Becker Muscular Dystrophy

BOULDER, Colo.--(BUSINESS WIRE)--Edgewise Therapeutics, Inc., (Nasdaq: EWTX), a leading muscle disease biopharmaceutical company, today announced its participation at the 29th International Annual Congress of the World Muscle Society (WMS) with an industry-sponsored symposium and the presentation of seven scientific posters. These presentations will highlight the effects of sevasemten in individuals with Becker based on findings from the DUNE and ARCH clinical trials, as well as provide perspectives on biomarker and functional endpoints being studied in the CANYON Phase 2 trial. Sevasemten is an orally administered small molecule designed to prevent contraction-induced muscle damage in muscular dystrophies including Becker and Duchenne muscular dystrophy. The conference will take place at The Prague Congress Centre in Prague, Czechia, October 8-12, 2024. Details of the Edgewise symposium and scientific posters at WMS: Edgewise Symposium with Key Opinion Leaders Date: Tuesday, October 8, 2024, at 4:30 pm CEST Title: Understanding disease progression and a potential novel agent to protect muscle Presenters: Luca Bello, M.D., Ph.D , Associate Professor, Department of Neurosciences, DNS, University of Padova and Craig McDonald, M.D., Professor and Chair, Department of Physical Medicine & Rehabilitation, Professor of Pediatrics, Director MDA Neuromuscular Disease Clinics, University of California Davis. The symposium will also include discussion of the positive two-year topline results from the ARCH trial, an open label, single-center study assessing safety, tolerability, impact on muscle damage biomarkers, pharmacokinetics (PK) and functional measures with sevasemten in adults with Becker. Only registered conference attendees can register for the symposium. Scientific Posters Title: Sevasemten, a fast myosin inhibitor, in adults with Becker muscular dystrophy results in reduced muscle damage biomarkers and functional stabilization (351P) Title: Rasch evaluation of North Star Ambulatory Assessment and North Star Assessment for Limb-Girdle Type Muscular Dystrophies in Becker muscular dystrophy (322P) Title: Exploring the content validity of patient-reported outcome (PRO) measures to capture the patient experience of Becker Muscular Dystrophy (BMD) (339P) Title: Comparison of short- and long-term proteomic response to the fast skeletal myosin inhibitor, sevasemten (EDG-5506), in Becker muscular dystrophy (BMD) (349P) Title: Protein biomarkers of muscle injury exhibit differential reduction with subject age in adults with Becker muscular dystrophy (729LBP) Title: Post-exercise biomarkers of muscle injury are reduced by sevasemten, a fast myosin inhibitor, in adults with Becker muscular dystrophy (732LBP) Title: Clinical trial readiness in rare and underserved disease: learnings from community engagement and the lived experience in Becker muscular dystrophy (Becker) (708LPB) All Edgewise posters are being presented on Friday, October 11, 2024, in Poster Session 4 (Forum Hall) from 3:45 to 4:45 pm CEST. The full WMS Congress program is available here . The Edgewise symposium presentation and posters will be available on the Edgewise website . About Sevasemten for Becker and Duchenne Muscular Dystrophies Sevasemten is an orally administered small molecule designed to prevent contraction-induced muscle damage in dystrophinopathies including Becker and Duchenne. Sevasemten presents a novel mechanism of action designed to selectively limit the exaggerated muscle damage caused by the absence or loss of functional dystrophin. By minimizing the progressive muscle damage that leads to functional impairment, sevasemten has the potential to benefit a broad range of patients suffering from debilitating neuromuscular disorders. In Becker, after completion of the two-year Phase 1 ARCH trial, the Company continues to advance sevasemten through the clinic with the Phase 2 CANYON trial, which is fully enrolled, evaluating safety and effects on function and biomarkers of muscle damage in adult males with Becker. The Company expects to report CANYON data in the fourth quarter of 2024. The CANYON trial has expanded to include an additional 120 adult participants in a pivotal cohort GRAND CANYON, which is currently enrolling in the United States, Europe, Israel, Australia and New Zealand. Data from GRAND CANYON, if positive, could support a marketing application. In Duchenne, the Company is advancing its Phase 2 clinical trials, LYNX, assessing safety, pharmacokinetics and biomarkers of muscle damage, and FOX, which includes children and adolescents previously treated with gene therapy. The Company expects to report LYNX data in the fourth quarter of 2024. The Company will rely on LYNX data, along with data from the FOX trial of Duchenne children previously treated with gene therapy, to guide the design and powering of a Phase 3 trial in Duchenne, planned to be initiated in the first half of 2025. For more information on Edgewise’s clinical trials . About Edgewise Therapeutics Edgewise Therapeutics is a leading muscle disease biopharmaceutical company developing novel therapeutics for muscular dystrophies and serious cardiac conditions. The Company’s deep expertise in muscle physiology is driving a new generation of novel therapeutics. Sevasemten is an orally administered skeletal myosin inhibitor in late-stage clinical trials in Becker and Duchenne muscular dystrophies. EDG-7500 is a novel cardiac sarcomere modulator for the treatment of hypertrophic cardiomyopathy and other diseases of diastolic dysfunction, currently in Phase 2 clinical development. The entire team at Edgewise is dedicated to our mission: changing the lives of patients and families affected by serious muscle diseases. To learn more, go to: or follow us on LinkedIn , X , Facebook and Instagram . