Despite its competitive nature, the drug discovery sector has embraced collaboration successfully, says Benedict Cross, Chief Technology Officer at Phoremost.
The drug discovery and biotechnology industry is historically a competitive arena, both intellectually and commercially, where the race to the finish line can be characterised by unseemly acts of avaricious behaviour. And yet over the past decade, a clear prevalence of institutional cooperation has delivered numerous unexpected alliances. Amplified by necessity and pragmatism, a new order of inspiring collaborations has established a route to success, and this is particularly apparent where platform technologies are core to the discovery effort.
It is first worth taking a critical consideration of what a platform really is in drug discovery, as it is a phrase that can often be misapplied. In essence, a discovery platform must have three key features: it must be a proprietary or unique approach or capability; it must be broadly applicable either in multiple successive programmes, multiple disease indications, or multiple applications; and finally (crucially) it must enable novel and successful discovery routes. If these features are met then the operators of a good platform can quickly find themselves in a position in which the potential of the applications outstrips the resource available to them in time to capitalise, and the conditions are therefore met for fruitful collaborative research and drug discovery.
The pharmaceutical industry has been increasingly receptive to embarking on these kinds of collaborative platform agreements, and although this can result in M&A and exclusivity barriers, in many cases the inventors of platforms are left free to operate multiple collaborations in parallel. This provides the opportunity to maximise the uptake and the value of the discovery mechanisms and is a welcome maturity in the industry of platform-based deals. In time, it should also lead to a greater breadth of non-competing drug development programmes.
Some notable recent examples are found in some of the fastest developing areas in biotech. CRISPR platforms have found excellent scope for collaboration and application in both therapeutics and target discovery. Pioneer companies such as CRISPR Therapeutics, which has been able to team up with Vertex to apply its platform in a strategic collaboration in multiple undisclosed indications and disease areas, are a good example of the early uptake and recognition of the synergy in expertise, research muscle and intellectual property. Similarly, REPARE therapeutics recently established an impressive and exciting alliance for target identification with BMS, to apply its CRISPR-based SNIPRx® platform to uncover new targets in precision oncology.
Beyond CRISPR there are now also next-gen platform technologies for target ID and drug development which have shown similar synergistic collaboration potential. PhoreMost, a drug discovery company based in Cambridge, UK, has developed a screening platform using a proprietary approach called PROTEINi, and has established multi-programme alliances with major pharmaceutical companies (Boehringer Ingelheim, Otsuka and others) as well as biotechnology companies (Oxford Biomedica and C4X). This is a good example of non-competing platform application, as each programme seeks to extract a distinct drug discovery potential from a broadly applicable novel technology. PhoreMost’s alliance with Oxford Biomedica also highlights another area ripe for development in immunotherapy and new therapeutic delivery technologies. The depth of expertise and intellectual property held by each party is a natural fit for collaborations, combining novel drug target discovery with a rapid route to the clinic.
Computational science and the spectacular rise of artificial intelligence (AI) in drug discovery have created vast excitement and a sense of expectation for substantial impact in drug discovery, and collaborations have duly flowed in pursuit of the promise. An alliance between AstraZeneca and AI biotech BenevolentAI has already shown this promise can potentially deliver, with the identification and progression of a lead candidate target in chronic kidney disease through the collaboration. Much is left to understand about the relative likelihood for similar late-stage success of such platform outputs, and AI in general (Bender & Cortés-Ciriano, 2021), but one area where it has already started to make a substantial impact is in virtual screening and drug modelling. Here quantitative and testable outputs are readily available and the outcomes more predictable than for the irreducibly complex nature of clinical response. Boston, US-based AI leader XtalPi recently also aligned its platform with the discovery outputs of PROTEINi, as part of a collaboration to exploit their proprietary approach in PhoreMost’s ambitious ‘drugging the undruggable’ mission. This is an exciting and relatively rare example of two leading platforms coming together for novel development opportunities, rather than an application-focused collaboration, and the results will be fascinating to see.
It would be remiss not to consider the targeted protein degradation space as a final notable biotech area particularly rich in collaborative potential. This field has matured and developed over the last five years, with early clinical assets now being progressed. There is opportunity for both corporate and molecular collaboration, as targeted protein degradation approaches often seek either bifunctional or monovalent tools to bring therapeutic protein targets together with cellular components known to cause their degradation, or elimination from the diseased cells.
The molecular collaboration element is interesting, but so far has not been fully tapped. Many laboratories have focused on the development of warheads (the part of the molecule which binds the disease target protein) whilst fewer have been able to identify new molecules which bind the degradation machinery. However, this is an area that is advancing quickly. For example, an adapted platform using PROTEINi is able to uncover such novel ligands of E3 ligases, and there is a strong expectation that corporate and platform-enabled collaborations will follow the molecular alliances between the two ends of these heterobifunctional molecules. Even so, the pioneers in this space, using only existing E3 ligase ligands, have already shown that their platforms are highly amenable to collaboration, with both Arvinas and Kymera aligning with multiple pharma companies eager to exploit their target programmes using a degradation strategy for therapy
One of the many unexpected outcomes of the terrible Covid-19 pandemic has been to emphasise even further this trend towards collaborative applied science. With numerous industrial and academic alliances forged in remarkable time under enormous pressure, the healthcare and research community has clearly demonstrated its ability and appetite for wide-reaching strategic scientific alliances. Thus, the scope for platform-oriented collaboration to contribute to a diverse and active R&D development portfolio in drug discovery is substantial. The benefits to both the individual companies advancing their science and to the patients, for whom the resultant discoveries are so important, is obvious, and growth of these arrangements is a very welcome sector trend.
Volume 22, Issue 2 – Spring 2021
About the author
Cross joined PhoreMost in 2019 to direct the evolution and development of its SITESEEKER screening platform. He is a geneticist and biotechnologist, with over ten years of professional research and management experience. He completed his PhD at the University of Manchester with postdoctoral training at the University of Cambridge exploring the mechanisms of control in the unfolded protein response using reverse chemical genetic screening.