Calypso Enters into Agreement to Be Acquired by Novartis

  • Calypso is a European biotech translating Interleukin-15 biology into medical breakthroughs by developing CALY-002, an anti-IL-15 monoclonal antibody, for an array of autoimmune indications

  • The acquisition of Calypso gives Novartis full rights to CALY-002, a pipeline-in-a-drug with potential in dermatology, gastro-intestinal and rheumatology indications


Calypso Biotech BV (‘Calypso’), a leader in the development of Interleukin15 (IL-15) targeted therapies, announced today that it has entered into an agreement to be acquired by Novartis AG (‘Novartis’). Calypso’s shareholders will receive an upfront payment of $250 million upon closing and are eligible to receive development milestones of up to $175 million based on the achievement of certain predetermined milestones.


Calypso, a spin-out from Merck, is focused on the research and development of monoclonal antibodies for an array of autoimmune indications, with an expertise in IL-15 biology. IL-15 is a broad, untapped immune axis that controls barrier function and downstream immune cascades in many chronic autoimmune diseases. Calypso’s lead product candidate, CALY-002, is a potential best-in-class therapeutic antibody that binds to and neutralizes Interleukin-15.


The acquisition gives Novartis full rights to CALY-002. Novartis intends to further explore CALY-002 across a wide variety of autoimmune indications with high unmet medical need. CALY-002 is currently evaluated in a Phase 1b trial in patients with Celiac Disease and Eosinophilic Esophagitis.


Alain Vicari, Chief Executive Officer & Co-Founder, Calypso, commented: “We are excited for this transaction with Novartis, a company with relentless commitment to the development of innovative therapies for autoimmune conditions. As part of the Novartis portfolio, CALY-002 is in the best position to be developed effectively, so that it can promptly address unmet medical needs in multiple indications”


Bernard Coulie, Chairman, Calypso, commented: “The transaction with Novartis constitutes the high point in the development path of CALY-002 for the Calypso team. Calypso has established a significantly de-risked profile for CALY-002 as a potential best-in-class therapeutic anti-IL-15 antibody”


Richard Siegel, Head of Immunology Research at Novartis, commented: “Novartis is committed to bringing innovative treatment options forward for patients living with immunological diseases. We’re thrilled to add Calypso’s potential best-in-class antibody to our Immunology pipeline and explore it in a spectrum of autoimmune indications.”


Lazard acted as financial advisor and Goodwin Procter LLP acted as legal counsel to Calypso.

About Calypso Biotech BV

Calypso is a private biotechnology company focused on the research and development of novel biologics to address unmet medical need in autoimmune and inflammatory diseases.

Calypso is developing a novel anti-IL-15 monoclonal antibody to treat a broad range of chronic autoimmune diseases by blocking Interleukin-15 (IL-15) and its wide-ranging functions at many levels of the immune response cascade. CALY-002, a highly potent monoclonal antibody, neutralizes all forms of IL-15 through a uniquely effective molecular mode of action to reduce inflammation and prevent tissue destruction.

Calypso was founded by M Ventures, the corporate strategic venture arm of Merck, and is headquartered in Amsterdam, The Netherlands, with offices and laboratories in Geneva, Switzerland. Investors include M Ventures, Inkef Capital, Gilde Healthcare, Fountain Healthcare Partners and Johnson & Johnson Innovation – JJDC, Inc.

Contact

Calypso Biotech BV
info@calypsobiotech.com

Corteria Pharmaceuticals appoints Mark Pruzanski as Chairman of its Board of Directors

Corteria Pharmaceuticals (“Corteria”), a biopharmaceutical company specialized in the development of transformative therapies for heart failure and obesity, today announced it has appointed Mark Pruzanski, MD, as Chairman of its Board of Directors. He replaces Thierry Laugel, Managing Partner at Kurma Partners, who remains a member of the Board.

Dr. Pruzanski has more than 30 years of experience as a life sciences executive, entrepreneur and investor. He most recently served as Chairman and CEO of Versanis Bio, a private clinical-stage biopharmaceutical company focused on the development of new medicines for the treatment of obesity and other cardiometabolic diseases, which was acquired by Eli Lilly in July 2023. He founded Intercept Pharmaceuticals and was the company’s CEO until 2021, having led its evolution from drug discovery stage to a global development and commercial organization with a focus on addressing chronic liver diseases. He serves as a Board member of several private and public biotechnology companies, the Emerging Companies Section of the Biotechnology Innovation Organization (BIO), and the Foundation for Defense of Democracies, a non-profit policy institute focusing on foreign policy and national security.


Dr. Pruzanski received his M.D. from McMaster University in Hamilton, Canada, a M.A. degree in International Affairs from the Johns Hopkins University School of Advanced International Studies in Bologna, Italy and Washington, D.C., and a bachelor’s degree in Political Science from McGill University in Montreal, Canada.


“We are thrilled to welcome Mark as the Chairman of the Board of Directors,” said Philip Janiak, founder and CEO of Corteria Pharmaceuticals. “Mark brings extensive expertise in drug development with a solid track record in the biotechnology industry. His strategic vision, outstanding leadership and passion for innovation make him a valuable addition to Corteria as we continue our mission to advance innovative therapeutic solutions for heart failure and obesity.”


“It’s a privilege to join the Board of Corteria,” said Mark Pruzanski. “This is an exciting time in the company’s evolution as it brings its exciting first-in-class assets into the clinic and on the heels of its recent Series A financing led by top tier biotech investors. I am looking forward to working with Philip and the rest of the Board to help ensure Corteria’s future success.”

About Corteria Pharmaceuticals

Founded in 2021, Corteria is a privately held biopharmaceutical company developing first-in-class drugs with an initial focus on the treatment of heart failure. Despite improvements in the management of this serious disease, the prevalence of heart failure keeps increasing with more than 60 million patients worldwide and there are large subpopulations of patients who are poorly served by currently available treatments.


More information available at: www.corteriapharma.com

Investors/media contacts

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


Andrew Lloyd & Associates
Juliette Schmitt / Celine Gonzalez
juliette@ala.associates / celine@ala.associates
UK: +44 1273 952 481
US: +1 203 724 595

US FDA grants Orphan Drug Designation to mocravimod to improve the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematologic malignancies

  • Mocravimod is the only S1P receptor modulator being developed as an adjunctive and maintenance treatment for blood cancers

  • Mocravimod is being investigated in a global registration-enabling Phase 3 trial

  • This is the second Orphan Drug designation for mocravimod

Priothera Ltd., a Phase 3 clinical stage biotechnology company pioneering the development of its S1P receptor modulator compound mocravimod, today announced that the US Food and Drug Administration (FDA) has granted Orphan Drug designation (ODD) to mocravimod for the ‘treatment to improve outcome following hematopoietic stem cell transplantation in hematologic malignancies’. This ODD aims to potentially increase leukemia-free survival by enhancing a graft-versus-leukemia (GvL) response.

Florent Gros, Co-Founder and CEO of Priothera, commented: “We are very pleased that the US FDA granted mocravimod this Orphan Drug designation. This designation emphasizes the importance of developing novel therapeutic options to improve the outcome and success of maintenance therapy following allo-HSCT in blood cancer patients. This is an important milestone as this ODD complements the first ODD granted for prevention of graft-versus-host disease.”

“The two ODDs highlight mocravimod’s dual mode of action which for the first time is being leveraged to improve the allo-HSCT treatment outcomes in hematological malignancies to potentially increase the leukemia free survival – graft-versus-leukemia response - while reducing tissue damage resulting from the graft-versus-host disease.”

The first ODD granted for mocravimod by the US FDA was for the ‘prevention of graft-versus-host disease (GvHD)’ – see press release here.

Mocravimod, a sphingosine-1-phosphate (S1P) receptor modulator, is being investigated in a pivotal global Phase 3 study - MO-TRANS (NCT05429632) - evaluating the efficacy and safety of mocravimod as an adjunctive and maintenance therapy to allo-HSCT. The study which is enrolling approximately 250 adult Acute Myeloid Leukemia (AML) patients, is ongoing in the US, Europe, Southeast Asia and Latin America.

Mocravimod, which has been previously tested in multiple autoimmune indications, is being developed to enhance the curative potential of allo-HSCT. Moreover, it has shown a clinically meaningful outcome in a Phase 1b/2a study[1] in patients with hematologic malignancies undergoing allo-HSCT.

The Orphan Drug designation is reserved for medicines treating rare, life-threatening or chronically debilitating diseases.

About mocravimod

Mocravimod (also known as KRP203) is a synthetic, S1P receptor modulator. This novel investigational drug has been assessed in Phase 1 and Phase 2 trials for safety and tolerability, as well as for efficacy in several autoimmune indications. Promising data from a Phase 1b/2a clinical study in patients with hematological malignancies led Priothera to further develop mocravimod for the treatment of blood cancers and the improvement of CAR-T cell therapy.

Mocravimod is currently being investigated as an adjunctive and maintenance treatment in a Phase 3 study for patients with AML receiving allogeneic HSCT. Allogeneic HSCT is the only potentially curative approach for AML patients, but current treatments have unacceptably high mortality and morbidity rates.

Priothera leverages mocravimod’s dual mode of action to maintain the beneficial graft-versus-leukemia/lymphoma (GvL) activity, while reducing tissue damage resulting from graft-versus-host disease (GvHD), both a consequence of allo-HSCT. This novel treatment approach – mocravimod being the only S1P receptor modulator treating blood cancers – tackles a high unmet medical need and aims to improve patients’ quality of life.

About Priothera

Priothera is leading the way in developing orally applied S1P receptor modulators for the treatment of hematological malignancies and for the improvement of CAR-T cell therapies. S1P receptor modulators are known to largely reduce egress of T cells from lymphatic tissues. Unlike immunosuppressive drugs, mocravimod does not suppress the GvL benefits in patients receiving allogeneic HSCT while inhibiting GvHD.

Priothera was founded in 2020 by an experienced team of drug development experts and is headquartered in Dublin, Ireland, and with a subsidiary in Saint-Louis, France. The Company is backed by international founding investors Fountain Healthcare Partners (Dublin, Ireland), funds managed by Tekla Capital Management, LLC (Boston, Massachusetts), HealthCap (Stockholm, Sweden), EarlyBird Venture Capital (Berlin, Germany), as well as non-dilutive financing in the form of loans from the European Investment Bank under its Venture Debt Instrument and Bpifrance (Grand Est Bpifrance) in the form of a R&D innovation loan.

