Page 109 - Binder2

So the system moves fast. Launches hard. And waits to deal
with tolerization after the revenue curve has already
peaked.

This is not a flaw in the science.
It’s a flaw in what the system chooses to value.

And until immune durability becomes a metric that matters
before approval, not after, the cycle will continue: build,
launch, escalate, switch.
A business model built on biological failure.

Designing for tolerance means more complexity, more
uncertainty, and more time.
It’s not a tweak—it’s a redesign. A foundational shift in
how we think about the relationship between the drug and
the immune system from the first day of development, not
the last.

It means investing in preclinical models that don’t just ask,
does this drug bind the right target?—but also, will the
immune system learn to live with it? That means building
animal studies and in vitro assays that capture T cell
activation, ADA formation risk, mucosal exposure
dynamics, and early signs of immune rejection. These
aren’t industry standard today—not because they don’t
work, but because they aren’t required.

It means designing delivery platforms that mimic how the
body naturally encounters and accepts proteins: through the
gut, across mucosal tissues, or in repeated low-dose
exposures. That runs counter to the dominant model of
infrequent, high-concentration injections. Oral tolerance
strategies, mucosal immunization pathways, nanoparticle
carriers—these are tools that teach the immune system

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