48 – Breaking Down Barriers in Rare Disease Research: Advantages and Obstacles in Data Sharing

Webinar Overview

This webinar includes three panelists, Deven McGraw, Charlene Son Rigby, and Dr. Jacob Donoghue, who dive into the importance of data sharing in rare disease research. Deven McGraw is the co-founder of Ciitizen, a company which works to put all of a patient’s health data into the hands of rare disease patients and families. Charlene Son Rigby is the CEO of Rare-X, a platform to gather, structure, and share patient-level data to support research and therapy development for rare disease patients. Finally, Dr. Jacob Donoghue is the CEO and co-founder of Beacon Biosignals, a platform for integrating brain data to support the development of novel precision medicines for neurologic and psychiatric disease. In this webinar, the panelists discuss the key barriers to rare disease research and what their companies are doing to remove them. These barriers include a lack of data for rare disorders, having trouble getting scientists interested in studying a rare disorder, and data access being competitive amongst scientists. However, their companies are combating these barriers by making advancements in data sharing – these advancements majorly shrink the time it takes for drug development or natural history studies. Throughout the webinar, all three panelists give incredible insights about rare disease research and data access which will shape the way data is shared in the future.

THIS IS A TRANSCRIPT ONLY:

0:04hello my name is Mike Graglia i am the founder  managing director of the SynGAP Research Fund a  

0:09rare disease group that I created for my son  who suffers from a rare neurological disease   called SYNGAP1 i’m excited to be with you today  and to moderate this incredible panel because  

0:19i know this is a topic that is very important i  get phone calls often from other people creating  

0:26rare disease groups struggling with this precise  issue so this is a this is a timely and relevant  

0:32panel that i’m excited to have recorded because  i will be referring many people to hear these   incredible experts let me introduce  them to you now deven mcgraw jd llm  

0:43three graduate degrees is the co-founder of  Ciitizen which was acquired by Invitae last year   and she is now the lead of data stewardship and  data sharing for the Ciitizen platform at invite  

0:53previously deven directed the u.s health privacy  and security department as the deputy director  

1:01health information privacy at HHS office for civil  rights she was the acting chief privacy officer in  

1:06the office national coordinator for health i.t  Deven is widely recognized for her expertise   in health privacy she directed the health privacy  project at the center for democracy and technology  

1:14for six years led the privacy and security policy  for the high-tech committee she was also the chief  

1:21operating officer at the national partnership for  women and families she advised health industry   clients on HIPAA compliance and data governance  while a partner at manat phelps and phillips  

1:30Devin graduated magna [ __ ] laude from georgetown  and from her has her mph from jhu thank you so  

1:37much for being with us demon Charlene son riggsby  MBA is the chief executive officer of RARE-X she  

1:44has spent her career building organizations at the  intersection of data technology and life sciences  

1:49Charlene was previously chief business officer  at fabric genomics and held executive roles as   enterprise software and genomics  companies including oracle and doubletwist  

1:57she started her career in neuroscience research  at Roche when Charlene’s daughter was diagnosed  

2:02with a rare genetic disease she co-founded the  STXBP1 foundation she is committed to finding  

2:08a cure for her daughter’s disorder Charlene’s  unplanned connection between her personal life   and profession has helped push forward the search  for a cure for her daughter and kids like her  

2:18and given her work deeper meaning she held  an MBA in human biology from Stanford and   a ba in human biology from Stanford and  an MBA from the haas school at berkeley  

2:29rounding out this star-studded panel jacob  donahue MD PhD is the CEO and co-founder  

2:35of Beacon biosignals a company that translates  scientific innovation into clinical interventions  

2:40he completed his MD from Harvard medical school  and his PhD in neuroscience from MIT leading  

2:46research into the effects of neuroactive compounds  on brain network activity his published work spent  

2:52epilepsy cognition and machine learning methods  for quantifying pharmacological effects on neural  

2:58activity so i think step one is to hear from  these speakers they all spend their time running  What is Citizen

3:08remarkable organizations and Deven if i could  start with you could you please describe what  

3:15your company the company you you now work with him  now you’re part of invitae but the company helped  

3:20create Ciitizen could you describe how it relates  to this issue of data serving data sharing pardon  

3:26me for rare disease research no sure happy to mike  thanks for having me so citizen is a platform that  

3:34helps patients or family members acting on their  behalf to gather all their health information  

3:41all of it from all the places where they’ve  been seen and to put it under their control  

3:47we were founded by anil sethi who lost his  little sister to metastatic breast cancer  

3:54and so we started in cancer but we we  added rare neurological diseases in part  

4:01through the advocacy of one of our key staff  members whose child who has a child with FOXG1  

4:08syndrome so we’ve been in the rare neurological  disease space almost since our inception and  

4:16and really you know the idea here is to put the  power of data back into the hands of the people  

4:22who are most likely to use it and to use it for  good and that’s again the patients and family   members acting on their behalf that’s it’s it’s  kind of exciting we were you know being acquired  

4:34by Invitae brings us into an organization that’s  like-minded with respect to being dedicated to  

4:39healthcare their genetic testing company for  folks who don’t know them and so it’s really  

4:45i hope will give us a lot more resources to  scale versus you know trying to do all of  

4:52this as a small company but again we really think  that the answer to some of these data obstacles  

4:57is put the data in the hands of patients and  their families and we’ll and see what happens

5:04great thank you for that charlene  can you tell us about rarex  What is RareX

5:11thanks mike so rare x is a health tech non-profit  and we’re also a patient advocacy organization  

5:19we really started with the perspective of what  do patients need to accelerate therapies and so  

5:26patients really are at the center of how we’ve  really developed our strategy and our approach  

5:32and so what are we doing we’ve developed  a platform to gather structure and share  

5:39patient-level data to support the acceleration  of research and therapy development for rare  

5:44disease patients and this is really across  the thousands of rare diseases and the growing  

5:50number of rare diseases and i kind of specific  to this discussion i wanted to highlight that a  

6:01core principle of our approach is eliminating data  silos so this includes upfront with our innovative  

6:10consent process and also through enabling  integration and federation with other data sources

6:19very nice you packed a lot in there i look  forward to unpacking that as we go through this  What is Beacon Biosignal

6:25jake can you tell us about beacon biosignals   sure thanks mike yeah so beacon biosignals is  a company building a machine learning platform  

