About Nyxoah

Nyxoah S.A. operates as a medical technology company. The company focuses on the development and commercialization of innovative solutions to treat Obstructive Sleep Apnea, or OSA. The company’s lead solution is the Genio system, a CE-Marked, patient-centric, minimally invasive, next generation hypoglossal neurostimulation, or HGNS, therapy for the treatment of moderate to severe OSA. The company’s innovative technology platform is a first-of-its-kind HGNS device designed to treat OSA through bilateral stimulation, by maintaining an open airway for a restful night’s sleep. The company started generating revenue from the sale of the Genio system in Europe in July 2020, and it is conducting its DREAM pivotal trial designed to support marketing authorization in the United States. The company is developing a significant body of clinical evidence to further support the strong value proposition of the Genio system and its ability to improve the health and quality of life of OSA patients. The company’s Genio system includes the first battery-free, leadless and minimally invasive neurostimulator, capable of delivering bilateral HGNS for moderate to severe OSA patients who did not tolerate, have failed or refused conventional positive airway pressure, or PAP, therapy. The company developed the Genio system with a patient-centric approach, designed for comfort and safety, to increase compliance and improve quality of life. The Genio system includes a single implanted device that can be placed through a minimally invasive, single-incision surgery under the chin. The power source for the stimulator is external. The company continues to develop a substantial body of clinical evidence on the Genio system. In 2019, the company completed its bilateral hypoglossal nerve stimulation for the treatment of Obstructive Sleep Apnea, or BLAST OSA, trial, a prospective, open label, non-randomized, single arm treatment trial involving 27 implanted participants. The company is seeking to expand indications of the Genio system by obtaining clinical evidence through its ongoing multicenter, prospective, open-label bilateral hypoglossal nerve stimulation for the treatment of Obstructive SLEEP Apnea With and Without Complete Concentric Collapse clinical trial in Australia and New Zealand, or the BETTER SLEEP trial, to evaluate the effectiveness of the Genio system for patients suffering from CCC. In June 2021, the company announced initial top-line results from the six-month data for the BETTER SLEEP trial. Based on this data, in October 2021, the EU Notified Body granted CE-Marked indication to include OSA patients with CCC (complete concentric collapse at the level of the soft palate) for the Genio system in Europe, which should eliminate the need for a DISE procedure. Additionally, in September 2021, the company received breakthrough device designation in the United States for the Genio system from the Food and Drug Administration, or FDA, for the treatment of OSA with CCC, based on the initial clinical evidence from the BETTER SLEEP trial. The company plans to continue to obtain authorization in additional target markets and is conducting its Dual-sided Hypoglossal nerve stimulation for the treatment of Obstructive Sleep Apnea clinical trial, or DREAM trial, a multicenter, prospective, open-label, pivotal Investigational Device Exemption, or IDE, trial designed to support marketing authorization in the United States. The company anticipates 12-month data for the DREAM trial will be available in early 2024. The company is initially targeting markets in Europe where it has identified a country- specific reimbursement pathway or execution strategy. The company began its commercial launch in Germany in July 2020. After obtaining reimbursement approval in Germany through the existing HGNS special innovation funding program, or NUB, In 2021, the company successfully obtained reimbursement in Germany under a dedicated DRG code for HGNS and also recently obtained reimbursement under an OSA-specific DRG code in Switzerland from the Federal Statistic Office, or BFS. In 2021, the company began marketing products in Switzerland and also secured first revenue in Spain and it began commercialization in Finland in 2022. Based on market access activities conducted by the company over the past several years, it has developed tailored reimbursement strategies using assessments of the local requirements of target countries. The company has established a systematic approach to commercializing the Genio system in its target markets, focusing on active engagement, education and market development across patients, physicians and hospitals. The company markets its therapy to physicians and hospitals where ear, nose, and throat doctors, or ENTs, sleep doctors and general practitioners see, diagnose and treat patients with OSA. The company is actively expanding its European sales and marketing organization with country-specific sales teams established in connection with obtaining reimbursement. The company’s sales teams are focused on prioritizing high volume ENT centers and sleep centers, and on building long-standing relationships