Business


The rise and demise of the CombinatoRx platform-DDD efforts


CombinatoRx was a blazing star in the firmament of platform-DDD companies. The company was founded in 2000 by a group of Harvard/MIT scientists and entrepreneurs. They developed a proprietary platform technology to evaluate the synergistic activity of combination-pair approved drugs. A high throughput, cell- based screening assay platform was used in combination with a novel dose-matrix regime against a broad swath of major diseases including assorted cancers, rheuma- toid arthritis, asthma, psoriasis and diabetes. Alexis Borisy (founding CEO) stated: “We wanted to explore how we could create platforms that would rapidly yield a portfolio of clinical product candidates. We took a very pragmatic approach of start- ing from known components: if you take a world of 2,000 known drugs, it gives you two million possible combinations. We created and patented the platform that allows us to systematically search for these novel combinations in multiple thera- peutic areas.” (Interview with Alexis Borisy. Wall Street Transcript (2003). http://www.twst.com/interview/15717). This innovative platform-DDD initiative garnered significant investment and grant


funding, IP and a vibrant early-stage drug development pipeline, which led to a suc- cessful IPO (~$42 million) in November 2005. However, by 2010 the company was in trouble. It had burned through $230 million in funding and had encountered the brutal world of conventional drug development. It sought to reinvent itself with a name change to Zalicus and the hiring of a new CEO, Mark Corrigan. The slump in high- flying performance had been caused in 2008 by the faltering of one of its lead candi- dates. Synavive failed to demonstrate any statistically significant benefits in a mid-stage clinical trial for the treatment of arthritis of the knee. In order to shore up its pipeline, CombinatoRx acquired the Canadian company NeuroMed Pharmaceuticals along with its opioid pain reliever, Exalgo. This single compound drug was subsequently approved by the FDA in April 2010. In addition it developed a new version of Synavive, but that failed to demonstrate improved efficacy in clinical trials when compared to marketed competitors, and the company abandoned all development efforts in September 2012. UK-based Horizon Discovery acquired the CombinatoRx/Zalicus service business and high throughput screening platform for $8 million in June 2014. Simultaneously, Zalicus announced a merger with Epirus, a Boston, US-based pharma- ceutical company focused on rheumatoid arthritis, in a 10-for-1 reverse stock split. The demise of CombinatoRx/Zalicus was complete, and a simple, creative platform- DDD idea had floundered on the jagged rocks of drug development.


Integrated platform-DDD company Moderna Therapeutics Moderna Therapeutics


(originally


called


ModeRNA https://www.modernatx.com/) was founded in 2010 by Derrick Rossi (Harvard University), Kenneth Chien (Harvard University), Robert Langer (MIT) and Noubar Afeyan (Flagship Ventures/Flagship Pioneering). In 2011 the company recruited Stephane Bancel away from bioMerieux to become CEO. Moderna operated in stealth mode for the first two years of operation and most analysts mistakenly believed it was a stem cell therapeutic company. As the company removed its ‘invisibility cloak’ it became clear that the Cambridge (Massachusetts, USA)-based entity was actually developing messenger RNA (mRNA) therapeutics. In addition it had already raised $40 million, led by Flagship Ventures/Pioneering and a host of private investors!


History and evolution of Moderna Noubar Afeyan has always thought expansively, and chased challenges most conservative investors avoid. The idea of being able to instruct a patient’s own cells to create therapeutic proteins and anti- bodies to fight off all types of disease indications could change the DDD paradigm. So, the stated original, visionary goal of Moderna Therapeutics was to use mRNA therapeutics to treat diseases such as diabetes, cancer, heart disease and certain viral infections.


molecular dynamic simulation hybridised with an array of other innovative biopharma DDD mod- ules. The implementation of this platform, even at such an early stage, has shown our ability to sys- tematically translate data content into functional biology in the form of innovative protein drug candidates. We are just at the beginning of our journey, which is in stark contrast to the ‘monster’ PD3 company Moderna Therapeutics.


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Secrecy, money and valuation: The early years of Moderna were shrouded in secrecy and some degree of uncertainty. An articulated, bold vision now had to be reduced to practice and in order to execute on the ‘plan’ monies had to be raised. The initial phase of such efforts followed a two-prong approach of federal grant funding and the more classical offering of services to large pharma in return for upfront as well as back-end loaded pay- ments. In terms of grant efforts, the company raised $24.6 million in the form of a grant provid- ed by the Defense Advanced Research Projects Agency (DARPA) in October 2013 (see Table 1). The funds were provided in order to develop an mRNA drug technology to fight infectious disease. Subsequently Moderna received a grant from the USA Department of Health and Human Services (Biomedical Advanced Research and Development Authority-BARDA) for $125 million (milestone driven) to develop mRNA-based vaccine against the Zika virus in September 2016 (see Table 1). The company also embarked, in parallel, on an aggressive service play to large pharma. In March


Drug Discovery World Fall 2018


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