MoIDX Open Public Meeting - October 22, 2019 - JE Part A

Initial portion of audio file for the October 22 MolDx open meeting in the San Diego Hilton Sapphire 400 Room was not transcribable due to ambient noise. In that brief several minutes Medical Director Dr. Gary Oakes opened the meeting, introduced himself as the event host/moderator, provided safety and logistic information indicating location of exits and restrooms, listed the thirteen topics that had been posted as open for responses from the public, indicating that responses and interest in presenting material and opinion had been received on only three of the thirteen topics. Transcripts of those three presentations follow. The third speaker did not speak clearly, distinctly, or loudly enough to be heard well in the room or on the audio file. Much of his message could not be understood or transcribed.

DR. GARY OAKES

This may be a shorter meeting than I thought. We're going to move along. Okay, give me Dr. Cao or Kao or how do you pronounce it?

Cao is good.

Cao good, the Chief Operating Officer from Althea Diagnostics. Here you go sir.

DR. FENG CAO, CHIEF OPERATING OFFICER - ALTHEADX, INC.

Uh thank you Dr. Oakes for the opportunity to uh discuss the PGx test from LCDX, which is a local biotech in town. Next slide please.

The computer keeps locking.

Oh no worries, it happens. So again, my name is Feng, I am the Chief Operating Officer of AltheaDX. I am here today to talk about the PGx assay from our company, it's called NeurolDgenetix, and I'd like to give a overview of the current Draft LCD that covers our test and discuss the current standard of care in depression as well as how our test could address the unmet medical needs in the area of mental health including uh depression. And last but not least I wanted to uh propose a few uh recommended changes to the Draft LCD. Next slide please?

So, we'd like to thank Palmetto and MolDX as well as Noridian for uh your recognition of the clinical utility of our test which has been demonstrated by one of the largest PGx randomized control trial. And currently the Draft LCD provides limited coverage of our test when ordered by psychiatrists for the treatment of psychiatric illness. Next slide Please?

So why depression? Number one, depression actually affects a lot of people globally. Did you know that depression actually is the leading cause of disability? And then in the U.S. it affects almost 7% of the adult population. It is actually an even bigger problem in the Medicare beneficiary population where the prevalence rate is up to 18%. And number two, depression is actually very hard to treat so even though there is over 30, 30 antidepressants that the FDA approved only up to 30% of patients are in remission after one year of treatment. So, depression, it affects a lot of people and it's very hard to uh treat depression as it represents a very high cost to our healthcare system. So, what can we do to uh help the patients? How do we improve their uh outcome? Next slide please? The one before? Yes, thank you.

So, in order to uh demonstrate the uh clinical utility of PGx what we did is we carried out one of the largest PGx psychiatric RCTs. RCT stands for randomized control trial. So, it was published in 2018 in the Journal of Psychiatric Research, and as I mentioned, over 600 patients were enrolled in the study, and the study was carried across 20 different clinical sites. These include psychiatry, internal medicine, OBGYN and family medicine. And the uh outcome was polled over 12 weeks by the HAM-D scores. Next slide please? No, the one before?

This slide shows the data from our Bradley Trial, uh the uh patient outcomes when measured by two different uh uh rates. On the left shown as the response rate, on the right shown as the remission rate. As shown here on the top of the graph is the uh intermediate and severe depressed populations, both the response rate and remission rate were statistically improved and compared to the control arm. And then on the bottom half of the graphic this shows even more importantly in the severe depressed population we see almost a doubling of the response rate and a tripling of the uh remission rate. And we feel like these are truly meaningful clinical improvements that could benefit our patients. Next slide please?

So not only do we show the strong clinical data our workflow is also very simple, straightforward and user-friendly. So essentially the test was ordered by the physicians who uh collect a cheek swab from the patient and the samples were sent to us for internal processing. And then in hand what were delivered to the, back to the doctors is a actionable report that puts all the antidepressants in either green or yellow bands. So green means use as directed, yellow means use with caution. Next slide please?

So, our RCT has been very well received by (could not transcribe) as well as industry groups. Next slide please?

