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.

XyloCor Therapeutics Reports Positive Topline Safety and Efficacy Results from Phase 2 EXACT Clinical Trial of XC001 Novel Gene Therapy for Refractory Angina

• No serious adverse events related to drug product were reported

• Patients demonstrated improvements in exercise capacity and reductions in episodes of chest pain

• Cardiac imaging results provide mechanistic evidence supporting the therapeutic potential of XC001 in cardiovascular disease

XyloCor Therapeutics, a clinical-stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, today announced completion of the Phase 2 portion of its Phase 1/2 clinical trial (EXACT) designed to assess the safety and preliminary evidence of efficacy of lead gene therapy candidate XC001 (encoberminogene rezmadenovec) in patients with refractory angina. EXACT met both safety and efficacy objectives. There were no safety issues related to drug product or unexpected serious adverse events related to XC001 administration. Six-month data from 28 patients in the Phase 2 portion of the study showed improvements in several key efficacy measures, including reduction in ischemic burden.

“We are excited to see EXACT completing its 6-month endpoint. The trial met all of its safety and exploratory objectives, showing intriguing benefits in these needy patients across a variety of objective and subjective measures,” said Thomas Povsic, M.D., Ph.D., Professor of Medicine, Duke University School of Medicine and National Principal Investigator for the EXACT study. “The strong range of mechanistic evidence demonstrate that administration of XC001 is a scientifically-sound approach for achieving a biological effect that has the potential to improve patients’ quality of life.”

XC001 is a one-time gene therapy designed to reduce ischemic burden by creating new blood vessels in the heart. In the Phase 2 portion of the EXACT trial, evidence of the drug’s mechanism of action was demonstrated by the reduction of ischemic burden measured by cardiac positron emission tomography (PET) imaging. The reduction in ischemic burden was accompanied by an improvement in total exercise duration, an important measure of exercise capacity. Prior to treatment, almost all subjects had marked limitations on ordinary physical activity. Six months after treatment, nearly half of all subjects were able to conduct ordinary physical activity without causing angina. The data from the Phase 2 EXACT study are potentially meaningful for patients with refractory angina, which includes more than one million people in the United States, who have no treatment options.

“We are excited to share this positive topline data from the Phase 2 portion of the EXACT trial, reinforcing our confidence in XC001 as a novel therapeutic approach with the potential to address the significant unmet medical needs of people with refractory angina,” said Al Gianchetti, President and CEO of XyloCor. "We now look forward to pursuing key upcoming milestones in XC001’s continued development, including finalizing our pivotal trial design through our ongoing discussions with the FDA and other regulatory authorities.”

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 recently completed 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.

Corporate and Investor Relations:

A. Brian Davis, XyloCor Therapeutics
brian.davis@xylocor.com
610-541-2056

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

Priothera announces first patients enrolled in pivotal MO-TRANS global Phase 2b/3 study with mocravimod as an adjunctive and maintenance therapy for patients with AML undergoing allogeneic HCT

• Mocravimod is the only S1PR modulator being developed to treat blood cancers and improve CAR-T therapy

• Phase 1b/2a data has shown mocravimod is safe and well tolerated

Priothera, a late-clinical stage biotechnology company pioneering the development of its S1P receptor modulator compound mocravimod today announced that the first patients have been enrolled in the pivotal MO-TRANS global Phase 2b/3 study evaluating mocravimod in AML patients undergoing allogeneic hematopoietic cell transplant (HCT).

Mocravimod, a sphingosine 1 phosphate (S1P) receptor modulator which has been previously tested in multiple autoimmune indications, is being developed to enhance the curative potential of allogeneic HCT. Mocravimod has shown a clinically relevant benefit in an early clinical study in patients with hematologic malignancies undergoing allogeneic HCT.

Priothera is initiating the pivotal MO-TRANS global Phase 2b/3 study in Europe, Israel, the US and in additional Asian and Latin American countries, to assess the efficacy and safety of mocravimod as an adjunctive and maintenance therapy in AML patients undergoing allogeneic HCT. The double-blind, placebo-controlled study assesses relapse-free and overall survival of two doses of mocravimod in comparison to placebo. Topline data from this study are expected in 2025.

Marcos de Lima, M.D., is the Principal Investigator for the MO-TRANS global Phase 2b/3 trial. Dr. de Lima is professor of medicine at The Ohio State University College of Medicine and a hematologist-oncologist at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

Prof de Lima said: “We are excited to be part of the important MO-TRANS global Phase 2b/3 study to investigate mocravimod, a potential new adjunctive and maintenance therapy for patients with Acute Myeloid Leukemia undergoing allogeneic Hematopoietic Cell Transplant. Maintenance therapy is fast becoming the new frontier in the treatment of AML and we are committed to bringing forth new innovative therapies to AML patients.”

Elisabeth Kueenburg, M.D., Chief Medical Officer at Priothera, commented: “This MO-TRANS global Phase 2b/3 study builds on pre-clinical and clinical proof of concept studies which demonstrated mocravimod’s ability to improve survival outcomes for patients with hematological malignancies requiring allogeneic HCT. The mode of action has been well-established in autoimmune indications, but never in hematology. Mocravimod has the potential to be a first-in-class therapy in maintaining the graft-versus-leukemia effect, while preventing graft-versus-host disease, one of the most serious complications of allogeneic HCT. We expect this trial to deliver important clinical data towards the registration of mocravimod in this indication.”

Florent Gros, Co-Founder and CEO of Priothera, said: “Having successfully enrolled the first AML patients undergoing allogeneic HCT in our MO-TRANS global study represents a significant milestone for Priothera as we believe mocravimod has the potential to address a significant unmet need. Furthermore, we anticipate a strong uptake in patient enrollment with a significant number of patients currently being identified. We look forward to seeing topline results in 2025."

