Research

MIT Sloan Professor Andrew Lo authored this blog post about the development of a mega-fund to finance research and drug development for orphan diseases.

The biotechnology and pharmaceutical industries are facing significant challenges to their existing business models because of expiring drug patents, declining risk tolerance of venture capitalists and other investors, and increasing complexity in translational medicine. In response to these challenges, new alternative investment companies have emerged to bridge the biopharma funding gap by purchasing economic interests in drug royalty streams. Such purchases allow universities and biopharma companies to monetize their intellectual property, creating greater financial flexibility for them while giving investors an opportunity to participate in the life sciences industry at lower risk. Royalty Pharma is the largest of these drug royalty investment companies, and in this case study, we profile its business model and show how its unique financing structure greatly enhances the impact it has had on the biopharma industry and biomedical innovation.

There exist scientifically promising treatments not being tested further because of insufficient financial incentives. Many of these therapies involve off-label uses of drugs approved by the Food and Drug Administration that are readily available and often inexpensive. Pharmaceutical companies—largely responsible for clinical drug development—cannot justify investing in such clinical trials because they cannot recoup the costs of these studies. However, without prospective data demonstrating efficacy, such treatments will never be adopted as standard of care.

In an era of increasing health care costs and the need for effective therapies in many diseases, it is essential that society finds ways to adopt these “financial orphans.” We propose several potential solutions for the non-profit sector, pharmaceutical companies, health insurers, patient driven research, and others to accomplish this goal.

Open-source software for "Financing Drug Discovery for Orphan Diseases" (with David E. Fagnan, Austin A. Gromatzky, Jose-Maria Fernandez, Roger M. Stein, Drug Discovery Today 19 (2014), 533-538).

Cancer is expected to continue as a major health and economic problem worldwide. Several factors are contributing to the increasing economic burden imposed by cancer, with the cost of cancer drugs an undeniably important variable. The use of expensive therapies with marginal benefits for their approved indications and for unproven indications is contributing to the rising cost of cancer care.We believe that expensive therapies are stifling progress by (1) encouraging enormous expenditures of time, money, and resources on marginal therapeutic indications and (2) promoting a me-too mentality that is stifling innovation and creativity. The modest gains of Food and Drug Administration–approved therapies and the limited progress against major cancers is evidence of a lowering of the efficacy bar that, together with high drug prices, has inadvertently incentivized the pursuit of marginal outcomes and a me-too mentality evidenced by the duplication of effort and redundant pharmaceutical pipelines. We discuss the economic realities that are driving this process and provide suggestions for radical changes to reengineer our collective cancer ecosystem to achieve better outcomes for society.

As the prevalence of Alzheimer’s disease (AD) grows, so do the costs it imposes on society. Scientific, clinical, and financial interests have focused current drug discovery efforts largely on the single biological pathway that leads to amyloid deposition. This effort has resulted in slow progress and disappointing outcomes. Here, we describe a “portfolio approach” in which multiple distinct drug development projects are undertaken simultaneously. Although a greater upfront investment is required, the probability of at least one success should be higher with “multiple shots on goal,” increasing the efficiency of this undertaking. However, our portfolio simulations show that the risk-adjusted return on investment of parallel discovery is insufficient to attract private-sector funding. Nevertheless, the future cost savings of an effective AD therapy to Medicare and Medicaid far exceed this investment, suggesting that government funding is both essential and financially beneficial.

Open-source software for "Can Financial Engineering Cure Cancer?" (with David E. Fagnan, Jose Maria Fernandez, and Roger M. Stein, American Economic Review 103 (2013), 406-411).

Traditional financing sources such as private and public equity may not be ideal for investment projects with low probabilities of success, long time horizons, and large capital requirements. Nevertheless, such projects, if not too highly correlated, may yield attractive risk-adjusted returns when combined into a single portfolio. Such "megafund" portfolios may be too large to finance through private or public equity alone. But with sufficient diversification and risk analytics, debt financing via securitization may be feasible. Credit enhancements (i.e., derivatives and government guarantees) can also improve megafund economics. We present an analytical framework and illustrative empirical examples involving cancer research. To download the open-source software, please click here.

Biomedical innovation has become riskier, more expensive and more difficult to finance with traditional sources such as private and public equity. Here we propose a financial structure in which a large number of biomedical programs at various stages of development are funded by a single entity to substantially reduce the portfolio's risk. The portfolio entity can finance its activities by issuing debt, a critical advantage because a much large pool of capital is available for investment in debt versus equity. By employing financial engineering techniques such as securitization, it can raise even greater amounts of more-patient capital. In a simulation using historical data for new molecular entities in oncology from 1990 to 2011, we find that megafunds of $5-15 billion may yield average investment returns of 8.9-11.4% for equity holders and 5-8% for 'research-backed obligation' holders, which are lower than typical venture-capital hurdle rates by attractive to pension funds, insurance companies and other large institutional investors. To download the open-source software, please click here.

Open-source software for "Commercializing Biomedical Research through Securitization Techniques" (with Jose-Maria Fernandez and Roger M. Stein, Nature Biotechnology 30 (2012), 964-975.