Choosing your lead clinical indication

In his recent blog on LinkedIn, Prabhu Velusami outlined crucial points for start-ups choosing their lead indication. This decision affects the feasibility of establishing proof-of-concept and determines which stakeholders, like VCs and pharma companies, may invest or partner.

In his role as Senior Director for Search and Evaluation EMEA, Prabhu identifies and evaluates early-stage pharmaceutical innovations aligned with J&J's strategic areas of interest. He is a former ophthalmic surgeon and previously served as Associate Director at Boston Consulting Group, specialising in life sciences and digital analytics.

"Making choices is hard... At J&J, I've had hundreds of conversations about first clinical indications.

And I've learned that choosing one is among the most consequential decisions an early company makes.

It shapes your development plan. Your trial design. Your fundraising story. And which partners will even consider engaging.

It also determines how quickly you can generate the kind of data that builds real conviction.

Across those conversations, a pattern repeats.

Some indication choices are intentionally designed. Others are driven largely by where the founding lab happens to sit.

Over time, I've found myself coming back to the same five questions.

1. Where is the unmet need still genuinely high?

   Unmet need isn't the same as a large market. It's where patients still lack effective options. If strong therapies already exist and your proposal is a modest incremental improvement, it becomes much harder to justify the risk. Starting with unmet need anchors everything in patient impact.

2. Is there a believable biological reason your mechanism should work here?

   This is where genetic validation and mechanistic clarity matter. Is the target relevant in this disease? Do the models tell a coherent story? Are you building on what's known, or contradicting it without a clear rationale?

   You can absolutely pursue novel biology. But partners need to see a clear line from mechanism to indication.

3. How actionable is the science today?

   Some indications are scientifically compelling but practically difficult. You may need biomarkers that don't yet exist, tools that aren't widely available, or trial designs regulators are still debating. Others allow for a clean, interpretable early study. Complexity is fine, unrealistic assumptions aren't.

4. How commercially meaningful is the space?

   Biology matters. But commercial reality matters too. This is why many teams demonstrate proof of biology in a smaller, tractable indication first, then expand once the mechanism is de-risked.

5. Is it feasible to recruit in this population?

   Even when everything else aligns, feasibility can derail a plan. Competing trials, slow recruitment, or lack of experienced centres can force painful pivots later. I've seen companies change course entirely for this reason alone.

These questions won't guarantee the "right" answer, drug development never does.

But they create a structured way to balance science, unmet need, feasibility and partnership potential.

If you're choosing (or revisiting) your first indication, which of these questions is weighing most heavily right now?"

As you explore these themes, it's essential to think about how feasible it is to generate the necessary data to demonstrate clinical proof-of-concept. If you're interested in understanding which types of data are required, this visual on data presentationcould be useful.