ASK A DOC. Clinical Trial Update May 28, 2014. Welcome!

ASK A DOC Clinical Trial Update May 28, 2014 Welcome!

ASK A DOC CLINICAL TRIAL UPDATE Dr. Gregory Cosgrove PFF Chief Medical Officer Dr. Kevin Flaherty Chairman Steering Committee PFF CCN and PFF Registry Dr. David Lederer PFF Senior Medical Advisor

ASK A DOC Agenda Welcome and Introduction Pirfenidone Ascend Clinical Trial Results Nintedanib - INPULSIS 1 & 2 trials NAC (N-acetylcysteine) - PANTHER-IPF (Prednisone, Azathioprine, N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis) Questions and Answers (Q&A)

ASK A DOC There is optimism and hope for patients with idiopathic pulmonary fibrosis (IPF) following the release of data from the ASCEND (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis) and INPULSIS 1 & 2 trials at American Thoracic Society (ATS) International Conference. The phase III clinical trials for both pirfenidone (ASCEND) and nintedanib (INPULSIS 1 & 2) met their primary endpoints, demonstrated a slower decline in lung function when compared to placebo. Applications will be submitted by the pharmaceutical companies to the US FDA (US Food and Drug Administration) for review and approval for the treatment of patients with IPF. Results from the PANTHER-IPF (Prednisone, Azathioprine, N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis) suggested that N-acetylcysteine did not slow declining lung function in the overall study group, but additional investigation of this therapy may be considered.

ASK A DOC For patients, these results represent a significant degree of hope in treating patients with IPF and major steps forward in the pursuit of understanding the cause and identifying a cure for this devastating disease. We encourage each patient to discuss future treatment option(s) with their personal physician. The PFF will provide patients with regular updates on the status of the FDA review and approval for both products.

Pirfenidone ASCEND (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis) 2013 Pulmonary Fibrosis Foundation. All rights reserved. 6

PIRFENIDONE: BACKGROUND Pirfenidone is a small molecule that is thought to have both anti-inflammatory and anti-fibrotic properties Taken by mouth Some previous studies suggested that pirfenidone might slow progression of idiopathic pulmonary fibrosis (IPF) Pirfenidone is not approved by the FDA as therapy for IPF in the United States but is approved in other countries including Canada, Europe, Japan, India, and China

PIRFENIDONE: THE ASCEND TRIAL Phase 3 clinical trial of 555 adults with mild-to-moderate IPF Forced vital capacity (FVC) was 50 to 90% predicted Diffusing capacity (DLCO) was 30 to 90% predicted Half took 801mg of pirfenidone three times daily for one year. The other half took a "placebo" three times daily for one year.

PIRFENIDONE: THE ASCEND TRIAL RESULTS Decline in lung function was decreased Fewer patients had a decline in FVC of 10% or more 46 patients (16.5%) Pirfenidone vs 88 patients (31.8%) Placebo More patients had no decline in lung function 23% of patients in the pirfenidone group 10% of patients in the placebo group Fewer patients dropped walk distance by 50 meters 26% for pirfenidone 36% for placebo No Difference in shortness of breath

PIRFENIDONE SIDE EFFECTS Most common compared to placebo Nausea (36% pirfenidone vs 13% placebo) Rash (28% pirfenidone vs 9% placebo)

Nintedanib INPULSIS 1 & 2 trials 2013 Pulmonary Fibrosis Foundation. All rights reserved. 11

NINTEDANIB: BACKGROUND Nintedanib is a drug that blocks the effect of important proteins that tell the lung to make scar tissue Taken by mouth A small previous study suggested nintedanib might slow progression of idiopathic pulmonary fibrosis (IPF) Not an FDA approved therapy for pulmonary fibrosis

NINTEDANIB: THE INPULSIS TRIALS Phase 3 clinical trial of 1,066 adults with mild-to-moderate IPF Forced vital capacity (FVC) was at least 50% predicted Diffusing capacity (DLCO) was 30 to 80% predicted 60% took 150mg of nintedanib twice daily for one year. 40% took"placebo" twice daily for one year.

