While its mRNA COVID-19 vaccination effort gets the most attention these days, Moderna Inc. is also moving in other directions as the company will lead mRNA discovery programs drawn from its early stage pipeline in new collaborations with Vertex Pharmaceuticals Inc. and Italy’s Chiesi Farmaceutici SpA.

These two deals highlight the “huge opportunity for mRNA beyond SARS-CoV-2 and vaccines,” Piper Sandler analysts wrote Sept. 16.

The Moderna and Vertex deal is the second for the two companies. In this newest effort, they struck a three-year agreement for discovering and developing lipid nanoparticles (LNP) and mRNAs to deliver gene-editing therapies for treating cystic fibrosis (CF). The venture first focuses on therapies to cells in the lungs allowing production of functional cystic fibrosis transmembrane conductance regulator proteins.

Moderna, which will conduct the initial research, will receive $75 million up front and is eligible to receive up to $380 million in development, regulatory and commercial milestones, plus tiered royalties on sales from products the collaboration produces.

Moderna is responsible for leading the charge for discovering and manufacturing the LNP and mRNA constructs encoding gene-editing endonucleases, while Vertex provides other gene-editing therapy components to eventually be formulated into LNPs. Vertex will also provide subsequent preclinical and clinical development and commercialization duties.

Stephen Hoge, president, Moderna

In a Sept. 17 conference call with investors, Moderna’s president, Stephen Hoge, said the two companies have looked at many different ways to deliver the therapy and “we obviously believe the fastest way to access the lung is going to be through an inhaled route. And so both of our partnerships with Vertex do look at pulmonary delivery through the group.”

Hoge added that about 10% of CF patients are not addressable with the CF transmembrane conductance regulator (CFTR) gene modulators that Vertex pioneered, so alternative approaches are needed. The two Moderna-Vertex deals focus on delivering mRNA that directly encodes for the CFTR protein that is either missing or non-functioning in CF patients. That CFTR protein then can normalize iron transport and address the disease, he added.

The first CF collaboration between the two companies was created in July 2016 and focused on using mRNA therapies to treat CF’s underlying cause by enabling cells in the lung to produce functional copies of the CFTR protein. At the time, the companies said they would explore using pulmonary mRNA delivery. The agreement called for Vertex to pay Moderna $20 million in cash up front and for Vertex to invest $20 million in Moderna, giving Vertex an ownership stake. Vertex also was called to pay Moderna future development and regulatory milestones of up to $275 million, including $220 million in approval and reimbursement milestones, as well as tiered royalty payments on future sales.

The Moderna-Chiesi deal

Moderna and privately held Chiesi, of Parma, Italy, will collaborate to discover and develop mRNA therapeutics to treat pulmonary arterial hypertension (PAH), a rare disease. Moderna will receive $25 million up front and could receive more than $400 million in development, regulatory and commercial milestones, plus tiered double-digit royalties on net sales. Chiesi is slated to help with development and worldwide commercialization and to pay all the expenses related to the collaboration.

PAH is a rare and life-threatening disorder marked by considerable morbidity and mortality, according to DRG. Despite the availability of a wide array of drugs for PAH management, high unmet need remains for options that offer improved survival, long-term efficacy and better quality of life for patients.

This is Moderna’s first deal with Chiesi, which specializes in researching rare disease therapies, including those for pulmonary diseases.

Elsewhere in its pipeline, Chiesi’s global rare disease unit is currently collaborating with Protalix Biotherapeutics Inc., of Carmiel, Israel, to develop pegunigalsidase alfa, an alpha-galactosidase stimulator, for treating Fabry disease. In August, the FDA accepted the companies’ BLA, granting a priority review and setting a Jan. 27, 2021, PDUFA date. No advisory committee meeting is expected, according to the companies.

In June, Chiesi’s global rare disease unit, based in Boston, signed an exclusive licensing agreement with Bioasis Technologies Group, of Guilford, Conn., for the xB3 BBB platform technology in treating rare diseases with a focus on four undisclosed lysosomal storage disorders. Chiesi will pay Bioasis an up-front fee of $3 million. Bioasis could receive additional development, regulatory and commercial milestone payments of up to $138 million, as well as additional royalties on net sales of licensed products, pending market approval. Chiesi will be responsible for all costs associated with research, development and commercialization of the four undisclosed programs.

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