My recent post on the Drugs for Neglected Diseases Initiative (DNDi) brought some emails from Robert Don at the organization. He has more details on the sleeping sickness project – pointing out, for example, that the contribution from Scynexis was not pro bono, as I’d assumed:
We actually contracted a team of 10 chemists at Scynexis for over 4 years at 320,000 USD per FTE p.a. plus additional for extraordinary expenses such as expensive starting materials. We also employed independent consultant medicinal chemists to challenge the team. They worked on a number of hit to lead projects but the contribution to SCYX7158 was the majority of the team for around three years. . .In addition we assigned all IP to Anacor and increased the size of their library with 20-30 FTE years of well annotated compounds. We retain a license to use the results for neglected diseases in our kinetoplastid disease portfolio. Since then, Anacor have also contributed very significantly in their own right to discovery research for neglected diseases in our portfolio as well as many not included in our portfolio.
I’m going to make a note of this in the earlier post as well. He he also provided many more details on how DNDi is trying to do what they do, and I thought I’d pass those along for comment as well:
Our ultimate goal is to provide modern medicines to neglected patients. We have short, medium and long term strategies and as you correctly stated we repurpose drugs, look for geographic extensions, prove and disprove the efficacy of treatments currently in use etc. In fact we look to any incremental change which can improve the lot of these patients in the shortest possible time. Our long term goal is development of field-suitable NCEs together with a guarantee of access to them. To ensure accessibility we seek an industrial/pharma partner who will file for marketing authorization and involve them from early in the development phase. These agreements delink the cost of research from that of manufacture and distribution. They ensure a low cost to patient and a small profit to the partner. We want sustainability and do not advocate agreements in which any player stands to make a loss e.g. donations.To delink the cost of R&D we need to find mechanisms for R&D in which the cost is not borne by the industrial partner – although we welcome any contribution if they are willing to do so.
We do not harbor any pretension that we can do the science/black art of medicinal chemistry any better than an industry which has been locked in competition for decades although I must admit that when we employed our head of discovery he did say that if he proposed nitroimidazoles as anti-infectives he would receive a severe warning if not dismissal by his previous employer and to follow that by fiddling with oxaboroles would definitely be a career limiting move. (We have one of each in GLP tox for leishmaniasis but the pipeline of candidates, leads and lead series behind is much more conventional)
We screen both pharma and commercial libraries and place no financial value on these assets but do pay all screening costs. We do however appreciate their inestimable scientific value. Following screening, all pro bono work (hit to lead, DMPK, tox and CMC) is fully costed by our partners and included in our financial reporting as in-kind income and expenditure.The core and bulk of my budget is medicinal chemistry, ADME, toxicology and CMC at the same CROs as contracted by pharma and at the same cost. It is supported by in-house medicinal chemistry and parasitology expertise, contracted medicinal chemistry support and retired mentors.Savings are made through novel partnerships. For example a multilateral agreement between five pharma covers much of our hit to lead at very little cost to them and us and in a period of a few months we get SAR around hundreds to a thousand plus compounds for each hit. (Don mentions that a manuscript on this process has been submitted – DBL). We also save considerably by not competing. We are not the only player in the field and if we become aware of others working in the same area we share our experiences and this is reciprocated by other PDPs. Our nitroimidazole currently in GLP tox grew out the TB Alliance program which yielded PA824. Within the industry for example, how many advanced DAA programs for HCV were dropped because one company got to market and a couple of others had good second generation pipelines? We have the capacity to go from screen to NDA and the only failures are scientific – never commercial.
In addition to providing modern relief to neglected patients, DNDi is a test-bed for new forms of collaboration between all players in the business of drug R&D. It is my joy to have tremendous freedom to experiment with this and my hope that some outcomes may stimulate a broader discussion on how we might reduce the costs for all drugs in a sustainable manner. I would certainly welcome any ideas, suggestions or offers from you and your readership on how we might constructively challenge the status quo.