So right now, there is a shortage of psychiatrists in the nation where only 2% of the people's registered physicians indicate psychiatry as their primary specialty and then as shown by those maps 96% of the U.S. counties actually have unmet needs of psychiatrists. Consequently nearly 80% of all antidepressants are actually prescribed by non-psychiatrists, 80%. Now to address this real-world issue when we designed the RCT in the clinical trial, what we have done is we wanted to address both psychiatric as well as non-psychiatric populations. So, in order to do that, of the 20 sites that we enrolled patients with, over half of them are actually non-psych clinics. And then the 600 patients uh over 1/3 of them are coming from non-psych clinics. Our RCT demonstrates the clinical utility in both psychiatric and non-psychiatric settings. Next slide please?

So, as it stands right now in the Draft LCD as I mentioned, it covers psychiatrists only. Based on the strong data that we have, we'd like to uh advocate the coverage to include both psych and non-psychs. Next slide please?

In addition, in the Summary Section, in the Summary of Evidence Section of the Draft LCD, there are a couple of uh key variables, data points, that are missing; for example, the response rate, the remission rate as well as the p-values. I feel like that these are very detailed and positive clinical evidence that should be included in the final LCD. Next slide please?

So in summary, we want to again thank Noridian and Palmetto MolDX for your recognition of the clinical utility of our test, and we would like to propose that the final LCD include non-psychs as well as to include additional clinical evidence which have been published through the uh Bradley trial. And we look forward to working with the MACs toward the common goal of improving the mental health of all Medicare beneficiaries. Thank you.

DR. GARY OAKES

I understand Dr. Dylan Miller is on the phone. So, Dr. Miller?

DR. DYLAN MILLER

Hi, can you hear me now?

DR. GARY OAKES

Try one more time, sir.

DR. DYLAN MILLER

Hello?

DR. GARY OAKES

We are good here, go ahead, sir. Dr. Miller, you can go ahead.

DR. DYLAN MILLER

How about now?

DR. GARY OAKES

Much better.

DR. DYLAN MILLER

Hi, can you hear me?

DR. GARY OAKES

Dylan, can you hear me?

DR. DYLAN MILLER

Hello?

DR. GARY OAKES

He's not hearing me.

He's coming through.

 DR. DYLAN MILLER

I can hear you speaking in the room. I'm sorry, can you hear me?

DR. GARY OAKES

Yeah, yes sir, go ahead with your presentation please.

DR. DYLAN MILLER

Okay, no, it's not a presentation, I'll be brief. And I'm actually speaking to the molecular microscope test uh from Kashi Labs being used in heart transplant biopsies. I think you mentioned another one of the MolDx tests but I'm not speaking to that one.

DR. GARY OAKES

Very well. Go ahead, sir.

DR. DYLAN MILLER

So I am a pathologist in Salt Lake City and I am representing um pathology and laboratory medicine; and it's not very often that we have a transplant related test come up, and that is my specialty so I felt like I needed to contribute something here. And I'm actually probably barely speaking against this um coverage determination. It's my feeling that um this molecular microscope test is not really ready for prime time in heart transplant biopsies. It was developed by the Edmonton Group in kidney transplant biopsies and studied fairly extensively there; but I think a lot of flawed assumptions were made when it was applied to heart transplant, specifically they, they only used the information markets in kidney and thereby excluded the potential to find uh informative markers in the heart that, that weren't potentially informative in the kidney. So, I think they kind of limited themselves there. Also, all of their validation work has come from really one center or two or three cooperating centers um and a very limited number of pathologists, just two or three pathologists. If you look through their data, they have about 100 positive biopsies um in a couple of groups. And while I know that you have to start somewhere and I admire them for the efforts that they've put in, I don't think you can generalize from that small number in a sufficiently powered way to the tens of thousands of biopsies that are done around the world every month and would like to see more clinical validation before this goes into routine practice. Um, also the technology that they use is really starting to fall by the wayside. They are using chip-based RNA gene expression and I think that there are newer assays being developed using the NanoString and NextGen sequencing technologies that will probably improve on this test and would rather have coverage for those tests when they uh come about. So, I've submitted all of my comments in writing and this is just a, a brief summary but appreciate the chance to um let my thoughts be known. Thank you.

