Page 107 - Binder2

The answer isn’t scientific.
It’s structural.

We didn’t ignore tolerance because we didn’t understand it.
We ignored it because the system never demanded it.

For decades, drug development has been governed by a
singular metric: statistically significant short-term
efficacy. If a biologic can show a clear response at Week
12 or Week 24—a drop in inflammatory markers, a
reduction in lesion size, a validated score improvement—it
clears the bar. That’s the win. Regulatory approval secured.
Market access unlocked. Sales projections justified. Bonus
structures triggered.

Everything else—durability, tolerability, immune
integration—is treated as optional.
As “nice to have” if it fits the timeline, but never essential
to the launch strategy. In a regulatory climate where only
18% of biologics see approval why risk it?

Tolerization?
That’s a post-launch problem—something tucked into the
domain of pharmacovigilance, handled by safety teams
who file periodic reports and monitor adverse events long
after the press release has gone out. It’s not something that
derails a submission, delays an approval, or shakes investor
confidence. So it rarely rises to the level of strategic
concern during development.

ADA rates?
They’re measured, yes—but inconsistently, often using
non-standardized assays, and almost always framed to
reassure, not to warn. If they appear at all in the trial data,
they’re buried deep in the appendix—footnoted, de-
emphasized, statistically defanged. What matters to

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