Page 93 - Binder2

dynamic, learning environment of the human immune
system.

We focused on what the drug could do to the body. We
never asked what the body would do to the drug.

Tolerization wasn’t unknown. Immunogenicity wasn’t a
secret. Scientists raised the alarm early, especially with
chimeric antibodies and early fusion constructs. But the
system had no mechanism for responding. There were no
regulatory benchmarks for long-term immune harmony. No
commercial incentives to redesign drugs that passed trials.
No clinical mandates to test for anti-drug antibodies before
switching therapies. The warning lights were there. We just
learned to ignore them.

And so, tolerization became normalized—not through
evidence, but through systemic omission.
It became routine to switch therapies after a year or two.
It became expected that efficacy would wane.
It became acceptable to escalate doses and add
immunosuppressants when biologics faltered.

And all the while, the core issue—the loss of immune
compatibility—went unnamed.

This is what we overlooked: not a scientific fact, but a
design principle.

We never built biologics to be welcomed by the immune
system.
We built them to perform, not to persist.

That decision—intentional or not—now defines the
limitations of an entire class of drugs.

91