12/22/05 — PTC Therapeutics Initiates Second Phase 2 Study of PTC124 in Patients with Cystic Fibrosis in Israel

12/19/05 — PTC Therapeutics names David P. Southwell to its Board of Directors

12/19/05 — Parent Project Muscular Dystrophy Announces Successful Completion of Stage 1 of Drug Discovery Collaboration with PTC Therapeutics, Inc.

12/06/05 - PTC Therapeutics Initiates Phase 2 Study of PTC124 in Cystic Fibrosis

PTC THERAPEUTICS INITIATES SECOND PHASE 2 STUDY OF PTC124 IN PATIENTS WITH CYSTIC FIBROSIS IN ISRAEL

SOUTH PLAINFIELD, NJ — December 22, 2005 — PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development, and commercialization of small-molecule drugs targeting post-transcriptional control mechanisms, today announced the initiation of a Phase 2 study of PTC124 at Hadassah University Hospital in Israel in patients with cystic fibrosis (CF) due to a nonsense mutation. This study is being conducted in parallel with a similar U.S.-based Phase 2 clinical trial in CF, which recently began recruiting patients.

PTC initiated the Israeli study in collaboration with Dr. Eitan Kerem and Dr. Michael Wilschanski who had previously conducted an important proof-of-concept clinical trial using local application of gentamicin, an aminoglycoside antibiotic, to the nasal mucosa of patients with nonsense-mutation-mediated CF. That study was published in the October 9, 2003 issue of The New England Journal of Medicine, and demonstrated that gentamicin could overcome the effect of the nonsense mutation and induce production of full-length, functional CFTR protein in the nasal mucosal cells. However, the investigators concluded that the long-term use of gentamicin for this purpose is limited by the need for intravenous administration and its potential for serious renal and otic toxicities. PTC124 is an orally bioavailable new chemical entity unrelated to gentamicin that was specifically designed to induce production of full-length protein in genetic disorders due to a nonsense mutation.

"In studying the efficacy of locally applied gentamicin in patients with CF, we were excited by the positive data, but knew that it would not be able to provide a long-term treatment option," commented Dr. Michael Wilschanski, Director, Pediatric Gastroenterology at Hadassah University Hospital. Dr. Eitan Kerem, Head, Department of Pediatrics and CF Center, Hadassah University Hospital remarked "PTC124 offers the potential of a potent, easy-to-deliver oral therapy for patients with CF due to a nonsense mutation, but without the toxicity of aminoglycoside antibiotics. We are delighted to have the opportunity to conduct studies of this promising new drug."

PTC124 is being investigated initially as a treatment for CF and Duchenne muscular dystrophy (DMD), but also has the potential to treat a number of other genetic disorders. It is estimated that, worldwide, approximately 10% of patients with CF and 15% of patients with DMD have these disorders because of a nonsense mutation. However, in Israel, it is estimated that over 60% of patients with CF have the disease due to a nonsense mutation.

As in the U.S. Phase 2 study in CF, the Israeli study is enrolling patients who have undergone genetic testing to determine that they have CF due to the presence of a nonsense mutation in the CFTR gene. The primary endpoint is assessment of nasal transepithelial potential difference (NPD or TEPD) as a measure of CFTR function in response to treatment with PTC124. Secondary assessments of CFTR function also include mRNA, immunofluorescence, sweat chloride and pulmonary function tests. Safety, pharmacokinetics and compliance studies will also be performed.

"The pioneering work of Dr. Kerem and Dr. Wilschanski has set the foundation for the PTC124 clinical trials program. The patient care expertise and research experience of these investigators will be extremely beneficial as we continue to evaluate PTC124 clinically," stated Langdon Miller, M.D, Chief Medical Officer of PTC.

Stuart Peltz, Ph.D., PTC's President and Chief Executive Officer, added, "The involvement of these two thought-leaders in the development of PTC124 is a wonderful endorsement of our science. Their participation will enhance our understanding of PTC124's efficacy, safety, and pharmacology, and will add to our efforts to improve outcomes for patients with CF and other debilitating genetic disorders." More information on the enrollment criteria and design of the Phase 2 clinical trials in Israel and the U.S. can be found at www.clinicaltrials.gov. A Phase 2 study of PTC124 in patients with DMD will also be initiated before the end of the year in the U.S.

Back to Top

PTC THERAPEUTICS NAMES DAVID P. SOUTHWELL TO ITS BOARD OF DIRECTORS

SOUTH PLAINFIELD, NJ — December 19, 2005 — PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development, and commercialization of small-molecule drugs targeting post-transcriptional control mechanisms, today named David P. Southwell to its Board of Directors.

