Empowerment of rare disease patients in modern healthcare delivery



By David Cavalla, Numedicus Limited.

If you’re fond of alliteration you’ll know that you can divide the stakeholders in modern healthcare into three ‘P’s: patients, payers and pharmaceutical companies, with physicians and pharmacists taking additional minor roles. Traditionally the patient has played a passive part, but over recent years the patient community has dramatically increased its involvement and influence in modern healthcare delivery, particularly in the rare disease sector.

Approved drugs do not exist for over 90% of the 7,000-8,000 rare diseases, and the commercialization of niche products for rare and orphan drugs has become the most favored growth opportunity over the conventional mass-market ‘blockbuster’. Repurposing is a common development option, but the development of drugs in these areas is dependent on access to patients in clinical trials.

Patients with rare conditions are increasingly organized into communities with a voice, and they are using their collective power to get what they want, namely access to better medicines.

Social media helps patients organize

Rare disease patients are much more likely to be ill as a child, and from inherited genes, than as an older person. This leads to highly motivated communities consisting of patients and their friends and relatives. Social media makes it possible for self-organizing communities to further the aims of rare disease patients.

Pharma companies are keen to form alliances with patient groups to further their case for payers to reimburse expensive medicines.

A key demand of patient groups is that that healthcare resources are allocated to the patients, even when such resources are scarce. The charity Action Duchenne, recently parked the wheelchairs of over 100 teenage boys outside the UK parliament to campaign for reimbursement of the first approved drug for the condition.

Some of the carers of rare disease patients and the patients themselves go to great lengths to educate themselves about the relevant condition. From this position, it is an easy step for them to ask themselves a simple question – what more can a patient or carer do to improve therapy?

Patient groups founding drug companies

John Crowley has two children with a severe neuromuscular lysosomal storage disease called Pompe Disease. He started a foundation to raise money for the condition, then took a job with Bristol Myers Squibb in order to learn all he could about the pharmaceutical business.

His next step was to found Novazyme Pharmaceuticals to develop an enzyme replacement therapy for his daughters’ condition. This was subsequently acquired by Genzyme corporation and the treatment was brought to market.

Later, John Crowley became CEO of Amicus Therapeutics which is also engaged in lysosomal storage disorder research for Pompe and Fabry diseases. His story featured in a book, and in 2010 was made into a film called Extraordinary Measures starring Harrison Ford.

This story is exceptional, but there are many other examples of patient- and carer-motivated drug development.

Charities taking on drug development

The Cure Parkinson’s Trust is a leading charity aiming to slow the progression, stop or even to reverse Parkinson Disease, the progressive neurodegenerative condition characterised by rigidity, tremor and bradykinesia.

The trust has rapidly acquired interests into the study of a wide range of potential therapeutic interventions, and is currently connected with over 50 pharmaceutical companies and associated with nearly 3,000 investigators. They are carrying out a number of advanced clinical trials, including a Phase III trial of the calcium L-type blocker isradipine; drug repurposing features frequently in the work they do, with studies underway on exenatide and liraglutide (GLP-1 agonists), simvastatin (HMG-CoA inhibitor) and N-acetyl cysteine (antioxidant).

They place particular emphasis on a network of key opinion leaders with interests in investigating novel mechanisms in the condition, and are led by Dr Richard Wyse, a former lecturer in various London hospitals as well as medical director at two biotech companies.

Another example of this is Dr Pan Pantziarka of the ReDO project (Repurposing Drugs in Oncology), which was formed from the AntiCancer Fund and Global Cures. This organization has 5 trials underway, mostly drug repurposing combinations such as metformin (antidiabetic)/zoledronate (anti-osteoporosis)/sirolimus (transplant rejection medicine).

A particular focus is on the treatment of the rare cancer angiosarcoma with propranolol. Dr Pantziarka has a personal reason for his interest in cancer, but is also scientifically trained. ReDO are looking at putting in place a regime of tax incentives from the UK Government for the development of generic repurposed drugs.

The wider scope for development models

These examples point out the complex ways in which charities are becoming integrated into the drug R&D landscape, far beyond their original role in fundraising and care support for their conditions, patients can be medical experts, drug developers and clinical investigators. This is particularly the case for rare diseases, but in the future the changes will almost certainly extend into more common diseases too.

