Point-of-Care Devices in Immunotherapy and Beyond

Rory McCann:
Hi everyone. I'm Rory McCann with the Next Generation Diagnostic Summit. I'm very pleased to have the opportunity to speak with Dr. Allen Northrup, CEO of MIODx, and Sean Givens, COO of MIODx, to talk with us about point-of-care devices and their role in immunotherapy.

Dr. Northrup will be giving a talk at the Enabling Point-of-Care Diagnostics track on August 15th in Washington, D.C. Thank you for joining us.

Allen Northrup:
You're welcome.

Rory McCann:
Is it feasible to use point-of-care devices in immunotherapy?

Allen Northrup:
Okay. So you have to define point-of-care devices. If you're in a hospital and the hospital has sequencing capabilities, then the answer is yes. If you think of point-of-care as some hand-held thing you can take into the field, to a clinic, or doctor's office, then the answer is no, because it requires a DNA sequencer. The only thing I would say about that is that there is some sequencing technology coming out from Oxford Nanopore that is essentially a thumb-drive, but that's pretty early and it's not going to have the kind of resolution we would need, but they said the same thing about PCR 20 years ago.

So the answer is, in point-of-care, if it's in a facility that has sequencing capabilities, then the answer is yes. However, the other question is when would they have to get the answer? So we need a day and a half.

Sean Givens:
I guess it depends on ... When you're determining point-of-care and you have immunotherapy versus infectious disease, that's really critical to get that information back within two hours, four hours. With immunotherapy, because they're on long-term regiments, that point-of-care isn't as critical in terms of getting that timely result. So, in terms of monitoring a patient for immuno response, the idea is to draw blood off patients there until they get a result back to the doctor within a week because you should keep their point-of-care.

Allen Northrup:
So it really depends on how you define point-of-care.

Rory McCann:
Is MIODx exploring point-of-care devices and how?

Allen Northrup:
Right now, I would say that we are, as others are, basically figuring out what information from sequencing ... We specifically sequence T Cells in this particular case ... Figuring out what are the markers, what are the sequences we're looking for ... It's pretty much still in a discovery mode. Our collaborators have published some papers, but it's several years out to have an analogous, like Sean said, device in the clinic or doctor's office that could give you a quick turn-around time on whether you have an infectious disease, HIV, or the flu, or something like that.

So right now, it's still early in discovery, but fundamentally it is point-of-care because the information would be used to modify treatments

Sean Givens:
What we're developing is, eventually, a sequencing kit. Our goal is to be able to have this kit delivered to research labs all over the world and gauge if they run this test, upload the data to our analyzer and get the results back. So I guess from that perspective, we consider that to be point-of-care.

Rory McCann:
Now, what are some challenges between now in the discovery phase, and the future when it is more commonplace, like you said, in doctor's office ... Being able to be used by doctors and their patients ... What are some challenges between now and then that you anticipate?

Allen Northrup:
Like Sean just said, basically, you're gonna have to have access to a sequencer. That could be us, for example, and you would provide a blood sample. We would do the analysis and as you mentioned, upload to, essentially, the cloud. And then doctors and patients would have access to those results remotely. That's the thing. No offensive against the word point-of-care, but it really has to be defined. And the information would be used to modify treatment and that's the point of what we're doing.

I think, in general, point-of-care typically means things like microfluidics, hand-held devices, things that you can widely distribute to doctors' offices; that's not really what we're doing. Maybe in the future, when sequencing becomes portable. That might be doable.

Andrew Ko:
Do you think that this kind of technology, that is in the discovery phase ... Do you think it can impact the future of immunotherapy, and how do you see the two working together?

Rory McCann:
Right now, what's happening in immunotherapy is that the physician makes a decision that a patient is a good candidate for immunotherapy. So you're a patient and you've been determined to be a candidate for immunotherapy, there are some companion diagnostics that are out there, pretty simple. And if you're a candidate, then you would undergo immunotherapy. And basically, right now, there really isn't any way to monitor the patient's response to immunotherapy.

