One of the few working quantitative models in biotech is to systematically purchase stocks after they have crashed on bad news. This low-batting-average, high-slugging-percentage approach is terrifying but can work by getting favorable odds on a recovery, provided the company has sufficient cash runway to survive.

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The firm discovered a reversal effect in stocks down 70-80%. The strategy's efficacy was confirmed when their own traders instinctively wanted to override these trades due to negative headlines. This emotional bias, even among professionals, is the inefficiency the model exploits.

The memo details how investors rationalize enormous funding rounds for pre-product startups. By focusing on a colossal potential outcome (e.g., a $1 trillion valuation) and assuming even a minuscule probability (e.g., 0.1%), the calculated expected value can justify the investment, compelling participation despite the overwhelming odds of failure.

Top growth investors deliberately allocate more of their diligence effort to understanding and underwriting massive upside scenarios (10x+ returns) rather than concentrating on mitigating potential downside. The power-law nature of venture returns makes this a rational focus for generating exceptional performance.

Standard quant factors like expanding margins and avoiding capital raises are negative signals for development-stage biotech firms. These companies must burn cash to advance products, rendering traditional models useless. The only semi-reliable quant metric is Enterprise Value to Cash.

Instead of raising money immediately after positive trial data, Rhythm waited. This allowed sell-side analysts time to understand the results, build financial models, and educate investors. This patience resulted in a stock that coalesced at a much higher valuation, maximizing the capital raise.

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.

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.

While biotech seems exceptionally volatile, data shows its average 60% annual peak-to-trough drawdown isn't dramatically worse than the ~50% for typical non-biopharma small caps. The perceived risk is disproportionate to the actual incremental volatility required for potentially asymmetric returns.