a global leader in women’s healthcare Bayer has a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. Bayer offers a wide range of effective short- and long-acting birth control methods as well as therapies for menopause management and gynecological diseases. Bayer is also focusing on innovative options to address the unmet medical needs of women worldwide and to broadening treatment choices such as in menopause. Additionally, Bayer intends to provide 100 million women per year in low-and-middle income countries by 2030 with access to family planning by funding multi-stakeholder aid programs for capacity building and by ensuring the supply of affordable modern contraceptives. This is part of the comprehensive sustainability measures and commitments from 2020 onwards and in line with the Sustainable Development Goals of the United Nations.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses amounted to 6.2 billion euros. For more information, go to www.bayer.com.

MMI Receives IDE Approval from FDA for First Robotic Microsurgical Study in Alzheimer’s Patients

First-of-its-kind study represents the potential for robotic-enabled microsurgical intervention for neurodegenerative diseases, including Alzheimer’s

MMI (Medical Microinstruments, Inc.), a robotics company dedicated to increasing treatment options and improving clinical outcomes for patients with complex conditions, today announced the U.S. Food and Drug Administration’s (FDA) approval of an Investigational Device Exemption (IDE) for a clinical study using a novel microsurgical intervention for Alzheimer’s disease.

The feasibility study, entitled REMIND, Robotic-Enabled Microsurgical Intervention for Neurodegenerative Disease, will collect safety and effectiveness data of the Symani® Surgical System and microsurgical techniques to reestablish lymphatic drainage pathways in the deep cervical lymph nodes (dCLNs) of patients with Alzheimer’s and confirmed lymphatic obstruction. The primary endpoint of the study is device-related serious adverse events through 30 days post procedure. Additional endpoints include adverse events, biomarker and imaging changes, and cognitive assessments through six months post procedure.

Breakthrough scientific discoveries over the past decade have improved our understanding of lymphatic vessels in the central nervous system and are exposing the potential need for microsurgical interventions for patients with neurodegenerative diseases such as Alzheimer’s disease. This potential therapeutic pathway, further enabled by robotics, could improve the clearance of harmful proteins like amyloid beta and tau and serve as a treatment for Alzheimer’s disease.

“This FDA approval is more than a milestone for our company—it’s a signal of what’s possible in science when we bring together the right experts, technology, and research,” said Mark Toland, CEO of MMI. “We’re at the threshold of a new era in microsurgery; one where robotic precision could play a central role in unlocking novel treatment pathways for devastating diseases like Alzheimer’s. With REMIND, we’re just beginning to explore the extraordinary potential of robotic lymphatic intervention in redefining a critical standard of care.”

Operating on the dCLNs requires precision at a supermicrosurgical scale, as these lymphatic vessels can be 0.2mm in diameter, equivalent to the thickness of 2 sheets of paper. Very few surgeons are able to dissect and suture such small, delicate structures in a reproducible manner without robotic assistance. This first ever surgical approach involves establishing a precise connection of lymphatic vessels or lymphatic nodes in the neck to neighboring veins utilizing Symani’s robotic precision, which would allow for the draining of neurotoxins from the brain and could support reduced variability in outcomes.

“The REMIND study offers the potential to open an entirely new chapter in the treatment of neurodegenerative disease,” added Kate Rumrill, Chief Scientific Officer of MMI. “Bringing robotic precision to more surgeons stands to change patient lives and medicine. Initiating such critical research may help pave the way for further studies to explore the promise of lymphatic microsurgery in improving the lives of more than 7 million Americans impacted by Alzheimer’s and bringing renewed hope to the caregivers who support them every day.”

The company is partnering with a select group of leading research institutions in the U.S. and Europe to initiate patient enrollment in this landmark study in the very near future. As MMI deepens its presence into critical clinical areas, this and future studies will generate essential data to strengthen the evidence for expanded robotic microsurgical applications. For more information about REMIND, visit the official study listing. For more information about Symani, visit www.mmimicro.com.

About Medical Microinstruments, Inc.

MMI is on a mission to advance robotic technology that pushes the limits of soft tissue open surgery and opens new opportunities for surgeons to restore quality of life for more patients with complex conditions. The company was founded in 2015 near Pisa, Italy, and its proprietary Symani® Surgical System combines the world’s smallest wristed microinstruments with tremor-reducing and motion-scaling technologies to address significant unmet patient needs across the globe. This first-of-its-kind surgical robotic platform for open, soft tissue micro-level surgery can help address microvascular repair and lymphatic repair. In Europe and APAC, it also addresses peripheral nerve repair. The Symani System is authorized for use in the U.S. by the FDA and is a CE Marked medical device in Europe. MMI is backed by global investors including Fidelity Management & Research Company, Andera Partners, BioStar Capital, Deerfield Management, Fountain Healthcare Partners, Panakès Partners, RA Capital, Sambatech, and Wellington Partners.

Bayer’s Lynkuet® (elinzanetant), the First and Only Neurokinin 1 and Neurokinin 3 Receptor Antagonist, Receives FDA Approval for Moderate to Severe Hot Flashes Due to Menopause

• This approval is supported by data from the Phase III OASIS clinical trial program evaluating Lynkuet for the treatment of moderate to severe hot flashes due to menopause1

• In OASIS 1 and OASIS 2, Lynkuet met the co-primary endpoints of reduction in number and severity of moderate to severe hot flashes day and night at weeks 4 and 12 from baseline1

• Hot flashes are a common symptom of menopause2 and one of the main reasons women seek treatment;3 hot flashes may impact women differently4 and some can be disruptive5

Bayer announced today the U.S. Food and Drug Administration (FDA) has approved Lynkuet® (elinzanetant) 60mg capsules, the first and only dual neurokinin (NK) targeted therapy,1 neurokinin 1 (NK1) and neurokinin 3 (NK3) receptor antagonist, for the treatment of moderate to severe hot flashes due to menopause.1 Inhibition of Substance P and Neurokinin B through antagonism of NK1 and NK3 receptor signaling on kisspeptin/neurokinin B/dynorphin (KNDy) neurons can modulate neuronal activity in the thermoregulation associated with hot flashes.1 Lynkuet soft gel capsules are taken once daily at bedtime, with or without food.1 The FDA approval is supported by data from three Phase III clinical trials (OASIS 1, OASIS 2 and OASIS 3) that evaluated the safety and efficacy of Lynkuet for the treatment of moderate to severe hot flashes due to menopause.1

"The FDA approval of Lynkuet is an important new option for women and providers who are treating moderate to severe hot flashes due to menopause," said Yesmean Wahdan, M.D., Head of Medical Affairs USA & North America at Bayer. "As a global leader in women’s healthcare with more than 100 years of research and experience, we are proud to bring this new treatment option to market for women who are going through menopause and seeking hot flash relief."

The efficacy of Lynkuet for the treatment of moderate to severe hot flashes due to menopause was demonstrated in the first 12 weeks of two randomized, double-blind, placebo-controlled, multicenter clinical trials, OASIS 1 and OASIS 2, in 796 menopausal women.1 The co-primary efficacy endpoints in both trials were the mean change in frequency and severity of moderate to severe hot flashes from baseline to weeks 4 and 12, including day and night hot flashes.1 The safety of Lynkuet was evaluated in three randomized, double-blind, placebo-controlled, multicenter clinical trials (OASIS 1, OASIS 2 and OASIS 3) in 1,420 women.1 In OASIS 3, 627 women received Lynkuet or placebo for up to 52 weeks to evaluate long-term safety.1

It’s important to know that women who are pregnant should not take Lynkuet. Lynkuet can cause serious side effects, including central nervous system effects and daytime impairment, increased liver blood test values, risk of pregnancy loss, and risk of seizures in people with a history of seizures. The common side effects of Lynkuet include headache, fatigue, dizziness, feeling drowsy or sleepy, stomach (abdominal) pain, rash, diarrhea, and muscle spasms.1 For more information, please see “Important Safety Information” below.

“These studies investigated the safety and efficacy of elinzanetant for the treatment of moderate to severe hot flashes due to menopause,” said JoAnn Pinkerton, M.D., Professor and Director of Midlife Health at UVA Health and Lead Investigator on the OASIS 2 trial. “Hot flashes, particularly when severe, can have an impact on women’s daily lives and this approval provides healthcare providers with a new treatment option that can be used first-line for moderate to severe hot flashes due to menopause.”

“It’s important that women know they have choices for treating moderate to severe hot flashes due to menopause, and today’s approval further expands a woman’s options for treating these symptoms,” said Claire Gill, President and Founder of the National Menopause Foundation.

As a leader in women’s healthcare, Bayer is committed to making Lynkuet accessible. Through the Lynkuet Access Savings & Support program (LASS), women can connect with a healthcare provider and receive their Lynkuet prescription from home and at the lowest cost available to them. Visit Lynkuet.com to learn more about how to save on Lynkuet. If a patient cannot afford their prescription, Bayer may be able to help. Eligible patients may receive their Bayer prescription medicine at no cost through the Bayer U.S. Patient Assistance Foundation. For more information, please visit www.patientassistance.bayer.us or call to speak with a member of Bayer’s team at 1-866-2BUSPAF (228-7723).

Lynkuet is expected to be available in the U.S. beginning in November 2025. Elinzanetant is approved under the brand name LynkuetTM in Australia, Canada, the United Kingdom and Switzerland. It is pending approval in the European Union and under review in other markets around the world.

INDICATION

What is LYNKUET® (elinzanetant)?

LYNKUET is a prescription medicine used to reduce moderate to severe hot flashes (also known as vasomotor symptoms) due to menopause. LYNKUET is not a hormone. Hot flashes are feelings of warmth in the face, neck, and chest, or sudden intense feelings of heat and sweating.