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

Contacts

Priothera
Florent Gros, CEO
E: info@priothera.com

MEDiSTRAVA Consulting
Sylvie Berrebi, Sandi Greenwood, Frazer Hall
E: priothera@medistrava.com
T: +44 (0) 203 928 6900

[1]*Ref: Dertschnig et al, 2023

Vivasure Medical Announces 100th Patient Enrolled in U.S. Pivotal Study

PATCH Clinical Study will evaluate the safety and efficacy of Vivasure’s PerQseal Closure Device System for large-bore vessel punctures

Vivasure Medical®, a company pioneering novel fully absorbable technology for percutaneous vessel closure, today announced it has enrolled the 100th patient in its PATCH Clinical Study, a multi-center, single-arm, pivotal study evaluating the safety and efficacy of the Vivasure PerQseal® Closure Device System. The U.S. Food and Drug Administration (FDA) granted investigational device exemption (IDE) approval earlier this year to advance the PATCH study forward.

"We’re grateful to the one hundred patients who have been enrolled in this study to date and the brilliant physician investigators working to gather data about our technology," said Andrew Glass, Chief Executive Officer of Vivasure Medical. "This marks an important milestone for Vivasure as it brings us closer to our goal of demonstrating PerQseal’s potential in supporting successful percutaneous cardiovascular therapies."

Large hole arterial access is required for clinicians to perform numerous life-saving percutaneous cardiovascular procedures such as transcatheter aortic valve replacement (TAVR), thoracic and abdominal endovascular aneurysm repair (TEVAR and EVAR), and the use of a cardiac assist device (CAD). The current approach to large-diameter arterial closure is a surgical repair or the use of suture- or collagen-based closure devices. Both can result in major vascular complications, such as vessel distortion at the closure site, which may lead to stenosis, thrombus formation or abrupt closure.

PerQseal is designed to be the first sutureless, fully absorbable synthetic implant for large-bore vessel punctures. Its low profile patch can be placed from inside the vessel and is intended to make deployment simpler and more controlled than conventional closure techniques. Clinical studies to date have shown a low complication rate and high technical success.

The PATCH pivotal study will enroll and follow up to 188 patients across the U.S. and Europe. The company intends to use the clinical study results to support an FDA pre-market approval submission as well as multinational commercial launch of the PerQseal system for large hole vessel closure.

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.

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

Neurent Medical Announces New CPT Code® for Chronic Rhinitis Treatment Offering Significant Symptom Improvements

CMS Assignment Empowers ENT Physicians and Offers Relief to Millions of Chronic Rhinitis Patients

Neurent Medical, a company pioneering innovative non-surgical interventions to treat chronic inflammatory sinonasal diseases, today announced a significant milestone for the chronic rhinitis market. The Centers for Medicare and Medicaid Services (CMS) has recently assigned a Category I Current Procedural Terminology (CPT®) reimbursement code for a breakthrough minimally invasive procedure designed to address the symptoms of patients suffering from chronic rhinitis.

Effective January 1, 2024, the assigned payment for CPT code 31242 for endoscopic destruction of the posterior nasal nerve (PNN) using radiofrequency ablation will be instated for use with Neurent Medical's NEUROMARK® System. The new code describes the procedure performed by otolaryngologists or ear, nose, and throat (ENT) physicians when disrupting overactive nerves that drive chronic rhinitis symptoms.

Marc G. Dubin, MD, FACS, a nationally recognized subspecialist in sinus and nasal disease expressed his enthusiasm for this upcoming assignment, stating, "The establishment of this CPT code is a significant milestone for physicians who treat chronic rhinitis patients with ablation of the posterior nasal nerves as we are now able to provide patients lasting relief and address chronic runny nose, post-nasal drip, and congestion more effectively." He continued, "I have been fortunate to use the NEUROMARK System throughout its development and with its demonstrated safety and efficacy in the recently published CLARITY study, I am eager to have this treatment option readily available to my chronic rhinitis patients who have had limited options for long term treatment to-date."

It is estimated that several million chronic rhinitis patients are seen by ENT doctors annually in the United States. The condition affects approximately one in four Americans1. Chronic rhinitis patients endure sinonasal discomfort characterized by persistent congestion, rhinorrhea (runny nose), sneezing, and nasal itching due to inflammation and swelling mucosal membrane in the nose. The high prevalence of chronic rhinitis and its negative impact on day-to-day life, including sleep, cognitive function, mood, and ultimately on performance at work or school, make chronic rhinitis a global public health issue2.

Currently available treatments have been shown to be effective in interrupting posterior nasal nerves (PNN). However, not all patients have adequate resolution of their symptoms. One hypothesis for this lack of improvement is inadequate treatment of nerves due to natural anatomic variations that are not addressed by current devices3.

The NEUROMARK System offers ENTs a novel and unique flexible leaflet design to help achieve precise placement across the PNN and accessory pathways. The proprietary Smart Algorithms monitor the treatment of targeted tissue to ensure it is delivered adequately to the intended area. The system can comfortably accommodate a range of anatomies. Microlesions disrupt the PNN pathway while maintaining mucosal and vascular integrity.

The significance of this milestone is further emphasized by Neurent Medical's CEO, Brian Shields, who commented, "The assignment of the CPT Code marks the next chapter of evolution and growth for Neurent Medical. We are extremely proud to be at the forefront of innovation, introducing a sustainable treatment option for patients who are suffering with chronic rhinitis." He added, "The NEUROMARK System uses a proprietary algorithm and biofeedback to tailor treatment for each individual patient. This achievement reflects our commitment to enhancing patient outcomes and our partnership with clinical investigators and the otolaryngology community as a whole."

The NEUROMARK System received U.S. Food and Drug Administration (FDA) 510(k) clearance in October 2021 and Neurent Medical announced the limited market release of the system in February 2023.

About the NEUROMARK® System

The NEUROMARK® System is indicated for use in otorhinolaryngology (ENT) surgery for creation of radio frequency (RF) lesions to disrupt posterior nasal nerves in patients with chronic rhinitis. The system is engineered to gently apply controlled low-power Radio Frequency (RF) energy to target regions of the nasal cavity to disrupt the parasympathetic nerve signals in order to reduce the inflammatory response, thereby reducing core 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 algorithmic control, physicians can 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 the US office located in Braintree, MA. For more information visit www.neurentmedical.com.


1 Settipane RA, Charnock DR. Epidemiology of rhinitis: allergic and nonallergic. Clin Allergy Immunol. 2007;19:23-34. PMID: 17153005.

2 Vandenplas O, Vinnikov D, Blanc PD, et al. Impact of Rhinitis on Work Productivi.: A Systematic Review. J Allergy Clin Immunol Pract. 2018;6(4):1274-1286.e9. doi:10.1016/j.jaip.2017.09.002

3 Fan T, Chandna M, Gorelik D, et al. Correlation between middle turbinate insertion in relation to sphenopalatine foramen and failure rates of cryotherapy and radiofrequency treatment for chronic rhinitis. Int Forum Allergy Rhinol. 2023;13(1):88-91. doi:10.1002/alr.23058

MMI Expands Global Footprint with Entry into Asia Pacific Market

Partnerships with Device Technologies and TRM Korea will strengthen Symani® Surgical System’s entrance into the world’s fastest-growing surgical robotics market.

MMI, (Medical Microinstruments, Inc.), a robotics company dedicated to increasing treatment options and improving clinical outcomes for patients with complex conditions, today announced that it will continue its global momentum with two distribution agreements covering nearly a dozen countries in the Asia Pacific (APAC) region. The first partnership, with Device Technologies, will help to introduce the Symani Surgical System to Hong Kong, Singapore, Vietnam, Malaysia, Indonesia, Thailand, Philippines, Macau, and New Zealand, upon applicable regulatory approvals, as well as Australia, where it recently received approval from the Therapeutic Goods Administration (TGA). The other partnership, with TRM Korea, will facilitate the system’s entry into South Korea upon regulatory approval and will introduce microsurgical robotic technology to interested surgeons and hospitals.

The Symani Surgical System is a first-of-its-kind robotic technology that uniquely addresses the scale and complexities of microsurgery and supermicrosurgery. By allowing surgeons to replicate the natural movements of the human hand at the micro scale, it can expand treatment options for patients in need of soft tissue open surgical procedures, such as free flap reconstructions, lymphatic surgery, and trauma reconstructions. It is designed to help restore quality of life for more patients, accelerate the number of surgeons able to push the boundaries of complex procedures for delicate anatomy, and enable hospitals to expand their open surgical programs.

“Through our new partnerships in Asia Pacific, we have established roots that will ultimately help us expand patient access to robotic microsurgical and supermicrosurgical capability in a region of the world with clear demand for the technology,” said Matt Lemay, VP of Asia Pacific of MMI. “Surgeons from the APAC region have long been at the forefront of innovation in microsurgery, and we look forward to helping further those capabilities with the Symani Surgical System. As we advance our mission of increasing treatment options for patients with complex conditions, we are enthusiastic about our global progress and look forward to continuing our momentum in APAC and beyond.”

Device Technologies has provided healthcare professionals access to innovative, high quality medical devices, including leading robotics solutions, for over 30 years. They will open a new research and education center for robotic microsurgery with a premier medical institution as part of their partnership with MMI. The center will represent the first site in Central Asia where interested surgeons can learn more about the system.

“MMI and the Symani Surgical System are well aligned with our core mission to provide physicians and healthcare facilities with solutions that can drive improved patient outcomes,” said Heath Priestly, Managing Director at Device Technologies. “Originating in Australia, we have broadened our presence throughout the Asia Pacific region, establishing expertise and strong connections. We are eager to use our footprint to support MMI’s health system partnerships across the region and further increase patient access to sophisticated surgical techniques for complex conditions.”

TRM is the largest microsurgery company in South Korea and a pioneer in the medical technology and innovation space. They are collaborating with a world-renowned medical institution to open their own education center where surgeons will have the opportunity for informational sessions and hands-on learning about the Symani Surgical System. To learn more about MMI, visit https://mmimicro.com.

About MMI

MMI (Medical Microinstruments, Inc.) 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, lymphatic repair, and peripheral nerve repair. The Symani System is CE Marked for commercial use in Europe. In the United States, the system is not approved or cleared for commercial use. MMI is backed by international medtech investors including Andera Partners, BioStar, Deerfield Management, Fountain Healthcare Partners, Panakès Partners, RA Capital, Sambatech, and Wellington Partners.