"Mr. Southwell brings additional broad-based biopharmaceutical expertise to PTC's Board of Directors," stated Dr. Stuart Peltz, President and Chief Executive Officer of PTC Therapeutics. "In particular, his extensive financial knowledge, as it relates to life sciences, will be of great value as PTC enters new stages of growth. We are honored and delighted that he has decided to join PTC's Board of Directors."

Mr. Southwell has been Executive Vice President and Chief Financial Officer of Sepracor Inc., a research-based pharmaceutical company dedicated to the treatment and prevention of human disease, since June 1994. During Mr. Southwell's tenure, Sepracor and its subsidiaries have raised approximately $3.0 billion in three equity and nine convertible financings, and the Company's market capitalization has risen from $70 million to approximately $6 billion. Prior to joining Sepracor, Mr. Southwell was a Vice President in investment banking with Lehman Brothers in New York. His career at Lehman spanned 10 years, and included mergers, acquisitions, leveraged buyouts, restructurings, and debt and equity financing transactions. While at Lehman, he managed the IPO of Sepracor in September 1991.

"I am honored to join the distinguished Board of Directors at this dynamic company," said Mr. Southwell. "PTC's approach to small-molecule drug discovery addresses major, intractable disorders and the management team has laid an outstanding foundation for success. I look forward to working with PTC's Board and team to accomplish the goals that lie ahead."

Mr. Southwell holds a BA from Rice University and an MBA from the Tuck School at Dartmouth College. Mr. Southwell is Chairman of the Board of BioSphere Medical and serves on the Board of the MBA Advisory Board of the Tuck School.

Back to Top

PARENT PROJECT MUSCULAR DYSTROPHY ANNOUNCES SUCCESSFUL COMPLETION OF STAGE 1 OF DRUG DISCOVERY COLLABORATION WITH PTC THERAPEUTICS, INC.

(MIDDLETOWN, Ohio) — December 19, 2005 — Parent Project Muscular Dystrophy (PPMD) announced today that Stage 1 (Discovery) of its collaboration with PTC Therapeutics, Inc. (PTC), of South Plainfield, NJ, has been completed successfully. PPMD and PTC are collaborating to discover new drugs to treat Duchenne muscular dystrophy (DMD). The Discovery stage involved PTC investigating five different gene targets believed to be medically relevant in DMD, developing high-throughput screening assays, and screening each target against PTC's compound library.

Following the high-throughput screening effort, the specificity of selected molecules toward their targets was determined and the compounds were tested for their ability to modulate the expression of the corresponding target. The results from these initial characterization studies identified a subset of molecules with the desired biological activity and promising pharmacological properties. Based on these results, and with input from PPMD's scientific advisors, PTC has identified a set of lead compounds that will undergo lead optimization (Stage 2).

PTC utilized its proprietary drug discovery platform technology called GEMS (Gene Expression Modulation by Small-molecules) to search for new potential drugs for DMD patients. The GEMS technology allows PTC to identify small molecules that up- or down-regulate the production of proteins. The GEMS technology has proven to be very robust and capable of addressing difficult drug targets. PTC has a number of drug discovery programs that have validated the applicability of GEMS technology across multiple therapeutic areas.

"It has been an exciting opportunity for the PPMD to collaborate with PTC," said H. Lee Sweeney, Ph.D., Professor and Chairman of the Department of Physiology at the University of Pennsylvania School of Medicine and Scientific Advisor to PPMD. "PTC's GEMS technology offers a promising path to identifying new treatments for DMD."



PTC and PPMD are pleased to complete the first stage of the program. A fund-raising effort by PPMD is currently underway to finance lead optimization efforts. Lead optimization is an intensive chemistry effort focused on improving the efficacy, potency and pharmaceutical properties of the lead compounds to warrant further drug development.

"This collaboration is a result of our shared determination to identify new treatments for DMD," stated Stuart W. Peltz, President and CEO of PTC Therapeutics, Inc. "Our collaboration with PPMD provided the framework to deploy this technology in an effort focused on DMD, enlisting guidance from outstanding thought leaders in the neuromuscular area. The direct interaction with parents and patients is extremely gratifying to our team and we feel our goals are well aligned in this critical project."

PTC currently has a drug (PTC124) in Phase 2 clinical trials for the treatment of DMD patients who have the disease due to a specific type of mutation (nonsense mutations). It is estimated that approximately 15% of patients with DMD have the disease due to nonsense mutations. PTC's experience with PTC124 validates the Company's ability to advance promising new therapies into clinical studies and will provide important insight for the development of Project Catalyst's targets.