IMPORTANT SAFETY INFORMATION

Do not take LYNKUET if you are:

• pregnant

Before you use LYNKUET, tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems

• have a history of seizures

• are pregnant or planning to become pregnant. LYNKUET may harm your unborn baby. Women who can become pregnant should talk to their healthcare provider to exclude pregnancy before starting treatment with LYNKUET and use effective birth control during and for 2 weeks after stopping treatment.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. LYNKUET may affect the way other medicines work, and other medicines may affect how LYNKUET works.

What should I avoid while taking LYNKUET?

• Avoid eating grapefruit or drinking grapefruit juice during treatment with LYNKUET.

• LYNKUET may cause you to feel drowsy, if you experience this avoid driving and other hazardous activities until these effects go away.

LYNKUET can cause serious side effects, including:

• Central nervous system (CNS) effects and daytime impairment. LYNKUET can cause difficulty staying awake (somnolence) and other nervous system effects including fatigue, having a spinning feeling (vertigo), dizziness, and feeling faint (presyncope). If you experience these effects, you should not drive or do hazardous activities until these effects go away.

• Increased liver blood test values. LYNKUET may cause increased liver enzymes. Your healthcare provider will do a blood test to check your liver before you start and 3 months after taking LYNKUET. Stop taking LYNKUET and tell your healthcare provider right away if you have the following signs or symptoms that suggest liver problems:

  • feeling more tired than you do usually

  • decreased appetite

  • nausea

  • vomiting

  • itching

  • yellowing of the eyes or skin (jaundice)

  • pale feces

  • dark urine

  • pain in the stomach (abdomen)

• Risk of pregnancy loss. Taking LYNKUET while pregnant may cause loss of pregnancy or stillbirth. If you think you are pregnant, stop taking LYNKUET and tell your healthcare provider right away.

• Risk of seizures in people with a history of seizures. Seek medical attention right away if you have loss of consciousness or seizure.

Common side effects of LYNKUET include:

• headache

• fatigue

• dizziness

• feeling drowsy or sleepy

• stomach (abdominal) pain

• rash

• diarrhea

• muscle spasms

Tell your healthcare provider if you have any side effects that do not go away. These are not all the possible side effects of LYNKUET.

LYNKUET is available by prescription only.

You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088. For Bayer products, you can report these directly to Bayer by clicking here.

For important information about LYNKUET, please see the accompanying Full Prescribing Information.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses amounted to 6.2 billion euros. For more information, go to www.bayer.com.

Find more information at www.pharma.bayer.com

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Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

Disclosures

Claire Gill of The National Menopause Foundation is a long-standing advocacy partner of Bayer and has received financial compensation for her contributions.

References

1 LYNKUET® (elinzanetant) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; October 2025
2 Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. Obstet Gynecol Clin North Am. 2011;38(3):489-501.
3 Kronenberg F. Menopausal hot flashes: a review of physiology and biosociocultural perspective on methods of assessment. J Nutr. 2010;140(7):1380S-5S.
4 Shepherd JA, Shiozawa A, Schild AL, et. al. Retrospective text and qualitative analyses of patient experience and management of vasomotor symptoms due to menopause: voices from the PatientsLikeMe community. Menopause. 2024;31(9):789-795.
5 US Food and Drug Administration. Estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy. FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/estrogen-and-estrogenprogestin-drug-products-treat-vasomotor-symptoms-and-vulvar-and-vaginal-atrophy. Accessed October 23, 2025.

NEUROMARK® Treatment for Chronic Rhinitis Demonstrates Durable 2-Year Clinical Benefits

PARAGON Study Confirms Sustained Efficacy and Safety of NEUROMARK® System in Allergic and Nonallergic Rhinitis Patients

Neurent Medical, a company pioneering innovative non-surgical interventions to treat chronic inflammatory sinonasal diseases, today announced positive two-year results from the PARAGON clinical study, published in Ear, Nose, & Throat Journal. The data confirm that treatment with Neurent Medical's NEUROMARK System, a radiofrequency ablation device indicated for chronic rhinitis, provides durable, clinically meaningful improvements in symptoms and quality of life for patients with both allergic and nonallergic rhinitis.

Key 2-Year Efficacy Findings

• The mean reflective Total Nasal Symptom Score (rTNSS) improved by 55% from baseline at 2 years (p<.0001).

• 76% of participants achieved the responder rate (≥30% reduction in rTNSS).

• 91% achieved the minimum clinically important difference (MCID) of ≥1 point reduction in rTNSS.

• All 4 rTNSS subscores (congestion, rhinorrhea, sneezing, and itching) and postnasal drip and cough demonstrated sustained and significant improvement through 2 years (p<.0001).

• The Nasal Obstruction Symptom Evaluation (NOSE) score and all 5 subscores remained significantly improved at 2 years (p<.0001).

• Quality of life, as measured by the mini-Rhinoconjunctivitis Quality of Life Questionnaire (mini-RQLQ), showed durable benefit, with 79% of participants achieving MCID (≥0.4-point reduction).

• The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) also demonstrated significant long-term improvement (p<.0001).

• Both allergic and nonallergic rhinitis subgroups had durable and significant improvement in rTNSS, NOSE, mini-RQLQ, and ETDQ-7 at 2 years, with no significant differences between groups.

"These long-term results provide robust evidence that NEUROMARK offers durable relief for patients suffering from chronic rhinitis, addressing not only nasal symptoms but also postnasal drip, cough, and ear-related complaints," said Dr. David Yen, MD, lead author of the publication. "The consistency of improvements through two years underscores the potential for NEUROMARK to be a transformative therapy for this difficult-to-treat condition."

"We are delighted to share these 2-year results, which build upon the strong 6-month findings and confirm the sustained efficacy and safety of our NEUROMARK System," said Brian Shields, CEO of Neurent Medical. "This milestone reinforces our mission to deliver innovative, minimally invasive solutions that improve patients' lives and provide ENT physicians with effective tools to manage chronic rhinitis."

About the NEUROMARK System

The NEUROMARK System is indicated for use in otorhinolaryngology (ENT) surgery for creation of radiofrequency lesions to disrupt posterior nasal nerves in patients with chronic rhinitis. By gently applying controlled low-power RF energy, the system disrupts parasympathetic nerve signaling to reduce the inflammatory response and alleviate symptoms such as congestion and rhinorrhea.

About Neurent Medical

Neurent Medical is pioneering innovative treatments for chronic inflammatory sinonasal diseases by targeting and safely disrupting hyperactive autonomic nerves that drive underlying inflammation. Its proprietary NEUROMARK technology, with a unique design and advanced smart algorithmic control, allows physicians to precisely target multiple nerve branches in a single procedure. Headquartered in Galway, Ireland, with U.S. operations in Braintree, MA, Neurent Medical is backed by leading venture capital investors.

MMI Completes World’s First Robotic Microsurgical Intracranial Brain Surgery

First-in-human cases lay the foundation for the next frontier in robotic microsurgery

MMI (Medical Microinstruments, Inc.), a robotics company dedicated to expanding treatment options and improving outcomes for patients with complex conditions, today announced completion of the first cases in a neurosurgical clinical trial sponsored by the Jacobs Institute for the Symani® Surgical System.

Dr. Adnan Siddiqui, a University at Buffalo Distinguished Professor and Vice Chairman in the Department of Neurosurgery (UBNS) at the State University of New York at Buffalo’s Jacobs School of Medicine and Biomedical Sciences and CEO of the Jacobs Institute, performed indirect bypass, encephaloduroarteriosynagiosis (EDAS) surgery to restore adequate blood supply to the brain in three adults suffering from Moyamoya Disease (MMD). The surgeries took place at Buffalo General Medical Center/Gates Vascular Institute, Kaleida Health’s largest facility and hub for heart, vein and brain care.

“This advancement to first-in-human application builds on our 2024 preclinical study at the Jacobs Institute which confirmed Symani’s potential in brain surgery,” said Mark Toland, CEO of MMI. “Dr. Siddiqui’s cases demonstrate how Symani delivers the precision required for the delicate, highly skilled maneuvers that neurosurgery demands – capabilities that facilitate and potentially even exceed what the human hands alone can achieve. This milestone represents meaningful progress toward expanding robotic microsurgery into one of the most technically challenging areas of patient care.”

The investigational cases are part of an Early Feasibility Study approved by the FDA and sponsored by the Jacobs Institute, a nonprofit medical device innovation center that aims to accelerate the development of next-generation technologies in vascular and neurologic medicine. The study assesses the safety and preliminary effectiveness of Symani in performing robotic-assisted neurosurgery for adult patients with MMD. In general, surgical treatment aims to reduce the occurrence of stroke, seizures, paralysis, and vision problems for patients, including serious and permanent damage to the brain.

“This study represents so much more than foundational work for robotic brain surgery,” said Dr. Siddiqui. “The early success of these first brain surface cases, and the ability to perform minute surgical moves on the pulsating brain, should make the world as excited as it makes me and my esteemed peers in the neurosurgery community as we explore more ways Symani can revolutionize brain surgery.”

The Symani Surgical System is designed to provide enhanced precision and control for the anastomosis and suturing of microscopic vessels with the thinnest available sutures. It has been used in over 2,000 cases globally to provide life-changing care to patients in need of complex surgical treatment. Its impact in lymphatic surgery has been extensively demonstrated, and this study further supports its potential to address growing demands in the treatment of neurovascular disease and transform the lives of more patients through robotic capabilities.

Dr. Siddiqui will present these cases during the Hopkins Lecture at the Congress of Neurological Surgeons (CNS 2025 Annual Meeting) in Los Angeles, CA, on Tuesday, October 14. The lecture honors the late founder of the Jacobs Institute and a pioneering figure in neurosurgery.

The Symani Surgical System has not been evaluated or cleared by regulatory agencies for use in neurosurgical applications.

About Medical Microinstruments, Inc. (MMI)

MMI is on a mission to advance robotic technology that pushes the limits of soft tissue open surgery and opens new opportunities for surgeons to restore quality of life for more patients with complex conditions. Founded in 2015 near Pisa, Italy, the company’s Symani® Surgical System combines the world’s smallest wristed microinstruments with tremor-reducing and motion-scaling technologies to address significant unmet patient needs. The first-of-its-kind robotic platform for open, soft tissue micro-level surgery is FDA-cleared in the U.S. and CE Marked in Europe. MMI is backed by global investors including Fidelity Management & Research Company, Andera Partners, BioStar, Deerfield Management, Fountain Healthcare Partners, Panakès Partners, RA Capital, Sambatech, and Wellington Partners.