NINTEDANIB: THE INPULSIS TRIALS RESULTS Slower decline in lung function on Nintedanib INPULSIS 1 FVC decline was 125 ml/year slower INPULSIS 2 FVC decline was 93.7 ml/year slower Longer time until acute worsening (exacerbations) in INPULSIS 1 but not INPULSIS 2

NINTEDANIB SIDE EFFECTS Most common compared to placebo Diarrhea (~60%% Nintedanib vs ~20% placebo) Nausea (~25% Nintedanib vs ~6% placebo) Vomiting (~11% Nintedanib vs ~2% placebo)

NAC (N-acetylcysteine) PANTHER-IPF (Prednisone, Azathioprine, N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis) 2013 Pulmonary Fibrosis Foundation. All rights reserved. 16

NAC: BACKGROUND NAC is an anti-oxidant NAC has been used to treat a wide variety of medical conditions, including Tylenol R overdose and chronic obstructive pulmonary disease. NAC has also been used in the past to treat Oxidative stress (the bad thing that anti-oxidants help treat) may contribute to the development of IPF A previous study suggested NAC slowed progression of IPF

NAC: THE PANTHER-IPF TRIAL Clinical trial of adults with mild-to-moderate IPF Forced vital capacity (FVC) was 50% predicted or greater Diffusing capacity (DLCO) was 30% predicted or greater Three treatment options NAC Placebo Triple therapy = NAC + prednisone + azathioprine The triple therapy option was stopped in 2012 because it was causing harm

NAC: THE PANTHER-IPF TRIAL No meaningful effect on the following: The risk of death Disease progression Lung function tests Breathlessness NAC did seem to prevent worsening of mental well being, but it isn't clear exactly what this means for people with IPF.

Q&A Dr. Gregory Cosgrove Dr. David Lederer Dr. Kevin Flaherty

QUESTIONS Treatment Related to Disease Stages Can these drugs be used as a preventative for high-risk people e.g. those related to people afflicted with IPF? I am 88 - recently diagnosed -would I be eligible for this treatment? How advanced does your IPF have to be to participate in a trial study??? Will patients with less than 50% FVC be allowed to try either of the treatments? Do you think this new drug would be helpful to someone who has passed the "early" stage of pulmonary fibrosis? Am I correct in understanding this is not an effective treatment for an IPF patient in a later stage of the disease?

QUESTIONS Impact of Findings on Other Forms of PF What impact does these new findings have on those of us who are chp patients? I have PF, but it is not idiopathic. It was apparently caused by vasculitis. Will these drugs be of any benefit to me? Are there any clinical trials in process for fibrotic NSIP? If a patient is currently in a clinical trial are they allowed to be in other studies?

QUESTIONS PIRFENIDONE Please discuss the InterMune EAP What options does a patient have if they are deemed ineligible to participate in the EAP? When will we get FULL access to pirfenidone? Is Pirfenidone of help to those with advanced PF? What must a patient do to be included in the Expanded Access Program?

QUESTIONS AVAILABILITY/FDA APPROVAL Where/when can I get Pirfenidone or Nintedanib? Now that we have these findings, what is a realistic date for approval by the FDA and for the medications to be on the market? When might we expect FDA approval? How long do they think it would take to get through FDA? Is there hope that these drugs will help us diagnosed now? How long will it take for Health Insurance companies to approve and pay for pirfenidone, once approved by FDA?

PIRFENIDONE: EXPANDED ACCESS PROGRAM (EAP) Inclusion Criteria Must have IPF FVC 50% or greater, DLCO 30% or greater Exclusion Criteria Receiving other experimental treatment Smoking within 3 months or unwilling to not use tobacco throughout the program Pregnancy or lactation More informa+on available at www.clinicaltrials.gov NCT 02141087

QUESTIONS Lung Transplantation and Trial Participation Do any of the medication trials allow patients to be currently on the transplant list? Is Transplant the only "cure?

QUESTIONS How will these results be communicated to medical doctors and others?

ADDITIONAL QUESTIONS

Thank you.