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding sevasemten; statements regarding the timing of reporting data (including the data from the CANYON trial and the LYNX trial); statements regarding Edgewise’s expectations relating to its clinical trials (including the CANYON trial, GRAND CANYON trial, LYNX trial and FOX trial); statements regarding the data from GRAND CANYON being able to support a marketing application; and statements regarding the commencement of trials (including the Phase 3 trial of sevasemten in Duchenne). Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon Edgewise’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with Edgewise’s limited operating history, its products being early in development and not having products approved for commercial sale; risks associated with Edgewise not having generated any revenue to date; Edgewise’s ability to achieve objectives relating to the discovery, development and commercialization of its product candidates, if approved; Edgewise’s need for substantial additional capital to finance its operations; Edgewise’s substantial dependence on the success of its sevasemten; Edgewise’s ability to develop and commercialize sevasemten and discover, develop and commercialize product candidates in future programs; risks related to Edgewise’s clinical trials of its product candidates not demonstrating safety and efficacy; risks related to Edgewise’s product candidates causing serious adverse events, toxicities or other undesirable side effects; the outcome of preclinical testing and early clinical trials not being predictive of the success of later clinical trials and the risks related to the results of Edgewise’s clinical trials not satisfying the requirements of regulatory authorities; delays or difficulties in the enrollment and/or maintenance of patients in clinical trials; risks related to failure to capitalize on other indications or product candidates; risks related to competition; risks relating to interim, topline and preliminary data from Edgewise’s clinical trials changing as more patient data becomes available; risks related to the regulatory approval processes being lengthy, time consuming and inherently unpredictable; risks related to regulatory authorities not accepting data from trials conducted in locations outside of their jurisdiction; risks relating to Edgewise’s ability to attract and retain highly skilled executive officers and employees; Edgewise’s ability to obtain and maintain intellectual property protection for its product candidates; Edgewise’s reliance on third parties; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Edgewise files from time to time with the U.S. Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Edgewise assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. This press release contains hyperlinks to information that is not deemed to be incorporated by reference into this press release. Contacts Edgewise Contacts Investors: Michael Carruthers, Chief Financial Officer ir@edgewisetx.com Media: Maureen Franco, VP Corporate Communications media@edgewisetx.com

Mean muscle content-adjusted dystrophin expression of 9.0% and unadjusted dystrophin of 5.5%, with high consistency across participants, in a prespecified analysis; dystrophin was comprised of two isoforms consistent with Becker muscular dystrophy patients who display milder disease Data demonstrated meaningful improvement in serum biomarkers for muscle health, with localization of WVE-N531 in myogenic stem cells and regeneration of myofibers Skeletal muscle concentrations of ~41,000 ng/g combined with 61-day tissue half-life support monthly dosing going forward; preclinical data suggest participants may have even higher concentrations in heart and diaphragm WVE-N531 was safe and well tolerated: treatment-related adverse events were all mild, no serious adverse events, no discontinuations and no oligonucleotide class-related events Wave expects feedback on a pathway to accelerated approval from regulators, as well as the complete 48-week FORWARD-53 data, in 1Q 2025 Wave to host investor conference call and webcast at 8:30 a.m. ET today CAMBRIDGE, Mass., Sept. 24, 2024 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today announced positive interim data from the ongoing Phase 2 FORWARD-53 study of WVE-N531, which is an exon skipping oligonucleotide being investigated in boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping. The interim analysis was conducted after 24 weeks of 10 mg/kg dosing every two weeks (Q2W), and WVE-N531 demonstrated substantial dystrophin expression and that it was safe and well tolerated. “The high and consistent dystrophin levels at this interim timepoint are compelling and speak to the potential of WVE-N531 for boys amenable to exon 53 skipping, where better therapeutic options are urgently needed,” said Anne-Marie Li-Kwai-Cheung, MChem, MTOPRA, RAPS, Chief Development Officer at Wave Life Sciences. “It is also known that dystrophin is expressed as multiple functional isoforms and we are encouraged that the two isoforms observed on our Western Blot data are consistent with Becker muscular dystrophy patients who