MMI’s Symani® Robotic Surgical System Surpasses 500 Clinical Procedures

  • Milestone case performed at HUS Helsinki University Hospital demonstrates MMI’s continued momentum in the soft tissue open surgery field

MMI, (Medical Microinstruments, Inc.), a robotics company dedicated to increasing treatment options and improving clinical outcomes for patients with complex conditions, today announced the successful completion of over 500 in-human surgeries with the Symani® Surgical System in the European Union. The Symani Surgical System is a first-of-its kind robotic technology that uniquely addresses the scale and complexities of microsurgery and supermicrosurgery. It aims to restore quality of life for more patients, accelerate the number of surgeons able to push the boundaries of complex procedures for delicate anatomy, and enable hospitals to expand their open surgical programs.

Millions of patients today with complex conditions lack access to treatment options that optimize outcomes due to human physical limitations on the microsurgical scale and a lack of specialists able to perform surgery on tiny, delicate anatomy. The Symani Surgical System is poised to help. It is a robotic platform that enables expanded options for patients in need of soft tissue open surgical procedures, such as free flap reconstructions, lymphatic surgery, trauma reconstructions, and peripheral nerve repairs. Since the first in-human cases in October 2020, the system has been used in over 500 procedures, rapidly increasing patient access to surgical treatment options as surgeons become comfortable using the technology.

“We believe that open surgery is long overdue for technological advancement. This major milestone for the Symani Surgical System is a testament to how robotics can elevate the standard of care by pushing the boundaries of complexity,” said Mark Toland, CEO of MMI. “People with hard-to-treat conditions deserve options that can give them a better quality of life, and we hope that by expanding access to microsurgical and supermicrosurgical procedures, we’re able to drive that initiative forward.”

The Symani Surgical System’s unique capabilities in open microsurgery are a result of its proprietary NanoWrist® instruments, which feature the world’s smallest surgical robotic wrist. This enables surgeons to replicate the natural movements of the human hand at the micro scale with seven degrees of freedom, tremor filtration, and motion scaling, ultimately increasing precision and control.

The 500th procedure was a lymphatic repair performed by Sinikka Suominen, PhD, MD, plastic surgeon at the HUS Helsinki University Hospital in Finland. HUS Helsinki University Hospital is one of the largest University Hospitals in Europe and is also a European and International Microsurgery Centre of Reference. In 2023, it was ranked No. 39 on Newsweek’s list of the World’s Best Hospitals. Of the 500 procedures completed to date, approximately 75 percent have been free flap surgeries, and 16 percent have been lymphatic repairs. The remaining 9 percent have consisted of other procedures such as peripheral nerve repairs and extremity replantation surgeries.

“Our hospital is using the Symani Surgical System across multiple procedure types, such as lymphatic repair and head and neck cancer-related reconstructive surgery, and I’ve experienced notable changes in the accuracy, stability, and reliability of my suture placement during lymphatic procedures,” said Dr. Suominen. “These are quality of life surgeries that enable patients to return to work or simply resume their normal daily activities. Lymphedema at its worst is a disabling condition, and advanced microsurgical procedures can give patients hope for a better quality of life. I’m proud to have completed this milestone procedure and look forward to many more opportunities to help patients through open, robotic microsurgery.”

To learn more about MMI, visit http://mmimicro.com.

About MMI

MMI (Medical Microinstruments, Inc.) 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, lymphatic repair, and peripheral nerve repair. The Symani System is CE Marked for commercial use in Europe. In the United States, the system is not approved or cleared for commercial use. MMI is backed by international medtech investors including Andera Partners, BioStar, Deerfield Management, Fountain Healthcare Partners, Panakès Partners, RA Capital, Sambatech, and Wellington Partners.

Contacts

Dan Ventresca
Matter Health for MMI
mmi@matternow.com

Corteria Pharmaceuticals Announces a €65M Financing to Advance Transformational Medicines in Cardiovascular Diseases

Corteria Pharmaceuticals (“Corteria”), a biopharmaceutical company specialized in the development of transformative therapies for unaddressed heart failure subpopulations, today announced an oversubscribed €65M ($71M) Series A co-led by US investment firm OrbiMed and EU-based leading investment firm Jeito Capital, with the participation of all existing seed investors (Kurma Partners, Fountain Healthcare Partners, V-Bio Ventures, Invivo Capital, Omnes Capital). As a result, Erez Chimovits from OrbiMed and Andreas Wallnoefer from Jeito Capital will join the board of Directors of Corteria.

The funding will be used to advance Corteria’s cardiovascular pipeline into the clinic.

Heart failure is a serious disease with a prevalence of more than 60 million patients globally and still growing. Corteria’s innovative approach is centered on selecting therapeutic targets involved in the worsening and acute forms of human heart failure, as well as a stratification strategy to identify specific subgroups that are most likely to benefit from the treatments. These forms of heart failure are widespread, life-threatening, and not directly addressed by the current standards of care.

Corteria was founded in 2021 by Sanofi’s former head of cardiovascular research, Philip Janiak, and Marie-Laure Ozoux, former cardiovascular project leader at Sanofi, around two cardiovascular programs in-licensed from Sanofi.

Since then, Corteria’s pipeline has expanded rapidly and comprises today three first-in-class therapies that are highly differentiated as they produce multi-organ benefits, acting on the kidneys, the heart, and the vessels:

  • A once daily subcutaneous Corticotropin-releasing hormone receptor 2 (“CRF2”) agonist for the treatment of Worsening Heart Failure

  • A once monthly subcutaneous CRF2 agonist for the treatment of Right Heart Failure

  • An AVP (arginine vasopressin) neutralizing monoclonal antibody for the treatment of Acute Heart Failure with Hyponatremia

The lead asset for Worsening Heart Failure is expected to enter the clinic in early 2024.

“This financing marks a major milestone in our mission to bring therapies to heart failure subpopulations with high unmet needs,” said Philip Janiak, Founder and President of Corteria Pharmaceuticals. “We are extremely grateful to Jeito and OrbiMed as our new investors for their trust in our science and team and to our existing investors for their support and commitment since inception. We are looking forward to working all together to develop next generation transformative therapeutics.”

Andreas Wallnoefer, Partner at Jeito Capital, said: “Despite current treatments, heart failure is a progressing disease that impacts severely the lives of many patients and remains one of the leading causes of mortality worldwide. Corteria focuses on translating important therapeutic innovation in cardiology into clinical practice. Our investment in Corteria reflects Jeito’s commitment to address significant unmet needs in the realm of cardiology. We are excited to join forces with Corteria’s dedicated team to develop a portfolio of medicines with important clinical benefit for patients.”

“We are proud to have been involved with Corteria since its early days and impressed with the progress made to date. The company is now at a turning point of entering the clinic with its lead asset early next year and validating its unique positioning in well-defined heart failure subpopulations with high unmet medical needs. Kurma Partners is pleased to continue supporting the company during this key step that we hope will bring transformative clinical outcome for patients,” said Thierry Laugel, Managing Partner at Kurma Partners, and Chairman of the board of Corteria.

About OrbiMed

OrbiMed is a healthcare investment firm, with over $17 billion in assets under management. OrbiMed invests globally across the healthcare industry through a range of private equity funds, public equity funds, and royalty/credit funds. OrbiMed’s team of over 100 professionals is based in New York City, San Francisco, Shanghai, Hong Kong, Mumbai, Herzliya, and other key global markets. www.orbimed.com

About Jeito Capital

Jeito Capital is a global leading Private Equity company 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 @Jeito_life on Twitter or LinkedIn.

About Corteria Pharmaceuticals

Founded in 2021, Corteria Pharmaceuticals is a privately held biopharmaceutical company developing first-in-class drugs in heart failure subpopulations. Despite some improvements in the management of this serious disease, the prevalence of heart failure keeps increasing with more than 60 million patients worldwide. Corteria’s strategy involves innovative patient stratification and target selection based on human evidence and a better understanding of disease biology in patients with a focus on worsening and acute heart failure and right heart failure. More information available at: www.corteriapharma.com

Investors/media contacts

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


Andrew Lloyd & Associates
Saffiyah Khalique / Celine Gonzalez
saffiyah@ala.associates / celine@ala.associates
UK: +44 1273 952 481
US: +1 203 724 595

Mainstay Medical Announces Completion of Enrollment of RESTORE Clinical Trial of ReActiv8® in the United States

Randomized controlled clinical trial expected to validate effectiveness of ReActiv8® Restorative NeurostimulationTM vs. optimal medical management

Mainstay Medical Holdings plc today announced the completion of enrollment in its RESTORE randomized clinical study of ReActiv8 for the treatment of intractable chronic low back pain. The study is designed to provide a direct comparison to optimized medical management for the purpose of testing the hypothesis that the addition of ReActiv8 Restorative Neurostimulation therapy to current care paradigms results in significant improvements in back pain-related disability.

The RESTORE (ReActiv8 Stimulation Therapy vs Optimal Medical Management: A Randomized Evaluation) clinical study is a prospective, randomized controlled trial conducted at 25 leading centers in the U.S. Eligible patients were randomized to either continue with their optimal medical management or ReActiv8 Restorative Neurostimulation therapy plus optimal medical management. Patient-reported outcomes are being collected at regular intervals out to the one-year primary endpoint, at which time the patients in the control arm are offered implantation with the ReActiv8 system. The Co-Principal Investigators of the RESTORE study are 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, Director of the Spine Center at Brigham and Women’s Hospital and assistant professor of Anesthesia at Harvard Medical School; and Dr. Kiran Patel, Director of Pain Medicine, Lenox Hill Hospital and Founder & CEO, NYC Neuromodulation Center of Excellence.

Jason Hannon, CEO of Mainstay Medical, stated: “We are proud to have reached this important milestone in the RESTORE clinical trial as we continue to demonstrate the clinical efficacy and positive economic impact of ReActiv8. We expect the initial data readout from the study in the second half of 2024, and we look forward to sharing the data with our physician customers and their patients, as well as using it to further engage managed care organizations in the United States to expand commercial insurance access to this incredible therapy. I would like to thank Dr. Frank Schwab, Dr. Chris Gilligan, and Dr. Kiran Patel for acting as Co-Principal Investigators of this important study, as well as each of the enrolling sites and all of the participating patients.”