***

About mocravimod

Mocravimod (also known as KRP203) is a synthetic, sphingosine 1-phosphate receptor (S1PR) 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 2b/3 study for patients with Acute Myeloid Leukemia (AML) receiving allogeneic hematopoietic cell transplantation (HCT). Allogeneic HCT is the only potentially curative approach for AML patients, but current treatments have unacceptably high mortality and morbidity rates.

Priothera leverages mocravimod’s unique mode of action to maintain the beneficial graft-versus leukemia (GVL) activity, while reducing tissue damage resulting from graft-versus-host disease (GVHD), both a consequence of allogeneic HCT. This novel treatment approach – mocravimod being the only S1PR 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 sphingosine-1-phosphate (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 graft-versus-leukemia (GVL) benefits in patients receiving HCT while inhibiting graft-versus-host-disease (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

Inotrem Receives Funding from the Crohn’s & Colitis Foundation to help develop new therapeutic approaches in Inflammatory Bowel Disease (IBD)

The funding will support the development of INO-02 a new long-acting therapeutic approach to modulate the TREM-1 pathway.

Inotrem, an advanced clinical stage biotech company specialized in immunotherapies for acute and chronic inflammatory syndromes, announced today it received funding from the Crohn’s & Colitis Foundation’s IBD Ventures under a program to accelerate research and development that aim to improve the quality of life for patients with IBD. The funding will support the development of a new therapeutic approach in IBD focusing on the TREM-1 pathway.

The funding follows a R&D collaboration between Inotrem, and the Crohn’s & Colitis Foundation announced in April 2022. The R&D collaboration seeks to pave the way of a personalized medicine approach in IBD patients based on TREM-1. Under the terms of the agreement, Inotrem has access to data and bio-samples from Foundation’s IBD Plexus®, which is the largest IBD database in the US with data from over 25,000 patients. Last over 18 months, the project will be a cornerstone in the design of Inotrem’s first-in-human clinical study with INO-02.

There are today 10 million people worldwide suffering from IBD, and the need for new therapeutic options remains very strong. Approximately 30% of patients are unresponsive to existing therapies and even among the initial responders, in up to 10% the drugs lose efficacy over time. For a decade, Inotrem has been elucidating the biology of TREM-1 as a regulator of the immune response in both acute as well as chronic inflammatory diseases. TREM-1 is a potential important contributor to IBD pathophysiology and targeting this pathway may offer a new treatment option for IBD patients with immune dysregulation.

“We are grateful for the support of such a well-respected organization as The Crohn’s & Colitis Foundation. This funding will help us to expand our patented technology platform centered around the TREM-1 pathway and dedicated to developing new therapies for chronic inflammatory syndromes next to our existing modalities for acute diseases,” indicates Sven Zimmermann, CEO of Inotrem.

“Beyond the financial support, this is a strong recognition of Inotrem’s scientific leadership regarding the role of the TREM-1 pathway in inflammatory processes as well as our robust therapeutic approaches targeting that biological target,” says Marc Derive, Chief Scientific Officer and Cofounder of Inotrem.

About Inotrem

Inotrem S.A. is an advanced clinical stage biotech company specialized in immunotherapies 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 and myocardial infarction. In parallel, Inotrem has also launched another 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. Sebastien Gibot and Dr Marc Derive. Inotrem is supported by leading European and North American investors. www.inotrem.com

About the Crohn’s & Colitis Foundation

The Crohn's & Colitis Foundation is the leading non-profit organization focused on both research and patient support for inflammatory bowel disease (IBD), with the mission of curing Crohn's disease and ulcerative colitis, and of improving the quality of life of the millions of Americans living with IBD. The Foundation’s work is dramatically accelerating the research process through investment in research initiatives, while also providing extensive educational and support resources for patients and their families, medical professionals, and the public. For more information, visit crohnscolitisfoundation.org, call 888-694-8872, or email info@crohnscolitisfoundation.org.

Calypso Biotech Announces First Patient with Eosinophilic Esophagitis Dosed in Anti-Interleukin-15 (IL-15) Monoclonal Antibody CALY-002 Phase 1a/b Trial, and Animal POC Data in Atopic Dermatitis

• Healthy volunteers phase completed showing differentiating target engagement biomarker data and favorable safety data

• On track for top-line histology data in 2023 in Celiac Disease and Eosinophilic Esophagitis

• Proof-of-concept data of CALY-002 in humanized Atopic Dermatitis model supports “pipeline-in-a drug” value proposition

Calypso Biotech, a leader in the development of Interleukin-15 (IL-15) targeted therapies, announces today dosing of the first Eosinophilic Esophagitis patient in the multiple dosing part of the Phase 1 clinical trial of CALY-002, a novel humanized - and highly differentiated - monoclonal antibody neutralizing IL-15. The ongoing Phase 1 clinical study of CALY-002 includes a single ascending dose (SAD) in Healthy Volunteers as well as multiple ascending dosing (MAD) in cohorts of patients with Celiac Disease or Eosinophilic Esophagitis, two indications with significant unmet medical need where IL-15 plays a critical role in their pathogenesis [NCT04593251].

The SAD part of the study has been completed. Across the wide range of tested dose levels in Healthy Volunteers, CALY-002 was well tolerated, with a PK profile typical for IgG monoclonal antibodies. Importantly, target engagement (i.e., IL-15 blockade) was demonstrated through the reduction of NK cell numbers in blood, owing to the well-known role of IL-15 as a homeostatic factor for NK cells. CALY-002 is the first IL-15-specific antibody to demonstrate blood NK cell reduction in humans, underpinning its unique and differentiated profile.

