The company is making far more machines than it is selling, leading to expenses being much greater than revenue. Further, he realizes that the employees appearing “busy” and working long hours does not necessarily translate to higher productivity. It would actually be better that they spend fewer hours focused on the specific tasks that lead to higher revenue. (Location 390)
Additionally, hiring such a large team solely for preclinical work demonstrates the extent of M’s focus on this single area of the business. (Location 471)
If the company had Built Backwards, it likely would have realized this sooner and invested the majority of its resources into preparing for clinical trials. Instead, the company ran out of capital and struggled to raise more funding due, in large part, to a lack of momentum over the multiple years prior. (Location 476)
Therefore, Sunovion sought to create a drug that would alleviate both negative and positive symptoms. Sunovion believed the best way to achieve this end was to find a drug that, for the first time, did not treat schizophrenia by binding to D2 receptors. D2 receptor-inhibiting molecules have a high side effect profile because such drugs hit multiple receptors (G-protein coupled receptors, or GPCRs for short). Thus, Sunovion Built Backwards to a clear end goal: FDA approval for a novel drug that did not bind D2 receptors and could treat both the positive and negative symptoms of schizophrenia. (Location 501)
In other words, the scientists used a novel drug screening method that leveraged artificial intelligence technology to analyze the behavior of mice exposed to hundreds of candidate compounds. Then they selected a drug that did not bind to D2 receptors but still seemed to address negative symptoms in mice. (Location 511)
By Building Backwards from its targeted market positioning (e.g., a schizophrenia drug that also treated negative symptoms with fewer side effects), (Location 533)
Sunovion shows that when both the research and business arms of a company are following the same, clearly defined goals, they can better achieve the larger outcome, bringing novel medicines to patients who desperately need them while building a valuable company. (Location 544)
These case studies help outline how Building Backwards can look in practice. Keep in mind, Building Backwards is a method of thinking, not a linear step-by-step process. (Location 546)
The problem? Pfizer had to select one disease (i.e., “indication”) to test the compound against in clinical trials, but animal models of pain are notoriously poor predictors of human pain syndromes. This made it especially difficult to select an indication for clinical trials based on the animal data. (Location 611)
With this, Pfizer understandably preferred indications with larger market size. Ultimately, Pfizer selected osteoarthritis, a large and underserved clinical population that matched its market requirements and commercial interests. Despite clear evidence of strong inhibition of FAAH in humans, the osteoarthritis trial unfortunately failed. (Location 615)
Cravatt gained insight into the business model necessitated by large pharma companies—namely, that large pharma companies must factor in commercial requirements of the business alongside the science. (Location 622)
In the case of FAAH, the “unrivaled” chemical matter that resulted from the project serves as an example of some of big pharma’s strengths while its “high risk” profile as a novel target highlighted some of the difficulties big pharma in particular can face when developing drugs for emerging areas of science. (Location 633)
human data each. • The company did not Build Backwards to define “inflection points” that could ensure the company was increasing its value (we will elaborate on this in chapter 9). (Location 486)
Sunovion started off by determining precisely which experiments to run based on the approval criteria used by the FDA. (Location 491)
Good science alone does not necessarily bring about the necessary money, time, resources, or know-how to fully develop a new medicine for patient use. (Location 727)
As demonstrated by the FAAH story, Big Pharma has particular strengths in the drug development process as well as certain limitations. (Location 731)
Since 96 percent of new drugs fail, when selecting an indication for which to develop a brand-new drug, the pharma company must account for both the cost of development for that particular drug and the costs of roughly nine other failed drugs. (Location 766)
Therefore, pharmaceutical companies spend an exorbitant amount of time and resources building relationships with physicians, which includes attending conferences where they can meet with key opinion leaders. (Location 797)
In contrast, it is not as common for Big Pharma to be the originators of a new drug. (Location 812)
Instead, most of their blockbuster drugs had been acquired from other academic groups or companies, many of which were small biotechs. (Location 816)
However, though a novel approach is high risk, it’s also high reward. For biotech start-ups, the ability to embrace risk provides an opening for them to try such novel approaches and assume the potential rewards of doing so. (Location 826)
For biotech specifically, Herper also discovered in his analysis that small biotech companies had per-drug R&D costs far lower than large pharma company averages. (Location 839)
While traditional drug development can easily take ten to fifteen years or more, biotech companies have the potential—and particular incentive—to be extraordinarily fast. (Location 847)