FDA NCTR

2018-10-04T10:14:17+00:00

The challenge

The U.S. Food and Drug Administration’s National Center for Toxicological Research (NCTR) is a global resource for collaboration providing consultation, training, and innovative scientific solutions in support of FDA’s mission to improve public health. Within NCTR, The Division of Bioinformatics and Biostatistics is developing bioinformatics methodologies and standards to support FDA research and regulation for regulatory and translational sciences.  The Division, led by Weida Tong, has tremendous expertise in computational biology, molecular modeling and quantitative structure-activity relationships (QSARs) and a wealth of new data and ideas to disseminate.  ApconiX was set the challenge to help refine and deliver a publication and communication strategy as well as helping to define new areas of potential impact for the team’s expertise.

The solution
We worked closely with the team at NCTR in individual and in syndicate sessions to identify key messages and match them to publication opportunities.  Based on the strength of the teams, we focused on two of their flagship projects:  developing and applying new computational approaches to the challenge of drug-induced liver injury (DILI) and to in vitro to in vivo extrapolation (IVIVE).   Using the expertise of individual scientists, we worked one-to-one to author papers through from first draft to submission and response to reviewers’ comments.

The benefit
By performing a systematic analysis of the new and unpublished data the team had generated, we developed a clear publication and dissemination strategy to maximise the impact of the team’s current and ongoing work.

The outcome

The collaboration has resulted in the submission of 5 papers in just 12 months.  In DILI, the in vitro to in vivo extrapolation (IVIVE) methodology and liver knowledge toxicology base (LKTB) classification of human liver injury papers are in press and a third paper on gene signatures is submitted 1-3.  In the area of drug repositioning, a TiPS paper on computational approaches to analyse two decades of experience of anti-cancer drugs was recently published 4 and a second paper looking for new opportunities in rare diseases 5 is in press.

  1. Liu, Z, Delavan, B, Roberts, R and Tong, W (2018). Gene Signature Reveals Differences among Preclinical Testing Systems for Rat Liver.  Frontiers in Genetics. Submitted.
  2. Thakkar, S, Chen, M, Fang, H, Liu, Z, Roberts, R, Tong, W (2018). The Liver Toxicity Knowledge Base (LKTB) and Drug-Induced Liver Injury (DILI) Classification for Assessment of Human Liver Injury. Expert review of Gastroenterology and Hepatology.  12, 31-38. https://doi.org/10.1080/17474124.2018.1383154
  1. Liu, Z, Fang, H, Roberts, RA and Tong, W (2017). In vitro to in vivo extrapolation (IVIVE) for drug-induced liver injury: A genome wide analysis using a drug pair ranking (DPRank) method. ALTEX.  https://doi.org/10.14573/altex.1610201
  1. Liu, Z, Delavan, B, Roberts, R and Tong, W (2017). Lessons learned from two decades of anticancer drugs. TiPS 38, 852-872.    http://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(17)30126-8
  1. Delavan, B, Roberts, R, Goldsmith, J, Fang, H, Thakkar, S, Huang, R, Bao, W, Tong, W and Liu, Z (2017). Computational Drug Repositioning for Rare Diseases in the era of Precision Medicine.  Drug Discovery Today.  In press Dec 2017.  DOI: http://dx.doi.org/10.1016/j.drudis.2017.10.009

The Testimonial

‘It has been a tremendous pleasure to work with Ruth @ApconiX for the past year. Her in-depth knowledge in toxicology in general and drug discovery/development in specific has contributed significantly to my division’s research in the area of drug-induced liver injury and in vitro to in vivo extrapolation.  I am expecting much great science will come out from the close collaboration with Ruth’.

Weida Tong, Director, Division of Bioinformatics and Biostatistics and NCTR/FDA

A Company Focused on Novel Oncology Targets

2018-10-04T10:07:23+00:00

The challenge

Our client had identified a clinical candidate aimed at a novel tumour target, with promising activity against a range of cancers.  Upon completion of suitable GLP toxicity studies, the company intended to move into Phase I in patients, in combination with chemotherapy. There were a number of pressing issues, including choice of the appropriate nonclinical species, dosing schedule, achieving adequate exposure as well as the potential for greater target organ toxicity when dosed in combination.

The solution

ApconiX joined the client’s project team by providing a dedicated project toxicologist, supported by our other experts.  With a clear understanding of the project goals and clinical objectives, we delivered a bespoke, focussed nonclinical safety package designed to ensure the right data were provided for regulatory success and rapid initiation of the Phase I patient studies.

