Pipeline

SAVI (STING-Associated Vasculopathy with Onset in Infancy) Skin phenotype

In SAVI patients, gain-of-function mutations in the STING1 gene drive constitutive type I interferon signalling, resulting in chronic inflammation, vasculopathy and high morbidity. Approximate 1/3 or the patients have a severe skin phenotype with ulcerations, infections and repeated amputations. Conventional immunosuppressive therapies and JAK inhibitors incompletely address skin lesions, leaving a significant unmet need for interventions that promote local tissue restoration. Preclinical and early clinical studies of ILP100 demonstrate accelerated wound healing via sustained local CXCL12 delivery, increased TGF-β-expressing macrophages, improved local blood flow, and antimicrobial activity against multidrug-resistant wound pathogens. These properties suggest that ILP100 has the potential to promote wound closure, limit tissue loss, and reduce infection risk in SAVI-related skin ulcers, supporting its clinical evaluation in this patient population. FDA have granted an Rare Paediatric Disease Designation (RPDD) for SAVI and the ILP100-Topical and Ilya Pharma have planned a confirmatory clinical trial with the patient organisation, the KOLs and lead sites, NIH, uPenn, Great Ormond Street Hospital and more. "An Open Label Dose Escalation Exploratory Phase 2 Study to Evaluate Safety and Biological Effect of ILP100-Topical in Subjects with STING-Associated Vasculopathy with Onset in Infancy and Skin Ulcers on Wound Healing and Limb Saving". 

Typical skin wounds in paediatric patient with SAVI, Figure from Munoz et al., 2015 JAMA Dermatology

Immune Checkpoint Inhibitor induced Colitis

58% of cancer patients receiving immune check point inhibitors (ICIs) develop gastrointestinal toxicities and cause of death is most often ruptures leading to sepsis, sepsis with multi drug resistant bacteria is >2.5x more common in cancer patients. ILP100-Oral covers the clinical PoC for a new first-line-treatment in patients with ICI-induced colitis in a multicenter first-in-human phase 1/2a with trial healthy subjects and cancer patients on ICIs suffering from ICI-induced colitis stage 1 and 2. The main hypothesis, and driver of value, is to allow the immune system to be aggressive fighting the cancer, as induced by the ICIs - but leaving the gut alone using local acting anti-inflammatory treatment, as opposed to systemic anti-inflammatory treatments used today. Standard of care today relies solely on systemic anti-inflammatory treatments being steroids and biologics and these come with a number of drawbacks such as their adverse event profiles and counteracting the ICIs-effects the cancer. The ultimate goal is to facilitate a larger portion of patients on ICI treatment to be able to complete the lifesaving treatment.

Colon with ICI-induced colitis where especially fibrosis is visual, Figure from Som et al., 2019 World J Clin Cases

SAVI with lung phenotype and Cystic Fibrosis

In SAVI patients, gain-of-function mutations in the STING1 gene drive constitutive type I interferon signalling, resulting in chronic inflammation, vasculopathy and high morbidity. Approximate 1/3 or the patients have a severe lung phenotype. Respiratory symptoms in SAVI can be insidious and are not specific (chronic cough, exertional dyspnea, and hemoptysis) and pulmonary function tests shows mainly a restrictive syndrome with diffusion impairment, sometimes associated with hyperinflation, but also obstruction or a mixed lung function impairment and biopsies shows increased inflammation and fibrosis. Repeated infections are common and problems with chronic multi drug resistant bacteria and may lead to the need of a lung transplant.

Cystic Fibrosis is a well studies genetic rare disease and patients are have recently experienced benefits from CTFR "correct and enhance" combination therapy. There is stilla significant treatment gap in further preserving or improving the declining lung function and adress the often chronic lung infection with MDR pathogens.

The overall aim of this project is to evaluate a novel, local bacterial immunotherapy based on Limosilactobacillus reuteri transformed to produce and release the chemokine CXCL17 for the treatment of inflammation and multidrug-resistant (MDR) bacterial infections in models of STING-Associated Vasculopathy with onset in Infancy (SAVI) and cystic fibrosis (CF). CXCL17 belongs to a group of mucosal chemokines where exact functions in homeostatis and disease are being uncovered. By delivering high local concentrations of CXCL17 directly to the respiratory mucosa, the therapy is designed to:

-Reduce inflammatory neutrophil recruitment

 - Enhance neutrophil- and macrophage-mediated bacterial clearance,

- Leverage the intrinsic antimicrobial effects of both CXCL17 and L. reuteri, and

- Promote resolution of inflammation and tissue repair in the subepithelial lung tissue.

- Preserve lung function following an infection 

Representative Lung Imaging and Pathology in SAVI showing fibrosis and inflammation from David and Frémond 2022 Cells.