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Measured Moments measured by moments 2019 ANNUAL REPORT OUR PROMISE. Rare diseases, real strides to treat them—this is why we’re here. No matter how uncommon the disorder, the life-limiting effects are a daily reality For those aFFected. When Stu Peltz Founded PTC over 20 years ago, he had this unique insight. That’s why we’re creating life-changing treatments every day. The Family Approach In Our DNA We are not simply there For you With every setback and on the rare disease journey, advance, we continue to push but we are with you, because forward every day because we know that family gets its this is not simply a job to us: strength from one another. it’s a calling. We’re in this together. Rare Resolve for The Science Rare Disease of Progress Our people choose to work here We use data and groundbreaking because they believe in the science in our search for moments that we build— progress—progress in in the labs and in the home. rare-disease treatments, of course, but also in the day-to-day lives of those affected. A Message to Our Shareholders Our exceptional team is well positioned to address whatever comes our way thanks to the progress we have made in past years. Stuart W. Peltz, Ph.D., PTC Therapeutics recently marked its We continue to invest in our clinical Chief Executive Ofcer 22nd anniversary, a proud moment stage programs and pipeline across for the company amid a diffcult our small molecule and gene time for all of us globally. As we look therapy platforms. We have multiple back upon 2019 in the context of our therapeutic platforms and therapies company’s long history, I’m proud to that were either internally discovered see that we’ve kept to our mission and developed or brought in to of providing access to best-in-class complement our deep scientifc roots. treatments for patients living with We continue to drive innovation with rare disorders. our platforms and therapies thereby creating shareholder value. We believe I’m also proud oF our response to the our multiplatform approach creates COVID-19 pandemic to date, which sustainable innovation and drives has been to remain calm, be prudent continuous value creation. and thoughtful, assess the situation, make appropriate decisions, execute, In 2019, we further diversifed our and then monitor the situation and innovative pipeline by acquiring assets change course as needed. This focused on inflammatory and central approach allows us to maintain focus nervous system (CNS) disorders, on our mission and successFully adapt which we call our Bio-e platform. to new challenges as they come. The platform’s novel small molecule approach targets inflammation and As founder and CEO, it is gratifying to oxidative stress to treat multiple see how more than 20 years of hard mitochondrial diseases via the redox work has built a company and team pathway. In 2020, we expect to start capable of sustaining, even thriving, two potential registrational trials with in this uncertain environment. Our the lead Bio-e compound, PTC743. exceptional team is well positioned to address whatever comes our way One example of being able to use our thanks to the progress we have made multiple platform approach to have in past years. products to treat all aspects of the 1 | PTC | 2019 ANNUAL REPORT OUR PIPELINE Nonsense Gene LatAm Splicing Bio-e Oncology Defazacort Mutation Therapy Commercial TRANSLARNA™ EMFLAZA® TEGSEDI™ WAYLIVRA® COMMERCIAL SMA AADC US DYSTROPHIN PTC743 MEDS PTC596 DIPG PTC743 FA PTC596 LMS CLINICAL PTC299 AML PTC857 HD FA GBA-PD UNDISCLOSED ANGELMAN UNDISCLOSED IRDs COG DISORDERS RESEARCH *Investigator-initiated study with NYU - As of April 2020 PTC | 2019 ANNUAL REPORT | 2 Shareholder Letter (Continued) disease are treatments we are devel- challenge of producing a large amount We are also very excited about the oping for patients living with Friedreich of product. Controlling manufacturing frst compound to come from our ataxia. In this case we are pursuing is key to our gene therapy strategy. alternative splicing platform, risdiplam, two distinct therapeutic approaches; a In 2019, we secured a manuFacturing which is partnered with Roche and systemic small molecule that reaches facility in Hopewell, N.J. This will allow the SMA Foundation as a potential the heart, and a gene therapy treat- us to begin manufacturing our own treatment for spinal muscular atrophy ment that has the potential to impact gene therapy products. (SMA). Results From two risdiplam neurological deterioration and stop pivotal clinical trials, Sunfsh and disease progression. We believe this I am proud oF our team’s collective Firefsh, demonstrated beneft in dual approach can potentially treat all efforts to submit our frst gene patients living with type 1, 2 and aspects of the disease. therapy treatment to regulators 3 SMA. Risdiplam has been well for AADC defciency (AADCd), a tolerated