Omigapil

Pratteln, Switzerland, September 10, 2019 – Santhera Pharmaceuticals announces the online publication of Phase I data with its human neutrophil elastase inhibitor POL6014 in the Journal of Cystic Fibrosis. Pratteln, Switzerland, September 10, 2019 – Santhera Pharmaceuticals (SIX: SANN) announces the online publication of Phase I data with its human neutrophil elastase (hNE) inhibitor POL6014 in the Journal of Cystic Fibrosis [1]. These data demonstrated that single dose inhalation of POL6014 can lead to high drug concentrations within the lung, resulting in inhibition of hNE in sputum of patients, an enzyme associated with lung tissue inflammation. POL6014 is an innovative, potent and selective inhibitor of human neutrophil elastase (hNE) in clinical development for the treatment of cystic fibrosis (CF). In CF, excessive release of enzymes like hNE accelerates lung tissue inflammation and damage, leading to an incapacitating and progressive decline in pulmonary function. The two double-blind, placebo-controlled studies now published evaluated the safety, tolerability and pharmacokinetics of single ascending doses of inhaled POL6014 in healthy volunteers and CF patients. In the two studies, a total of 48 healthy volunteers and 24 patients with CF were randomly allocated to various doses of POL6014 or placebo. Healthy volunteers received POL6014 at doses ranging from 20 mg to 960 mg; CF patients were dosed at 80 mg, 160 mg or 320 mg. Shortly after inhalation of POL6014, a clear reduction of active hNE in sputum was observed at all doses tested in patients with CF. Furthermore, levels of POL6014 in sputum for these patients appeared to be up to 1000-fold higher compared to plasma levels at 3 and 24 hours post inhalation, indicating high exposure to POL6014 in the lung, with very limited systemic drug exposure. Doses of up to 480 mg POL6014 were assessed as safe and well tolerated. “We are encouraged by these early data in healthy volunteers and patients with cystic fibrosis. POL6014 brings new promise to current CF treatment which, despite recent developments, is still lacking a solution to lung tissue inflammation, a cause of pulmonary exacerbations. In addition, inhalation of POL6014 shows a strong advantage over the oral route as it delivers the drug directly to the lung with a low systemic burden,” said Kristina Sjöblom Nygren, MD, Chief Medical Officer and Head of Development at Santhera. “As an innovative inhibitor of human neutrophil elastase, POL6014 could have potential in a range of other pulmonary diseases.” On the basis of the successful Phase I data, Santhera is currently conducting a Phase Ib/IIa MAD (multiple ascending dose) study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally inhaled multiple doses of POL6014 in patients with CF. Santhera obtained the worldwide, exclusive rights from Polyphor AG to develop and commercialize POL6014 in CF and other pulmonary diseases. The Cystic Fibrosis Foundation (CFF) is providing funding support for the conduct of the safety trials with POL6014. Reference: [1] Barth P. et al (2019). Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis. Journal of cystic fibrosis 2019. DOI: 2019.08.020 About POL6014 POL6014 is a highly potent and selective inhibitor of human neutrophil elastase (hNE) and was shown to reach high concentrations in the lung when administered by inhalation via an optimized eFlow® nebulizer (PARI Pharma GmbH). POL6014 may also show therapeutic benefit for a range of neutrophilic pulmonary diseases with high medical need such as non-cystic fibrosis bronchiectasis (NCFB), alpha-1 antitrypsin deficiency (AATD) or primary ciliary dyskinesia (PCD). POL6014 has EU orphan drug designations (ODD) for the treatment of AATD, PCD and CF. About cystic fibrosis and human neutrophil elastase (hNE) Cystic fibrosis (CF) is a rare, hereditary, life-threatening, progressive disease affecting approximately 70,000 patients in the U.S. and Europe and is characterized by persistent lung infection and chronic inflammation thereby limiting the ability to breathe over time. Activated or necrotic neutrophils liberate human neutrophil elastase (hNE) in the lung that causes damage to structural, cellular and soluble components of the pulmonary microenvironment. High levels of hNE play a central role in the pathophysiology of CF and correlate with disease severity as measured by functional lung