The MAD part of the study in patients with Celiac Disease or Eosinophilic Esophagitis is currently progressing into the highest dose cohorts. This phase investigates safety, PK, pharmacology, disease biomarkers and clinical efficacy endpoints including histology of multiple doses of CALY-002 or placebo over either an 8-week treatment period in a gluten-challenge setting (Celiac Disease) or a 12-week period of open label CALY-002 treatment (Eosinophilic Esophagitis). Top-line histology data will be generated in 2023 for both indications.

Further, CALY-002 was demonstrated to be active in a recently developed humanized model of Atopic Dermatitis, results presented at the 51st European Society for Dermatological Research conference (Amsterdam, 28 September – 01 October 2022). These important data further highlight the potential of CALY-002 in multiple auto-immune indications.

Calypso Biotech Chief Medical Officer, Dr. Jos Houbiers, MD, PhD, comments “the demonstrated pharmacological efficacy highlights the potency of CALY-002 and is promising for the clinical histology results in the MAD parts of the study. New and improved treatments are much needed for Celiac Disease and Eosinophilic Esophagitis patients who have limited treatment options. For patients with celiac disease, clinical practice learns that adherence to a gluten-free diet is very difficult and many patients continue to experience symptoms; in asymptomatic patients, histological damage to the small intestine can be present unnoticed, studies show.’’

About Calypso Biotech BV

Calypso Biotech BV is a private biotechnology company focused on the research and development of novel biologics to address unmet medical need in autoimmune and inflammatory diseases, with a unique expertise in IL-15 biology. IL- 15 controls immune pathways critically involved in disease onset and maintenance (‘’disease memory’’), as well as tissue destruction, in addition to its broad effect on inflammation. Calypso’s approach offers significant advantages over traditional cytokine interventional therapies and could provide for unprecedented long lasting disease-modifying effects in multiple autoimmune diseases. Calypso Biotech is a spin-off by the healthcare business of Merck KGaA and is headquartered in Amsterdam, The Netherlands, with offices and laboratories in Geneva, Switzerland.

Inotrem Announces That Its ESSENTIAL Phase II Study for the Treatment of Critically ill COVID-19 Patients Meets Its Primary and Key Secondary Endpoints

• Results demonstrate statistically significant efficacy of drug candidate nangibotide in the treatment of patients with severe forms of COVID-19

• Nangibotide treatment improves patients’ clinical status and shows a relative 43% reduction in mortality

• The company will consult with regulatory authorities to advance a new treatment option to severe COVID-19 patients

• ESSENTIAL was made possible thanks to the strong support from French public authorities and their commitment to fight COVID-19

Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory syndromes, announced today at the European Society of Intensive Care Medicine’s Annual Congress, held in Paris, positive results for ESSENTIAL, its Phase II clinical trial in COVID-19 patients hospitalized in critical care units and experiencing acute respiratory distress. The study was funded as part of the Capacity Building call for proposals, financed by the Programme d’Investments d’Avenir (PIA), operated on behalf of the French government by Bpifrance, the French national investment bank.

The ESSENTIAL study was terminated at 220 randomized ICU patients requiring ventilatory support (stage 5 or 6 on a 7-point clinical status ordinal scale) and compared infusion of nangibotide at 1mg/kg/hr for up to 5 days of treatment with standard of care. Despite a lower than anticipated sample size, the study met its primary endpoint of an improvement in clinical status according to 7-point clinical status ordinal scale from baseline to Day 28 (p value = 0.040).

Nangibotide treatment also showed a statistically and clinically meaningful 12% absolute and 43% relative reduction in Day 28 mortality (key secondary endpoint) in the overall trial population (p value = 0.030). Among the subpopulation of patients with levels of the TREM-1 pathway activation marker, soluble TREM-1 (sTREM-1) above the median, the absolute and relative reduction in mortality was even more pronounced, amounting to 20% and 47%, respectively (p value = 0.023).

The study showed that nangibotide has a significant and positive impact on the progression of the disease in patients receiving ventilatory support due to COVID-19, as well as on the severity of the respiratory failure, and length of stay in ICU. The trial showed that sTREM-1 is an effective prognostic marker of outcome in severe COVID-19 and, consistent with the results from the company’s prior ASTONISH study, confirmed that sTREM-1 is a predictive marker of a positive response to the treatment by nangibotide.

Jean-Jacques Garaud, Senior VP Head of scientific and medical affairs at Inotrem said: "This new trial brings compelling evidence that the TREM-1 pathway plays a central role in major life-threatening immune dysregulations caused by severe infections, whether it is severe forms of COVID-19 or septic shock. This study strongly suggests 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."

Sven Zimmermann, CEO of Inotrem, added: "We are grateful for the continued financial support and confidence awarded to us by the French public authorities to fight COVID-19. This attests of the relevance of our innovative approach to treat inflammatory diseases. The data we obtained is extremely encouraging, and we plan on quickly consulting regulatory authorities in the US and EU."

Thierry Hercend, Independent Board member at Inotrem, said: "The effect of nangibotide on severe forms of COVID 19 added to the recent announcement of the ASTONISH Phase II data in septic shock confirms that targeting the TREM-1 pathway is beneficial in other conditions, infectious or not, leading to severe immune dysregulation in the critical care setting."

Substantial support from public funding to fight COVID-19

At the start of the pandemic in 2020, Inotrem team set out to build on the similarities between the immune dysregulation in severe forms of COVID-19 with those observed in septic shock patients. Building on its deep scientific and medical understanding of the TREM-1 pathway, and with the strong support of the French government, Inotrem launched ESSENTIAL, its clinical trial to assess the efficacy of its drug lead candidate, nangibotide, for COVID-19 patients in the ICU.

In July 2020, the CoviTREM-1 consortium which includes the Nancy and Limoges university hospitals and Inotrem, obtained a first public funding of 7.5 million euros under a call for projects operated by the Secretary General for Investment and Bpifrance. In December 2020, the trial was declared a "Research National Priority" by the French government. In July 2021, Inotrem was authorized to pursue the clinical development of nangibotide up to registration for COVID-19 patients and can draw on additional public funding of up to 45 million euros from Bpifrance, as part of the Programme d’Investments d’Avenir ("PIA").