About the Jacobs Institute

The Jacobs Institute is a non-profit organization whose mission is to accelerate the development of next-generation technologies for vascular and neurologic diseases through collisions of physicians, engineers, entrepreneurs, and industry. The JI’s vision is to improve the treatment of vascular and neurologic disease in Western New York and the world, while fostering local economic development. The JI fosters medical collaboration and innovation through partnerships with the University of Buffalo (UB), Kaleida Health, and industry to be a fitting tribute to the work and memory of Lawrence D. Jacobs, MD. Additionally, the JI’s i2R, or Idea to Reality Center, is taking ideas for vascular and neurologic medical devices and moving them through the proof-of-concept process. Finally, the JI also increases physician and industry knowledge of vascular and neurologic diseases through clinical education programs.

Corteria Pharmaceuticals initiates Phase 2 trial in heart failure and Phase 1 trial in obesity with its first-in-class CRF2 agonists

• CRAFT-WHF Phase 2 trial of COR-1167 initiated in patients with worsening heart failure

• Phase 1 trial of COR-1389 ongoing in subjects with obesity

Corteria Pharmaceuticals, a clinical-stage biopharmaceutical company focused on the development of transformative therapies for heart failure and obesity, today announces the clinical advancement of its two first-in-class corticotropin‑releasing factor receptor 2 (CRF2) agonists, COR‑1167 and COR‑1389.

CRAFT-WHF Phase 2 trial of COR-1167 in worsening heart failure

COR-1167 is a once‑daily, subcutaneous CRF2 peptide agonist being developed for the treatment of worsening heart failure (WHF). In a randomized, placebo‑controlled Phase 1 trial, COR‑1167 was generally safe and well tolerated in healthy volunteers and patients with chronic heart failure. A single dose administered to patients demonstrated clear CRF2 target engagement based on improvement in a variety of cardiac function parameters, with no adverse impact on blood pressure.

Following the positive Phase 1 trial results, Corteria has initiated the CRAFT-WHF Phase 2 randomized, double-blind, placebo-controlled trial in patients with WHF (NCT06815471/EU CT 2024-518951-52). It will enroll a targeted 300 patients to assess the safety and cardiorenal effects of three different doses of COR-1167 administered for one month. Topline results are expected by the end of 2026.

Phase 1 trial of COR-1389 in obesity

COR-1389 is a long-acting once-weekly subcutaneous CRF2 peptide agonist being developed for the treatment of obesity with associated heart failure and right-sided heart failure due to pulmonary hypertension (Group 2).

A Phase 1 randomized, placebo‑controlled, trial of COR-1389 is ongoing (EU CT 2024-514853-31). The single ascending dose (SAD) phase investigating the safety, tolerability and pharmacokinetics in healthy volunteers has been completed and a 12-week multiple ascending dose (MAD) phase is now underway to assess the safety and efficacy of COR-1389 in subjects with obesity, including the evaluation of its effects on weight and body composition by whole-body MRI. Topline results are expected in the second half of 2026.

In a mouse model of diet induced obesity (DIO), COR-1389 showed substantial metabolic benefits associated with an increase in energy expenditure. It drove weight loss comparable to GLP1 agonists, while reducing fat mass and increasing lean (muscle) mass. When co-administered with tirzepatide or semaglutide, COR-1389 demonstrated additive benefits on fat loss while preventing the lean mass loss observed with these agents.

COR-1389 has also shown cardiopulmonary benefits in animal models of right-sided heart failure, improving cardiopulmonary hemodynamics and reversing maladaptive right ventricular and pulmonary artery remodeling. A Phase 1b trial is being planned to evaluate acute hemodynamic responses in patients with group 2 pulmonary hypertension, with topline results expected in the second half of 2026.

“Advancing both COR‑1167 and COR‑1389 in the clinic underscores our commitment to delivering first‑in‑class CRF2‑targeted therapies for patients with limited treatment options,” said Philip Janiak, founder and CEO of Corteria Pharmaceuticals. “The robust preclinical data, together with the emerging clinical data, strengthen our confidence as we move into Phase 2 and expand our footprint in cardiometabolic diseases.”

About Worsening Heart Failure

Chronic heart failure afflicts more than 60 million people worldwide. It is characterized by periods of clinical stability being frequently interrupted by episodes of worsening symptoms and signs, defined as worsening heart failure (WHF). Episodes of WHF impact more than 20% of heart failure patients and are among the most common causes for hospitalization, accelerating the progression of disease and resulting in substantial risk of morbidity and mortality. Given the central role of congestion in WHF, loop diuretics are the standard of care treatment. However, while effective acutely, these do not improve rehospitalization rates or patient outcomes. Therefore, WHF remains a critically important unmet medical need that continues to have a major impact on quality of life and imposes a major economic burden on the global healthcare system.

About Obesity with Associated Heart Failure

Obesity impacts more than one billion people worldwide and is a causal factor in heart failure and other serious health complications such as Type 2 diabetes, obstructive sleep apnea and sarcopenia. Implementing diet and exercise regimens are the first line of treatment, but this approach is frequently inadequate and can be accompanied by metabolic readjustment resulting in eventual regain of excess weight. The most effective currently available drug therapies for weight loss are GLP-1 and GLP-1/GIP peptides, but in many cases these drugs are associated with side effects such as bloating, nausea, and vomiting, leading to challenges with adherence and maintenance of weight loss. These therapies also often result in substantial loss of muscle mass, which can negatively impact patient health. Therefore, obesity remains a global health crisis and novel therapies are urgently needed that target fat loss with preserved lean mass, while also directly ameliorating comorbidities such as obesity-associated heart failure, which affects an estimated 30 million people worldwide.

About Right-Sided Heart Failure

Right-sided heart failure (RHF) is typically caused by pulmonary hypertension (PH) often associated with left-sided heart disease and afflicts approximately 10 million people worldwide. It is a fatal disease with no approved therapies and involves the development of right ventricular dysfunction (RVD) that leads to a progressive deterioration in exercise capacity and quality of life, and ultimately to a high risk of cardiovascular mortality. Despite therapeutic advances for left-sided heart disease, there are no therapies which specifically aim at improving RVD. Pulmonary vasodilators such as endothelin receptor antagonists, PDE-5 inhibitors and prostacyclin analogs are approved for pulmonary arterial hypertension, another smaller subgroup of PH, but these drugs have not been shown to be effective in the more common form of PH resulting from left-sided heart disease (classified as Group 2). The standard of care remains limited to diuretics for relieving symptoms of congestion. Therefore, novel therapies are urgently needed for the treatment of RHF due to Group 2 PH.

About Corteria Pharmaceuticals

Corteria is a privately held, clinical-stage biopharmaceutical company developing first-in-class medicines for the treatment of heart failure and obesity. The company is advancing a daily CRF2 peptide agonist, COR-1167, for the sub-chronic treatment of worsening heart failure; a long-acting once-weekly CRF2 peptide agonist, COR-1389, for the chronic treatment of obesity-associated heart failure and right-sided heart failure; and an arginine vasopressin neutralizing monoclonal antibody, COR-2007, for the treatment of acute heart failure with hyponatremia and autosomal dominant polycystic kidney disease.
www.corteriapharma.com

Contact

Stéphane Durant des Aulnois, CFO
Corteria Pharmaceuticals
stephane.durant_des_aulnois@corteriapharma.com

Andrew Lloyd & Associates
Juliette Schmitt / Saffiyah Khalique
juliette@ala.associates / saffiyah@ala.associates
UK: +44 1273 952 481
US: +1 203 724 5950

First Patient Dosed in XyloCor Therapeutics’ Phase 2b EXACT-2 Trial Evaluating XC001 for the Treatment of Coronary Artery Disease

• XC001 is a novel investigational therapy that previously demonstrated compelling efficacy and safety results, with disease-modifying potential, in patients with refractory angina in the EXACT-1 Phase 1/2 trial.

• In the global EXACT-2 trial, XC001 is injected directly into the heart muscle in a catheterization-lab setting, using the novel Extroducer® Infusion Catheter System, thereby eliminating the need for surgical administration.

XyloCor Therapeutics, a clinical-stage biopharmaceutical company focused on developing novel therapies for cardiovascular disease, announced the first patient has been dosed in the Phase 2b EXACT-2 trial, designed to evaluate its gene therapy candidate XC001 (encoberminogene rezmadenovec) in individuals with coronary artery disease and refractory angina. XC001 is an adenoviral vector-based gene therapy encoding for vascular endothelial growth factor (VEGF), uniquely designed as a one-time catheter-based treatment to reduce cardiac ischemia by creating new blood vessels in the heart and thereby reducing episodes of chest pain and improving patient ability to perform everyday activities. This percutaneous administration approach, injecting directly into the heart muscle, allows XC001 to achieve higher gene expression levels locally in the heart while minimizing systemic vector circulation and associated side effects.

“Initiating the EXACT-2 trial is an important milestone as we continue to develop XC001 for the treatment of refractory angina in patients who have exhausted available treatment options and have a debilitating quality of life,” said Albert Gianchetti, President and CEO of XyloCor. “Building on the positive results from EXACT-1, we are now focused on advancing the EXACT-2 trial to bring this potentially transformative treatment to patients as quickly as possible.”

EXACT-2 is a Phase 2b, multicenter, randomized, double-blind study in 100 patients with refractory angina to evaluate the safety and efficacy of a one-time gene therapy with XC001, delivered using the Extroducer® Infusion Catheter System, an endocardial delivery catheter designed to inject advanced therapies directly into the heart in a simple injection procedure in the cardiac catheterization lab. Additional information can be found here. The first patient was dosed by Timothy Henry, MD, at The Christ Hospital Health Network in Cincinnati, OH.

