Citoxlab Newsletter – March 2018

President keynote

Dear Valued Customers,

2017 was a fruitful year for Citoxlab Group, another year of marked growth.
Thanks to your continued trust and to the robust trend in R&D outsourcing in the pharma and biotech industries, Citoxlab revenues increased by 21.5% and reached 130 Mi Euros (160 Mi USD). Our organic growth was 14.3% and the growth from acquisition was 7.2%.
After the integration of Accelab in 2016, we acquired Xenometrics in Kansas, USA, during the 4th quarter of 2017, which allows us to accommodate projects from our US clients locally as well as increase global capacity. I am very happy to state that the integration of our new colleagues from Kansas within the Citoxlab organization is going smoothly and efficiently thanks to a remarkable team spirit. Several improvements and synergies have already been achieved less than 100 days after the closing.
Today, projects on drug development represent 81% of our revenues with 39% from mid and big pharma (Citoxlab works with 8 out of 10 largest pharma companies) and 42% from biotechnology companies. Chemical/Agrochemical industries as well as medtech contribute to the remaining 14% and 5% respectively.
We continue to invest heavily to refine and increase our scientific capabilities in order to accommodate your R&D needs. For example, we have increased our capacities and built a robust flow-cytometry and soluble biomarkers catalogue, as those readouts are increasingly requested in studies. Those are particularly useful to assess and interpret immuno-oncology as well as for autoimmune indications endpoints (see below in the present newsletter). Biomarkers are strategic to our group and therefore human and material investments are a key focus for us, it includes mass spectrometry, ligand biding assays, cell cytometry, genomics, NGS and immuno-histochemistry. As requested by some of you, Citoxlab has also extended those biomarker services to clinical stage development; this proved not only to be timely and financially sound but also to reduce the risk factor associated with switching CRO/partner through the first clinical assessments.
Finally, I would like to emphasize the investments we are making on all of our sites to propose the best setting in terms of global capacity, environmental and animal welfare standards. We are more than aware that this is important to you and we, as scientific professionals, are also committed to ensuring the best possible study conditions. For this reason we have invested heavily over the years to implement group housing and enrichment programs in accordance with international standards.
I hope that this newsletter will be of interest and we will help keep you informed about the services we provide with our best efforts to meet your needs, in particular with our scientific expertise, relevance and quality of the data as well as comprehensive evaluation of the products you are committed to develop.

Jean-Francois Le Bigot, PhD, President and CEO

Citoxlab heavily invests in immuno-oncology services

Immunomodulatory treatments have gained precedence over the last several years, especially due to the great success of immune stimulating agents in the field of immuno-oncology. With numerous immunomodulatory drugs now in development, specific preclinical models were developed at Citoxlab to answer the increasing customers’ needs and to assess the breadth and depth of immune system modulation following treatment.

The T-cell dependent antibody response (TDAR) model, historically used to evaluate immunosuppression, can also be used to evaluate immunostimulation. With non-human primate still being the species of choice for such immuno-stimulating agents, Cynomolgus monkey models were developed at Citoxlab using sub-optimal doses of keyhole-limpet hemocyanin (KLH), and Incomplete Freund’s Adjuvant (IFA), or an immune check-point inhibitor monoclonal antibody as positive controls. In addition, a multi-antigen TDAR protocol was also developed to mitigate the inter-individual variability related to major histocompatibility complex (MHC) haplotype restrictions.

Several immunomonitoring endpoints were used or developed and validated to evaluate the humoral as well as the cellular immune response enhancement. All these endpoints are now available for Citoxlab’s clients.

The anti-KLH humoral immune response was monitored by the evaluation of anti-KLH IgM and IgG antibodies concentrations. In the multi-antigen study, a multiplex electrochemiluminescent (ECL) assay was used to track the immune response mounted against each of the four antigens administered.

Peripheral Blood Mononuclear Cells (PBMC) were isolated at multiple timepoints for the evaluation of the antigen specific ex-vivo lymphocyte proliferation (using carboxyfluorescein succinimidyl ester (CFSE)) and cytokine secretion (using ELISPOT and ECL). Cell proliferation and cytokine production were further monitored by flow cytometry using Ki67 and Intra-Cellular Staining (ICS), respectively, and the results compared to other end-points.

MHC haplotyping was also performed on all animals to identify genetic markers of the immune response magnitude.

