IDP Pharma begins clinical trial for its drug IDP-121 in patients with small-cell lung cancer

IDP Pharma, a leading biotechnology company in the development of therapies targeting intrinsically disordered proteins (IDPs), has announced the enrolment of the first patient in the multicentre Phase 1b/2 clinical trial. The MYCROCYTIC study will evaluate the safety and tolerability of IDP-121, a therapeutic peptide designed to inhibit the activity of the MYC protein, key in the development and progression of cancer. The drug will be administered in combination with standard treatments for small-cell lung cancer (SCLC). 

Headquartered at the Parc Científic de Barcelona of the University of Barcelona (PCB-UB), the company thus takes a new step in the clinical development of this therapeutic candidate and enters the realm of solid tumours, following the positive Phase I results obtained in the previous CASSANDRA study in patients with various MYC protein-dependent haematological cancers. In many cancer cells, the MYC protein is often dysregulated or overexpressed. With this first evaluation of IDP-121 in a solid tumour, IDP Pharma aims to characterise its safety profile and obtain the first evidence of its clinical potential in this type of tumour.

For Dr Santiago Esteban, CEO of IDP Pharma, "The start of this study represents a significant milestone in the development of our clinical pipeline and reflects our strategy of transforming innovative scientific advances into medicines for patients with unmet medical needs. We believe that IDP-121 exemplifies the potential to develop differentiated therapies against some of the most complex biological mechanisms involved in cancer". 

The project, which will continue recruiting patients until 2028, coinciding with the publication of the first results, has received support from the public-private partnership grants programme of the State Research Agency (AEI), part of the Spanish Ministry of Science, Innovation and Universities (CPP2023-010510).

A new therapeutic approach against the most aggressive and silent lung cancer 

Small-cell lung cancer (SCLC) remains one of the most aggressive solid tumours and accounts for approximately 15% of all lung cancer cases, with a five-year survival rate of less than 10%. Despite recent therapeutic advances, such as chemotherapy with lurbinectedin or immunotherapy with tarlatamab, relapses are very common and long-term outcomes remain limited. There is therefore a need to develop new therapies with innovative action mechanisms capable of combating treatment resistance and halting disease progression, while also demonstrating the high clinical potential of these new therapeutic approaches. 

"Patients with recurrent small-cell lung cancer continue to have limited treatment options, especially those whose disease progresses shortly after first-line platinum-based chemotherapy. This study allows us to evaluate a new MYC-targeted approach in the two main second-line clinical settings, while maintaining established chemotherapy regimens. We hope to determine whether MYC inhibition can translate into a clinically relevant benefit for patients with relapsed small-cell lung cancer," said Dr Hugo Arasanz Esteban, principal investigator of the study at Hospital Universitario de Navarra, where the first patient for the trial was recruited. 

IDP-121 targets the intrinsically disordered MYC protein, a key regulator of tumour proliferation, lineage plasticity and resistance to treatment in small-cell lung cancer. Alterations of the MYC protein family (MYC, MYCL and MYCN) are found in 20-30% of cases and are more frequently detected in advanced tumours and after relapse. There is growing evidence that the activation of this pathway promotes the transition to less differentiated tumour states, associated with greater aggressiveness, resistance to treatments and the loss of certain therapeutic targets, such as the DLL3 protein. These observations reinforce the potential of MYC-targeted therapies in patients with relapsed small-cell lung cancer. 

In this context, by inhibiting MYC, IDP-121 could help to halt tumour transition and preserve the initial neuroendocrine phenotype, maintaining sensitivity to chemotherapy and the expression of targets such as DLL3. Taking this as its starting point, the trial will evaluate two 2 second-line patient populations with differentiated prognostic profiles: Patients with platinum-refractory or platinum-resistant cancer will receive IDP-121 in combination with topotecan, while patients with platinum-sensitive cancer will receive IDP-121 together with a new platinum-based treatment.

Intrametrics™, a platform for targeting intrinsically disordered proteins 

According to Dr Laura Nevola, the company's CSO, "for decades, intrinsically disordered proteins such as MYC have been one of the great challenges in the development of new medicines, because they do not have a defined structure on which to act with conventional approaches." Now, the company's proprietary Intrametrics™ platform overcomes this barrier by enabling the drug to inhibit the MYC protein, promoting its degradation. 

"IDP-121's entry into Phase 1b/2 testing for the treatment of small-cell lung cancer highlights this technology's potential to develop new therapies against targets that until now were considered intractable," said Nevola. 

Unlike other current therapeutic approaches, such as CAR-T therapies or biosimilars, IDP Pharma's technology is not based on modifying immune system cells or replicating existing biologic drugs. Intrametrics™ instead acts directly on intrinsically disordered intracellular proteins, such as MYC, which until now were considered intractable because they lack a fixed structure on which to design a conventional drug. 

This ability to design drugs against targets previously considered intractable places IDP Pharma in a distinctive position in the field of targeted therapies, with potential applications beyond small-cell lung cancer.