About the drug candidate 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 and has recently reported positive results from a Phase IIb trial (ASTONISH) in septic shock patients.

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 American investors Inotrem is part of the French Tech 120, a government program dedicated to support the development of fast-growing startups. www.inotrem.com

Corteria Pharmaceuticals strengthens its Executive Leadership Team, Board of Directors, and Scientific Advisory Board

Corteria Pharmaceuticals, a biotechnology company developing innovative treatments for certain forms of heart failure, announced today the recruitment of Dr. Francesca C. Lawson as Chief Medical Officer. Corteria Pharmaceuticals also expanded its Board of Directors with the addition of Dr. Marc Semigran as an independent Director, as well as its Scientific Advisory Board with the addition of Dr. Jeffrey Testani.

"We are highly pleased to welcome Drs. Lawson, Semigran and Testani to our team to accelerate the development of our programs. Their expertise and in-depth knowledge of these diseases will be invaluable to Corteria," commented Philip Janiak, founder and CEO of Corteria Pharmaceuticals.

Francesca C. Lawson, M.D., based in Philadelphia, USA, is a specialist in cardiometabolic diseases with more than 30 years of experience in drug development, from Phase 1 to Phase 3. Dr. Lawson joins Corteria Pharmaceuticals from Applied Therapeutics, where she spent three years overseeing the development of new drug candidates for the treatment of diabetic cardiomyopathy as Vice President, Clinical and Regulatory Strategy. Prior to Applied Therapeutics, she led the clinical trials of cardiometabolic drug candidates at Sanofi where she successfully developed sotaglifozin in worsening heart failure.

Marc Semigran, M.D., a cardiologist with subspecialty in heart failure based in Cambridge, USA, joins the Board of Directors of Corteria Pharmaceuticals as an independent Director. Dr. Semigran currently serves as Chief Medical Officer at Renovacor, and previously as Head of Clinical Development of MyoKardia, a biopharmaceutical company pioneering new approaches for the treatment of cardiomyopathies. There, he led the development of mavacamten in hypertrophic cardiomyopathy. Dr. Semigran is the author of numerous scientific peer-reviewed publications, for which he has received several prestigious awards. While Medical Director of the Heart Failure and Cardiac Transplant Program at Massachusetts General Hospital and Harvard Medical School, he served as principal investigator in major clinical trials.

Jeffrey Testani, M.D., a cardiologist, associate professor of Medicine and Director of Heart Failure Research at Yale University, USA, is an expert on heart failure and cardiac transplantation. Dr. Testani also runs a large research program focusing on cardio-renal syndrome at the Yale Heart and Vascular Center and has published several seminal papers in peer-reviewed journals.

About Corteria Pharmaceuticals:

Founded in 2021 and based in Paris, France, Corteria Pharmaceuticals is a biotechnology company specialized in the development of first-in-class drugs for the treatment of heart failure subpopulations. Despite advances in the management of this serious disease, the prevalence of heart failure continues to rise, with over 60 million cases worldwide. Corteria Pharmaceuticals' innovative approach is based on a selection of therapeutic targets involved in the worsening of heart failure and in the acute form of the disease in humans, as well as a stratification strategy to identify patients likely to respond best to its treatments.

More information is available on the company's website: www.corteriapharma.com

Inotrem announces the outcome of its Phase II ASTONISH trial in septic shock patients demonstrating efficacy of nangibotide

• ASTONISH confirms the therapeutic potential of nangibotide in septic shock patients with excessive activation of the TREM-1 pathway

• ASTONISH confirms that the soluble TREM-1 biomarker predicts response to nangibotide treatment.

Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory syndromes, disclosed for the first time today at the International Sepsis Forum held in Barcelona the results for its Phase IIb ASTONISH clinical trial in septic shock patients.

ASTONISH was designed to show the efficacy of nangibotide in septic shock with a precision medicine approach aiming to identify patients who benefit the most from this innovative treatment. This global study enrolled 361 patients across 41 clinical sites in 6 European countries and the United States and succeeded in demonstrating a therapeutic benefit of nangibotide in patients with high levels of the TREM-1 pathway activation marker, soluble TREM-1 (sTREM-1).

ASTONISH studied as a primary endpoint the improvement of a well-established morbidity score evaluating patient clinical evolution and organ function, the SOFA score. The change of this score at 5 days after initiation of treatment in the nangibotide-treated arms was compared to the placebo arm in all patients and in patients with a high level of sTREM-1. Importantly, and as part of the prespecified analysis for defining the optimal sTREM-1 cut-off, the benefit of nangibotide high dose treatment versus placebo was clinically and statistically significant at higher concentrations of sTREM-1, representing about 50% of the study population.

Consistent with prior preclinical, observational and Phase IIa trial data in this setting, ASTONISH confirmed that excessive TREM-1 activity is associated with severe immune dysregulation, organ dysfunction and ultimately death.

ASTONISH demonstrates that TREM-1 modulation with nangibotide improves respiratory, cardiovascular and renal function. The study also provided evidence that nangibotide meaningfully impacts other relevant clinical parameters, displaying a trend towards improvement in All-Cause Mortality at day 28 and the proportion of patients Alive and free of organ support at day 28.

Jean-Jacques Garaud, Senior VP Head of scientific and medical affairs at Inotrem, said: “The ASTONISH trial was designed as a Phase III enabling trial and it did generate important insights about nangibotide’s therapeutic activity and our precision medicine approach in septic shock. We are enthusiastic about this study and Inotrem’s capacity to bring a first in class product in an area with a major unmet medical need”.

