Trajectum Pharma is an innovative biopharmaceutical company, aiming to pave the way in establishing tolerance inducing cell therapies for autoimmune inflammatory diseases. The company is built on a deep-rooted understanding of immunologic functions in health and disease.
This expertise was built up over several decades at the Faculty of Veterinary Medicine, Department of Infectious Diseases & Immunology of Utrecht University. The management team has significant experience in converting science-based solutions to a feasible business case.
Clinical manifestations of rheumatoid arthritis (RA) are manageable in 70% of patients, yet it is not curable, nor reversible. Current treatments are life-long and lead to high yearly costs (€25,000-30,000). The remaining group of patients suffers a range of side effects and secondary pathologies that make treatment a challenge, with due implications to the patient’s quality of life. Current treatment is directed at disease management and current product development efforts are focused on improving disease management. Curative approaches are therefore highly desired.
The latest acquisition for the flow cytometry facility is the Cytoflex LX from Beckman Coulter Life Sciences. With this machine single cells can be analyzed on an individual basis. For this purpose 6 lasers are available (blue, red, violet, yellow-green, near UV and infrared) with which 23 parameters can be studied per cell. This can be performed at a speed of 30.000 cells per second.
Trajectum Pharma developed a potentially curative, first in class treatment for RA that consists of ex vivo loading and modifying of dendritic cells (DCs) with a proprietary peptide (B29, derived from a heat shock protein, HSP), and administration of the autologous DCs in RA patients. These loaded dendritic cells (tolDCB29) subsequently stimulates HSP-specific peripheral regulatory T-cells. These Tregs quantifiably respond to HSP (e.g. by releasing IL-10, an anti-inflammatory cytokine), which is typically present during inflammation at the site of inflammation (i.e. the joint), restoring the balance. This represents a unique mode of action.
Path to succes
Trajectum Pharma largely completed the preclinical work required to define the product. Due to the ex vivo nature of the treatment and based on prior art, Trajectum Pharma can continue on the clinical path with Phase II trials in different types of RA patients. If the endpoint criteria are met successfully, Trajectum Pharma aims to continue with a pivotal Phase III trial, prior to registration and commercialisation. The long-term vision of the company is to develop an off-the-shelf vaccine for RA, or possibly use CAR-T cells to induce tolerance.
tolDCB29 therapy: Correcting repeated activation of disease-causing lymphocytes
Under natural circumstances, regulatory T-cell induction occurs to protect the body from overreacting to e.g. infection. In case of autoimmune diseases, these mechanisms are malfunctioning. Our approach is to mimic this natural self-controlling system by actively immunizing with the peptide B29 derived from heat shock protein (HSP), which has been shown to induce regulatory T-cells in vivo. Such T-cells are both prophylactically and therapeutically active. As physiological (natural) mechanisms of immunity are involved, the treatment concept can be considered as a (therapeutic) vaccine, and leads to the cure of the disease as opposed to transient suppression of symptoms.
Thus, the basic principle that underpins the therapy is to educate tolerance-invoking regulatory T-cells. An orchestrated series of events needs to happen to achieve this, and hence to allow it to be an effective approach to treatment of RA.
The approach to be used in the clinic will be as follows:
- The presence of tolerogenic B29-specific Treg-cells in the patient is verified with specific assays
- The patient is treated with anti-TNF (or other biologicals) to induce a state of disease remission
- Dendritic cells (DCs) are obtained from the patient by expanding peripheral blood obtained monocytes with growth factors ①, using standardized protocols.
- The dendritic cells are ex-vivo made into tolerizing DCs with Vitamin D/dexamethasone and loaded with B-29 ②, so that they can present this epitope to regulatory T-cells
- The cells are re-introduced into the patient ③ (remission allows for better tolerance induction)
- The epitope is presented to Treg-cells by the tolerizing DCs ④, to activate the tolerogenic cells
- The patient now has a Treg repertoire that naturally suppresses inflammation ⑤ (in the joint)
Meet Our Team
Paul Leufkens, PharmD, MBA, CEO
Paul holds MSc and PharmD degrees from Utrecht University (the Netherlands) and obtained his MBA at Bradford University (UK). Over the past 20 years he has spun out a variety of technologies from University-based research groups. Previously, he was a co-founder of AM-Pharma, Neurophyxia, CART-Tech Trajectum Pharma and is currently CEO at ICC International. He held senior positions in product development at Exponential Biotherapies Inc. (Washington, DC), Reliance Life Sciences (Mumbai, India) and Pharming (Leiden, the Netherlands). Earlier in his career Paul worked in clinical development with Sanofi and Yamanouchi Europe. As a mentor to starting biotechnology entrepreneurs, Paul shares knowledge, experiences and pitfalls from his area of expertise (biotechnology, medical devices and clinical development).
Prof. Dr. Willem van Eden, MD, Scientific Director
Willem is immunologist and medical microbiologist and has made a set of landmark discoveries at the edge of infectious diseases and autoimmunity. He discovered the role of stress proteins in self-tolerance. This serendipitous finding was published in Nature and was for two years in the top-100 of mostly cited paper in the biomedical domain. Resulting from this original finding are still current. Activities of van Eden and his group directed towards development of an immuno-modulatory vaccine against chronic inflammatory diseases on the basis of heat shock proteins.
Prof. Dr. Jaap van Laar, MD, PhD, Principal Investigator, Tolerant Study
Jaap is Head Rheumatology and Clinical Immunology Department at the UMCU and he is involved with Trajectum Pharma as the Principal Investigator of the Tolerant Phase I/IIa clinical study Dr. van Laar has a vested interest in the use of heat shock proteins in immune-mediated therapies, as his career started in this field. Throughout his career, he has been closely involved in many projects that bridge development and practice. He has been the lead investigator in numerous clinical trials in the area of rheumatology.
Prof. Dr. Femke Broere PhD, DMV, Head of the department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University
Femke is heading the preclinical development effort of her department in support of the Tolerant clinical study, particularly in the area of assay development and data-management and evaluation of study results.