Inflazome’s Somalix Demonstrates Positive Safety, Tolerability and Pharmacodynamic Profile in its Phase I Study

• Results from the first-in-human study showed excellent safety, tolerability and pharmacokinetics in healthy subjects resulting in target engagment at all doses tested. These results support the progression of Somalix into Phase II studies this year.

• Somalix is a potent and selective NLRP3 inflammasome inhibitor under development as an orally available, peripherally-restricted drug for inflammatory diseases.

Dublin (IE), Cambridge (UK), Brisbane (AU) | Inflazome (inflazome.com), the pioneering inflammasome biotech company developing multiple drugs that stop harmful inflammation, today announces the successful completion of a Phase I study of its investigational drug, Somalix. Somalix is a small molecule, peripherally-restricted inhibitor of the NLRP3 inflammasome. The Phase I data showed excellent safety and tolerability, while pharmacokinetics showed linear increase with dose which could be correlated with pharmacodynamic response. The results further validate Inflazome’s technology platform and support the progression of Somalix into Phase II clinical trials in the second quarter this year.

Activation of the NLRP3 inflammasome in the body is implicated in many diseases caused by chronic, uncontrolled inflammation. The Phase I study was a first-in-human, single-centre, double blinded and randomised trial that demonstrated excellent safety or tolerability in healthy, adult participants.

Subject to positive Phase I study results, Inflazome also intends to subsequently progress its second investigational drug, Inzomelid, into Phase II studies this year. Inzomelid is an orally available, brain-penetrant small molecule, intended for treatment of debilitating inflammatory diseases of the brain.

Thomas Jung, Chief Medical Officer of Inflazome, commented, “We are very pleased to have progressed our investigational drug, Somalix, through a first-in-human Phase I study and to have demonstrated safety, tolerability and pharmacodynamic response. We can now accelerate Somalix to fulfill its potential through multiple Phase II studies. We are expecting further data read outs for our investigational brain-penetrant drug Inzomelid very soon and look forward to progressing our pipeline to address inflammatory diseases with significant unmet medical need.”

About Inflazome

Inflazome is a biotech company leading the development of orally available drugs to address clinical unmet needs in inflammatory diseases by targeting inflammasomes. Inflammasomes are understood to drive many chronic inflammatory conditions, from Parkinson’s and Alzheimer’s to asthma, inflammatory bowel disease, chronic kidney disease, cardiovascular disease, arthritis and NASH. Inflazome has two clinical-stage investigational drugs. Inzomelid is under development as an orally available, brain-penetrant drug and Somalix is under development as an orally available, peripherally-restricted drug. Both will address clinical unmet needs in inflammatory conditions. Inflazome is headquartered in Dublin, Ireland, with offices in Cambridge, UK and Brisbane, Australia. To learn more visit: inflazome.com

About the NLPR3 Inflammasome

Activated NLRP3 acts as a ‘danger sensor’ in the body to release the pro-inflammatory cytokines IL-1β, IL-18 and induce uncontrolled, lytic cell death (pyroptosis). These processes lead to chronic inflammation, and as such, NLRP3 has been implicated in a large number of diseases.

Inotrem expands Series B financing to €58 Million with a mix of Equity and Debt, adding new investors Fountain Healthcare Partners, Kreos and BPI France

• New investor Fountain Healthcare Partners provides a further €5 M capital increase adding on the initial €39 M announced last September

• Inotrem also secured a €13 M credit line from Kreos Capital and a €1 M loan from BPI France.

• Proceeds will be used to advance the Company’s applications in septic shock and chronic inflammatory diseases.

Inotrem S.A., a biotechnology company specialized in the development of immunotherapies targeting the TREM-1 pathway with potential applications for acute and chronic inflammatory syndromes, announced a €5M capital increase financed by Fountain Healthcare Partners, a leading Irish venture capital firm with offices in Dublin and New York. This fundraising brings Inotrem’s Series B financing to a final closing amount of €44M. In addition, the Company secured a €13M credit line from Kreos Capital, Europe's largest provider of specialty finance to growth companies, and a €1M loan from BPI France, France’s public investment bank.

The financing will support Inotrem’s R&D effort, in particular of its lead drug candidate, nangibotide, which is currently undergoing a global multicentric Phase IIb trial in septic shock patients (ASTONISH trial) in 5 European countries and the United States, and of a companion diagnostic tool aimed at selecting those septic shock patients that are more likely to respond favorably to treatment. Financing will also allow the Company to expand its TREM-1 franchise to address chronic inflammatory diseases.

“With Fountain Healthcare Partners joining our pool of world-class investors, Inotrem is in an ideal position to advance its market-breaking technology platform centered on the TREM-1 pathway and bring new immunotherapies to patients and the medical community” said Jean-Jacques Garaud, CEO of Inotrem.

Based on a novel approach of immunomodulation which targets the TREM-1 pathway, Inotrem has developed a proprietary technology platform and leverages its extensive knowledge of the TREM-1 pathway biology to develop programs in several indications with inflammatory syndromes for which there is a major and today unsatisfied therapeutic need. Its lead compound, nangibotide, targets septic shock which is the ultimate complication of sepsis. The incidence of septic shock continuously raises and mortality remains elevated (35%) in developed countries. There is currently no specific mechanism-based therapy approved for this indication. Inotrem’s solution has the potential to become the first mechanism-based treatment for septic shock.

“Inotrem has demonstrated its ability to reach several critical milestones and we are delighted to back this team. The TREM-1 pathway is extremely compelling and has great potential to bring solutions to patients that today lack effective therapies”, indicated Ena Prosser of Fountain Healthcare Partners.

In conjunction with the financing, Ena Prosser of Fountain Healthcare Partners will become a member of Inotrem’s Board of Directors, and Aris Contantinides of Kreos Capital will become an observer on Inotrem’s Board of Directors.

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, LR12 (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. Sébastien Gibot and Dr. Marc Derive. Inotrem is supported by leading European and North American investors. Inotrem is a FrenchTech120 company: it was chosen to join the program launched by the French President of the Republic and the Prime Minister to support the development of fast growing startups. For more information please visit: www.inotrem.com

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 €294 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. The Fountain Healthcare Partners team brings to investees over 70 years of collective experience in the pharmaceutical industry, corporate venture capital and VC across multiple investment and market cycles. For more information please visit: www.fh-partners.com

About Kreos Capital

Kreos Capital is the leading provider of growth-debt financing to high-growth companies in Europe and Israel with revenues up to EUR 300 million. Since 1998, as the pioneer growth debt provider across Europe and Israel, Kreos has completed 540 transactions and committed more than EUR 2.3 billion in 16 different countries. Kreos is dedicated to supporting management teams and their equity investors with flexible loan structures for all stages of a growth company's development and to address the needs for growth capital, working capital, acquisition financings, lower mid-market buy-outs, roll-up strategies, banks re-financings as well as pre- and post-IPO financings. Kreos's most recent fund, EUR 700 million Kreos VI, was launched in January 2019. The Kreos global team has extensive debt financing, management and equity investing experience, covering the markets in Europe and Israel from its locations in London, Tel-Aviv and Stockholm.

Media contact for Inotrem

Anne REIN S&I | STRATEGIES&IMAGE

anne.rein@strategiesimage.com

+33 6 03 35 92 05

Inflazome IP Portfolio Strengthened with Patents Granted in US and Europe

• USPTO and EPO grant patents licensed exclusively to Inflazome

• Patent claims cover Inflazome’s brain penetrant drug Inzomelid

DUBLIN, Ireland, CAMBRIDGE, United Kingdom & BRISBANE, Australia - Inflazome (inflazome.com), the pioneering inflammasome biotech company developing multiple small molecule drugs that block harmful inflammation, today announces that the United States Patent and Trademark Office (USPTO) and the European Patent Office (EPO) will grant the patent application WO 2016/131098 as US 10,538,487 on 21 January 2020 and EP 3,259,253 on 15 January 2020.

The patents provide for compounds which have advantageous properties and show useful activity in the inhibition of NLRP3 inflammasome activation. Such compounds are useful in the treatment of a wide range of disorders, including Parkinson’s, Alzheimer’s and Motor Neuron Disease, in which inflammation arising from the NLRP3 inflammasome is implicated as a key factor. Inflazome currently has two ongoing Phase I studies with Inzomelid and Somalix.

These new patents strengthen Inflazome’s intellectual property portfolio that extends to 43 patent families, reinforcing the company’s leading innovative position in discovering targeted therapies for inflammatory-driven diseases.

Matt Cooper, Chief Executive Officer of Inflazome, commented: “The granting of these pioneering patents marks another milestone for Inflazome and strengthens our IP portfolio. The patents granted in the US and Europe cover our lead clinical candidate, Inzomelid. Both Inzomelid and our second drug, Somalix, are in the final stages of Phase I safety and tolerability trials for inflammatory diseases. We look forward to driving these drugs into further trials to help people with debilitating diseases.”

The patent was originally filed by the University of Queensland and Trinity College Dublin following a highly productive collaboration between Inflazome founders, Professor Matt Cooper (University of Queensland) and Professor Luke O’Neill (Trinity College Dublin). It was licensed exclusively to Inflazome when the company was founded.

About Inflazome

Inflazome is a biotech company leading the development of orally available drugs to address clinical unmet needs in inflammatory diseases by targeting inflammasomes. Inflammasomes are understood to drive many chronic inflammatory conditions, from Parkinson’s and Alzheimer’s to asthma, inflammatory bowel disease, chronic kidney disease, cardiovascular disease, arthritis and NASH. Inflazome has two ongoing Phase I studies, the first with Inzomelid which is under development as an orally available, brain-penetrant drug, and the second with Somalix which is under development as an orally available, peripherally-restricted drug to address clinical unmet needs in inflammatory conditions. Inflazome is headquartered in Dublin, Ireland, with offices in Cambridge, UK and Brisbane, Australia. To learn more visit: inflazome.com

About the NLPR3 Inflammasome

Activated NLRP3 acts as a ‘danger sensor’ in the body to release the pro-inflammatory cytokines IL-1β, IL-18 and induce uncontrolled, lytic cell death (pyroptosis). These processes lead to chronic inflammation, and as such, NLRP3 has been implicated in a large number of diseases.