“After seeing the convincing results from the EXACT-1 trial, we were eager to participate in EXACT-2,” commented Dr. Timothy Henry, a cardiovascular interventionist and the Lindner Family Distinguished Chair in Clinical Research and Medical Director of The Carl and Edyth Lindner Center for Research at The Christ Hospital. “We believe that XC001 delivered through the Extroducer® Infusion Catheter System will maintain the accuracy of delivery of XC001 to the heart and improve the safety over the surgical administration approach used in EXACT-1.”

The XC001 Phase 1/2 EXACT-1 trial results supported the transformative, disease-modifying potential of XC001 to reduce cardiac ischemia, reduce anginal symptoms and improve the quality ‑of ‑life for cardiac patients who have no other treatment options. The results demonstrated the potential for XC001 to be safely administered and achieve durable clinical improvements, including increases in exercise duration, decrease in ischemic burden as measured by Positron Emission Tomography (PET) imaging and a reduction in angina frequency. Notably, 93% of patients in the trial entered with chest pain so severe that it markedly limited daily activities, whereas at six months 43% reported no chest pain with ordinary activities. XC001 was well tolerated in the patient population and there were no serious adverse events related to the study drug.

XyloCor is also initiating a second clinical trial this year – a double-blind Phase 2 trial of XC001 as an adjunctive treatment to coronary artery bypass graft surgery (CABG).

About XC001

XC001 is designed to reduce cardiac ischemia by creating new blood vessels in the heart that will bypass diseased blood vessels and improve blood flow. By restoring blood flow, chest pain associated with refractory angina may decrease, potentially improving patients’ quality of life by enabling them to engage in daily physical activities that would otherwise cause pain. XC001 is designed to avoid toxicity issues observed with other gene therapies through a strategy of one-time, local administration and delivery through an adenoviral vector. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects.

About Extroducer® Infusion Catheter System

The Extroducer® Infusion Catheter System is a first-in-class endovascular delivery device which enables direct-to-tissue drug delivery. The Extroducer® addresses a significant unmet need in the field of novel therapies, enabling targeted delivery of a wide range of treatment modalities to otherwise hard to reach tumors and organs. Using standard fluoroscopy equipment and routine interventional radiology approaches, the Extroducer provides access to hard-to-reach tissues by safely penetrating the vessel wall and delivering payload directly to the target location, or inside the heart ventricle. Smartwise received U.S. Food and Drug Administration (FDA) clearance under 510(k) for the Extroducer® delivery catheter in June 2022. In 2024, XyloCor entered into a licensing agreement with SmartWise, a unit of SmartCella, to deliver XC001 via the Extroducer® Infusion Catheter System.

About Chronic Refractory Angina

In the United States, coronary artery disease is a leading cause of death and disability. Chronic angina pectoris occurs when the heart muscle does not receive sufficient oxygen, resulting in chest pain. This is usually due to atherosclerotic plaques that block the coronary arteries. Refractory angina is a growing problem that occurs in patients with chronic angina who are symptomatic despite optimal medical therapy and are no longer eligible for mechanical interventions like percutaneous coronary intervention (PCI) and coronary artery bypass gracing (CABG). These patients currently have no treatment options and are frequently highly symptomatic, which severely impacts their quality of life, and may exacerbate comorbidities and cause further deterioration of their health status. Refractory angina results in significant consumption of healthcare resources, including visits to the emergency department as a result of patients’ chest pain.

About XyloCor

XyloCor Therapeutics, Inc. is a private, clinical-stage biopharmaceutical company developing potential best-in-class gene therapies to transform outcomes for patients with cardiovascular disease. The Company’s lead product candidate, XC001, is in clinical development for use in patients with coronary artery disease and refractory angina for whom there are no treatment options. XyloCor has a second preclinical investigational product, XC002, in the discovery stage, being developed for the treatment of patients with cardiac tissue damage from heart attacks. The company, which was co‑founded by Ronald Crystal, MD, and Todd Rosengart, MD, has an exclusive license from Cornell University. For more information, visit www.xylocor.com.

About SmartCella

SmartCella, founded in 2014, is a global biotech company pioneering the future of targeted therapies through delivery solutions and advanced therapy development. SmartCella combines novel delivery platforms, such as the Extroducer® (an endovascular delivery device that enables direct injection to hard-to-reach organs and tumors), with cutting-edge development and manufacturing of cell therapies. For more information, visit www.smartcella.com.

Contacts

XyloCor Corporate and Investor Relations Contact:
A. Brian Davis, XyloCor Therapeutics
brian.davis@xylocor.com
610-541-2056

XyloCor Media Contact:
Mike Beyer
Sam Brown Inc. Healthcare Communications
mikebeyer@sambrown.com
312-961-2502

Priothera Secures EUR1.7 million i-Nov Funding by Bpifrance for Rare Blood Cancer Clinical Program

Funding to support MOCART, a clinical programme evaluating mocravimod added to standard CAR-T cell therapy

Priothera, a late-stage biopharma company pioneering the development of mocravimod, a novel oral sphingosine 1 phosphate (S1P) receptor modulator, to treat hematologic malignancies, today announced that it has been awarded nearly EUR1.7 million in non-dilutive funding through the i-Nov innovation competition. Part of the France 2030 initiative, i-Nov is a flagship French government program operated by Bpifrance to support breakthrough innovation from high-potential French companies across strategic sectors. The funding will support Priothera's clinical programme to evaluate whether adding mocravimod to commercial CAR-T cell therapies could improve patient outcomes.

CAR-T cell therapies represent a novel and promising modality for the treatment of hematological malignancies. They have demonstrated the potential for remarkable clinical responses and durable disease control in patients with acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma and multiple myeloma. However, their use is still associated with significant challenges, as 40-60% of patients treated with CAR-T cells experience high-grade toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), a form of severe neurological toxicity.

Mocravimod is a novel, oral S1P receptor modulator with a unique dual mechanism of action that has the potential to enhance the effectiveness of CAR-T cell therapy by:

• Reducing the incidence and severity of CRS and ICANS, and

• Improving response rates and durability of treatment

"We are honoured to receive this i-Nov funding from Bpifrance, which underscores the innovation and therapeutic potential of mocravimod beyond allo-HCT," said Florent Gros, Co-Founder and CEO of Priothera. "With its unique immunomodulatory properties, mocravimod is well-positioned to become a key component in the next generation of cell therapy regimens. The MOCART trial represents an exciting expansion of our clinical development into CAR-T therapy, building on our deep expertise in allo-HCT and momentum from our ongoing global Phase 3 MO-TRANS trial in acute myeloid leukemia."

Priothera continues to advance mocravimod in the MO-TRANS global Phase 3 study for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The company remains focused on unlocking the full therapeutic potential of S1P receptor modulation across multiple settings in blood cancers.

About mocravimod

Mocravimod (KRP203) is a synthetic S1P receptor modulator being developed for the adjunctive and maintenance treatment of AML to enhance the curative potential of allo-HCT. Mocravimod's dual mechanism of action preserves the graft-versus-leukemia (GvL) effect, critical for eliminating cancer cells while reducing the risk of graft-versus-host disease (GvHD), a major complication following allo-HCT. This novel treatment approach -- mocravimod being the only S1P receptor modulator in development to treat blood cancers -- tackles a high unmet medical need and aims to improve treatment outcomes and patients' quality of life.

About Priothera

Priothera is a late-stage biopharma company pioneering the development of mocravimod, a potential new standard of care in hematologic cancers, in addition to cellular therapies such as hematopoietic cell transplantation and CAR-T cell therapies. Mocravimod is being developed as an adjunctive and maintenance therapy for hematological malignancies requiring allogeneic hematopoietic cell transplant (allo-HCT), focusing initially on acute myeloid leukemia (AML). Mocravimod is currently the only treatment with the potential to reduce transplant side effects of graft-versus-host disease (GvHD) without compromising the graft's anticancer effect against leukemia (Graft-versus-Leukemia, or GvL), thereby enhancing the curative potential of allo-HCT.

Founded in 2020, Priothera operates in France, with headquarters in Dublin. The company is led by a highly experienced management team with deep expertise in hematology, oncology, immunology and cell-based therapies. Priothera is backed by leading international life sciences investors, including Fountain Healthcare Partners, abrdn, EarlyBird Venture Capital, BEI and Bpifrance Grand Est.

For more information please visit www.priothera.com or follow Priothera on LinkedIn www.linkedin.com/company/priothera/

Vivasure Medical Submits PMA Application for PerQseal® Elite and Secures Expanded Venous Indication in Europe

Regulatory progress underscores global momentum for PerQseal Elite in transforming large-bore vascular closure

Vivasure Medical®, a company pioneering novel fully absorbable technology for percutaneous vessel closure, today announced the submission of a Premarket Approval (PMA) application to the U.S. Food and Drug Administration (FDA) for its PerQseal® Elite vascular closure system for arterial procedures. The submission builds upon the successful results of the PATCH study as well as positive clinical use in Europe, reinforcing the system’s potential safety and performance profile. In addition, the company received European CE mark approval for an expanded indication for PerQseal Elite covering large-bore venous closure. This follows its first CE mark approval in April 2025 for arterial procedures and positions PerQseal Elite as the first fully bioresorbable, sutureless solution in Europe for both arterial and venous access closure.

“With the increasing adoption of minimally invasive therapies in structural heart and electrophysiology procedures, managing large-bore access sites remains a critical consideration,” said Azeem Latib, M.D., section head and director of interventional cardiology and director of structural heart interventions at Montefiore Health System in New York City. “PerQseal Elite was designed to address the growing need with a novel, fully bioabsorbable approach and we look forward to further progress in the program.”

Leveraging Vivasure’s PerQseal technology, the PerQseal Elite vascular closure system is designed for fully absorbable, sutureless closure following percutaneous cardiovascular procedures. Currently, there are no fully bioresorbable devices available on the market for closure following large-bore procedures. Moreover, unlike other current devices, PerQseal Elite does not require any pre-procedure steps, further simplifying the process.