display milder disease. This observation is further supported by our interim data showing myofiber regeneration and improvements in muscle health. We look forward to delivering data from the complete FORWARD-53 study in the first quarter of 2025, and would like to express our deepest gratitude to the boys, families and study staff who are participating in the study.” “Exon skipping is a promising approach to treat DMD and is compatible with all others that are approved or in development. However, it has been challenging for the field to achieve dystrophin levels that can significantly improve clinical outcomes. Achieving mean muscle content-adjusted dystrophin of 9% is a meaningful step forward,” said Laurent Servais, MD, PhD, Professor of Paediatric Neuromuscular Disease at the University of Oxford and Principal Investigator in FORWARD-53. “The safe and tolerable profile and the option for monthly dosing is also encouraging and has the potential to greatly contribute to quality of life of treated boys in comparison with current weekly dosing.” Detailed Interim Results from FORWARD-53Eleven boys amenable to exon 53 skipping (age 5-11; 10 ambulatory and 1 non-ambulatory) are enrolled in the ongoing, open-label FORWARD-53 trial. The study is designed to administer 10 mg/kg infusions of WVE-N531 Q2W and muscle biopsies are taken after 24 and 48 weeks of dosing. Results from this interim analysis include: Safety and Tolerability WVE-N531 was safe and well tolerated. Treatment-related adverse events (four events total in three participants) were mild in intensity. There were no serious adverse events and no study discontinuations due to any causes.There were no oligonucleotide class-related safety events. Efficacy Dystrophin: Dystrophin results from a pre-specified analysis of ambulatory boys showed: Mean absolute muscle content-adjusted dystrophin expression was 9.0% (range: 4.6-13.9%) and mean absolute unadjusted dystrophin expression was 5.5% of normal (range: 3.3-8.3%), as measured by Western Blot.The dystrophin expression was quantified from two isoforms consistent with those observed in Becker muscular dystrophy patients who display milder disease.89% of ambulatory participants achieved muscle content-adjusted dystrophin levels of at least 5%. Exon skipping: Mean exon skipping was 57% (range: 31-75%) as measured by RT-PCR.Localization: WVE-N531 was detected in myocyte nuclei in all participants and in myogenic stem cells in the majority of participants. Myogenic stem cells are the progenitor cells for new myoblasts, which give rise to new myocytes and ultimately aid in skeletal muscle regeneration.Improvements in muscle health: Participants showed multiple indicators of improvement in muscle health, including an increase in the mean percentage of myocytes with internalized nuclei and an improvement in myofiber size and diameter between the previously completed Part A study and FORWARD-53.Serum biomarkers for muscle health: Creatine kinase (CK) and aspartate aminotransferase (AST) are serum biomarkers that are elevated in the presence of muscle damage. In the interim data, there were significant decreases in CK and AST levels from baseline. The reduction in CK was numerically larger than is typically seen with the introduction of steroids in DMD. Changes in CK and AST were highly correlated (p<0.0001).Muscle concentration: Mean muscle concentration was ~41,000 ng/g (~5,900 nM). Preclinical data for WVE-N531 demonstrate significantly higher drug concentrations in the heart and diaphragm versus skeletal muscle, suggesting the FORWARD-53 data from skeletal muscle biopsies may be underrepresenting activity in heart and diaphragm. Half-life: The muscle tissue half-life of WVE-N531 is estimated to be 61 days. Along with muscle concentration, this supports a monthly dosing regimen for WVE-N531 moving forward. In the first quarter of 2025, Wave expects to complete the FORWARD-53 trial and receive feedback from regulators on a pathway to accelerated approval. Wave is also advancing a broader DMD pipeline of oligonucleotides for skipping other exons, with the goal of providing new and best-in-class treatment options for up to 40% of boys with DMD. “We have long believed that our novel platform chemistry offered an opportunity to reimagine therapeutics for Duchenne, and we are looking forward to sharing further updates on WVE-N531,” said Paul Bolno, MD, MBA, President and CEO of Wave Life Sciences. “We are also hard at work advancing our lead RNA editing and RNAi programs, which offer differentiated, best-in-class therapeutic approaches. In the fourth quarter of 2024, we expect proof-of-mechanism data for our WVE-006 program in Alpha-1 antitrypsin deficiency. In the first quarter of 2025, we expect to initiate our clinical trial for WVE-007 – a potentially breakthrough approach to obesity that leverages GalNAc-siRNA to target INHBE and induce healthy weight loss with muscle maintenance. Finally, we are looking forward to our annual R&D Day, which will take place this fall and where we will discuss the next wave of RNA innovations being advanced by our organization.” Investor Conference Call and WebcastWave will host an investor conference call today at 8:30 a.m. ET to review the interim data from FORWARD-53. A webcast of the conference call can be accessed by visiting “Investor Events” on the investor relations section of the Wave Life Sciences website: https://ir.wavelifesciences.com/events-publications/events. Analysts planning to participate