“This type of randomized, controlled clinical trial in this difficult-to-treat and underserved patient population will produce high-quality data comparing ReActiv8 to the current standard of care,” said Drs. Frank Schwab, Chris Gilligan, and Kiran Patel, Co-Principal Investigators of the RESTORE study. “Once the data is published, it will meaningfully add to the growing body of clinical evidence regarding ReActiv8 and firmly establish the role of this therapy in treating mechanical low back pain patients.”

Drs. Schwab, Gilligan, and Patel continued: ”The RESTORE trial represents a substantial addition to the clinical evidence behind treatment options for this patient population who have extremely limited options beyond temporary palliative treatments and drugs. Directly addressing the underlying issue of muscular dysfunction can represent a substantial advancement in treatment options. We would like to express sincere thanks to the patients who agreed to be screened for this study, the trial investigators and their hard-working staff, and the Mainstay team for their passion and commitment to the program. We look forward to the results of this trial to prove the degree to which ReActiv8 can improve the lives of these patients above and beyond what is currently used to treat them.”

About the RESTORE Clinical Study

The RESTORE clinical study is a multi-center, prospective, randomized trial with one-way cross-over. A total of 226 patients were randomized in the study at 25 leading centers in the U.S. Eligible patients were randomized to either continue with their optimal medical management or ReActiv8 Restorative Neurostimulation therapy plus optimal medical management. Patient-reported outcomes are being collected at regular intervals out to the one-year primary endpoint, at which time the patients in the control arm are offered implantation with the ReActiv8 system. Assessment of the patients will continue for an additional year.

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 Neurostimulation 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.

XyloCor Therapeutics Presents Phase 2 Data Highlighting Safety and Efficacy of XC001 at the European Society of Cardiology (ESC) Congress 2023

  • Positive Phase 2 EXACT Trial results at 6-months underscore significant potential of investigational therapy in refractory angina

  • Six-month data have since been sustained out to 12-months supporting durability of XC001 safety and efficacy profile

  • XC001 targets unmet medical need among patients with refractory angina who have a debilitating quality-of-life burden and no available treatment options

XyloCor Therapeutics, Inc., a clinical‑stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, today presented results from the Phase 2 portion of its Phase 1/2 clinical trial (EXACT) of its lead gene therapy candidate XC001 (encoberminogene rezmadenovec) for refractory angina at the European Society of Cardiology (ESC) Congress 2023. During the ESC Congress poster session, Dr. Thomas Povsic, Principal Investigator of the EXACT trial, presented the primary six-month outcome data from the recently completed EXACT trial, which demonstrated that treatment with XC001 resulted in improvements across all key efficacy endpoints. The findings underscore its strong potential as a novel therapeutic approach for the treatment of this disabling condition.

XC001 is a one‑time gene therapy designed to reduce ischemic burden by creating new blood vessels in the heart through the local expression of multiple vascular endothelial growth factor (VEGF) isoforms. In the Phase 2 portion of the EXACT trial, 32 patients with class II-IV angina were dosed with the maximal dose of XC001 through transepicardial delivery (direct administration to the heart). XC001 met all of its safety and exploratory objectives and showed potential transformative benefits for the patient population. Among the notable topline results presented at the ESC Congress 2023 included:

  • VEGF gene therapy with XC001 administered via minimally invasive transepicardial delivery was generally well tolerated.

  • There were no serious adverse events related to the drug or unexpected serious adverse events related to XC001 administration.

  • Patients demonstrated improvements in key efficacy measures most notably total exercise time, time to the development of ST-depression (an objective measure of ischemia), angina frequency, and reduction in ischemic burden as measured by Positron Emission Tomography (PET) imaging.

  • The six-month results showed that XC001 achieved a clinically meaningful biologic effect, warranting further study in larger randomized clinical trials.

“Refractory angina is a debilitating and chronic condition that is growing in prevalence and these patients have exhausted all treatment options,” said Thomas Povsic, M.D., Ph.D., Professor of Medicine, Duke University School of Medicine and National Principal Investigator for the EXACT study. “The six-month results from the EXACT trial – which have now been sustained out to 12 months – demonstrate that gene therapy with XC001 has the potential to be safely administered while improving quality of life for these cardiac patients.”

“The clinical research results presented at ESC Congress 2023 highlight XyloCor's continuing efforts to transform the treatment paradigm in refractory angina through the promise of one-time gene therapy,” said Al Gianchetti, President and CEO of XyloCor. “We are excited to share data that provides evidence for angiogenesis and a promising efficacy and tolerability profile for XC001. These results strongly support our continued development of this novel therapeutic approach.”

Further background and results presented in the ESC Congress 2023 poster session titled “Angiogenic gene therapy for refractory angina: Results of the Epicardial delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) Phase 2 Trial” can be found here.

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 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. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects.

About the EXACT Study

The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) clinical trial was a Phase 1/2 multicenter, open‑label, single‑arm trial. Twelve subjects (n=3 per dose cohort) who have refractory angina were enrolled into four ascending dose groups, followed by an expansion phase of the trial in which additional subjects were enrolled at the highest tolerated dose (1 x 1011 vp, the highest tested dose). In the EXACT trial, this investigational gene therapy is administered directly to the heart muscle through a mini‑thoracotomy by a cardiac surgeon.

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 grafting (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 to investigate use for patients with refractory angina 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.

Results from XyloCor Therapeutics’ Phase 1 Portion of EXACT Trial of XC001 for Cardiovascular Disease Published in Circulation: Cardiovascular Interventions

  • Findings from the Phase 1 dose escalation portion of the EXACT trial of XC001 in refractory angina provided the dose selection and safety justification for the recently completed Phase 1/2 study

  • XC001 is a one-time gene therapy candidate designed to reduce ischemic burden by creating new blood vessels in the heart through the local expression of multiple VEGF isoforms

  • XyloCor is moving forward with urgency to address potential of XC001 as transformative therapy for patients with ischemic heart disease with significant unmet need

XyloCor Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, announced today that Circulation: Cardiovascular Interventions has published results from the Phase 1 portion of its Phase 1/2 clinical trial (EXACT) of lead gene therapy candidate XC001 (encoberminogene rezmadenovec) in patients with refractory angina. The findings from the Phase 1 dose escalation study, previously reported at the American Association for Thoracic Surgery (AATS) and the American Society of Gene and Cell Therapy (ASGCT) in May 2022, revealed that XC001 is well tolerated at all dose levels and provided justification to proceed to Phase 2 with the highest dose tested.

“The results from the Phase 1 study provided the mechanistic underpinning that was the catalyst for the successful completion of the Phase 2 EXACT trial,” said Thomas Povsic, M.D., Ph.D., lead author of the journal article, Professor of Medicine, Duke University School of Medicine and National Principal Investigator for the EXACT study. “Patients with refractory angina are highly symptomatic and have an exceedingly poor quality of life. With a robust body of positive and sustained safety and efficacy out to 12 months from the EXACT trial, we believe that XC001 has the potential to fill the significant unmet need for this patient population who currently lack treatment options.”

"We are thrilled with the publication of these EXACT trial results in Circulation: Cardiovascular Interventions, a highly-regarded and influential international journal for cardiovascular research," said Howard Dittrich, Chief Medical Officer of XyloCor. “We would like to acknowledge all of the authors for their contributions in highlighting the promise of XC001 and thank patients and their families for their participation in the EXACT trial. Our team is singularly focused on continuing to unlock the transformative potential of XC001 for improving outcomes in cardiovascular disease.”

The Phase 1 portion of the Phase 1/2 EXACT study was a first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of increasing doses of XC001, and to establish the best dose to carry forward for additional study in Phase 2. Twelve patients were enrolled into four dosing cohorts. Notably, the study demonstrated that adenoviral vector doses higher than those used in previous studies were well tolerated and more robust efficacy was demonstrated at the higher doses. This established a dose of 1×1011 viral particles for future clinical research of XC001.

The Circulation: Cardiovascular Interventions full article is available at https://www.ahajournals.org/doi/abs/10.1161/CIRCINTERVENTIONS.123.012997

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 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. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects.

About the EXACT Study

The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) clinical trial was a Phase 1/2 multicenter, open-label, single-arm trial. Twelve subjects (n=3 per dose cohort) who have refractory angina were enrolled into four ascending dose groups, followed by an expansion phase of the trial in which additional subjects were enrolled at the highest tolerated dose (1 x 1011 vp, the highest tested dose). The investigational gene therapy is administered directly to the heart muscle through a mini-thoracotomy by a cardiac surgeon.

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 grafting (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 to investigate use for patients with refractory angina 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.

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

Mainstay Medical Announces Publication of Three-Year Clinical Trial Data from Post-Market Clinical Follow-up Registry of ReActiv8® in the United Kingdom

Further real-world evidence supporting the efficacy and use of ReActiv8® Restorative NeurostimulationTM for the treatment of intractable Chronic Low Back Pain

Mainstay Medical Holdings plc today announced the publication of three-year clinical data from the Post-Market Clinical Follow-up (PMCF) study of 33 ReActiv8 patients from five medical centres across the United Kingdom. The three-year results, published in British Journal of Pain, demonstrated that a substantial portion of patients experienced statistically significant improvements in measures of pain (NRS), disability (ODI) and quality of life (EQ-5D-5L). The publication can be found here: https://journals.sagepub.com/doi/10.1177/20494637231181498.

These results indicate that the response to ReActiv8 for these patients is durable and improves over time, validating ReActiv8’s restorative mechanism of action. In addition, these real-world outcomes are consistent with the three-year data from the pivotal ReActiv8-B clinical trial, announced in September 2022, as shown in the following table:

Dr. Simon Thomson MBBS FFPMRCA, Consultant Lead at the Pain and Neuromodulation Centre, Mid and South Essex University Hospitals NHS, Essex, UK, stated: “These results demonstrate durability and safety of this therapy in chronic back pain sufferers who would have continued to be crippled and dominated by their symptoms but for ReActiv8. These patients, drawn from usual UK Pain clinics, are now as good as those seen in the continuation cohort from the more highly selected randomised ReActiv8-B trial.”

Jason Hannon, CEO of Mainstay Medical, stated: “We are pleased to add these compelling results to the growing global body of positive peer-reviewed evidence supporting the ability of ReActiv8 to provide positive long-term outcomes to this severely affected patient population. Most importantly, the continued improvement in patient outcomes observed in the real-world setting is consistent with the results from our controlled clinical trials.”

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 Neurostimulation 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.

