Moderna Therapeutics

Introduction

From wiki

Moderna Therapeutics is a biotechnology company that researches and develops protein therapies based on novel messenger RNA (mRNA) technology.[3] The company’s technology uses mRNA made of nucleotide analogs to trigger the body’s natural processes to produce proteins inside the human cell.[4] This approach has the potential to produce therapeutic proteins in vivo to treat a wide range of diseases, including those that cannot be effectively treated with existing methods to develop and manufacture drugs.[5]

Moderna’s pipeline of mRNA product candidates covers a broad expanse of drug modalities, including vaccines (both for infectious diseases and personalized cancer vaccines), intracellular/transmembrane proteins, intratumoral expression, and secreted antibodies and proteins.[6] Each modality represents a distinct approach to using the mRNA platform to encode proteins that achieve a therapeutic benefit, enabling the company to develop numerous drug candidates across a wide array of therapeutic areas.[7]

The company was founded in 2011 in Cambridge, Massachusetts through funding from Flagship Ventures.[8][9][10] Moderna’s founders include Noubar Afeyan of Flagship Ventures, Kenneth R. Chien of Harvard University and the Karolinska Institutet, Robert S. Langer of the Massachusetts Institute of Technology and Derrick Rossi of Boston Children’s Hospital.[11] Moderna is led by Stéphane Bancel, CEO and Director of the Board; Stephen Hoge, M.D., President; Marcello Damiani, Chief Digital Officer; Steve W. Harbin, SVP, Human Resources; Jim R. Kasinger, J.D., General Counsel; Lorence Kim, M.D., CFO and SVP, Business Development, and Tal Zaks, M.D., Ph.D., CMO.[12]

History

Moderna received venture capital and grant funding of $40 million from Flagship Ventures’ VentureLabs unit and other private investors by December 2012.[3][13]

In March 2013, Moderna Therapeutics and AstraZeneca signed a five-year exclusive option agreement to discover, develop and commercialize mRNA therapeutics for the treatment of serious cardiovascular, metabolic and renal diseases as well as selected targets in oncology.[14][15] The agreement included a $240 million upfront payment to Moderna, a payment that is “one of the largest ever initial payments in a pharmaceutical industry licensing deal that does not involve a drug already being tested in clinical trials.”[14]

In October 2013, the Defense Advanced Research Projects Agency (DARPA) awarded Moderna a grant worth up to $24.6 million to research and develop its mRNA drug technology to fight infectious diseases and biological weapons.[16][17]

In November 2013, Moderna secured an additional $110M in equity financing to further develop its mRNA Therapeutics platform as a private company.[18] In January 2014, Moderna and Alexion Pharmaceuticals entered a $125 million deal to aid in the discovery and development of messenger RNA therapeutics used to treat rare diseases. Alexion paid Moderna $100 million exchange for 10 product options to develop rare-disease drugs using Moderna’s mRNA Therapeutics platform, and also made another $25 million preferred equity investment in Moderna.[19]

In June 2014, CNBC recognized Moderna as one of the top 50 companies whose innovations are having a dramatic impact across their industries, and are poised for hyper-growth.[20]

In October 2014, Moderna announced a strategic research and clinical partnership with Karolinska Institutet and Karolinska University Hospital, and established Moderna Therapeutics Sweden in Stockholm as its first expansion outside the U.S.[21]

At the beginning of January 2015, Moderna announced that it had raised $450 million in new funding to support further expansion of its mRNA Therapeutics platform across multiple modalities and therapeutic areas. As of this announcement, Moderna had secured $950 million in funding through financing activities and commercial partnerships.[22]

On January 8, 2015, Moderna launched Valera, a venture focused exclusively on the advancement of vaccines and therapeutics for the prevention and treatment of viral, bacterial and parasitic infectious diseases.[23]

Also in January 2015, Moderna announced a license and collaboration agreement with Merck for the discovery and development of vaccines and passive immunity treatments against viral diseases using modified messenger RNA (mRNA). Merck made an upfront cash payment to Moderna of $50 million to commercialize five product candidates, as well as a $50 million equity investment in Moderna.[24]

