Moderna changes up R&D model, posts cancer, CV trial updates

These changes comes amid claims that the high-valued company is being overly secretive.

Moderna has once again dumped a whole load of updates as it looks to take an AstraZeneca-partnered med into phase 2 and start on I-O, while making changes to its venture model.

First up, the mRNA biotech says it “has decided to move from its venture-based R&D model to a therapeutic area R&D model,” bringing four former units back under one umbrella corp. 

A spokesperson for the company said: “We’ve decided to set aside our venture model (i.e., names and branding going away) in favor of ‘Therapeutic Area’ R&D. There will be three main TAs: infectious diseases, immuno-oncology and rare diseases.

“As we continue to progress more programs into and through the clinic, the ventures were inadvertently creating unnecessary silos given all the sharing we do across programs since we’re all based on a common platform.”

The spokesperson said this would not involve any job/headcount cuts from the mini startups. One position was eliminated, but that person is just taking on a different role, not leaving the company, they added.

“More just changing reporting structures internally to allow more cross-team collaboration. And then no more venture brands,” as Valera, Elpidera, Caperna and Onkaido will all be dissolved. “All just one Moderna,” the company said.

Under this new structure, the company says that research/preclinical development will report to Moderna’s president Stephen Hoge, M.D., and clinical development will report to Tal Zaks, M.D., Ph. D., Moderna’s CMO.

The company has been under pressure from the media, with medical news site STAT devoting a number of articles questioning its worth.

Last week, London’s Financial Times also weighed in with a piece called "Secretive Moderna yet to convince on $5bn valuation," with the newspaper speaking to some biotech execs who question how such an early-stage biotech, with a focus on traditionally low-margin vaccines and no approved meds, can be worth such a high amount.

It does boast some major Big Pharma tie-ups, including with AstraZeneca, Vertex and Merck, although in July Alexion dropped out as it continues its R&D re-tooling.

RELATED: Alexion scraps Moderna pact as new CEO cleans house

But a lack of data from the company has caused consternation from some. The biotech’s CEO Stéphane Bancel told the FT earlier this month that the company has “not published for competitive reasons. We said let’s not teach the world how this works because we’ve invested a lot of money.”

He added that: “We will publish product data; you’re going to see much more, quite a number of studies.”

Today, as it did at the start of the year at the J.P. Morgan conference, it released a batch of updates, although these were confined to fairly standard moves across its trials.

One of the headlines is its phase 1 test of mRNA AZD-8601, the “first-ever mRNA therapeutic to be evaluated” in a clinical study, according to the biotech (CureVac has also, however, been in this area, starting clinical trials of mRNA vaccines a few years back), which “has been successfully completed,” with the AZ-partnered med now set for phase 2.

The candidate works to express a local and transient surge of vascular endothelial growth factor-A (VEGF-A) as a potential treatment for cardiovascular diseases. The early, randomized, double-blind, placebo-controlled, single ascending dose study primarily looked at safety as a single dose in male patients with type 2 diabetes.

Full details and a data breakdown were not shared, but Moderna says: “The study met its primary endpoint of safety and tolerability and also demonstrated proof of mechanism as measured by expression of VEGF-A protein in the skin (protein PK).”

Zaks says: “We’ve reached an important milestone with the successful completion of the phase 1 study of mRNA-AZD-8601. And the phase 2a study of mRNA-AZD-8601 in patients undergoing coronary artery bypass grafting surgery will provide further insight into the potential of VEGF-A mRNA to provide a unique regenerative treatment option for patients with cardiovascular disease. Seeing the first mRNA therapeutic program move to phase 2 study will be an important step for the entire mRNA field.”

It’s also started a phase 1 of mRNA-2416, an intratumoral immuno-oncology therapeutic that encodes for the membrane expression of the co-stimulatory protein OX40 Ligand, or OX40L, to potentially enhance T-cell attacks against tumors. This is Moderna’s first I-O therapeutic to enter clinical study, and it began dosing last month.

A number of Big Pharmas such as Pfizer are working with OX40, although in the summer, Swiss pharma Roche announced in its financials that it had in fact cut its phase 1 efforts on RG7888, an OX40 mAb in solid tumors.

Moderna’s also working on mRNA-4157 in combo with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab), with Moderna seeking out neoepitopes present in a patient’s tumor, and then aiming to use this to create an mRNA-based PCV encoding for about 20 neoepitopes.

“When injected into the patient, the mRNA-based PCV will direct the patient’s cells to express the selected neoepitopes,” the company says in its update. “In turn, this should help the patient’s immune system to better recognize cancer cells as foreign and eradicate them.”

It says in total, it now has phase 1 studies underway for seven mRNA medicines, with its pipeline now comprising 16 development candidates.

“2017 is a major inflection point for Moderna, as we’ve made significant progress advancing mRNA therapeutics for unmet needs across several disease areas,” said Bancel. “I’m very thankful to the Moderna team for their commitment, dedication and continued progress to deliver on our mission.”

At the end of June, Moderna has just over $1 billion in cash, down $300 million compared with the end of last year.