About
Who is AlloCyte Pharmaceuticals AG ?
AlloCyte Pharmaceuticals AG is a Swiss-based company discovering, developing and commercializing next generation allosteric small molecule integrin modulators to address major unmet medical needs of severe chronic autoimmunity. AlloCyte was founded by reputated drug developers, private investors and integrin experts of pharma-industrial, academic, business and clinical backgrounds. AlloCyte’s drug development programs are fueled by cutting-edge drug discovery, driven by scientific rigor and advanced therapeutically by the resilience to take the route less travelled if this is the pathway to transformative therapeutic innovation.
'The hardest thing to see is what is in front of your eyes.'
Johann Wolfgang von Goethe
What does 'next generation' mean ?
Next generation refers to (1) AlloCyte’s proprietary allosteric small molecule integrin platform pharmacology (differentiated to all former non-allosteric integrin-targeted modes of action) and (2) the company’s integrin-recalibratory (rather than grossly integrin-suppressive) therapeutic translation, advanced in close cooperation with internationally leading translational and clinical immunologists.
AlloCyte's allosteric mode of action is integrin-selective and devoid of paradoxical effects (i.e. integrin effects counter to the intended effects). AlloCyte's platform pharmacology will thus resolve profound limitations of the former anti-integrin antibody efalizumab (associated with broadly immunosuppressive effects) and of non-allosteric small molecule integrin ligand mimetics (associated with paradoxical effects).
The dual advance of AlloCyte’s allosteric (rather than non-allosteric) pharmacology and its integrin-recalibratory (rather than grossly integrin-suppressive) therapeutic translation may permit to recalibratorily target, for the first time, serious integrin-dysregulatory syndromes hitherto labelled as enigmatic. Integrin dysregulatory syndromes are disease states in which a distinct integrin network dysregulation dominantly and non-redundantly defines the disease phenotype. AlloCyte aims to selectively recalibrate the disease-driving integrin dysregulation so to restore integrin network balance and to resolve integrin-dysregulatory disease.
Which diseases does AlloCyte target ?
AlloCyte develops a novel type of oral immune-regulatory precision intervention to treat severe immune-mediated diseases associated with major (in part devastating) chronic morbidity, including, in principle, systemic lupus erythematosus, systemic sclerosis, IBD, sight-threatening non-infectious posterior uveitis and amyotrophic lateral sclerosis among other rare yet serious chronic immune-mediated diseases. These diseases affect different organs yet share the pathology of serious self-destructive cell killing (autologous cytotoxicity) directed against fully differentiated, non-malignant tissue cells of the patient's own organism. The aberrant phenomenon is not seen in health. There are no approved therapies to effectively control aberrant self-destructive cell killing.
AlloCyte has accumulated data evidence to suggest that the self-destructive cytotoxicity observed in these severe immune-mediated diseases may be driven by self-perpetuating cycles aberrantly over-activating and over-engaging a distinct integrin. The pathways underlying this aberrant integrin over-activation of autoimmunity appear to be categorically different to pathways activating the same integrin within self-protective (non-autoimmune) immune defense. Specifically, the aberrant integrin over-activation appears to alter the effector function of distinct subsets of so-called helper T cells, conveying the aberrant capacity to attack and kill fully differentiated (non-malignant) and functional tissue cells which naturally would be protected as self cells. Self-perpetuating cycles of aberrant integrin over-activation and aberrant cellular self kill can destroy tissue architectures and function over time. AlloCyte’s oral small molecule allosteric integrin-targeted intervention may have the capacity to recalibratorily (rather than grossly integrin-suppressively) halt these self-perpetuating cycles of aberrant integrin over-activation, restoring natural immune balance as well as tissue integrity.
AlloCyte estimates that its first oral product, if developed successfully, may vastly alter therapeutic landscapes across severe tissue-destructive autoimmunity. As AlloCyte’s pharmacology is a platform pharmacology designed to deliver multiple potential drug candidates, AlloCyte foresees the future stratification of its compound portfolio to the different needs of different serious tissue-destructive diseases.
