Interview with Dr. Jostein Dahle, CSO and Co-Founder of Nanovector, on Betalutin® ARC (Antibody-Radionuclide Conjugates) for the treatment of non-Hodgkin Lymphoma.
Cambridge Healthtech Institute recently spoke with Dr. Dahle who will be presenting at the Antibody-Drug Conjugates II: Advancing Toward the Clinic track on Friday May 5th at 11:35am, as part of the 13th Annual PEGS Summit in Boston, MA. Learn about ARCs, what they are and how they work, the application for NHL, as well as hear updates on Nanovector’s latest clinical results of their Betalutin® ARC.
About the Speaker:
Jostein Dahle, Ph.D. is Chief Scientific Officer (CSO) and a co-founder of Nordic Nanovector. He has more than 20 years’ of experience in cancer research and drug discovery and development, gained at Nordic Nanovector and as leader of the Radioimmunotherapy group at Institute for Cancer Research at the Norwegian Radium Hospital. He holds a Ph.D. in radiation biology from University of Oslo (2000) and a M.Sc. in biophysics from Norwegian University for Science and Technology in Trondheim (1995). Dr. Dahle is one of the inventors of Betalutin® and has published more than 50 papers in the field of cancer and biotechnology.
1. Nordic Nanovector is developing a first-in-class Antibody Radionuclide Conjugates (ARCs) for the treatment of non-Hodgkin Lymphoma. Can you tell us more about ARCs, what they are and how they work?
ARCs are biopharmaceutical molecules consisting of tumour-targeting antibodies conjugated, via a chelator, to a radionuclide payload. The antibody in our most advanced ARC (Betalutin®) targets the CD37 antigen on B-cell tumours and is linked to lutetium-177. Betalutin® is currently in clinical development (Phase 1/2) for relapsed/refractory NHL. It is administered as a single injection and causes targeted tumour cell death through irreversible DNA breaks, inhibition of tumour cell division and apoptosis. Interestingly Betalutin® also appears to upregulate CD20 expression on tumour cells, re-sensitizing them to anti-CD20 immunotherapies that are the gold standard NHL treatment.
2. What’s the current state of non-Hodgkin Lymphoma, who does it impact and what are the current treatment options?
Non-Hodgkin Lymphoma (NHL) is the most common type of blood cancer and the 10th most common cancer overall, accounting for 4.3 % of all cancers and 3.2 % of all cancer deaths. In the US and the five largest EU countries, there are approximately 150,000 NHL patients that require treatment.
NHL is not a single disease but a group of closely related cancer types, which are typically divided into two sub-groups, indolent and aggressive, according to if the tumors are slow- or fast-growing. Nordic Nanovector is planning to evaluate Betalutin® for treatment of both types of NHL.
Follicular Lymphoma (FL) is an indolent form of NHL and accounts for roughly 22 % of NHL cases, making it the most common type of indolent lymphoma and the second most common NHL overall. FL is an incurable disease and there is a need for new treatments with low side-effect profiles, both in earlier lines to replace the highly toxic chemotherapy regimens currently used and in late lines, as over time patients have shorter remission periods between treatments, and eventually become refractory to therapy (especially to anti-CD20 agents which are part of standard therapy).
Diffuse Large B-cell Lymphoma (DLBCL) is an aggressive form of NHL, which accounts for roughly 35 % of NHL cases and is the most common NHL subtype. DLBCL is treated with the anti-CD20 antibody rituximab in combination with different chemotherapies. Patients with relapsed DLBCL have a poor prognosis with a median survival of approximately 12 months for those who are unable to undergo stem cell transplantation.
3. Why does Nordic Nanovector decide to go into the NHL space and what are the benefits of Betalutin?
We decided to go into the NHL space because there is a high medical need for new treatments against another target than CD20 and because we discovered an opportunity. We knew that first-generation ARCs (radioimmunotherapy), using iodine-131 and yttrium-90 instead of lutetium-177 and targeting CD20 instead of CD37, had very good results in NHL.
In addition, CD37-targeting molecules had been tested with promising results. So when we discovered that an antibody against CD37 had been developed at the Norwegian Radium Hospital in the 1980s we decided to start Nordic Nanovector and see if we could develop a better treatment for NHL.
The lutetium-177 radionuclide emits beta-radiation with a much lower range than the beta-radiation from yttrium-90, which keeps the tumour cell-killing activity very localized, minimizing impact on healthy cells, and may be more useful for well vascularized and radiation sensitive tumors like NHL.
Furthermore, the half-life of lutetium-177 is 6.7 days, matching the circulation time of the anti-CD37 antibody, which is an important safety consideration. In addition, the longer half-life of lutetium-177 versus that of yttrium-90 (2.7 days) also facilitates centralized production and shipping of ready-to-use Betalutin® to hospitals worldwide. Finally, the radiation from Betalutin® is mainly contained inside the patient’s body and the treatment can therefore be administered on an out-patient basis, as patients don’t need to be isolated nor there is a risk for medical staff or relatives.
4. Can you share the latest results from your clinical trial of Betalutin® ARC?
Betalutin® is being tested in a Phase 1/2 clinical trial in relapsed/refractory NHL patients with four arms testing different doses and pre-dosing regimens. So far, the study has generated encouraging results, with Betalutin® treatment demonstrating a promising efficacy, i.e., durable responses, and a favorable safety. It compares very well to other treatments in development and on the market. We believe we have identified an optimal dose regimen to take into a pivotal Phase 2 trial, which we expect to start this year.
5. What exciting development/therapies do you foresee for future treatments for NHL and other types of cancer?
I think the success stories of Xofigo and SirSpheres have opened up a new era of nuclear medicine for cancer, where Betalutin® has the potential to be one of the new successful treatments alone and in combination with other leading drugs. We are also developing ARCs with characteristics aimed at targeting other types of haematological cancers. As therapies become more personalised, a more precise targeting and combination treatments represent two key elements of the medicines of the future.