“These results represent a major advancement for patients suffering from septic shock. They provide compelling evidence that Inotrem’s innovative solution targeting the TREM-1 pathway has the potential to become the first causal treatment for this severe and often fatal indication,” said Sven Zimmermann, CEO of Inotrem. “Based on these data, we intend to advance nangibotide towards registration studies in septic shock. We look forward to discussing next steps with regulatory authorities.”

Professor Bruno François, Limoges University Hospital and coordinating investigator added: “We observed that the TREM-1 pathway was activated in severe infections leading to septic shock. Nangibotide is the first TREM-1 inhibitor and ASTONISH confirms its potential as a new therapeutic option for the septic shock patient population. We are looking forward to bringing definitive evidence, in a Phase III clinical study that nangibotide can reduce mortality in these critically ill patients”.

Septic shock is the ultimate complication of sepsis and currently constitutes a high unmet medical need. The incidence of septic shock continuously raises, and mortality remains elevated: it is the 10th leading cause of death in developed countries and the 1st cause of death in intensive care units. There is currently no specific therapy approved for this indication besides antibiotics and symptomatic treatment. Inotrem’s solution has the potential to become the first mechanism-based treatment for septic shock.

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. Nangibotide has also been tested in a Phase II trial in severe forms of COVID-19 (ESSENTIAL). ESSENTIAL data will be communicated on October 25. 2022 at the next ESICM meeting in Paris.

About ASTONISH Study

The Efficacy, Safety and Tolerability of nangibotide in Patients with Septic Shock (ASTONISH) phase IIb 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.

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 American investors Inotrem is part of the French Tech 120, a government program dedicated to support the development of fast-growing startups. www.inotrem.com

Mainstay Medical Announces Publication of Three-Year Patient Outcomes Data from ReActiv8-B Clinical Trial Demonstrating Long-Term Efficacy of ReActiv8® Restorative Neurostimulation™

Data continue to show compelling efficacy and safety, including improvement on all key measures of pain and disability, as compared to the one-year and two-year study results

Mainstay Medical Holdings plc today announced the publication of the three-year patient outcomes data from its pivotal ReActiv8-B clinical trial. The data, published in the journal of the International Neuromodulation Society, Neuromodulation, further establish the efficacy and safety of ReActiv8 Restorative Neurostimulation, including compelling long-term durability and improvement over time on key outcome measures in the treatment of intractable chronic low back pain.

The three-year data show improvements over results from the patients’ one-year and two-year visits on virtually all key efficacy measures. Of note:

*Percent of patients that were on opioids at baseline: (1-year=31/65), (2-Year= 34/57), (3-Year= 36/51).

Overall, 83% of patients experienced substantial and clinically meaningful improvements in pain or disability, or both, at three years.

Chris Gilligan, Director of the Brigham and Women’s Spine Center at Brigham and Women’s Hospital, assistant professor of Anesthesia at Harvard Medical School (Boston, USA), and Principal Investigator of the study, said: “The recently published data from the ReActiv8-B clinical trial continued to show clinically meaningful improvements in both pain and function for patients with refractory chronic low back pain who received three years of neurostimulation. The long-term trajectory and durability of clinical benefits are consistent with the restoration of neuromuscular control and muscle rehabilitation, which gives us confidence that we are able to treat the underlying cause of chronic low back pain in these patients.”

“Multifidus dysfunction in patients with chronic low back pain has historically been a challenging etiology for the spine surgeon community to properly treat,” said Frank Schwab, Chair of Orthopedic Spine Surgery at Lenox Hill Hospital, and Chief of Orthopedic Spine Surgery for Northwell Health System. “These patients are not indicated for surgery, with existing treatment options being temporary and palliative. ReActiv8 therapy has proven to maintain effectiveness long-term and provides this challenging patient population with a safe and restorative solution.”

Jason Hannon, CEO of Mainstay Medical, said: "These 3-year results further validate ReActiv8’s restorative mechanism of action, which treats a primary underlying cause of mechanical chronic lower back pain, multifidus dysfunction. We are proud to have the only commercially available device with a strong safety profile and long-term, peer-reviewed evidence supporting the rehabilitation of this severely affected patient population, and we look forward to continuing to generate clinical and other research to compel physicians and their patients to further utilize the therapy.”

The full publication can be downloaded free of charge at Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction - ScienceDirect

About ReActiv8®

ReActiv8 is an implantable medical device designed to treat adults with intractable chronic low back pain (CLBP) associated with multifidus muscle dysfunction. Multifidus muscle dysfunction may be evidenced by imaging or physiological testing in adults who have failed therapy including pain medications and physical therapy, and who 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.

United Kingdom National Institute for Health and Care Excellence (NICE) Publishes Interventional Procedure Guidance (IPG) for ReActiv8® Restorative Neurostimulation™

ReActiv8 Neurostimulation therapy recommended to be used in the National Health Service; Special arrangements designation to increase access to ReActiv8 for patients

Mainstay Medical Holdings plc announced today that the National Institute for Health and Care Excellence (NICE), a public body of the Department of Health that carries out evidence-based health technology assessments by independent committees, has issued a recommendation that ReActiv8® Restorative Neurostimulation™ can be used in the National Health Service in the U.K., with special arrangements for clinical governance, consent, and audit or research. ReActiv8 is currently the only technology offering restorative neurostimulation to the NHS for refractory mechanical chronic low back pain (CLBP).

“U.K. physicians have some of the most extensive experience with ReActiv8 globally. We are thankful to NICE for recognizing this experience, as well as the substantial body of global evidence we have developed in support of the efficacy and safety of this ground-breaking therapy, “ said Jason Hannon, CEO of Mainstay Medical. “This new guidance will enable patients to have greater access to the therapy when previous treatment options have not proven successful. We look forward to supporting physicians across the U.K. going forward and to continued improvement in patient outcomes.”