6:35for interrogating brain data at scale and to  enable the development of novel precision measure  

6:40medicines for neurologic and psychiatric disease  really you know inspiration for for this uh  

6:48this workers seeing the sort of developments  that were occurring in companies working in  

6:53digital pathology and thinking about how you  know novel precision measurements can enable  

6:59precision therapies especially in oncology  and seeing firsthand taking care of patients  

7:07just the limitations in the the way that data  is collected and the inability to interpret the  

7:12full depth and breadth of the brain data in this  case EEG that there was an enormous opportunity  

7:18to bring modern machine learning tools to  understand this this critical data modality  

7:23to enable these types of therapies to to be driven  forward for patients with neurological psychiatric  

7:29and sleep disorders nice i remember when i  started syngap research fund somebody told me  

7:36if you want to know what’s happening in what’s  going to happen in rare neuroscience tomorrow  

7:41look at what’s happening in cancer today because  cancer’s so much bigger and so much better funded  

7:46and you know it’s exactly what you just said and  i think as devon alluded to citizen was started   for cancer and then thank goodness they rolled  into neurology so it’s it’s interesting to see  

7:57that you’re you’re validating that all right so  let’s let’s jump into our first question i think  

8:04before we talk about breaking down the barriers  it would be useful to name them right so what   do you see as the key barriers to rare disease  research and why is it necessary to remove them  Barriers in Rare Disease Research

8:15jake let’s let’s stay with you for a  second can you just talk you almost   started to answer that already so can you just  talk a little bit about the barriers that you see  

8:23and and and uh and i don’t know if you want  to talk more about beacon or just the barriers  

8:30yeah in general i think so the key for us we’re  you know data-driven company applying tools to  

8:37better understand you know eeg you know brain  data about in the patients with rare diseases  

8:43rare genetic neurological diseases for beacon in  particular the key to allowing these tools to be  

8:50useful and provide actionable information is you  actually have to have at least a reasonable amount  

8:56of data and in rare disease where the number  of you know eeg data may be hard to obtain  

9:03for a number of reasons that limitation makes it  really hard to actually identify patterns that  

9:09could be critically useful to understanding  which patients are going to benefit the most  

9:15and then in early studies you know in phase one  trials if a new treatment is actually having an   effect so that limitation uh in the inability  to acquire the data both at the site in the  

9:26hospital settings or in community hospitals  where there’s a limitation of eeg hardware   and the fact that eeg data is often not part of  the standard data types that can be requested  

9:38from the hospitals if a patient asks for  EEG their EEG data they often will be given  

9:44a report of what was read on that data so all of  that really important information about you know  

9:51that child or that patient is really buried not  only within the data but within this you know  

9:56hospital system so i think that without access to  these individual you know files no one is able to  

10:02really interrogate sometimes the most important  defining characteristics of disease got it so  Barriers to Rare Disease Research

10:10low low n and then certain data types specifically  EEG for neurology incredibly hard to move around  

10:18charlene let me move to you what do you what do  you see is the barriers to rare disease research  

10:23yeah i think i can just really build on what jacob  and you just described so you know giving a little  

10:31bit of my personal perspective i also have a  child as mike mentioned in my intro who has a rare  

10:40neurodevelopmental disorder and she’s eight and  she was diagnosed in 2016 so almost six years  

10:47ago and we still have a long way to go before we  get to a cure or even precision therapies with  

10:54any wide access and there’s such painful urgency  you know as parents and as advocates to you get  

11:03to something that’s truly going to change the  future for our kids and yet getting to this data  

11:10that’s going to inform these therapies  is difficult so you know mike you said   small n i mean the n is small for any individual  disorder and you know it’s even very very small  

11:21for certain disorders and you know patients in  these small in rare disease often have difficulty  

11:29getting researchers interested in putting together  a study to actually understand that disease  

11:37and when they are successful those studies are you  know they can find challenges in providing input  

11:44into the study and then getting access to the data  on the back end and as jacob mentioned oftentimes  

11:51you know health care systems and studies they’re  really generating silos of data and it’s very  

11:56difficult to bring those data sets together and i  think this is you know true broadly and you know  

12:01the EEG example is you know just a a sore example  of how you know this ends up becoming you know  

12:10kind of a magnified problem and you know i think  that this is due to a host of issues including  

12:15data governance and misalignment of incentives  and it’s very frustrating because especially in  

12:23rare disease when we have this challenge of small  numbers of patients we really need to maximize  

12:29the utility of the data that we’ve gathered  from these patient populations and you know  

12:34it’s really data that these patients have  contributed you know to hopefully accelerate  

12:40the process toward therapies you know i  really feel that this is a moral imperative

12:49you pack so much into your answers so there’s  data governance issues there are data silos  Data Governance Issues

12:55and then misaligned incentives and i just  want to make sure i heard this correctly   between researchers who are maybe doing it  early on an industry who need to use that  

13:03that data sometimes to actually get a real therapy  through trials right did i am i putting words in  

13:09your mouth or is that right yeah yes i think  that’s right and then you know i’ll add in   also the patients where you know it really  needs to be you know having the patience  

13:21around the table as true research partners and  you know that’s uh you know unfortunately not the  

13:28norm today right which is a great setup for deven  but i also want to underscore one other thing you  Barriers to Research

13:33said which was moral imperative so this isn’t an  academic exercise right there are sick children  

13:39and what stands between these sick children  and therapies that exist in labs right now  

13:44is the data and the data being used and shared  between the players to make that happen so I   love i’m going to bar i’m going to use that term  liberally and occasionally give you credit we have  

13:54a moral imperative to do this work devin what do  you see as the barriers to rare disease research  

14:02well i you know i agree with my co-panelists to me  i think there’s two that sort of rise to the top  

14:10one would be proprietary business interests right  or or you know sort of lack of motivation to share  

14:19or motivation not to share right with data is  considered to be a competitive asset then you  

14:24don’t want to share it with anybody similarly the  the data governance rules are truly a challenge  

14:30and this it that challenge gets particularly acute  for rare because of the need to gather data across  

14:37many jurisdictions in order to have a a meaningful  data set if you’re just dealing with u.s patients  

14:44and using the HIPAA right of access for example  you’re you’re likely to to not have a sufficient  

14:50amount of data to to power studies you need to be  able to get data from patients who live in other  

14:56countries and that means that you know they’ve got  their you know data governance laws their privacy  

