Mogrify: Using Big Data To Transform Development Of Cell Therapies

Money in the bank, biotech legacies onboard, a fresh partnership, an emerging internal cell therapy pipeline and a grand vision for the broad-scale application of its technology – has Mogrify got it all? The biotech’s chief business officer, Karin Schmitt, talks to In Vivo about the group’s near- and long-term goals.

UK-based Mogrify, Ltd., which emerged from stealth mode in 2019, is using a big data-based platform technology to transform the development of ex vivo cell therapies and pioneer a new class of in vivo reprogramming therapies. The company boasts Jane Osbourn, former vice president of R&D at MedImmune, as its chair, and Darrin Disley, former CEO of gene-editing firm Horizon Discovery Group PLC, as its CEO.

In May 2019, Karin Schmitt joined the company as chief business officer to lead Mogrify’s commercial operations and its R&D function. Schmitt was previously an early employee in several successful start-ups, including Millennium Pharmaceuticals, Exelixis, Inc. and Horizon Discovery, making significant contributions to the growth of those companies to IPO and beyond. In an exclusive interview, she spoke to In Vivo about how COVID-19 had challenged Mogrify in 2020 and her expectations for the coming year.

Schmitt told In Vivo she liked to join a company when it was small and developing. “I always look at the people, the existing leadership that I’d be working with, and of course the science. The science was very interesting at Mogrify,” she said. Schmitt was also enticed to join Mogrify as she saw the potential to be able to build a successful biotech in the UK. “I wanted to build a company here, in the UK, and I think Mogrify offered the foundation for that, intending to transform cell therapy; the company is well placed in the UK’s emerging environment for cell therapy development.”

Mogrify’s technology has deep foundations and has been under development for more than 10 years. Based in Cambridge, UK, the biotech's origins lie in the long-running international FANTOM (Functional Annotation of the Mammalian Genome) consortium led by Japan’s Riken scientific research institute. Mogrify co-founders Julian Gough and Owen Rackham were members of the FANTOM5 consortium, a project which undertook deep transcriptomic analysis of a representative set of more than 150 human cells. In January 2016, the researchers published a paper in Nature Genetics outlining a predictive system for transdifferentiation, or converting one cell type to another without going through a pluripotent state.

Current cell therapy development approaches generally involve starting with stem cells or delivering transcription factors into mature cells such as skin fibroblasts to turn them into induced pluripotent stem cells (iPSCs) and then reprogramming them. The latter method, which won Shinya Yamanaka a Nobel Prize in 2012, got around the ethical issues of using embryonic stem cells (ESCs) and helped to transform the field of regenerative medicine.

In contrast, Mogrify offers a scalable, systematic and efficient method of converting any human cell from any state (whether mature or immature) to any other human cell of any state. The company’s founders were able to develop a system to combine gene expression data with regulatory network information to predict which factors would be necessary to induce a cell to convert from one state to another. By applying it to multiple cells and tissue types, the researchers created “an atlas of cellular reprogramming.” It was this system that they dubbed MOGRIFY. In addition to identifying transcription factor-driven cell conversions, small molecules that are able to affect the expression of the key predicted transcription factors can be identified to create a small molecule conversion cocktail. This approach has the added benefit of not requiring the transduction of transcription factors and consequently holds greater potential as an in vivo reprogramming therapy.

Schmitt said the company’s technology “has a great potential to address some of the bottlenecks we have seen in the cell therapy field as well as pioneer new therapeutic modalities.” Mogrify has positioned itself, leveraging the MOGRIFY and now EpiMOGRIFY platforms, to enable the allogeneic cell therapy field by driving the speed, efficiency and maintenance of cell conversions. Allogeneic cell therapy involves transferring cells from one individual to another, as compared with autologous cell therapy, which involves extracting cells from an individual, manipulating the cells in a lab, and then transplanting the cells back into the same individual. “Our platform permits us to use any scalable source cell type, such as iPSCs or fibroblasts … these are not our ultimate product, but a starting point for us to produce any clinically valuable cell type.”

Internal Programs And COVID-19 Delays

Mogrify has established a number of internal projects to move forward. “We are focusing on immunology and ophthalmology for our internal programs,” Schmitt said. These programs are at the “functional validation stage.” In the near future, the company will be deciding which product candidates to progress to the next level and “starting to plan for process development” Schmitt predicted. Then in the medium term, “we will be thinking about in vivo proof of concept.”

The COVID-19 pandemic has presented some challenges but also opportunities for Mogrify. The company was able to keep staff in the labs and continue its work throughout 2020. However, Schmitt noted that “some of the services we rely on and the supplies we need were slowed down, so it slowed us down a bit.” Also, Mogrify had planned to do some in vivo work through university facilities, but these sites were closed or prioritized for work against SARS-CoV-2. “Other facilities had also become prioritized for COVID work,” Schmitt said. “There were some challenges but overall, I felt we maintained momentum.”

An unexpected impact of the pandemic was that it caused Mogrify to reassess what it wants to achieve. “It brought focus to the company which was great, the timing for that was good and we came out of it positively, with a strong road map for the next few years ahead … All of a sudden there was a pressure that made you think, but there was also a little bit more time available because a lot of the travel fell away.”