As immunotherapy has been expanding and used, the doctors and researchers are starting to discover that there are side effects. One of the things that we're working on with technology from UCSF is by monitoring with a blood sample from those patients. For example, before treatment and then at time periods immediately after, within several months after, we're looking at how the T Cells are responding, in terms of their genetic repertoire. Basically, how are the T Cells responding?

So, you can have no expansion of the T Cells. They look the same as they did before. You can have an expansion of the T Cells, an increase in number. And if it's an increase in number, there can be an increase in diversity or an increase in the number of clones. If it's an increase in the number of clones, the immunotherapy is essentially doing what it's supposed to do because you're generating T Cells specifically for the treatment of the cancer cells.

And the other possibility is that they could be expanding in what they call a, "diversified mode," which means you've triggered your immune system to respond, but it's responding non-specifically and that can create side effects. That's the thing we're monitoring is those three different conditions, basically: No response, a good response, and a bad response. That does affect treatment, of course.

Sean Givens:
I'd like to expand on that a little. When you're looking at what Allen is referring the clonality, which is essentially the precision of the T Cell response. When you see clonality, it typically executes a precise response, so if you start to develop off the platform of me getting more fidelity is one of the things we're looking at with these types of cells. Eventually, what we would like to be able to identify is: which T Cell population is actively responding to the immunotherapy so that we can help doctors and drug companies develop better, targeted immunotherapy.

Rory McCann:
Do you have anything else you'd like to add on this topic?

Allen Northrup:
In a broader sense, we're focused on monitoring the patient's physiological, immunological response to drug treatment, to therapy, and at a very high level. And that's not a very typical thing. We also work with a transplant doctor at Stanford. It's kind of an analogous situation where they will match tissues from donors to recipients as much as possible in advance by looking at their genetic make-up or their histocompatibility complex, but that's the best they can do. And then they do the transplant and then for a period of several months, the doctors really don't know how the body of the recipient, or the immunological system of the recipient, is responding.

So they bombard the patient with immunosuppressive drugs to keep the immune system from overreacting, or reacting to the foreign tissue. And they'll do that and then they'll do typical blood tests, typical clinical blood tests, and look for symptoms of rejection and then, if there looks like an indicator of some kind of physiological response from a typical clinical test, then they may go in and do a biopsy. And that becomes highly invasive.

The point is that basically, at least in those two cases, and probably many others, there really isn't a way to monitor the effect of therapy. We focused on immunotherapy because it's, first of all, very expensive therapy, as is transplantation of organs. But I would imagine, in the future, there would be point-of-care technology that would allow physicians and patients to monitor their own response to a variety of therapies.

I think that's a big, big opportunity for, "point-of-care devices," to monitor how patients are responding to therapies directly. In our case, we're monitoring the T Cells, which are the cells that respond to either an immunotherapy or to a transplant. In a broad sense, there's a real need for, "point-of-care devices," for monitoring therapy, the response of a patient to therapy.

I think point-of-care devices in the infectious disease world, essentially monitors in the blood level of the virus. Or maybe the immunological, the response of the immune system by looking at antibodies to a disease. I think that there is a huge need for point-of-care, point-of-treatment monitoring of therapies in patients.

Rory McCann:
Thank you. That's really interesting. It's pretty clear that point-of-care devices do have a future in infectious diseases and oncology. Thank you very much for flushing out and describing how it could be useful in immunotherapy, and where MIODx is going with it. I appreciate you taking the time to talk to us and I'm looking forward to your talk in Washington, D.C.

That was Allen Northrup, CEO of MIODx, and Sean Givens, COO of MIODx. Dr. Northrup will be speaking in the Enabling Point-of-Care Diagnostics track on August 15th in Washington, D.C., in the Next Generation Diagnostics Summit.

I'm Rory McCann. Thank you for listening.