Inconsistent Preclinical Results Delay NXP002’s Potential Move to Trials
Inconsistent results in the final planned preclinical study of NXP002, Nuformix’s experimental inhaled therapy for idiopathic pulmonary fibrosis (IPF), delayed completion of the preclinical data package needed for a potential advancement into clinical trials.
The U.K.-based company, through an outsourced contract research organization (CRO), now plans to conduct additional studies, including with a new inhaled formulation of NXP002. Results are anticipated no later than March 2023.
“We have sufficient funds to conduct the studies on NXP002 and, based on our current projections, to continue to [the last quarter of] 2023,” Riddell added.
IPF is characterized by excessive inflammation and tissue scarring, or fibrosis, in the lungs, making it difficult for patients to breathe.
NXP002, Nuformix’s lead therapy candidate, is a new formulation of tranilast, an antiallergic oral medication that has anti-fibrotic effects, but is poorly absorbed into the body and tissues and has whole-body toxicity issues.
The inhaled NXP002’s improved pharmacological properties allow it to be delivered directly into the lungs, which is expected to reduce both the dose necessary to promote therapeutic effects and whole-body toxicity, compared with oral dosing.
Previous studies showed NXP002 reduced fibrosis and inflammation in lab-grown lung tissue collected from IPF patients. These effects were increased when the therapy was combined with standard IPF treatments — Genentech’s Esbriet (pirfenidone) and Boehringer Ingelheim’s Ofev (nintedanib).
Researchers next evaluated the pharmacokinetics and pharmacodynamics of an inhaled formulation of NXP002 with the potential to be effectively delivered through commonly used nebulizer devices in rats. Pharmacokinetics refers to the therapy’s movement into, through, and out of the body, while pharmacodynamics refers to its effects on the body.
Results showed that when delivered through nebulization, NXP002 achieved significant levels of exposure in the animals’ lungs while limiting exposure to the rest of the body compared with oral dosing.
The therapy also led to a dose-dependent reduction in inflammation and fibrosis-relevant mediators after exposure to lipopolysaccharides (LPS) — components of the cell wall of certain bacteria that have both pro-inflammatory and pro-fibrotic effects.
As part of NXP002’s preclinical data package, a final study of the durability of NXP002’s effects in these rats was commissioned to a CRO, with results expected early this year.
The study was designed to assess the duration of these effects, with the gap between treatment and LPS exposure extending from 30 minutes, as in the prior rat study, to eight hours.
However, the study’s protocol was not adequately followed, invalidating the study and making it necessary to repeat it according to the protocol. Results from the recently concluded repeat study were, however, inconsistent with those observed in the first rat study.
Given that Nuformix and its development advisers believe that no positive or negative conclusions can be drawn from this study, the company, in consultation with the CRO, decided to move forward with further studies, including evaluation of a new inhaled formulation of NXP002.
The new studies will examine both the pharmacokinetics and effectiveness of this new formulation, and results are expected on or before the first months of next year, depending on the CRO’s availability.
“We continue to believe that NXP002 is a valuable asset that can overcome the limitations and issues of tranilast being delivered orally,” Riddell said.
Should the new studies provide positive results, the company will likely seek licensing and partnering opportunities to advance the therapy into clinical trials.
Nuformix has filed two patent applications on new formulations of tranilast for therapeutic use. One has been granted globally. The second patent application was issued in the U.S. last year and is undergoing examination in other territories.