parameters. Inhibition of hNE is expected to reduce airway inflammation and slow the damage to lung tissue and may help to improve the overall quality of life for individuals with CF. About Santhera Santhera 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. Santhera is building a leading Duchenne muscular dystrophy (DMD) franchise. A marketing authorization application for Puldysa® (idebenone) is currently under review by the European Medicines Agency. Santhera has an option to license vamorolone, a first-in-class dissociative steroid currently investigated in a pivotal study in patients with DMD to replace standard corticosteroids. The clinical stage pipeline also includes POL6014 to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases, as well as omigapil and an exploratory gene therapy approach targeting congenital muscular dystrophies. Santhera out-licensed ex-North American rights to its first approved product, Raxone® (idebenone), for the treatment of Leber’s hereditary optic neuropathy (LHON) to Chiesi Group. For further information, please visit . Raxone ® and Puldysa® are trademarks of Santhera Pharmaceuticals. For further information please contact: public-relations@santhera.com or Eva Kalias, Head External Communications Phone: +41 79 875 27 80 eva.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. # # #

Santhera Pharmaceuticals reports first half-year results as of June 30, 2019, and provides an update on its pipeline and strategic focus. Pratteln, Switzerland, September 3, 2019 – Santhera Pharmaceuticals (SIX: SANN) reports first half-year results as of June 30, 2019, and provides an update on its pipeline and strategic focus. Thomas Meier, PhD, Chief Executive Officer of Santhera , said: “Following a series of transactions which strategically reshaped the direction of the Company, we are well positioned to advance our long-term growth strategy of focusing on medicines to treat neuromuscular and pulmonary diseases. For 2019, we are on track to achieve our strategic objectives, having filed for conditional marketing authorization of Puldysa® (idebenone) in Europe for the preservation of respiratory function in Duchenne muscular dystrophy (DMD) patients. We expect an opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) mid-2020. Our goal is to help all DMD patients, irrespective of causative mutations, disease stage or age. We were therefore very pleased about the recent publication by ReveraGen of positive Phase IIa-extension study results with vamorolone in the journal Neurology . These data together with previous publications provide proof-of-concept that vamorolone can improve gross muscle function outcomes in young patients with DMD and indicate a better tolerability pro standard corticosteroids.” “During the period, we announced an exclusive agreement with Chiesi Group to out-license Raxone® for the treatment of Leber’s hereditary optic neuropathy (LHON) for a total consideration of up to EUR 93 million with an upfront payment of EUR 44 million. In monetizing this commercial product, we have strengthened our financial position to focus on upcoming regulatory milestones and commercialization activities for our neuromuscular and pulmonary product candidates, which are core to our long-term growth strategy.” Financial highlights: 1H-2019 sales on track with CHF 18.3 million, an increase of 14% compared to 1H-2018 Operating expenses of CHF 38.2 million (1H-2018: CHF 39.9 million) Operating result of CHF –22.4 million (1H-2018: CHF –26.3 million) leading to a net result of CHF –26.9 million (1H-2018: CHF –27.4 million) Cash and cash equivalents of CHF 43.7 million (August 31, 2019) Full-year sales guidance of CHF 25-27 million First half-year overview: Regulatory momentum for Puldysa in DMD In June, the European Medicines Agency (EMA) validated Santhera’s application for conditional marketing authorization (CMA) for Puldysa (idebenone) in the treatment of respiratory dysfunction in patients with Duchenne muscular dystrophy (DMD) who are not using glucocorticoids. The review process by the EMA’s CHMP has begun and the Company expects an opinion by the CHMP around mid-2020. In addition, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) renewed its positive scientific opinion for idebenone for patients with DMD in respiratory function decline who are not taking glucocorticoids, under the Early Access to Medicines