Pharma and academia - how opposites attract

Of the many elements that are drawing industry and academia together in pursuit of drug discovery, one of the driving forces is the development of novel targets and the complex biology that underlies those targets. No longer can big pharma go it alone with in-house R&D: instead, industry is looking to re-engage with basic scientific research in a collaborative, rather than contract, relationship.

A case in point is the recent announcement of the Translational Oncology Research Collaborative Hub (TORCH) between the Peter MacCallum Cancer Centre and Pfizer Australia. The collaboration is an extension of a long-standing relationship between Peter Mac and Pfizer, which in the past has been instrumental in helping Pfizer develop Sutent, a multi-kinase inhibitor approved for renal cell carcinoma and gastrointestinal stromal tumours.

The collaboration will see Pfizer commit $15 million to support further research at Peter Mac, particularly in three areas: molecular imaging, cancer genomics and early stage clinical trials. "[PET imaging and genomics] are important in the early validation of our compounds," Pfizer's head of strategic alliances, Dr Dan Grant, says.

"By bringing these two processes together, getting different markers of response, we are able to streamline the process of drug development and hopefully get drugs to market quicker.

"The real value of the collaboration is that the same people who do our early stage pre-clinical imaging programs, helping us to find what drugs are effective, also take those drugs and use them in the early stage clinical trials."

Pfizer is working in particular with clinical oncologist Associate Professor Grant MacArthur; the director of Peter Mac's Centre for Molecular Imaging, Professor Rod Hicks; and a host of collaborators in protein chemistry, led by Dr Rick Pearson. It has also funded Associate Professor Ricky Johnstone from Peter Mac's gene regulation lab through a five-year research fellowship in genomic oncology.

"The collaboration is aimed at taking our pre-clinical compounds into phase I, first-in-human trials," Grant says. "It is marrying our philanthropic or grant activities with our commercial activities."

Dr Julian Clark, head of business development at the Walter and Eliza Hall Institute (WEHI), is a big fan of industry-academia collaborations too. Clark believes that it is time to kill the stereotypes held by both research and industry scientists. "Yes there are horror stories out there on both sides, but I think there are enough of us now that we can say we cut the mustard."

---PB--- Kill the stereotypes

WEHI is Australia's oldest medical research institute but it has long-standing - and commercially valuable - relationships with the private sector. For Clark, the most important factor is scientist-to-scientist alignment throughout all collaborations. "Get them aligned and you are half-way there," he says. "[Scientists] are the drivers, not business developers. They are the heroes and the ones who make it happen, contrary to popular belief."

He takes a pragmatic approach to the commercialisation route: whether it is industry-sponsored research or institutes spinning out a baby biotech, whatever suits the situation. "I think many in the past haven't realised what an extraordinary amount of heavy lifting is required for a spin-out and how you are chronically undercapitalised, particularly now that big pharma and big biotech are re-engaging."

This was the situation facing WEHI several years ago with its ground-breaking apoptosis research: whether or not to spin it out when "ten-ton gorillas" like Abbott and Genentech were on the playing field. "It would have been absolute madness," Clark says, "so we thought a collaboration was the way to go, and so did Genentech."

The apoptosis collaboration that WEHI is now involved in with both Genentech and Abbott began in the late 90s between, as expected, research scientists. WEHI's Professor Andreas Strasser and Dr David Huang had developed a research relationship with Vishva Dixit, then head of early stage oncology at Genentech. The researchers published together and set the scene for the flow of information.

"Initially Genentech were not that interested in a discovery collaboration because they were unaware of the speed at which we'd set up our own facility and skill base, but by the time we developed early stage compounds, Genentech were very interested," Clark says. "The initial collaboration was purely scientific but that led to a collaborative agreement in 2006."

The other gorilla, Abbott, was at that stage a competitor, but having worked with Genentech on another project, Abbott decided that a three-party collaboration was the way to go. The collaboration is now in the lead optimisation stage for small molecule cancer drugs targeting pathways that control apoptosis.

"During the lead up we put a lot of focus on developing genuine project management systems and getting our lab notebooks as good as they could be, so when Genentech came along to do their due diligence we were on top of it," Clark says. "There is the tendency to assume that academia can be a bit leaky and chaotic. Our goal was to prove that we could work at the same level as they demanded."

---PB--- Valley of lost opportunities

The Genentech/Abbott partnership is just one of many that WEHI is involved in. Another is the new CRC for Cancer Therapeutics (CTx), which Clark was heavily involved in establishing.

While CTx is a CRC and as such has a heavy research focus, it most definitely has an eye on commercialisation. One of the partners is the UK's Cancer Research Technology (CRT), the commercialisation arm of Cancer Research UK, one of the world's largest charities with donations of around $700 million per year.

"The CRC is unashamedly established on the fundamental idea of copying and improving on CRT," Clark says. "They come in and pop training wheels around us, and by the end we aim to be a self-sufficient company just as they are."

In addition to WEHI and CRT, the other partners are CSIRO Molecular Health Technologies, Monash University, Peter Mac, the St Vincent's Institute, the Bio21 Cluster and the Cancer Council Victoria, all in Melbourne. Griffith University's Eskitits Institute is on-board, as is Adelaide biotech Bionomics, and US equipment giant Millipore.

CTx is also unashamedly a product development CRC, he says. Bionomics will be doing some commercialisation of their own targets while also contributing skills in medicinal chemistry and high-throughput screening. All other commercialisation will be handled by CRT.

"This is [a project] that is taking the issue of industry and academia and addressing the funding gap, what we call the Valley of Lost Opportunities," Clark says. "As taxpayers we generously pour money into great cancer research that can't go anywhere because there are not these bridging funds. And the cruel irony for us is that medical research institutes are not eligible for pre-seed funds. We do have opportunities but they can't go anywhere.

"We deliberately set out not to be dominated by a single big pharma because they have their own agenda and they tend to cherry-pick. Whereas CRT is the translational conduit for Cancer Research UK ... by definition they are not allowed to cherry-pick. So long as it is related to cancer and it is valid and sensible they have to run with it. That's exactly what we want to do - to be a portal and gatekeeper for Australian science."

As Clark points out, regulatory authorities like the US FDA are requiring more information and evidence from basic science at earlier stages in the drug development process. "Because a lot of our drug development these days is addressing novel targets, the science is less understood," he says.

"What it highlights is the high risk of drug development in the cancer area and the fact is that the biology is still not well understood. That's why my emphasis is that you must have multi-disciplinary teams all the way from laboratory molecular biologists through to clinicians, to chemists and onwards. These are first in class drugs, very high risk, no guarantee whatsoever.

"You have to have those disciplines - the clinical oncologists and the chemists - sitting around the same table. It makes sense and it's a lot more fun, because you have cultural diversity, which is great."

This is something that Dan Grant agrees with. Each year, Pfizer Australia invests about $50 million in science, a large portion of which is on clinical trials. It also spends a large portion on collaborations with leading universities and research institutes. Globally, Pfizer spends approximately $7.5 billion on R&D, much of it external. Why so much, when it employs 12,000 people in R&D alone?

"We are very good at doing in-house research and we have been very successful over the years but we've come to realise that we represent a very small portion of what's being done in health and medical research," Grant says. "We are about three to five per cent, which is quite a lot, but we still need to be interacting with the world's best scientists."