at all doses across studies Our gene therapy platform leverages a rare neuromuscular disorder that and there have been no drug related diFFerentiated approach with a current is often misdiagnosed as cerebral safety fndings leading to withdrawal. focus on treating rare monogenic CNS palsy or epilepsy. The clinical trials A New Drug Application has been fled disorders where the gene therapeutic demonstrated transformative results with the FDA and it has been assigned is directly injected into a targeted for these patients. We have submitted a target PDUFA date of Aug. 24, 2020. location in the brain where cells have a Marketing Authorization Application low turnover. This allows us to deliver to the European Medicines Agency PTC’s commercial teams have signifcantly lower, or micro-doses, of for approval, and we are also working continued to make signifcant the gene therapeutic to patients. This towards fling a Biologics Licensing contributions. Over the last 12 is an advantage with gene therapy Application with the U.S. Food and months, our Duchenne muscular since you don’t have the additional Drug Administration (FDA). dystrophy (Duchenne) franchise 3 | PTC | 2019 ANNUAL REPORT continued to grow in markets around sense of purpose. The PTC team the world, resulting in annual net grew by 45 percent in 2019; we revenue of $291 million in 2019. We are a multinational group with $291 have treated more than 90 percent more than 800 employees in MILLION IN ANNUAL NET of nonsense mutation Duchenne 22 countries. REVENUE IN 2019 patients in the EU5, with a compli- ance rate of more than 85 percent. I am proud that we continue to And we plan to launch Translarna™ in innovate and invest to bring the the United States, pending dystrophin best therapies from our laboratories trial results and FDA approval. to patients around the world. I am as energized as ever about the potential In addition, we released long-term, of our company, as I see frsthand real world data of nonsense mutation the impact we are having on patients’ Duchenne patients on Translarna in lives. Together, we will make a bigger our STRIDE registry, which showed difference around the world as PTC long-term benefts from treatment. continues to evolve and thrive well 45% Patients on treatment had a delay in into the future. COMPANY GROWTH ambulation of approximately three IN 2019 and a half years compared to natural Considering the unique and history, and importantly, Translarna challenging circumstances we all fnd showed preservation of lung function. ourselves in, we are exceptionally proud of how our team has come Another product in the Duchenne together and executed thus far franchise is Emflaza® for which in 2020. Our focus remains on we received a label expansion into executing our strategy, while 800 patients as young as 2 years old. ensuring the health and safety of EMPLOYEES IN... We continue to identify and treat our employees and patients, which new patients in the 2- to 5-year-old includes providing continued access population. Through our efforts and to critical therapies. scientifc publications demonstrating the beneft of Emflaza over predni- PTC is well positioned to continue sone, payers continue to see the to achieve our goals in 2020, with a beneft of using Emflaza in Duchenne strong capital position, commercial 22 patients and have eased restrictions. products that are administered at COUNTRIES home and are well suited for the In Latin America, we achieved an current environment, a diverse important milestone for our patients rare disorder pipeline and multiple with the approval of Tegsedi™ in upcoming catalysts expected to Brazil. Tegsedi is the frst RNA- continue to drive value creation targeted treatment approved in Brazil going forward. for the underlying cause of hereditary 85% transthyretin-mediated (hATTR) Sincerely, EU5 COMPLIANCE RATE amyloidosis with polyneuropathy. With the approval of Tegsedi, PTC now has 3 commercially available products in Brazil. Stuart W. Peltz, Ph. D. All oF the progress that we have made Chief Executive Offcer for patients over the last 12 months would not have been possible without the passionate people of PTC. Each PTC employee is driven by a strong PTC | 2019 ANNUAL REPORT | 4 LOSSAR AADC: AADC Defciency is a rare central nervous typically lose walking ability by their early teens, HD: untingtons Disease (D) is a rare system disorder arising from reductions in the reuire ventilation support in their late teens and, genetic disorder that is caused by a CA repeat enzyme aromatic L-amino acid decarboxylase eventually, die due to heart and lung failure. The expansion in the TT gene. The mutated TT (AADC) that result from mutations in the dopa average age of death for DD patients is in their protein leads to severe neuron degeneration decarboxylase (DDC) gene. This reduction leads to mid-twenties.
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