15:02laws there are research laws that apply when  you’re collecting data from patients overseas so  

15:08that that does get challenging and i again i think  that challenge becomes particularly acute and rare  

15:13it’s interesting i i and i don’t think about  removing these obstacles because some of them  

15:19you’re not going to remove right you’re not going  to you’re not going to you know sort of not have   competitive instincts of companies of researchers  you’re not gonna not have data governance laws  

15:29that are gonna vary i consider it as doing an end  run around them like what what are some of the  

15:35the holes and the crevices that you can kind of  crawl through and and figure this out and for and  

15:41for us with the citizen platform it’s about you  know every privacy law gives patients the right  

15:47to a copy of their data and every privacy law  allows patients and and or families acting on  

15:55their behalf to direct that data to where it  needs to go and when you pull on that thread  

16:00you’ve got the possibility i think of creating  that you know moving with some more urgency  

16:06rather than waiting for the wheels to turn  very slowly in all of these traditional models  

16:12and hoping that that somebody agrees with you  that it’s a moral imperative for us to act fast

16:21yes yes thousand times yes so it’s great so  proprietary business interests are a reality  HIPAA and Right of Access

16:29and we need to find that’s probably a whole  other discussion how to navigate that and then  

16:36the different jurisdictions  i i take your point i mean   i the group i lead SynGAP research fund does  work with citizen i’m very proud of that and and  

16:47consider myself very lucky and have lived through  exactly what you’ve said right we’ve enrolled more  

16:52than half of our us population but getting people  from certain other countries is tricky and that’s  

16:58that’s that’s difficult deven in your introduction  which was so dense i might have mangled parts  

17:05of it but can you just talk a little bit about  HIPAA and patient right of access because I just  

17:11i do think that that is at the heart of some of  the genius of what you do at citizen and as you  

17:17just alluded to one of the ways that we’re going  to do an end run around some of these challenges  

17:22yeah so i the under hipaa which  is the the hipaa regulations are  

17:29privacy laws that apply to most  of them significant holders of   clinical data clinical and claims data health  healthcare facilities doctors hospitals labs

17:44and uh and also to the companies that work  with them health plans as well the there’s  

17:50no mandate to share data under hipaa except for  two one is with the government when you’re being  

17:56investigated i used that a lot when i worked  for the government but but the most important   one for this conversation is the right of the  patient to have access to all of the data that  

18:06is generated about them and in the case of  of children that right belongs to a parent  

18:12to be able to collect all of the data and it’s  so much broader than people realize it’s it’s all  

18:18data in medical records and any data that exists  in another system that’s used to make decisions  

18:24about individuals so so so jake mentioned the  difficulty of getting eeg tracings they’re  

18:30part of the designated record set which is what  patients have a right to access the problem is   that a lot of times organizations didn’t realize  that that was part of their right of access or  

18:42they tried to discourage patients by saying we  don’t have a way to get these to you these files   are really large so so you know you have to be you  have to be able to kind of break through some of  

18:51that clue genius and i’m convinced that this is  probably why i got hired to help start citizen in  

18:57the first place is because i you know i i did have  the advantage of knowing those regs like the back   of my hand having worked in that organization  and being able to say to healthcare systems  

19:07that turned us down or made things hard for us to  get records for you nope that’s not you can’t do  

19:12that and here’s the piece of guidance that says  that you can’t and you know slowly but surely  

19:18kind of amassing a track record of being able to  cut through some of that noise we we have not been  

19:25uh we we don’t have that kind of machinery  set up to do that in other countries yet and  

19:30so there’s a little too much dependency for us  on patients sourcing their own records but we  

19:36do hope that that will change because again  the law the law is on the patient side here  

19:41yeah but but it still doesn’t mean you still  don’t have to take a pickaxe to some of that   you know some of that rock that stands in  your way which is it’s unfortunate which  Moral Imperative

19:52and if we have time we might come back to the the  ways in which you have thrown a pickaxe at some   problems and i think made the whole us healthcare  system better for it but i wanna i wanna so we’ve  

20:02shifted from defining the barriers to talking  about how important they are Charlene said moral   imperative Devin devin reminded us that if the  patients have right to this data and what i really  

20:12like that you said devin that i want to underline  is doesn’t matter which legal system you’re in  

20:17most of these rules and regs do have that premise  the patient has an access to their data and those   first principles are great for people like me  who aren’t lawyers and when someone’s like well  

20:26in Germany blah blah blah or where then pick a  country blah blah blah i can just be like look   do they or do they not have a right to their own  data and if the answer is yes then let’s let’s  

20:34figure out how to execute that i think that’s a  important point but then before we before we go   to that next slide I just want to come back to  jake and and talk about one of the things one  

20:44of the reasons i invited you here jake is is  because what your company is doing is i think

20:52making possible through technology um the creation  of something that is critical which is endpoints  

21:00out of data right and and i think but you can’t  do that if you can’t get your hands on the data so  

21:07can you just double click on like why this is so  important that we figure out a way i think devin’s  

21:15pickaxe is a beautiful answer right so here’s jake  with beacon biosignals here’s a bunch of parents  

21:20who have kids who’ve had countless eegs and to  be clear just to editorialize for a hot minute  

21:26getting a kid with a rare neurological disease  an eeg is a non-trivial experience you go to  

21:31the hospital you put them in front of screens  clinicians come in things are taped to their   heads bandages are put on their heads they either  wear a backpack or you’re walking around with a  

21:39video camera and then for 4 6 8 28 48 72 hours  this poor child has stuff stuck to their head  

21:46while this precious data is gathered and you know  blood sweat and tears all happen in this process  

21:53blood hopefully not but occasionally and  then it sits on a shelf and a computer   and then jake meets family and says i  want to make end points for your disease  

22:02in partnership with pick a company  and they’re like how do i get the ed   eeg tracings and what so i don’t wanna i don’t  want to talk for you jake but can you just  

22:12double click on like the speed that’s possible  if we could just connect the data yeah with youQuantitative Data

22:20yeah and it’s like you mentioned  that we’ll see a lot firsthand   getting this is an unbelievable burden on patients  and their families and that when in these clinical  

22:30settings you’re able to get all this data what a  shame that it’s only you know one interpretation  

22:36uh by one clinician and then that data is buried  within these silos and makes it not accessible  

22:41for the types of work that we’re doing so to to go  into what you’re saying basically what we think is  

