About
Who is AlloCyte Pharmaceuticals AG ?
AlloCyte Pharmaceuticals AG is a Swiss-based company discovering, developing and commercializing next generation oral integrin modulators of allosteric mode of action to protect the integrity of tissues afflicted by autoimmunity. The company’s next target milestone is clinical therapeutic proof-of-concept in a severe tissue-destructive autoimmune disease.
'The hardest thing to see is what is in front of your eyes.'
Johann Wolfgang von Goethe
Why target integrins allosterically ?
AlloCyte's targets, integrins, are a 24-membered family of cell surface receptors mediating cell-cell and cell-matrix interactions. Integrins are known to play key roles in autoimmunity, fibrosis, cancer as well as in neurodegenerative and cardiovascular diseases. They are recognized as powerful therapeutic targets, in consequence. However, first generation integrin targeted pharmacological interventions (antibodies, small molecule ligand mimetics) found themselves confronted with profound challenges, in part eliciting effects on integrins which were much broader than or even opposite to the intended effects. AlloCyte’s next generation allosteric platform pharmacology has been shown experimentally to resolve these challenges. AlloCyte's allosteric pharmacology is anticipated, therefore, to unlock the full therapeutic potential of integrin targeting by enabling a novel type of integrin-recalibratory (rather than integrin-suppressive) intervention of therapeutic game change potential.
What is the game change ?
A. Allosteric mode of action: AlloCyte's next generation allosteric integrin platform pharmacology is orally available with therapeutically attractive pharmacokinetic characteristics, is integrin-selective and lacks both integrin cross-regulatory and paradoxical effects (i.e. integrin effects counter to the intended effects). AlloCyte's pharmacology will thus resolve profound limitations of both earlier non-allosteric anti-integrin antibody (associated with broadly immunosuppressive effects) and earlier small molecule integrin ligand mimetics (associated with paradoxical effects). Based on its unique profile, the novel platform pharmacology is destined to enable integrin-recalibratory precision interventions not achieved and not achievable by earlier non-allosteric integrin targeted modalities.
B. Protecting tissue integrity in MHC-II associated autoimmunity: Therapies currently in use to treat severe tissue-destructive autoimmune diseases suppress disease-associated pathways yet fail to potently restore and durably protect tissue integrity. Allosteric recalibration of a distinct aberrant integrin hyper-activity observed in severe autoimmunity (yet not observed the same in natural self-protective immunity) directly targets cellular and molecular mechanisms of autoimmune self-tissue destruction. Those mechanisms were dissected earlier by clinical investigators at a leading US academic clinical institution. In cooperation with this institution, AlloCyte recently bridged in patient biomaterials the pharmacological effect profile of its next generation allosteric pharmacology to an earlier used non-allosteric integrin pharmacology, showing the induction of therapeutically intended and the absence of non-intended (in part paradoxical) effects of the former pharmacology. Once validated by clinical therapeutic testing, oral-use allosteric integrin-directed restoration of immune balance (rather than gross integrin- and immune-suppression) is foreseen to revolutionize the treatment of tissue-destructive autoimmunity, superseding suppressive interventions currently in use and still in development. AlloCyte's immune-recalibratory (rather than immune-suppressive) precision intervention is advanced in close cooperation with the international clinical and translational immunologist community.
Who patients will benefit ?
AlloCyte targets serious tissue-destructive MHC-II associated autoimmune diseases including lupus erythematosus, inflammatory bowel disease (IBD) and rare tissue-destructive autoimmune diseases of grave prognoses and pressing medical needs. The key role of AlloCyte's first target integrin in these indications is well-documented and even validated therapeutically in part by earlier non-allosteric first generation integrin pharmacology. Effective next generation oral allosteric integrin products resolving the profound limitations of earlier non-allosteric integrin pharmacology are projected to vastly alter therapeutic landscapes in autoimmunity.
AlloCyte's integrin recalibratory intervention is directed at a fundamental abnormality observed across autoimmunity, with 5-8% of the general population afflicted with autoimmune diseases. Once therapeutically validated in its lead indication, AlloCyte's intervention is projected to become of therapeutic impact in other currently difficult-to-treat autoimmune diseases. As AlloCyte's patent-protected platform pharmacology delivers multiple potential drug candidates, the company foresees the future stratification of its compound portfolio to the different therapeutic demands of different tissue-destructive autoimmune diseases afflicting different organs and tissue compartments.