with key physicians, such as sleep doctors, ENTs and general practitioners who have strong connections to the OSA patient population that may be eligible for its therapy. The company supports physicians using the Genio system through all aspects of the patient’s journey, starting from initial diagnosis through surgical support and post-implantation patient follow-up. The company also seeks to establish long-term partnerships with key opinion leaders, or KOLs, and patient associations that are oriented towards the needs of its patients and customers. The company’s sales and marketing organization is focused on building physician awareness through referral network development, education, targeted KOL development and training, and direct-to-consumer marketing. In addition to its ongoing clinical studies, the company is committed to continuing its research and development efforts related to the Genio system, with an emphasis on improving clinical outcomes, optimizing patient adoption and comfort, increasing access for a greater number of patients, and allowing more physicians to perform the implantation procedure. Strategy The key elements of the company’s strategy include obtaining marketing authorization in the United States; promoting awareness of the Genio system among physicians, patients and payors to accelerate market adoption; continuing to enhance the Genio system and expand its indications; pursuing and establishing favorable reimbursement coverage of the Genio system; and continuing to build a commercial infrastructure in selected geographies. Solution The company developed the Genio system to provide patients suffering from moderate to severe OSA with an alternative HGNS system that addresses their unmet needs. The company’s minimally invasive and clinically proven solution has the potential to become the leading neurostimulation solution for many patients suffering from moderate to severe OSA, including patients with CCC. The Genio system has obtained CE-Mark and the company is pursuing FDA marketing authorization. The Genio system The Genio system is the first neurostimulation system for the treatment of OSA to include a battery-free and leadless neurostimulator capable of delivering bilateral HGNS. The system includes an implanted component that can be implanted in a minimally invasive procedure requiring only a single incision. The company developed the system using a patient-centric approach to offer patients a convenient alternative design to overcome the limitations of competing neurostimulation devices. Components of the Genio system Implantable Stimulator: The implantable stimulator consists of a saddle-like antenna with two legs, each containing two metal pads, called paddle electrodes. The paddle electrodes are placed in contact with both branches of the hypoglossal nerve and deliver bilateral stimulation to the hypoglossal nerve. Pulses from the stimulator trigger a slight forward movement of the posterior portion of the tongue in order to maintain an open airway throughout the night. The implantable stimulator is FDA and CE labeled as MR conditional for 1.5T and 3T full body MRI scans. Activation Chip: The activation chip is a detachable, external power source for the implantable stimulator and is composed of a chipset, which provides the patient’s personalized therapy program, and a rechargeable battery. The chipset is programmable, which allows the company to make future updates and upgrades, or to provide additional services to the Genio system without having to replace the implantable stimulator during an additional surgery. The company advises that patients charge the activation chip with the charging unit after use. Disposable Patch: The disposable patch is a single-use, medical grade adhesive patch, which also contains a transmitting coil. The patch is placed on the skin under the chin each time before the patient goes to sleep. The patient attaches the activation chip to the disposable patch, which then activates the implantable stimulator. After use, the patient detaches the activation chip from the chin, places it in the charging unit, and disposes of the patch. Charging Unit: The charging unit and its power adapter are used to charge the activation chip’s battery. A fully depleted activation chip can be charged on the charging unit within 3 hours. External Stimulator: In addition to the patient-use components described above, the system includes an external stimulator which is a disposable single-use device that is used during the implantation procedure by the surgeon to test activation and function of the implantable stimulator. The company continues to invest in developing a substantial body of clinical evidence to support the safety and efficacy of the Genio system. The company’s clinical strategy consists of obtaining authorization in its target markets, demonstrating long-term clinical data for the Genio system and expanding authorized indications to reach a broader patient population, including patients with CCC. The company has completed one clinical trial and is conducting three clinical trials globally with the goal of generating compelling and reproducible