Contacts

Inflazome: Dr Jeremy Skillington | VP Business Development E: j.skillington@inflazome.com
Media: FTI Consulting: UK & International | Ciara Martin/Tim Stamper T: +44 20 37271000 Ireland & International | Jonathan Neilan/Patrick Berkery T: +353 1 7650800 E: StratCommEMEAInflazome@fticonsulting.com

KaNDy Therapeutics Announces Positive Phase 2b Data in Post-Menopausal Women with its Lead Non-Hormonal Product NT-814

• Phase 2b dose range finding study showed rapid and highly significant reductions in the frequency of hot flashes (primary endpoint) for the full 12-week treatment period

• Reduction in hot flashes was associated with statistically significant improvements in quality of life, mood and sleep – all key secondary endpoints

• All doses of NT-814 were well tolerated during the study, demonstrating a safety profile that supports progression to Phase 3 ~

Stevenage, UK – KaNDy Therapeutics, a UK clinical-stage biotech company, today announces positive data from the Phase 2b “SWITCH-1” clinical trial with its lead non-hormonal drug candidate, NT-814, for the treatment of symptoms of the menopause.

Following on from the clear benefits NT-814 demonstrated in the Phase 2a RELENT-1 study, the SWITCH-1 trial provides further compelling evidence that NT-814, a first in class, once-daily, oral neurokinin-1,3 receptor antagonist, can produce a rapid and marked reduction in the most troublesome and frequent symptoms of the menopause, hot flashes and night sweats (vasomotor symptoms). The clinical relevance of the marked improvements shown on the vasomotor symptom endpoints was supported by highly statistically significant improvements across patient reported assessments of quality of life, mood and sleep.

The SWITCH-1 study was a randomised, double-blind, placebo-controlled trial conducted in the US, UK and Canada. One hundred and ninety-nine women experiencing at least 7 moderate or severe hot flashes/flushes (HF) per day were recruited into the study and randomised to receive one of four doses of NT-814 or placebo. Treatment with NT-814 once daily for 12 weeks at the most effective dose evaluated resulted in:

• Statistically significant reductions compared to placebo in average hot flash frequency (primary endpoint), starting during the first week of treatment and continuing throughout the 12-week treatment period. Least squares mean reductions in average hot flash frequency were -6.7 for NT-814 vs -2.7 for placebo at week 4, and -7.8 vs -4.7 at Week 12 (p<0.0001 and p=0.0092, respectively).

• Marked improvements in all key secondary endpoints: improved quality of life was shown by highly significant improvements over placebo in the MenQoL menopause-specific quality of life scores, benefits on mood were demonstrated by significant improvements in the Beck Depression Inventory (II), and improved quality of sleep was shown by statistically significant improvements compared to placebo in the Pittsburgh Sleep Quality Index scores.

• NT-814 was well tolerated across the dose range with a safety profile that supports progression to Phase 3.

Dr. James A. Simon, Clinical Professor of Reproductive Endocrinology & Infertility at George Washington University, and the study’s Lead Investigator, commented: “These top-line results of the SWITCH-1 study are very exciting. They demonstrate that NT-814, a truly novel therapy, offers a rapidly effective, non-hormonal approach to treating menopausal hot flashes and night sweats, debilitating symptoms of menopause. Unique to this trial, patients also reported improvements in quality of life, mood and sleep with NT-814.”

Dr Mary Kerr, Co-Founder and CEO KaNDy Therapeutics, said: “The SWITCH-1 study started in November 2018, and so we are excited to share such positive results on schedule. The data confirms and validates Phase 2a observations, providing more evidence that neurokinins are fundamental to sex hormone biology and the pathophysiology of the menopause, resulting in almost immediate symptom relief. The Company looks forward to presenting these data at future scientific meetings and discussing it with regulatory agencies in advance of progressing the compound into pivotal registration studies.”

For more information, please contact:

KaNDy Therapeutics
Email: info@kandytherapeutics.com
Consilium Strategic Communications
Mary-Jane Elliott/ Lindsey Neville/ Carina Jurs
Tel: +44 (0) 20 3709 5700
KaNDyTherapeutics@consilium-comms.com

About the SWITCH-1 Study:
The Phase 2b SWITCH-1 study was a randomised, double-blind, placebo-controlled study conducted at 25 sites in the UK, US and Canada. It included an adaptive randomisation design that enabled the randomisation ratio to be modified to focus on doses of greatest interest based on emerging data. The study was initiated in November 2018 and completed, ahead of schedule, at the end of 2019. A total of 199 post-menopausal women experiencing at least 7 moderate or severe HFs per week were recruited into the study and randomized to receive one of four doses of NT-814 or placebo. Study drug was taken once daily in the evening for 12 weeks. Subjects completed electronic diaries twice daily for the two weeks before and throughout treatment and underwent routine safety assessments periodically throughout the trial. Patient reported assessments of sleep, quality of life and mood were also completed periodically during study visits. Further information on the study design can be found on www.clinicaltrials.gov and full results of the study will be published at scientific congresses and in peer-reviewed journals over the coming months.

NT-814 is an orally administered, potent and selective small molecule dual antagonist of both the neurokinin-1 and 3 receptors under development by KaNDy as a therapy for a range of Women’s Health conditions. NT-814 addresses vasomotor symptoms by modulating a group of oestrogen sensitive neurones in the hypothalamus in the brain (the KNDy neurones), that in menopausal women due to the absence of oestrogen, become hyperactive and consequently disrupt body heat control mechanisms resulting in the debilitating vasomotor symptoms of hot flashes and night sweats.

KaNDy Therapeutics is a clinical-stage company focused on optimizing the potential of NT-814 in the treatment of common, chronic debilitating female sex-hormone related conditions. These conditions, such as post-menopausal vasomotor symptoms, are debilitating for women often over many years and associated with significant healthcare and economic costs. NT-814 is wholly owned by KaNDy.

Syndesi Therapeutics announces the expansion of its management team with the appointment of Torsten Madsen, MD, PhD as Chief Medical Officer

Syndesi Therapeutics SA, a clinical stage biotechnology company developing novel modulators of the synaptic vesicle protein SV2A for the treatment of cognitive impairment, today announced Torsten Madsen MD, PhD has joined its management team as Chief Medical Officer.

Dr. Madsen brings over 12 years’ industry experience in CNS drug development in pharma/biotech. As a senior leader at Lundbeck in Denmark and the US he guided clinical development and registration of the anti-depressant vortioxetine. More recently, he has held senior roles at the CNS focused biotech companies Naurex and Aptinyx. Dr. Madsen earned his MD and a PhD from Copenhagen University, doing clinical training in psychiatry and general medicine and holding a postdoc position at Yale, conducting basic research in neural and synaptic plasticity.

Commenting on the appointment, Jonathan Savidge, CEO of Syndesi, said, “I’m delighted to welcome Torsten to the Syndesi team at an exciting time for the development of our lead molecule SDI-118. Torsten brings a wealth of experience specifically in CNS drug development and this will be invaluable to the company as we plan the next phases of clinical development for SDI-118.”

On his appointment as CMO, Torsten Madsen said, “It’s very exciting to be joining Syndesi to work on a novel synaptic mechanism with potential for broad applicability for treatment of cognitive impairment. I look forward to working with the Syndesi management team to progress SDI-118 into the next stage of clinical development to fully explore its potential to improve symptoms of cognitive impairment across a range of indications.”

About Syndesi Therapeutics

Syndesi Therapeutics was established to develop a series of novel, pro-cognitive small molecule SV2A modulators licensed from UCB. Syndesi is investigating the potential of these molecules to improve cognition in diseases such as Alzheimer’s Disease and other dementias, as well other conditions such as major depression and cognitive impairment associated with schizophrenia. The lead molecule, SDI-118, has successfully completed a First-in-Human Phase I study which demonstrated target engagement with PET imaging. The company has raised a total €17M in Series A funding from a syndicate of Belgium and international investors and has been awarded a total of up to €3.2 M in non-dilutive funding from the Walloon Region to support the development of the lead molecule SDI-118. For more information please visit www.syndesitherapeutics.com.

Mainstay Medical Announces Completion of Day 100 Meeting with FDA Regarding Pre-Market Approval (PMA) Application for ReActiv8

Mainstay Medical International plc (“Mainstay” or the “Company”, Euronext Paris: MSTY.PA and Euronext Growth operated by Euronext Dublin (MSTY.IE), a medical device company focused on bringing to market ReActiv8, an implantable restorative neurostimulation system to treat disabling Chronic Low Back Pain, today announced that on 10 December 2019 the Company completed a Day 100 meeting with the U.S. Food and Drug Administration (FDA) regarding a Pre-Market Approval (PMA) application submission for ReActiv8.

Jason Hannon, CEO of Mainstay, said: “We appreciate the opportunity to meet with FDA to discuss their review of the data we included in the PMA. The productive dialogue will help us submit an amendment to the PMA to reflect FDA’s feedback. We continue to expect a decision regarding approval around the end of 2020.”

FDA generally meets with the PMA sponsor approximately 100 days after filing of the PMA for the purpose of discussing the status of the review of the application. Prior to the meeting, FDA provided Mainstay with its initial feedback on the PMA, consisting of questions regarding the data included in the PMA and the interpretation of such data. The Company currently has no plans to conduct another premarket pivotal IDE trial for ReActiv8.

Mainstay will include the information requested by FDA in an amendment to the PMA, which the Company expects to file in the first quarter of 2020.

Mainstay Medical Announces Regulatory Approval from Australian Therapeutic Goods Administration (TGA) for ReActiv8

Application for inclusion on Australian Prostheses List for private reimbursement planned for first quarter of 2020, with an approval decision expected in the third quarter of 2020.

Mainstay Medical International plc (“Mainstay” or the “Company”, Euronext Paris: MSTY.PA and Euronext Growth operated by Euronext Dublin (MSTY.IE), today announced that it has received regulatory approval from the Australian Therapeutic Goods Administration (TGA) for ReActiv8, its implantable restorative neurostimulation system to treat disabling Chronic Low Back Pain. This approval confirms admission of ReActiv8 to the Australian Register of Therapeutic Goods (ARTG), enabling commercialization throughout Australia.

