PTC Therapeutics : 2020 Annual Report

2020 Annual Report

youHERE FOR

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.

IN OUR DNA

With every setback and advance, we continue to push forward every day because this is not simply a job to us: it's a calling.

THE FAMILY APPROACH

We are not simply there for you on the rare disease journey, but we are with you, because we know that family gets its strength from one another. We're in this together.

RARE RESOLVE FOR RARE DISEASE

Our people choose to work here because they believe in the moments that we build- in the labs and for our patients.

THE SCIENCE OF PROGRESS

We use data and groundbreaking science in our search for progress-progress in rare-disease treatments, of course, but also in the day-to-day lives of those affected.

A MESSAGE TO

OUR SHAREHOLDERS

2020 was a year like no other in our lifetime. It was marked by a global pandemic that impacted all of us and made life more challenging on both personal and professional levels. Even in the face of these issues, however, I am pleased to report that PTC rose to the occasion, making 2020 an incredibly productive and successful year. Having just celebrated our 23rd anniversary, I am proud that our company is better positioned to drive innovation and capitalize on our diversified and robust scientific platforms and programs.

Even at the beginning of the pandemic, PTC was able to pivot quickly and adjust the way we worked in the "new normal" environment. We recognized the potential issues that a pandemic would cause and closed our facilities earlier than almost any other company, stopping

all non-essential business travel in late February and subsequently went to fully remote operations within the first week of March last year. We created several task forces to deal with multiple aspects of the crisis, with the emphasis on continuing to be productive and to ensure patients would still receive their therapies. New approaches to communicate

with employees were developed, with weekly video messages and constant and consistent transparent public discussions. The safety of our employees and our patients was paramount in all the decisions we made.

Clinical trials became a particular challenge, but we had an advantage because most of our therapies in development are small molecule drugs that are orally administered. This means no injection or infusion is needed, so that dangerous trips to hospitals overwhelmed

Stuart W. Peltz, Ph.D., Chief Executive Officer

with the COVID-19 response were not necessary. Therefore overall, we were uniquely positioned to ensure the continuation of our clinical trials even in these most difficult times. We were able to initiate five clinical trials, including three registration-directed trials, of which two are from our Bio-e platform.

We have had substantial revenue growth this year and have increased our capabilities to discover, develop and commercialize our diversified pipeline. As the pandemic unfolded, we suspended the financial guidance for the year. Nonetheless, I am proud to report that revenues for the year were in line with our pre-pandemic estimates, with 14 percent year-over-year growth, and total net product revenue was $331 million. The increased revenue was driven by our Duchenne muscular dystrophy franchise consisting of Translarna™ (ataluren) and Emflaza® (deflazacort). Of note, revenue for Emflaza increased 38 percent year-over-year. Translarna's growth

was driven by new patients in existing geographies, geographic expansion, and label updates driving broader access. The revenue generated helps drive the continued investment in developing new treatments for patients with high unmet need.

I am incredibly proud of how we weathered the storm. It is a testament to our employees -- their ingenuity and

"Having just celebrated our 23rd anniversary, I am proud that our company is better positioned to drive innovation and capitalize on our diversified and robust scientific platforms and programs."

>>

PTC 2020 ANNUAL REPORT 1

resultsDRIVING

CONTINUED STRONG DMD FRANCHISE GROWTH

(USD MILLIONS)

Emflaza® Net Sales

Translarna™ Net Sales
		+58%			291	331
			263		139
				101
				92
		174			190	192
		29		171
	81	145
34
2015	2016	2017	2018		2018	2020

MULTIPLE PLATFORMS PROVIDE OPPORTUNITY

TO TREAT OVER 500,000 PATIENTS BY 2030

PTC-AADC

DMD SMA AADC	ME	PKU	FA	HD	GBA-PD	AS
~50K	~20K	~58K	~25K	~135K	~190K	~75K
2021						2030

2

Shareholder's Letter Continued

perseverance in the face of multiple challenges; their resilience and adaptability as circumstances changed; and their passion for our mission to provide innovative treatments to patients with debilitating rare diseases that have few or no treatment options. PTC has emerged a stronger and more resilient company.

Perhaps the most significant milestone achieved in 2020 was in August with the FDA approval of Evrysdi™ (risdiplam), the first at-home, orally administered treatment for spinal muscular atrophy (SMA) in adults and children two months and older. SMA is a devastating neuromuscular disease that is the leading genetic cause of death in infants and young children. Evrysdi was discovered from PTC's splicing platform and was developed in collaboration with Roche and the SMA Foundation.

The development of Evrysdi provides an example of the level of dedication and perseverance that is a hallmark of PTC. Back in 2005, the SMA Foundation approached us to develop therapies for SMA. One program was the identification of molecules that selectively and specifically affect splicing. We screened our compound library of more than 300,000 molecules. The program

had well over fifty scientists including biologists, chemists, pharmacologists, and toxicologists. It also took enormous resources and dedication from our collaboration partners, including the SMA Foundation and in 2011 F. Hoffmann La Roche Ltd. (Roche), who joined us in this effort.

More recently, the European Commission approved Evrysdi for SMA patients two months and older. Roche has stated publicly that Evrysdi is expected to become the treatment of choice for SMA patients in the United States in 2021,

and we are pleased to have brought such a game-changing therapy to market. While our journey was not always straightforward, we believe that the results of bringing such an important therapy to patients with such high unmet need are a testament to all that makes PTC great.

We continue to build on our splicing platform and have multiple programs based on this technology. I am happy to report that another development candidate from our splicing platform, PTC518,

has moved into clinical development in 2020. PTC518 is being developed as a potential treatment for Huntington's disease. PTC518 alters huntingtin (HTT) splicing that causes the reduction of HTT levels, which is critically important for treating Huntington's disease. We recently shared our preliminary results from the phase 1 healthy volunteer trial. We are pleased to report that PTC518 treatment resulted in dose-dependent reduction of HTT messenger RNA levels. PTC518 was well-tolerated at all dose levels with no safety findings observed. Like risdiplam, it is a small molecule that distributes

to all tissues in the body and therefore PTC518 is able to get to all tissues in the brain. This is a critical attribute of PTC518 because of the neurodegenerative nature of Huntington's disease. We feel confident that, with our experience with SMA drug development, we are well positioned for success to drive PTC518 development to treat Huntington's Disease.

Let me turn to our gene therapy platform to treat rare monogenic diseases. Our most advanced gene therapy product, PTC-AADC, is a gene therapy for the treatment of Aromatic L-Amino Acid Decarboxylase, or AADC deficiency.

In 2020, we submitted a marketing authorization application to European regulatory authorities and expect an opinion from the EMA's Committee for

"I am incredibly proud of how we weathered the storm. It is a testament

to our employees

• their ingenuity and perseverance in the face of multiple challenges."

>>

PTC 2020 ANNUAL REPORT 3