For the larger charities, this is not an entirely new phenomenon: Cancer Research UK supports a lot of research activity already – in 2015/6, amounting to £376 million, including nearly £120 million into the biology of cancer. The British Heart Foundation, too, spends over £100 million per annum, mostly on basic research. The focus on drug repurposing as a more efficient translational strategy is likely to grow, however, because of the cost and time advantages which characterise this approach, and it will be interesting to see what changes accrue when some of the larger charities adopt it to the same degree as some of the examples cited above.

July 2017 newsletter

Flare release announcement

Flare™ is released and ready for you to evaluate. Flare brings you new insights for structure-based design in a modern, easy to use interface that provides a framework for future growth. Combining the best of Cresset research with cutting edge methods from academia and selected commercial partners, Flare gives you a deeper understanding of protein-ligand complexes that will inform and improve new molecule design.

See Flare in action

This video gives an introduction to analyzing proteins and informing new molecule design with Flare.

Comprehensive Medicinal Chemistry III

In Lessons and Successes in the Use of Molecular Fields, Paolo Tosco and Mark Mackey have reviewed over thirty years of work on molecular interaction fields. Read how a field-centric perspective on molecules has enabled a range of everyday in silico applications, from bioisosteric replacement and molecular similarity assessment to virtual screening.

In silico methods to streamline optimization

In silico methods streamline the optimization process by giving you more understanding of your target and your hits, and by making it easier to manage your data. Martin Slater describes how Cresset Discovery Services can help streamline your optimization.

Presentations from The Cresset User Group Meeting

Thank you to the speakers, and delegates from around the globe, who contributed to the success of the meeting. Download the presentations we have permission to publish.

Save the date for 2018

The Cresset User Group Meeting: June 21 – 22, 2018.

Presentations from The Cresset User Group Meeting 2017

Thank you to the invited speakers, and delegates, who contributed to the success of The Cresset User Group Meeting.

The presentations we have permission to publish can be downloaded upon completion of the form below.


Cresset releases Flare: Powerful structure-based design application with outstanding new methods for protein-ligand systems

Cambridge, UK – 29 June 2017 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, announces the release of Flare, an intuitive desktop application that provides outstanding new methods for understanding protein-ligand systems. Flare enhances Cresset’s existing excellent product range focused on ligand-based design, and becomes their first product explicitly designed to support structure-based design.

“Cresset has been pushing the boundaries of ligand-based design for many years,” says Dr Robert Scoffin, CEO of Cresset. “Flare introduces structure-based design into our portfolio, giving companies access to outstanding new methods for investigating protein-ligand systems.”

Computational, medicinal and synthetic chemists working on small molecule design and optimization will use Flare to:

  • Gain vital knowledge ofprotein and ligand electrostatics to improve new molecule design
  • Compare electrostatic patterns across a protein family to design more selective ligands
  • Design new molecules anddock them to a protein target
  • Minimizeprotein-ligand complexes to achieve the optimal interaction for each compound
  • Calculate the location andstability of water molecules in a protein to guide compound design.

“Flare represents the next generation of structure based design applications,” says Dr Tim Cheeseright, Director of Products. “It has a modern, intuitive interface and is easily configured to enable cloud-based calculations, making excellent science immediately available to all users whatever their experience level.”

Users will benefit from:

  • Simple drag and drop to import/export molecules to the desktop or other compatible applications
  • Ready access to powerful tools through a modern ‘ribbon bar’ interface
  • Simple yet powerful selection capabilities and cutting-edge display options producing highly insightful molecular graphics.

“Flare integrates cutting edge approaches from Cresset with significant open source and commercial methods,” explains Dr Mark Mackey, CSO. “Throughout the product development we have worked alongside users from major pharmaceutical and biotech companies to ensure that we deliver the best science in the most intuitive format.”

Flare can be evaluated free of charge.

Download press release.

June 2017 newsletter

Flare release imminent: New insights for structure-based design

With the release of Flare imminent, Tim Cheeseright acknowledges the dedicated alpha and beta testers who have contributed to this exciting new application for structure-based design.

Molecular design towards Protein-Protein Interaction inhibitors

Martin Slater explores a powerful combination of cutting edge ligand and structure-based modeling using Flare and Blaze to see what could usefully be done with PPIs.