In May 2015, Moderna launched Elpidera, a venture focused exclusively on developing messenger RNA (mRNA) based medicines for the treatment of rare diseases.[25]

Also in May 2015, CNBC recognized Moderna the #1 Disruptor on its third-annual CNBC Disruptor 50 list.[26]

On October 22, 2015, Moderna launched its fourth venture, Caperna, focused exclusively on the advancement of personalized cancer vaccines.[27]

Research

In September 2013 Moderna co-founder Kenneth Chien served as senior author to a study published in Nature Biotechnology, which showed that Moderna’s messenger RNA therapeutics platform induced in vivo production of proteins to stimulate blood vessel growth, repair damaged heart tissue, and improve outcomes in a mouse model of myocardial infarction.[28][29][30][31] Researchers injected mice with a single dose of VEGF-A-coded messenger RNA in the heart shortly following myocardial infarction to trigger production of the VEGF-A protein.[28] Researchers found that “the presence of VEGF-A caused progenitor cells in the heart that would normally become scar tissue following a myocardial infarction to become vascular tissue.”[29] Mice injected with messenger RNA went on to generate new cardiovascular cells and show improvements on measures of cardiac function and survival when compared with controls.[28][31]

2015 DISRUPTOR 50

Founders: Noubar Afeyan, Robert Langer, Kenneth Chien, Derrick Rossi Date launched: 2011 Funding: $1 billion Industries disrupted: Pharmaceuticals, biotechnology

Imagine helping the human body make the medicine it needs to cure a disease. That’s what Moderna Therapeutics is setting out to do. The Cambridge, Massachusetts-based company, founded by a team steeped in the fields of medicine and biology, uses messenger RNA—or mRNA—to give the body’s cells the instructions, or code, they need to create the proteins and antibodies to fight all kinds of diseases, from diabetes and heart disease to certain cancers.

One of the chief advantages that Moderna has over other early-stage biotech companies is that its mRNA can focus on fighting multiple diseases at once rather than the typical and time-consuming path of defining and creating a drug therapy for each individual disease.

The company already has 45 preclinical programs under way in cardiovascular disease, oncology and other areas and expects to be in clinical trials testing drugs and vaccines for a variety of therapeutic areas within the next two years.

Investors—and partners—find this incredibly attractive. The company recently raised an additional $500 million in equity financing and signed pharma giant Merck as a strategic partner to help develop treatment for viral diseases. This adds to Moderna’s existing strategic relationships with AstraZeneca for cardiovascular disease; Alexion for rare diseases, such as life-threatening blood disorders; and the government’s Defense Advanced Research Projects Agency (DARPA) for biodefense. Stéphane Bancel, president and founding CEO, Moderna Therapeutics Source: Moderna Therapeutics Stéphane Bancel, president and founding CEO, Moderna Therapeutics

“We are advancing a platform with widespread reach across multiple therapeutic areas and modalities. The broad potential impact of our technology compelled us to rethink how biotech companies develop drugs.” -Stéphane Bancel, CEO of Moderna Therapeutics

A ‘Moderna’ Cinderella Story: AstraZeneca’s $240M Up Front Share

By Randy Osborne

Moderna Therapeutics Inc.’s major win, in the form of a $240 million up-front licensing deal with battered AstraZeneca plc for technology still at the preclinical stage, put the spotlight on messenger RNA therapy (mRNA) and sparked guesswork about whether the wager by the pharma giant can bring enough revenue soon enough.

“They wanted a piece of the action, and they wanted a big piece,” Stephane Bancel, president and founding CEO of Moderna, told BioWorld Today.

Under the terms, London-based AstraZeneca gets exclusive access to select any target of its choice in cardiometabolic diseases, as well as selected targets in oncology, over a period of up to five years, and Moderna, of Cambridge, Mass., could get as much as $180 million more if three unspecified technical milestones are reached.

AstraZeneca has the option to pick as many as 40 drug products for clinical development, and Moderna stands to gain milestone payments related to clinical and commercial progress, along with royalties on drug sales ranging from high single digits to low double digits for each product.