22:47that we need more rigorous quantitative precision  measurements for these new next generation  

22:54precision therapies and so for us in our data  modality looking at brain activity is a great  

23:02way of understanding how a novel treatment  is affecting the brain so currently  

23:08we don’t really have the tools  to efficiently do this and so   oftentimes we use surrogates in clinical trials  like the seizure diary where you know parents  

23:19are given this additional burden to have to count  you know what they see you know by eye as clinical  

23:26events which of course is a extremely meaningful  uh end point for the patient and the parents  

23:35that’s something that again is not an equitable  end point a lot of times parents aren’t able to   always be at home watching their parents they’re  watching their their children and then it of  

23:45course is not capturing the subclinical activity  in the brain there’s a lot going on that isn’t  

23:50seen by by an observer whether that’s a parent or  an epileptologist can’t just look at the patient  

23:56and so for us we think that there’s a really  interesting opportunity to at least supplement  

24:02these endpoints so you have more shots on goal  when you create a new precision therapy to see oh  

24:08no even at this early stage trial in a small small  end we can see that this new treatment is actually  

24:16affecting brain activity something like the  epileptiform spikes or seizures these quantitative  

24:22you know pathologic events we can now rapidly  capture these automatically more reliably than any  

24:28epileptologist with our tools and we can do this  almost instantaneously when we have the data  

24:34and so this is the type of possibilities we open  up when you have quantitative tools that have been   validated to actually interrogate this data more  shots on goal more if you can get it more shots  

24:46on goal for treatments to hopefully advance to the  next phase yeah i mean i just want to jump in and  

24:52jacob i think this is so important because you  know at the end of the day why are we trying to   put together all this data it’s so that we can get  therapies and cures for our kids and yeah the the  

25:03point that you’re making around you know EEGs and  endpoints really hits home for me so my daughter  

25:09has a rare neurodevelopmental disorder and for you  know for this i guess class of disorders seizures  

25:18as counting seizures is typically you know the  primary endpoint and this is really problematic  

25:25for you know the broader set of neurodevelopmental  disorders where you know a lot of kids you know  

25:31for instance in STXBP1 have variable seizure  profiles over their lifetime and you know in  

25:37the case of my daughter she doesn’t have seizures  but she has you know a spectrum of other you know  

25:43symptoms and so being able to you know equip  ourselves with you know the data that has been  

25:51generated you know i was laughing when mike was  talking about the EEGs because i barely survived  

25:58my daughter’s last 24-hour EEG but you know we’ve  never seen that data um and so being able to mine  

26:08that you know so that we can have endpoints that  can be successful across our spectrum of patients  

26:16is so critical for us to be able to  achieve getting these therapies to them  

26:22yep yep okay i wanna um you all lead  very innovative organizations devon  What would happen if you didnt exist

26:29with citizen jake with beacon charlene with  rare x actually and STXBP1 i would i would  

26:35dare say STXBP1 as a leader in the rare  disease space someone i copy as often as i can  

26:43and when you’re dealing at the cutting edge and  you’re innovating like this it’s easy to forget  

26:48what would happen if you didn’t exist right if  people weren’t working on these cutting edge   scenarios what would happen so i think can we  just take a second and paint a picture of what  

26:59patients researchers and companies would do if  if your organization and your and the peer group  

27:05right if these solutions that we’re talking  about that address these barriers didn’t exist  

27:11let’s just quickly go around and remind  people what we’d be up against so devin  

27:16what did what did it look like  before before citizen and it’s ilk  

27:22well i mean i can’t imagine where we would be  without the sort of the organizations that you  

27:27all started because honestly you you are the  ones who sort of pushed us it was is really  

27:33family members we were founded by a family of  of someone who who who died too young uh of a  

27:40disease that should have been caught earlier and  you know my colleague nasha fitter from FOXG1  

27:47similarly like you all push us to do the things  you know to to sort of put the ideas we have in  

27:53our head and direct them into the right space so  i will say that i i feel like our maybe one of the  

28:00biggest value adds that we put into this mix is  the data gathering is the you know what you you  

28:08should not have to depend on on you shouldn’t have  to do this yourself you shouldn’t have to depend  

28:14on a research company doing it for you because  it’s actually so hard to do that maybe some of   them would would only be interested in studying  your disease if you came to them with the data  

28:24already or let’s say you had a partnership with  someone who gathered a bunch of data and then they  

28:29changed their minds or they lost their funding  and rather than giving you back the data that you  

28:35helped them gather or that was about you no it  just disappeared it went on a shelf or it never   got extracted in the first place um and then of  course there’s the issue of you know once you get  

28:45reams and reams of data how do you how do you make  sense of that data right and it’s another piece of   innovation that layers on top of all of this but i  but i sort of feel like if we you know it’s really  

28:54the the groups the patient advocacy organizations  many of them led by parents that that kind of  

29:01push the folks who think they’ve got a big idea  or a good idea into sort of pursuing something  

29:07that’s actually going to be meaningful for  people yep yep and so without and without  What would happen without Citizen

29:14but without citizen then you just just push on it  a tiny bit you know you’re like what would happen  

29:20it would be basically researchers reaching  out to parents parents reaching out to the   clinician sending the files to the researcher who  hopefully has time and money to get through them  

29:29and may or may not choose to share them  i mean i will tell you being in citizen   there’s one researcher a number of our  families have gone to and he promptly  

29:37takes lots of tests and readings makes you sign a  consent you’re there with a doctor you’re trying   to help your kid you sign the consent all these  tests they go on a shelf fast forward two years  

29:46i go to citizen citizen collects my son’s  data from him and i say hey what about those   all those EEGs and this and that he’s like  oh no that was research that’s different i  

29:54don’t have to share that because that was a  research study and it just kills me i’m like   i flew my son two time zones and subjected him  to this and you won’t even share the data it’s  

30:07but with citizen you know we we get all the  other testing that tony’s had over his life   and we’re able to share it again and again  with researchers and companies can license it  

30:17yeah that’s right with it without having this sort  of silo that that we spoke to before and it’s it’s  

30:23really the data access issue that jake brought up  right from from the get-go as did as did Charlene  

30:28right if you can’t access this data you are  nowhere and yet it’s getting generated every day  

30:35either in clinical encounters or in things  that that parents and family members see   and carrying caring for someone at home right  and then jake you know without without by beacon  What would happen without Beacon