Scheme (EAMS). Long-term data with Puldysa In February, Santhera announced the results of its SYROS study, which investigated long-term efficacy with idebenone in slowing respiratory function loss in patients with DMD. The study demonstrated that long-term treatment with idebenone consistently contributed to the preservation of respiratory function for up to 6 years in a real-world setting. This long-term data further supports the potential for idebenone to positively modify the course of respiratory function decline and delay the time to clinically relevant milestones. Strong Raxone performance underscores Santhera’s commercial expertise Net sales of Raxone in Europe amounted to CHF 18.3 million (1H-2018: CHF 16.0 million) which corresponds to a 14% increase year-on-year, in line with the previous full-year product sales guidance. In May, the Company announced that it had entered into an exclusive license agreement with Chiesi Group for Raxone for the treatment of LHON, for a total consideration of up to EUR 93 million. With the closing at the end of July, Santhera has now transferred all rights to Chiesi Group for the development, commercialization and distribution of Raxone for the treatment of LHON and any other potential ophthalmological indications for all territories worldwide except the US and Canada. After the closing and for an interim period, Santhera will provide support services to Chiesi Group to enable a seamless handover of the business and will continue to commercialize Raxone for LHON in France. Positive study data with vamorolone published– pivotal study enrolling Last month, positive data from 6-month Phase IIa-extension study (VBP15-003) with vamorolone in DMD were published by ReveraGen in Neurology [1]. The data demonstrated dose-related improvement of gross muscle function in patients with DMD treated with vamorolone. Vamorolone was reported to be safe and well tolerated up to the highest dose tested (6.0 mg/kg/day). Biomarker data indicated reduced occurrence of side effects typical for traditional corticosteroid drugs. Based on these data, vamorolone has potential to replace standard corticosteroids currently used in patients with DMD. ReveraGen is presently enrolling the Phase IIb VISION-DMD study [2] (VBP15-004; clinicaltrials.gov : NCT03439670), designed as a pivotal efficacy and safety trial. The study is expected to be fully enrolled by the end of 2019. Accordingly, the 6-month randomized placebo-controlled treatment period would end by mid-2020, followed by data analysis. NDA submission could be towards year end 2020. Collaboration to advance gene therapy research for rare neuromuscular disease Santhera initiated a collaboration with the Biozentrum of the University of Basel to advance gene therapy research for the treatment of LAMA2-deficient congenital muscular dystrophy (LAMA2 MD or MDC1A). The preclinical research collaboration builds on previous work with omigapil, which was recently studied in a Phase I clinical trial and could act complementary. The program is supported by public funding for innovation in Switzerland through a grant from Innosuisse – the Suisse Innovation Agency. Continued investment in clinical development Santhera is running several late-stage clinical trials, among them SIDEROS, the largest ever conducted study in patients with DMD. The SIDEROS study is 84% recruited and positive outcome of the study will form the basis for NDA submission for patients with DMD irrespective of glucocorticoid status, currently expected in 2H-2021. In addition, the preparation of the MAA for Puldysa, remaining post-approval clinical work for Raxone in LHON and increased clinical development work with POL6014 entailed slightly higher development expenses of CHF 19.3 million (+2% year-on-year). Overall, operating expenses showed a small decline (–4%) driven by lower expenses for commercial activities (–10%). Liquidity base allows for the continuation of the strategy as planned In April, Santhera raised CHF 7.1 million by the placement of 500,000 shares. As of the end of June 2019, Santhera had cash and cash equivalents of CHF 12.7 million (December 31, 2018: CHF 22.0 million). Together with the net proceeds from the initial payment from Chiesi Group following closing of the licensing transaction, liquid funds amounted to CHF 43.7 million (August 31, 2019), allowing the Company to proceed with its clinical trial