Jason Hannon, CEO of Mainstay, said: “We are excited to receive TGA approval and take the next step toward making ReActiv8 available to patients in Australia. Australian physicians who have been part of our clinical studies to date are among the most experienced globally in selecting and treating patients with ReActiv8 therapy. The clinical data in support of ReActiv8 continues to build and was instrumental in demonstrating to TGA that ReActiv8 is a valuable therapy that should be available to Australian patients. This approval was received ahead of our expected timeline, and we will now move to the next step in the process, which is applying for inclusion of Reactiv8 on the Prostheses List. We plan to launch ReActiv8 commercially after securing a place on the Prostheses List.”

The Company plans to submit an application for ReActiv8 to be included in the Prostheses List of reimbursed products, with a reimbursement decision expected in the third quarter of 2020. The Prostheses List identifies implantable devices eligible for reimbursement from all private health insurance funds in Australia.

About ReActiv8

ReActiv8 is an active implantable medical device designed to treat people with chronic low back pain (CLBP). ReActiv8 electrically stimulates the nerves that supply the lumbar multifidus muscle, a key stabilizing muscle of the low back, to elicit contraction of the muscle which can lead to restoration of control over time, allowing the back to recover from CLBP.

Low back pain is the number one cause of years lived with disability worldwide and is a leading cause of activity limitation and work absence throughout much of the world, imposing a high economic burden on individuals, families, communities, industry, and governments. While treatment options exist for patients with CLBP of a predominantly neuropathic origin, for the large portion of patients whose pain is predmoniantly nociceptive (or mechanical) in nature there are few therapies beyond drugs and injections, both of which offer temporary relief at best.

ReActiv8 is intended for those patients without indications for spine surgery or spinal cord stimulation and who have continuing pain despite medical management. The Company estimates that there are approximately two million people in the EU and the U.S. alone who could be candidates for ReActiv8 today.

ReActiv8 has a CE Mark allowing for commercialization in the European Economic Area and has been focused on building clinical validation in Germany in select centers ahead of wider commercial availability in the future. The Company submitted the final module of its Pre-Market Approval (PMA) application to the U.S. FDA relating to ReActiv8 in August 2019, and it expects an approval decision around the end of 2020.

Inflazome Progresses Two Drugs Into Clinical Trials

• Two Phase I studies are underway for Inzomelid and Somalix, Inflazome’s NLRP3 inflammasome inhibitors, with data due in Q1 2020

• Inzomelid is under development as an orally available, brain-penetrant drug for neuroinflammatory diseases such as Parkinson’s, Alzheimer’s and Motor Neuron Disease as well as orphan diseases such as CAPS (Cryopyrin-associated periodic syndromes)

• Somalix is under development as an orally available, peripherally-restricted drug to address clinical unmet needs in inflammatory conditions such as arthritis and cardiovascular disease

Inflazome (inflazome.com), the pioneering inflammasome biotech company developing multiple drugs that stop harmful inflammation, today announces that healthy volunteers have been successfully dosed in the company’s Phase I clinical trials of Inzomelid and Somalix, two small molecule inhibitors of the NLRP3 inflammasome. These trials represent an important milestone for Inflazome and confirm its leadership in the inflammasome space.

Activation of the NLRP3 inflammasome in the body drives harmful inflammation, and is implicated in many diseases. Inzomelid and Somalix are two potent small molecules designed to inhibit activation of NLRP3 and reduce the damage caused by chronic, uncontrolled inflammation.

Inzomelid is a brain-penetrant drug intended for the treatment of neuroinflammatory and neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Motor Neuron Disease as well as the orphan disease CAPS.

Somalix is intended for the treatment of debilitating conditions such as cardiovascular disease, arthritis and many other diseases.

Both Phase I studies are first in human, single-centre, double blinded, randomised trials and are designed to evaluate safety and tolerability in healthy adult participants. The Inzomelid trial is expected to complete in January 2020, whilst Somalix will complete in March 2020. The Company intends to progress Inzomelid and Somalix into multiple Phase II studies in 2020.

Thomas Jung, Chief Medical Officer of Inflazome, commented, “We are delighted to see our two leading candidates, Inzomelid and Somalix, progress into the clinic and take a step closer towards finding a treatment for patients suffering from a range of diseases caused by harmful inflammation.”

Matt Cooper, Chief Executive Officer of Inflazome, commented, “This achievement represents an important milestone for Inflazome and for the field of inflammatory diseases more generally. We are excited to advance two drugs into safety trials in preparation for multiple proof of concept Phase II trials in 2020. We have pioneered the development of inhibitors of inflammasome-driven inflammation and will use our expertise to bring benefits to patients as quickly as possible.”

About Inflazome

Inflazome is a biotech company leading the development of orally available drugs to address clinical unmet needs in inflammatory diseases by targeting inflammasomes. Inflammasomes are understood to drive many chronic inflammatory conditions, from Parkinson’s and Alzheimer’s to asthma, inflammatory bowel disease, chronic kidney disease, cardiovascular disease, arthritis and NASH. Inflazome has two ongoing Phase I studies, the first with Inzomelid is under development as an orally available, brain-penetrant drug for neuroinflammatory diseases such as Alzheimer’s, Parkinson’s and Motor Neuron Disease. Somalix is under development as an orally available, peripherally-restricted drug to address clinical unmet needs in inflammatory conditions such as arthritis and cardiovascular disease. Inflazome is headquartered in Dublin, Ireland, with offices in Cambridge, UK and Brisbane, Australia.

To learn more visit: inflazome.com

About the NLPR3 Inflammasome

Activated NLRP3 acts as a ‘danger sensor’ in the body to release the pro-inflammatory cytokines IL-1β, IL-18 and induce uncontrolled, lytic cell death (pyroptosis). These processes lead to chronic inflammation, and as such, NLRP3 has been implicated in a large number of diseases.

Contacts

Inflazome: Dr Jeremy Skillington | VP Business Development

E: j.skillington@inflazome.com

Media: FTI Consulting

UK & International | Ciara Martin/Tim Stamper

T: +44 20 37271000

Ireland & International | Jonathan Neilan/Patrick Berkery

T: +353 1 7650800

E: StratCommEMEAInflazome@fticonsulting.com

Syndesi Therapeutics announces successful completion of first-in-human Phase I study of novel SV2A modulator, SDI-118, in development for the treatment of cognitive impairment

Syndesi Therapeutics SA, a biotechnology company developing novel modulators of the synaptic vesicle protein SV2A for the treatment of cognitive impairment, today announced that the first-in-human Phase I study of its lead molecule, SDI-118, has been successfully completed.

The first-in-human Phase I study was a randomized, placebo controlled, single ascending dose study in healthy male subjects designed to investigate the safety, tolerability and pharmacokinetics of oral doses of SDI-118. The study also included PET imaging in a group of subjects to directly measure SV2A target engagement by SDI-118 in the brain.

SDI-118 was safe and well tolerated at all doses administered, with no serious adverse events. All adverse events considered to be related to SDI-118 administration were reported as mild. SDI-118 also showed favorable pharmacokinetic properties suitable for once daily dosing. Data from PET imaging following administration of a range of SDI-118 doses demonstrated a clear relationship between central SV2A occupancy and plasma exposure. Importantly, these results also demonstrated that the plasma exposures reached in the study, shown to be safe and well tolerated, provided essentially complete brain SV2A occupancy.

Commenting on the results, Jonathan Savidge CEO of Syndesi, said “We are very pleased with the excellent data generated in this first-in-human study. Single doses of the compound that result in high SV2A occupancy were shown to be safe and well tolerated. The results of the study provide an excellent basis for further clinical development, with the PET data informing the choice of doses in future studies. We will be initiating a further Phase I trial investigating multiple doses of SDI-118, including in elderly subjects.”

About Syndesi Therapeutics

Syndesi Therapeutics was established to develop a series of novel, pro-cognitive small molecule SV2A modulators licensed from UCB. In February 2018 the company announced €17M in Series A funding from a syndicate of Belgium and international investors. In March 2019, Syndesi announced the award of up to €3.2 M in non-dilutive funding from the Walloon Region to support the development of the lead molecule SDI-118 through Phase I clinical development. Syndesi is investigating the potential of these novel SV2A modulators to improve cognition in diseases such as Alzheimer’s Disease and other dementias, as well other conditions such as major depression and cognitive impairment associated with schizophrenia. For more information please visit www.syndesitherapeutics.com

Mainstay Medical Announces Acceptance For Filing by US FDA Of Pre-Market Approval (PMA) Application for ReActiv8

Mainstay Medical International plc (“Mainstay” or the “Company”, Euronext Paris: MSTY.PA and Euronext Growth of Euronext Dublin: MSTY.IE), a medical device company focused on bringing to market ReActiv8®, an implantable neurostimulation system to treat disabling Chronic Low Back Pain, today announces that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s Pre-Market Approval (PMA) application for ReActiv8.

Mainstay submitted the PMA to the FDA in August. By regulation, the FDA will notify the applicant whether the PMA has been accepted for filing within 45 days after submission. By accepting the Company’s PMA for filing, the FDA has made a threshold determination that the application is sufficiently complete to begin an in-depth review. Mainstay continues to expect a decision on approval around the end of 2020.

About Mainstay

Mainstay is a medical device company focused on commercializing an innovative implantable restorative neurostimulation system, ReActiv8®, for people with disabling Chronic Low Back Pain (CLBP). The Company is headquartered in Dublin, Ireland. It has subsidiaries operating in Ireland, the United States, Australia, Germany and the Netherlands, and is listed on regulated market of the Euronext Paris (MSTY.PA) and the Euronext Growth market of Euronext Dublin (MSTY.IE).

About Chronic Low Back Pain

One of the root causes of CLBP is impaired control by the nervous system of the muscles that dynamically stabilize the spine. ReActiv8 is designed to electrically stimulate the nerves responsible for contracting these muscles to improve dynamic spine stability, allowing the body to recover from CLBP.

