Business


approximately 150 years of history and to whether there is a paradigm that could explain how the public-private sector interaction has both driven the growth of this industry and brought economic, social and healthcare benefits for society. Back in 2004, one of the authors (Ibis Sanchez-


Serrano) was investigating the multiple factors that could account for the success and failure of biotechnology firms in the United States and Europe. Some of the variables involved in this analysis – -eventually published in 2006 in Nature Reviews Drug Discovery7 – were the rela- tionship between early-stage biotechnology firms and their parental academic organisations and other academic institutions; the collaborations that these firms established with pharmaceutical companies and private investors; the role of fed- eral-funding agencies in the translational process between academia-industry/private-public sector; the support that early stage firms received from philanthropic organisations and advocacy groups; and considerations of the impact of secre- cy and intellectual property (IP), as described by the ‘Tragedy of the Anticommons’, a type of para- doxical setting, in which too many separate rights-holders of a single resource can block each other’s use of that resource8. In studying the story-case of many successful


and failed biotechnology companies throughout the world, the story-case of the development of bortezomib for the treatment of multiple myeolo- ma by the Cambridge (US)-based biotechnology company Myogenics/ProScript (later acquired by Millennium Pharmaceuticals), seemed both highly unusual and a quintessential example of what it takes to develop a drug in the biotechnological field. On May 13, 2003, the FDA-approved Velcade


(bortezomib), a proteasome inhibitor (Figure 1), under ‘Fast-Track’ Application for the treatment of multiple myeloma, an incurable cancer of the blood that affects approximately 14,000 patients in the US annually. The story behind the develop- ment of this drug is quite unique and remarkable for many reasons, including: (i) The initial fragile funding base of the original company that discovered and developed it (Myogenics/ProScript). (ii) The risks involved in pursuing a new molecular target (the proteasome) with a new and ill-reputed class of inhibitor (boronates). (iii) Internal struggles and disagreements in the firm between the academic founders and the man- agement regarding the indication for which the drug was to be developed.


Drug Discovery World Spring 2018


(iv) Change of the original company’s business model (from cachexia to inflammation to cancer) and subsequent change of the firm’s name – from Myogenics to ProScript. (v) Enormously-disruptive drop by Hoechst Marion Roussel of proteasome inhibitors for inflammation and cancer and its return of its license rights on the drug to ProScript. (vi) Change in leadership. (vii) Depletion of initial funding and inability to secure further funding for clinical trials. (viii) The general lack of interest and total disbelief of the biopharmaceutical industry on bortezomib. (ix) The resulting merging of ProScript into Cambridge-based LeukoSite and, six months later, purchase of LeukoSite by Millennium Pharmaceu- ticals. In spite of all these major obstacles, that would


have quickly destroyed any company or drug development programme, bortezomib managed not only to make it to the market, but to do so in record time and at a significantly lower cost than the biopharmaceutical industry’s average. Why did bortezomib – which was doomed to


failure from the beginning – became a success story unlike other countless well-funded examples in the industry? How did it manage to reach the market in record time?


The Core Model Without


knowing or planning it,


Myogenics/ProScript used an organisational model, coined ‘The Core Model’ (Figure 2), grounded on the ‘trade of assets’ (exchange of per- sonal connections, knowledge, materials, animal models, etc) between academia and industry, between the public and private sectors, in a very systematic and effective way to advance scientific research. According to this model, the company’s ‘Core’, formed by the founders, internal people and resources and the drug ‘champions’, were very focused on demonstrating the revolutionary thera- peutic application of using proteasome inhibitors – and in this specific case, of boronates – based exclusively on the scientific data available and fol- lowing the biology at every turn. From the begin- ning, the ‘Core’ realised that, given its extremely low economic and technological resources, they needed to acquire more knowledge about the effects of inhibiting the proteasome in vivo, and this could only be accomplished via collaboration and bi-directional interaction with academia and with external, non-competing scientists interested in similar mechanisms or problems. These external collaborators were crucial in securing, in many


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