“We are proud to advance PerQseal Elite through these two key regulatory milestones as part of our commitment to delivering next-generation technologies for large-bore vascular closure,” said Andrew Glass, CEO of Vivasure Medical. “Achieving CE mark expansion for venous indications and submitting our PMA application are important steps toward making our fully absorbable, sutureless solution more broadly accessible, while continuing to build a strong foundation for global commercial growth.”

The PerQseal Elite vascular closure system is placed from inside the vessel, making deployment simpler and more controlled than conventional closure techniques and returning the vessel to its natural state without leaving materials like collagen, metal implants, or sutures behind.

About Vivasure Medical

Based in Galway, Ireland, Vivasure is focused on the development of advanced polymer implants and delivery systems, primarily focused on minimally invasive vessel closure in cardiology, interventional radiology, and vascular surgery. Vivasure operates a fully integrated R&D and ISO 13485 certified manufacturing facility and is backed by leading international medtech investors. For more information, please visit www.vivasuremedical.com.

In 2023, Vivasure Medical received a €30 million strategic investment from Haemonetics Corporation (NYSE: HAE), in an agreement which includes an option to acquire Vivasure Medical upon completion of certain milestones. The company is also backed by Fountain Healthcare Partners, Orchestra BioMed Holdings Inc. (Nasdaq: OBIO), LSP Health Economics Fund managed by the EQT Life Sciences team, Panakès Partners, and Evonik Venture Capital. In addition, Vivasure Medical has received support from Enterprise Ireland and the European Investment Bank.

The PerQseal® and PerQseal® Elite are not available for sale in the United States.

Neurent Medical Announces 510(k) Clearance of its Next Generation NEUROMARK® System

Developed in Collaboration with Leading ENT Experts, the Enhanced NEUROMARK® System Reflects Meaningful Innovation and Delivers Real-Time Feedback to Improve Patient Care

Neurent Medical, a leader in pioneering non-surgical solutions for chronic sinonasal inflammatory diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted 510(k) clearance for the company's Next Generation NEUROMARK®  System, marking a major milestone in advancing care for patients suffering from Chronic Rhinitis. This latest advancement in the NEUROMARK platform delivers a new level of control, confirmation, and confidence for otolaryngologists.  

The new system is designed to optimize the treatment of posterior nasal nerves by providing real-time feedback, guiding proper electrode placement, and confirming successful treatment delivery. The flexible shaft and atraumatic leaflets conform to patient anatomy, enabling physicians to reach challenging areas in the nasal cavity while maximizing treatment coverage. The NEUROMARK System delivers impedance-controlled, low-power radiofrequency (RF) energy to disrupt the parasympathetic nerve signals, addressing key symptoms of Chronic Rhinitis such as persistent nasal congestion and rhinorrhea (runny nose).

"We have just completed a highly successful commercial validation phase, positioning the NEUROMARK system at the forefront of Chronic Rhinitis care," said Brian Shields, CEO of Neurent Medical. "During this phase, we have collaborated with leading General ENT and Rhinology specialists across both private practice and academic settings. Their insights were instrumental in shaping this next-generation system. I am incredibly proud of how their feedback translated into meaningful technological improvements. This milestone highlights our continued commitment to innovations that empowers ENTs to treat patients with greater confidence."

"I have worked closely with the Neurent Medical team from the beginning and continue to be impressed by their dedication to ENT surgeons and our patients." said Dr. Marc Dubin, Chief Medical Officer, ENT Specialty Partners. "The latest generation of the NEUROMARK System reflects this commitment, incorporating usability enhancements and real- time feedback capabilities to support precise treatment delivery."

This FDA clearance paves the way for broader U.S. availability of the NEUROMARK System as Neurent Medical continues its mission to redefine the standard of care for Chronic Rhinitis, affecting nearly 1 in 4 Americans1.

About Neurent Medical

Neurent Medical is pioneering innovative treatments for chronic inflammatory sinonasal diseases by targeting and safely disrupting hyperactive autonomic nerves that drive underlying inflammation. Its proprietary NEUROMARK® technology, with a unique design and advanced smart algorithmic control, allows physicians to precisely target and safely disrupt multiple underlying nerve branches in a single procedure to alleviate chronic rhinitis symptoms and improve patient quality of life. The venture capital-backed company is headquartered in Galway, Ireland, with US HQ in Braintree, MA. For more information visit www.neuromark.com.

1. Settipane RA, Charnock DR. Epidemiology of rhinitis: allergic and nonallergic. Clin Allergy Immunol. 2007;19:23-34

Priothera Strengthens Board with Appointment of Industry Veteran, Dr. Hans Menssen

Highly experienced clinical development executive joins Priothera Board as mocravimod progresses through global Phase 3 trial as adjunctive and maintenance treatment in AML patients undergoing allo-HCT

Priothera Ltd., a late-stage biopharma company pioneering the development of mocravimod, a novel oral sphingosine 1 phosphate (S1P) receptor modulator, to treat hematologic malignancies, today announced the appointment of Dr. Hans Menssen, MD, PhD, BBA, to its Board of Directors.

Dr. Menssen most recently served as Senior Global Program Clinical Head at Novartis Oncology, where he led clinical programs across acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), multiple myeloma, chronic myeloid leukemia (CML), myelofibrosis, acute and chronic GvHD, and B-cell malignancies, with a focus on registration-stage development. Over his career, in addition to Novartis, he has held senior roles at Bayer Schering Pharma and Philogen SpA, with a track record of supporting oncology innovation across modalities including small molecules, antibodies, and cell therapies.

"Hans brings deep strategic insight in hematology, clinical development, and regulatory science," said Florent Gros, Co-Founder and CEO of Priothera. "His experience across global drug development programs and his understanding of what it takes to bring innovative therapies to patients will make him a valuable voice on our Board as we progress the global Phase 3 MO-TRANS study of mocravimod in AML patients undergoing allo-HCT. We are very pleased to welcome him to the Board."

A board-certified hematologist and oncologist, Dr. Menssen also holds academic appointments at Charité -- University Medicine Berlin in his capacity as assistant professor (Priv-Doz. Dr. med), where he continues to teach and supervise medical research. He has contributed to numerous clinical and translational research efforts throughout his career. He earned his medical degree from the University of Cologne, completed postdoctoral research at the Wistar Institute at the University of Pennsylvania, and holds a Bachelor of Business Administration in health economics from GSBA Zurich in partnership with SUNY (State University of New York).

"I am very pleased to join Priothera's Board at such a key point in its evolution," said Dr. Hans Menssen. "Mocravimod represents a promising and differentiated approach to improving outcomes in AML patients undergoing allo-HCT, and I look forward to supporting the team in advancing this important program."

Priothera's Board of Directors is composed of:

• Dr. Manus Rogan (Chair) -- Managing Partner, Fountain Healthcare Partners

• Mr. Florent Gros - CEO

• Dr. Marten Steen -- Managing Partner, Healthcap Ventures

• Dr. Henry Skinner -- CEO, AMR Action Fund

• Mr. Lionel Carnot -- Partner, Earlybird Health

• Dr. Hans Menssen -- former Senior Global Program Clinical Head, Novartis Oncology

Priothera Appoints Dr. Jens Hasskarl as Chief Medical Officer to Drive Late-Stage Clinical Development of Mocravimod, a S1P Receptor Modulator for Acute Myeloid Leukemia (AML)

Dr. Hasskarl to lead global Phase 3 MO-TRANS study evaluating mocravimod as an adjunctive treatment to allo-HCT in AML

Priothera Ltd., a late-stage biopharma company pioneering the development of mocravimod, a novel oral sphingosine 1 phosphate (S1P) receptor modulator, to treat hematologic malignancies, today announced the appointment of Jens Hasskarl, MD, PhD, as Chief Medical Officer (CMO). Dr. Hasskarl will oversee the global Phase 3 clinical study MO-TRANS of mocravimod, which is being developed as an adjunctive treatment in acute myeloid leukemia (AML) to enhance the curative potential of allogeneic hematopoietic cell transplantation (allo-HCT).

Dr. Hasskarl brings over two decades of international leadership experience in clinical development, translational science and medical affairs across top-tier pharma, biotech and academic institutions. Most recently, he served as CMO at Advesya AG, where he led the strategic development of novel immunotherapies in haemato-oncology and autoimmunity. He previously held senior executive roles at Tigen Pharma, Celgene and Novartis, where he was instrumental in the development and global approval of multiple cellular therapies including Breyanzi®, Abecma® and Kymriah®.

"Jens’ deep expertise in hematology, cellular therapy and translational drug development, combined with his entrepreneurial mindset and proven track record in leading successful global clinical programs, make him the ideal fit," said Florent Gros, Co-Founder and CEO of Priothera. "His insight and leadership will be critical as we prepare for the final phase of clinical execution and regulatory engagement for mocravimod. We would like to thank Dr. Elisabeth Kueenburg, Priothera’s former CMO, for her contributions and wish her every success in her future endeavors."

“I am thrilled to join Priothera during such an exciting phase,” said Dr. Hasskarl, CMO of Priothera. “The company’s science-driven approach and commitment to improving outcomes for patients with AML aligns perfectly with my focus on advancing innovation in hematology. I look forward to working closely with the team to bring this promising therapy to patients worldwide.”

Dr. Hasskarl holds an MD and PhD from Heidelberg University and the German Cancer Research Center. He completed a postdoctoral fellowship at Harvard Medical School and holds a diploma in Health Economics. He is a board-certified Internist with a specialty in hematology and oncology and continues to lecture at Freiburg Medical School in Germany.