during the Q&A portion of the live call can join the conference call at the audio-conferencing link available here. Once registered, participants will receive the dial-in information. Following the live event, an archived version of the webcast will be available on the Wave Life Sciences website. About WVE-N531WVE-N531 is an exon skipping oligonucleotide being developed as a disease modifying treatment for boys with Duchenne muscular dystrophy amenable to exon 53 skipping. WVE-N531 was designed using Wave’s best-in-class oligonucleotide chemistry modifications, including PN backbone chemistry. WVE-N531 is being investigated in the ongoing Phase 2 FORWARD-53 clinical trial, with additional data expected in the first quarter of 2025. WVE-N531 has received Orphan Drug Designation and Rare Pediatric Disease Designation from the U.S. Food & Drug Administration. About FORWARD-53FORWARD-53 is a potentially registrational, open-label, Phase 2 clinical trial evaluating WVE-N531 as a treatment for boys with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping. Eleven boys are currently enrolled. WVE-N531 is being dosed at 10 mg/kg every two weeks, and endpoints include dystrophin expression after 24 and 48 weeks of treatment, as well as pharmacokinetic, safety and tolerability data, and functional assessments. FORWARD-53 is fully enrolled with final data from the study, including muscle biopsies after 48 weeks of treatment, expected in the first quarter of 2025. About Duchenne Muscular DystrophyDuchenne muscular dystrophy (DMD) is a fatal X-linked genetic neuromuscular disorder caused predominantly by out-of-frame deletions in the dystrophin gene, resulting in absent or defective dystrophin protein. Dystrophin protein is needed for normal muscle maintenance and operation. Because of the genetic mutations in DMD, the body cannot produce functional dystrophin, which results in progressive and irreversible loss of muscle function, including the heart and lungs. Worldwide, DMD affects approximately one in 5,000 newborn boys. Approximately 8%-10% of DMD patients have mutations amenable to treatment with an exon 53 skipping therapy. Exon skipping aims to address the underlying cause of DMD by promoting the production of dystrophin protein to stabilize or slow disease progression. About Wave Life SciencesWave Life Sciences (Nasdaq: WVE) is a biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health. Wave’s RNA medicines platform, PRISM®, combines multiple modalities, chemistry innovation and deep insights in human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders. Its toolkit of RNA-targeting modalities includes editing, splicing, RNA interference and antisense silencing, providing Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s diversified pipeline includes clinical programs in Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency and Huntington’s disease, as well as a preclinical program in obesity. Driven by the calling to “Reimagine Possible”, Wave is leading the charge toward a world in which human potential is no longer hindered by the burden of disease. Wave is headquartered in Cambridge, MA. For more information on Wave’s science, pipeline and people, please visit www.wavelifesciences.com and follow Wave on X (formerly Twitter) and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, our understanding of the anticipated therapeutic benefit of WVE-N531 as a therapy for DMD; our plan and estimated timing to engage regulators with the interim results and complete the trial and deliver the results of the complete trial; our understanding of the dystrophin isoforms we are observing with WVE-N531; our understanding of the safety profile of WVE-N531; and the potential benefits of PRISM, including our novel PN backbone chemistry modifications, and our stereopure oligonucleotides compared with stereorandom oligonucleotides. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release and actual results may differ materially from those indicated by these forward-looking statements as a result of these risks, uncertainties and important factors, including, without limitation, the risks and uncertainties described in the section entitled “Risk Factors” in Wave’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other filings Wave makes with the SEC from time to time. Wave undertakes no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances. Investor Contact:Kate Rausch+1 617-949-4827krausch@wavelifesci.com Media Contact:Alicia Suter+1 617-949-4817asuter@wavelifesci.com DMD Community Contact:Chelley Casey+1 617-949-4830ccasey@wavelifesci.com

Ad hoc announcement pursuant to Art. 53 LR A conference call will be held on September 12, 2024, at 14:30 CEST / 13:30 BST / 08:30 EDT. Details are at the end of this news release. Revenue from contracts with customers of CHF 14.1 million (H1-2023: CHF 3.9 million)Operating result of CHF -17.7 million (H1-2023: CHF -20.3 million) and net result of CHF -15.3 million (H1-2023: CHF -23.3 million)AGAMREE® (vamorolone) launched in Germany and Austria as first European markets; North America partner has launched in the U.S.Approval of AGAMREE in the UK for the treatment of Duchenne muscular dystrophy (DMD); new drug application (NDA) in DMD under regulatory priority review in China Cash and cash equivalents of CHF 16.5 million (June 30, 2024); bolstered by financing of up to CHF 69 million (closed in August 2024) to provide funding into 2026 when cash flow break-even is expectedBusiness now fully