Radiopharm Theranostics advances cancer treatment with RAD 301 and RAD 302 developments

Radiopharm Theranostics (ASX: RAD) has welcomed the release of new data identifying a promising pathway for its innovative RAD 301 and RAD 302 oncology developments.

Multiple new data covering the RAD 301 and RAD 302 programs were featured at the 2024 European Molecular Imaging Meeting (EMIM) in Portugal this week.

RAD 302, which is currently in preclinical development, is a 177Lu-labelled peptide-based therapeutic agent that targets αvβ6-integrin, a cellular marker for tumour invasion and metastatic growth, the expression of which correlates with decreased survival in several carcinomas.

177Lu is a radioactive drug that can be used to treat adults with tumours that are somatostatin receptor positive.

RAD 301 granted FDA ODD rating

In May 2023, the FDA granted Radiopharm with an orphan drug designation (ODD) for RAD 301 – also a peptide-based imaging agent targeting αvβ6-integrin – in pancreatic ductal adenocarcinoma (PDAC).

Radiopharm has recently dosed the first participant in a Phase I clinical trial for RAD 301 being conducted under the direction of Dr Lionel Zuckier at the Albert Einstein College of Medicine in New York.

The study will assess the safety, radiation dosimetry and imaging characteristics of RAD 301 in patients with advanced PDAC.

Lung cancer trials

Professor Susanne Kossatz from the Technical University of Munich made a presentation at EMIM on data from a lung cancer mouse model demonstrating that the reduction of kidney uptake of the αvβ6-integrin targeting therapeutics and diagnostics, such as the developmental radiotherapeutic 177Lu-D0301 and the imaging agent 68Ga-Trivehexin (RAD 301), was much stronger following administration of succinylated gelatine, a blood plasma replacement.

The kidney protective effects of succinylated gelatine on αvβ6-integrin targeting agents pave the way towards a safe and effective clinical application of RAD 302 in many carcinomas that highly express αvβ6-integrin including PDAC, non-small cell lung cancer (NSCLC) and head-and-neck squamous cell carcinoma (HNSCC).

Radioactivity reduction

Doctor Johannes Notni, co-inventor of the RAD 301 and RAD 302 technologies and a scientific advisory board member to Radiopharm, said the investigation of different renal protection strategies for 177Lu-labelled αvβ6-integrin targeted therapeutic radiopharmaceuticals and the reduction of radioactivity levels in the kidneys by gelatine infusion was found to be more efficient than in any preceding study, as the tumour-to-kidney ratio was tripled.

“Since these results are readily transferable to Radiopharm’s RAD 302 development pipeline, the prospects of its clinical success are greatly improved by such data.”

Nora Schmid from the Technical University of Munich presented a talk on the first comprehensive analysis to evaluate the localisation and expression density of ITGB6 based on more than 3,200 specimens from approximately 1,400 patient cases covering 14 αvβ6-integrin expressing carcinomas including PDAC, NSCLC, HNSCC and the most prevalent female cancers.

Tumour-agnostic potential

The results confirmed that αvβ6-integrin is highly expressed across a variety of common cancers, highlighting its potential as an attractive tumour-agnostic target for theranostic treatment in a large diversity of eligible patients.

The findings further support Radiopharm’s development strategy for the imaging of αvβ6-integrin cancers with RAD 301 and their treatment with RAD 302.

“In view of the massive number of investigated cases and specimens, this is a truly authoritative analysis of the fraction of ITGB6 that is located on tumour cell membranes, which means that it can actually be addressed with αvβ6-integrin targeted pharmaceuticals (both radiolabelled or not),” Dr Notni said.

“We have confirmed unexpectedly high levels of this biomarker in a broad range of cancers, including the female-exclusive entities cervical, ovarian, and endometrial (uterine) cancer.”

“Notably, currently approved radiopharmaceuticals are only applicable to very rare neuroendocrine tumours or male-only prostate carcinoma.”

“αvβ6-Integrin-targeted theranostics, such as the RAD 301 / RAD 302 theranostic pair, may eventually prove to be a promising approach to addressing the unmet medical needs of the world’s female population with tailored radiopharmaceuticals.”