Voyager CEO Al Sandrock outlines a focused strategy: remain specialists in neurology, but broaden the therapeutic modalities (gene therapy, proteins, oligonucleotides). This allows them to pursue well-validated CNS targets that are considered "undruggable" by traditional small molecules, which have historically been the only option for crossing the blood-brain barrier.

Serenatus Bio is developing a novel COMT inhibitor based on Tolcapone, an old drug that showed efficacy in OCD but had severe liver toxicity. This strategy uses a flawed predecessor's clinical signal as proof-of-concept, de-risking the biological hypothesis while focusing innovation on solving the safety issues.

Moonwalk's fundraising strategy uses its $70M Series B to achieve clinical proof-of-principle for at least two, and possibly three, different programs. This "multiple shots on goal" approach significantly de-risks the company by creating a pipeline rather than betting everything on a single lead asset, generating more value for the next financing round.

Despite having three assets, Zura Bio's strategy is to be ruthless with capital allocation. The primary focus—development dollars, time, and team attention—is overwhelmingly on its lead program. This demonstrates that a portfolio approach still demands singular, disciplined focus on the most promising asset to succeed.

Many biotechs start with a single technology to solve a single problem. Dispatch Bio's co-founders believed a superior company could be created with a suite of technologies that addresses numerous field observations at once, creating a more robust therapeutic platform.

Neurocrine mitigates the high risk of its late-stage psychiatry programs, which have uncertain outcomes until Phase 3, by investing in an obesity asset. This program offers the ability to see clear efficacy signals in early Phase 1B trials, providing faster data for decision-making and balancing portfolio risk and cost.

Tortugas Neuroscience's startup strategy focuses on in-licensing new chemical entities that have already cleared Phase 1, bypassing early toxicity and IND risks. Their criteria demand that each asset be extensible to multiple indications within CNS, creating operating leverage and maximizing the chances of success.

Leal Therapeutics intentionally built a team capable of developing both oral small molecules and nucleic acid drugs. This dual-modality platform provides strategic agility, allowing them to select the optimal therapeutic approach for a given disease, such as an intrathecal ASO for ALS and a brain-penetrant small molecule for broader indications.

Andrew Lo advocates funding a diverse portfolio of drug candidates. By taking “multiple shots on goal,” the high risk of individual failures is mitigated. The immense success of just one or two approved drugs can financially cover the costs of the entire portfolio, making early-stage biotech investment more viable and rational.