Next-generation business models are emerging through collaborative networks to help move candidates through tough terrain during drug discovery process. A Q&A roundtable discussion.
It’s a cliché, but it is still true that when it comes to drug development we live in the best of times and the worst of times. The effectiveness of early immuno-oncology drugs are transforming how we treat cancer and gene therapy has re-emerged as a promising strategy in conquering incurable diseases. Science is about solving big problems and today’s extremely high-tech tools and innovative partnering are providing incredible opportunities to meet that goal.
At the same time, the statistics for getting drugs onto the pharmacy shelf have never seemed more difficult. The Pharmaceutical Research and Manufacturers of America (PhRMA) estimates that for every 5,000 to 10,000 compounds that enter the pipeline, only one receives approval. Even medicines that reach clinical trials have only a 7-15% chance of being approved, in large part because it’s been so hard to translate promising preclinical findings to efficacy in patients. Added to this are serious threats to public research dollars—the lifeblood of academic research.
The high cost of drug development along with regulatory and scientific challenges have put so much pressure on biopharmaceutical companies that they are now focused on external collaborations for innovative ideas through the earliest and often stormiest phases of drug discovery—the 3-5 years between target selection and IND approval/Phase 1 studies that is sometimes referred to as the Valley of Death.
Next-generation business models are emerging through collaborative networks to support frontier science and innovation, address the early drug development gap and help move a good idea through the rocky terrain that separates upstream research on promising genes, proteins and biological pathways from downstream drug candidates.
Alliances with CRO/CMOs are becoming an integral part of R&D approaches as they contribute to building key scientific evidence for drug development programs for clinical success. CROs often have infrastructure to handle work that used to be the domain of basic science laboratories within Big Pharma. CROs also have highly-skilled workers—many began their careers in Big Pharma—in indispensable areas with deep clinical exposure.
Eureka recently spoke with representative from two of these innovative early discovery business models—Kathryn Chapman, Executive Manager of The Milner Therapeutics Institute and Charles McOsker, Senior VP of Technical Operations at BioMotiv—to talk about what it is like working in this space, how CROs fit into it and ways in which these collaborations can expand. Also participating in the discussion was Swati Prasad, Senior Manager of Business Development and Scientific Alliances at Charles River who works closely with both Milner and BioMotiv.
The Milner Therapeutics Institute was launched 2 years ago with a £5 million donation from Jonathan Milner, the co-founder of the antibody producer Abcam. It will consist of academic-based drug discovery laboratories on the Cambridge Biomedical Campus (opening September 2018) and an already active outreach program that involves a consortium of seven pharmaceutical companies, three academic institutions and 36 affiliated partner companies, including Charles River.
BioMotiv is a for-profit accelerator that is part of the Harrington Project, a $300 million international drug development effort launched by University Hospitals Cleveland Medical Center to advance discoveries sourced from academic research and non-governmental organizations into new medicines. BioMotiv provides a novel link between academic projects and late stage commercialization partners.
Below is an edited version of the discussion, which occurred in May.
What is the most significant challenge you face in moving drug candidates forward?
KC: If the therapeutic area of a target is directly relevant to our pharmaceutical partners, the challenge is getting more data, the right data and making sure that it is human relevant data. If it is generally outside the scope of Pharma, then the challenge is access to independent funding to do the chemistry and clinical trials.
CM: Certainly, one of the challenges is identifying funding to do what many government funding agencies consider to be applied research. The level of funding and even more importantly the lack of expertise available to many academic investigators on how to take exciting foundational research and turn it into a candidate that can be developed is a huge challenge for academic investigators.
Why is it so difficult to get reliable data?
KC: It’s a number of things. A company may request a certain type of data and then later want another type of data so what you need to do is establish exactly what data you would need to allow the client to have confidence that the target is credible. Finding funding can also be an issue. This isn’t basic research and it’s not necessarily funded publicly. And absolutely, expertise matters.