focused on European commercialization and further geographic expansion of AGAMREE in DMD Pratteln, Switzerland, September 12, 2024 – Santhera Pharmaceuticals (SIX: SANN) announces the Company’s financial results for the six months ended June 30, 2024, reports on progress with AGAMREE® (vamorolone) for the treatment of Duchenne muscular dystrophy (DMD) and provides updates on its corporate and financing initiatives. “We are extremely encouraged by the strong early uptake of AGAMREE in Germany and Austria, which has exceeded our expectations. Our North American partner, Catalyst Pharmaceuticals, has also seen a successful launch in the U.S., further validating the potential of AGAMREE in treating DMD,” said Dario Eklund, CEO of Santhera. “While we are delaying the decision on a new indication for AGAMREE until at least the end of 2025 to allow Catalyst to conduct additional exploratory clinical work, this strategic pause gives us an exciting opportunity. We are reallocating resources and are intensifying our efforts in DMD by expanding our launch into the Nordics, Portugal, and Ireland, hereby retaining full control of all the markets in western Europe. Additionally, we have decided to invest in additional studies to further strengthen the evidence behind AGAMREE’s differentiated safety profile and drive continued growth in the DMD space.” BUSINESS AND CORPORATE UPDATE Half-year 2024 key events and post-period events AGAMREE approved in the UK for the treatment of DMD, following prior approvals in the U.S. and EU The UK MHRA, in accordance with EU regulators, acknowledged safety benefits of AGAMREE with regards to preserving bone health and maintaining growth compared to standard of care corticosteroidsLaunches of AGAMREE in Germany and Austria (by Santhera) and the U.S. (by Catalyst Pharmaceuticals) as first markets, experiencing strong market uptakePreparations for market entry are advancing across Europe, with pricing negotiations currently underwayExpansion of self-commercialization reach (to include the Nordics, Ireland and Portugal) and new distribution agreements established, representing coverage of all of EU and some non-EU markets in EuropePriority review for AGAMREE NDA in DMD granted by China’s regulatory authority; early access program started by Sperogenix AGAMREE approved across the U.S., EU and UK—NDA under priority review in ChinaOn January 11, 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK approved AGAMREE for the treatment of DMD, following earlier approvals in the U.S. (by FDA on October 26, 2023) and the European Union (by the European Commission on December 18, 2023). AGAMREE became the first DMD treatment approved across these three territories. In the EU, AGAMREE is the first and only approved medication for treating all patients from age 4 years with DMD. The European Medicines Agency (EMA) and the MHRA acknowledged clinically important safety benefits of AGAMREE with regards to maintaining normal bone metabolism, density and growth compared to standard of care corticosteroids, while demonstrating similar efficacy. In March 2024, the National Medical Products Administration (NMPA) in China accepted the new drug application (NDA) filing for AGAMREE in DMD for patients aged 4 years and older, incorporating it into both the Priority Review Program and the Breakthrough Therapy Program. Subject to a positive review outcome, approval could be obtained by Q1-2025. First launches in Germany and the U.S. met with strong market acceptanceThe first market launch of AGAMREE (available as a 40 mg/ml oral suspension) for the treatment of DMD occurred on January 15, 2024, in Germany, where around 2,300 patients are affected by DMD. In the following month, AGAMREE became available in Austria. The reception in both markets has been very positive, evidenced by strong demand and proactive inquiries from patients and caretakers. Currently, after only a few months of availability, AGAMREE has been prescribed to around 300 patients in Germany and Austria. In March 2024, Catalyst Pharmaceuticals, Inc. (NASDAQ: CPRX), executed the U.S. commercial launch of AGAMREE and reported yielding solid results and surpassing initial expectations by the end of June 2024. Catalyst Pharmaceuticals holds an exclusive license for AGAMREE for North America. Further, in July 2024, Catalyst entered into an exclusive license, supply, and commercialization agreement for AGAMREE with a partner in Canada, marking a pivotal strategic milestone in expanding the product's North American footprint. Paid early access programs started in first countries—broader interest expressedSanthera received a number of named patient requests from European as well as global markets and is exploring sustainable supply mechanisms with a selection of partners. Meanwhile, programs have started in Spain and China. In June, Santhera started a paid-for named patient program (NPP) in Spain. Under a well-defined regulatory framework, with the approval of the national as well as regional regulatory bodies, this allows patients with serious or life-threatening conditions to access medicines, even before they are commercially available in the country. In China, partner Sperogenix Therapeutics has launched a paid-for early access program (EAP) for AGAMREE for patients with DMD. In April 2024, the Hainan Medical Products Administration (HMPA) authorized the EAP for AGAMREE in China, where approved treatments are currently unavailable, based on local policies, AGAMREE’s existing overseas