Technology: Radiolabeled PARP Inhibitors
Core Message
At MTR, we develop diagnostic products for optical imaging and robotic surgery of cancerous mucosal leasions as well as radiodiagnostic and -therapeutic drugs for cancer patients based on PARP inhibitors. Our drug development pipeline consists of a family of labelled small molecules allowing fast targeted delivery of diagnostic or therapeutic compounds to the DNA of cancer cells while sparing healthy tissues. MTR leverages small molecules to labeled probes featuring an excellent biodistribution, rapid cell membrane penetration and superior target affinity.
Our selected lead compounds and product formulations constitute a new class of anti-cancer drugs combining effective targeting of cancer cells with an excellent safety profile. Their theranostic feature, whereby the same compound can be used for both imaging and therapy, embodies the ultimate form of personalised precicion oncology.
Diagnosis, Monitoring & Staging
The development of diagnostic PARP inhibitor imaging agents opens up a new realm of clinical possibilities. Optical PARPi agents may be used for both diagnostic purposes and improvement of surgical procedures through intraoperative imaging. RadioPARPi allows diagnostic work up, precise stratification of patients, quantification of target engagement, and monitoring of non-invasive treatment. To date, no imaging technologies are available to monitor the efficacy of PARP inhibition.
Therapy
The ultimate goal of therapeutic radioPARPi is utilizing the overexpression of PARP in tumor tissue to induce irreparable DNA damage and subsequent cell death.
Therapeutic strategies in oncology comprise among others:
- Add on (adjuvant) therapy to cold PARPi potentiating its cytotoxic effect.
- Last option for drug resistant subgroups (monotherapy)
- Last option for refractory (therapy resistant) small lesions (monotherapy)
Currently there are no radiolabeled PARP inhibitors for Dx or Tx on the market.
By developing this new class of drugs with a distinct mode of action, we aim to support patients developing resistance to the currently marketed non-labeled anti-cancer drugs. In addition, our compounds demonstrate an excellent safety profile and the possibility of concomitant therapy (pharmaceutical, internal or external beam radiation).
Mechanism of action
The MTR focus will be on drug candidates with a targeting potential in various types, sizes, grades and stages of solid cancer. The benefits are huge as the intended mechanism contemplated concerns most types of prominent cancers (breast, lung, prostate, ovary, skin & brain). The majority of cancer patients would benefit from such innovative molecular radio-nuclide therapy once a superior patient outcome in comparison to standard-of-care therapies is established.
Radionuclide therapy is a proven cancer treatment on the market for several decades. The first non-sealed radionuclide therapy was radio-iodine (I-131) for thyroid cancer dating back to the 1940’s. However, due to the advancement of precision Dx optimising tumor targeting, increasing availability of radionuclide supply & logistics, the implementation of multidisciplinary tumor boards and recent commercial successes driving the market, the field of radio nuclide therapy is on the verge of breakthrough.
Analysis of the personalised medicine market shows that site-specific drug delivery is becoming critical to medicine.
Diagnostics
Data in cancer models show that the uptake of our compound is specific for PARP activity and correlates with biochemically determined PARP activity. Additional preliminary data also suggests that a decreased uptake of a labeled PARP inhibitor like olaparib may predict tumor response to cytotoxic therapy. Therefore, we will focus on the development of radiolabeled PARP inhibitor for PET/CT molecular imaging in cancer patients.
Therapy
The use of a PARP inhibitor labeled with a therapeutic radioisotope offers much more promise and could lead to more powerful therapy due to the combination of the cell-specific characteristics of a PARP inhibitor and the additional tumor-cell specific internal radiation therapy on molecular level provided by a radionuclide with short half life time, high local energy and a very short radiation range to avoid damage of healthy tissues.