AstraZeneca, Moderna in Up to $420M+ mRNA Drug Development Deal

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AstraZeneca will use Moderna Therapeutics’ messenger RNA technology to develop and commercialize new drugs for cancer and “serious” cardiovascular, metabolic, and renal diseases, under a multi-year deal that could net Moderna more than $420 million.

AZ agreed to pay Moderna $240 million up-front, plus up to an additional $180 million tied to three technical milestones. Moderna is also eligible for payments tied to development and commercial milestones, as well as royalties on drug sales ranging from high single digits to low double digits per product.

How quickly the agreement becomes effective hinges on expiration or termination of the waiting period under the Hart Scott-Rodino Antitrust Improvements Act.

AZ will lead preclinical, clinical development, and commercialization of therapeutics resulting from the agreement, while Moderna will design and manufacture the messenger RNA against selected targets. AZ has the option to select up to 40 drug products for clinical development. AZ will have exclusive access to select any target of its choice in cardiometabolic diseases, as well as selected targets in oncology, over five years for subsequent development of what the companies are calling messenger RNA therapeutics™.

Moderna’s technology uses messenger RNA to produce, in vivo, human proteins or antibodies inside patient cells that activate intracellularly or are secreted into the serum. The messenger RNA contains naturally occurring nucleotide analogues designed to stimulate the body’s ability to produce intracellular and secreted therapeutic proteins without triggering an immune system response. The secreted proteins will be released into the bloodstream with the goal of restoring function elsewhere in the body.

The messenger RNA technology could dramatically reduce the time and expense associated with creating therapeutic proteins using current recombinant technologies, AZ and Moderna say.

“Where current drug discovery technologies can target only a fraction of the disease-relevant proteins in the human genome, we have the potential to create completely new medicines to treat patients with serious cardiometabolic diseases and cancer,” AZ CEO Pascal Soriot said in a statement.

Earlier today at AZ’s Investor Day briefing in New York, Soriot led company executives in declaring the company’s commitment to growing its pipeline, in part through new partnerships and business-development deals.

Stephane Bancel, president and founding CEO of Moderna, said in the statement, “We share a common vision with AstraZeneca for how mRNA therapeutics™ will enable many new innovative drugs for targets which are totally undruggable today. We look forward to this unique opportunity where Moderna can apply its research platform, broad intellectual property portfolio, and know-how to potentially contribute significantly to AstraZeneca’s pipeline.”

Headquartered in Cambridge, MA, privately held Moderna was founded in 2010 by Flagship VentureLabs in association with scientists from Harvard University and Massachusetts Institute of Technology.

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Related questions

01How stable is the antibody?

A crucial question often addressed during preclinical development focuses on the in vivo stability of therapeutic antibodies. Increasing the half-life of a therapeutic antibody has several benefits ranging from higher treatment efficacy to increased advantages for the patients who will have a fewer number of therapy sessions and a reduced cost. Given these compelling benefits, following the identification of therapeutic antibodies with the desired specificity, developers usually subject them to a refinement step to increase their stability. This process is often hindered by the lack of reliable experimental tools to predict the half-life of antibodies in patients. The major hurdle of using mouse models to predict antibody stability in the serum lies in the way immunoglobulin proteins are processed by the organism. In mammals, most proteins circulating in the serum undergo constant uptake by endothelial cells and are routed through the endosomes to the lysosomal compartment for degradation. In the endosomes, immunoglobulin G (IgG) proteins are recognized and bound by a transmembrane protein, called the neonatal Fc receptor (FcRn), which mediates their recycling to the plasma membrane and subsequent release back into the serum. As a result, the half-life of IgGs are significantly extended by this mechanism. Since most therapeutic antibodies belong to the IgG class, this recycling system is very relevant for their relative stability in the body. Remarkably, the relative affinity between IgGs and FcRn is extremely disparate between different species, with the mouse receptor showing a much higher affinity than its human counterpart.

Source: www.genengnews.com ↗

02Undruggable or unscreenable?

Another obstacle to discovering new PPI inhibitors is the lack of libraries designed to hunt for them, points out Philippe Roche, PhD, senior scientist at the Integrative Structural and Chemical Biology team at the Cancer Research Center of Marseilles, France. “If you screen PPIs using libraries that were designed for kinases or GPCRs, that’s why you don’t get a lot of good results,” he says. To that end, his group began assembling a library focused on orthosteric inhibitors of PPIs. The result was 2P2Idb, a hand-curated, structural database cataloguing orthosteric inhibitors of PPIs for which the interface had been 3D characterized. From analyzing these known PPI inhibitors, and what structures they had in common, Roche and his colleagues developed a model to predict whether compounds would likely inhibit PPIs. Using this method, 2P2Idb creates an enriched screening library that dramatically increases the hit rate compared to standard libraries. Having proven their success with a small library of 1600 compounds, they are in the process of expanding the library to 10,000 compounds. Once that’s published, “the idea is to make this library available to labs around the world,” Roche says. “We will provide the library free of charge for people to be able to screen PPI targets.”

Source: www.genengnews.com ↗

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Peptide Therapy Guide Editorial Team

Editorial team for Peptide Therapy Guide.

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