DR. GARY OAKES

Thank you Dr. Miller and thank you for going ahead and submitting them in writing and we will make sure that you have a response to that, appreciate your time. All right, Elai Davicioni, is that right? (Could Not transcribe) you need to correct me then. (Could Not transcribe.)

ELAI DAVICIONI, CHIEF SCHEINTIFIC OFFICER - DECIPHER BIOSCIENCES, INC.

Thanks. Thanks again for having us.

Yes, so good morning. My name is Elai Davicioni, I'm one of the founders of (not understandable) Decipher Biosciences. I'm here to tell you a little bit about the Decipher Prostate Cancer Classifier (not understandable) and it's Draft DL38339.

Just briefly we are also located in San Diego and serving Vancouver, Canada. What differentiates us is the approach that we took in prostate cancer, we took a (not understandable) approach where we were collecting all the data that we need and submitting improvements to (not understandable) and offering signatures that our physicians and (not understandable) need and want. And then we have probably the world's largest collection of data in prostate cancer and so we I think are approaching this as we hope to share this data with treatment in order to accelerate the pace of innovation in (not understandable). So prostate cancer is especially important to Medicare beneficiaries in the Medicaid/Medicare system and health systems all. The one thing to know about prostate cancer it's a little different than solid tumors, it has a highly variable range of optimization diagnoses. There is low rates in these where you can live with a tumor inside your body for 20 or 30 years and probably die of something else. Very effective (not understandable) like pancreatic cancer where patients don't have very much time and another aspect of (not understandable) from a medication standpoint but also from a physician standpoint there is many, many, really a plethora of treatment options. Although the guidelines are quite liberal in what medications (not understandable) in the correct way to treat a patient. The important thing for us as a society is to emphasize that most hospitals treating prostate cancer the potential cost and other (not understandable) costs are actually from treating metastatic disease. And so this is just like we all know that managing cancer in the first place is the best way to save our society from (not understandable) for the future population, so preventing metastatic cancer is probably the best way really to save costs because people will inevitably (not understandable) prostate cancer. So, 80% to 90% (not understandable) metastatic disease, and 90% of patients with metastatic disease are actually Medicare age determining 80% of the cost of prostate cancer (not understandable). And again, if you live longer (not understandable).

So prostate cancer is quite different than for example lung cancer, (not understandable) and colorectal cancer as well. Lung cancer for example (not understandable) indications that actually dictate who actually ends up getting it. And that's actually (not understandable) for treating the cancer. Prostate cancer is different. It (not understandable) metastatic potential, (not understandable) the risk of the actual tumor from spreading, we basically can cure localized prostate cancer and then metastatic prostate cancer you cannot cure, but you can (not understandable) and keep people from dying from prostate cancer. So how do we make decisions on prostate cancer? Currently (not understandable) some of the risk factors. These are our actual (not understandable) biological validation for (not understandable) tumor grade and stage of the tumor, how big it is. This is also (not understandable)

The problem with the clinical data prospectus is that various (not understandable) 80% of patients (not understandable) Genomics has recently grown in terms of (not understandable). About 10 years ago our partner (not understandable) prostate cancer (not understandable) Cyclosporin (not understandable) a pretty large cohort and then (not understandable) against other men. (not understandable) These are statistical ways of furthering (not understandable). So, one of the metrics (not understandable) these are statistical ways of furthering (not understandable)

Just blind.

(not understandable) Basically what this shows is that of (not understandable) and really what the diagrams tell us is that the risk is higher (not understandable) So it's a little bit complicated I think, here you've got a single (not understandable) in prostate cancer but more to test future (not understandable) from (not understandable) requested since we are allowed the (not understandable) on the left is the diagnosis and on the right there is (not understandable) and then there is the interpretation (not understandable), and the interpretation based on the studies optimization (not understandable) As I mentioned earlier there are three publications and also a huge (not understandable) We are committed to (not understandable) Because this is a very complex disease (not understandable) who to treat, when to treat them and how to treat them (not understandable) And so we take very careful (not understandable) of my comments and go from there. Thank you.

DR. GARY OAKES

Okay, that ends our meeting for today. (Could Not transcribe) and thanks for the previous presentations. And good afternoon.