XyloCor Therapeutics Reports Sustained Results in 12- Month Extension of Phase 2 EXACT Clinical Trial of XC001 Novel Gene Therapy for Refractory Angina

  • XC001 demonstrated durable improvements across multiple efficacy measures 12 months after treatment, underscoring its scientifically-sound approach to achieve biological effect and improve angina symptoms

  • Patients showed continued improvements in exercise capacity and reductions in episodes of chest pain that were sustained to 12 months

  • Robust body of mechanistic evidence from EXACT trial highlights significant potential of XC001 in cardiovascular disease

XyloCor Therapeutics, a clinical-stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, today reported positive 12-month data from the Phase 2 portion of its Phase 1/2 clinical trial (EXACT) designed to assess the safety and provide preliminary evidence of efficacy of lead gene therapy candidate XC001 (encoberminogene rezmadenovec) in patients with refractory angina.

At the 12-month mark in the extension period of the trial, XC001 demonstrated durable improvements across multiple efficacy measures, including continued improvement in total exercise duration and reductions in ischemic burden and ischemic symptoms.

Earlier this year, XyloCor reported positive results from the primary study period for the Phase 2 portion EXACT trial at six months. New results at 12 months highlight significant, clinically-meaningful impacts that are now sustained out to 12 months, pointing to the potential of XC001 as a novel therapeutic approach for the significant unmet medical need in refractory angina.


“The durability and, in the case of exercise time, continued improvements observed at 12 months signals a sustainable activity which is an exciting step forward in the advancement of gene therapy for cardiovascular disease,” said Thomas Povsic, M.D., Ph.D., Professor of Medicine, Duke University School of Medicine and National Principal Investigator for the EXACT study. “These 12- month data build upon the positive results achieved at the 3- and 6-month marks of the trial. In total, the outcomes of the EXACT study form a robust body of mechanistic evidence to propel the next stage of XC001’s development, suggesting that a single treatment may have long-term benefit.”

XC001 is a one-time gene therapy candidate designed to reduce ischemic burden by creating new blood vessels in the heart. The six-month primary study period in the Phase 2 portion of the EXACT trial was followed by a month 12 follow up period. At 12 months, patients demonstrated sustained and continued increases in total exercise duration (TED) over baseline, representing a significant and clinically meaningful change. In addition, there was a sustained and robust decrease in episodes of chest pain (angina) and nitroglycerin use. Cardiac imaging at 12 months provided additional evidence of the potential mechanism of action to achieve a biological effect, confirmed by a sustained reduction in ischemic burden observed over time.

“With the 12-month results from our EXACT trial, XyloCor continues to take a lead role in fulfilling the promise of gene therapy for people with cardiovascular disease,” said Al Gianchetti, President and CEO of XyloCor. "These results further enhance our confidence that we are on the right path for transforming outcomes in cardiovascular disease.”

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 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. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects.

About the EXACT Study

The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) clinical trial was a Phase 1/2 multicenter, open-label, single-arm trial. Twelve subjects (n=3 per dose cohort) who have refractory angina were enrolled into four ascending dose groups, followed by an expansion phase of the trial in which additional subjects were enrolled at the highest tolerated dose (1 x 1011 vp, the highest tested dose). The investigational gene therapy is administered directly to the heart muscle through a mini-thoracotomy by a cardiac surgeon.

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 grafting (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 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 refractory angina 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

Inotrem Announces Publication of Two Key Articles on Nangibotide Phase II Programs in Peer-reviewed Medical Journals

  • Data of ASTONISH Phase 2 trial in septic shock patients is published in The Lancet Respiratory Medicine and data of ESSENTIAL Phase 2 study in critically ill COVID-19 patients is published in eClinicalMedicine.

  • Both studies show that a therapeutic intervention with nangibotide can control the TREM-1 pathway in major life-threatening immune dysregulations caused by severe infections, whether it is septic shock or severe forms of COVID-19, leading to improved patient outcome.

Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory conditions, announced today the publication of the results of two phase 2 clinical studies in the The Lancet Respiratory Medicine and in eClinicalMedicine. The first article presents the ASTONISH Phase 2b trial in septic shock patients and the second one the ESSENTIAL Phase 2 trial for the treatment of critically ill COVID-19 patients. Both studies reveal that the TREM-1 pathway plays a central role in major life-threatening immune dysregulations caused by severe infections, whether it is septic shock or severe forms of COVID-19. The findings presented further validate Inotrem’s innovative approach to treat inflammatory diseases by targeting TREM-1.

The two studies suggest that nangibotide, which targets TREM-1, is pathogen agnostic and has the potential to treat those very severe inflammatory conditions caused by both viral and bacterial infections. Both studies highlight the potential of nangibotide in the treatment of septic shock patients and of patients with severe forms of COVID-19 with a biomarker guided approach using soluble TREM-1 as predictive marker of response to targeted therapy.

The first manuscript in The Lancet Respiratory Medicine is entitled “Prospective evaluation of the efficacy, safety, and the optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock: a double-blind, randomized, controlled, phase 2b trial” and presents results from 355 septic shock patients. The primary outcome was the change in SOFA at day 5 compared to placebo in the pre-defined high soluble TREM-1 (≥ 400 pg/ml) group and in the overall population. Planned evaluation of the optimal sTREM-1 cut-off revealed increased clinically relevant benefits of high dose nangibotide at higher cutoffs (sTREM-1 ≥ 532 pg/ml). The manuscript can be accessed via the following link: The Lancet Respiratory Medicine.

The second manuscript in eClinicalMedicine, entitled “Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID19 receiving respiratory support: results of the ESSENTIAL randomized, double-blind trial” presents the Phase 2 results obtained in 220 COVID-19 patients receiving ventilatory support. In this study, nangibotide has a significant and positive impact on the clinical progression of the disease, as well as on the severity of the respiratory failure, secondary infection rates and notably mortality. The trial showed that sTREM-1 is an effective prognostic marker of outcome in severe COVID-19. The manuscript can be accessed via the following link: eClinicalMedicine.

“Nangibotide is the first TREM-1 inhibitor and has the potential to become the first causal treatment of life-threatening immune dysregulations. This is an area with a major unmet medical need” said Professor Bruno François, Limoges University Hospital, and lead author on the two manuscripts.

“We are excited to see this data published in The Lancet Respiratory Medicine and in eClinicalMedicine, two of the most established peer-reviewed medical journals in our field. These two publications come as a strong recognition of Inotrem’s innovative scientific leadership regarding the role of the TREM-1 pathway and of our solid therapeutic approaches” said Sven Zimmermann, CEO of Inotrem. “We look forward to bringing this potential new treatment option to patients suffering from severe and often fatal inflammatory conditions.”

About nangibotide

Nangibotide is a TREM-1 inhibitor peptide with the potential to restore appropriate inflammatory response, vascular function, and improve post septic shock survival. Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical septic shock models, nangibotide was able to restore appropriate inflammatory response, vascular function, and improved animals’ survival post septic shock. Nangibotide in septic shock has been granted the fast-track status in September 2019 by the FDA and the PRIME status in 2017 by the EMA.

About ASTONISH Study

The Efficacy, Safety and Tolerability of nangibotide in Patients with Septic Shock (ASTONISH) phase 2b trial is a Randomized, Double-blind, Placebo Controlled Dose Selection Study that was performed in Europe and in the US. The study compared the effect of nangibotide at two different doses (0.3 and 1mg/kg/h continuous i.v. infusion for 3 to 5 days) versus standard of care. Results for Phase IIb ASTONISH clinical trial in septic shock patients were disclosed for the first time at the International Sepsis Forum held in Barcelona on October 13. 2022.

About ESSENTIAL Study

The ESSENTIAL phase 2 trial is a double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1·0 mg/kg/h) compared to placebo. The study was stopped after 220 patients had been recruited; of them, 219 were included in the mITT analysis. Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 hours of onset invasive or non-invasive respiratory support because of COVID-19-related ARDS. ESSENTIAL data were disclosed for the first time at the ESICM meeting held in Paris in October 25. 2022.

About Inotrem

Inotrem S.A. is a biotechnology company specialized in immunotherapy for acute and chronic inflammatory syndromes. The company has developed a new concept of immunomodulation that targets the TREM-1 pathway to control unbalanced inflammatory responses. Through its proprietary technology platform, Inotrem has developed the first-in-class TREM-1 inhibitor, nangibotide, with potential applications in a number of therapeutic indications such as septic shock, severe forms of COVID-19 and myocardial infarction. In parallel, Inotrem has also launched an antibody-based program to develop a new therapeutic modality targeting chronic inflammatory diseases. The company was founded in 2013 by Dr Jean-Jacques Garaud, a former head of research and early development at the Roche Group, Prof. Sébastien Gibot and Dr Marc Derive. Inotrem is supported by leading European and North America

Dualyx raises €40 million to progress Treg therapies for autoimmune diseases into the clinic

  • Use of proceeds will enable the development of the Company’s lead autoimmune program DT-001, targeting TNFR2, as well as its pipeline of Treg candidates

  • Financing co-led by Fountain Healthcare Partners, Forbion and Andera Partners with support from existing investors

  • Bernard Coulie appointed as Independent Chairman with immediate effect

Dualyx NV, a Ghent based biotech developing next generation immune modulators, today announces that it has completed a €40 million ($44 million) Series A financing. The fundraise has been co-led by Fountain Healthcare Partners, Forbion and Andera Partners, with support from existing investors V-Bio Ventures, BGV, PMV, VIB, HTGF, and GFF. The funds raised will enable Dualyx to progress its lead autoimmune program DT- 001, as well as its pipeline of Treg candidates. Ena Prosser, Partner at Fountain Healthcare Partners, Juliette Audet, Partner at Forbion, and Aneta Sottil, Director at Andera Partners will join Dualyx’s Board as non-execu;ve directors.

Dualyx’s lead program DT-001 targets the highly aTractive TNF receptor 2 (TNFR2), widely regarded as a master control switch in immune modulation. Through state-of-the-art antibody development, Dualyx has developed an agonist to the receptor which shows highly selective activation of regulatory T cells (Tregs).

To date, promising results have been observed from pre-clinical research with DT-001 and investigational new drug (IND)-enabling studies have begun. DT-001 holds promise to be a game-changing treatment option for a broad range of autoimmune diseases. The funds will be used to progress Dualyx’s DT-001 program into its early clinical proof-of-concept phase. The company has a pipeline of additional Treg focused programs in early-stage development.

