The Unplanned Work

The people building cell and gene therapy programs are some of the most determined, mission-driven professionals I have encountered in more than two decades in this industry.

They do not cut corners. They do not lack discipline. They work with a commitment to patients that most industries never come close to.

Which is exactly why this conversation matters.

The most consequential gap I see in these programs is not scientific. It is not regulatory. It is not even manufacturing.

It is the budget that was built for a world where everything goes according to plan.

That world does not exist. And in cell and gene therapy, where the science is truly novel, the manufacturing is genuinely complex, and the regulatory pathway is constantly evolving, the distance between the budget and reality is wider than in almost any other area of medicine.

This is not a failure of the people. It is a failure of the planning system around them. And it is completely fixable.

The programs I have watched struggle most are not the ones with weak science. They are the ones where the budget was built for the best case and the team was left to navigate everything else without the resources to do it. The science held.

The money did not.

And when the money does not hold in a novel therapeutic program, the consequences are not just financial. They are scientific, regulatory, and human.

Capital in CGT is now organized around first in human data, and the budgets being built to get there are still sized for a journey that rarely exists.

Investors are no longer organizing funding around IND filing as the primary milestone. First in human data is the proof point that moves markets, attracts partners, and justifies the next round. That shift is real and it is right.

But here is what I see repeatedly. A company raises a Series A or B specifically sized to reach First In Human. The model is built, the assumptions are reasonable, the timeline is defensible. The board approves it. The team executes against it with genuine discipline and competence.

And then reality arrives.

An unplanned, but necessary, manufacturing change adds three months and several hundred thousand dollars that were not in the plan. A regulatory question about comparability of the drug product requires additional analytical work. A patient in the first cohort experiences an adverse event that triggers a clinical hold. A key scientific hire takes six months longer than the model assumed.

None of these are catastrophic individually. Each one is the kind of thing that happens in novel programs.

Together they consume the buffer that was never really there.

And when the buffer is gone the choices become very difficult very quickly. Do you slow the program, go back to investors earlier than planned, or make decisions about the science that are driven by the capital position rather than by what the data actually requires.

Those are not the decisions anyone built the company to make.

The assumption that process development can wait is one of the most expensive assumptions in this industry.

The old model was file the IND, run Phase I, think about scale up at Phase II or Phase III.

That model is over.

Competition in CGT is present and accelerating. In any given indication there are now multiple programs competing for the same patients, the same partners, and the same commercial position. Discovering at Phase III that your manufacturing process cannot reliably produce at the volume, cost, and consistency that commercial scale requires is not a setback.

It is a program-ending event.

Scale up readiness is not a manufacturing question. It is a commercialization systems question.

It requires investment in process development, analytical methods, and manufacturing platform decisions that have long lead times and significant cost. Investment that needs to be planned for and funded before the first in human trial begins, not after it succeeds.

The companies that are winning in this space are making those investments now. Their budgets reflect that understanding even when it makes the near-term capital ask harder to justify.

In tools and technology, funding the science without funding the commercial build produces one outcome — curiosity without commitment.

The tools and technology companies serving CGT right now are building genuinely extraordinary things. Platforms that automate what used to take teams of people. Analytics that surface insights no human could find in the data alone. Technologies that make the manufacturing of complex therapies more reliable, more scalable, and more accessible.

The science and engineering in this space deserves to win.

But winning requires more than having the best platform. When a tools or technology company funds the engineering comprehensively and treats commercial infrastructure as an afterthought, customers will engage. They will run evaluations. They will generate data. They will say genuinely positive things about the technology.

And then they will not buy it at scale.

The phrase I hear most often in this situation is: sure, I will try it.

That is not traction. It is curiosity.

The gap between I will try it and I will buy it is not a product gap. In most cases the technology is genuinely differentiated.

It is a commercial infrastructure gap.

Nobody built the systems to educate the market, to turn a trial into a committed integration, to give a procurement committee the confidence to standardize on a new tool in a regulated environment.

Those systems require budget. Deliberate, planned, early budget.

The companies achieving real commercial traction in the CGT tools space are not the ones with the best technology alone.

They are the ones that funded the commercial build at the same time they funded the science.

Buffer is not fat. It is what sustains.

There is a moment in almost every budget conversation where someone looks at the contingency line and asks whether it is really necessary.

That moment is where programs are won and lost.

Buffer is not inefficiency. It is not evidence that the team lacks confidence in their own plan.

It is the only intellectually honest acknowledgment that you are doing something genuinely novel.

Something where surprises are not a sign of failure but a sign that you are at the frontier of what is known and possible.

The programs that navigate the unplanned work and come out the other side are not the ones that avoided surprises.

They are the ones that had the resources to absorb them.

Without compromising the science. Without making decisions driven by the capital position rather than the data. Without losing the time they cannot get back.

That requires a different conversation between founders and investors than the one most people are having. Founders need to be honest about what the journey actually costs when things go wrong. Investors need to understand that the contingency line is not evidence of weakness in the plan.

It is evidence of strength in the thinking.

The budget that was never real is built in every room where the pressure to make the number work overcame the honesty about what the work actually requires.

That is the conversation this industry is ready to have.

I have watched it happen at companies that made the decision early enough — founders and investors who chose honesty over optimism in the budget room and came out the other side with programs intact, timelines protected, and science that reached patients.

The budget that was never real does not have to be the story.

The budget built for reality, for first in human in a world where not everything goes to plan, for scale up readiness that does not wait for Phase III, for commercial infrastructure that turns curiosity into commitment — that budget exists.

It just requires the courage to ask for it and the discipline to defend it.

Buffer is not fat. It is what sustains. And the programs that understand that are the ones that make it.

Susan Nichols is Managing Director and CEO of Propel Biosciences. With more than two decades spanning diagnostics and cell and gene therapy, as a drug developer, as a CEO, as a Chief Commercial Officer, and as a Chief Business Officer in the CGT industry, she has sat on every side of this table. She works across both industries because the commercialization challenges in each inform the other.