approvals (U.S., EU, UK) and its demonstrated ability to address urgent clinical needs in DMD. The EAP started in the Bo’ao Lecheng Pilot Zone, located in Hainan Province, in mid-May, where strong interest has been received and approximately 70 patients are currently on active treatment with AGAMREE. Pre-commercialization measures advancing across Europe—pricing negotiations ongoingSanthera plans to make AGAMREE available to patients across Europe. After Germany and Austria, the build-up of a core commercial organization is well advanced in UK, France, Italy, Spain, and Benelux. Activities surrounding market access, stakeholder and key opinion leader engagement in the target countries advanced throughout the period under review. Across key European markets, Santhera is currently engaged in various national processes of health technology assessments (HTA), pricing negotiations, and reimbursement decisions. In Germany, considering that Santhera launched AGAMREE on January 15, 2024, the pricing negotiations are expected to be concluded by January 15, 2025. Owing to the complex and lengthy nature of these evaluations, anticipated timelines for upcoming market entries are likely to be slightly later than previously indicated. The UK is expected to be concluded later this year, France and Spain by mid-2025 and Italy by late 2025. Meanwhile, mid-sized European countries will progress in parallel with the big five markets. Self-marketing territory expanded—additional distribution agreements securedMarket uptake in the first launch countries has been strong and exceeded Santhera’s expectations. On this basis, Santhera has decided to expand its self-marketing strategy for AGAMREE to include the Nordic countries (Denmark, Sweden, Finland, Norway, and Iceland), along with Portugal and Ireland, and the organizational build-up has started. This approach reflects confident economic projections, while ensuring that margins are kept in-house, and allows the Company to maximize value and revenue potential from Agamree in DMD. For all other markets in Europe, Santhera has signed up GENESIS Pharma as its distribution partner. GENESIS Pharma, with domiciles in Greece and Cyprus, is a regional biopharma company specialized in the commercialization of innovative medicines targeting severe and rare diseases in Central and Eastern Europe. The company will market AGAMREE in DMD in Greece, Cyprus, Malta, Romania, Bulgaria, Slovenia, Croatia, Poland, Czech Republic, Hungary, Slovakia, Lithuania, Latvia, Estonia, Serbia, North Macedonia, Bosnia & Herzegovina, Montenegro, Albania, and Kosovo. A supply and distribution agreement has also been signed with Megapharm Ltd. Megapharm is a leading specialty marketing and distribution company in Israel’s healthcare sector and will market AGAMREE for the treatment of DMD in Israel and the Palestinian territories. In addition, Santhera has entered into discussions with multiple potential partners for additional territories outside of Europe. Clinical programs with AGAMREE AGAMREE has been developed to provide an anti-inflammatory and muscle preserving treatment with a favorable safety and tolerability profile as an alternative to the current standard of care with glucocorticoids. In addition to long-term efficacy and safety data with AGAMREE, recent publications and presentations further characterized AGAMREE’s differentiated profile mainly with regard to bone health. Clinical studies with AGAMREE in Duchenne muscular dystrophy (DMD) were initiated to investigate its effects in a broader patient age group and additional clinical work was started to differentiate the safety profile over the next couple of years. The clinical development program for AGAMREE until now included patients 4 to <7 years old and, as part of the pediatric investigational plan (PIP) requested by EMA, a new Phase 2 study aims at collecting information on AGAMREE outside this age range through inclusion of patients starting at an age of 2 years and up to 18 years. In addition, a Phase 1 study in healthy volunteers aims to confirm AGAMREE's mineralocorticoid antagonistic properties, a key mechanism in current standard therapies to slow cardiomyopathy progression, further distinguishing AGAMREE as the only corticosteroid that may offer early cardioprotective benefits alongside its proven efficacy in DMD. Separately, a Phase 2 pilot study in Becker muscular dystrophy (BMD) is evaluating the safety, tolerability and exploratory clinical efficacy on motor function outcome. Santhera is committed to fully realizing AGAMREE’s potential in the treatment of DMD by investing in its market potential and refining its clinical development priorities for potential new indications. While the Company initially planned to provide more details on the development of a second indication in Q4 this year, Catalyst Pharmaceuticals, the partner in North America, will begin further clinical exploratory and development studies in 2025 to inform the strategy for future indications thereafter. FINANCIAL PERFORMANCE Half-year results Revenue from contracts with customers of CHF 14.1 million (H1-2023: CHF 3.9 million)Operating result of CHF -17.7 million (H1-2023: CHF -20.3 million) Net result of CHF -15.3 million (H1-2023: CHF -23.3 million)Cash flow from operating activities of CHF-15.3 million (H1-2023: CHF -15.4 million)Cash and cash equivalents of CHF 16.5 million (Dec 31, 2023: CHF 30.4 million) Subsequent events and financing outlook Close of financings with Highbridge and