Alongside the financing, Bernard Coulie, CEO of Pliant Therapeutics, joins the company as Independent Chairman with immediate effect. Bernard brings with him a wealth of experience in founding and leading successful biotech companies.

“It’s clear to me that TNFR2 is a validated and exciting target for autoimmune therapies, and I am confident that Dualyx has all the ingredients for success with its lead program. I’m therefore delighted to join the Board as Chairman while Dualyx heads towards the clinic,” commented Bernard Coulie, Independent Chairman of Dualyx. “I look forward to working closely with Wouter, Luc and the rest of the Dualyx management team over the coming years.”

“Attracting the expertise and support of top tier investors to Dualyx highlights the potential of the work to date in our DT-001 program and more importantly, completes our high-quality international investor base. We extend a warm welcome to Bernard as Chairman and I am confident that the combined support of our new board will enable progress with our highly promising TNFR2 program, and ultimately our goal of addressing hard-to-treat autoimmune diseases,” added Wouter Verhoeven, CEO of Dualyx.

Dualyx was founded two years ago by CSO Luc Van Rompaey, in a collaborative model with Wurzburg University, Argenx, VIB, Ghent University and KU Leuven. The company has been supported to date by a EUR 7 million seed round from V-Bio Ventures, BGV, PMV, VIB, HTGF, and GFF.

Contact Us
Dualyx
Wouter Verhoeven
contact@dualyx.com


Consilium Strategic Communications
Lucy Featherstone, Kris Lam
Dualyx@consilium-comms.com

About Dualyx

Dualyx is a Ghent-based biotech company dedicated to the development of novel Treg based therapies to address the needs of patients with difficult-to-treat autoimmune diseases. The company was founded in 2020 by Luc van Rompaey in a collaborative model with Wurzburg University, Argenx, VIB, Ghent University and KU Leuven. Dualyx has developed a pipeline of highly promising immune modulating programs including DT-001, an antibody agonist program targeting the TNF receptor 2 (TNFR2) which is currently in IND-enabling studies. TNFR2 is widely regarded as a master control switch in for immunosuppression, making it highly aTractive for Treg therapies. Dualyx also has a pipeline of additional Treg programs in early development. Dualyx is backed by a group of well-respected investors including: Fountain Healthcare Partners, Forbion, Andera Partners, V-Bio Ventures, BGV, PMV, VIB, HTGF and GFF.

Neuromod Devices Closes €30 Million Financing to Expand Availability of Tinnitus Treatment Device Lenire®

  • Equity investment led by Panakès Partners with venture debt provided by European Investment Bank

  • Financing round follows recent US FDA granting of De Novo approval to Neuromod's Lenire tinnitus treatment device

Neuromod Devices Ltd, an Irish medical device company specialising in neuromodulation, has successfully closed a €30 million financing to further commercialise its tinnitus treatment device, Lenire.

Tinnitus, commonly referred to as 'ringing in the ears', is the perception of sound without an external source and affects 10-15% of the global adult populationi. Lenire has shown in large scale clinical trials to reduce tinnitus severityii,iii,iv. The device has recently been granted De Novo approval from the US Food and Drug Administration (FDA) and is available throughout Europe.

As part of the overall financing, a €15m expansion of the Series B was led by Panakès Partners with participation from existing investor Fountain Healthcare Partners. An additional €15m in venture debt was provided by the European Investment Bank.

Proceeds from the financing will be used to launch Lenire in the USA and pursue opportunities in the US Departments of Defense and Veteran Affairs following the device's recent FDA De Novo approval. The first US patients will start treatment for their tinnitus in April 2023.

Neuromod will also expand the availability of Lenire to additional European countries, including Italy, the Netherlands, Portugal, and Sweden, and further next generation product development.

Since Neuromod's previous round of funding in October 2020, the organisation has made significant progress commercialising Lenire, expanding the device's availability throughout Europe, establishing a wholly owned US subsidiary, Neuromod USA Inc, and securing US market approval from the FDA.

Commenting on the news, Dr. Ross O'Neill, Founder & CEO of Neuromod said "We are delighted to announce the successful completion of our Series B2 financing and to welcome new investors Panakès and the European Investment Bank. Europe has a long history in leading the world in hearing innovation. We are proud to add to that tradition by bringing our landmark tinnitus treatment Lenire to the millions of sufferers in Europe and the USA. This investment will help us to expand availability of Lenire in Europe, launch the product in the US and pursue opportunities in the USVA and DoD following our recent De Novo grant from the FDA."

"There are more people in the world with tinnitus than with hearing loss. Tinnitus is one of the largest unmet clinical needs globally and is the number one cause of service-connected disability among US veterans and military personnel. Despite this, there has been practically no innovation in the tinnitus area. This financial support will ensure that, once again, Europe leads the way as Neuromod addresses this huge unmet need in the hearing area." Dr. O'Neill continued.

Thomas Östros, Vice President of the European Investment Bank, commented, "Tinnitus impacts the lives of millions of people and investment to develop new treatments is essential. The European Investment Bank supports cutting edge world class medtech companies and is pleased to provide €15 million venture debt financing to enable Neuromod to commercialise and expand access to tinnitus treatment technology."

The management of tinnitus continues to pose a significant burden on healthcare systems. A recent study estimated the socioeconomic costs of tinnitus in Germany at €21.9 billion per annumvi. In the USA, tinnitus was the most prevalent service-connected disability compensated for by the US Veterans Benefits Administration with more than 2.7 million veterans compensated in 2022vii. It's also estimated the Veterans Benefits Administration paid out more than $4.9 billion through its Veterans Compensation benefits program for tinnitus alone in 2022viii.

Alessio Beverina, Managing Partner of Panakès, who will join Neuromod's board, said, "Tinnitus remains a significant problem for patients around the world and an important cost for healthcare systems globally. Panakès is proud to support Neuromod's continued work to meet this challenge with their ground-breaking product Lenire; I'm particularly excited at the possibility to improve the life of tinnitus patients and looking forward to working closely with Neuromod's team."


Dr. Manus Rogan, Chairman of Neuromod and Managing Partner of Fountain Healthcare Partners commented, "We're proud to continue to support Neuromod as the organisation takes the next step forwards in their mission to improve quality of life for millions of people living with tinnitus. I'm delighted to welcome Alessio Beverina to Neuromod's board at an exciting time for the company as they work towards making Lenire more widely available."

Lenire is a bimodal neuromodulation device which works by delivering mild electrical pulses to the tongue, through an intra-oral component called the 'Tonguetip®', combined with auditory stimulation through headphones to drive long-term changes in the brain to treat tinnitus. To date, the device has been used in large-scale clinical trials with over 700 patients.

The first of these trials, TENT-A1, represents one of the largest and longest followed-up clinical trials ever conducted in the tinnitus field and was the cover story for the scientific journal Science Translational Medicine in October 2020. The trial enrolled 326 participants and 86.2% of treatment-compliant participants reported an improvement in their tinnitus symptom severity after a 12-week treatment periodii,iv.

In June 2022, the results of the second large-scale clinical trial, TENT-A2, were published in the highly-regarded journal Nature – Scientific Reports. TENT-A2 showed that changing the stimuli patients received after six weeks of treatment could result in a further clinically significant reduction in their tinnitus severityiii,iv. 95% of treatment-compliant participants reported an improvement in their tinnitus symptom severity after 12 weeks of treatmentiii,iv. When followed up with 12 months after treatment had ended, 91% of treatment-compliant participants reported sustained improvement in their tinnitus severityiii,iv.

A third large-scale clinical trial, TENT-A3, was designed to meet the FDA's rigorous De Novo requirements and carried out from March to October 2022 at three independent sitesix. 70.5% of patients with moderate or worse tinnitus reported a clinically significant improvement in their tinnitus severity following six weeks of treatment with Lenire, after six weeks of sound-only treatment provided clinically insignificant improvement. Further results from the trial are currently in preparation for peer-review and publication in a scientific journal.

About Neuromod Devices Ltd

Founded in 2010, Neuromod Devices Ltd. is a medical technology company headquartered in Dublin, Ireland. Neuromod specialises in the design and development 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 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 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.

About Panakès Partners

Panakès Partners is a Venture Capital firm, based in Milan, which invests in the most ambitious companies and teams, developing revolutionary technologies and products, in the field of life sciences, aiming to improve the lives of people around the world. Panakès, founded in 2015 by Fabrizio Landi, Alessio Beverina and Diana Saraceni, has €250 million under management. www.panakes.it.

About Fountain Healthcare Partners

Fountain Healthcare Partners is a life science venture capital fund with offices in Dublin and New York. Founded in 2008, Fountain is Ireland's largest dedicated life science venture capital fund with more than €300 million under management.

Fountain invests in entrepreneurs and companies with disruptive technologies or products that have a clear pharmacoeconomic benefit and a defined pathway to commercialisation, value enhancement and exit. Fountain typically leads or co-leads its investments and has sourced private and public deals from start-ups, corporate spin-outs and turnaround situations. For more information please visit: www.fh-partners.com.

Connect with Neuromod Devices Ltd

LinkedIn: linkedin.com/company/neuromod
Twitter: twitter.com/NeuromodDevices
Website: neuromoddevices.com

References & Notes

(i) Baguely et al., Tinnitus, The Lancet (2013), https://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, https://doi.org/10.1038/s41598-022-13875-x (2022)
(iv) As measured by THI. THI or Tinnitus Handicap Inventory is a clinical standard for measuring the impact of tinnitus on someone's day-to-day life. Measured on a scale of 100, the higher the score, the greater the impact of tinnitus. Reducing a person's THI score should correspond to improved quality of life by reducing how their tinnitus is affecting them.
(v) R. Biswas et al., Tinnitus prevalence in Europe: a multi-country cross-sectional population study, The Lancet Regional Health (2021), https://doi.org/10.1016/j.lanepe.2021.100250
(vi) 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.
(vii) US VA Benefits Report Fiscal Year 2022: https://benefits.va.gov/REPORTS/abr/docs/2022-abr.pdf
(viii) According to https://www.va.gov/disability/compensation-rates/veteran-rates/past-rates-2022/ the 2022 10% disability rate was $152.64 per month. 2,703,665 veterans (https://benefits.va.gov/REPORTS/abr/docs/2022-abr.pdf) receiving 12 payments of $152.64 for tinnitus results in $4.952 billion. The VA assigns a 10% disability rating to tinnitus: https://benefits.com/veterans-disability/tinnitus-most-common-va-disability
(ix) https://clinicaltrials.gov/ct2/show/NCT05227365

New Data show NEUROMARK® Chronic Rhinitis Treatment Offers Significant Symptom Improvements

Results from the CLARITY Study Show the NEUROMARK® System Provides Safe and Effective Treatment for Patients with Chronic Rhinitis

Neurent Medical, a company pioneering innovative non-surgical interventions to treat chronic inflammatory sinonasal diseases, today announced three-month data from the CLARITY study, a prospective, single-arm, multicenter safety and efficacy study of its NEUROMARK® System for patients with chronic rhinitis. These data, published in Laryngoscope Investigative Otolaryngology, show that patients receiving the NEUROMARK therapy demonstrated significant improvement in rhinorrhea and nasal congestion symptoms at 3 months.