About mocravimod

Mocravimod (KRP203) is a synthetic S1P receptor modulator being developed for the adjunctive treatment of AML to enhance the curative potential of allo-HCT. Mocravimod’s dual mechanism of action preserves the graft-versus-leukemia (GvL) effect, critical for eliminating cancer cells while reducing the risk of graft-versus-host disease (GvHD), a major complication following allo-HCT. This novel treatment approach – mocravimod being the only S1P receptor modulator in development to treat blood cancers – tackles a high unmet medical need and aims to improve patients’ quality of life.

About Priothera

Priothera is a late-stage biopharma company pioneering the development of mocravimod, a potential new standard of care in hematologic cancers, in combination with cellular therapies such as hematopoietic cell transplantation and CAR-T cell therapies. Mocravimod is being developed as an adjunctive and maintenance therapy for hematological malignancies, focusing initially on acute myeloid leukemia (AML), in combination with allogeneic hematopoietic cell transplant (allo-HCT). Mocravimod is currently the only treatment with the potential to reduce transplant side effects of graft-versus-host disease (GvHD) without compromising the graft’s anticancer effect against leukemia (Graft-versus-Leukemia, or GvL), thereby enhancing the curative potential of allo-HCT.

Founded in 2020, Priothera operates in France, with headquarters in Dublin. The company is led by a highly experienced management team with deep expertise in hematology, oncology, immunology and cell-based therapies. Priothera is backed by leading international life sciences investors, including Fountain Healthcare Partners, abrdn, EarlyBird Venture Capital, BEI and Bpifrance Grand Est.

For more information please visit www.priothera.com or follow Priothera on LinkedIn www.linkedin.com/company/priothera/

Contacts:

Florent Gros, CEO
E: info@priothera.com

Mainstay Medical Announces Exclusive Coverage of ReActiv8® by Anthem Blue Cross/Blue Shield

Mainstay Medical Holdings plc today announced that Anthem Blue Cross and Blue Shield (“Anthem”) has established favorable coverage for the company’s ReActiv8 Restorative NeurostimulationTM therapy for the treatment of intractable chronic low back pain. ReActiv8 is the only therapy considered medically necessary by the policy when the conditions for coverage are met. The coverage went into effect on April 16, 2025, and expands access to the procedure, when clinically appropriate, to Anthem’s policyholders.

“We have been on a 17-year mission to prove the value of ReActiv8 through careful and thorough research,” said Jason Hannon, CEO of Mainstay Medical. “We have made a commitment to developing a large body of robust clinical and real-world evidence proving the efficacy and safety of the therapy in an indication where patients are desperately seeking durable solutions. We are pleased to see a leading payer like Anthem recognize the evidence we have built, and we look forward to discussing our data with other major health plans with the goal of securing further coverage for ReActiv8. Our evidence has been generated by scores of clinical investigators around the world who care for chronic back pain patients. We are extremely grateful for the work these physicians continue to do.”

Under its policy, Anthem considers ReActiv8 to be medically necessary for the treatment of chronic low back pain when a number of clinical criteria are met. These include a diagnosis of lumbar multifidus muscle dysfunction and patient selection criteria consistent with FDA approval guidelines and Mainstay’s clinical trial protocols.

About ReActiv8®

ReActiv8 is an implantable medical device designed to treat adults with intractable chronic low back pain (CLBP) associated with multifidus muscle dysfunction, which may be evidenced by imaging or physiological testing. Candidates for ReActiv8 are patients with multifidus muscle dysfunction who have failed other forms of therapy (including pain medication and physical therapy) and are not candidates for spine surgery. ReActiv8 has received regulatory approval in several geographic areas, and is commercially available in the European Economic Area, Australia, the UK, and the US.

About Mainstay Medical

Mainstay Medical is a medical device company focused on commercializing its innovative implantable Restorative NeurostimulationTM system, ReActiv8®, for people with disabling mechanical CLBP. Mainstay Medical is headquartered in Dublin, Ireland and has subsidiaries operating in Ireland, the United States, Australia, Germany, and the Netherlands.

Further information can be found at www.mainstaymedical.com.

Vivasure Medical Receives CE Mark Approval in Europe for PerQseal Elite Vascular Closure System

First fully absorbable, sutureless closure system designed for large-bore procedures aims to improve procedural efficiency and patient outcomes in structural heart interventions

Vivasure Medical®, a company pioneering novel fully absorbable technology for percutaneous vessel closure, today announced European CE mark approval of the PerQseal® Elite vascular closure system, a sutureless and fully bioresorbable large-bore vessel closure device. The company plans to launch the product in select European markets this summer.

Leveraging Vivasure’s PerQseal technology, the PerQseal Elite vascular closure system is designed exclusively for sutureless and fully absorbable large-bore closure following percutaneous cardiovascular procedures such as transcatheter aortic valve replacement (TAVR) and Endovascular Aortic Repair (EVAR). Currently, there are no fully bioresorbable devices available for closure following large-bore procedures. Moreover, unlike other current devices, PerQseal Elite does not require any pre-procedure step, further simplifying the procedure.

“Vascular closure remains a challenge for the growing cardiovascular procedures that require large bore access. The introduction of PerQseal Elite is an exciting advancement for large-bore cardiovascular procedures,” said Dr. Mohamed Abdel-Wahab, Professor of Interventional Cardiology and Head of Structural Heart Disease Department at the Heart Center in Leipzig, Germany. “Having a fully absorbable, sutureless closure option simplifies the procedure and has the potential to reduce complications associated with traditional closure methods. We look forward to utilizing this technology to treat our patients.”

“Securing CE Mark approval for PerQseal Elite marks a major milestone for Vivasure and for patients undergoing complex structural heart procedures,” said Andrew Glass, CEO of Vivasure Medical. “PerQseal Elite represents a significant advancement in procedural efficiency and patient care. We’re proud to bring this innovative technology to clinicians across Europe.”

The PerQseal Elite vascular closure system is placed from inside the vessel, making deployment simpler and more controlled than conventional closure techniques and returning the vessel to its natural state without leaving materials like collagen, metal implants or sutures behind.

About Vivasure Medical

Based in Galway, Ireland, Vivasure is focused on the development of advanced polymer implants and delivery systems, primarily focused on minimally invasive vessel closure in cardiology, interventional radiology and vascular surgery. Vivasure operates a fully integrated R&D and ISO 13485 certified manufacturing facility and is backed by leading international medtech investors. For more information, please visit www.vivasuremedical.com.

In 2023, Vivasure Medical received a €30 million strategic investment from Haemonetics Corporation (NYSE: HAE), in an agreement which includes an option to acquire Vivasure Medical upon completion of certain milestones. The company is also backed by Fountain Healthcare Partners, Orchestra BioMed Holdings Inc. (Nasdaq: OBIO), LSP Health Economics Fund managed by the EQT Life Sciences team, Panakès Partners and Evonik Venture Capital. In addition, Vivasure Medical has received support from Enterprise Ireland and the European Investment Bank.

The PerQseal® and PerQseal® Elite are not available for sale in the United States.

Neuromod Closes €10m Financing to Accelerate Commercialisation

• Financing led by existing investors Fountain Healthcare Partners and Panakès Partners

• Neuromod will use funds to accelerate commercialisation in the USA and Europe.

Neuromod Devices Ltd. (Neuromod), an Irish medical device company specialising in tinnitus, has successfully closed a €10 million equity financing to expand the availability of its tinnitus treatment device, Lenire.

Oversubscribed Financing to Drive Commercialisation

Neuromod has raised €10 million of equity in an expansion of its Series B fundraisings. The financing was oversubscribed and was led by existing investors Fountain Healthcare Partners and Panakès Partners, backing Neuromod’s mission to advance tinnitus care for patients globally.

Neuromod has been making Lenire available through audiology and ENT practices throughout the USA and Europe. Proceeds from the financing will be used to meet demand for Lenire through sustainable commercial expansion in the USA and Europe and expand on existing opportunities in the US Department of Veteran Affairs (USVA).

Following FDA approval in March 2023, more than 100 clinics throughout the USA now treat tinnitus patients with Lenire. Availability of Lenire has also expanded in Europe with clinics in 14 countries now using the device. In the last 6 months, the number of clinics in the UK trained to use Lenire has doubled, and it is available to patients in Sweden for the first time.

In June 2024, Neuromod was awarded a Federal Supply Schedule 65 II Medical Equipment and Supply Contract from the US Government, making Lenire a treatment option for the 2.9 million US Veterans living with tinnitus [v] through the USVA.

35 USVA facilities have been trained to provide treatment with Lenire with more scheduled for training in 2025.

Real-World Evidence – Substantial Momentum

Positive results for tinnitus patients treated with Lenire in real-world settings at independent USA-based clinics have been compiled with a base of over 1,500 patients that continues to grow. In what will be the first of a series of planned real-world evidence publications, results from Alaska Hearing & Tinnitus Center showed that 91.5% of 220 patients reported clinically significant improvement in their tinnitus [vi]. This data is consistent with, and in many instances outperforms, data from Lenire’s large-scale clinical trials.

These results followed the publication of Lenire’s pivotal controlled clinical trial results, which led to US FDA approval and featured as the cover-story in peer-reviewed journal, Nature Communications [iv]. This article is in the 99th percentile of more than 250,000 tracked Nature articles.

Neuromod Closes €10m Financing Comments

Commenting on the news, Dr. Ross O’Neill PhD, Founder & CEO of Neuromod said “We are delighted to announce an oversubscribed financing at a pivotal time when we are driving forward with our mission of making Neuromod the category creator for tinnitus globally.”

“Tinnitus is the largest unmet need in hearing healthcare globally and is the number one service-connected disability among US veterans and military personnel. I am proud of the progress Neuromod is making to deliver our market-surpassing treatment to as many tinnitus patients as possible while enabling care providers’ expertise to be commercially rewarded. I am also grateful for the continued support of our investors who share our vision of advancing tinnitus care globally.” Dr. O’Neill continued.

Dr. Manus Rogan, Chairman of Neuromod and Managing Partner of Fountain Healthcare Partners commented, “Recent results from tinnitus patients using Lenire in the real-world show that it represents a new standard of care for tinnitus. The successful closing of this financing ensures more patients will get access to this standard of care as quickly as possible.”