R-Bridge (August 12, 2024) provided initial receipt of CHF 58 million net of transaction costs with future sales milestones of up to USD 8 millionRepayment of maturing listed convertible bonds (CHF 14 million including interest)Extension of CHF 7 million private convertible bond until August 2025Cash reach into 2026 when cash flow break-even is expected Net RevenueIn the first half-year 2024, Santhera reported revenue from contracts with customers of CHF 14.1 million (H1-2023: CHF 3.9 million). Net sales amounted to CHF 6.5 million following the launch of AGAMREE in Germany and Austria (H1-2023: CHF 1.0 million arising from RAXONE which ceased following the disposal during H2-2023). Additionally, Santhera recognized CHF 7.7 million (H1-2023: CHF 3.0 million) from partners in China and North America reflecting milestones and product supply. Cost of goods soldCost of goods sold amounted to CHF 5.2 million and increased on the prior year level (H1-2023: CHF 1.9 million), reflecting initiation of commercial supply and the amortization of intangible assets. Cost of goods for the six months includes non-cash intangible amortization of CHF 2.5 million (H1-2023: CHF 1.5 million), royalties payable of CHF 1.0 million (H1-2023: nil) as well as early-stage logistics and CMC set up expenses. Operating expenses and resultOperating expenses of CHF 26.7 million (H1-2023: CHF 22.5 million) were 20% higher year-on-year, primarily due to an increase in activities to support the commercialization of AGAMREE. Development expenses amounted to CHF 13.8 million (H1-2023: CHF 9.7 million). The increase of 40% arises from additional longer-term studies and CMC (chemistry, manufacturing, and controls) development activities to further enhance the commercial success of AGAMREE. Marketing and sales expenses were CHF 4.7 million (H1-2023: CHF 4.3 million). This represents a slight increase due to higher activities for AGAMREE in Europe to support launches offset by reduction in expenses incurred in H1-2023 to support pre partnering US activities. General and administrative expenses amounted to CHF 8.3 million (H1-2023: CHF 8.4 million), with activities focused in 2024 on supporting commercial growth. The operating result amounted to a loss of CHF 17.7 million (H1-2023: loss of CHF 20.3 million). Financial income and expenses The financial income amounted to CHF 8.6 million (H1-2023: CHF 5.7 million). The increase was predominantly related to net positive changes in fair value of financial instruments, interest receivable and in (un)realized foreign exchange gains. Financial expenses were CHF 6.0 million (H1-2023: CHF 8.8 million), primarily driven by interest payable and in (un)realized foreign exchange losses. In summary, this resulted in a net financial income of CHF 2.7 million, compared with a net expense of CHF 3.1 million for H1-2023. Net resultThe net result in 2024 was a loss of CHF 15.3 million, compared to a net loss of CHF 23.3 million for H1-2023. Cash balance and cash flows As of June 30, 2024, the Company had cash and cash equivalents of CHF 16.5 million compared to CHF 30.4 million as of December 31, 2023, a decrease of CHF 13.9 million (H1-2023 an increase of CHF 0.3 million) Net cash flow used in operating activities amounted to CHF 15.3 million (H1-2023: net cash outflow of CHF 15.4 million). There was negligible cash flow from investing activities (H1-2023 income of CHF 5.7 million from proceeds of sale of shares). Net cash flow used in/from financing activities was CHF -0.4 million (H1-2023: CHF 10.0 million). There were no financing inflows during the period due to the available cash balances, while additional finance was raised following the period end. Assets and liabilitiesIntangible assets decreased by CHF 2.5 million to CHF 71.5 million reflecting amortization in the period. Total assets decreased by CHF 1.4 million to CHF 108.2 million as a result of a reduction in cash of CHF 13.9 million, offset by an increase in inventory and trade receivables following initial commercialization and milestones receivable. Total liabilities increased by CHF 10.5 million to CHF 60.2 million mainly due to increase in trade payables relating to inventory purchases. Shareholders’ equityTotal consolidated equity as of June 30, 2024, amounted to CHF 48.1 million compared to CHF 59.9 million as of December 31, 2023. Financing activitiesAs previously announced, additional funding was required to support ongoing activities and service debt obligations. In August, Santhera closed two financing agreements that provided the Company with gross funding totaling approximately CHF 69 million. CHF 35 million received from Highbridge under a new term loan agreement Santhera received CHF 35 million from a term loan financing from certain funds managed by Highbridge Capital Management, LLC (Highbridge). The loan has a four-year maturity with amortization in the amount of 15% per year, commencing after 24 months, and will pay a cash interest of 3-month SARON (floor of 2%) plus 9.75% per year. The transaction includes changes to the existing Highbridge private convertible bonds, extending CHF 7 million with a strike price of CHF 10 by 12 months to August 2025, and converting CHF 4 million, with a strike price of CHF 5 as well as issuing the new warrants to Highbridge. USD 30 million received from R-Bridge for partial and capped royalty monetization Upon closing of the royalty monetization financing agreement, R-Bridge paid an upfront of USD 30 million to Santhera and will