Approximately one in four Americans have chronic rhinitis1, a condition that results in persistent congestion, rhinorrhea (runny nose), sneezing, and nasal itching caused by inflammation and swelling of the mucosal membrane in the nose. NEUROMARK’s unique device and intelligent technology platform enable otolaryngologists to treat chronic rhinitis with precision and control, which in turn allows for an enhanced patient experience from treatment through recovery.


The CLARITY Study enrolled thirty-six participants and all completed follow-ups at one and three months. Primary endpoints were device-related serious adverse events (SAEs) at 1 month and change from baseline in visual analog scale nasal symptom scale (VAS NSS) for rhinorrhea and nasal congestion at 3 months. Total Nasal Symptom Score (rTNSS) and mini Rhinoconjunctivitis Quality of Life Questionnaire (mini RQLQ) score were also evaluated.


The data demonstrated the following benefits of NEUROMARK’s posterior nasal nerve (PNN) ablation procedure at 3 months post procedure:

  • The mean VAS NSS scores for rhinorrhea and nasal congestion significantly improved from baseline (both p<0.0001), achieving a mean percent change of 53% and 55%, respectively.

  • Total rTNSS scores and all individual items demonstrated significant improvement (all p<0.001).

  • Percent responder rate (≥30% reduction from baseline in total rTNSS) was 78%.

  • Total mean mini RQLQ scores and all subdomains improved significantly (p<0.0001).

  • 89% of participants reported a minimal clinically important difference (MCID) of ≥0.4 point improvement in the mini RQLQ score.

  • No serious adverse events occurred during the study, and there were no reports of epistaxis or headaches.

“People living with chronic rhinitis have had limited options when traditional therapies fail. Other therapies on the market don’t always adequately address symptoms for every patient,” said Douglas D. Reh, MD, FARS, Otolaryngology Specialist at ENT Associates and the study’s principal investigator. “The data showed statistically significant and clinically meaningful improvement in symptoms and quality of life assessments at 3 months post NEUROMARK procedure.”


NEUROMARK is designed to gently apply controlled low-power radio frequency (RF) energy to target regions of the nasal cavity, disrupting the parasympathetic nerve signals that can trigger an inflammatory response. This unique system offers ENTs a novel and unique leaflet design to help deliver precision neurolysis of posterior nasal nerves, with the intelligence and flexibility to comfortably accommodate a range of anatomies.


“We’re encouraged by the three-month CLARITY data demonstrating the safety, efficacy and relief from chronic rhinitis symptoms that can be achieved with NEUROMARK,” said Neurent Medical CEO Brian Shields. “I’m grateful to Dr. Reh and each of the study’s investigators for adding to the growing body of clinical evidence supporting PNN for these patients.”


The NEUROMARK System has received U.S. Food and Drug Administration (FDA) clearance and Neurent Medical announced the limited market release of the system in February 2023.


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 algorithmic control, physicians can 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. For more information visit www.neurentmedical.com.


1 Settipane RA, Charnock DR. Epidemiology of rhinitis: allergic and nonallergic. Clin Allergy Immunol. 2007;19:23-34. PMID: 17153005.

Vivasure Medical Announces FDA IDE Approval to Initiate U.S. Pivotal Study

  • Pivotal study expected to be completed by year-end 2023 and set the stage for commercialization of PerQseal® system for large hole vessel closure

  • Company announces €30 million strategic investment from Haemonetics as part of its previously disclosed Series D financing

Vivasure Medical® Limited (“Vivasure” or the “Company”), a company pioneering novel fully absorbable technology for percutaneous vessel closure, today announced that the U.S. Food and Drug Administration (FDA) has granted an Investigational Device Exemption (IDE) to advance the company’s PATCH Clinical Study, a multi-center, single-arm, pivotal study evaluating the safety and effectiveness of the Vivasure PerQseal® Closure Device System.


The PATCH pivotal study will enroll up to 188 patients across the U.S. and Europe. The company intends to use the clinical study results to support an FDA pre-market approval submission as well as multinational commercial launch of the PerQseal system for large hole vessel closure.


The company also announced that Haemonetics Corporation (NYSE: HAE) (“Haemonetics”) invested €30 million in the company as part of its Series D financing, the initial tranche of which closed in May 2022. Haemonetics is a global healthcare company providing innovative medical products and solutions for interventional cardiology and electrophysiology procedures, the surgical suite, hospital transfusion services, and blood and plasma component collection. The strategic investment by Haemonetics includes an option to acquire Vivasure Medical upon completion of certain milestones. Large hole arterial closure represents a high growth global market opportunity currently estimated at over $300 million annually, with double-digit growth.


“We are excited to be moving forward with this multi-center pivotal study which we expect will affirm the safety and effectiveness of PerQseal for large hole arterial closure. Moreover, we are delighted to now be partnered with Haemonetics, which has quickly established itself as a market leader in advanced vessel closure,” said Andrew Glass, Chief Executive Officer of Vivasure Medical. “We strongly believe in the potential of our fully absorbable patch-based approach to large hole closure, and these steps mark important progress toward fulfilling our mission of enabling safe and effective advanced structural and percutaneous cardiovascular therapies.”


“Vascular closure is a key focus of Haemonetics’ growth strategy, and we are excited about the long-term potential of Vivasure’s innovative technology to advance large hole percutaneous procedures,” said Stew Strong, President, Global Hospital at Haemonetics.


Large hole arterial access is required for clinicians to perform numerous life-saving percutaneous cardiovascular procedures such as transcatheter aortic valve replacement (TAVR), thoracic and abdominal endovascular aneurysm repair (TEVAR and EVAR), and the use of a cardiac assist device (CAD). The current approach to large-diameter arterial closure is a surgical repair or the use of suture- or collagen-based closure devices. Both can result in major vascular complications, such as vessel distortion at the closure site, which may lead to stenosis, thrombus formation or abrupt closure.


PerQseal is designed to be the first sutureless, fully absorbable synthetic implant for large-bore vessel punctures. Its low profile patch can be placed from inside the vessel and is intended to make deployment simpler and more controlled than conventional closure techniques. Clinical studies to date have shown a low complication rate and high technical success.


Existing investors include 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. Vivasure Medical has also received support from Enterprise Ireland and the European Investment Bank.


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.

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


Contacts

Media contact:
Sarah Lundberg
Health+Commerce
sarahlundberg@healthandcommerce.com
612.770.0359

FDA Grants Lenire® Tinnitus Treatment Device De Novo Approval

  • Neuromod Devices' non-invasive device, Lenire, is the first of its kind granted approval to treat tinnitus in the US market.

  • At least 25,000,000 Americans are suffering from tinnitus, 2,700,000 are veterans.

  • FDA approval based on results of 112-patient pivotal TENT-A3 clinical trial supported by confirmatory Real-World Evidence from 204 patients.

  • TENT-A3 primary endpoint analysis showed that patients at least moderately impacted by tinnitus1 achieved a clinically meaningful improvement following the bimodal phase of the trial. This was consistent with what was observed in the Real-World Evidence submitted to the FDA.

  • Over the entire trial, 79.4% of patients experienced a clinically significant improvement. 82.4% were compliant to bimodal treatment and 88.6% would recommend Lenire as a tinnitus treatment.

  • When compared to sound therapy alone, patients at least moderately impacted by tinnitus1 were significantly more likely to achieve a clinically meaningful improvement using Lenire's bimodal stimulation.

  • Treatment with Lenire to be available for Americans with tinnitus from April 2023.

Neuromod Devices Ltd. announced today that the US Food and Drug Administration (FDA) has granted De Novo approval to Lenire, the first bimodal neuromodulation device of its kind to be approved by the FDA for the treatment of tinnitus.


Tinnitus, which is commonly known as 'ringing in the ears', is a complex neurological condition that causes a perception of sound when there is no external source. It is estimated that at least 25 million Americans2 are currently suffering from tinnitus.


Tinnitus is a silent burden on the USA's national healthcare system, costing an estimated $660 per patient per year for visits to clinics alone3. Tinnitus is also the most prevalent and fastest-growing service-connected disability compensated for by The US Veterans Administration (VA), with more than 2.7 million veterans compensated in 20224 and 12% year-on-year growth5. It is estimated that the VA paid out more than $4.9 billion through its Veterans Compensation benefits program for tinnitus alone in 20226, with further undisclosed expenditure on treatments, such as hearing aids, sound therapy and counselling, which deliver varying levels of success.


"Lenire's approval not only means that millions of Americans living with tinnitus can get the treatment they need but further validates over a decade of research and development that resulted in a safe solution that provides relief for tinnitus patients. Lenire is the first bimodal neuromodulation device to go through the rigors of the FDA's De Novo process. For patients that are at least moderately impacted by their tinnitus1, Lenire has now been shown to be more effective than sound therapy, which is one of the current clinical standards of treatment." said Ross O'Neill, Neuromod Devices' Founding CEO.


The FDA's De Novo approval is based on the success of Lenire's third large-scale clinical trial, TENT-A3, supported by Real-World Evidence from 204 patients. Over the entire trial, 79.4% of the patients experienced a clinically significant improvement, 82.4% were compliant to bimodal treatment, and 88.6% responded that they would recommend Lenire as a tinnitus treatment7. The TENT-A3 primary endpoint analysis showed that patients that were at least moderately bothered by tinnitus, which includes patients in the moderate, severe and catastrophic categories as defined by the Tinnitus Handicap Inventory (THI)1, achieved a clinically meaningful improvement in tinnitus following the bimodal treatment phase of the trial. The analysis showed that this patient group were more likely to achieve a clinically meaningful improvement using Lenire's bimodal sound and tongue stimulation than sound therapy alone7. TENT-A3 also demonstrated that Lenire is inherently safe with zero serious adverse events7. These efficacy, compliance and safety findings were highly consistent with the Real-World Evidence from 204 patients included in the De Novo submission.