"The completion of Project Catalyst's Stage 1 represents incredible progress for Parent Project Muscular Dystrophy and for all young men with DMD and their families," stated Pat Furlong, Executive Director and Founder of Parent Project Muscular Dystrophy. "PTC's progress feels like a ray of sunshine in a place that once was dark. Each new discovery and each new measurable scientific result takes us a step closer to the day we can turn the tides on DMD forever."

About Project Catalyst

Project Catalyst is a first-of-its-kind research initiative designed to identify new drugs to treat this generation of young men with Duchenne muscular dystrophy (DMD). What drives this catalyst is the collaboration between Parent Project Muscular Dystrophy (PPMD), a national nonprofit organization leading the DMD community, and PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development, and commercialization of small-molecule drugs. Together, PPMD and PTC are moving DMD research to new levels — and giving hope for a long, independent future to all young men with DMD and their families. For more information on PPMD, please visit www.parentprojectmd.org or call Kimberly Galberaith, PPMD's Executive Vice President, at 201-944-9985.

For more information on PTC or the GEMS technology please visit www.ptcbio.com. For more information on the drug discovery and development process, please visit www.fda.gov.

Back to Top

PTC Therapeutics Initiates Phase 2 Study of PTC124 in Cystic Fibrosis

SOUTH PLAINFIELD, NJ — December 6, 2005 — PTC Therapeutics, Inc. (PTC), a biopharmaceutical company focused on the discovery, development, and commercialization of small-molecule drugs targeting post-transcriptional control mechanisms, today announced the initiation of a Phase 2 study of PTC124 in patients with cystic fibrosis (CF) due to a nonsense mutation. PTC124 is a novel, orally administered drug that targets nonsense mutations and is being investigated initially as a treatment for CF and Duchenne muscular dystrophy (DMD), with the potential to treat a number of other genetic disorders.

Langdon L. Miller, M.D., PTC's Chief Medical Officer, commented, "Through conduct of the Phase 2 trial, we intend to establish proof of principle for PTC124 by demonstrating production of full-length, functional cystic fibrosis transmembrane conductance regulator (CFTR) in patients with CF due to a nonsense mutation. We hope that the pharmacodynamic effects of PTC124 can eventually be translated into clinical benefit for CF patients with this life-threatening disease."

The Phase 2 clinical study is enrolling patients who have CF due to the presence of a nonsense mutation in the CFTR gene. The primary endpoint of this Phase 2 clinical study is assessment of nasal transepithelial potential difference (NPD or TEPD) as a measure of CFTR function in response to treatment with PTC124. Secondary assessments of the induction of CFTR cellular protein, pulmonary function, safety, pharmacokinetics, and compliance will also be performed.

"The initiation of Phase 2 is an important milestone in the development of PTC124 and a wonderful achievement for PTC and our multiple collaborators," stated Stuart W. Peltz, Ph.D., President and CEO of PTC. "PTC124 is a new type of treatment, aimed at the root cause of the disease, and the progress we have been able to achieve is due to the dedication and support of multiple researchers, investigators, clinicians, and patient advocacy groups."

"We are excited that this innovative therapy, that addresses the basic CF defect, has moved into the next stage of clinical trials," said Preston W. Campbell, III, M.D., Executive Vice President for Medical Affairs at the Cystic Fibrosis Foundation. "PTC has been a great partner every step of the way."

PTC has commenced recruitment for the Phase 2 study in CF at the University of Alabama, Birmingham (UAB), AL and the Denver Children's Hospital in Denver CO. Additional sites in the United States include the Johns Hopkins Hospital in Baltimore, MD; and the Rainbow Babies' and Children's Hospital in Cleveland, OH; More details regarding the design and conduct of this study is available at www.clinicaltrials.gov.

"We are thrilled to have begun the Phase 2 study of PTC124 in CF patients. It is particularly rewarding for us because Dr. David Bedwell and his team here at UAB were the first scientists to investigate the concept of readthrough of nonsense mutations as a potential treatment strategy for CF, and developed the preclinical data that support the PTC124 clinical research program in CF," commented JP Clancy, M.D., Director of Pediatric Pulmonary Medicine at UAB. "The protocol will be performed at four sites across the US, and there has already been quite a bit of interest expressed by patients from other CF centers about how they can participate. All of the centers are nearly ready to go, and we hope to have preliminary results to report in 2006."

PTC also has plans to initiate a separate CF study of PTC124 in Israel, where nonsense-mutation-mediated CF is particularly prevalent, and hopes to initiate a Phase 2 study of PTC124 in DMD within the fourth quarter of 2005.

Back to Top