Dr David J Mazzo from Caladrius Biosciences introduces CLBS20, which has recently moved into its phase three trial – named the Intus trial. He explains how the drug works, discusses the stage two findings, and outlines his hopes for FDA approval in 2018.

The New Economy: Being diagnosed with cancer was once likened to receiving a death sentence. But great scientific innovations have helped patients in the fight against the disease. Here to put a spotlight on just one cancer immunotherapy that is in a phase three clinic trial stage: Dr David J Mazzo of Caladrius Biosciences.

First, can you tell me about your therapy that’s under development: what is it called, and how does it work?

David J Mazzo: Our therapy is actually called CLBS20, formerly known as NBS20. It is a therapy that is derived from the isolation of the cancer inducing cells that one finds in a melanoma tumour: those cells that are self-proliferating, and actually cause the metastases that ultimately result in in death when someone has late stage melanoma.

We teach that patient’s immune system, using their dendritic cells, to specifically target and attack those cells. The idea is to prevent the distant metastases and to prolong life.

The New Economy: Now, who is this treatment really targeted for? I mean, how is it different from other melanoma therapies, both on the marketplace and in development right now?

David J Mazzo: Well, the treatment is currently being studied in patients with late-stage melanoma – those that have what’s known as recurrent stage three or metastatic stage four melanoma. These are the people who are in the end stages of the disease, and have had an opportunity to try many other therapies, often without much success.

The other therapies that exist really fall into two general categories. There are those that are chemotherapeutic, and then there are those that are immunotherapeutic. And the chemotherapeutic agents are, if you will, selective poisons that try to kill cancer cells without doing much harm to the cells adjacent to the cancer – often without great success.

And then, the other immunotherapies that are in development are really looking at trying to unleash a latent immune response in a patient that is a naturally occurring response. And many patients don’t have that, so those types of immunotherapies – checkpoint inhibitors would be one example – have a limited success thus far in prolonging life.

Ours, because it focuses principally on the cancer inducing cells, looking to prevent the distant metastases, has shown in phase two a great potential to prolong life.

The New Economy: I see. Now tell me: what did the phase two data then show you?

David J Mazzo: Well, the phase two data actually was really compelling, from really a multitude of perspectives. In the first study that was done, which was just a single arm uncontrolled study, we demonstrated over the course of a five year follow-up a true, 50 percent survival rate in patients with the late stage melanoma.

That is somewhere between three and five times greater than the expected survival rate at five years for patients undergoing standard of care at the time of the study.

We then followed that study with a controlled, randomised study, where the control group was actually just our isolated and immobilised cancer-inducing cells, without the dendritic cell component. And of course the therapy was as described previously.

And in that study we demonstrated a 72 percent two year survival rate, versus 31 percent for the control group against the backdrop of approximately 25 percent anticipated survival rate for people receiving standard of care at the time.

So clearly a very statistically significant improvement in the reduction of mortality, and also great consistency of results from study to study.

The New Economy: So can you tell me now about a grant from the California institute for Regenerative Medicine that you received for this trial?

David J Mazzo: The achievement of a grant from them not only represents additional financial support – which is always helpful when conducting a large clinical trial – but also represents an endorsement of the potential that is viewed from this particular therapy in this particular medical indication.

The New Economy: Okay. So what are the details, doctor, of the phase three trial; and when do you hope for the treatment to reach the marketplace?

David J Mazzo: Well, our phase three trial, which has been named the Intus trial, is a trial that we hope will be confirmatory in comparison to the two phase two trials.

It is studying patients from the same patient population, using the same therapy, with the same dosing regimen and the same overall survival endpoint.

It’s enrolling 250 patients; it has actually been screening patients since earlier this calendar year. We’ve already randomised our first patient, and the goal is to have all patients enrolled within a 24 month period, and to be at the point of analysis of the first interim analysis after 99 events, sometime in the second half of 2017.

The anticipation is that we’ll be able to demonstrate a statistically significant improvement in the reduction of mortality at that time – and then the earliest possible biologic licence application will be filed in early 2018. With the fast-track designation that this programme has received from the FDA, we expect the earliest approval could come late in 2018.

The New Economy: Okay, very interesting. Dr Mazzo, thank you so much for joining me today.

David J Mazzo: I appreciate the interest in our company. Thank you very much.