People with CLBP usually have a greatly reduced quality of life and score significantly higher on scales for pain, disability, depression, anxiety and sleep disorders. Their pain and disability can persist despite the best available medical treatments, and only a small percentage of cases result from an identified pathological condition or anatomical defect that may be correctable with spine surgery. Their ability to work or be productive is seriously affected by the condition and the resulting days lost from work, disability benefits and health resource utilization put a significant burden on individuals, families, communities, industry and governments.

Further information can be found at www.mainstay-medical.com

CAUTION – in the United States, ReActiv8 is limited by federal law to investigational use only.

Neuromod Successfully Closes €8 Million Capital Raise

• Proceeds to accelerate ongoing European commercialisation, manufacturing scale-up and US regulatory strategy

• Fountain Healthcare Partners, a major investor, led the financing round with participation from another existing investor, Moffett Investment Holdings

• Venture-debt investors Kreos Capital and Silicon Valley Bank also participated in the capital raise

Neuromod Devices Limited (“Neuromod” or the “Company”), the Irish medical technology company specialising in non-invasive neuromodulation technologies, today announces the closing of an €8 million capital raise, comprised of equity investment and venture-debt.

Proceeds from the financing will be used to accelerate ongoing European commercialisation of the Company’s Lenire® tinnitus treatment device; to scale-up manufacturing capacity to meet anticipated European demand; and to progress the Company’s US regulatory strategy to secure market entry into the United States. This financing round was led by existing investors Fountain Healthcare Partners and Moffett Investment Holdings, with venture-debt provided by new investors Kreos Capital and Silicon Valley Bank.

Centre of Excellence in Tinnitus Care and Neuromodulation

This investment marks a significant milestone for Neuromod as the Company recently opened its first Centre of Excellence specialising in neuromodulation and tinnitus at the Hermitage Medical Clinic in Dublin. The centre, Neuromod Medical, a wholly-owned subsidiary of Neuromod Devices Limited, offers tinnitus assessments and treatment with the Lenire® tinnitus treatment system, a breakthrough evidence-based, home-use medical device. The first facility to offer treatment with Lenire® outside of Ireland will be in Hannover, Germany which will be opened before the end of 2019. Additional locations throughout Europe have been identified and will become operational during the course of 2020.

Lenire® Tinnitus Treatment

Lenire® is the first non-invasive bimodal neuromodulation tinnitus treatment shown to soothe and relieve tinnitus. Lenire® has CE-mark certification for the treatment of tinnitus under the supervision of an appropriately qualified healthcare professional in Europe.

Dr. Ross O’Neill, CEO of Neuromod commented: “We are very pleased to have Kreos Capital and Silicon Valley Bank join our existing investors Fountain Healthcare Partners and Moffett Investment Holdings. This investment will allow us to ramp-up the manufacturing of our Lenire® tinnitus treatment product, ensuring it will be more widely available for many underserved patients suffering with tinnitus across Europe. We will also build on European commercialisation through a regulatory submission to the FDA to make way for a launch in the United States”.

Cian O’Driscoll from Kreos Capital commented: “Neuromod is an exceptional business with a unique technology and product. We are excited to be working with them to fund their expansion across Europe and the United States. It is estimated that 150 million people suffer with chronic tinnitus globally and we believe Lenire® offers an important breakthrough to address this large unmet medical need”.

Clive Lennox from Silicon Valley Bank commented: “We are delighted to join Fountain Healthcare and Moffett Investments to support the growth of Neuromod Devices. Neuromod are yet another example of Ireland’s innovative life-science companies and we look forward to helping them bring their Lenire® tinnitus treatment to the millions of sufferers across Europe and the US.”

Dr Manus Rogan, Managing Partner of Fountain Healthcare Partners, commented: “As an early stage investor in Neuromod, we are excited to be at a point where we are ramping up manufacturing and European commercialisation of Lenire® and looking towards US regulatory filing. The market potential for Neuromod and Lenire® is clearly significant necessitating investment in manufacturing sufficient inventory to meet the existing and anticipated demand.”

About Neuromod Devices Limited

Neuromod, headquartered in the Digital Hub, Dublin, Ireland, is an emerging medical technology company, specialising in the design and development of neuromodulation technologies to address the clinical needs of underserved patient populations who live with chronic and debilitating tinnitus. The company was founded in 2010, by Dr. Ross O’Neill, as a spin-out from Maynooth University.

Neuromod has conducted the largest and longest followed-up clinical trials in tinnitus to confirm the efficacy of its non-invasive neuromodulation treatment device for this extremely common disorder for which no standard of care has yet been established. Tinnitus affects between 10 and 15% of the global population, and the lives of at least 1 in every 100 people worldwide are severely compromised because of the incessant nature of the illusory sound that is often described as a ringing or buzzing in the ears.

www.NeuromodDevices.com

Contacts

Patrick Berkery

+353-1-765-0884

patrick.berkery@fticonsulting.com

EIB unveils financing for Irish innovation as Galway medtech firm Vivasure Medical gets EUR 10 million backing

Vivasure Medical second Irish medtech firm to get EIB Venture Debt financing

EIB and IBEC brief business leaders on new long-term financing for Irish innovation

EIB confirms strengthened direct support for Irish companies

Galway based Medtech Company Vivasure Medical Ltd. is the latest Irish company to agree Venture Debt financing with the European Investment Bank.

The second long-term EIB financing for an Irish medical technology company was confirmed ahead of a briefing for Irish business leaders on new innovation financing opportunities supported by the EU Bank.

IBEC-EIB briefing on new innovation financing opportunities

Company representatives and innovation partners were briefed on new tailor made EIB financing at workshop in Dublin hosted by IBEC and the EIB, part of a series of corporate finance briefings being held across Ireland.

“Ireland is home to world class innovation and the European Investment Bank recognises the crucial need to ensure that research driven companies can expand and succeed in new markets. The new EUR 10 million backing for Vivasure Medical will contribute to efforts to improve cardiology and endovascular treatment through pioneering medtech innovation. In partnership with IBEC we wish to ensure that companies across Ireland can consider how streamlined innovation financing can turn research ideas into commercial success.” said Andrew McDowell, European Investment Bank Vice President.

“Access to diversified funding streams help boost the competitiveness, resilience and innovation of fast growing companies in Ireland. Companies across Ireland are securing EIB financing, allowing them to continue to develop, innovate and compete on a global level. Today’s joint event with the EIB allows companies across a range of sectors to gain a direct insight into new innovation financing at our fourth specialist finance briefing” said Danny McCoy, Ibec CEO.

Over the last three years research focussed companies across Ireland have benefited from European Investment Bank Venture Debt financing. These include world class companies developing artificial intelligence, pharmaceutical and telecommunication products.

Expanding development of cardiology treatment for high risk patients

The EUR 10 million new financing will be used by Vivasure to expand research and development of medical devices to provide non-invasive cardiology treatment. Vivasure has developed pioneering non-invasive biodegradable devices to treat cardiology patients with conditions that require vascular surgery.

“Over the last decade Vivasure Medical has developed innovative and easy to use medical devices that transform cardiology and endovascular treatments and avoid the need for access and closure surgery. We welcome the European Investment Bank’s firm support and agreement of EUR 10 million of new financing that will enable Vivasure to accelerate innovation and expand into new markets. This is a vote of confidence in the Irish Medtech.” said Gerard Brett, CEO and co-founder of Vivasure Medical.

Last year the European Investment Bank Group provided EUR 970 million of long-term financing to strengthen higher education, improve healthcare, transform transport and harness clean energy across Ireland, as well as enhancing corporate research and innovation.

Mainstay Medical Provides Company Update and Reports 2019 Half Year Financial Results

ReActiv8 Pre-Market Approval (PMA) application submitted to U.S. FDA in August 2019; acceptance for FDA review expected October 2019

European commercial validation efforts continue to progress

Successful completion of financing transactions providing approximately $28 million of cash runway extension

Mainstay Medical International plc (“Mainstay” or the “Company”, Euronext Paris: MSTY.PA and Euronext Growth of Euronext Dublin: MSTY.IE), a medical device company focused on bringing to market ReActiv8®, an implantable neurostimulation system to treat disabling Chronic Low Back Pain, today provides a company update and reports its financial results for the half year ended 30 June 2019.

Jason Hannon, CEO of Mainstay, said: “We continue to make significant progress on our key corporate objectives of pursuing regulatory approval in the U.S. and advancing the commercial validation effort in Germany and other select European markets. I am pleased to report that we submitted the pre-market approval (PMA) application for ReActiv8 to the U.S. Food and Drug Administration (FDA) in August. Pending the FDA’s acceptance of the PMA for review, anticipated in October 2019, we expect a decision regarding approval around the end of 2020. We also continue to make progress working with key physician partners in Germany who are incorporating ReActiv8 into their practices in order to validate commercial adoption, refine patient selection strategies and follow ongoing patient progress.”

Business Update

• In August 2019, Mainstay submitted the PMA application to the FDA based upon the totality of its clinical data for ReActiv8. Pending acceptance of the submission by the FDA, anticipated in October 2019, a decision regarding approval is expected around the end of 2020. The pivotal clinical trial upon which the PMA submission was based is the 204-patient ReActiv8-B clinical study. A summary of the clinical trial results is as follows:

  • The primary efficacy endpoint of the study was a comparison of responder rates between the treatment and control groups as measured on the visual analog scale (VAS) of pain, with responders defined as having a 30% or greater improvement on this measure between baseline and 120 days after randomization, without any increase in pain medication and/or muscle relaxants taken in the two weeks prior to the primary endpoint assessment visit. In the treatment group the responder rate at 120 days was 57%, compared to 47% in the control group, resulting in a difference that is not statistically significant.

  • The protocol included a pre-specified analysis of the primary endpoint data examining the cumulative proportion of responders, which is a comparison of ranks and inherently preserves information over a dichotomized endpoint, thereby improving statistical power. In that analysis, a statistically significant difference between the treatment and control groups was demonstrated, with the treatment group showing a higher proportion of responders across all threshold levels.

  • The protocol also included a pre-specified analysis of the primary endpoint where Mainstay adjusted for patients who increased their pain medications for reasons unrelated to their back pain. In that analysis, the responder rate at 120 days in the treatment group was 61%, compared to 47% in the control group, resulting in a difference that is statistically significant.

