Emerging biotechs applying today’s revolutionary technologies face two interrelated questions: which indications to develop first and when to seek partnerships for program development. Leading platforms appear to offer seemingly endless possibilities for therapeutic applications. However, today’s development landscape largely consists of many competitors circling relatively few high-value therapeutic targets. Understandably, the highest concentrations of development have historically been in areas where patient numbers are high and unmet need is large or where the technology first established proof-of-concept. As the first therapeutics move through development, the new question is where to go next. The answer depends on a variety of factors, including the technical feasibility of the platform, the internal appetite for development risk, the potential commercial opportunity of the therapeutic, and the strategic fit for the company. The path also depends on whether company leadership and investors are committed to independence vs. navigating the partnering landscape. A large partner endorsement may bring important validation and the funding necessary to move quickly, but it comes at the cost of sharing the innovative platform’s value.