Using computational methods to elucidate protein-ligand interactions

Developing a robust binding hypothesis can lead to the discovery of new actives, broaden your optimization options, or help secure a back-up series. Cresset Discovery Services routinely uses homology modeling to move projects on to the next step.

Latest Spark reagent databases

The latest version of the Spark reagent databases is available now. Updated information on reagent availability from over 150 trusted suppliers can be downloaded using the Spark Database Updater. Contact us for other ways to keep up-to-date with Spark reagents.

Cresset applications licensed by Shiv Nadar University, India

Cresset supports teaching of computational chemistry though flexible software licenses and educational discounts. This month Shiv Nadar University, India, have licensed Forge and Spark to educate the computational chemists of the future.

We’re hiring!

Cresset applications licensed by Shiv Nadar University, India, to teach computational chemists of the future

Cambridge, UK – 20 June 2017 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, announces that the Shiv Nadar University, India, has licensed the following applications to educate the computational chemist of the future: Forge – powerful ligand-focused workbench for SAR and design; and Spark – scaffold hopping application for progressing through lead optimization faster.

“Cresset actively supports academic research by providing flexible licensing terms,” says Dr David Bardsley, Commercial Director at Cresset. “We are delighted that Shiv Nadar University, India, joined the growing number of academics who are using our applications globally.”

“We pride ourselves on providing our students with the best tools for computational modeling and design,” says Professor N. Sukumar, Department of Chemistry, Shiv Nadar University. “By using Cresset technology through hands-on use of Forge and Spark, our students will be better prepared for a career in computational chemistry.”

Download press release.

Re-Pharm and Cresset Discovery Services to attend BIO International for partnering

Cambridge, UK – June 13, 2017 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, and Re-Pharm, an early-stage drug discovery and development company that uses computational chemistry for re-profiling, will attend BIO International in San Diego on June 19-22.

“I am looking for partners to progress the anti-inflammatory compound RP0217 through early clinical development and clinical trials” says Dr Robert Scoffin, CEO of Re-Pharm. “RP0217 is a novel anti-inflammatory showing excellent standalone activity plus a strong steroid-sparing synergy with standard glucocorticoids. Re-Pharm holds patents on the use of RP0217 for the treatment or prevention of respiratory and gastrointestinal inflammatory disorders and for its use with and without co-formulated or co-administered steroids in topical ophthalmic indications, specifically conjunctivitis and uveitis, and prophylactic use in surgical applications such as LASIK.”

 “Cresset Discovery Services consultants bring a fresh perspective, years of industry experience, outstanding science and a complete professional service” says Dr David Bardsley, Commercial Director of Cresset Discovery Services. “Having delivered more than 200 early phase discovery projects to many leading pharmaceutical, biotech, agrochemical, flavor and fragrance companies, I look forward to discussing how we can advance company research projects.”

May 2017 newsletter

Last chance to register for The Cresset User Group Meeting

Register by 16th June to secure your place at our 15th Anniversary User Group Meeting.

  • June 29th, Scientific program
    • Official launch of Flare, our new structure-based design application
    • Update on science and ligand-based design applications
    • Customers share their experience of Cresset technology
    • Limited accommodation available at The Møller Centre
  • June 30th, Hands-on software workshops. Limited spaces remain for the following workshops:
    • Introduction to Flare for computational chemists
    • Introduction to Flare for medicinal and synthetic chemists
    • 3D-QSAR
    • Torch

Water stability is key to designing novel patentable chemistry

Read about how Cresset Discovery Services informed the design of novel ligands for a customer target, which led to patent.

Help with writing your grant application

See how we can help before you even start writing your grant application.

What can Torch do for you that TorchLite can’t?

We hope you enjoy using TorchLite, our freeware 3D molecule viewer, editor and design tool, but did you know how much more you can do with the full power of Torch?

Web clips

We’ve added to our GUI tips and tricks with the following tutorials, which use TorchLite, our free powerful 3D molecule viewing, editing and design application.