Trials and commercialization of therapeutics will be AstraZeneca’s job, and Moderna will be responsible for designing and manufacturing the mRNA against selected targets.

Beset by trial failures and facing the patent cliff, AstraZeneca needs the kind of help that Moderna may be able to provide relatively quickly. The firm’s mRNA drugs, intended to trigger cells to make therapeutic proteins without causing an immune response, “enable [developers] to go after new drug targets that are not druggable today, using either small or large molecules,” Bancel said. “This is something very exciting, especially when you think about cardiology, where AstraZeneca is very strong.”

The time from target identification to trials is shortened greatly by the approach. “Your body makes proteins like the Amgen plant or the Genzyme plant makes proteins in tanks,” Bancel said, and the method is much less expensive than recombinant proteins.

AstraZeneca has other bets. Phase III programs are under way with lesinurad (an inhibitor of the URAT1 transporter in the kidney for gout), olaparib (a PARP inhibitor for BRCA1/BRCA2-mutant ovarian cancer) and selumetinib (a MEK inhibitor for lung cancer), all of which look promising to Leerink Swann analyst Seamus Fernandez, he wrote in a research report.

The company could file for approval of olaparib in Europe this year, based on subset analyses that regulators there may find acceptable. “When asked about fostamatinib (a SYK inhibitor for rheumatoid arthritis), management conviction was less clear to us,” Fernandez wrote.

Deal Shows Pharma’s Willingness to Risk

Earlier this week, AstraZeneca said it would cut the payroll by 1 ,600 employees and relocate 2,500 jobs, for a one-time restructuring tab of $1 .4 billion, along with a $500 million capital investment in Cambridge, UK. The company aims to save about $190 million per year, though even that will not be sufficient if R&D does not pan out. Revenues dropped last year and will sink more this year, AstraZeneca has said, due largely because patents have expired and continue to do so in territories around the globe for such stars as Seroquel IR (quetiapine fumarate), Atacand (candesartan cilexetil), Nexium (esomeprazole magnesium delayed-release capsules) and Merrem (meropenem). (See BioWorld Today, March 19, 2013.)

In the U.S., patents for proton pump inhibitor Nexium – viewed as particularly important for AstraZeneca – start expiring in 2014. Generics drugmaker Ranbaxy Inc. has gained tentative FDA approval for its version, and others are formulating theirs. For Seroquel, the depression drug that sold more than $4 billion last year, the challenge comes from Teva Pharmaceutical Industries Ltd.

“It’s a complete open door now, in mRNA technology,” said Ingmar Hoerr, CEO of Tuebingen, Germany-based CureVac GmbH, reacting to the AstraZeneca deal with Moderna. The speed, efficiency and lower cost of mRNA likely will now come to the attention of other pharma firms, he said.

“In regard to speed, it’s the same for us – this is not a problem,” Hoerr told BioWorld Today, adding that “how you get access to targets is just a strategic topic. There are lots of different possibilities. You can just screen what is off patent, just take it, or you can license [your technology] to existing targets, or do your own screening. We already have more than 2,000 different RNA constructs encoding for 2,000 different proteins expressed in cells.”

Hoerr likened the mRNA route as a way to “reinvent the gene therapy approach from the 1990s and make it much safer. Messenger RNA was, for a long time, a forgotten biomolecule. Everybody was jumping on proteins or antibodies. I think it’s quite natural that everybody now has begun to explore this new approach.”

The AstraZeneca-Moderna deal is likely the largest up-front payment awarded in a preclinical, purely licensing deal on record. Some likened it to the deals in 2010 and 2011 between Abbott and Reata Pharmaceuticals Inc., but that arrangement was structured more like a joint venture. Others compared it to the 2007 agreement between Roche AG and Alnylam Pharmaceuticals Inc., but that one involved an equity stake. (See BioWorld Today, July 10, 2007, Sept. 24, 2010, and Dec. 13, 2011.)

Hoerr said AstraZeneca’s move shows “how far they want to take risks right now. It’s quite good news. The vision is very strong.”