“Historically, mechanical CLBP pain therapies were aimed at only managing the symptoms, which is the pain associated with this pathology,” said Dr. Ganesan Baranidharan, Consultant in Anaesthesia and Pain Medicine, Leeds Teaching Hospitals NHS Trust. “ReActiv8 is the only therapy available I am aware of where patients with many years of CLBP actually reverse and effectively rehabilitate their condition durably over a long period of time. ReActiv8 targets the cause of mechanical CLBP, not just the symptoms. The new NICE guidance is a major victory for patients and clinicians, which further confirms the positive patient outcomes we have seen to date. This new guidance will allow more patients to gain access to ReActiv8 within the U.K. and further afield.”

The NICE publication can be found here: Evidence | Neurostimulation of lumbar muscles for refractory non-specific chronic low back pain | Guidance | NICE

About ReActiv8®

ReActiv8 is an implantable medical device designed to treat adults with intractable chronic low back pain (CLBP) associated with multifidus muscle dysfunction. Multifidus muscle dysfunction may be evidenced by imaging or physiological testing in adults who have failed therapy including pain medications and physical therapy, and who 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.

Medical Microinstruments Secures $75M to Advance Robotic Microsurgery

Series B financing will accelerate clinical trials and global commercialization of the company’s Symani® Surgical System

Medical Microinstruments, Inc. (MMI), a robotics company dedicated to improving clinical outcomes for patients undergoing microsurgery, today announced it has raised $75 million in Series B financing. Deerfield Management led the round with participation from new investors, RA Capital Management and Biostar Capital, as well as existing investors, Andera Partners, Fountain Healthcare Partners, Panakès Partners and Sambatech. The company also announced the addition of three new members to its board of directors.

In addition, the company announced its corporate redomicile from Italy to the United States. The recently opened Center of Excellence facility in Pisa, Italy, with nearly 100 employees will continue to be the hub of the company’s research and development, manufacturing, and other business activities.

Proceeds from this financing round and the company’s planned U.S. presence will launch MMI into its next stage of growth as it continues its mission to improve the quality of patient care by pushing the boundaries of microsurgery. The company seeks to expand indications and support ongoing commercialization efforts for the Symani® Surgical System in Europe where it received CE mark in 2019. MMI also intends to accelerate plans to commercialize in the U.S. and Asia-Pacific, as well as advance clinical research including securing an Investigational Device Exemption (IDE) from the U.S. Food and Drug Administration to conduct a pivotal study. The Symani System was developed specifically to address the challenges of microsurgery and is the only system that offers NanoWrist® Instruments designed to improve a surgeon’s ability to access and suture small, delicate anatomy.

“This financing round, coupled with our commitment to access the U.S. market and the addition of visionary leaders to our board, is an exciting moment for the surgical robotics space,” said Mark Toland, CEO of MMI. “We’re pleased to have bridged the Atlantic with premier U.S. life science investors, and existing European investors, who share our same vision of bringing microsurgical robotics to the world.”

The company’s new board members are Andrew ElBardissi, MD, Tess Cameron and Arturo Baroncelli. Dr. ElBardissi is a partner at Deerfield Management, with extensive experience serving as a board member for innovative healthcare companies. Ms. Cameron serves as principal for RA Capital Management and currently sits on the boards of Avilar Therapeutics and Nodexus Inc. Baroncelli previously worked as a robotics business development manager for Comau and will represent MMI’s founders on the board.

“We are thrilled to add further depth and experience to the MMI Board and look forward to working with our new board members to build the robotic microsurgical space,” said Andrew Cleeland, Chairman of the Board for MMI.

“The MMI technology is one of the most significant transformational advancements in surgical robotics that we have seen,” said Dr. ElBardissi. “Having the world’s smallest wristed instruments opens up the field of ‘micro’ robotics to a completely new level of treatment spanning microsurgery for cancer, trauma, orthopedic, pediatric, and one day, neurosurgery patients. Symani will be the future of how microsurgery is performed worldwide.”

“Robotic microsurgery has enormous potential to both improve the standard of care for patients and help surgeons manage procedures that require delicate precision,” said Ms. Cameron. “I look forward to supporting MMI and its world-class team as it begins this exciting chapter.”

The Symani Surgical System is designed to improve a surgeon’s ability to repair anatomical structures such as veins, arteries, nerves and lymphatic vessels as small as 0.3 mm in diameter. The platform provides motion scaling and tremor reduction to allow precise micromovements. Its NanoWrist technology is the world’s smallest wristed instrumentation and is intended to improve a surgeon’s natural dexterity and range of motion beyond the capability of the human hand.

About Medical Microinstruments, Inc.

Medical Microinstruments, Inc. (MMI) was founded in 2015 near Pisa, Italy to enhance surgical performance through the development of a robotic system that enables surgeons to achieve better outcomes in microsurgery. The Symani Surgical System combines proprietary innovations including the world’s smallest wristed microinstruments as well as tremor-reducing and motion-scaling technologies. Together, these powerful capabilities allow more surgeons to successfully perform microsurgery while expanding the field of supermicrosurgery. MMI is backed by international medtech investors including Andera Partners, BioStar, Deerfield Management, Fountain Healthcare Partners, Panakès Partners, RA Capital and Sambatech.

Media Contact:

Sarah Lundberg
Health+Commerce
sarahlundberg@healthandcommerce.com

Ermium Therapeutics extends its initial €6.3 M funding to €12.3 M to further advance breakthrough auto-immune disease therapeutics

Ermium Therapeutics, a Paris-based biotech company developing innovative health products for auto-immune diseases, announced today the extension of its initial funding of €6.3 M to €12.3 M with Kurma Partners and Fountain Healthcare Partners.

