Academic Drug Discovery

Translational research has been a hot topic amongst the academic life science research community for the last couple of years.  As research centers across the country attempt to form their own translational groups, a common thread amongst those institutions has emerged - the desire to have in-house drug discovery and early clinical validation capabilities.  Academic research centers are known for their ability to identify novel biologic targets and providing in-house drug discovery services enables academics to take their work to the next stage of product development.  

While proponents of translational research are quick to laud the vision of universities in creating soup to nuts drug development capabilities, others are not so supportive.  

Many critics challenge the notion that academic research centers should veer from their mission of conducting basic research.  Politics aside, it is very much an open question as to whether or not academic centers can execute the drug development process at the same level as pharmaceutical companies or CROs.

The Old Days

Historically, universities created compound libraries through the generosity of pharmaceutical companies.  In return for gifting compound libraries, pharma companies would receive modest tax breaks and academic goodwill.  However, the reality is that most of those libraries were gifted for a reason - either having little strategic value for the pharma company, or they were already picked over (scaffold fatigue).  Universities also found that it was challenging to use the libraries (not your typical post-grad skill set) and often cost $10,000+ to run large-scale screens.  This is turn caused university screening cores to run smaller, more directed screens, which limited their ability to find attractive leads.  

New Models

According to a recent Nature Reviews Drug Discovery article, there are 78 small molecule–focused drug discovery centers at universities or nonprofit research organizations in the US.  The report discussed some interesting stats:

• 2/3 of the drug discovery centers have high throughput screening infrastructure
• 2/3 have hit-to-lead medicinal chemistry expertise
• 1/2 have in vivo efficacy capabilities

In looking at those numbers, roughly half of the drug discovery centers appear to have the ability to perform IND-enabling work.  Building a competency in preclinical drug development takes lots of time, money, and talent, and it might be a stretch to say that 35+ research centers truly have that capability.  Even simple (if there is such a thing) drug discovery programs require scores of medicinal chemists, formulation chemists, toxicologists, etc.  Pharma is able to support disease-focused teams with deep preclinical drug development expertise, a luxury that universities cannot afford. Therefore, universities must work extra hard to find super talented researchers who can wear multiple hats during the development process. A good example of one university that seems to be doing all the right things is Duke University.

In 2006, Duke founded the Duke Translational Research Institute (DTRI) to expedite the translational development of drugs that were being discovered within the institution.  DTRI became the umbrella organization that was to oversee the management of the university’s clinical research activities.  Aided by a $52 million NIH grant, the DTRI hired a strong management team with start-up, VC, and CRO experience.  The DTRI provides CRO-like services for Duke faculty, as well as for outside groups, and is now self-funded.  In 2008, Duke hired Allen Roses, the former head of pharmacokinetics for GSK, to helm the Duke Drug Discovery Institute (DDRI).  Folding DDRI into DTRI gave Duke the ability to provide drug discovery, lead optimization, clinical development services for all faculty members, as well as outside groups.  DTRI is a good example of the kind of university-wide coordination, recruiting of talent, and capital required to execute a successful drug discovery program.

Engaging Venture Capital Funds

Ultimately, the goal of university drug discovery centers is to advance technologies to the point where investors and pharma companies become interested in licensing those technologies.  Pharma companies are more likely to fund collaborations with individual PIs or research groups around a specific indication than VCs, which prefer to license technologies directly into a start-up.  For pharma companies, they have a vested interest in developing long term relationships with Key Opinion Leaders, whereas VCs focus more on investing in a specific technology that fits into that particular fund’s investment thesis and timelines.  

As pharma pipelines have dried up and VC dollars become more scarce, both groups are increasingly looking for similar attributes when they evaluate technologies that are derived from university drug discovery units:

• Viable biology 
• Novel target in a relevant disease area
• Target is druggable (at least theoretically) / responder studies

The Future

Generally speaking, academic institutions are good at identifying interesting biologic targets, while pharma companies are good at generating molecules against those targets (See Osage blog - June 13, 2011).  Creating drug discovery centers at universities challenges that paradigm and co-locates drug discovery and development functions within the university.  Going it alone for universities enables them to have greater oversight and ownership of the development process, but at what cost?

With the NIH budget being flat for the past five years, it is hard to believe that drug discovery units at universities will be able to grow through grants.  Instead, universities will increasingly need to serve outside customers to cover their overheard and to subsidize services they provide to faculty.  Targeting outside customers brings the institutions into competition with CROs which likely can beat them on service offerings and prices.  

Despite these headwinds, there are a number of roles that academic drug development centers can play:

1. University talent could be directed to solve problems that hinder drug development for all stakeholders, such as creating models that better predict human versus animal toxicology, or generating improved disease models.  
2. VCs are hesitant to invest in cardiovascular, diabetes, and obesity diseases due to increased FDA regulatory burdens.  These are diseases that effect a large part of the US population and academic drug discovery units could certainly play a role in driving innovation in those areas.

It is too soon to tell if the academic drug discovery effort will be successful.  Ultimately, I think a couple of models will emerge and the early success of Duke’s discovery program certainly provides a blueprint for others to follow.