companies spans a considerable range that includes behemoths such as publicly-traded entities like Ionis Pharmaceuticals, Akcea Therapeutics and Ablynx. However the list also contains much smaller, privately-held companies such as Sirenas. We now discuss and compare a number of these smaller companies along with their business mod- els and valuations.

RNA PD3 companies RNA-based therapeutic approaches have generated significant attention in recent years. They include antisense, RNAi, aptamers, microRNA, mimics/ anti-miRs and synthetic mRNA technologies. Moderna is the epitome of such companies, and has enjoyed marked financial success in its PD3 mRNA drug therapy endeavours. It is interesting to compare and contrast Moderna’s success (cur- rent market capitalisation of $7.12 billion-March 18) with that of some of its PD3 competitors. For example consider:

CureVac ( is a biopharmaceuti- cal company that develops mRNA therapeutics in direct competition to Moderna. The company was founded in 2000 and is located in Tubingen, Germany. It has ~390 employees and an annual revenue stream of ~$300,000. The company has raised $431.5 million, and it remains privately held. The drug therapy pipeline consists of 17 potential drug candidates in cancer, prophylactic vaccines and molecular-based therapies. Four can- didates are in Phase I, eight in preclinical stages, and the other five are still in discovery. It is current- ly valued at ~$1.65 billion.

Regulus Therapeutics ( devel- ops microRNA drugs for fibrosis, cardiovascular and immune-related disorders. The company was founded in 2007 and is based in San Diego, California (USA). The company sprinted to an IPO in October 2012, and has raised ~$175 million that includes the IPO of $45 million. It currently employs ~60 individuals. The pipeline consists of eight potential drug candidates, one Phase II, one Phase I and the remaining six in preclinical evalua- tion. Revenues for 2018 were < $1 million and the current market capitalisation (March 2019) is only $9.53 million, down from the IPO valuation of $136.5 million.

Alnylam Pharmaceuticals ( was the very first commercial entity to attempt the development of RNAi therapeutics in a variety of disease states. The company is based in


Cambridge, Massachusetts, USA and was founded in 2002. The company filed for an IPO in February 2004 raising $26.4 million, and has accrued $417.5 million to date in equity investments. The company has more than 1,000 employees. The platform built by the company was not as focused and directed as a typical PD3 company. It was assembled out of necessity since Alnylam pio- neered the therapeutic use of RNAi therapeutics. This has resulted in a robust pipeline of drug can- didates that includes five Phase III and four Phase II drug candidates. One candidate, Givosiran, is being registered as a commercial drug in an NDA filing. In addition Patisiran (brand name Onpattro) was the first ever FDA-approved RNAi therapy for the treatment of hereditary transthyretin-mediated amyloidosis. The current market capitalisation of Alnylam is $9.1 billion.

Moderna is a purpose-built PD3 company. The

articulation by Noubar Afeyan on the value of such an approach has been leveraged by a lucrative fund raising and valuation/market capitalisation effect in the past ~eight years. This is in spite of the company being several years away from demon- strating the efficacy and validation of the platform by producing a regulatory-approved drug. It is edi- fying to compare the fortunes of CureVac, a direct competitor of Moderna. The former has not been aggressive in promoting its PD3 capability and has a much longer history, but with a comparable drug candidate pipeline to Moderna. However, private- ly-held CureVac only comprises ~25% of the mar- ket cap of Moderna! Even more noteworthy is the comparative performance metrics of Regulus Therapeutics. This PD3 company, in its 12-year existence, has experienced dramatic highs (IPO 2012) and lows (current market capitalisation $9.53 million). Ben-Joseph and Manning might argue (see above) that Regulus Therapeutics is a company which allowed platform development to be distractive from the true mission of producing new RNA therapeutic drugs2. The contrast in the history and performance

metrics of Moderna versus Alnylam is instructive. The latter has been active for 17 years and pio- neered the use of RNAi therapeutics. Alnylam developed a PD3 approach out of necessity and has for the most part in its history emphasised its DDD capabilities and the development of a robust pipeline. The current Alnylam pipeline is impres- sive and includes a marketed product Onpattro. The regulatory approval of this RNAi drug is a val- idation of the Alnylam platform. This is in stark contrast to the more modest pipeline of Moderna

Drug Discovery World Spring 2019

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