Journey in a Rare Disease
The story of XTMAB-16 is one of trust, collaboration, expertise and tenacity combining to create an outcome that matched the ambition of our partners. XTMAB-16 is currently under investigation. The safety and effectiveness for its uses have not yet been established.
A monoclonal antibody, originally thought of as a potential biosimilar to infliximab, XTMAB-16 started as a tumor necrosis factor alpha (TNFα) inhibitor targeted to stabilize immune dysregulation. After receiving input from sarcoidosis experts, the development journey began.
Xentria’s great desire to listen, learn, and adapt shaped the developmental process and relationships, ultimately leading to vested buy-in from all major stakeholders to form a collective experience-based approach.
Unmet Needs of Sarcoidosis
- As Xentria assessed the disease landscape, non-clinical testing was underway.
- We recognized sarcoidosis as a rare disease with several unmet needs. Due to varied presentations, the path to care may be long and difficult where individuals struggle with symptoms for years before an accurate diagnosis. There have been limited efforts to bring sarcoidosis-specific drugs to market. Available real-world evidence for this rare disease has been limited. Understanding the disease burden and clinical gaps in pathways to diagnosis and management were our top priority.
- The diagnostic cost is high and patients bear a notable burden in disease navigation.
- While certain medications can reduce some symptoms, there are currently no treatments to change the course of this disease. Patients have expressed a desire for focused, disease-modifying therapy (FSR 2022 FDA Patient Listening Session).
- The two main determinants for initiating treatment are an impaired quality of life and the development of precarious clinical conditions. In order to get treatment, patients must be seen and heard by their physician.
- TNFα is a key regulator of inflammation and is essential for granuloma formation often leading to disease progression. Some biologics have demonstrated therapeutic benefits for patients with sarcoidosis.
- Each patient with sarcoidosis can have granulomas on one or multiple organs. The high level of inter-patient variability makes this complex disease even more difficult to model for drug delivery assumptions.
- Xentria is studying XTMAB-16’s potential for this underserved patient population.
- In evaluating the situation, Xentria decided to pursue clinical drug development for XTMAB-16. We began by building a risk-stratified framework and further engaging the challenging sarcoidosis landscape.
- Xentria used a data-driven approach to evaluate the risks of entering rare disease drug development.
- We recognized the growing community of dedicated advocacy efforts and stakeholders including patients, researchers and healthcare providers fighting for additional treatment options.
- Even with so much variability and so many unknowns, we committed to pursuing informed drug development specifically for this patient population.
- We identified the uncommon opportunity for tailored, rare-disease drug development focused on the intended patient population.
- Xentria began creating a patient-centered development program – well before initiation of Phase 1 in healthy volunteers.
- Early on, Xentria team members invested time and resources to learning by listening to key opinion leaders, patients, and healthcare providers.
- We held a patient-advisory listening session to better understand common burdens, treatment barriers and the disease itself from the everyday experience of patients.
- We met with key opinion leaders to gain insight into treatment guidelines and the current prescriber landscape.
- Collaborators helped us effectively position Xentria to enrich the sarcoidosis research space.
- We created a dedicated space in the program for patient-engagement and advocacy.
- Xentria collaborated with academics to leverage in vitro and pharmacokinetic (PK) models for biosimulations to support investigations of XTMAB-16. Phase 1 findings, combined with non-clinical models of the drug’s effect on granuloma growth, were used to support clinical dosing regimens for the initial trial in patients. The simulation modeled the propensity of the drug to reach pulmonary granulomas and induce an immune response at different doses and at different timepoints, which helped inform trial dosing decisions. We will continue to update inputs in the predictive tool to estimate the magnitude of immune responses and simulated clinically relevant endpoints (Offman et all 2022).
The Regulatory Interactions
- Xentria obtained FDA Orphan Drug Designation for XTMAB-16 in November 2020.
- We continue working within rare-disease drug development guidelines to build an inclusive protocol that includes endpoints and doses clinically meaningful for the patient population.
- The Xentria team has continued interacting with the FDA throughout clinical development.
- XTMAB-16 has the potential to inhibit TNFα.
- As we continue collecting data, we gain confidence that we have a solid candidate in our specific TNFα inhibitor.
- Our platform of strong scientific advisory counsel includes key experts, prescribers, patients, researchers, and advocates.
- A clinical-development program with a focus on commercialization for optimal market growth was established.
- We created value for the product to undergo commercial out-licensing in early stages of clinical development.
- Xentria is proud to be a vested community partner committed to continuing growth and momentum for sarcoidosis research.
XTMAB-16 Phase 1
A study conducted in “healthy” volunteers tested an investigational medication for safety and dose ranges and monitored for any side effects.Get the Details
XTMAB-16 Phase 2
A study in patients living with the condition to continue evaluating the safety of the investigational medication, along with monitoring for potential efficacy and side effects.Details Coming Soon