program and regulatory filings as planned. Outlook and Guidance Based on the performance in the first half-year of 2019, the Company expects to achieve annual net sales with Raxone in the currently approved indication LHON of CHF 25-27 million in 2019, taking into account that Chiesi Group has taken over commercial sales for Raxone from August in all European countries except France. The operational priorities for 2019 are the preparation of European market entry with Puldysa in DMD in 2020, completing enrollment into the DMD SIDEROS trial to support the planned US-submission of Puldysa in DMD, and advancing the other clinical stage candidates in the pipeline, particularly vamorolone and POL6014. References: [1] Hoffman EP et al. (2019). Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology 2019. lookup/doi/10.1212/WNL. 0000000000008168 [2] Half-year Report The Santhera Half-year Report 2019 is available for download on the Company’s website at and-media/investor-toolbox/ financial-reports . Conference Call Santhera will host a conference call on September 3, 2019 at 13:00 CEST / 12:00 BST / 07:00 EDT. Thomas Meier, PhD, CEO of Santhera, will discuss the half-year 2019 financial results and will provide an update on corporate developments. Participants are invited to call one of the following numbers 10-15 minutes before the conference call starts (no dial-in code is required): Europe: +41 58 310 50 00 UK: +44 207 107 06 13 USA: +1 631 570 56 13 2019 Half-year Financial Information Santhera’s 2019 Half-year Report see and-media/investor-toolbox/ financial-reports . Condensed consolidated income statement (reviewed, IFRS, for half-year ended June 30, in CHF thousands) 1H-2019 1H-2018 Net sales 18,315 16,027 Cost of goods sold (of which amortization intangible assets: 2019 –1,519 / 2018 –1,519) –2,557 –2,441 Development –19,325 –18,854 Marketing and sales –11,611 –12,921 General and administrative –7,206 –8,051 Operating expenses –38,208 –39,883 Operating result –22,434 –26,297 Financial result –4,065 –961 Income taxes –401 –93 Net result –26,900 –27,351 Basic and diluted loss per share (in CHF) –2.47 –4.25 Condensed consolidated balance sheet (IFRS, in CHF thousands) June 30, 2019 (reviewed) Dec. 31, 2018 (audited) Cash and cash equivalents 12,698 21,971 Other current assets 25,774 21,112 Noncurrent assets 67,620 67,211 Total assets 106,092 110,294 Equity 9,254 27,829 Noncurrent liabilities 69,609 62,756 Current liabilities 27,229 19,709 Total equity and liabilities 106,092 110,294 Condensed consolidated cash flow statement (reviewed, IFRS, in CHF thousands) 2019 2018 Operating cash flow for the half-year ended June 30 –20,219 –22,154 Investing cash flow for the half-year ended June 30 1,448 137 Financing cash flow for the half-year ended June 30 9,465 –1,107 Cash and cash equivalents at January 1 21,971 45,195 Cash and cash equivalents at June 30 12,698 22,082 Net change in cash and cash equivalents –9,273 –23,113 Share capital (number of shares with par value of CHF 1) June 30,2019 (reviewed) Dec. 31, 2018 (audited) Shares issued 11,164,563 10,664,563 Conditional capital for equity rights plans 687,552 687,552 Conditional capital for conversion rights 2,500,000 930,000 Authorized capital 3,000,000 500,000 About Santhera Santhera 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. Santhera is building a leading Duchenne muscular dystrophy (DMD) franchise. A marketing authorization application for Puldysa® (idebenone) is currently under review by the European Medicines Agency. Santhera has an option to license vamorolone, a first-in-class dissociative steroid currently investigated in a pivotal study in patients with DMD to replace standard corticosteroids. The clinical stage pipeline also includes POL6014 to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases, as well as omigapil and an exploratory gene therapy approach targeting congenital muscular dystrophies. Santhera out-licensed ex-North American rights to its first approved product, Raxone® (idebenone), for the treatment of Leber’s hereditary optic neuropathy (LHON) to Chiesi Group. For further information, please visit . Raxone® and Puldysa® are trademarks of Santhera Pharmaceuticals. For further information please contact: public-relations@santhera.com or Eva Kalias, Head External Communications Phone: +41 79 875 27 80 eva.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.