Focus is the key for growing biotech companies, Schmitt believes. “I think start-up companies tend to want to do too much. Also, a start-up environment can be somewhat chaotic, you hire very quickly, bring in new people, whilst the support functions may not be in place.” At Mogrify, Schmitt said, “Very early on we made sure we have the appropriate infrastructure in place to support the growth of the company, starting with both human resources and finance functions.”

She added, “I want to provide an exciting start-up environment where people feel inspired and a part of the journey. To me, one of the things I keep on thinking about is my time at Millennium and the culture we had there. It just was a great place to work and I’d like to recreate that here.” Schmitt has devoted some of her time at Mogrify to aligning core values for the company with the leadership team, with a focus on an innovative and collaborative culture. “We are very ambitious in our vision and our lab work; one of our core values is ‘Nothing is impossible’, which drives us on our mission to deliver world-class science, commercial success and patient impact.”

Raising More Cash

In October 2019, before the COVID-19 pandemic took hold, Mogrify raised $16m in a series A financing round, led by existing investor Ahren Innovation Capital. The group previously raised $3.7m seed funding in February 2019. Schmitt noted that Mogrify had been in good shape financially to deal with the coronavirus outbreak.

Despite having raised funds before the pandemic, the company continues to speak with other investors. Schmitt said this activity was driven by the fact that “money is available and there is excitement around venture capital placing money into new and innovative companies.” Investor sentiment would rise and fall, Schmitt noted. “We want to be in it whilst we’re seeing this buoyancy, especially with the COVID situation. Some people have predicted it is not going to stay this buoyant, so it’s a good window for us to be active knowing that we will need more money to move into the clinic.”

Schmitt noted that raising cash in Europe was different from her experience in the US. In Silicon Valley, she said, investing was driven by a shared vision for a company. In Europe, financing is pushed by milestone achievements. “There are differences in the way investors operate” in the US versus Europe, Schmitt said.

Sangamo Alliance

In April 2020, Mogrify and Sangamo Therapeutics signed a collaboration and exclusive license agreement for Sangamo to develop allogeneic cell therapies from Mogrify’s proprietary iPSCs and ESCs and Sangamo’s zinc finger protein (ZFP) gene-engineered chimeric antigen receptor regulatory T (CAR-Treg) cell technology.

“Sangamo, for us, is a premier partner. They have an excellent track record. We liked the people but we also saw that they are committed to this field, so we’re very excited to work with them on this Treg collaboration,” Schmitt said of the arrangement.

Mogrify will be responsible for the discovery and optimization of the cell conversion from iPSCs or ESCs to regulatory T cells, and Sangamo will be granted exclusive rights to use Mogrify’s technology to create Tregs from iPSCs or ESCs. Sangamo expects to then use its ZFP gene-engineering technology and therapeutic development capabilities to transform these Tregs into novel ‘off-the-shelf’ allogeneic CAR-Treg cell therapy candidates and hopes to take them through to registration for the treatment of inflammatory and autoimmune diseases.

On the one hand, Schmitt said Mogrify’s deal-making activity is driven by milestone and upfront payments. On the other hand, though, the company seeks collaborative partners it can glean insights from as it advances its own internal pipeline. “We can afford to go after a good deal and we don’t need to take any deal,” she noted. Mogrify also feels some responsibility to provide access to its technology more broadly. “It’s maybe a humanitarian goal in a way, but we want to see the platform used extensively and not just internally.”

Mogrify’s door is always open for partnerships and deals that will benefit the business, but deal-making is not its driving force. “We roughly have a formula for it. We think 60% of the company’s efforts should be on the internal work, 30% dedicated to partnerships, and there is a 10% effort aimed at exploratory work,” Schmitt explained.

“Discovery and development partnerships must be a good fit”, she added. The company may seek larger partnerships encompassing more than one specific cell type. While other deals will be “very specifically defined in the immunology and ophthalmology areas because that’s where our assets are very strong, and we continually look at the idea of a co-development.”

Outside of its key development areas of immunology and ophthalmology, Mogrify has an interest in exploratory projects in diabetes and the neuronal field, among other underdeveloped cell therapy areas.

Technology With Open Doors

Schmitt envisions Mogrify progressing with two key internal programs, with the aim of reaching the clinic by 2023/2024. As a small business, it would be feasible for Mogrify to run early-stage clinical studies itself, “but after that, we would seek to license an asset to a bigger partner to take it to market.”

Schmitt highlights that the continual evolution of the company’s existing platforms, MOGRIFY and EpiMOGRIFY, will see the inclusion of additional transcriptomic and epigenetic datasets, to improve prediction quality and accuracy. “The adoption of a systematic approach to the conversion and maintenance of clinically valuable cell types offers unique opportunity to transform the development of cell therapy.”

The company will also continue to explore, both internally and through research collaborations, novel applications for its technology within cell therapy and beyond. “There are so many applications for this technology, including other disease areas with a high unmet clinical need,” Schmitt said.