Redesigning paclitaxel: expanding the therapeutic window through oral delivery

The problem 

Despite major advances in targeted treatments and immunotherapies, chemotherapy remains a cornerstone in breast cancer treatment. Among available cytotoxic agents, taxanes – and particularly paclitaxel – continue to play a central role thanks to their potent antitumour activity, broad applicability and proven efficacy across multiple cancer types. 

Paclitaxel acts by stabilising microtubules, thereby halting cell division in cancer cells. However, its extremely poor water solubility and resulting minimal oral bioavailability (less than 2 percent) have forced clinicians to rely exclusively on intravenous (IV) delivery. 

Though effective, IV administration has some major drawbacks. Producing a sharp initial spike in plasma levels – often exceeding 900 ng/ml – this delivery method leads to acute toxicities such as neutropenia, alopecia and nausea. Furthermore, concentrations quickly fall below the therapeutic threshold, shrinking the effective treatment window to roughly eight hours. This combination of high peak toxicity and short duration of efficacy limits both patient tolerance and therapeutic potential. 

The solution 

InnoUp Farma has developed an innovative oral formulation of paclitaxel, INP12, designed to overcome these pharmacological barriers and fundamentally reshape the safety–efficacy balance of this critical chemotherapy. 

Using proprietary nanoparticle technology, paclitaxel molecules are embedded in a bioadhesive matrix that shields them from degradation and facilitates gradual, controlled release. The nanoparticles adhere preferentially to the ileum, where they linger to maximise absorption and improve systemic bioavailability. 

The goal of this design is twofold: 

1. To avoid the toxic plasma peaks characteristic of IV dosing

1. To extend the therapeutic window, maintaining sustained, effective concentrations in the bloodstream for 24 hours or more. 

This re-engineering of paclitaxel’s pharmacokinetics offers significant improvement to both patient safety and therapeutic consistency. 

Preclinical validation of INP12 

Extensive preclinical testing, encompassing laboratory work, animal studies using murine models, and an initial Phase 1a study, have to date produced encouraging results. 

In an orthotopic model of HER2-positive breast cancer in mice, four dosing regimens of INP12 were tested against once-weekly IV paclitaxel (10 mg/kg) and a no-treatment control. The four INP12 regimens included 20 mg/kg given twice a week, 40 mg/kg once a week, 40 mg/kg twice a week and 80 mg/kg twice a week. Tumour volume was measured over a 35-day period following initial dosing. 

After 35 days, mice given the highest dose of INP12 showed a 60 percent reduction in tumour volume compared with those treated with IV paclitaxel, demonstrating the potential of oral INP12 to maintain therapeutic efficacy while mitigating toxicity. 

These preclinical findings provided the foundation for progression into the clinic, confirming that the formulation achieves strong antitumour activity through improved bioavailability and sustained plasma exposure. 

Early clinical findings 

Preliminary results from an ongoing Phase I clinical study in patients with advanced solid tumours have been highly encouraging. INP12 has demonstrated no dose-limiting toxicity and the maximum tolerated dose (MTD) has not yet been reached in the evaluated dose range. On this basis, the trial is now expanding to explore higher paclitaxel doses, seeking to further enhance efficacy while maintaining the favourable safety profile observed to date. 

The trial aims to examine the safety and tolerability of oral INP12 monotherapy, determine the pharmacokinetic profile of paclitaxel in blood plasma and assess how plasma concentrations evolve in the hours and days following administration. 

Equally notable are the high levels of systemic absorption achieved with INP12 – levels consistent with those expected to yield clinical efficacy. These findings strongly support the concept that oral paclitaxel can deliver effective exposure with a markedly improved safety margin, potentially transforming how taxanes are administered in oncology practice. 

Next steps 

Building on these promising results, InnoUp plans to initiate a Phase II trial in 2026, focusing primarily on patients with advanced breast cancer, alongside a smaller cohort with other solid tumours. The study will evaluate both clinical efficacy and continued safety, as well as confirm whether the strong pharmacokinetic performance observed in Phase I translates into meaningful therapeutic benefit. 

Summary 

Paclitaxel remains one of the most important chemotherapies in oncology – but its utility has long been constrained by its toxicity and delivery challenges. By enabling safe, effective oral administration, INP12 offers a way to expand paclitaxel’s therapeutic window, reduce adverse effects and improve patient quality of life. 

This achievement also highlights the broader promise of InnoUp’s nanoparticle platform: a new paradigm for oral oncology therapies capable of transforming drugs once considered too insoluble or toxic for oral use into precisely controlled, patient-friendly treatments. 

INP12 exemplifies how nanoparticle technology can unlock new therapeutic possibilities for established drugs, bringing precision, safety and accessibility to patients.