Scientific Approach
Advancing Science for a New Generation of CNS Therapies
With over 1 in 3 people affected by neurological conditions, and limited availability of effective treatment options, the demand for innovations to counter these unmet medical needs has never been higher. Existing medications often work on a narrow subset of the patient population, come with side-effects detrimental to patient compliance, and tend to slow disease progression and dampen the symptoms rather than treating the cause.
Alzheimer’s, as one of the most striking examples, was defined more than 115 years ago, and to this day no medical breakthroughs have been achieved. Why have we not advanced beyond this? The answer to the question is partly found in the complexity of the central nervous system (CNS), a processing center composed of neurons with unique, yet complex interconnections to provide brain function.
This intricacy makes it difficult to identify and target specific CNS conditions. TETRAPHARM acknowledge this complexity and believe that a polypharmacological approach is necessary to not only treat but also cure patients from their disease. By combining neuroscience and mechanism-based disease classification, we’ve identified key hallmarks of several CNS-related disorders indicating causative mechanisms in addition to the more well-established symptoms. Such a ‘multitarget’ approach, deeply anchored in CNS pathology understanding, is required to address the underlying causes of homeostatic imbalance and ultimately disease.
A given TETRAPHARM pipeline candidate, from new chemical entity (a mix of ‘hallmark’ ligands) to clinical formulation, is progressed within the framework of our zIQube™ development platform: ZEEK™, ZELEKT™, ZYNDIKATE®, ZYNTAKS™ (described below). The elements of zIQube™ allow us to build novel drug candidates that are:
Effective in both symptom relief and disease modification
Engineered around off-targets for better safety profiles
Optimized for early integration with scalable delivery systems
-
ZEEK™ holds a molecular database of proprietary and reference ligands designed to engage the hallmark targets as well as a set of disease specific targets. As a further value-adding element, the ligands are “designed around” selected off-targets, identified as being overall responsible for causing serious psychiatric side-effects. All ligands are validated experimentally deploying a tailored test battery of in-vitro assays covering mode of action and toxicity. In a nutshell: The same molecule will often support several pipeline candidates using a shared discovery/tox package. Once a pipeline program is selected for further advancement, the development proceeds to ZELEKT™.
-
Drug molecules, supporting the disease mechanism, are selected from the molecular library of ZEEK™ and assembled into a collective New Chemical Entity (NCE). Preclinical studies, including in-vivo efficacy testing and follow-up ADME-TOX are conducted. Together with information on the individual molecules captured in ZEEK™, this phase provides key IND-enabling data for first-in-human testing. The non-clinical data generated at this stage are also leveraged to prepare a first version of a target product profile (TPP) describing, among other, early clinical metrics to further guide the development.
-
A prototype delivery system is selected from TETRAPHARM’s proprietary, and fully owned, collection of enabling technologies to facilitate effective transport of the poorly soluble CNS-molecules to the target site. ZYNDIKATE® offers a palette of drug delivery systems supporting various routes of administration such as the oral route, sublingual, intra-nasal and transdermal. These formulations are designed to accommodate drug molecules within a predefined range of physicochemical property descriptors compatible with most ligands from the ZEEK™ phase. ZYNDIKATE® enables the early introduction of a delivery system that resembles the intended commercial formulation. This reduces the CMC burden, while also eliminating the need for reformulation of the investigational medicinal product as the drug candidate progresses through the clinical phases. The latter eliminates the need for (often unpredictable) bioequivalence testing, significantly derisking the pipeline program as a whole. Decreasing the CMC burden is a central aspect of the TETRAPHARM way of doing science. It is also an essential part of our strategy to reduce the cost of our products to the benefit of patients and society.
-
ZYNTAKS™ represents the final assembly before clinical testing. CMC development actitivies are completed and ultimately compiled with all relevant non-clinical data into required formats for regulatory IND submission. Scientific advice from relevant authorities is sought (if not already done) to align on a viable regulatory pathway for the upcoming human trials. At this stage a clinical synopsis is also drafted for interaction with clinical CROs and trial sites. Finally, the IP status for the given drug candidate is given a final review to ensure that priority dates have been secured. The drug candidate is now sufficiently matured to begin formal preparations for clinical trials.