  • Statistically significant differences on a number of key secondary endpoints and supplemental analyses were observed in the treatment group as compared to the control group at 120 days, including reduction from baseline in pain as measured by both mean reduction in VAS and percent of pain relief (PPR), change from baseline in disability measured by the Oswestry Disability Index (ODI), change from baseline in quality of life measured by the European Quality of Life Score on Five Dimensions (EQ-5D), subject global impression of change (SGIC), clinician global impression of change (CGI) and patient treatment satisfaction as measured by the treatment satisfaction questionnaire (TSQ).

  • Improvements in the percentage of patients reporting pain reduction continued beyond the 120-day assessment through one year for both groups. The percentage of the 160 patients in the treatment and control groups that had completed the one-year assessment having a 30% or greater reduction in low back pain VAS at that assessment without a significant increase in pain medication was 66%. These data are subject to change as the remaining patients reach the one-year assessment.

  • The protocol permitted patients to adjust their back pain medication usage after the 120-day assessment point. At one year, 49% of the 61 patients in both groups combined who were on opioids at baseline had discontinued or decreased their use of opioids. These results are subject to change as the remaining patients reach the one-year assessment.

  • The incidence and type of adverse events (AEs), including serious AEs, compares favorably to that of spinal cord stimulator devices, with no unanticipated AEs related to the device, procedure or stimulation.

• In Germany, Mainstay’s initial European market, the Company’s re-focusing of its commercial validation efforts was undertaken throughout 2018. Mainstay is now solely dedicated to building a small number of reference sites where high volumes of patients are treated with ReActiv8, allowing the Company to gather associated clinical data, refine patient selection processes for commercial markets, and gain the learnings needed to accelerate commercial launch in future markets.

Financial Update

• Since the beginning of 2019, Mainstay has conducted financing activities that have resulted in approximately $28 million of cash runway extension:

• On 29 July 2019, Mainstay completed financing transactions consisting of the issuance of 4,649,775 new ordinary shares at a purchase price of €3.00 per share and the drawdown of €3.0 million in additional debt from the Company’s existing lender, IPF Partners, resulting in aggregate gross proceeds of €16.9 million (US$18.9 million).

• On 18 April 2019, Mainstay and its subsidiary, Mainstay Medical Limited, entered into an amendment to their agreement with IPF Partners relating to the existing debt facility. Pursuant to the amendment:

  • The repayment schedule for the three existing tranches drawn under the debt facility was amended such that no principal or interest will be repaid until 2021, with the principal and accrued interest to be amortized over the period from January 1, 2021 through September 30, 2023.

  • A new tranche of €3.0 million (approximately $3.34 million) was made available to Mainstay, which was drawn down by Mainstay on 29 July 2019. The repayment schedule for the new tranche will be the same as the amended repayment schedule for the three existing tranches.

  • The interest rate for all tranches will be 8% per annum, with interest accruing but capitalized prior to January 1, 2021. The interest rates previously applicable to the initial three tranches ranged from 10.5% to 12.5%.

  • The 5% repayment fee applicable to each existing tranche was eliminated.

  • All principal and accrued interest from all tranches will automatically convert into ordinary shares of the Company at a price per share of €8 upon the earlier of (a) FDA approval of Mainstay’s PMA application for ReActiv8, (b) the date by which at least 900,000 ordinary shares of the Company are publicly sold on-market by non-affiliates of Mainstay since April 2019 at a price per share of at least €8, or (c) IPF Partners’ election to undertake such conversion, in each case unless the Company elects to satisfy such obligation in whole or in part in cash.

  • The minimum cash covenant was amended so that Mainstay is required to hold cash at least equal to its projected cash expenditures for operations and debt repayment for the next three months, and the covenant relating to the achievement of commercial milestones was eliminated.

  • Mainstay issued to IPF Partners warrants to purchase 1.5 million of its ordinary shares at a price per share of €6 at any time prior to the 6th anniversary of the amendment date.

• Revenue during the six-month period ended 30 June 2019 was $0.6 million ($0.36 million in 1H18).

• Operating expenses for the six-month period ended 30 June 2019 were $9.5 million ($15.8 million in 1H18). The decrease was driven primarily by reduced costs relating to activities for the ReActiv-8 B clinical trial following the completion of all implants, as well as a decrease in payroll related costs following a reduction in headcount within 2019.

• Cash on hand as at 30 June 2019 was $5.8 million (31 December 2018: $29.7 million). Cash on hand at 31 July 2019 was $23.5 million.

Details of ReActiv8-B Clinical Trial

The ReActiv8-B clinical trial is an international, multi-center, prospective, randomized, active sham-controlled, blinded trial with one-way cross-over, conducted under an IDE from the FDA. A total of 204 patients with chronic low back pain refractory to physical therapy were implanted with ReActiv8 at leading clinical sites in the U.S., Europe and Australia and randomized 1:1 to therapy or control. In the treatment group, the ReActiv8 pulse generator was programmed to deliver electrical stimulation expected to elicit episodic contractions of the multifidus muscle. In the control group, the ReActiv8 device was programmed to provide a low level of electrical stimulation. Following assessment of the primary endpoint at 120 days, patients in the control group crossed-over to receive levels of electrical stimulation similar to those in the treatment group. The FDA’s review of the PMA may result in the FDA not agreeing with Mainstay’s interpretation of its clinical data, including whether statistical significance was achieved for one or more endpoints.

About Mainstay

Mainstay is a medical device company focused on commercializing an innovative implantable restorative neurostimulation system, ReActiv8®, for people with disabling Chronic Low Back Pain (CLBP). The Company is headquartered in Dublin, Ireland. It has subsidiaries operating in Ireland, the United States, Australia, Germany and the Netherlands, and is listed on regulated market of the Euronext Paris (MSTY.PA) and the Euronext Growth market of Euronext Dublin (MSTY.IE).

About Chronic Low Back Pain

One of the root causes of CLBP is impaired control by the nervous system of the muscles that dynamically stabilize the spine. ReActiv8 is designed to electrically stimulate the nerves responsible for contracting these muscles to improve dynamic spine stability, allowing the body to recover from CLBP.

People with CLBP usually have a greatly reduced quality of life and score significantly higher on scales for pain, disability, depression, anxiety and sleep disorders. Their pain and disability can persist despite the best available medical treatments, and only a small percentage of cases result from an identified pathological condition or anatomical defect that may be correctable with spine surgery. Their ability to work or be productive is seriously affected by the condition and the resulting days lost from work, disability benefits and health resource utilization put a significant burden on individuals, families, communities, industry and governments.

Further information can be found at www.mainstay-medical.com

Mainstay Medical Announces Completion of Financing Transactions

• Funds to be used to support PMA process for ReActiv8® in US and to further European commercial validation efforts

• Gross proceeds, together with savings from previously-announced debt restructuring, provides approximately $28 million in cash runway extension

Dublin, Ireland: Mainstay Medical International plc (Mainstay or the Company, Euronext Paris: MSTY.PA and Euronext Growth of Euronext Dublin: MSTY.IE), a medical device company focused on bringing to market ReActiv8®, an implantable neurostimulation system to treat disabling Chronic Low Back Pain, announces today that it has completed financing transactions to raise gross proceeds of €16.9 million (US$18.9) million.

Jason Hannon, CEO of Mainstay, commented: “Our objectives for the remainder of 2019 and 2020 are clear: file the pre-market approval (PMA) application for ReActiv8 with the U.S. Food and Drug Administration (FDA) this summer; advance the PMA review process with the FDA, with an approval decision expected in late 2020; and continue the commercial validation effort in Germany and other select European markets by working with key physician partners who identify appropriate ReActiv8 patients in their centres in order to validate commercial adoption, refine patient selection strategies and follow ongoing patient progress. We are pleased with the outcome of this financing, which was oversubscribed. These deals will provide the capital to expeditiously advance each of these goals and, together with our previously-announced debt restructuring, expands our expected cash runway into 2021.”

The total cash runway extension achieved by Mainstay amounts to approximately $28.0 million: approximately $18.9 million in gross proceeds from the financing transactions and approximately $9.1 million in savings that resulted from the Company’s restructuring of its debt completed in April.

Specific information regarding the Financing

The financing transactions consist of the issuance of 4,649,775 new ordinary shares (New Shares) at a purchase price of €3.00 per New Share and the drawdown of €3.0 million in additional debt from the Company’s existing lender. The investors in the equity financing are primarily existing shareholders in the Company (principally Sofinnova Partners, KCK Limited, Fountain Healthcare Partners and several individual investors).

The New Shares, when issued, will represent an increase of approximately 53.0% from the Company's existing issued ordinary share capital. Following issuance of the New Shares, the Company’s issued share capital will consist of 13,421,504 Ordinary Shares of €0.001 each (which carry voting rights) and 40,000 deferred shares with a nominal value of €1.00 each (which do not carry voting rights). Therefore, the figure that should be used by shareholders as the denominator for the calculations by which they will determine if they are required to notify their holdings of voting rights, or a change to their holdings of voting rights, over the Ordinary Shares of the Company under the Transparency (Directive 2004/109/EC) Regulations 2007 of Ireland, as amended and the Transparency Rules of the Central Bank of Ireland is 13,421,504.

The New Shares, when issued, will be fully paid and rank pari passu in all respects with the existing issued Ordinary Shares, except that the New Shares will not be admitted to trading on Euronext Paris or the Euronext Growth market (Euronext Growth) of Euronext Dublin (Admission) until the Company has published a prospectus that is required to effect the admission to trading of the New Shares on Euronext Paris in accordance with EU prospectus law. Under the terms of the subscription agreements for the New Shares, the Company has agreed that if Admission does not occur by 120 days after the issuance of the New Shares, then for all or part of one or more of the consecutive 30 day periods following that date (a Relevant Period) during which Admission does not occur the Company shall separately pay to each investor, as liquidated damages, a cash payment of 0.5% of the total subscription price paid by the relevant investor for each Relevant Period (or partial Relevant Period) during which Admission has still not occurred; provided, however that in no event shall the Company be required to pay to any investor an aggregate amount that exceeds 5% of the total subscription price paid by that investor. Any such payment(s) shall be made within five Business Days of the end of each such Relevant Period.

