Page 111 - Binder2

This is not a scientific blind spot.
It’s a business calculation.

And until the structures change—until regulators start
prioritizing immune durability, until payers reward
therapies that last, and until investors understand the
cost of tolerization as a margin killer—biologic
developers will continue to treat immune tolerance as an
academic curiosity, not a design mandate.

The irony is: we have the science.
We’ve had it for years.
We know how the immune system learns. We know how to
build drugs it might accept.
But in a system built for quarterly milestones and launch
metrics, long-term solutions don’t just struggle to
succeed—they struggle to even get started.

And that’s the cost of treating tolerance as a luxury, rather
than a prerequisite for permanence.

It adds time. It adds clinical uncertainty. It creates hurdles
in a system that already penalizes delay and risk.

Worse, there’s no clear mechanism to recoup those
investments. Payers don’t reimburse extra for durability.
Regulators don’t require long-term tolerance data. Investors
don’t reward it in early funding rounds. And the market
doesn’t punish failure until it’s too late—when patients
cycle off the drug, and the company is already marketing
the next one.

This is why immune rejection is rarely discussed in
preclinical meetings. Why ADA rates are buried deep in
trial appendices. Why delivery platforms that activate oral
tolerance are seen as exotic, rather than essential.

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