The decline in R&D productivity (

A significant portion of biotech's high costs stems from its "artisanal" nature, where each company develops bespoke digital workflows and data structures. This inefficiency arises because startups are often structured for acquisition after a single clinical success, not for long-term, scalable operations.

The biotech sector lacks mid-cap companies because successful small firms are typically acquired by large pharma before reaching that stage. This creates a barbell structure of many small R&D shops and a few commercial giants. The assets, not the companies, transition from small to large.

The most lucrative exit for a startup is often not an IPO, but an M&A deal within an oligopolistic industry. When 3-4 major players exist, they can be forced into an irrational bidding war driven by the fear of a competitor acquiring the asset, leading to outcomes that are even better than going public.

Astute biotech leaders leverage the tension between public financing and strategic pharma partnerships. When public markets are down, pursue pharma deals as a better source of capital. Conversely, use the threat of a public offering to negotiate more favorable terms in pharma deals, treating them as interchangeable capital sources.

In a capital-constrained market, positive clinical data can trigger a stock drop for biotechs with insufficient cash. The scientific success highlights an immediate need for a highly dilutive capital raise, which investors price in instantly. Having over two years of cash is now critical to realizing value.

A massive disconnect exists where scientific breakthroughs are accelerating, yet the biotech market is in a downturn, with many companies trading below cash. This paradox highlights structural and economic failures within the industry, rather than a lack of scientific progress. The core question is why the business is collapsing while the technology is exploding.

Unlike in tech where an IPO is often a liquidity event for early investors, a biotech IPO is an "entrance." It functions as a financing round to bring in public market capital needed for expensive late-stage trials. The true exit for investors is typically a future acquisition.

The past few years in biotech mirrored the tech dot-com bust, driven by fading post-COVID exuberance, interest rate hikes, and slower-than-hoped commercialization of new modalities like gene editing. This was caused by a confluence of factors, creating a tough environment for companies that raised capital during the peak.