Alessio Beverina, Managing Partner of Panakès Partners said, “Panakès is pleased with the progress of Neuromod since our investment, with significant clinical trial, FDA approval, real-world evidence, and commercial success in both Europe and the USA; and it is proud to continue supporting Neuromod’s work to bring a new standard of care to a historically underserved patient population.”

Emily E. McMahan, Owner of Alaska Hearing and Tinnitus Center and author of the clinic’s Real World Evidence Paper said, “Impressive clinical trial results for Lenire led me to early adoption of the landmark tinnitus treatment technology.”

“In my clinic, and my colleagues’ clinics, we are seeing results that are superior to clinical trial results.” Dr. McMahan continued.

About Neuromod Devices Ltd

Founded in 2010, Neuromod Devices Ltd. is a medical technology company headquartered in Dublin, Ireland. Neuromod specialises in the design, development, and commercialisation of neuromodulation technologies to address the clinical needs of underserved patient populations who live with chronic and debilitating conditions. The lead application of Neuromod’s technology is in the field of tinnitus, where Neuromod has completed extensive clinical trials to confirm the efficacy of its non-invasive neuromodulation platform in this common disorder. For more information visit www.neuromoddevices.com.

About Tinnitus

Tinnitus, commonly known as ‘ringing in the ears’, is a complex neurological condition that causes a perception of sound when there is no external source. Tinnitus affects an estimated 15% of the global adult population.

The management of tinnitus poses significant burden on healthcare systems. A 2021 study estimated the socioeconomic costs of tinnitus in Germany at €21.9 billion per annum. In the USA it’s estimated the Veterans Benefits Administration paid out approximately $5.8 billion through its Veterans Compensation benefits program for tinnitus in 2023.

The American Tinnitus Association, the leading advocacy body in the USA for people living with the condition, has recently revised its estimate that 50 million Americans live with tinnitus upward to 70 million.

About Lenire

Lenire is the first non-invasive bimodal neuromodulation tinnitus treatment device shown to soothe and relieve tinnitus in a large-scale clinical trial. Lenire works by delivering mild electrical pulses to the tongue, through an intra-oral component called the ‘Tonguetip®’, combined with auditory stimulation through headphones. This combination drives changes in the brain to treat tinnitus. To date, the device has been used in large-scale clinical trials with over 700 patients.

Lenire has CE-mark certification for the treatment of tinnitus under the supervision of an appropriately qualified healthcare professional in Europe and has received a De Novo grant of approval by the US FDA. Further details about Lenire including a list of providers can be found at www.lenire.com.

Connect with Neuromod

LinkedIn: linkedin.com/neuromod
X: x.com/NeuromodDevices
Facebook: facebook.com/neuromoddevices/

References & Notes

(i) Baguely et al., Tinnitus, The Lancet (2013), sciencedirect.com/science/article/pii/S0140673613601427
(ii) Conlon et al., Sci. Transl. Med. 12, eabb2830 (2020)
(iii) Conlon et al., Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial, Sci Rep, doi.org/10.1038/s41598-022-13875-x (2022)
(iv) Boedts M, B. A., Khoo G, et al. Combining sound with tongue stimulation for the treatment of tinnitus: a controlled pivotal trial. Nature communications (2024)
(v) US VA Benefits Report Fiscal Year 2023: https://www.benefits.va.gov/REPORTS/abr/
(vi) McMahan, E.E. and Lim, H.H., 2024. Effectiveness of bimodal neuromodulation for tinnitus treatment in a real-world clinical setting in United States: A retrospective chart review. medRxiv., pp.2024-08; doi: https://doi.org/10.1101/2024.08.22.24312175 [preprint]
(vii) Tziridis K, Friedrich J, Brüeggemann P, Mazurek B, Schulze H. Estimation of Tinnitus-Related Socioeconomic Costs in Germany. Int J Environ Res Public Health. 2022 Aug 22;19(16):10455. doi: 10.3390/ijerph191610455. PMID: 36012089; PMCID: PMC9407899.
(viii) https://www.linkedin.com/posts/patrickalynch_tinnitus-activity-7270503831304654848-VbWN/

Mainstay Medical Announces Positive Outcomes from Landmark RESTORE Clinical Trial of ReActiv8®

• ReActiv8® Restorative NeurostimulationTM demonstrated statistically significant and clinically meaningful superiority vs. standard of care in all primary and secondary measures of disability, pain and quality of life

• Safety profile consistent with prior ReActiv8 clinical trials and favourable to other neuromodulation procedures

• ReActiv8 is now supported by the most complete and robust set of clinical evidence of any neuromodulation therapy for axial back pain globally.

Mainstay Medical Holdings plc today announced the publication of positive one-year primary assessment results of the RESTORE randomized clinical trial of ReActiv8 for the treatment of intractable chronic low back pain. The data show that the addition of ReActiv8 Restorative Neurostimulation therapy to current standard of care results in superior improvements in back pain-related disability, pain and quality of life compared to standard of care treatments alone. The results were published in Pain and Therapy, a leading peer-reviewed journal, and the article is available free of charge here: doi.org/10.1007/s40122-024-00689-0.

The study included 203 patients, with 99 randomized into the treatment arm and 104 randomized into the control arm. Key results from the study include:

• The primary endpoint of the mean improvement in Oswestry Disability Index (ODI) score between the treatment and control arms at the one-year follow-up visit (using mixed model for repeated measures (MMRM) for missing data) was statistically significant (p<0.001), with a clinically meaningful mean change in the ReActiv8 group compared to the control arm: ODI -19.7 ± 1.4 for the ReActiv8 group vs. -2.9 ± 1.4 for the control group.

• All secondary endpoints showed statistically significant differences between the ReActiv8 and control arms (using MMRM for missing data), as well as clinically meaningful improvements for the ReActiv8 arm, at one year, including:

  • Mean improvement in back pain measured using the 11-point Numeric Rating Scale (NRS): -3.6 ± 0.2 for the ReActiv8 group vs. -0.6 ± 0.2 for the control group (p<0.001); and

  • Mean improvement in healthcare related quality of life measured using the EQ-5D-5L assessment: +0.155 ± 0.012 for the ReActiv8 group vs. +0.008 ± 0.012 for the control group (p<0.001). The improvement in the ReActiv8 group resulted in a mean quality of life score approaching the average quality of life score from the overall US population.

• The proportion of patients who reached the composite endpoint of ∶15-point ODI improvement and/or ≥ 50% NRS improvement and no worsening in either measure at one year was 72% in the ReActiv8 group and 11% in the control group (p< 0.001).

• Pain remission, defined as NRS of ≤ 3 at one year, was observed in 52% of patients in the ReActiv8 group and in 6% of those in the control group.

• The profile of related adverse events was similar to previously reported ReActiv8 studies and favourable to other neuromodulation treatment procedures.

“This patient population has historically had extremely limited options beyond temporary palliative treatments and drugs. The results in this study demonstrated that ReActiv8 Restorative Neurostimulation provided superior improvements to the lives of patients above and beyond what is currently used to treat them,” said the steering committee of the RESTORE study, Dr. Frank Schwab, Dr. Chris Gilligan, Dr. Nagy Mekhail, and Dr. Kiran Patel. “These exciting results further validate ReActiv8’s restorative mechanism of action treating multifidus dysfunction, a primary underlying cause of mechanical chronic lower back pain in certain patients. Combining these impressive results with the newly-issued ICD-10 code for multifidus dysfunction, this study further demonstrates the ability of clinicians to confidently select and treat patients with chronic mechanical low back pain who were previously very difficult to treat.”

“These high-quality data showing the treatment benefit of ReActiv8 compared to the current standard of care meaningfully add to the growing body of clinical evidence regarding ReActiv8 and firmly establishes the critical role of this therapy in treating intractable mechanical low back pain patients. We are proud to have the only commercially available device with a strong safety profile and long-term, peer-reviewed evidence supporting the rehabilitation of this severely affected patient population,” said Jason Hannon, CEO of Mainstay Medical. “We look forward to leveraging these data, along with the compelling results from our ReActiv8-B clinical trial and our numerous other studies, to further engage payers in the United States to expand commercial insurance access to this transformational therapy, which has the potential to deliver significant reductions in overall healthcare costs. I would like to thank Drs. Frank Schwab, Chris Gilligan, Nagy Mekhail and Kiran Patel for acting as our steering committee for this important study, as well as each of the enrolling sites, investigators and all of the participating patients.”

About the RESTORE Clinical Study and the Steering Committee

The RESTORE (ReActiv8 Stimulation Therapy vs Optimal Medical Management: A Randomized Evaluation) clinical study is a multi-center, prospective, randomized trial with one-way cross-over. A total of 203 patients were randomized and followed in the study at 23 leading centers in the U.S. Eligible patients were randomized to either optimized medical management or ReActiv8 Restorative Neurostimulation therapy plus optimal medical management. Patient-reported outcomes were collected at regular intervals out to the one-year primary endpoint assessment, at which time the patients in the control arm were offered implantation with the ReActiv8 system. Assessment of the patients will continue for an additional year.

The steering committee for the study consists of Dr. Frank Schwab, Chair of Orthopedic Spine Surgery at Lenox Hill Hospital and Chief of Orthopedic Spine Surgery for Northwell Health System; Dr. Chris Gilligan, Chief Medical Officer, Chief Quality Officer & Senior Vice President of Robert Wood Johnson University Hospital; Dr. Nagy Mekhail, Professor and Director of Evidence-Based Pain Management Research, Cleveland Clinic, and Professor of Anesthesiology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; and Dr. Kiran Patel, Director of Pain Medicine, Lenox Hill Hospital and Founder & CEO, NYC Neuromodulation Center of Excellence.

