Like many others – except, as usual, for significantly more money – Moderna Therapeutics Inc. took advantage of a generous market to raise $500 million from new U.S. and international institutional investors, as well as institutional supporters already on board.
The Cambridge, Mass.-based company said it will use the funds to help move along the pipeline of 19 products, with two trials to start as the company continues to invest in messenger RNA science and technology. With the latest round, Moderna boasts about $1.4 billion in cash, and noted that it has potential access to almost $250 million in grants from the Bill & Melinda Gates Foundation and the U.S. government. The still-private firm has become known for its whopping financial rounds. (See BioWorld Today, Sept. 8, 2016.)
Moderna touted its many efforts ongoing and in the near future at the recent J.P. Morgan Healthcare Conference, where attendees heard about a soon-to-begin phase IIa study of mRNA AZD-8601, a localized therapeutic encoding for VEGF-A, in development with partner Astrazeneca plc, of London. Still to be disclosed are details of the study, including design and target indication. Led by Astrazeneca, this will be Moderna's first phase II experiment.
The company also described a new development candidate, mRNA-3927, described as targeting a rare disease within the liver modality. MRNA-3927 directs liver expression of a deficient enzyme in patients with propionic acidemia (PA), a potentially life-threatening disorder that is part of a family known as organic acidemias. There are no approved therapies for PA. In September, Moderna talked about its mRNA-3704, to treat methylmalonic acidemia, or MMA, another serious and often deadly organic acidemia.
At the San Francisco meeting, Moderna also told investors about the filing of an IND application for mRNA-5671, a K-Ras cancer vaccine. K-Ras is one of the most frequently mutated oncogenes in human cancer – about 30 percent of all cases – and mRNA-5671 encodes for the four most commonly found mutations, which will cover most that occur in non-small-cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer.
K-Ras, tough to target because it largely lacks binding pockets, made news late last month when a team from San Diego-based Wellspring Biosciences Inc. published work in Cell showing that its cysteine-binding candidate, ARS-1620, inhibited K-Ras in mice with patient-derived xenografts. A separate paper published in Nature detailed how researchers developed new methods to look at the genetic landscape of K-Ras mutations in pancreatic cancer, with findings that could inform future clinical work in the challenging tumor type. (See BioWorld, Jan. 29, 2018.)
Moderna at last month's J.P. Morgan meeting also made known the start of two phase I prophylactic vaccine studies for mRNA-1647, a cytomegalovirus vaccine (CMV), and mRNA-1653, a human metapneumovirus and parainfluenza virus type 3 (HMPV+PIV3) combo. MRNA-1647 is made of six mRNAs, one coding for the herpesvirus glycoprotein antigen and five coding for the pentamer. HMPV and PIV3 are the second and third most common causes, respectively, of lower respiratory hospitalizations in children, behind respiratory syncytial virus, and no approved vaccines exist for CMV, HMPV or PIV3.
Another new development candidate, mRNA-1944, directs liver expression of an antibody that can potentially neutralize chikungunya virus circulating in the blood. Moderna has a phase I study underway with its prophylactic vaccine, mRNA-1388, to prevent infection from chikungunya. An antibody approach would be more desirable in certain settings, the company noted, such as in immunocompromised populations when rapid post-exposure treatment or prophylaxis is warranted, or when protection is needed only for short periods of time. The program is sponsored by the Defense Advanced Research Projects Agency.
Message: space is hot
The mRNA approach has meant good things for other firms, too, such as Curevac AG, with a vaccine platform that in October bagged the Tubingen, Germany-based firm's largest collaboration to date, a pact with Eli Lilly and Co., of Indianapolis, that brought a $50 million up-front payment, an equity investment of €45 million (then US$53 million) and up to $1.7 billion in potential milestones if all five cancer vaccine candidates are developed, plus tiered royalties on any products that see market daylight. Other deals in the space have popped over the years, such as Mainz, Germany-based Biontech AG's $1.5 billion-plus pact with Sanofi SA, of Paris, in 2015, Moderna's agreements with Merck & Co. Inc., of Kenilworth, N.J., and Astrazeneca, and Planegg, Germany-based Ethris GmbH's five-year collaboration, also with Astrazeneca. (See BioWorld Today, March 22, 2013, Nov. 4, 2015, June 30, 2016, Aug. 22, 2017, and Oct. 19, 2017.)
Biontech deploys a particularly interesting technology. By treating mice with mRNA that encodes a bispecific antibody, rather than with the antibody itself, researchers from the company and from the German University of Mainz eliminated tumors. In a direct comparison, the mRNA worked as well as the protein antibody did, and needed to be administered less often. The research was published last summer online in Nature Medicine. Biontech calls the mRNA-encoded bispecific antibodies Ribomabs. (See BioWorld, June 15, 2017.)
Curevac's other deals provided $45.4 million up front in 2014 from Ingelheim, Germany-based Boehringer Ingelheim GmbH, which licensed global development rights to CV-9202, a therapeutic vaccine targeting NSCLC, and signing an infectious disease-focused deal with Sanofi's vaccines arm in 2011. (See BioWorld Today, Nov. 16, 2011, and Sept. 19, 2014.)
Another firm to make a move in the space is the former Rana Therapeutics Inc., of Cambridge, Mass., which near the start of 2017 acquired the mRNA replacement therapy (MRT) platform developed by units of Shire plc, of Dublin, which took an undisclosed equity stake in Rana and is set to receive undisclosed milestones and royalties on products developed with the technology. Rana said it had already identified therapeutic applications for the late preclinical mRNA platform and planned to file its first IND in the following 12 to 18 months. Programs in cystic fibrosis and urea cycle disorders were to represent the first targets for MRT. Later in the same year, the firm relaunched as Translate Bio Inc. (See BioWorld Today, Jan. 5, 2017.)
In the latest money round by Moderna, new backers include a wholly owned subsidiary of the Abu Dhabi Investment Authority, BB Biotech AG, Julius Baer, Singapore-based EDBI and Sequoia Capital China. Existing investors taking part: Fidelity Management & Research Co., Pictet, Viking Global Investors, Arrowmark Partners and Alexandria Venture Investments.
Placement agents for the financing were Goldman Sachs & Co. LLC, JP Morgan Securities LLC and Morgan Stanley & Co. LLC. Goodwin Procter provided legal counsel.