Finally, non-specific cellular activation was also monitored by measurement of activation markers at the surface of B, NK and T-cells including T-helper, T-cytotoxic cells, as well as T-regulatory cells by flow cytometry.

The models established herein are now available for our clients to evaluate immunostimulation. The incorporation of multiple immunomonitoring end-points in non-human primate studies allows for a comprehensive monitoring of various aspects of the immune response involved, and can be used for compounds with various mechanisms of action. These models are very valuable in evaluating the immune response induced by immunostimulatory compounds such as immuno-oncology drugs.

Citoxlab acquires US-based CRO – Xenometrics, and adds to strength in experience and service while increasing capacity

On October 31, 2017 Citoxlab announced the acquisition of Xenometrics, an American CRO specializing in preclinical pharmacokinetics (PK) and safety testing. Through this acquisition, the Citoxlab Group reinforces its position as a major preclinical CRO player, adding to their strength in experience and service, whilst increasing Citoxlab’s North American capacity by over 30%.

Xenometrics is a GLP compliant, USDA registered, AAALAC accredited preclinical CRO located in the Kansas City area, providing nonclinical research services to the pharmaceutical, biotech, companion animal health, industrial-chemical and agro-chemical industries. Xenometrics has a staff of around 100 people, located in 78,000 sq. ft. of dedicated study rooms.

Xenometrics’ study services include: Metabolism and PK, general toxicology, safety pharmacology, and reproductive and developmental toxicology studies.

The Citoxlab Laval, Quebec and Kansas City (Xenometrics) sites will be harmonizing their operations to better serve their clients.

Dr. Alfred Botchway, President and CEO of Xenometrics said: “Xenometrics has been steadily growing its business and client base since its inception almost 12 years ago, and we’re excited that Citoxlab decided to invest in us as their first US based acquisition.”

Dr. Jean-Francois Le Bigot, Chairman and CEO of Citoxlab Group said: “The integration of Xenometrics into the Citoxlab Group is well underway, and we are already identifying many synergies, efficiencies, and growth opportunities that will lead to us better serving our clients as we continue to grow our client base and market share in North America.”

Interbody fusion cage development programs: the ovine lumbar intervertebral spinal fusion model

Low back and neck pain represents the third-highest estimated healthcare spending in the US at $87.6 billion according to the Journal of American Medical Association1. The clinical conditions include spinal instability and degenerative disc diseases (DDD) such as disc height herniation, infection, and disruption. Intervertebral spinal fusion cages have been widely used in spinal surgery to treat these since their introduction in 1988. Combined with autogenous bone grafting, this arthrodesis technique induces bone bridging between adjacent vertebrae using hollow intervertebral fusion implants that re-establish intervertebral height, provide mechanical stability, and potentially alleviate back and leg pain.

With today’s dynamic R&D programs in the orthopedic field, the state-of-the-art intervertebral cage implants [termed interbody cages] manufactured from diverse metallic and composite polymers, whether porous or surface-treated, must be evaluated for safety and performance. AccelLAB has optimized an ovine interbody fusion safety and efficacy model that involves the positioning of intervertebral fusion cages at lumbar levels with either iliac crest bone or synthetic graft supplementation using a lateral surgical approach. Following 4-6 months of implantation, the quantification of new bone bridging and bone apposition in addition to histopathology scoring takes place using non-decalcified and microground bone histology slides. Results are also corroborated by high-resolution radiography and micro-computed tomography imaging modalities.

AccelLAB’s latest ovine interbody cage fusion model will be presented by Dr. Michel Assad at the 64th Annual Meeting of the Orthopaedic Research Society at the Hyatt Regency New Orleans, LA, USA on March 12, 2018. It is entitled: “Novel Accelerated Neutral Atom Beam Processing as a PEEK Surface Treatment: A Four-Month Preliminary Study using an Ovine Lumbar Intervertebral Spinal Fusion Model”.

1Dieleman JL et al. US Spending on Personal Health Care and Public Health, 1996-2013. Journal of American Medical Association (JAMA). 2016 Dec 27; 316(24):2627-2646.