The company is discovering and developing small molecules, orally available, that are aimed at addressing a range of chronic auto-immune diseases, affecting millions of people worldwide, and particularly type I interferon-mediated diseases such as systemic lupus erythematosus (SLE), dermatomyositis, Sjögren syndrome, and monogenic interferonopathies. Ermium proprietary compounds are intended to be first-in-class acting on a well-known G protein-coupled receptor (GPCR), namely the CXCR4 chemokine receptor, via a totally novel mechanism of action. The main property of Ermium CXCR4-targeted functionally selective immunomodulators is to potently abolish the release of type I interferons by immune cells, and also other key inflammatory cytokines.

The €6 M proceeds will be used to reach the milestones of drug candidate selection, extend the non- clinical development package, and drive continued efforts on the pharmacological package in support of the early clinical development program in SLE and other auto-immune diseases.

Fountain Healthcare Partners, a transatlantic life science investor, is joining and widening the Ermium Therapeutics initial investment syndicate composed of Kurma Partners, Eurazeo, Domain Therapeutics, and Erganeo.

“I am thrilled to close this extension funding which reflects the confidence of our historical investors along with the commitment of Fountain Healthcare Partners which we are welcoming with enthusiasm. Altogether, this further validates all the efforts the company team has made since the company inception, and also the promising therapeutic potential of the first in class immunomodulators we are developing; Moreover, it will allow our program to move on up to the selection of a drug candidate, with the goal to address a huge medical need for patients suffering from interferonopathies”, said Joël CROUZET, CEO of Ermium Therapeutics.

“We were very impressed by the work accomplished by the team at Ermium Therapeutics. We were quickly convinced of the significant commercial opportunity that could be realized with this investment and the potential application of Ermium’s lead development candidate across a variety of auto-immune disease indications. We are particularly delighted to join Kurma, Eurazeo, Domain Therapeutics, and Erganeo in advancing Ermium Therapeutics first in class compounds to address the high unmet medical need in interferonopathies such as SLE”, added Aidan KING, Managing Partner of Fountain Healthcare Partners and newly appointed member of Ermium Therapeutics board of directors.

“We are particularly proud and impressed by the advances performed by Ermium Therapeutics since the initial funding, based on breakthrough science and a highly innovative approach for critical medical needs such as SLE. This extension funding will accelerate the company development and allow its exciting program to move on towards the first steps of non-clinical development”, concluded Thierry LAUGEL, Managing Partner of Kurma Partners and member of Ermium Therapeutics board of directors.

About Ermium Therapeutics

Ermium Therapeutics, a discovery stage company, was founded in June 2019 by Dr Jean-Philippe Herbeuval (CNRS – Université Paris Cité), Kurma Partners, Domain Therapeutics, and Erganeo. Ermium Therapeutics breakthrough first in class compounds are CXCR4- targeted functionally selective immunomodulators; those orally available compounds are aimed to be developed for auto-immune disease indications, particularly interferonopathies, including SLE. Such immunomodulators exhibit potent anti-inflammatory properties by efficiently downmodulating the release of type I interferons, and also other key proinflammatory cytokines. The company has obtained in vivo POC in different auto-immune / inflammatory disease models. Ermium Therapeutics is based at the Paris Biotech Santé Incubator – Accelerator located at the Cochin Hospital in Paris. The company has signed a worldwide exclusive license agreement on intellectual property from the CNRS and the Université Paris Cité through an agreement with Erganeo. Ermium Therapeutics has received grants and soft loans from Bpifrance, the French agency for innovation. www.ermium.com

About Fountain Healthcare Partners

Fountain Healthcare Partners is a life science focused venture capital fund with over EUR 300 million under management. Within the life science sector, specific areas of interest to Fountain Healthcare Partners include biotechnology, medical devices, specialty pharma and diagnostics. 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’s main office is in Dublin, Ireland, with a second office in New York. The firm deploys the majority of its capital in Europe, with the balance in the United States. www.fh-partners.com

About Kurma Partners

Kurma Partners is a key European Venture Capital firm specialized in healthcare, with more than €700 million under management, with two dedicated franchises: “Kurma Biofund” focused on venture investments in therapeutics (current active fund KBIII) and “Kurma Diagnostics” focused on venture investment in diagnostics and digital health (current active fund Kurma Dx2). Kurma Partners has launched its first “Growth Opportunity Fund” further to its first closing in early 2022. Kurma Partners is part of the Eurazeo Group. www.kurmapartners.com

Contacts

Ermium Therapeutics
Joël Crouzet, PhD, CEO
contact@ermium.com

Ulysse Communications – Press Relations
Bruno Arabian
barabian@ulysse-communication.com
Tel: +33 (0) 6 87 88 47 26

XyloCor Therapeutics Achieves Target Enrollment in Phase 2 EXACT Study of XC001 Novel Gene Therapy for Ischemic Heart Disease

• Positive Phase 1 results reported at the American Association for Thoracic Surgery (AATS) and the American Society of Gene and Cell Therapy (ASGCT) revealed XC001 is well tolerated at all dose levels

• Phase I data support XC001 therapeutic effect and potential dose response

• Topline Phase 2 data readout expected in February 2023 with interim results in the second half of this year

XyloCor Therapeutics, a clinical-stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, today announced it has achieved enrollment of target number of subjects in the Phase 2 portion of its ongoing Phase 1/2 clinical trial (EXACT) for refractory angina. Topline results from the Phase 2 study are expected in February 2023 with interim results in the second half of this year.

“Achievement of this important milestone in the Phase 2 portion of the study is a testament to the clinical need in this patient population and I am eager to see the Phase 2 results as they emerge,” said Thomas Povsic, M.D., Ph.D., Professor of Medicine, Duke University School of Medicine and National Principal Investigator for the EXACT study. “Patients with refractory angina have no treatment options, and the results from the Phase 1 portion of the EXACT trial suggest a dose response and therapeutic potential which is encouraging for the development of XC001 as a treatment to improve these patients’ quality of life. We are very excited to see this more definitive evaluation of the safety and efficacy of this approach.”