make staged sales-related milestone payments that, if achieved, would result in total payments to Santhera of a further USD 8 million. The royalty agreement with R-Bridge is partial and capped. Santhera is monetizing 75% of the future royalty income streams (net of any agreed payment obligations of Santhera to ReveraGen and Idorsia) from its licensing agreements for AGAMREE with Catalyst Pharmaceuticals, Inc. and with Sperogenix Therapeutics Ltd., in respect of net product sales occurring from July 1, 2024. Once the agreed threshold or duration of royalty payments is met, the North America and China royalty payments will revert back to Santhera. In addition, Santhera retained certain rights to buy back the royalty income stream. Following closing of the financings, the proforma cash balance was CHF 72 million (August 13, 2024) after receipt of CHF 58 million net of transaction fees. After repayment of the maturing listed convertible bonds and interest in the amount of CHF 14 million, the remaining cash balance is expected to provide for a cash runway into 2026 and to expected cash flow break-even. 2024 Half-year Financial Information Interim condensed consolidated income statement(for the six months ended June 30, in CHF thousands, except per share data)H1-2024(unaudited)H1-2023(unaudited)Net sales6,464969Revenue from out-licensing transactions6,3611,921Net sales to licensing partner1,2891,049Revenue from contracts with customers14,1143,939Cost of goods sold of which amortization intangible assets(5,215)(2,487)(1,928)(1,519)Development(13,771)(9,748)Marketing and sales(4,660)(4,257)General and administrative, other(8,276)(8,452)Operating expenses (26,707)(22,457)Operating result(17,741)(20,305)Financial result, net2,652(3,115)Income tax (expense)/benefit17484Net result(15,263)(23,336)Basic and diluted loss per share (in CHF) (1.35)(2.09)Interim condensed consolidated balance sheet (in CHF thousands)Jun 30, 2024(unaudited)Dec 31, 2023(audited)Cash and cash equivalents16,49130,370Other current assets17,1494,287Noncurrent assets74,60674,972Total assets108,246109,629Equity48,05759,943Noncurrent liabilities7,1395,371Current liabilities53,05044,315Total equity and liabilities108,246109,629Interim condensed consolidated cash flow statement(for six months ended June 30, in CHF thousands)H1-2024(unaudited)H1-2023(unaudited)Net cash flow from/(used in) operating activities (15,282)(15,358)Net cash flow from/(used in) investing activities 105,682Net cash flow from/(used in) financing activities (358)9,979Cash and cash equivalents at January 130,3701,353Cash and cash equivalents at June 3016,4911,674Net increase/(decrease) in cash and cash equivalents(13,879)321Share capital(number of shares with par value of CHF 0.10)Jun 30, 2024(unaudited)Dec 31, 2023 (audited)Ordinary shares issued 12,620,37612,620,376Treasury shares918,8141,305,167Conditional capital for employee participations (Art 3b)542,450542,450Conditional capital for financing purposes (Art 3c)5,500,0005,500,000 Half-year ReportThe Santhera Half-year Report 2024 is available for download on the Company’s website at www.santhera.com/financial-reports. Conference Call Santhera will host a conference call on September 12, 2024, at 14:30 CEST / 13:30 BST / 08:30 EDT. CEO Dario Eklund, CFO Andrew Smith and CMO Shabir Hasham, MD, will discuss the 2024 half-year financial results and comment on ongoing corporate developments. Participants are invited to call one of the following numbers (no dial-in code is required): Switzerland/Europe: +41 58 310 50 00United Kingdom: +44 207 107 06 13USA: +1 631 570 56 13 A replay will be accessible at https://www.santhera.com/ad-hoc-news from about two hours after the call has ended. References Publications and applicable drug labeling to which this press release makes reference to: Labeling: United States Prescribing Information; European Union Summary of Product CharacteristicsDang UJ et al. (2024) Neurology 2024;102:e208112. doi.org/10.1212/WNL.0000000000208112. Link.Guglieri M et al (2022). JAMA Neurol. 2022;79(10):1005-1014. doi:10.1001/jamaneurol.2022.2480. Link.Liu X et al (2020). Proc Natl Acad Sci USA 117:24285-24293Heier CR et al (2019). Life Science Alliance DOI: 10.26508Ward et al., WMS 2022, FP.27 - Poster 71. Link.Hasham et al., MDA 2022 Poster presentation. Link. About SantheraSanthera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular and pulmonary diseases with high unmet medical need. The Company has an exclusive license from ReveraGen for all indications worldwide to AGAMREE® (vamorolone), a dissociative steroid with novel mode of action, which was investigated in a pivotal study in patients with Duchenne muscular dystrophy (DMD) as an alternative to standard corticosteroids. AGAMREE for the treatment of DMD is approved in the U.S. by the Food and Drug Administration (FDA), in the EU by the European Medicines Agency (EMA), and in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA). Santhera has out-licensed rights to AGAMREE for North America to Catalyst Pharmaceuticals and for China to Sperogenix Therapeutics. For further information, please visit www.santhera.com. AGAMREE® is a trademark of Santhera Pharmaceuticals. For further information please contact: public-relations@santhera.com orEva Kalias, Head Investor Relations & CommunicationsPhone: +41 79 875 27 80eva.kalias@santhera.com Disclaimer / Forward-looking statements This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements. # # # Attachment 2024 09 12_HY2024_e_finalz