30:45biosignals and actually being able to look at the  tracings can you just take us back into a hospital  

30:5310 15 20 years ago like kid has EEG what happens  to that EEG how is that how is that those hours  

31:01and hours of you know god knows how many  electro data points processed and shared  

31:07well i don’t i don’t think we even need to go back  15 or 20 years again what i what i had witnessed  

31:13you know recently right now when we actually  are able to get an eg in a clinical setting  

31:20sometimes it can be a long eg um there is you know  an epileptologist so somebody that’s gone through  

31:28um in medical school neurology residency training  and specialization fellowship and you know  

31:34epilepsy that has to sit and read this entire EEG  recording often with a long backlog on a given day  

31:43and really has a hard time when being able to  actually review an entire say 72 hour EEG so you  

31:50can never actually look at all the data in all  the different ways that you might want to let’s   say if it were much shorter so you’re limited by a  human having to go through these very long records  

32:00second there is you know profound uh evidence  showing the amount of inter-rater disagreement  

32:08on uh epileptologists so that to be specific you  see a given event and you know one epileptologist  

32:17may say this is normal and another one may say  that this is abnormal in fact there’s evidence   that if you show the same data to the same  epileptologist either later in time they may  

32:26disagree with themselves and so before you know  beacon you know you really have to rely on sort  

32:34of reports of what a what a single epileptologist  might review for a given file some of our you know  

32:40biopharma partners before beacon would have to  ask you know an epileptologist just to look at   five minutes of the 60 minutes of data you know  just we know it’s too much data for you to look  

32:50at so just look at this small subset even though  we know this is not capturing the full breadth   of the data and the disease so you know  we just unlock this opportunity to be  

32:59able to actually assess all of the data and  quantitatively and you can do it today tomorrow   and two years from now it’s going to give you the  exact same result and i think that’s how you build  

33:08quantitative end points that actually move  the needle right if you can get the dataWhat would happen without RareX

33:15and then uh charlene without rare can you can  you just elaborate on the data silos and and  

33:23what it what it what it would take without rare  x and the ability to do what you’re doing yeah  

33:30maybe i can start by talking about you know  what were the critical challenges that we saw  

33:35um in terms of you know trying to address  with rare x and you know clearly data silos   we’ve been talking about that a lot um and  you know related to data lack of usable data  

33:48lack of data and patient empowerment challenges  and so um moving to lack of usable data um  

33:56you know what we’ve seen is that studies might  not include key data that’s actually the key data  

34:02to drive drug development forward and information  might not be collected um information might not  

34:10be collected using data standards and so this  complicates downstream analysis in rare disease  

34:17we also have this big challenge that data often  doesn’t exist so if you’re a new or emerging um  

34:24community um you need to start collecting data and  how do you start collecting it if you don’t have  

34:30any baseline data so what do you measure and  you know what do you collect and then finally  

34:36um you know we’ve been i i really love that we’ve  been talking about patients so much during this  

34:42panel because i feel that the one of the most  important challenges that rare x was started to  

34:49address was that patients aren’t empowered to  make decisions on the data they’re contributing   and so then maybe i can flip and answer your kind  of question which is what’s a world without rare  

35:00x and our like-minded contemporaries um well  first the traditional consent um where you know  

35:09participants are consenting for data  and it’s limited to the current study   and there isn’t any downstream use i mean you just  talked about that with the um with your example  

35:20of um uh of tony going to a researcher  and you know data isn’t produced in a way  

35:28data would not be produced in a way that it  would be openly available for researchers   for all researchers and also in a research  ready format um much more limited data would  

35:40be available for rare disease especially for  emerging and ultra-rare disorders and finally  

35:47patients would have a much more limited role in  deciding how their data can be used for research

35:55yep it’s all true i am i um i sent a newsletter  out to my group and i always sign it time is brain  

36:03because i want to remind people  that we all love someone whose child   uh is is has a brain that is being  built badly right now because of some  

36:11identified genetic deficiency and the sooner we  get these precision therapies which jake mentioned  

36:17um the sooner we can rectify that so moving fast  and being efficient is so is so key anyone want to  

36:24say anything before i go to the next question okay  so we’ve we’ve talked about what we’re doing we’ve  Whats next for RareX

36:31talked about what the barriers are we’ve talked  about what the world would look like without us   so hopefully now we know with citizen we can get  the data fast hopefully we’ll figure out the eeg  

36:40tracing jake can find the endpoints charlene and  rarex can gather all that data working with rare  

36:46disease groups like stxbb1 and syngap1 very  exciting what’s what’s around the corner so  

36:57as you as you think about data sharing and you’re  sitting where you sit doing the work you do   i’m curious when you look around the corner  what what what what you get excited about  

37:05being possible like it’s really it’s important  to focus on the barriers and break them down   but it’s also exciting to assume success and say  okay what’s next i that’s that’s where i get going  

37:16so jake let me let me start with you what’s  possible give us some give us some good news  

37:23yes i think we have great news i think that you  know with with groups like that of our panelists  

37:30we can do things like shrink the time  that we do natural history studies   and drug development right now again for  everyone this is oftentimes we will do a  

37:40one or two year long study you know either  retrospective or identify patients where we  

37:45need to better understand the disease because it  was too hard to obtain the data on these patients   in the first place so that we can now inform  our studies when we start giving treatment  

37:55with you know advances in data sharing we can grab  all that data or work with beacon in our database  

38:02and identify the biomarkers of interest you know  in weeks not years and so now we’ve you know  

38:08de-risk components of new novel clinical trials  so that you can move forward much much faster  

38:13so i think that’s that’s what  really makes it exciting for us   to start and then we can compare you  know when we do start a clinical trial  

38:21how you know these you know 10 or 12 patients in  a phase one how do they compare to you know the  

38:27patients in this larger group that we’ve collected  across the country or the world to make sure this   is really representative of the disease that we’re  trying to study and that when we make a treatment  

38:36it’s really going to impact you know patients all  over and not just these particular individuals  

38:43very cool so we can move faster time is brain and  i think you can yeah i’m really excited here we go  What do you get excited about

38:50charlene what what what do you get excited about  when you look to the future i’m excited about  

38:55what jacob talked about um i mean that is you know  what we really want to shrink that time from years  

39:02to weeks and that is tremendously exciting from  a rare disease patient perspective um you know  

