Cancer Research Technology and FORMA Therapeutics: An excellent marriage

2014-03-27 00:00:00

FEATURE INTERVIEW: Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics.

This interview appeared in the Spring 2014 issue of Insight, CRT's industry newsletter.

In July 2013, FORMA Therapeutics and Cancer Research Technology (CRT) announced a bold research initiative to discover innovative tools, technologies and therapeutic drug candidates against a variety of protein homeostasis regulators called deubiquitinating enzymes (DUBs).

Under the agreement, FORMA is pairing its ultra-efficient drug discovery capabilities with CRT’s expertise in translating academic discoveries through its Discovery Laboratories (CRT-DL) and initially five principal investigators from the academic network of Cancer Research UK: Professors Michael Clague and Sylvie Urbé (University of Liverpool), Dr. Benedikt Kessler (The University of Oxford), Dr. David Komander (Medical Research Council, Laboratory of Molecular Biology, Cambridge) and Dr. Huib Ovaa (Netherlands Cancer Institute, Chemical Biology Laboratory).

We caught up with Dr Steven Tregay to discuss how the alliance was established and, eight months in, how it is progressing.

CRT’s relationship with the FORMA team developed over several years, and numerous interactions, prior to signing the deal. As Steve explains, this period helped FORMA to fully appreciate the breadth and capabilities of CRT.

“Our relationship with CRT evolved over time. As we got into deeper discussions, we had an increased appreciation of what CRT could bring to the table – the drug discovery capabilities of CRT-DL as well as the tremendous breath of CRUK-funded science that CRT has access to.”

After identifying DUBs as an area of mutual interest, and exploring options for working together, the next evolution in the relationship between CRT and FORMA was to speak to the academic collaborators involved.

“What was exciting to us was that the academic team not only brought incredible skills across a range of capabilities – crystallography, cell-based assays, chemistry – but that they also knew each other well and were already working together. It wasn’t independent labs working on independent projects; they had been bought together under the CRT umbrella.”

This key aspect of CRT’s alliance model – bringing together multiple academic PIs to work together around a themed area of cancer biology – offered FORMA the opportunity to hit the ground running.

“Progressing from understanding what the deal was to engaging with the PIs was almost instantaneous. What’s often an incredibly time consuming step was readily catalysed by virtue of their pre-existing relationships, providing FORMA the ability to actively jump-start engagment with the PIs. This is the first time we’ve had all of the academic networks fully established from the get-go.

“CRT’s model of having established relationships with each of the universities at which the PIs are funded, with Business Development Managers already interacting with the technology transfer offices, to my knowledge is unique to CRT. No other foundation has that in place to the same extent as what CRT has built.

“This integration supports what FORMA could bring to the table – a high-throughput drug discovery engine which enables us to progress quickly to tool compounds. It really was an excellent marriage.”

When asked about the role each party plays within the alliance, Steve explains, “Each party brings their expertise to the alliance at the relevant stage. When it makes sense to do it in academia, we do it in academia. The in-house scientific capabilities of CRT-DL means questions can be immediately explored locally, executed by extremely well-trained drug discovery scientists. And then FORMA provides its unique skills, whether that’s our high-speed synthesis capabilities – where we’re able to make upwards of 100,000 compounds per year –our ability to screen upwards of 40 targets, or providing ultra-selective tool compounds to facilitate testing biological hypotheses.

“The groups work in tangent with each other, which allows you to align resources effectively. And all of this is coupled with the very close alliance management function within CRT. Together, these aspects enable the alliance to move very quickly. It’s the interplay of what academia does well and what is required to enable rapid drug discovery.”

FORMA has a broad approach – to enable, through advanced technologies, a new paradigm in drug discovery.

“We [FORMA] look at new areas of biology and design strategies to rapidly explore their potential for drug discovery, where our engine provides a unique approach. This is why the breadth of biology that CRUK funds is particularly attractive. They are willing to invest aggressively in emerging areas of biology that have promise to become cornerstones of cancer therapy. We’re all aligned to interrogate innovative pathways that are going to change the treatment of cancer.”

DUBs is a prime example of one such area, representing an attractive area for drug discovery exploration. The alliance has the potential to significantly accelerate understanding of the relevant biological applications of DUBs, a key class of enzymes involved in regulating protein homeostasis.

“We have tried to be flexible in our approach, initially profiling panels of related protein targets within a family for chemical tractability.” says Steve. “It’s very important to CRT and FORMA to fully evaluate the therapeutic potential of each asset toward a patient benefit. By focusing on key regulatory protein targets, it’s anticipated that multiple paths forwards for an asset or target may be realized. We first understand the family and the biology, and then prioritise the targets for clinical hypothesis exploration using ultra-selective quality tool compounds. We’re fundamentally driving the biology and turning target validation on its head.”

“The speed at which we were able to hit the ground running with this alliance is testament to having all of the groups already working together and no learning curve. There wasn’t a lag to establish all of the relationships. As a result, we’ve already established the breadth and scale of the alliance and leveraged the core capabilities of CRT-DL and each of the PIs. Over time we expect lots of exciting announcements to emerge in the literature.”

Finally, we asked Steve how he sees the relationship between FORMA and CRT developing in the future.

“Given the large number of targets we’re executing together, there will be a natural evolution of the relationship as the pipeline advances. Right now we’re focused on DUBs biology but over time this will take us into clinical directions and the next evolution will be to bring in PIs with disease biology expertise.

“Together we’re laying out new paradigms both in terms of drug discovery and academia-industry collaboration. I’d love to see a new target family emerge as another potential area of collaboration between CRT and FORMA.”

Notes to editors