Is AlloCyte’s pharmacology active upon oral use ?
Yes, AlloCyte’s first small molecule allosteric integrin targeted drug candidate prevented disease activity in animals upon oral dosing. Treatment was taken up avidly and well-tolerated throughout the course of the study. The need for concomitant symptomatic medication was abrogated, completely.
The tolerability and safety profile of this first drug candidate is affirmed by repeat dose studies across different species. AlloCyte’s first drug candidate is further found to exhibit excellent oral biovailability and PK/PD characteristics, projected to potentially support an once daily oral dosing regimen, in the future.
Is AlloCyte’s pharmacology active in human disease ?
When tested in vitro in human patient tissue samples and patient cells, AlloCyte’s pharmacology was found to elicit the therapeutically intended effect profiles. Upon IND readiness of its first oral drug candidate, AlloCyte’s next major target milestone (i.e. the potential next value inclination point) will be therapeutic proof-of-concept in patients. Indication selection has been informed by immune-mechanistic data of an experimental in vitro study in patient biomaterials.
Will AlloCyte's intervention be immunosuppressive ?
Allosteric integrin recalibration is directed at rebalancing the immune response, controlling autoimmunity, and avoiding immunosuppression. Therapeutic objective of AlloCyte's first oral target product is to allosterically recalibrate a distinct aberrant integrin over-activation observed in serious self-destructive autoimmunity yet not observed the same in normal self-protective immune responses. This integrin over-activation is thought to trigger aberrant self-perpetuating cycles of cellular self kill, gradually destroying normal tissue architecture and organ function. The target intervention aims to halt these aberrant self-perpetuating cyles and to restore self-protective immune balance as well as tissue integrity. AlloCyte's target intervention represents a novel type of oral immune regulatory precision intervention, foreseen to replace current and still emergent immunosuppressive therapies, in the future.
Why integrins, why now ?
Integrins are a 24-membered family of cell surface receptors mediating cell-cell and cell-matrix interactions. Integrins are the only receptor family known to signal bidirectionally, integrating intra- and extracelluar information. Integrin activity is regulated at conformational levels, i.e. integrin conformation changes upon activation from an inactive bent to an active extended conformation. This conformational activation can be modulated allosterically.
Integrins play key roles in autoimmunity, fibrosis, cancer as well as in neurodegenerative and cardiovascular diseases. Integrins were recognized early for their potential as therapeutic targets yet their pharmacological targeting turned out to be challenging. AlloCyte has demonstrated experimentally that its novel small molecule allosteric platform pharmacology resolves profound limitations of earlier integrin targeted modalities, removing obstacles which blocked successful therapeutic translation in the past. Further, AlloCyte demonstrated recently that integrin selective allosteric targeting can be extended to integrins other than AlloCyte's first target integrin.
Earlier integrin directed therapies have targeted (and continue to target with marketed products) integrins suppressively with the aim of controlling integrins’ biologic functions. Historically, such integrin-suppressive concepts were without alternative as recalibration of integrin activity was not achievable pharmacologically. Allosteric integrin targeting now opens the opportunity to target diseases driven by aberrant conformational integrin over-activation with molecular precision, integrin-selectively recalibrating aberrant integrin over-activity to natural activity ranges. Allosteric integrin recalibration promises to vastly alter, in the future, the therapeutic landscapes of integrin dysregulatory syndromes in autoimmunity, infectious diseases, fibrosis, cancer as well as in degenerative and cardiovascular diseases.
How does AlloCyte work ?
Founded and fully owned by senior professionals and private investors of industrial and academic backgrounds, AlloCyte is fortunate in having access, since its inception, to professional networks in academia and industry which span a broad spectrum of drug developmental competencies. Supported by public and matching private and corporate funds, AlloCyte engages in drug-developmentally integrated cooperations with leading investigators, reputated institutions and pharma companies. The convergence of AlloCyte’s pharmacological advance with novel immune mechanistic and translational concepts of integrin dysregulatory syndromes has created and continues to create AlloCyte’s potentially transformative drug developmental opportunity of small molecule allosteric integrin recalibration.