CM: I think if there were significant increases in the amount of basic academic research funding, you would see a big improvement in the quality of data coming out of academic labs. I’m sure you’ve seen the recent studies showing there is a significant amount of academic research that cannot be repeated by an outside party, such as a CRO or other academic lab. This is attributed not to fraud or malfeasance but the pressures of publishing, especially in high-impact journals. This leads to [the idea] that “well I did one experiment and I got the result I wanted so I’m going to publish’ rather than having the time and funding to do the study the way most scientists would probably want to do it.
KC: A critical point is that industry repeats those experiments that academic labs have done. If there was more industry-academic interaction on some of these contracts that are likely to move forward you would find, I think, that the gap is not as far away. It would also mean that the transfer of assays and disease models and all the things that currently don’t replicate in industry would be much more fluid and you could then actually get that target validation. This is even more important as more and more R&D is externalized. Potentially, a number of experiments using CRISPR, phenotypic screening, organoids, 3D screens can’t be repeated inhouse because pharma companies don’t have all the expertise.
CM: That’s a really good point. In fact, when we are doing our due diligence on work that we are thinking about taking on as a Biomotiv project we will often identify experiments that are key to validating a hypothesis or a target and take them to a CRO to try to repeat them.
SP: From our perspective, we are seeing a lot more engagement with academic labs in repeating these kinds of experiments in a GLP-type setting. This helps to bring confidence to the data.
How does partnering with CRO’s work and vice versa?
KC: We are doing two things. We are partnering academics throughout the University of Cambridge with CROs. This happens when there is enough data for an academic to think about applying for more applied, translational grant funding. We have 36 affiliated companies and about 70% of them are CROs. They range from companies working on a single thing, such as an ion channel assay, to ones like Charles River that work across the board. We see them as absolutely essential to drug development.
CM: For those studies that help move a project along toward commercialization our strong preference is to use CROs. We try to use a relatively small number of CROs who we work with extensively.
SP: From the CROs perspective, we also work as consultants for our academic and biopharma partners, and provide inputs on how to de-risk their scientific and proof-of-concept programs. A lot of times we’re engaged quite early and they look forward to our ideas and our experiences on how a particular candidate can be developed. We also have an integrated drug discovery (IDD) team which encompasses a wide range of therapeutic areas and internal disciplines and expertise, including in vitro biology, synthetic and medicinal chemistry, structural biology, in vivo pharmacology, and subsequently, pharmaceutics and process chemistry. The IDD has delivered over 70 candidates to various biopharmaceutical partners and is a successful format.
CM: That’s an important point. For the past 1 ½ years we have been working with the IDD group on two major projects and it truly does work as a collaboration. It has provided us with valuable confirmation and new ways of thinking. The consultancy piece is, I think, somewhat unique and we have even taken it a bit further. A CRL advisor on one of our projects sat alongside our investigators and participated in the planning process, which let us integrate CRL’s capabilities and expertise in real-time, rather than engaging in the usual back-and-forth discussions on ‘can you do this?’.
Are there other gaps CROs can fill in the drug discovery process?
KC: When we go to pharmaceutical companies, the first bit of data they need is human data or clinical data. We are doing a lot of stuff right now with Big Data, such as genomics or transcriptomics that come from human datasets but also from experiments in the lab. I really think there is a role for CROs in some of their data curation, data interrogation and analyzing of the data, but with a drug development perspective, that an academic lab doesn’t necessarily have the time, resources or expertise to do.
Finally, there is a lot of tension right over potential cuts in biomedical research funding, both in the US and Europe, and drug pricing. What is your take on all of this?
CM: If the Pharma balance sheets start to look different it almost certainly will have an effect on the breadth and magnitude of outside investments. On the basic science side, if there is a cut in NIH funding it will have a direct impact on research coming out of academic labs. This means intuitively the opportunities for breakthrough drugs will go down.
KC: It is a complicated picture in terms of public funding in the UK given the current political environment. In general, funders want to see more demonstrable impact related to translational research. This will need cultural change and in my view greater academic/industry collaboration. I suspect there will be a greater dependency on private funding for the type of model we have. The current funding environment for biomedical research is tough.