
Notable Labs (YC W15): Personalized Medical Testing for Brain Cancer Patients - katm
http://techcrunch.com/2015/03/10/yc-backed-notable-labs-provides-personalized-medical-testing-for-brain-cancer-patients
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M_NotableLabs
Hi I'm Matt, one of the founders of Notable Labs. Here are more specifics on
our process:

Step 1: The patient undergoes surgery to remove their brain tumor, which is
sent to our lab where the cells are grown. Step 2: We use lab robotics to
apply thousands of combinations of FDA-approved drugs directly to the cancer
cells. Step 3: Notable Labs analyzes the test results and provides them to the
patient’s doctor, who can prescribe the drugs immediately without a clinical
trial. Step 4: Each treatment result allows us to algorithmically improve the
drug selection process for future patients.

Glad to answer any questions!

~~~
refurb
What is in this set of "thousands of FDA-approved drugs"? Just oncolytics? Or
more broad than that?

A few potential challenges:

1\. Just because a combination of drugs works on a cell culture, doesn't mean
it works in a human body; there are just so many more variables in vivo

2\. You're just testing for efficacy, not safety; what happens if one drug
potentiates the other and results in the patients getting very sick or dying?
Likely a small risk since most drugs list contraindications, but a few
problems might slip through

3\. How are you planning on dealing with reimbursement? Insurance companies
(Medicare/Medicaid included), won't pay for cancer drugs unless there is proof
that they work; that proof is usually a clinical trial or at least some
published data supporting it; there may be some pushback if insurance
companies either don't believe your data or just don't know how to interpret
it

Not trying to shit on your company, just curious if you've looked at these
issues yet. It's definitely a cool idea!

~~~
vobios
> You're just testing for efficacy, not safety

The drugs being tested are all already approved, so safety would not be really
a concern.

> Insurance companies (Medicare/Medicaid included), won't pay for cancer drugs
> unless there is proof

After some time to collect the data, you could fairly easily compare outcomes
of patients who undergo this test versus those who do not.

~~~
ejstronge
> The drugs being tested are all already approved, so safety would not be
> really a concern

I think the problem is that Notable Labs would be testing _combinations_ of
FDA-approved drugs:

    
    
      Step 2: We use lab robotics to apply thousands of combinations of FDA-approved drugs...
    

> After some time to collect the data, you could fairly easily compare
> outcomes of patients who undergo this test versus those who do not

Until then, this won't be broadly available. I do think such a comparison
would be interesting.

I guess you'd need to compare the expected benefit of using the Notable Labs-
suggested combination to using the standard of care. You'd need to have cells
from patients who did not use the Notable Labs-suggestion. This requirement
could turn an 'easy comparison' into a lengthy clinical trial.

~~~
M_NotableLabs
Thanks for your questions!

Yes we'll be testing combinations, as this brain cancer has not responded
historically to single agent therapy for decades.

With combinations of existing drugs it is possible to affect multiple driver
pathways in the tumor at once. Similar to the dramatic improvement of AIDS
therapy and infectious disease treatment with cocktails, tumors could respond
much differently to combinations instead of a "one at a time approach" that
has resulted in very small survival gains in this disease.

Please see this paper for more detail on the scientific approach to mutli-
agent combinations to target many pathways at once.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226667/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226667/)

Patients have been taking the CUSP-9 protocol without any serious adverse
affects on a compassionate use basis. This has now moved into a prospective
clinical trial for recurrent glioblastoma patients in Germany
[http://www.anticancerfund.org/projects/cusp9-a-combination-o...](http://www.anticancerfund.org/projects/cusp9-a-combination-
of-9-repurposed-drugs-for-the-treatment-of-glioblastoma)

Personalized medicine services like this could allow clinicians to move beyond
traditional randomized controlled trials. Commercial services such as
Foundation Medicine provide test results to oncologists who then use their
discretion to treat the patient outside of a clinical trial with scientific
rationale based on the test itself as opposed to a standard of care.

In a severe disease like Glioblastoma where average survival is 15 months, if
the majority of patients using a system like Notable Labs live substantially
longer, is a control arm necessary? The HAART cocktail for AIDS treatment
never went through a phase 3 trial, so there is precedent in high need
diseases.

I also would like provide a link to a recent documentary that highlights the
combination approach in brain cancer by telling the story of a 20 year
survivor of Glioblastoma, Ben Williams. Other patients who safely used
combinations of existing drugs are featured as well.
[http://www.survivingterminalcancer.com/](http://www.survivingterminalcancer.com/)

~~~
newman8r
I have not looked into your company - but what's your opinion on crowdsourcing
some of this? Some of these devices are remarkably similar to 3d printers and
not so tough for the hobbyist to assemble.

If you do that then the community can start banding together to test
formulations and then send the promising ones to you for further analysis.

Good luck. I love the idea and I personally have a few ideas of my own in the
field that I want to start in 2016/2017

Edit * of course everyday people won't necessarily have access to approved
therapies - but perhaps they can test other compounds and environmental
conditions (or get the FDA to somehow approve tiny little test pellets for
different drugs that would be legal for hobbyists to use in testing)

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rgejman
No doubt GBM patients are in major need of novel therapeutic options. My major
concern with this kind of a project is that the drugs may end up killing
patients faster than the tumor will. For instance, some drugs are known to
inhibit tumor growth AND immune cell signaling because they target shared
pathways. The tumor can out-grow this interference; the immune system cannot.
You will not know if your interventions are helping or hurting the people you
are treating until you do a properly controlled study.

Second: in my experience, one of the major problems with screens for
synergistic (or additive) therapies is multiple testing. If you test 100
compounds (10,000 combinations), a large number of combinations will appear to
work by chance. Do you have a secondary screening approach to reduce false
positives?

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dankohn1
Matt, I'm very sorry for the loss of your father. Notable Labs is an amazing
idea and I wish you great success.

~~~
M_NotableLabs
Thanks so much, I consider myself fortunate to have the opportunity to work on
a problem that is so personal. It is empowering to go from a passive
participant in his care to actively helping others with the disease.

