Please tell us about your clinical practice, background in treating IPF and research in the space. How many patients do you treat, and what is the first line of choice?

Fibrogen is currently enrolling 565 patients in P3 Zephyrus trial, where the primary endpoint is change in forced vital capacity (FVC) from baseline. How relevant is this data point, and what drugs compete well in FVC change?

In Fibrogen’s Phase 2 trial of 103 patients, quantitative lung fibrosis volume was 24.8 ml for pamrevlumab-treated patients versus 86.4 ml for the placebo group at week 24, and after 48 weeks, pamrevlumab-treated patients reached a volume of 75.4 ml, vs placebo-treated patients volume of 151.5 ml. How significant of a change is it, and how does it compare to what you’re using?

Galapagos is enrolling 1500 patients in its Phase 3 trial, of which changes in disease progression, frequency of respiratory-related hospitalizations, quality of life, and mortality are the secondary endpoints. Which of those would you be most interested in seeing data points and why?

In Galapagos’ Phase 2 Flora trial, patients taking GLPG1690 had an increase of 8 mL in FVC), while those on placebo showed a reduction of 87 mL, after 12 weeks. How does it compare to Pamrevlumab’s P2 data?

Which of the 3 upcoming therapies are you most excited about and why? How much of a need is there for them?

Promedior and BMS PRM-151 (pentraxin 2 protein)received FDA breakthrough designation in March 2019. While FVC results are in line with current and pipeline agents (Fibrogen/GLPG), PRM-151 has a 6 minute walk benefit.
 
1. What are your thoughts on the 6 minute walk as a new IPF endpoint either as co-primary with FVC or as a secondary

2. How meaningful is the PRM-151 6 minute walk results? 

Toby Maher said that he believes combinations will be the key to efficacy in IPF. What are your views on the future IPF paradigm? What role will combinations play? - especially MOAs with non-overlapping components. Do you feel that inhaled combinations like those in COPD (triple inhalers) may some day be the future of IPF? 

Current IPF drugs are oral and given systemically. They have known tolerability issues that lead to patient discontinuations and/or dose reductions.  Avalyn Pharma is developing nebulized Pirfenidone. Shionogi is developing dry power pirfenidone. What are your thoughts on inhalation as a route of drug admin in IPF? Inhaled drugs typically allow for high drug concentration with lower systemic exposure leading to the ability to maximize efficacy while increasing the therapeutic window for safety. What are your thoughts on inhalation? How does it compare to oral, vs IV in IPF?

With regards to inhalation as a delivery method. What your thoughts on dry powder (Shionogi for Pirfenidone) vs. Avalyn Pharma (Modern day hand held nebulizer)? DPI need negative pressure, can cause significant cough initially and is technique sensitive while nebulizers allow patients to breath normally. Is one likely better for patients given that IPF patients are older and have diminished lung fuction?

With regards to route of delivery, do you see any major hurdle for an inhaled drug vs an oral drug vs IV or SubC injection from other IPF physcians and from patient adopting it? Inhaled is very common for COPD. 

How much read-thru do the BMS-986020 results offer to GLPG-1690? Mechanistically how different are the two?
https://www.ncbi.nlm.nih.gov/pubmed/30201408

Fibrogen's pamrevlumab is an IV infusion. This means it will be a Medical Benefit and likely reimbursed by Medicare for most IPF patients under buy-and-bill. Are there other IV drugs that IPF specialist (pulmonologist) typically use? How comfortable would most IPF specialist be with buy and bill reimbursement where they will take the risk in drug procurement? 

Current IPF drugs and many emerging targets are also oncology targets -  pamrevlumab  is in Phase 3 for pancreatic cancer, Ofev is a non small cell lung cancer drug in Europe, Pirfenidone is a failed oncology drug and PRM-151 has positive proof-of-concept in Myelofibrosis. What are your thoughts on this trend? Other potential IPF targets that are in oncology in TAM receptor kinases, HDACs, PD1, CD47, and Bromodomain inhibitors. Any thoughts on those targets?  

Biogen's BG00011 is an integrin inhibitor. How will it differentiate to other drugs with the same MOA such as Pliant Therapeutics or GSK's 3008348, an integrin alpha V beta 6 antagonist that is inhaled (nebulized)?

Would you rather see a drug that is an add-on to current SoC (pirfenidone / nintedanib) or one that shows significant monotherapy results (Better efficacy in FVC and better tolerability) head-to-head vs them? 

What percentage of your patients have pulmonary hypertension? Do you treat this co-morbidity? For Pulmonary hypertension WHO group 3 that is associated with ILD and or inflammation like COPD or hypoxia, is this treated by pulmonologists or cardiologists?  

How come no company is actively pursuing moderate-to-severe IPF? What is your definition of this patient segment? What percent of patients would you say are moderate-to-severe IPF at diagnosis? Does current IPF SoC less effective in more advanced patients? How would you compare the unmet need in moderate-to-severe IPF vs Mild-Moderate IPF?

What are your thoughts on Cedars Sinai IPF research group led by Dr. Paul Noble and Cory Hogaboam?

Does the trial design of GLPG1690/Biogen (with/without background therapy) vs. Fibrogen's monotherapy impact how you would use those therapies in practice (if all are approved)?

How eager are patients to enroll in the three programs?  Is one more likely to enroll more rapidly than the others? Why?

Galapagos reported data using FRI by Fluida
https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-018-0918-5
which they claim shows disease progression earlier than FVC because effects in lower lobes can be detected before impact is made on FVC.  The paper above actually is with Fibrogen data.   If you are familiar, what are you thoughts on the technology particularly how it may pertain to ability to predict clinical success based on what Galapagos has seen with their 12 week study?

Berenberg Capital Markets recently had a report on Galapagos.  In it they indicate SPIRIT (BG00011/STX-100) was recently halted.  They said Galapagos confirmed this to them as well.  Any insights as to what may be the reason and what future prospects are?