Megan Pane¹, Curtis Johnston¹*, Rena Eudy-Byrne¹, Tyler Dunlap¹, Nikolas Onufrak²*, Sonja Hartmann²*, Steve Choy²
¹Metrum Research Group, Boston, MA, U.S.A., ²Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, U.S.A.
(*Affiliation during time of analysis)

Mechanism of Action
• Nerandomilast (JASCAYD®) is an orally administered, preferential inhibitor of the
phosphodiesterase-4B (PDE4B) isoenzyme
• PDE4B hydrolyzes and inactivates cyclic adenosine monophosphate
Therapeutic Indication
• Approved by the U.S. FDA and China’s CDE for the treatment of idiopathic pul-
monary fibrosis (IPF) and progressive pulmonary fibrosis (PPF)
• IPF is a specific type of interstitial lung disease (ILD) and PPF is associated with a
subset of ILDs distinct from IPF
• Both IPF and PPF lead to lung scarring that progresses over time, with a median
survival time of 3-5 years
Chemical and Metabolic Properties
• Nerandomilast (R-enantiomer) contains a chiral sulfoxide group and undergoes a
minor level of metabolic chiral inversion following oral administration
• The resulting S-enantiomer is pharmacologically inactive
• Both nerandomilast and the S-enantiomer were characterized in this analysis

Presented at the ASCPT 2026 Annual Meeting. An exposure-response model was developed to evaluate the effect of nerandomilast on forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) , capturing both an initial “offset effect” and a long-term “disease-modifying effect” on the rate of FVC decline. The analysis confirmed a positive exposure-response relationship that is maintained regardless of the underlying diagnosis. Furthermore, simulations support using an 18 mg twice-daily dose to mitigate the reduced drug exposure associated with background pirfenidone use, ensuring a robust treatment response for patients on multi-drug regimens.

Simulated efficacy of nerandomilast on forced vital capacity decline in idiopathic pulmonary fibrosis and progressive pulmonary fibrosis across background antifibrotic therapies Samuel P. Callisto1, Kyle Baron1, Elias Clark1, Curtis Johnston1∗, Nikolas Onufrak2∗, Sonja Hartmann2∗, Steve Choy2 1Metrum Research Group, Boston, MA, U.S.A., 2Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, U.S.A. ∗Affiliation during time of analysis Introduction.   

Leveraging a sophisticated Bayesian framework and latent variable models, this research compared treatment effects against placebos, setting a new benchmark for assessing efficacy in SLE treatments. This novel MBMA not only benchmarks the efficacy of these compounds but also showcases the application of latent variable models in understanding chronic disease trajectories.

Presented at ACoP14. The objective of this work is to integrate multiple PD clinical studies, harmonize the data, and deploy a user interface for rapid data interrogation and analysis subset generation.

Katherine Kay, Justin Goodwin, Hanna Ehrlich, Joyce Ou, Tracey Freeman, Kaicheng Wang, Fangyong Li, Martina Wade, Jonathan French, Liusheng Huang, Francesca Aweeka, Norah Mwebaza, Richard Kajubi, Matthew Riggs, Ana Ruiz-Garcia, Sunil Parikh. Clin Pharmacol Ther. Published online October 19, 2022. doi:10.1111/cpt.2768

Janelle L. Lennie, John T. Mondick, Marc R. Gastonguay. PLoS One. 2022 Apr 28;17(4):e0247286. doi: 10.1371/journal.pone.0247286.

Kevin J. Downes, Austyn Grim, Laura Shanley, Ronald C. Rubenstein, Athena F. Zuppa, Marc R. Gastonguay. Antimicrob Agents Chemother. 2022;66(5):e0237721.

Yin O, Zahir H, French J, Polhamus D, Wang X, Van de Sande M, Tap WD, Gelderblom H, Wagner AJ, Healey JH, Greenberg J, Shuster D, Stacchiotti S. CPT: Pharmacometrics & Systems Pharmacology. 2021; 10: 1422– 1432. doi:10.1002/psp4.12712

Lennie, J.L., Mondick, J.T. & Gastonguay, M.R. Latent process model of the 6-minute walk test in Duchenne muscular dystrophy. J Pharmacokinet Pharmacodyn (2020).

Ophelia Yin, Jonathan French, Daniel Polhamus, Hamim Zahir, Michiel van de Sande, William D. Tap, Hans Gelderblom, Andrew J. Wagner, Jon Greenberg, Dale Shuster, Silvia Stacchiotti

Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 23 October 2019.

Hajjar J. Poster presented at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018. Abstract #T-011.

Hajjar J. Poster presented at 2018 Annual Meeting of the American College of Clinical Pharmacology. Bethesda, MD. 23 Sep 2018.

Troy S, Wasilewski M, Godfrey CJ. Poster presented at the 14th Annual WORLDSymposium. San Diego, CA. 5-9 February 2018.

Hajjar J, French JL, Gastonguay MR.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Hajjar J, Fisher J, Gastonguay MR.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

Rogers JA, Tortorici MA, Viti O, Brexon M, Sandhaus RA, Burdon J, Piitulainen E, Seersholm N, Stocks J, McElvaney NG, Chapman KR, Edelman JM.  Presented at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, San Diego, CA, March 2016.

Hajjar J, Fisher J, Gastonguay MR.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA; October 2015.

Gastonguay MR and Godfrey CJ.  American College of Clinical Pharmacology (ACCP) Workshop, September 26, 2015.

Mascarenhas MR, Mondick J, Barrett JS, Wilson M, Stallings VA, Schall JI.  The Journal of Clinical Pharmacology, 55: 854–865. doi:10.1002/jcph.484