Insmed's recent earnings call (NASDAQ:INSM) was a whirlwind of positive news, dominated by the upcoming brensocatib ASPEN trial results and the promise of a potential $5 billion market. But while everyone is fixated on brensocatib, a subtle detail in the TPIP data might be revealing a hidden gem, a potential blockbuster quietly building momentum beneath the surface.

Wall Street seems largely focused on brensocatib, viewing TPIP with a "show me" skepticism. However, the subtle clues in the blinded PAH data suggest that this skepticism might be misplaced. The observed 21.5% average reduction in PVR, even when including placebo patients, is impressive. But the real kicker lies in the responders: those whose PVR decreased experienced an average reduction of 47%, with several nearing the normal PVR range.

Insmed views a 30% PVR reduction as a clear best-in-class result when the PAH data is fully unblinded. This benchmark is rooted in the performance of sotatercept, a drug acquired after Phase 2 for its impressive 33.4% PVR reduction. Comparing this to TPIP's blinded 47% average reduction in responders paints a picture of a drug potentially exceeding expectations, even if this number moderates upon unblinding.

The potential for exceeding the 30% PVR reduction target is further bolstered by the proposed protocol amendment allowing for dose escalation in the PAH open-label extension. The current maximum dose of 640 micrograms could be doubled to 1,280 micrograms, potentially unlocking further clinical benefit. The fact that over 90% of PAH trial participants opted to continue into the open-label extension speaks volumes about their experience with TPIP and their willingness to explore higher doses.

The PH-ILD data, while focused on safety, also offers encouraging hints. Over 80% of patients reached the maximum 640 microgram dose, a remarkable achievement given the short five-week titration period and the severity of PH-ILD. This suggests not only impressive tolerability but also the potential for achieving the "more is better" principle that drives prostanoid efficacy.

TPIP Peak Sales Potential Breakdown (Hypothetical)

Insmed estimates TPIP's peak sales potential at $2 billion, split between PAH and PH-ILD. The following table provides a hypothetical 50/50 split for simplicity, with each indication targeting a $1 billion peak.

Considering the market dynamics, these numbers seem achievable, if not conservative. The PAH market is competitive, but the potential for TPIP to demonstrate best-in-class efficacy with once-daily dosing could translate into significant market share. Similarly, the PH-ILD market is ripe for disruption, with Tyvaso currently holding a dominant position. TPIP's potential for a superior safety and tolerability profile could entice both physicians and patients seeking a more convenient and manageable treatment option.

TPIP Tolerability in PAH Trials

The chart below illustrates the encouraging tolerability of TPIP in the ongoing Phase 2 PAH trial, with a high percentage of patients successfully reaching the maximum dose of 640 micrograms.

Here's where the hidden gem analogy comes in. While brensocatib shines brightly on center stage, TPIP is like a valuable gem tucked away in a treasure chest, waiting to be discovered. As the year unfolds and the full TPIP data emerges, Wall Street might find itself surprised by the magnitude of this opportunity, realizing they've been overlooking a potential blockbuster in the making.

"Fun Fact: Insmed's name is a combination of "inspired medicine," reflecting their dedication to developing therapies for patients with serious and rare diseases. Perhaps this hidden gem in the TPIP data is a testament to this inspiration, paving the way for a treatment that could significantly improve the lives of patients with PAH and PH-ILD."