39:09something else that i think bringing all of this  data together and breaking down this silos enables  

39:15is looking at diseases cross disorder so um you  know with with rex that’s one of the things that  

39:22we’ve really you know um architected the platform  to do is to analyze to gather data in a structured  

39:29and consistent way across disorders and so  we’re really excited about this idea to not only  

39:36enable analysis within a disorder but also  for disorders where their shared symptomology  

39:42or shared pathways to be able to analyze those  disorders together and potentially come up   with therapeutic strategies that can address a  number of disorders instead of just a single one  What are the new endpoints for trials

39:55yeah i i i’ve already started to see this with  with your i mean this is sdxbp1 and syngap1 when  

40:01when we share some data sets when i see one of  which is citizen when i see side-by-side analysis  

40:06of our kids i actually know okay your kids have  more motor issues than my kids my kids have more  

40:11aggression than your kids gi et cetera et cetera  it’s utterly fascinating and if you think about   the doctors like jake back when he was in the  hospital they actually have a reference point  

40:20they’ve seen five singap kids but they’ve never  seen an stxr they could reference this research   and get a sense okay these are the things i need  to look at it’s so exciting and then devin when  

40:31you look at the sorry go ahead jake i was just  going to add one more thing to that because i   think it’s such an important point not only are  the other features of disease that may be similar  

40:40and when you think about from our perspective and  more broadly you know what are the new endpoints   for trials that really we can build a community  across you know rare disease organizations to  

40:50say hey this quantitative seizure metric or  quantitative epileptiform spike burden this is  

40:55not just important for this one disease but we’re  going to come together as a community that we know   mike and myself and many others are thinking about  really how do we go to the regulators and really  

41:05move the whole field forward because this is not  something specific to one niche disease we’re   seeing this across the spectrum and think that we  can move the whole field forward and that type of  

41:13amazing work you know the rarics and others are  doing allows these opportunities so we can do this  

41:19yes yes yes because i think you know it’s  important to know while there’s only a handful of  The future of rare disease research

41:28amazing rare disease groups like the one  charlene’s leads there’s hundreds of rare diseases   and growing and as and as we and people are easy  oh there’s 200 patients here three oh rare disease  

41:37is so small it’s not it’s a huge cohort of kids  who are suffering and if we can process that data  

41:42at scale we can help them all which is important  it’s more again it’s it’s a moral impairment but  

41:48devin um what what do you get excited about  as you look to the future um so uh in on on  

41:56the theme of go faster be more efficient get there  more quickly um this is also more of a us-based um  

42:05uh advancement but i’m pretty excited about it  so so one of the things that still slows us down  

42:11uh at citizen is that it takes us it can take us  up to 30 days um and potentially sometimes longer  

42:18to gather all of uh one of our users information  from all the places where they’ve been seen  

42:25and then we are we have to have the parent  or the patient themselves it’s an adult tell  

42:31us when they’ve been seen again so that we can  go back and collect any new records so there’s   there’s it it doesn’t look very silicon valley  right there’s a lot of sort of manual effort  

42:42involved it takes a lot of time and and and  there’s there are some policy developments in  

42:47the us that are going to make it it should make  it easier for patients to get data in a way that  

42:53does that that gets them at least a solid set of  data quickly within even you know 24 hours or less  

43:02and the amount of data that is is sort of going  through that very fast pathway is expanding  

43:08so the idea of sort of driving this through the  patient i think for a lot of companies it looked  

43:14daunting because of the work involved in gathering  the data in the first place and so some of these  

43:21innovations around getting getting data quicker i  think are going to be quite brown groundbreaking  

43:28um now in rare again where some of the data that  we’re trying to get is for example eeg tracings  

43:34and other data that might not is not going to  be on the short list of data that’s going to be  

43:40available quickly there’s still going to be effort  involved but if i can get most of the data that i  

43:45need for our users in 24 hours and then i’ve got  to spend you know to use the time of my people who  

43:51who are who collect records to to to to chase  down the hard stuff that allows us to scale  

43:58that allows us to scale much more quickly that  allows us to put data in the hands of researchers   much more quickly takes some of the burden off of  the parents to you know let us know when that when  

44:08they’re when their child has been seen again so we  can go back and collect the records there there’s   some more opportunities for automatic refresh so  i’m i’m i’m actually pretty excited about data  

44:19access only getting better and quicker from here  at least in the us and then hopefully the us will   serve as an example for where other countries  need to go and i i also would say you know some  

44:30of the fda guidances around how they will consider  real world data and real world evidence is pretty  

44:36critical to the rare disease space i think the  the the sort of orphan drug and vote and other  

44:43departments at the fda that work in in rare sort  of understand that what they’ve got is something  

44:48different and requires more attention to be paid  to real world data as opposed to reliant on you  

44:55know the sort of pristine clinical trial data but  that’s another sort of development that came out   of the 21st century cures act that is that’s  appears to be making a difference and is again  

45:06another place where it’s quite possible that the  u.s may be ahead of other countries uh in terms of  

45:14you know leveraging data generated in clinical  and home settings to power with drug discovery

45:27mike i think you’re on mute wow this shouldn’t be a our webinar there  should be like a day-long session okay so  

45:35there’s so much here that you just explained and  i’m just gonna kind of try to synthesize how i  

45:41explain what citizen does right you the parent  consent citizen collects all your records in 30   days and devon you just said that’s too long and  it’s too much work it’s as a parent it feels like  

45:50light speed and it’s great that you guys are doing  the work right um but then after 30 days that data  

45:55has to be processed and then it’s made available  to researchers and clinicians and then that’s used  

46:01like cuckoo clock is going off in the background  and then that’s used to create real world evidence   right it’s important to just spell it out for  people because people don’t people think these  

46:09terms are interchangeable right and and you’re  i suspect you’re being a little modest i mean   you say maybe the u.s is ahead i mean you  you basically managed hipaa for years right  

46:17so you you’ve been in the trenches of this of  how it’s how it’s working and it’s important to   remind people that there’s that pathway and what i  heard you say was that collection effort that took  

46:2830 days now that we figured it out we cannot we’re  learning how to use robots to do it and there’s a  

46:34regulatory environment that permits that right so  we got the rules in place and the robots in place   to make that happen and then you layer on rare  x which would allow these different data things  

46:43to connect and then hopefully now the trouble  is those pipes are built for medical records  