Is AlloCyte’s pharmacology proven active upon oral use ?
Yes, AlloCyte’s first small molecule allosteric integrin targeted drug candidate prevented disease activity in an experimental animal model of autoimmunity upon oral dosing. Treatment milled into food was taken up avidly and well-tolerated throughout the course of the study, delivering the therapeutically intended systemic exposure levels. The need for concomitant symptomatic medication observed in the vehicle control cohort was abrogated in actively treated animals, completely.
The tolerability and safety profile of this first drug candidate is affirmed by repeat dose studies across species. AlloCyte’s first drug candidate is further found to exhibit a clean ADME profile as well as excellent oral biovailability and PK/PD characteristics, projected to potentially support an once daily oral dosing regimen, in the future.
Is AlloCyte's pharmacology proven active in human disease ?
Exploratory clinical therapeutic proof-of-concept in AlloCyte's lead indications has been established by an earlier non-allosteric pharmacology directed against AlloCyte's first target integrin. AlloCyte recently successfully bridged to this clinical-therapeutic proof-of-concept by testing its differentiated orally available allosteric integrin platform pharmacology in human patient tissue samples and cells, confirming the therapeutically intended cytokine effect profile and the absence of unintended effects induced by first generation non-allosteric integrin pharmacology. These bridging data affirm the validity of AlloCyte's therapeutic concept. They will also inform future biomarker development. Based on the successful bridging of pharmacological effect, AlloCyte has defined the activities of its lead program up to oral-use therapeutic proof-of-concept in a target indication of high need and high therapeutic promise, ready for execution.
Will AlloCyte's intervention be immunosuppressive ?
Allosteric integrin recalibration is directed at rebalancing the immune response, controlling autoimmunity, and avoiding immunosuppression. The therapeutic objective of AlloCyte's first oral target product is to allosterically recalibrate the aberrant integrin-mediated hyper-adhesiveness of distinct auto-reactive cell subsets observed in self-destructive autoimmunity yet not observed the same in normal self-protective immune responses. Integrin-mediated hyper-adhesiveness of naturally dormant auto-reactive cell subsets is thought to trigger and sustain aberrant self-perpetuating microenvironmental cycles of tissue destruction and remodeling. A decisive insight deriving from experimental translational research conducted at AlloCyte's academic clinical partner site is that these aberrant cycles do not seem backed by integrin redundancy which naturally backs-up and safeguards self-protective immune responses. This critical difference is expected to render the aberration uniquely sensitive to integrin selective recalibration. AlloCyte's target intervention thus represents a novel type of oral immune recalibratory precision intervention, foreseen to restore self-protective immune balance, to protect tissue integrity and to eventually replace currently used and still emerging immunosuppressive therapeutic interventions for severe tissue-destructive autoimmunity.
Will further integrins become targetable allosterically ?
Computerized drug discovery technologies employed by AlloCyte suggest that allosteric targeting will be extendable to therapeutically attractive integrins other than AlloCyte’s first target integrin. Such extension is projected to widen therapeutic horizons of small molecule allosteric integrin targeting far beyond the spectrum of diseases driven by dysregulation of AlloCyte’s first target integrin.
What is AlloCyte's path to therapeutic game change ?
Founded by a team of drug developmental competency, i.e. successful developers of market-leading drugs and reputated professionals of pharma-industrial and academic backgrounds, AlloCyte is fortunate in having access, since its inception, to leading professional networks in academia and pharmaceutical industry which span a broad spectrum of drug developmental expertise. Supported by public and matching private and corporate funds, AlloCyte engages in drug-developmentally integrated cooperations with leading investigators, reputated academic institutions and pharmaceutical companies. With pharmacological bridging to earlier clinical therapeutic proof-of-concept accomplished, AlloCyte is currently extending its institutional and investorial networks to enable therapeutic proof-of-concept of its oral allosteric integrin platform pharmacology in AlloCyte's first autoimmune target indication of high unresolved need, with activities defined and ready for effective execution.