Sofinnova Partners, KCK Limited and Fountain Healthcare Partners (who are considered substantial shareholders under the Euronext Growth Markets Rule Book (Euronext Growth Rules)) will subscribe for 533,333, 654,000 and 1,333,333 New Shares, respectively. Their participation in the financing will constitute related party transactions under Rule 5.18 of the Euronext Growth Rules. The Directors, with the exception of Antoine Papiernik (with respect to Sofinnova Partners) and Nael Karim Kassar and Greg Garfield (with respect to KCK Limited), consider, having consulted with J&E Davy, the Company’s Euronext Growth Adviser, that the terms of the participation of Sofinnova Partners, KCK Limited and Fountain Healthcare Partners in the financing are fair and reasonable insofar as Mainstay shareholders are concerned.

David Brabazon, who is a Director, will also participate in the financing, subscribing for 155,000 New Shares, so that following completion of the financing, he will hold 212,828 Ordinary Shares, representing 1.6% of the enlarged issued ordinary share capital of the Company.

This announcement contains inside information for the purposes of the Regulation (EU) No 596/2014 of the European Parliament and of the Council of 16 April 2014 on market abuse (the “Market Abuse Regulation” or “MAR”). Market soundings, as defined in MAR, were taken in respect of the financing, with the result that certain persons became aware of inside information, as permitted by MAR. That inside information is set out in this announcement. Therefore, those persons that received inside information in a market sounding are no longer in possession of inside information relating to the Company and its securities.

The person responsible for arranging release of this announcement on behalf of Mainstay is Matt Onaitis.

About Mainstay

Mainstay is a medical device company focused on bringing to market an innovative implantable neurostimulation system, ReActiv8®, for people with disabling Chronic Low Back Pain (CLBP). The Company is headquartered in Dublin, Ireland. It has subsidiaries operating in Ireland, the United States, Australia, Germany and the Netherlands, and is listed on regulated market of the Euronext Paris (MSTY.PA) and the Euronext Growth market of Euronext Dublin (MSTY.IE).

About Chronic Low Back Pain

One of the root causes of CLBP is impaired control by the nervous system of the muscles that dynamically stabilize the spine. ReActiv8 is designed to electrically stimulate the nerves responsible for contracting these muscles to improve dynamic spine stability, allowing the body to recover from CLBP.

People with CLBP usually have a greatly reduced quality of life and score significantly higher on scales for pain, disability, depression, anxiety and sleep disorders. Their pain and disability can persist despite the best available medical treatments, and only a small percentage of cases result from an identified pathological condition or anatomical defect that may be correctable with spine surgery. Their ability to work or be productive is seriously affected by the condition and the resulting days lost from work, disability benefits and health resource utilization put a significant burden on individuals, families, communities, industry and governments.

Further information can be found at www.mainstay-medical.com

CAUTION – in the United States, ReActiv8 is limited by federal law to investigational use only.

PR and IR Enquiries:

LifeSci Advisors, LLC

Brian Ritchie

Tel: + 1 (212) 915-2578

Email: britchie@lifesciadvisors.com

FTI Consulting (for Ireland)

Jonathan Neilan or Patrick Berkery

Tel. : +353 1 765 0886

Email: mainstay@fticonsulting.com

Euronext Growth Advisers:

Davy

Fergal Meegan or Barry Murphy

Tel: +353 1 679 6363

Email: fergal.meegan@davy.ie or barry.murphy2@davy.ie

Mainstay Medical Announces Completion of Pre-Submission Meeting with FDA Regarding Pre-Market Approval (PMA) Application for ReActiv8

PMA submission for ReActiv8 expected this summer

Dublin – Mainstay Medical International plc (“Mainstay” or the “Company”, Euronext Paris: MSTY.PA and Euronext Growth operated by Euronext Dublin (MSTY.IE), a medical device company focused on bringing to market ReActiv8, an implantable restorative neurostimulation system to treat disabling Chronic Low Back Pain, today announces that on 25 June 2019 the Company completed a pre-submission meeting with the U.S. Food and Drug Administration regarding a Pre-Market Approval (PMA) application submission for ReActiv8.

Jason Hannon, CEO of Mainstay, said: “We believe in a rigorous, evidence-based approach to the evaluation of ReActiv8, and we appreciate the opportunity to meet with the FDA on the data we have generated to date relating to the efficacy and safety of this novel therapy. We expect to submit the final module of our PMA application to the FDA relating to ReActiv8 this summer, with a decision on approval expected around the end of 2020.”

Separately, Mainstay also announced that it has entered into an amendment to its agreement with IPF Partners relating to its existing debt facility. Under the amendment, the deadline for Mainstay to qualify to draw down a new tranche of €3.0 million (approximately $3.34 million) in debt was extended from June 30, 2019 to July 31, 2019.

About Mainstay

Mainstay is a medical device company focused on commercializing an innovative implantable restorative neurostimulation system, ReActiv8®, for people with disabling Chronic Low Back Pain (CLBP). The Company is headquartered in Dublin, Ireland. It has subsidiaries operating in Ireland, the United States, Australia, Germany and the Netherlands, and is listed on the regulated market of Euronext Paris (MSTY.PA) and the ESM of Euronext Dublin (MSTY.IE).

About Chronic Low Back Pain

One of the root causes of CLBP is impaired control by the nervous system of the muscles that dynamically stabilize the spine. ReActiv8 is designed to electrically stimulate the nerves responsible for contracting these muscles to improve dynamic spine stability, allowing the body to recover from CLBP.

People with CLBP usually have a greatly reduced quality of life and score significantly higher on scales for pain, disability, depression, anxiety and sleep disorders. Their pain and disability can persist despite the best available medical treatments, and only a small percentage of cases result from an identified pathological condition or anatomical defect that may be correctable with spine surgery. Their ability to work or be productive is seriously affected by the condition and the resulting days lost from work, disability benefits and health resource utilization put a significant burden on individuals, families, communities, industry and governments.

Further information can be found at www.mainstay-medical.com

CAUTION – in the United States, ReActiv8 is limited by federal law to investigational use only.

PR and IR Enquiries:

LifeSci Advisors, LLC

Brian Ritchie

Tel: + 1 (212) 915-2578

Email: britchie@lifesciadvisors.com

FTI Consulting (for Ireland)

Jonathan Neilan or Patrick Berkery Tel. : +353 1 765 0886

Email: mainstay@fticonsulting.com

Euronext Advisers:

Davy

Fergal Meegan or Barry Murphy

Tel: +353 1 679 6363

Email: fergal.meegan@davy.ie or barry.murphy2@davy.ie

NeRRe Therapeutics announces positive findings from Phase 2b study with orvepitant in chronic cough

~ Statistically significant and clinically relevant improvements in patient reported outcomes in refractory chronic cough

~ Findings support further development of orvepitant in refractory chronic cough and meetings with the FDA and EMA are planned for Q4 2019 to discuss next steps

~Results provide important insights into the evolving field of chronic cough and methods used to clinically evaluate symptoms

Stevenage, UK – NeRRe Therapeutics today announces important results from the Phase 2b clinical trial (VOLCANO-2) with its neurokinin-1 receptor antagonist, orvepitant, in refractory chronic cough.

VOLCANO-2 was a 12-week, randomised, double-blind, placebo-controlled, Phase 2b dose-ranging clinical study designed to evaluate the efficacy, safety and tolerability of orvepitant in the treatment of refractory chronic cough in 315 patients from sites in the UK and North America. This was only the second Phase 2b dose ranging study in refractory chronic cough and the first with this mechanism.

Orvepitant, 30 mg once daily, resulted in statistically significant and clinically relevant improvements compared to placebo in the three key patient reported outcomes in the full analysis set at Week-12: Leicester Cough Questionnaire (p=0.009), Cough Severity VAS (p=0.034) and Urge-to-Cough VAS (p=0.005). The primary endpoint of awake cough frequency was not significant in this full analysis set, however in a pre-defined sub-group of higher frequency coughers, the reduction in cough frequency was near significant (p=0.066) at 12 weeks despite this sub-group analyses not being powered in the study. The trial confirmed the effectiveness of once daily dosing with orvepitant, and there were no safety concerns in this population; the excellent tolerability shown is seen as a major advantage of this class.

Professor Jaclyn Smith, Professor of Respiratory Medicine and Honorary Consultant, Director NIHR Manchester Clinical Research Facility added:

“Refractory chronic cough is a common and disabling condition and, with no proven therapies to treat the condition, there is a clear unmet medical need. The hypothesis being tested in this trial was that orvepitant could suppress the dysfunctional cough reflex and neuronal hypersensitivity which is thought to cause excessive coughing in patients with refractory chronic cough. The VOLCANO-2 study confirmed that orvepitant significantly improves the cough symptoms reported by patients and in so doing improves the quality of their lives. Orvepitant represents a novel first in class, non-opioid option to treat this common and debilitating condition.”

Commenting on the study outcome, Dr Mike Trower, Chief Scientific Officer and Founder at NeRRe Therapeutics said:

“Our intention was to design and execute a robust refractory chronic cough clinical study and, although there wasn’t a statistically significant reduction in awake cough frequency, the fact that patients are unequivocally reporting benefits cannot be underestimated.

“Awake cough frequency was monitored using an Ambulatory Cough Monitor and, whilst a very valuable tool, our data suggest that cough frequency is a more variable endpoint in patients with lower cough frequencies. In contrast, the cough frequency signal in this study was less variable in those patients with higher cough frequency at baseline, allowing a clear separation from placebo to be seen with the 30 mg once daily dose on all efficacy parameters, including cough frequency. This important observation will be incorporated in the design of the planned Phase 3 studies, thereby maximising their probability of success.”

The study outcomes support further development of orvepitant in refractory chronic cough and we intend to meet with the FDA and the EMA during Q4 this year to discuss next steps. The VOLCANO-2 data will be presented in full at a forthcoming international scientific meeting.