Citoxlab Denmark now approved to run any preclinical studies with transgenic minipigs and genetically modified organisms

The use of minipigs in nonclinical research has increased significantly during the last decades. At Citoxlab, we are committed to fast adapt to our clients’ emergent needs by offering relevant models for developing tomorrow’s new drugs and therapies.
Many companies are evaluating the opportunity of using transgenic minipigs for the evaluation of new drugs or therapeutic concepts safety that are critical for the success of translational research. In this context rodent models are most widely used. At present, transgenic pigs are increasingly started as large animal models for selected human diseases such as neurodegenerative diseases, cardiovascular diseases, cystic fibrosis, diabetes, etc. The first pig whole genome sequence and many other genomic resources are now available. Efficient and precise techniques for the genetic modification of pigs have been established, facilitating the generation of tailored disease models. Citoxlab Denmark, being less than 1 hour drive from Ellegaard Göttingen Minipigs, where these minipigs are bred, has now received authorisation to house and run studies in genetically modified minipigs.

In addition to this approval to house GM minipigs, Citoxlab Denmark also has a genetically modified organisms (GMO 1) approval for the minipig facility. This means that our Danish site is fully approved to run minipig studies involving GMO 1 test items and we are already running a number of studies with them.

Citoxlab increases pathology expertise by recruiting 2 new pathologists

We are pleased to announce the appointment of two new pathologists at Citoxlab Hungary (Veszprém) and AccelLAB (Montreal).

Dr Babu Gangadharan, B.V.Sc.& A.H, M.V.Sc, PhD has joined Citoxlab Hungary as a Pathologist, effective 1 January 2018. Babu started his career in India before moving to the UK where he held a number of academic research positions in Scotland and Northern Ireland.
He then moved into industry and has worked as a toxicologic pathologist for contract research organisation for the past 9 years, latterly at Envigo. Babu has experience of evaluation and reporting short term to carcinogenicity studies with a particular interest in those conducted via the inhalation route, which supplements the extensive inhalation toxicology capabilities at the Hungarian site. He has experience in various species, and he is proficient in molecular pathology techniques, including immunohistochemistry and in situ hybridisation.

AccelLAB is pleased to announce that Dr. Nicolette (Nikki) Jackson, an ACVP board-certified veterinary pathologist, is fulfilling the position of Principal Pathologist at the Montreal-based medical device site. Nikki brings with her a wealth of knowledge and experience in cardiovascular, orthopedic, and wound healing studies.
Nikki obtained her BS in biological engineering and doctor of veterinary medicine (DVM) at Kansas State University prior to completing an anatomic and cardiovascular pathology residency at Texas A&M University. During her residency, she worked in the Texas A&M Cardiovascular Pathology Laboratory and assisted with numerous medical device studies in a GLP setting. After passing her board exams in 2013, Nikki worked at Alizée Pathology until joining AccelLAB in November of 2017.

Joining the Citoxlab pathology team of experienced board-certified pathologists; Babu Gangadharan and Nikki Jackson will supervise and coordinate activities in toxicologic pathology and clinical pathology, respectively, oversee analyses, evaluate and write pathology reports. Babu and Nikki will be valuable assets to Citoxlab as they will be offering our clients and teams the benefits of their scientific and technical expertise.

An Atlanbio’s team leader crossed the atlantic ocean in a solo and unassisted race

Atlanbio was very proud to support its team leader in immunochemistry, Élodie Pedron, in her pursuit of adventure, challenge and sailing excellence.  This past fall she embarked on a solo, unassisted crossing of the atlantic ocean from La Rochelle (France) to the Caribbean port town of La Marin, Martinique, as one of the 200 participants in the 2017 Mini-Transat Race.

For 30 days, Elodie lived to the rhythm of the ocean without internet or a satellite phone. The only connection to the outside world were weather forecasts transmitted by race organizers. She had to deduce her own position on the map and then decide which course to choose.

Starting in November, 3000 nautical miles separate her and her sailboat from the final destination. The crossing was intense; punctuated by naps of a mere 20 minutes, adjustment of the boat and sails and constant analysis of weather conditions; while sustaining on food prepared from a kitchen that was limited to “a stove that hangs in the cockpit to warm freeze-dried portions”.

There were many unforeseen developments and challenges during the race.  However, Elodie never gave up and showed the unshakeable strength and motivation it takes to compete: “I’ll be in Martinique no matter what”.

After a grueling 18 days, 9 hours and 30 minutes, her tremendous showing of 39th place was secondary to the experience. “The arrival was magic, my father, friends, flowers, little words and drawings from France… I am still stunned by all the attention and few words can describe what I feel. A huge thank you to you all. »

Meetings and conferences:


To continue to receive this newsletter in your inbox, please add to your address book.