46:48and then one of the one of the obvious little  obvious why i invited jake to be here but one   of the troubles is that eegs don’t flow neatly  through those pipes right that’s a big ugly data  

46:59set that lives in different computers and we need  to think about that and i and i will throw in that   you know whole exome and whole genome sequencing  also does not fit neatly through those pipes right  

47:10people get whole excellent sequencing this massive  amount of data and they get told you have one   one snip and this is your cause of disease but the  truth is as as compute and research evolves to the  

47:20point where we could actually process that data  we’re going to have the same problem how do we get   these massive files that are that are different  based on the version and the company and the  

47:30heart of so many reasons they’re different aren’t  interoperable and how do we get them to the place   where they can be used to facilitate precision  therapies it’s it’s really it’s it’s really  

47:39exciting and important and um i i just i’m so  glad that we have had this time all right i need  Alignment of incentives

47:45to take questions or i’ll get in trouble i get i  don’t get in trouble so let’s let’s take questions   for the audience um but before i do charlene  jake devin any thoughts you want to make before  

47:56we open it up because the questions could take  us in new directions charlene last last thought  

48:01or go to question i just wanted to bring something  up that we touched on earlier but didn’t really  

48:06um kind of talk much about which is alignment of  incentives in research and yeah i think that this  

48:14is really important because it’s an issue that  we still have to tackle and you know obviously   as as discussed on today’s panel there’s a lot  of work that’s happened in terms of changing  

48:24many aspects and many processes around um you know  access to data and you know and um utilizing it  

48:31for research but research incentives are still  a huge challenge you know in academia publisher  

48:38parish is still you know kind of the the dominant  um approach and so researchers i don’t think that  

48:45you know many intend to or would even think that  they’re hoarding data but because they need to  

48:51write their paper before allowing others to access  the data that becomes a challenge because that  

48:56delays access you know to the data um and then the  other thing on the um commercial side with pharma  

49:05is that i think that pharma are starting to  understand that having natural history data  

49:10is not a competitive advantage unto itself like  pharma is going to differentiate and win based on  

49:16their technology and their ability to move their  pipeline forward um but we need a way to transform  

49:23um you know the current way that research  is being done and initiated and make it easy  

49:30for pharma to collaborate in a pre-competitive way  on shared data sets and um you know i’ll just say  

49:36that i think that public private partnerships are  a way to establish and scale this model very nice  Next steps

49:46jake closing thought before i go to questions

49:53muted i think you’re muted jake

50:00i was just going to uh sort of  double click on that as i think   that was even more eloquently stated than  i would have so i think that’s those are  

50:08the next steps that hopefully will enable  these the future that we all want quickly  

50:13pre-competitive natural history studies and  addressing the the conflicts the inherent   conflicts of interest in the way academia is  structured in the sense of emergency the specifics  

50:23on the academia side you know one of the things  that we’re trying to do is again for us we’re not   motivated by publications only um because we’re  trying to accelerate novel therapies so we’re  

50:33experimenting what happens if we give our tools  you know for free to some of these academic groups  

50:38that give them super powers to be able to analyze  their data using some of beacon’s tools and now   they can publish papers on you know which is their  currency for advancing their careers but now we  

50:49can use some of this data to better understand the  disease and build better biomarkers but yeah like  

50:54you guys like we’ve talked about this requires  creativity to be able to you know work within the  

51:00existing structures as opposed to thinking about  how to break them down yeah last thought devin  

51:07no i mean i couldn’t agree more i’m uh it’s i  feel like we’ve surfaced a lot of really good  

51:14stuff on this call and i’m i’m i’m excited  to work with everyone on this because we’re  

51:20again oh we just want to be we just want to  give you the data that’ll power what you need  

51:26so that’s that’s our kind of niche role in this  whole equation so i would love you to do it

51:38that would be amazing all right  i got to take some questions

51:44um so a few questions have rolled in i will  if you’re looking at the chat i’ll start at  Questions

51:49the i’ll start with number one and i’ll  i’ll work my way up so i’m at the bottom   what strategies are used to address european  privacy challenges changes in view of covet impact  

52:00i mean i could have stopped it european privacy  challenges before i even said covet but let’s make  

52:06that two questions any thoughts on european data  regs and and sort of a european approach to data  

52:11privacy versus what we what we’re what we’ve  really focused on here which is the u.s one   and then has covitt had an impact on  data sharing and collaboration anyone

52:23well i i you know so i can take a stab at the  first stab at a couple of both of those actually  

52:29so um you know again everyone sort of looks at  gdpr european privacy regimes as oh you know  

52:37they are more astringent than what’s going on in  the u.s and again the fact of the matter is is  

52:43that they are have you know patient consent plays  a very strong role in provisioning access to data  

52:51and patients have strong rights in their data  including the right to get a copy of it so in  

52:56many respects the the the gdpr so-called obstacles  actually play very well in sort of patient and  

53:05family driven models of data gathering and  collection it i i just i just think it’s   been underutilized as a tool over there because  it’s less familiar than maybe it is over here um  

53:19and then in terms of covet 19 and we we did  see an amazing dedication of resources across  

53:26the globally really toward fighting the pandemic  it’s like you know we all had a common foe  

53:33all of a sudden and some of the silos around data  sharing um melted away i mean it’s not like we  

53:40didn’t struggle to gather data especially even  here in the u.s in a timely way but but i saw  

53:47lots and lots of collaborations scientific  collaborations uh for-profit organizations  

53:53creating databases that they basically you know  the data broker saying we’re opening up our data  

53:59for free for covid researchers to come and take  a look at it and and to do studies on it and at  

54:05no charge and you know that kind of a kind of  all hands on deck approach is absolutely amazing  

54:12and it does make you wonder why we can’t deploy  that more toward you know diseases that are not  

54:18epidemic or pandemic but are you know really ones  that we’re still struggling with and that for the  

54:26families involved are are as bad if not worse  than what we’ve been going through with covid

54:34jake charlene thoughts on europe or kovid

54:40i’ll just say that um we have to be able to be global because rare  disease patients are all over the world and so  

54:51this is a critical thing for us to  figure out in terms of being able to   um really bring together these cohorts  of patients across country borders yep

55:02okay keep going i mean i will only say that in  addition to the regulatory environment which which  

55:07um devin has pointed out is more maybe more the  same than different there is the cultural approach   right there is i have i have talked people a  lot of nationalities into signing up for citizen  