For more information, please contact:

NeRRe Therapeutics

Mary Kerr, CEO of NeRRe Therapeutics

Tel: +44 1438 906960

Email: info@nerretherapeutics.com

Consilium Strategic Communications

Mary-Jane Elliott/ Lindsey Neville/ Carina Jurs

Tel: +44 (0) 20 3709 5700

Email: NeRReTherapeutics@consilium-comms.com

About NeRRe Therapeutics

NeRRe Therapeutics, a private UK based clinical-stage company founded in 2012 as a spin out from GSK, is developing a unique pipeline of three neurokinin (NK)-1 antagonists for the treatment of chronic cough caused by neuronal hypersensitivity associated with neurokinin-1 receptor system dysfunction.

The company is led by an experienced management team and is backed by leading international life sciences investors: Advent Life Sciences, Fountain Healthcare Partners, Forbion Capital Partners, and OrbiMed. NeRRe Therapeutics is based at Stevenage Bioscience Catalyst.

You can find more information about NeRRe Therapeutics at www.nerretherapeutics.com

About VOLCANO-2

VOLCANO-2 was a randomised, double-blind, placebo-controlled, parallel group study that recruited subjects with refractory chronic cough of ≥1 year in duration and baseline awake cough frequency >10 coughs/hr. Subjects received placebo or one of three orvepitant doses (10, 20 or 30mg) once daily (OD) for 12-weeks. The primary endpoint was awake cough frequency at Week-12, recorded on a VitaloJAK ambulatory cough monitor. Other efficacy assessments included the Patient Recorded Outcomes (PROs): the Leicester Cough Questionnaire, Cough Severity Visual Analogue Scale (VAS) and Urge-to-Cough VAS. In total 315 subjects were randomised and 275 were evaluable at Week-12.

About Orvepitant

Orvepitant is a neurokinin-1 receptor antagonist that acts to reduce the central neural hypersensitivity that underlies chronic cough.

Fountain Healthcare Partners Raises €118M for Third Fund

Fund Raise Exceeds Target of €100m

Total Capital Under Management Reaches €294 million

DUBLIN & NEW YORK - Fountain Healthcare Partners (“Fountain”) today announces the initial closing of its third fund, Fountain Healthcare Partners Fund III, L.P. (“Fund III”) with €118 million of committed capital, exceeding its initial target raise of €100 million.

Fund III is a dedicated life science venture capital (“VC”) fund and brings Fountain’s total capital under management to €294 million. Within the life science sector, Fund III will primarily focus on specialty pharmaceuticals, biotechnology and medical devices.

Fountain will invest a majority of the capital in Fund III within Europe but expects to also make investments in the US market. Fund III is expected to make 10 to 12 investments in predominantly private life science companies.

The €118 million capital raised was sourced from major domestic and international institutional investors, including fund of funds, sovereign funds, corporate investors and family offices. Investors in Fund III include the European Investment Fund (EIF); Coolidge Limited, an investment vehicle of Mr Dermot Desmond; the Ireland Strategic Investment Fund (ISIF) and Allied Irish Bank (AIB).

Dr Manus Rogan, co-Founder and Managing Partner at Fountain, commented:

“Fountain’s investment strategy focuses on building a balanced portfolio of companies with complementary risk and return profiles within the life science sector. This strategy has resulted in a strong portfolio of investments for both Fund I and Fund II. The performance of our first and second funds is reflected in both the level and quality of new and existing investor participation in Fund III. With €118 million raised we are also pleased to have exceeded our initial close target of €100 million.

With almost €300 million of capital under management, we are Ireland’s largest dedicated life science venture capital fund. We will continue to seek opportunities to identify life science investment opportunities with exciting potential both in Ireland and internationally. Our ability to deploy significant capital together with our proven track record of helping early stage companies commercialise their potential, positions us a partner of choice for ambitious life science growth companies.”

Aidan King, co-Founder and Managing Partner at Fountain, added:

“Life sciences continues to be one of the best performing sectors for investor returns, driven by a consistent stream of IPOs and trade sales. Strong demand for life science investments is a reflection of investor’s belief in the underlying growth dynamics of the sector and the investment return opportunities presented by innovative life science companies.

In addition to financial returns, we are proud of the fact that to date, funding by Fountain has resulted in US FDA approval of three products in the areas of Parkinson’s disease, stroke and cardiovascular disease. These products are transforming the standard of care in these therapeutic areas and will greatly benefit patients worldwide”

Andrew McDowell, European Investment Bank Vice President said:

“The new €45 million European Investment Fund support for Fountain Healthcare represents our largest backing in more than a decade of successful cooperation with venture capital funds. It will further strengthen Ireland’s impressive venture capital ecosystem. Fountain’s third dedicated healthcare venture capital fund will benefit from proven success enabling world-class companies across Europe to develop impressive new treatments and technologies.”

Paul Saunders, Senior Investment Director, ISIF said:

“Fountain is an excellent example of ISIF co-investing with private sector partners to attract significant levels of international capital to Ireland, supporting economic activity and employment here and generating commercial returns.

This investment, our third with Fountain, builds on the success of our earlier investments in the biotech, medtech and life science sectors in which Ireland has emerged as a leading global hub. It will also help drive ISIF's commitment to regional development by supporting these sectors in clusters located throughout Ireland and helping them to thrive.”

Finlay McFadyen, Head of Investment Banking of AIB said:

“We are delighted to continue our support for Fountain Healthcare Partners in this fund which will invest in international and Irish early stage life science companies. These companies will benefit from Fountain’s expertise and experience. Fountain’s previous track record demonstrates their successful investment strategy of identifying companies and entrepreneurs with growth potential and assists to create value as they transition to the next phase of their business lifecycle. This strategy aligns to AIB’s strong focus on this growth sector.”

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 €294 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. The three principals at Fountain Healthcare Partners Fund III, Manus Rogan, Aidan King and Ena Prosser brings to investees over 70 years of collective experience in the pharmaceutical industry, corporate venture capital and VC across multiple investment and market cycles.

For more information please visit: www.fh-partners.com

Contacts

Manus Rogan | Managing Partner

Manus.Rogan@fh-partners.com

T: +353 1 5225111

Jonathan Neilan | FTI Consulting

jonathan.neilan@fticonsulting.com

T: +353 1 7650886

M: +353 86 231 4135

Neuromod Broadens Senior Leadership Team in Preparation for Global Commercialisation of Lenire™ Tinnitus Treatment

DUBLIN - Neuromod Devices Limited (“Neuromod” or “The Company”), the Irish medical technology company specialising in non-invasive neuromodulation technologies, today provides an update on organisational and leadership growth in preparation for European commercialisation and US regulatory clearance application.

Following the completion of two of the largest clinical trials ever conducted in tinnitus; including 517 participants, the Company is now advancing towards initial commercialisation of its CE-marked product in Ireland and Germany, which will be marketed under the brand name Lenire™. To support commercialisation activities, Neuromod is investing in establishing the appropriate quality, regulatory and supply chain infrastructure to support near term European plans and lay the foundation for the Company’s US strategy.

Senior Leadership Appointments

Neuromod is delighted to announce the appointment of Deborah Arthur as Head of Quality and Regulatory Affairs, Suzanne O’Rourke as Director of Quality and Regulatory Affairs and Cathal Mc Fadden as Director of Operations. Deborah and Suzanne bring more than 45 years of combined experience in medical device regulatory and quality matters. They will be supported by a team of qualified industry experts in navigating the regulatory pathway to market the treatment in the United States and transitioning to the new EU Medical Devices Regulation (MDR (EU) 2017/745). Cathal’s experience in manufacturing scale up and supply chain management will ensure that Neuromod is ready to meet the anticipated demand for Lenire™ in Europe and globally.

Dr. Ross O’Neill, CEO of Neuromod commented: “This is a very exciting time for Neuromod as we move towards commercialisation, supported by encouraging data from our recent clinical trials. I am delighted that industry leaders of the calibre of Deb, Suzanne and Cathal have agreed to join our team. Neuromod is investing in growing our organisation; we have been working tirelessly to ensure that all systems are in place to bring our much-anticipated breakthrough treatment to the large population of people living with tinnitus globally.”

About Neuromod Devices Limited

Neuromod, headquartered in the Digital Hub, Dublin, Ireland, is an emerging medical technology company, specialising in the design and development of neuromodulation technologies to address the clinical needs of underserved patient populations who live with chronic and debilitating tinnitus. The company was founded in 2010, by Dr. Ross O’Neill, as a spin-out from Maynooth University. Neuromod has conducted extensive clinical trials to confirm the efficacy of its non-invasive neuromodulation treatment for this extremely common disorder for which no standard of care has yet been established. Tinnitus affects between 10 and 15% of the global population, and the lives of at least 1 in every 100 people worldwide are severely compromised because of the incessant nature of the illusory sound that is often described as a ringing or buzzing in the ears.

www.NeuromodDevices.com

Contacts

FTI Consulting
Media Relations
Melanie Farrell
neuromod@fticonsulting.com

Syndesi Therapeutics announces initiation of Phase I study of novel SV2A modulator, SDI-118, in development for the treatment of cognitive impairment

Belgium – Syndesi Therapeutics SA, a biotechnology company developing novel modulators of the synaptic vesicle protein SV2A for the treatment of cognitive impairment, today announced that its lead molecule, SDI-118, has entered into Phase I clinical development.

The first-in-human Phase I study is investigating the safety, tolerability and pharmacokinetics of single ascending doses of SDI-118 in healthy subjects. The study also includes PET imaging in a group of subjects to directly measure the binding of SDI- 118 to SV2A in the brain and to assess the relationship between SV2A occupancy and plasma exposure.

Jonathan Savidge, CEO of Syndesi, said “We are delighted to announce the entry of SDI- 118 into clinical development following successful completion of pre-clinical studies during the first year following Syndesi’s incorporation. Conducting PET imaging in parallel with the dose escalation provides us with highly valuable data very early in the development program. This ability to measure the degree of target engagement of our compound in humans greatly facilitates the choice of doses in future trials, de-risking one of the major challenges in CNS drug development.”