“We are pleased to announce this important milestone in enrollment for our Phase 2 study especially during this unprecedented and challenging time,” said Al Gianchetti, President and CEO of XyloCor. "An estimated one million people suffer from refractory angina in the United States, and we are encouraged that XC001 may address the high unmet need in this patient group. XyloCor also plans to study XC001 in other patient groups as well, including as adjunctive therapy in patients undergoing bypass surgery."

Individuals with refractory angina experience pressure or intense pain in the chest due to insufficient blood flow to the heart muscle. These symptoms can severely impact quality of life and may worsen comorbidities.

XyloCor’s lead investigational drug, XC001 (encoberminogene rezmadenovec) is a locally administered, single-dose gene therapy currently in development as a novel approach to treating patients with refractory angina who have no other medical and surgical options. The treatment strategy is to use local administration to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects. 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.

About the EXACT Study

The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) clinical trial is 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 with target enrollment of 27 additional subjects at the highest tolerated dose (1 x 1011 vps, the highest tested dose). The investigational gene therapy is administered directly to the heart muscle through a mini-thoracotomy by an experienced cardiac surgeon at top cardiovascular research sites across the United States.

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 which there are no treatment options. XyloCor has a second preclinical investigational product, XC002, in discovery stage, being developed for the treatment of patients with cardiac tissue damage from heart attacks. The company, which was co-founded by Ronald Crystal, M.D., and Todd Rosengart, M.D., has an exclusive license from Cornell University. For more information, visit www.xylocor.com.

Contacts

Corporate and Investor Relations:
A. Brian Davis, XyloCor Therapeutics
brian.davis@xylocor.com

610-541-2056

Media Contact:
Mike Beyer, Sam Brown Inc. Healthcare Communications
mikebeyer@sambrown.com
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Clinical Mocravimod Data in Hematological Malignancies Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (aHSCT) Presented at the 2022 EHA Congress

Phase 1b/2a data shows that mocravimod is safe and well tolerated

Priothera, a late-clinical stage biotechnology company pioneering the development of its S1P receptor modulator compound, mocravimod, presented first clinical data on mocravimod (also known as KRP203) in hematological malignancies patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) at the European Hematology Association (EHA) 2022 Congress, which was held in Vienna, Austria, June 9-12th, 2022.

The oral presentation, which took place on 12th June, was entitled A two-part, single- and two-arm randomized, open-label study to evaluate the safety, tolerability and pharmacokinetics of KRP203 in subjects with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation. The study showed that in the Phase 1b/2a study mocravimod was safe and well tolerated with promising overall survival.

Key take aways from the data presentation were:

• The study provided first ever human data of a S1P receptor modulator administered to patients undergoing allogeneic HSCT

• S1PR modulator class effects, such as bradycardia, were of no clinical concern

• Promising overall survival (OS) data

• Limited number of relapses, acute and chronic graft-versus-host disease (GVHD)

• Data supportive for conducting the planned MO-TRANS pivotal study to investigate efficacy (Relapse-free survival and OS) and GVHD in AML patients undergoing allogeneic HSCT

Priothera is initiating the pivotal MO-TRANS global Phase 2b/3 study in Europe, US and Japan, to assess the efficacy and safety of mocravimod as an adjunctive and maintenance therapy in adult AML patients undergoing allogeneic HSCT. The study is expected to start in the second half of 2022 and preliminary data from this study are expected by the end of 2024.

Florent Gros, Co-Founder and CEO of Priothera, said: “We are delighted to have been given the opportunity to present the full first human clinical data on mocravimod at the European Hematology Association Congress this year. Based on these results mocravimod has the potential to be a first-in-class therapy in maintaining graft-versus-leukemia responses while preventing graft-versus-host disease. This novel approach would provide a tremendous benefit to AML patients undergoing an allogeneic hematopoietic stem cell transplant. We are excited about mocravimod which leverages a well-described mode of action in a hematology/oncology setting and has been successfully used in autoimmune indications. Pre-clinical and clinical proof of concept studies have herewith demonstrated mocravimod’s ability to improve survival outcomes for this devastating disease. We look forward to advancing the global pivotal Phase 2/3 trial which is due to start in the second half of 2022.”

Priothera’s abstract is available on EHA2022 Congress Abstract Book, here: https://journals.lww.com/hemasphere/Documents/EHA2022%20Congress%20Abstract%20Book.pdf

About Mocravimod

Mocravimod (also known as KRP203) is a synthetic, sphingosine 1-phosphate receptor (S1PR) 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 CART cell therapy.

Mocravimod will be investigated as an adjunctive and maintenance treatment in a Phase 2b/3 study as a potential treatment for patients with Acute Myeloid Leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT is the only potentially curative approach for AML patients, but current treatments have unacceptably high mortality and morbidity rates.

Priothera leverages S1PR modulator’s unique mode of action to maintain anti-leukemia activity – graft-versus leukemia (GVL) while reducing tissue damage resulting from graft-versus-host disease (GVHD), a consequence of allogeneic HSCT. This novel treatment approach – mocravimod being the only S1PR modulator treating blood cancers – tackles a high unmet medical need and intends to add quality life to patients.

About Priothera

Priothera is leading the way in developing orally applied sphingosine-1-phosphate (S1P) receptor modulators for the treatment of hematological malignancies and for the improvement of CART cell therapies. S1P receptor modulators are known to largely reduce egress of T cells from lymphatic tissues. Not being an immunosuppressant, mocravimod maintains the graft-versus-leukemia (GVL) benefits in patients receiving HSCT while inhibiting graft-versus-host-disease (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) and EarlyBird Venture Capital (Berlin, Germany).

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