results with the Genio system for the large and underpenetrated population of patients with moderate to severe OSA. BLAST OSA Trial The BLAST OSA trial was a prospective, open-label, non-randomized, multicenter, single-arm trial initiated in April 2017 with enrollment completed in February 2018. The objective of this trial was to evaluate and assess the safety, performance and efficacy of the Genio system in adult patients with moderate to severe OSA. The trial measured safety and efficacy endpoints at six months following five months of treatment. In 2019, the BLAST OSA trial protocol was amended to include a long-term safety follow-up phase. All participants who received the Genio system were eligible to enroll in the long-term follow-up phase of the trial. While the long-term follow-up phase was not initiated, subjects were nevertheless followed up for an additional 36 months before the study was closed out. The BLAST OSA results were published in the European Respiratory Journal in October 2019. The BLAST OSA trial demonstrated that the Genio system’s therapy was well-tolerated, met its performance endpoints, and was associated with high compliance. The trial showed significant reduction of OSA severity and improvement of sleepiness and quality of life, while being well-tolerated. BETTER SLEEP Trial The company is conducting the BETTER SLEEP trial, a multicenter, prospective, open-label, two-group clinical trial, designed to assess the long-term safety and performance of the Genio system for the treatment of adult OSA patients with and without CCC over a period of 36 months post- implantation. The BETTER SLEEP trial includes a subgroup of CCC patients, which is a patient population that is contraindicated for unilateral HGNS. In October 2021, Nyxoah received CE-mark indication approval to treat OSA patients with CCC, based on clinical evidence from the BETTER SLEEP trial. Additionally, in September 2021, the company received breakthrough device designation in the United States for the Genio system from the FDA for the treatment of OSA with CCC, based on the initial clinical evidence from the BETTER SLEEP trial. EliSA Trial After having obtained certification in Europe for the Genio system in March 2019, the company initiated the EliSA post-marketing trial in Europe for the treatment of OSA in adult patients with moderate to severe OSA. The primary objective of this trial is to evaluate the long-term safety and clinical efficacy of the Genio system in adult patients suffering from moderate to severe OSA. The trial is expected to follow patients over a five-year period. EliSA is a multicenter prospective single-arm post market clinical follow-up trial and is expected to enroll at least 110 patients across approximately 25 investigational centers in Europe. Pivotal DREAM Trial In June 2020, the FDA approved the company’s IDE application, allowing it to commence its pivotal DREAM trial of the Genio system. In June 2022, the company announced that the FDA approved the use of the Genio 2.1 system in its DREAM trial. The company’s DREAM trial is a multicenter, prospective, open-label trial in which each participant who undergoes implantation of the Genio system will be followed for five years post-implantation to assess the safety and efficacy of the system in patients with moderate to severe OSA. The company initiated the DREAM trial as an IDE pivotal trial to support an application seeking FDA marketing authorization and ultimately, reimbursement in the United States for bilateral HGNS for the treatment of moderate to severe OSA. The trial enrolled 115 patients who have all been implanted as of the date of this Annual Report, with 12-month effectiveness and safety primary endpoints. The company has identified 20 centers for the trial, including 15 in the United States. Fifteen of them were active and enrolling patients as of December 2022. The company anticipates 12-month data will be available in early 2024. Sales and Marketing The company has grown its commercial team to more than 15 individuals, including sales representatives, field engineers and marketing professionals, who collectively bring substantial medical device sales, education and clinical experience to support commercialization of the Genio system. The company is initially targeting markets in Europe where it has identified a clear reimbursement pathway or execution strategy. In Germany, the company has successfully obtained reimbursement under a dedicated DRG code for HGNS, and, in Switzerland, it recently obtained reimbursement under an OSA-specific DRG code by the BFS. The company began its commercial launch of the Genio system in July 2020. The company’s sales team in Germany consists of one country director and several representatives and field engineers, with support provided by its corporate team. The company began marketing products in Switzerland and also secured first revenue in Spain in 2021 and it began commercialization in Finland in 2022. The company has established a systematic approach to commercializing the Genio system in select European countries which centers on active engagement and market development across