About Syndesi Therapeutics

Syndesi Therapeutics was established to develop a series of novel, pro-cognitive small molecule SV2A modulators licensed from UCB. In February 2018 the company announced €17M in Series A funding from a syndicate of Belgium and international investors. In March 2019, Syndesi announced the award of up to €3.2 M in non-dilutive funding from the Walloon Region to support the development of the lead molecule SDI- 118 through Phase I clinical development. Syndesi is investigating the potential of these novel SV2A modulators to improve cognition in diseases such as Alzheimer’s Disease and other dementias, as well other conditions such as cognitive impairment associated with schizophrenia. For more information please visit www.syndesitherapeutics.com

Mainstay Medical Provides Company Update and Publishes 2018 Full Year Results

• ReActiv8-B study results received; pre-PMA submission meeting with FDA expected during the second quarter

• European commercialization continues to advance

• Cash on hand of $15.5m at 31 December 2018

Dublin,Ireland – Mainstay Medical International plc (“Mainstay” or the “Company”, Euronext Paris: MSTY.PA and Euronext Growth operated by Euronext Dublin (MSTY.IE), a medical device company focused on bringing to market ReActiv8, an implantable restorative neurostimulation system to treat disabling Chronic Low Back Pain, today provides a company update and announces the publication of its 2018 Full Year results and Annual Report.

Jason Hannon, CEO of Mainstay, said: “I believe fully in ReActiv8 as a therapeutic option for patients suffering from disabling Chronic Low Back Pain, and I believe that the value we can deliver to both our physician customers and their patients, as well as the investing market, will be demonstrated in the months and years to come. The primary endpoint of our ReActiv8-B clinical trial was not achieved due to a higher response (at 120 days) in the control (active sham) patient group than was expected. However, we believe the overall results from the trial represent solid evidence of the efficacy and safety of ReActiv8. This belief is based on, among other things:

• A pre-specified analysis of the primary endpoint where we adjusted for patients who increased their pain medications for reasons unrelated to their back pain. As a reminder, to be considered a “Responder” in the clinical trial, a patient must have reported 30% or greater pain relief on the VAS scale and not increased their pain medications leading up to the 120 day measurement point;

• Statistically significant differences between the treatment and control groups on key secondary efficacy endpoints at 120 days;

• A responder rate of 72% in the patients in the treatment and control groups combined that have reached one year since implantation; and

• A significant reduction in the use of pain medications (including opioids) by patients at one year.

We believe these results will support sales growth in Germany and other markets under our existing CE Mark, as well as our plan to file a Pre-Market Approval Application with the U.S. Food and Drug Administration. We plan to submit a PMA to the FDA in mid-2019, with a decision on approval expected in late 2020.”

Business Update

• In November 2018, Mainstay announced top line results from the ReActiv8-B clinical study, its international, multi-center, prospective, randomized, active sham-controlled, blinded trial with one-way cross-over, conducted under an Investigational Device Exemption (IDE) from the U.S. Food & Drug Administration (FDA). A total of 204 patients with chronic low back pain refractory to physical therapy were implanted with ReActiv8 at leading clinical sites in the U.S., Europe and Australia and randomized 1:1 to therapy or control. The average duration of symptoms was 14 years. In the treatment group, the ReActiv8 pulse generator was programmed to deliver electrical stimulation expected to elicit contractions of the multifidus muscle. In the control group, the ReActiv8 device was programmed to provide a low level of electrical stimulation. Following assessment of the primary endpoint at 120 days, patients in the control group crossed-over to receive levels of electrical stimulation similar to those in the treatment group. A summary of the clinical trial results is as follows:

  • The primary efficacy endpoint of the study was a comparison of responder rates between the treatment and control groups as measured on the visual analog scale (VAS) of pain, with responders defined as having a 30% or greater improvement on this measure between baseline and 120 days after randomization, without any increase in pain medication and/or muscle relaxants taken in the two weeks prior to the primary endpoint assessment visit. In the treatment group the responder rate at 120 days was 57%, compared to 47% in the control group, resulting in a difference that is not statistically significant.

  • Statistically significant differences on a number of key secondary endpoints were observed in the treatment group as compared to the control group at 120 days, including change from baseline in disability measured by the Oswestry Disability Index (ODI), change from baseline in quality of life measured by the European Quality of Life Score on Five Dimensions (EQ-5D), percent pain relief (PPR) compared to baseline and subject global impression of global change (SGIC).

  • Improvements in the percentage of patients reporting pain reduction continued beyond the 120-day assessment through one year for both groups. The percentage of the 116 patients in the treatment group and control groups that had completed the one-year assessment having a 30% or greater reduction in low back pain VAS at that assessment without a significant increase in pain medication was 72%. These data are subject to change as the remaining patients reach the one-year assessment.

  • The protocol permitted patients to adjust their back pain medication usage after the 120-day assessment point. At one year, 44% of the 50 patients in both groups combined who were on opioids at baseline had voluntarily eliminated (28%) or significantly reduced (16%) their use of opioids. These results are subject to change as the remaining patients reach the one-year assessment.

  • The incidence and type of adverse events (AEs), including serious AEs, were comparable to AEs in clinical trials reported for other neurostimulation devices, with no unanticipated AEs related to the device, procedure or stimulation.

• Mainstay is preparing to submit a PMA application to the FDA based upon the totality of its clinical data for ReActiv8. The Company expects to have a pre-PMA submission meeting with the FDA during the second quarter to obtain feedback on its filing content and strategy. A PMA application filing is expected in mid-2019 after that meeting, with a decision on approval expected in late 2020. The FDA’s review of the PMA may result in the FDA not agreeing with Mainstay’s interpretation of its clinical data, including whether statistical significance was achieved for one or more endpoints.

• In Germany, Mainstay’s initial European market, the commercial team was repositioned in order to better focus efforts on key physician targets. Commercialization efforts in line with this strategy began in earnest in late-2018. We are beginning to see the early fruits of these efforts as we regularly onboard new implanting physicians. We expect this early momentum to continue, leading to meaningful sales and revenue by the end of this year and the beginning of 2020.

Financial Update

• Since the beginning of 2018, Mainstay has conducted significant financing activities:

  • On 18 April 2019, Mainstay and its subsidiary, Mainstay Medical Limited, entered into an amendment to its agreement with IPF Partners relating to their existing debt facility. Pursuant to the amendment:

    • The repayment schedule for the three existing tranches drawn under the debt facility was amended such that no principal or interest will be repaid until 2021, with the principal and accrued interest to be amortized over the period from January 1, 2021 through September 30, 2023.

    • A new tranche of €3.0 million (approximately $3.34 million) was made available to Mainstay, conditioned upon Mainstay raising at least $10 million in gross proceeds from one or more offerings of equity prior to June 30, 2019. The repayment schedule for the new tranche will be the same as the amended repayment schedule for the three existing tranches.

    • The interest rate for all tranches will be 8% per annum, with interest accruing but capitalized prior to January 1, 2021.

    • The 5% repayment fee applicable to each existing tranche was eliminated.

    • All principal and accrued interest from all tranches will automatically convert into ordinary shares of the Company at a price per share of €8 upon the earlier of (a) FDA approval of Mainstay’s PMA application for ReActiv8, (b) the date by which at least 900,000 ordinary shares of the Company are publicly sold on-market by non-affiliates of Mainstay since 18 April 2019 at a price per share of at least €8, or (c) IPF Partners’ election to undertake such conversion, in each case unless the Company elects to satisfy such obligation in whole or in part in cash.

    • The minimum cash covenant was amended so that Mainstay is required to hold cash at least equal to its projected cash expenditures for operations and debt repayment for the next three months, and the covenant relating to the achievement of commercial milestones was eliminated.

    • Mainstay issued to IPF Partners warrants to purchase 1.5 million of its ordinary shares at a price per share of €6 at any time prior to the 6th anniversary of the amendment date. Mainstay has issued further conditional warrants to IPF Partners that will become exercisable only to the extent Mainstay elects to repay the debt in cash rather than issue ordinary shares when a conversion of the debt is triggered. As such, the conditional warrants are intended to ensure that, notwithstanding any such election to repay in cash, IPF Partners retains the right to subscribe for ordinary shares of the Company on the terms and conditions that would otherwise have applied.

  • On 15 February 2018, the Company announced the completion of a €30.1 million financing (approximately $37.5 million) through a placement of 2,151,332 new ordinary shares to new and existing shareholders.

• Revenue during the year ended 31 December 2018 was $0.7 million (2017: $0.3 million).

• Operating expenses related to on-going activities were $29.6 million during the year ended 31 December 2018 (2017: $27.9 million).

• Cash on hand as at 31 December 2018 was $15.5 million (2017: $10 million).

About Mainstay

Mainstay is a medical device company focused on commercializing an innovative implantable restorative neurostimulation system, ReActiv8®, for people with disabling Chronic Low Back Pain (CLBP). The Company is headquartered in Dublin, Ireland. It has subsidiaries operating in Ireland, the United States, Australia, Germany and the Netherlands, and is listed on the regulated market of Euronext Paris (MSTY.PA) and the ESM of Euronext Dublin (MSTY.IE).

About Chronic Low Back Pain

One of the root causes of CLBP is impaired control by the nervous system of the muscles that dynamically stabilize the spine. ReActiv8 is designed to electrically stimulate the nerves responsible for contracting these muscles to improve dynamic spine stability, allowing the body to recover from CLBP.

People with CLBP usually have a greatly reduced quality of life and score significantly higher on scales for pain, disability, depression, anxiety and sleep disorders. Their pain and disability can persist despite the best available medical treatments, and only a small percentage of cases result from an identified pathological condition or anatomical defect that may be correctable with spine surgery. Their ability to work or be productive is seriously affected by the condition and the resulting days lost from work, disability benefits and health resource utilization put a significant burden on individuals, families, communities, industry and governments.

Further information can be found at www.mainstay-medical.com

CAUTION – in the United States, ReActiv8 is limited by federal law to investigational use only.

PR and IR Enquiries:

Investor Relations:

LifeSci Advisors, LLC

Brian Ritchie

Tel: + 1 (212) 915-2578

Email: britchie@lifesciadvisors.com

Euronext Advisers:

Davy

Fergal Meegan or Barry Murphy

Tel: +353 1 679 6363

Email: fergal.meegan@davy.ie or barry.murphy2@davy.ie