  • Structural changes and fields
  • Visualizing field changes to understand SAR

Electrostatics of heterocyclic rings and the Topliss tree

TorchLite has been used to illustrate 2D structures next to their 3D charge distribution patterns. Download the following illustrations:

  • Electrostatics of heterocyclic rings
  • Electrostatics of the Topliss Tree

Scientific program and workshops announced for The Cresset User Group Meeting, 29th – 30th June 2017, Cambridge, UK

Cambridge, UK – 10 May 2017 – Cresset, innovative provider of software and contract research services for small molecule discovery and design, announces full line-up for The Cresset User Group Meeting, 29th – 30th June 2017 in Cambridge, UK.

The scientific program on 29th June 2017 features speakers from 4 continents. Cresset scientists will present ‘New Insights for Structure-based Design with Flare’, ‘Peeking into the Heart of New Cresset Science’ and ‘What’s New in Ligand-based Design’. In addition, delegates will hear from:

  • AbbVie, USA: Important Aspects of Fragment Screening Collection Design
  • Bayer Pharma, Germany: In SilicoADMET at Bayer: Technologies and Applications
  • BioBlocks Inc., USA: The CFL: A 3D Enabled Fragment Library for Medicinal Chemistry Discovery
  • Cancer Therapeutics CRC, Australia: Integrating the Cresset Platform into Cancer Therapeutics CRC (CTx)
  • Evotec, UK: What Should I Make Next?
  • Institute for Stem Cell Biology and Regenerative Medicine, India: Representation of Small Molecule as Molecular Field Points Empowers Computational Chemists
  • International Flavors and Fragrances, USA: Can Cresset Tools Inform Fragrance Molecule Design?
  • Lilly, UK: Structure-blinded Virtual Screening: Use of Cresset Blaze in the Lilly Open Innovation Drug Discovery Program
  • University of Bristol, UK: Understanding Protein-ligand Binding at the Molecular Level: Using Swap-based Methods to Visualise Binding Free Energy Components
  • University of Bristol, UK: Virtual Reality and Real-time Molecular Dynamics for Chemistry
  • University of Edinburgh, UK: Molecular Simulation and Experimental Approaches to Ensemble-based Drug Design

Workshops on 30th June give computational, medicinal and synthetic chemists the opportunity to get hands-on with Cresset applications:

  • Flare, new insights for structure-based design
  • SAR with Forge using Activity Atlas models and Activity Miner
  • Spark, to quickly generate novel ideas and bioisosteres for molecule cores and R-groups
  • Virtual screening, using Blaze Cloud
  • 3D-QSAR, using Forge to improve compound design
  • Torch, for optimizing more than potency

“We have an exciting, diverse and varied program of speakers this year and I’m looking forward to hearing the latest on their research,” says Dr Robert Scoffin, CEO at Cresset. “The meeting will also mark the launch of Flare, our new workbench for structure-based design. Workshop places are almost fully booked for hands-on sessions with Flare and our other innovative applications for molecule design.”

Read abstracts, biographies, workshop schedule and register: http://www.cresset-group.com/cugm17/

April 2017 newsletter

Last chance for early access to Flare, new structure-based design application

Contact your account manager to join the final round of Flare testing and gain early access to this cutting edge structure-based design method with intuitive GUI.

The Cresset User Group Meeting

June 29th, Scientific program

  • Official launch of Flare, our new structure-based design application
  • Update on science and ligand-based design applications
  • Invited speakers from 4 continents share their use of Cresset applications on topics including fragment screening, library design, protein-ligand binding, virtual screening and fragrance molecule design.

June 30th, Hands-on software workshops

Due to demand which meant some workshops were fully booked, we have now created additional spaces. If the workshop you were interested in was fully booked then check back to see if space is now available.

Hit to lead

A long-standing customer had a hit series with good activity but poor properties. See how Cresset Discovery Services worked closely with the customer to formulate a plan of action to optimize the compound properties while maintaining potency.

Recent citations

See the following new citations:

  • Discovery of Compounds that Positively Modulate the High Affinity Choline Transporter
  • Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils
  • Structure-Based Library Design and Fragment Screening for the Identification of Reversible Complement Factor D Protease Inhibitors
  • Field Based 3D-QSAR Model of KATP Channel Activation by 4, 6 Di-substituted Benzopyran Derivatives

Presentations from ACS

Download our presentation and posters from the 253rd ACS National Meeting. Also available are the presentation and poster by the University of Bristol which feature Flare, our new structure-based design application.