Biotechnology Innovation Organisation (BIO) have released the results of a huge study on clinical development success rates.
The study included 9,985 clinical trails and covered a wide number of therapeutic ares including Allergy, Autoimmune, Cardiovascular, Chronic High Prevalence Diseases, Endocrine, Gastroenterology, Hematology, Infectious Disease, Metabolic, Neurology, Oncology, Ophthalmology, Psychiatry, Rare Diseases, Respirator, and Urology.
Key findings from the study include:
- Clinical trial programs that used selection biomarkers saw an overall likelihood of approval (LOA) from Phase I of 25.9%, compared to 8.4% when no selection biomarkers were used.
- The overall LOA from Phase I for all developmental candidates was 9.6%, and 11.9% for all indications outside of Oncology.
- Of the 14 major disease areas studied, Hematology had the highest LOA from Phase I (26.1%) and Oncology had the lowest (5.1%).
- Oncology drugs were approved the fastest of all 14 disease areas.
- Rare disease programs had higher success rates at each phase of development vs. the overall dataset.
- Chronic diseases with high populations had lower LOA from Phase I vs. the overall dataset.
- Phase II clinical programs continue to experience the lowest success rate of the four development phases, with only 30.7% of developmental candidates advancing to Phase III
A webinar describing the work undertaken by the Open Source Malaria Consortium was held on 24th May and a recording of the meeting is now available.
The meeting lasted around 1 hour and be viewed online here
Open Source Malaria (OSM) is aimed at finding new medicines for malaria using open source principles, embodied in the 6 Laws of Open Research. At the moment the majority of work involves the synthesis of analogs of compounds identified by big pharma, with the aim of improving their potency while making the molecules more "druggable", what is known as a "hit-to-lead" campaign.
The questions raised in the webinar are highlighted as “Meeting Discussion Points” on the github page. Please feel free to join in the discussions.
Date Monday, 5th December 2016 Place Mathematical Institute, Andrew Wiles Building, Oxford, U Organisers RSC-BMCS (Royal Society of Chemistry – Biological and Medicinal Chemistry Sector)
Late Stage Functionalization (LSF) holds the potential to revolutionise the logic of chemical synthesis and open new ways to prepare novel natural products and medicines. The introduction of important chemical groups for medicinal chemistry in the very last steps of the synthesis through LSF could also dramatically speed up the preparation of NCEs and have a major impact on drug discovery. The availability of new powerful catalytic chemistries showing a high degree of functional group tolerance and that can be performed under mild conditions offer tremendous opportunities for chemists to access new molecules that cannot be made easily by conventional approaches.
A joint meeting Organised by SCI's Fine Chemicals Group and RSC's Chemical Information and Computer Applications Group
A little while ago I mentioned The Community for Open Antimicrobial Drug Discovery effort to provide free compound screening against a variety of infective agents. .
Primary Screening of a 1mg sample Test against key ESKAPE pathogens, E. coli, K. pneumoniae, A. baumannii, P. aeruginosa, S. aureus (MRSA), as well as the fungi C. neoformans and C. albicans, at a single concentration.
Hit Confirmation:- Confirm activity with minimum inhibitory concentration and counterscreen for cytotoxicity and membrane interaction.
Hit Validation:- Test the positive hit against a broader panel of microbes and evaluate the basic drug qualities of actives. CO-ADD will screen your compounds for free and make no claim to IP. The linked flyer gives full details
You can also read more details in this Nature article DOI
It looks like they have achieved an important milestone!
Thanks to our research community we have received 100,000 compounds from 30 countries in 15 months! Make a difference: clear the fridge, empty the shelves and send through your compounds for free antimicrobial screening against 5 bacteria and 2 fungi. We would also like to acknowledge the contribution of the French National Chemical Library that has safely arrived in Brisbane last week!
So if you have compounds sitting in the back of cupboards why not send them to be tested
The Drug Discovery Resources pages are intended to act as a resource for scientists undertaking drug discovery, they were initially based on a course I give but have been expanded to give much more detail and to cover subjects not covered in the course. The other advantage of an online resource is that I can include features not possible in static pages.
You can read more about it here DOI.
The first page to include an interactive structure is Aldehyde Oxidase, the PDB structure 4UHW is interesting because it shows the binding of both a substrate and an inhibitor binding at a site remote from the active site.
I hope you find this useful and please feel free to contact me with comments and/or suggestions.
I have updated the drug discovery resources on predicting sites of metabolism, I've added several new tools and web-based resources.
The next strategy meeting for the Open Source Malaria team is on May 24th. This is great chance to find out more about this effort and to look for opportunities where you might be able to contribute
- Project background & scientific objectives (5)
- Overview of project information sources - ie what's where (5)
- Data sources & summary of analyses (5-10)
- SAR overview, questions for the audience (20)
- Discussion (10-15)
- Final guidance on what's required from the audience & how to submit your suggestions & what happens next (5)
You can register here https://attendee.gotowebinar.com/register/7722880987090170883 - you need to register in order to receive the link for the meeting itself. Please forward this on to anyone you think might be interested,
I have updated the drug discovery resources page on Aldehyde Oxidase. In particular I have included more detail on the species differences and added the recent X-ray structure of AOX1 with substrate and inhibitor bound.
A little while back I mentioned the Centre for Therapeutic Target Validation, well it seems that it has now been renamed Open Targets.
The Target Validation platform brings together information on the relationships between potential drug targets and diseases. The core concept is to identify evidence of an association between a target and disease from various data types. A target can be a protein, protein complex or RNA molecule, but we integrate evidence through the gene that codes for the target. In the same way, we describe diseases through a structure of relationships called the Experimental Factor Ontology (EFO) that allows us to bring together evidence across different but related diseases.
There is a video online describing it in more details https://vimeo.com/149309356
This is an absolutely invaluable resource for anyone involved in drug discovery, simply type your query into the text box and submit the query.
This update also bring programmatic access to the data via a series of REST services, the API is fully documented. All the methods are available via a GET request and will serve the output formatted as json. There is a getting started tutorial available.