patients, physicians and hospitals. The company’s Genio System has CE-Mark for OSA in patients with moderate to severe OSA in Europe. The company markets its Genio System to physicians and hospitals where ENTs, sleep doctors and general practitioners who see, diagnose and treat patients with OSA. The company has developed a methodical marketing strategy to educate and develop the market and a commercial strategy tailored to suit local market needs in order to maximize therapy penetration and patient base expansion. The company’s initial strategy is to employ a targeted approach to increase therapy penetration within specific physician practice groups instead of a broad outreach strategy to physicians. The company’s sales and marketing organization is focused on prioritizing high volume centers that are strategically located and building long-standing relationships with key physicians with strong connectivity to the population of OSA patients indicated for the Genio system. The company is focusing its efforts on developing ‘Centers of Excellence’, where it plans to invest in developing the Genio system as the preferred treatment option for appropriate moderate to severe OSA patients in need of an alternative to conventional first-line therapies. Using a direct commercialization model in most of its target countries, the company plans to utilize account managers to support the Centers of Excellence to strengthen the referral physician network, guiding new patients to these Centers of Excellence. The company’s direct sales representatives and field engineers, which it refers to as its market development team, generally have substantial experience, specifically with patients, physicians and payors in the ENT or neurostimulation space. The company’s market development team is focused on prioritizing high volume ENT centers, sleep centers, and building long-standing relationships with key physicians, such as sleep doctors, ENT and general practitioners who have strong connectivity to the OSA patient population that may be eligible for the Genio system. Additionally, the company targets cardiac electrophysiologists, cardiologists, cardiovascular surgeons and dentists, which are a second OSA patient referral base for ENT physicians. The company supports its physicians through all aspects of the patient journey, starting from initial diagnosis through surgical support and post implantation patient follow-up. The company’s marketing organization is focused on building physician awareness through referral network development, education, and targeted KOL development and training. Additionally, it has established and implemented a dedicated direct-to-patient marketing strategy aligned with local regulations in selected countries. Manufacturing and Supply The company’s principal suppliers of components are Meko, Medistri SA, Resonetics, VSI Parylene, Reinhardt Microtech GmbH (Cicor), Abatec, Specialty Coating Systems (SCS), VSI Parylene, Resonetics, Medistri SAMeko, and S&D Tech SRL. Collaboration and License Agreements The company and Cochlear Limited, or Cochlear, have entered into a collaboration agreement, dated November 2018, under which the company and Cochlear agree to collaborate to further develop and progress commercialization of implantable treatments for sleep disordered breathing conditions. Cochlear has significant expertise in the development of implantable devices. Man & Science Agreement The company, Man & Science SA, Cephalix SA, Glucobel SA and Surgical Electronics SA, among others, have entered into a multiparty agreement regarding their respective ownership and licensing rights in relation to multiple inventions, including but not limited to inventions generally related to implantable, flexible neurostimulators and inventions for specific medical indications, including sleep disordered breathing, head pain, glucose monitoring, hypertension and other indications. This agreement provides that the company fully owns all rights in relation to the inventions specifically related to the sleep disordered breathing field, which includes sleep disordered breathing conditions, such as sleep apnea and snoring, and comorbidities of these conditions and Man & Science SA is the owner of the generic inventions and granted a fully paid-up, exclusive and worldwide, license with respect to these inventions to several parties, including the company in the field of sleep disordered breathing. Pursuant to the terms of the agreement, no party may terminate the licenses. In June 2016, the company, Cephalix SA, Surgical Electronics SA, and Man & Science SA entered into a confirmatory addendum, aiming to confirm that the company fully owns all rights in relation to the inventions specifically related to the sleep disordered breathing field as further detailed in the agreement, Man & Science SA granted an exclusive, worldwide, fully paid-up, royalty free and transferable license to the company covering certain patents in the sleep disordered breathing field, and the company granted an exclusive, fully paid-up, royalty free, transferable license to use certain of those patents outside the sleep disordered breathing