About ReActiv8®

ReActiv8 is an implantable medical device designed to treat adults with intractable chronic low back pain (CLBP) associated with multifidus muscle dysfunction, which may be evidenced by imaging or physiological testing. Candidates for ReActiv8 are patients with multifidus muscle dysfunction who have failed other forms of therapy (including pain medication and physical therapy) and are not candidates for spine surgery. ReActiv8 has received regulatory approval in several geographic areas, and is commercially available in the European Economic Area, Australia, the UK, and the US.

About Mainstay Medical

Mainstay Medical is a medical device company focused on commercializing its innovative implantable Restorative NeurostimulationTM system, ReActiv8®, for people with disabling mechanical CLBP. Mainstay Medical is headquartered in Dublin, Ireland and has subsidiaries operating in Ireland, the United States, Australia, Germany, and the Netherlands.

Further information can be found at www.mainstaymedical.com.

PR and IR Enquiries:

LifeSci Advisors, LLC
Brian Ritchie
Tel: + 1 (212) 915-2578
Email: britchie@lifesciadvisors.com

FTI Consulting (for Ireland)
Jonathan Neilan or Patrick Berkery
Tel. : +353 1 765 0886
Email: mainstay@fticonsulting.com

Mainstay Medical
Corporate Communications
Email: Media@mainstaymedical.com

XyloCor Therapeutics Raises $67.5 Million in Series B Financing to Advance Clinical Development of Novel Gene Therapy in Cardiovascular Disease

• Financing round led by new investor Jeito Capital with participation from existing investors

• Proceeds will support two double-blind Phase 2 clinical trials of lead candidate, XC001, which has demonstrated transformative potential for treatment of refractory angina

XyloCor Therapeutics, Inc., (“XyloCor”), a clinical stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, today announced the completion of a $67.5 million Series B financing.

New investment will support a randomized, double-blind Phase 2b clinical trial (EXACT-2) of XC001 (encoberminogene rezmadenovec), in refractory angina, using a new non-surgical method of endocardial administration via a novel injection catheter. The financing will also fund a second randomized, double-blind Phase 2 trial of XC001 as an adjunctive treatment to coronary artery bypass graft surgery (CABG). XC001 offers a new therapeutic approach for debilitating and chronic conditions that impact over one million people in the United States who have no treatment options.

New investor Jeito Capital, a global leading private equity fund, led the Series B financing round which also included existing institutional investors EQT, Fountain Healthcare Partners, and Lumira Ventures. Rachel Mears, Partner at Jeito Capital, will join the XyloCor Board of Directors.

“We are delighted to have Jeito Capital join our strong investor syndicate and Board of Directors,” said Al Gianchetti, president and chief executive officer of XyloCor Therapeutics. “The support of this prominent group of life sciences investors is recognition of the progress we have made and confidence in our ability to reach important milestones in the path ahead. With this financing, we can accelerate our clinical development of XC001, completing two phase 2 clinical trials, and achieve our mission to help people with cardiovascular disease who have no treatment options.”

XyloCor is pioneering the application of one-time gene therapy to address significant unmet treatment needs among underserved patients with cardiovascular disease. In its initial target indication in refractory angina, XC001 has demonstrated potential to transform outcomes for patients who have exhausted available treatment options and have a debilitating quality of life. Positive results from the recently published Phase 1/2 clinical trial (EXACT-1) demonstrate the disease-modifying potential of XC001 to relieve chest pain in patients with refractory angina by reducing ischemic burden, as published in Circulation: Cardiovascular Interventions.

Based on the foundation of efficacy and safety data for XC001 demonstrated in EXACT-1, XyloCor plans to launch a randomized, double-blind Phase 2b in refractory angina in 2025 to further build upon the clinically-meaningful evidence generated to-date. XyloCor intends to deploy a catheter‑based endocardial delivery of XC001 in the Phase 2b EXACT-2 study, eliminating the need for surgical administration in this population.

XyloCor also aims to initiate a second Phase 2 trial of XC001 in 2025 as an adjunctive therapy to augment the effectiveness of CABG: a procedure used to treat coronary artery disease. CABG is generally recommended when there are significant blockages in the major coronary arteries with the objective to improve oxygen-rich blood flow, resulting in improvement in cardiovascular disease symptoms and quality of life, and reduction in future cardiac events. There are approximately 400,000 CABG procedures performed annually in the United States, in which an estimated one-third of procedures result in incomplete coronary revascularization, which can result in increased mortality, hospitalizations, repeat revascularizations, and angina symptoms.

Administering XC001 during the CABG procedure is intended to promote the growth of new blood vessels in the areas of the heart not treated by the bypass grafts and therefore reduce symptoms and improve outcomes beyond the bypass alone. XyloCor plans to dose the first patient in the Phase 2 study by year end 2025.

“We are thrilled to support XyloCor as it advances its clinical trials to evaluate XC001 as a potential treatment for patients struggling with the burden of cardiovascular disease,” said Rachel Mears, Partner at Jeito Capital. “The company has strong support from an experienced leadership team, world-class cardiologists and scientists and has made impressive achievements in a short time in advancing its novel gene therapy approach. We look forward to collaborating with the company as it progresses to the next steps in its clinical program.”

About Jeito Capital

Jeito Capital is a global leading Private Equity fund with a patient benefit driven approach that finances and accelerates the development and growth of ground-breaking medical innovation. Jeito empowers and supports managers through its expert, integrated, multi-talented team and through the investment of significant capital to ensure the growth of companies, building market leaders in their respective therapeutic areas with accelerated patients’ access globally, especially in Europe and the United States. Jeito Capital has €534 million under management and a rapidly growing portfolio of investments. Jeito Capital is based in Paris with a presence in Europe and the United States. For more information, please visit www.jeito.life or follow us on LinkedIn or X.

About XC001

XC001 is designed to promote new blood vessels in the heart that will bypass diseased blood vessels and improve blood flow. By restoring blood flow, chest pain associated with ischemic heart disease may decrease, potentially improving patients’ quality of life by enabling them to engage in daily physical activities that would otherwise cause pain. XC001 is designed to avoid toxicity issues observed with other gene therapies through a strategy of one‑time, local administration. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects.

About XyloCor

XyloCor Therapeutics, Inc. is a private, clinical‑stage biopharmaceutical company developing potential best‑in‑class gene therapies to transform outcomes for patients with cardiovascular disease. The Company’s lead product candidate, XC001, is in clinical development to investigate use for patients with ischemic heart disease for whom there are no treatment options. XyloCor has a second preclinical investigational product, XC002, in discovery stage, being developed for the treatment of patients with cardiac tissue damage from heart attacks. The company, which was co‑founded by Ronald Crystal, M.D., and Todd Rosengart, M.D., has an exclusive license from Cornell University. For more information, visit www.xylocor.com.

Contacts:

Corporate and Investor Relations:
A. Brian Davis, XyloCor Therapeutics, Inc.
brian.davis@xylocor.com
610-541-2056

Media Contact:
Mike Beyer
Sam Brown Inc. Healthcare Communications
mikebeyer@sambrown.com
312-961-2502

Vivasure Announces Positive Results of PATCH IDE Pivotal Study Indicating Safety and Efficacy of PerQseal® Large Hole Closure Device

• Data from U.S. IDE PATCH Pivotal Study presented at the Transcatheter Cardiovascular Therapeutics (TCT) 2024 annual conference will support a pre-market approval submission to the FDA

• Results demonstrate Vivasure’s PerQseal® Closure Device achieved closure with very low rates of major vascular complications and rapid times to hemostasis

Vivasure Medical®, a company pioneering novel fully absorbable technology for percutaneous vessel closure, today announced initial positive results from its U.S. IDE PATCH Pivotal Study evaluating the safety and efficacy of the Vivasure PerQseal® Closure Device System, at the Transcatheter Cardiovascular Therapeutics (TCT) 2024 annual conference in Washington, D.C.

The Vivasure PerQseal® Closure Device System (PerQSeal) is the first sutureless, fully absorbable synthetic implement for large-bore vessel punctures, and is an alternative to the use of suture- or collagen-based closure devices. It is used for large hole arterial access and is needed for a variety of procedures including transcatheter aortic valve replacement (TAVR) and numerous other large hole cardiovascular procedures. The goal of the device is to reduce vascular complications while simplifying the closure.

Vivasure’s U.S. IDE PATCH Clinical Study, a multi-center, single-arm, pivotal study, enrolled over 145 patients across 17 U.S. and European investigational sites and evaluated the safety and efficacy of PerQseal when used to achieve hemostasis of common femoral arteriotomies created by 12 to 22F sheaths (arteriotomies up to 26F) in subjects undergoing percutaneous catheter-based interventional procedures.

Data presented at TCT show an impressively low 0.8% Valve Academic Research Consortium 3 (VARC-3) major complication rate at discharge in 124 patients included in the study’s primary intention-to-treat analysis. Times to hemostasis following percutaneous procedures were rapid, with a median time of zero minutes.

“Complications from large hole vascular closure remain vexing, impacting patients and requiring additional time and resources. As interventionalists, we need new technologies to improve both outcomes and procedural efficiency,” said William A. Gray, MD, principal investigator of the PATCH study and system chief in the division of cardiovascular disease at Main Line Health, Philadelphia. “The PATCH study results presented today show real promise for the PerQseal technology and positions it to meaningfully improve patient care.”

“We are addressing an unmet need in the market by delivering the first sutureless, fully absorbable synthetic implement for large-bore vessel punctures that, for the first time, delivers a minimally invasive approach to conventional venous closure,” explained Andrew Glass, CEO, Vivasure Medical. “The results from our U.S. pivotal study, as well as the previous PerQseal studies, indicate that the PerQseal System is safe and effective for patients around the globe.”

About Vivasure Medical

Based in Galway, Ireland, Vivasure is focused on the development of advanced polymer implants and delivery systems, primarily focused on minimally invasive vessel closure in cardiology, interventional radiology and vascular surgery. Vivasure operates a fully integrated R&D and ISO 13485 certified manufacturing facility and is backed by leading international medtech investors. For more information, please visit www.vivasuremedical.com.

The PerQseal® is not available for sale in the United States.