A study that provided safety and DMPK data on the novel agent dosed with chemotherapy was also designed and conducted. Although not a regulatory requirement, this allowed a better understanding of the impact of the combination and supported a higher start dose in combination with chemotherapy.

ApconiX managed all aspects of the preclinical safety package, working closely with CROs to ensure appropriate study design, costs, dose level selection, data interpretation as well as timely delivery of quality study reports.  Concurrently, we authored the nonclinical sections of the regulatory submission documents and represented the client at a regulatory agency meeting.

The benefit

With ApconiX as part of the team, our client benefited from our many years of collective experience in preclinical safety, DMPK and drug development.   The package was designed to ensure regulatory and clinical objectives were met, keeping to budget and agreed timelines.

The outcome

The Clinical Trial Authorisation was approved, allowing the compound to move into clinical trials, in combination with chemotherapy.  During this phase, we also assisted in the out-licencing of this asset to a third party.   We continue to work with the new owners to ensure its further success.

Synergy Partners R&D Solutions

2018-10-01T15:55:28+00:00

“ApconiX target reviews are of outstanding quality and obviously created by people with a thorough understanding of what is needed to help guide decisions”

James S. MacDonald PhD, Synergy Partners R&D Solutions

Blueberry Therapeutics

2018-10-01T15:55:28+00:00

“The support that we received from the ApconiX team has been excellent and they have helped us both in developing our nonclinical safety thinking and in providing direct support for the clinical trial application. We’re looking forward to continuing our collaboration as we progress our exciting new medicines into later-stage development and hopefully the clinic”

Dr. David Cook, Chief Scientific Officer, Blueberry Therapeutics

RedX

2018-10-01T15:55:28+00:00

“ApconiX has provided hERG data to Redx Pharma from June 2016 to help support our discovery projects. Data turnaround times over this period have been rapid (under 1 week) and this has been critical in progressing projects quickly; outsourcing the assay with this turn-around has had no impact on our “design-make-test” cycle times.

Additionally, ApconiX’s approach is very collaborative providing expert advice on these data as part of their service. Another vital component to this screening is flexibility over compound numbers which enables us to maintain progress during the peaks and troughs of compound supply and prevents delays which can occur if you have to wait to reach a trigger point for submission of an assay.”

Dr Stuart Best, Redx Pharma

FDA

2018-10-01T15:55:28+00:00

“It has been a tremendous pleasure to work with Ruth @ApconiX for the past year. Her in-depth knowledge in toxicology in general and drug discovery/development in specific has contributed significantly to my division’s research in the area of drug-induced liver injury and in vitro to in vivo extrapolation.  I am expecting much great science will come out from the close collaboration with Ruth”

Weida Tong, Director, Division of Bioinformatics and Biostatistics and NCTR/FDA

CellCentric

2018-10-01T15:38:46+00:00

“We would not be here without your excellent input and help.  You and ApconiX have been absolutely fantastic.  Great planning and execution…..strong, straightforward communication…..pragmatic and a strong sense of team”

Sygnature Discovery

2018-10-01T15:38:46+00:00

“Toxicology and functional electrophysiology assessments are essential aspects of the drug discovery and development process to ensure the safety of a potential drug prior to administration in humans.  The specialists at ApconiX are world renowned scientists in non-clinical safety strategies and their skills will be of great benefit to our clients.  The alliance between Sygnature Discovery and ApconiX will be mutually beneficial and together we can offer a more comprehensive integrated approach to any clients’ drug discovery programme.

We are very much looking forward to working with ApconiX and introducing them to our clients.”

Dr Clewlow, Sygnature Discovery

Evgen

2018-10-01T15:23:13+00:00

“We are delighted to have found a flexible way to access specialist technical expertise and operational support to complement our existing internal capabilities to support the ongoing development of our lead product, SFX-01.  We selected this excellent group of providers as our partners as they have a proven track record of working well together and they are all co-located at Alderley Park where we too have a presence.”

Dr Stephen Franklin, Founder and CEO, Evgen Pharma

Bugworks

2018-10-01T15:38:46+00:00

“Your data turnaround time is incredibly good and it really helps us track the SAR and progress our compounds in a rapid and efficient manner. Thanks ApconiX for your wonderful support to Bugworks.”

V Balasubramanian, Ph.D., Bugworks Research India Pvt. Ltd.