field, namely to Cephalix SA in the head pain field, Surgical Electronics SA in the hypertension field and Man & Science SA outside the head pain field and the hypertension field. In February 2020, the company entered into a clarification of the Confirmatory Addendum, or Clarification, with Man & Science SA. The Clarification confirms that the license granted to the company by Man & Science SA under the agreement and the Addendum are irrevocable, transferable, fully paid up, royalty-free and include the right to grant sublicenses in the sleep disordered breathing field, which are retroactive as from the filing date of the oldest of the patents and patent applications and will continue in effect until the last to expire patent, which is expected to occur in 2032 (excluding any potential patent term extension). Intellectual Property As of December 31, 2022, the company had 186 granted or pending patent applications (both utility and design) consisted of 53 issued or allowed U.S. patents, 10 pending U.S. non-provisional applications, 1 pending U.S. provisional applications, 2 pending international patent applications filed under the Patent Cooperation Treaty, or PCT, and 33 pending patent applications and 87 granted patents in jurisdictions outside the United States, including Australia, Canada, China, Europe, Hong Kong, Israel and Japan. The exclusivity terms of the company’s patents depend upon the laws of the countries in which they are obtained. In the countries in which the company files, the patent term is 20 years from the earliest date of filing of a non-provisional patent application. Issued patents and patent applications covering the company’s Genio system will expire on dates ranging from 2032 to 2034, if the applications are issued. In addition to the patent portfolio owned by it, the company holds exclusive licenses granting it a fully paid-up, transferrable and sub-licensable, worldwide, irrevocable license and royalty free in the field of sleep disordered breathing in relation to multiple inventions, including but not limited to inventions generally related to implantable flexible neuro-stimulators. Such licenses were granted to the company by Man & Science SA (a company held and governed by Robert Taub, TOGETHER Partnership, Jürgen Hambrecht and Noshaq SA). The company also holds an exclusive worldwide license from Vanderbilt University, to develop, use, grant sublicense and commercialize products, with a different mechanism of action than the Genio system, in the field of sleep disordered breathing conditions and comorbidities of such conditions. The company will also work together with Vanderbilt University to continue prosecution of patent applications made by Vanderbilt. With respect to trademarks, the company uses its corporate name, Nyxoah, and associated logo, as well as the tagline, in creating awareness of its expertise and in marketing its Genio system technology. The company uses the trademark Genio to identify its Genio system. The company has obtained registration for the Nyxoah name and the Genio trademark in seven jurisdictions around the globe. Government Regulation The company obtained the CE-Mark for the Genio system under the Active Implantable Medical Device Directive (AIMDD) in March 2019. In addition, the company is registered as a legal manufacturer in Belgium under the EU Medical Devices Regulation 2017/745 (MDR). In addition, the company’s manufacturing facility is certified as compliant with ISO 13584:2016. DEKRA Certification B.V., a Notified Body designated for regulatory review of medical devices and their manufacturers under applicable European Union (EU) regulations, conducted the assessment of the technical dossiers and the manufacturers’ quality system for the Genio system and Genio 2.1 system and issued the certificate of conformity for the device. The Genio system is regulated by the FDA as a medical device under the FDCA, as implemented and enforced by the FDA. The FDA regulates the development, testing, manufacturing, labeling, packaging, storage, installation, servicing, advertising, promotion, marketing, distribution, import, export, and market surveillance of the company’s medical devices. The Genio system is not yet approved or cleared for marketing in the United States. The company’s advertising for its products is subject to federal truth-in-advertising laws enforced by the Federal Trade Commission, or FTC, as well as comparable state consumer protection laws. In addition, the General Data Protection Regulation (GDPR) requires the company to implement appropriate technical and organizational measures to ensure a level of security appropriate to the organization’s processing requirements and risk. Privacy regulations, like the GDPR, concerning the use of web analysis are particularly relevant to the company’s online platform. The company’s operations are subject to anti-corruption laws, including the U.S. Foreign Corrupt Practices Act of 1977 (FCPA); the UK Bribery Act 2010 (the Bribery Act); and other anti-corruption laws that apply in countries where the company does business. History Nyxoah S.A., a Belgian corporation, was incorporated in 2009.