Most biotech programmes don’t fail because the science is weak; they fail because the strategy isn’t built early enough. But turning that science into a therapy that reaches patients is a different kind of challenge, one that requires decisions across CMC, non-clinical, clinical strategy, and stakeholder alignment. And those decisions happen much earlier than many teams expect.
In a recent X4 Talks episode, our VP Regulatory & Development Bruno Speder shared a view we strongly recognise at Aletheia: regulatory should be a driver of development, especially in the earliest stages rather than a late-stage.
“The counterintuitive truth: early development is where the irreversible decisions happen.”
It can feel counterintuitive to invest in regulatory leadership early. Many teams associate regulatory with marketing authorisation, late-phase trials, and post-approval maintenance. Bruno challenges that logic: the early stage is where the most fundamental program decisions are made. And for early companies, often operating under tight funding, aggressive milestones, and investor pressure, those decisions carry disproportionate risk.
Some choices are reversible. You can “walk back through the revolving door,” adjust, learn, and iterate. But other choices are fundamental: they shape the product, the development pathway, and the credibility of your story for years.
The three pillars: CMC, non-clinical, and clinical must move together
Bruno frames early development around three big pillars:
1. Non-clinical development (beyond efficacy): safety toxicology choices matter
Many academic spinouts start with a compelling non-clinical efficacy package, that’s often why the company exists in the first place. The next step is safety tox. And here, strategy matters:
- What’s required for your indication and modality?
- What can run in parallel later?
- Where can you leverage existing knowledge (e.g., for “me-too” approaches) instead of repeating a full program as if it were first-in-class?
These are not shortcuts, they’re risk-managed decisions that benefit from early regulator dialogue.
2. CMC: the overlooked bottleneck that can make or break your program
In early research, you may have milligrams or grams made on a lab bench. Clinical development changes that game entirely: formulation, scale-up, first GMP batch, process development, assay development, suddenly you are building a product that must be reproducible and defensible.
Small early choices can become “locked in". For example, selecting an excipient because of solubility issues can influence the entire downstream CMC strategy. In other words: if you build your foundations poorly, you will pay for it later, often when you can least afford it.
3. The first clinical trial: your development blueprint
Bruno highlights a common underestimation: the first-in-human study is not just a checkbox. It is often the basis of your development strategy.
- For small molecules, robust PK characterisation is crucial. Half-life and exposure inform dosing schedules and later modelling/simulation work.
- For vaccines, early design choices matter: which population do you include? Do you add an elderly cohort for an older-target population? Do you include an arm with an existing vaccine for benchmarking, especially when you lack a correlate of protection and need investor-relevant comparisons?
Regulatory input here isn’t about “compliance.” It’s about designing trials that generate the right evidence for the next scientific and business milestone.
Why science alone isn’t enough
Bruno’s message is direct: without science, you don’t have a product, but science alone doesn’t guarantee success.
You can have a scientifically brilliant therapy that fails because:
- It can’t be manufactured at scale,
- It’s too complex to administer,
- Its real-world logistics make adoption unrealistic.
Drug development must produce something clinicians can use in practice. The best programs build early awareness of feasibility, usability, and supply realities alongside scientific validation.
A real-world lesson: human challenge trials and regulatory as enabler
Bruno also reflects on a particularly novel setting: human challenge trials, where volunteers are deliberately infected in a controlled environment to test vaccines or antivirals (e.g., influenza, RSV, malaria, COVID). During the pandemic (second half of 2020 into early 2021), Bruno served as regulatory lead for the first COVID challenge trial approved and performed in the UK. His key takeaway: success required deep collaboration: academics, taskforce stakeholders, regulators (MHRA), and ethics committees working tightly together. Crucially, regulatory also played a role in enabling ethical recruitment: ensuring the right tools and boundaries were in place to recruit volunteers responsibly and transparently.
Recruitment and informed consent: where regulatory meets human reality
Trial recruitment is a universal bottleneck. Without participants, there is no trial. Bruno argues that regulatory leadership doesn’t stop at approvals. It includes ensuring sites and teams have what they need to recruit within ethical and regulatory boundaries, such as fair compensation for healthy volunteers. He also stresses the importance of patient-centred informed consent, especially for advanced therapies like cell and gene therapy, where participation may imply years of follow-up and a life-changing commitment. Informed consent should not be treated as a dry template, it must accurately communicate risks, benefits, and burden so patients and families can make truly informed decisions.
Final message: embrace the reality of drug development
Bruno closes with a line that captures the lived truth of the industry:
“In drug development, things go often wrong. What matters is solving the problem and learning from it.”
Early-stage teams win by building systems and leadership that absorbs surprises, interpret ambiguous data, and turn setbacks into learning. Because tomorrow is always another day and the teams that keep moving, thoughtfully, are the ones that reach the clinic and beyond.