TENT-A3 was a controlled clinical trial, designed by Neuromod to meet the FDA's requirements, that compared the effects of 6 weeks of bimodal neuromodulation with 6 weeks of sound therapy alone. The trial was conducted at three independent sites from March to October 2022 with 112 enrolled participants8. The De Novo approval of Lenire is significant as it acknowledges Lenire as a technological and clinical pioneer for tinnitus treatment. This approval establishes a new regulatory category for medical devices in the USA.


"With this FDA approval of the Lenire device, it will provide me and tinnitus specialists across the United States with an exciting new tinnitus treatment option for our clinical toolbox," explained Dr. Jason Leyendecker (AuD). "Many tinnitus patients are not availing of currently available options, such as hearing aids and counseling, and success with these options is varied. What is especially encouraging about this new bimodal treatment is that it can deliver clinical benefits in as short as 6 weeks of treatment, which can greatly improve our capacity issues since more patients can be helped in a shorter period of time." Dr. Leyendecker is a leading tinnitus specialist and owner of The Tinnitus and Hyperacusis Clinic of Minnesota. He is the past President of Minnesota Academy of Audiology and President Elect of Academy of Doctors of Audiology.


The TENT-A3 trial builds upon the success of two previous landmark clinical trials that included more than 500 patients. TENT-A1 was one of the largest and longest followed-up clinical trials ever conducted in the tinnitus field. The study was the cover story for the prestigious scientific journal Science – Translational Medicine in October 2020. TENT-A1 was a double-blind randomized trial involving 326 patients who were evaluated over a 12-week treatment period and a 12-month post-treatment phase9. 86.2% of those who completed the 12 weeks of treatment reported improvement in their tinnitus severity9. These therapeutic improvements continued for 12 months after cessation of treatment. 83.7% of patients were treatment compliant and there were zero serious adverse events in the trial9.


The results of Lenire's second large-scale clinical trial, TENT-A2, were published in the highly regarded scientific journal Nature – Scientific Reports. The findings of this 192-patient double-blind randomized trial showed that changing stimuli midway through treatment enhanced the effectiveness of bimodal neuromodulation. 95% of patients that completed 12 weeks of treatment reported improvement in their tinnitus severity10. These therapeutic effects were sustained up to 12 months after treatment ended9. 83.8% of patients were treatment compliant and there were zero serious adverse events in the trial10.


"What is most remarkable is the consistency of the efficacy, safety and compliance data across our TENT-A1, TENT-A2 and TENT-A3 clinical trials. Taken together, we have demonstrated the effectiveness and inherent safety of Lenire in over 600 clinical trial patients. De Novo approval from the FDA is another significant achievement in what has been an exciting journey for our bimodal stimulation technology," said Prof. Hubert Lim, Chief Scientific Officer at Neuromod Devices.


Patients with tinnitus are prescribed Lenire by an appropriately qualified healthcare professional, such as an Audiologist or ENT Surgeon, after an assessment for suitability and can complete treatment from home in between follow-up appointments with their clinician.


"FDA approval of the Lenire Tinnitus Treatment System is a quantum leap forward in the caring of patients with bothersome tinnitus. The otolaryngologist now has access to innovative Lenire technology and can prescribe it to patients who are at least moderately impacted by their tinnitus. The majority of these tinnitus patients are either inadequately relieved or are opting not to pursue existing options, such as hearing aids. These patients can now move forward with this impressive treatment system." expressed Dr. Steven W. Cheung, who is a Professor of Otolaryngology-Head and Neck Surgery at the University of California, San Francisco, and Staff Otorhinolaryngologist at the Veterans Affairs San Francisco Healthcare System.


Neuromod Devices was founded by Dr. Ross O'Neill in 2010 to develop bimodal neuromodulation technologies for tinnitus and is supported by venture capital firms Fountain Healthcare Partners and Panakes Partners. In 2021, Neuromod established Neuromod USA Inc. as a wholly owned subsidiary to prepare for the market entry of Lenire in the USA pending FDA approval. Since then, Neuromod USA has convened a clinical advisory board of specialist tinnitus clinicians from across the US. These clinical experts will advise on and ensure that patients who will use Lenire receive unrivalled care throughout their treatment.


Following the FDA's granting of approval, Neuromod will train Audiologists and ENT Surgeons specialising in tinnitus care with the intention of treating the first tinnitus patients based in the USA as soon as April 2023.


References & Notes

1. As measured by Tinnitus Handicap Inventory (THI). THI is the most widely used clinical standard for measuring the impact of tinnitus on someone's day-to-day life. The THI is a validated instrument that is measured on a scale of 100, the higher the score, the greater the impact of tinnitus. THI scores are categorized into five severity levels: slight, mild, moderate, severe and catastrophic. Patients that are at least moderately affected by their tinnitus have a THI score of 38 and above and fall into the moderate, severe and catastrophic categories.

2. https://www.nidcd.nih.gov/health/tinnitus

3. Goldstein E., Ho C.X., Hanna R., Elinger C., Yaremchuk K.L., Seidman M.D., Jesse M.T. Cost of care for subjective tinnitus in relation to patient satisfaction. Otolaryngol. Head Neck Surg. 2015;152:518–523. doi: 10.1177/0194599814566179.

4. US VA Benefits Report Fiscal Year 2022: https://www.benefits.va.gov/REPORTS/abr/docs/2022-abr.pdf

5. Calculated based on average annual increase in tinnitus benefit recipients from 2008 to 2022: https://www.benefits.va.gov/REPORTS/abr/archive.asp

6. According to https://www.va.gov/disability/compensation-rates/veteran-rates/past-rates-2022/ the 2022 10% disability rate was $152.64 per month. 2,703,665 veterans (https://www.benefits.va.gov/REPORTS/abr/docs/2022-abr.pdf) receiving 12 payments of $152.64 for tinnitus results in $4.952 billion. The VA assigns a 10% disability rating to tinnitus: https://www.benefits.com/veterans-disability/tinnitus-most-common-va-disability

7. TENT-A3 clinical trial data in preparation for publication

8. https://clinicaltrials.gov/ct2/show/NCT05227365

9. Conlon et al., Sci. Transl. Med. 12, eabb2830 (2020)

10. Conlon et al., Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial, Sci Rep, https://www.nature.com/articles/s41598-022-13875-x (2022)

For More Information

Joe Roche
Head of Communications
Neuromod Devices
joe.roche@neuromoddevices.com
+353 87 416 0138

About Neuromod Devices Ltd

Founded in 2010, Neuromod Devices Ltd. is a medical technology company headquartered in Dublin, Ireland. Neuromod specialises in the design and development of bimodal neuromodulation technologies to address the clinical needs of patients suffering from chronic and debilitating tinnitus. Neuromod's tinnitus treatment device, Lenire, is currently available throughout Europe and has received a granting of De Novo approval from the FDA in the USA. For more information visit www.neuromoddevices.com.

About Lenire

Lenire is a combined acoustic and electrical intraoral stimulation device for the relief of tinnitus. The device's novel bimodal neuromodulation technology includes three parts. Bluetooth® headphones, which play custom sounds to the ear to activate the auditory nerve, a Tonguetip®, which is a proprietary intraoral device that also activates nerves by sending mild electrical stimulation to the surface of the tongue, and a controller that allows patients to adjust the duration and treatment intensity.


The custom sounds and tongue stimulation work together to reduce patients' tinnitus severity. It is the first non-invasive bimodal neuromodulation tinnitus treatment device shown to relieve tinnitus in three large-scale clinical trials.


Lenire has been granted De Novo approval for the treatment of tinnitus in the USA by the FDA and CE-mark certification in Europe. Further details about Lenire including a list of providers can be found at www.lenire.com.


Connect with Neuromod Devices Ltd

LinkedIn: linkedin.com/company/neuromod

Twitter: twitter.com/NeuromodDevices

Website: neuromoddevices.com

Neurent Medical Announces Limited Market Release of NEUROMARK® System to Treat Chronic Rhinitis

NEUROMARK received new Category I CPT code and support from AAO position statement

Neurent Medical, a company pioneering innovative non-surgical interventions to treat chronic inflammatory sino-nasal diseases, today announced its NEUROMARK® Rhinitis Neurolysis Therapy (RNT) is now commercially available in limited U.S. markets. Commercialization comes as the American Medical Association (AMA) issued a new Category I Current Procedural Terminology (CPT®) code for posterior nasal nerve ablation (PNN) procedures, which includes NEUROMARK, to treat chronic rhinitis. The code will go into effect in January 2024. Furthermore, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) endorses this procedure.

Approximately one in four Americans suffer from chronic rhinitis, which can result in irritating symptoms including rhinorrhea (runny nose), persistent congestion, swelling of the mucosal membrane in the nose, and sneezing and nasal itching caused by inflammation. NEUROMARK’s unique device and intelligent technology platform enable Otolaryngologists to treat chronic rhinitis patients with precision and control and enhance the patient experience from treatment through recovery.

“Our goal is to provide an easy-to-operate, smart treatment that provides clinicians with more precise control and confidence, and patients with a safe, comfortable experience,” said Brian Shields, CEO of Neurent Medical. “The new CPT code underscores the value of this technology as we further grow our commercial presence in the U.S. and work to make NEUROMARK more accessible to the millions of patients living with chronic rhinitis today.”

NEUROMARK is designed to gently apply controlled low-power radio frequency (RF) energy to target regions of the nasal cavity, disrupting the parasympathetic nerve signals that can trigger an inflammatory response. This unique system offers ENTs a novel and unique leaflet design to help deliver precision neurolysis of posterior nasal nerves, with the intelligence and flexibility to comfortably accommodate a range of anatomies.

The recent endorsement of PNN by the AAO-HNS, a specialty society representing almost 12,000 ENT surgeons, further validates Neurent Medical’s long-term future in the treatment of chronic rhinitis.

About Neurent Medical

Neurent Medical is pioneering innovative treatments for chronic inflammatory sino-nasal diseases by targeting and safely disrupting hyperactive autonomic nerves that drive underlying inflammation. Its proprietary NEUROMARK® technology with a unique design and advanced algorithmic control, physicians can 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. For more information visit www.neurentmedical.com.