LONDON – Mogrify Ltd. raised $16 million in the first close of a series A that it expects to at least double before closing the round in the next 12 months.
This first tranche provides funding for the next two years as the company further develops and flexes its technology for directly converting one cell type to another without first reprogramming them to progenitor or pluripotent stem cells.
The aim is to transform the cell therapy business, opening up the repertoire of cells that can be generated, making it possible to readily generate allogeneic cell lines, and simplifying the process of scaling up and manufacturing cells.
"We're going to try and disrupt this industry," Darrin Disley, CEO of Mogrify, told BioWorld.
The new funding will support further development of in-house cell therapy programs in osteoarthritis, ocular diseases, immunotherapy and blood disorders; "inbound" projects in which companies look to Cambridge-based Mogrify to engineer specific cell conversions; and internal "speculative" research using the technology to stake out intellectual property.
The round was led by existing investor Ahren Innovation Capital LP, a venture fund that is supported by eight of Cambridge University's leading scientists. Parkwalk, a fund that has had successful exits from other companies formed and run by Disley and by Mogrify's founding scientists, also followed on, as did 24Haymarket.
The investors previously put $3.7 million into the seed round to get Mogrify – short for transmogrify – off the ground. (See BioWorld, Feb. 21, 2019.)
"I'm really pleased. We didn't have to go out and formally open the series A," Disley said. "That's why we are referring to an initial close. For the second close, we now have flexibility about when we do that."
The ability to transmogrify cells rests on the "Atlas of Transcriptomics" which details the exact set of genes that is expressed in each cell type in the body. The data were generated in the international collaboration Fantom5 (functional annotation of mammalian genomes) led by Japan's public research funding agency, Riken, in which Mogrify's founding scientists were involved.
Mogrify has added other sources of genetic and epigenetic information, enabling it to compare gene expression in the source and target cell types and determine what changes in gene expression are needed to induce the conversion.
As a second step, transcription factors are scored against the required changes in gene expression levels. That provides the input for a local transcriptome regulation network, which is used to calculate the effect of the transcription factors on the gene expression levels, informing the choice of factors needed to bring about these changes.
"The real advantage of the technology is that it's systematic," said Disley.
Other researchers are using trial and error to hunt for a handful of transcription factors in hundreds of thousands. "You can't do it experimentally," Disley said. "We can identify factors to reprogram cells and then optimize them, like a small-molecule drug discovery approach."
To date, adult fibroblast cells have been the convenient and conventional starting point for generating induced pluripotent stem cells and then converting these on to the desired cell type.
Mogrify can start with any cell type
Because it encompasses the transcriptome of so many different cells, its system also can prescribe which cell will make the best starting point for generating any other.
This is not driven by "hierarchical biology," in which cells transform one stage at a time. Rather, there is a tipping point at which the reprogramming makes enough changes in transcription to flip the cell over to the desired phenotype.
The lead in house program, MOG-001 has received funding from the government backed Small Business Research Innovation scheme to derive chondrocytes for treating osteoarthritis. The cells, which spontaneously form cartilage in vitro, are about to enter safety testing in mice and efficacy testing goats, Disley said. He expects to file an IND by the end of 2020 or the start of 2021.
The work also has informed a more conventional drug discovery program, in which Mogrify has identified a cocktail of small molecules that it intends to develop as an injected formulation, for stimulating the formation of chondrocytes in vivo.
Two other programs have both had grant funding from the public innovation agency Innovate UK. In one of these, Mogrify has derived allogeneic cells for treating an unspecified ocular disease. In the second, it is aiming to develop an allogeneic T cell that could provide a universal off-the-shelf starting point for any T-cell immunotherapy product.
Mogrify also has as yet unnamed partners that want the company to develop new routes to generate existing cell-based therapies.
"They are asking us 'can you generate this cell type?' The answer is, we can systematically identify how to do it," said Disley. That can lead to composition of matter patents on cells, he said.
With the series A in place, Mogrify is now expanding its staff roster from 20 to 60 employees, to support and grow the in-house pipeline and attract more external partners.