55:17and um that you’ve got a there’s a different  conversation around privacy with different   nationalities and it’s that’s that can’t  be missed yeah we had a question what is  

55:25your experience sorry i said for sure yeah and  and having our platform available in different  

55:31languages would sure help too yeah we’ll  get there hopefully with translation then  Patient Advocacy Groups

55:37it’s all software what is your experience  collaborating with patient advocacy groups   so i quickly go through that because i  think we’ve talked a little bit about it but  

55:46charlene do you work with patient advocacy groups  yeah in fact we on board disease communities by  

55:54collaborating with um patient advocacy groups and  so we feel that that’s really important because  

56:00you know at the end of the day the trust is within  the community and you know so we want to work with  

56:06the you know that group to enable that group  to be successful with you know onboarding and  

56:12initiating data collection so if somebody wants  to work with you they should just call you up  If somebody wants to work with you

56:18yes absolutely great devin same question   yeah i was going to say ditto we wouldn’t be where  we are without patient advocacy groups we depend  

56:29on them to help us recruit people to the platform  we wouldn’t we probably wouldn’t really have  

56:35a way to function without an advocacy group at the  other end you know as a as a startup for so long  

56:42we only got acquired towards the end of last  year like we we were limited by our bandwidth  

56:47in terms of the number of advocacy  groups that we would support but i   uh you know again on the horizon see us being able  to scare scale more quickly to more groups and  

56:58more diseases in uh in the very near future um  with the additional resources of a larger company  

57:05plus the ability to sort of combine the genetic  and phenotypic data from the can’t wait okayWhat are your plans for the future

57:15yeah we’re as a very very early stage startup you  know we’re just sort of getting getting getting  

57:21started ourselves we’ve obviously been in our  conversations with mike and we’ve had groups   approach ours which we we want to support  um going forward we definitely you know in  

57:32the indications where we’re going after first  you know i think the patient advocacy groups  

57:37and beacon are you know 100 aligned and  we want to understand the data as quickly  

57:42as possible and often going through the  academic medical centers and otherwise   um can be very difficult and encumbering  so you know with mike and syngap1  

57:55for example we’re talking about how to think about  you know getting large amounts of data so that we   can do these types of studies really quickly and  bring that information to the world to be able  

58:03to you know have actionable insights so i think  that for us over the next few years i can imagine  

58:08we’ll have you know very strong relationships as  we grow our company and support our capabilities   to go go after a number of these rare neurologic  disorders okay one and a half more questions  

58:19because i think the last one i’m just going to  try to take what degree of this one’s this one’s  What degree of clinical lab data is required or necessary

58:24this one’s interesting what degree of clinical  lab data and ehr standardization is required

58:32or necessary i guess to understand strength  of evidence for regulatory decision support  

58:38that’s a that’s a do we do everything have  to be standardized or we can’t use it or   not charlene devin well maybe i can take a first  um stab at this so um you know we feel that data  

58:52standardization is really important so mapping you  know data to um you know standards whether they be  

58:59hpo or hl7 and you know i know that citizen  also you know does a similar thing um and there  

59:06is fda guidance um you know for uh that i  think it’s draft guidance that’s come out  

59:13on real world data the of the necessity  of mapping to standards and so this is a  

59:19really important aspect of building a data set  that can be used um you know for you know both  

59:26generating evidence and then you know also moving  forward to support regulatory decision support

59:34yeah you know when the data are already   standardized in the electronic record and coming  from the labs it makes our job so much easier  

59:45but we’ve certainly found that there’s just a  mother load of data in non-standard non-structured  

59:51formats um a lot of it in clinical notes for  example progress notes are are almost like  

59:59the gold mine for understanding what’s happening  with a patient in addition of course to to to labs  

1:00:06in the case of of um neurological diseases eeg  tracings all of that stuff complete the whole  

1:00:12picture you’ve got to have the ability to sort of  take the non-structured data and standardize it  

1:00:18you know if there are standards available and and  you know again that’s something that that we have  

1:00:24really worked on since the very beginning and  continue to improve our capacity to do that  

1:00:30so now in terms of sort of how the fda feels  about non-structured data i mean i think if  

1:00:37they can um understand the origin of the data feel  comfortable in the provenance of the data points  

1:00:45that are coming before them they have a a a decent  enough size data set um i mean that’s supposed to  

1:00:52be the whole point of gathering real world data  that turns into real world evidence that supports  

1:01:00clinical and regulatory and research decision  making so it the fda is just at least in the u.s  

1:01:07again just starting to i think place more reliance  on real world evidence versus requiring the sort  

1:01:14of pristine standardized collection as  part of like through a clinical trial   um and so i i think the next couple of years will  be very telling in terms of just how willing the  

1:01:25regulatory agency is is in accepting some of this  data that comes out of non-traditional sources  

1:01:32jake any thoughts on this question about  standardization i for example does an amazing job  

1:01:40being able to organize even though this sort of  additional uh clinical real world data may come  

1:01:48in different formats being able to think about  how what is common across these different data   types so that you can then build models to better  understand what is being seen in the real world  

1:01:58of course you know that type of control isn’t  always there but that is supporting evidence   as you’re building out you know these natural  history studies for example uh can be critically  

1:02:07valuable to making you know decisions about  go no go to make this new therapy yeah  

1:02:14so the last question is and then i’ll give  it back because i realize we’re at time   what is the best platform slash database if  you’re starting from scratch so if you’re a  

1:02:20brand new rare disease group whatever i mean i’m  gonna editorialize here my answer is on the screen   right call citizen get on the list call charlene  sign up for rare ex call call jake get on his  

1:02:31dance card like if you’re starting from scratch  when i was asked to host this i called the three   best people i knew and they’re on the screen  right now but until you get on their dance cards  

1:02:42my advice to every rare disease group is make sure  you know your patience do not do not delegate this  

1:02:47to a well-meaning researcher with a little bit of  funding because they’re going to fund a natural   register for two years and they’re going to go to  another institution and you will be precluded from  

1:02:55seeing that data by some irb that is attempting to  protect the patients makes me bananas so my answer  

1:03:01is get to know your community keep a contact  list and find professional partners because  

1:03:07as you saw today this is highly complicated and  you need people who really think about it all day  

1:03:12long that’s that’s i’m that’s my thought would  anyone amend that before i hand it back to tom

1:03:20no i totally agree build your community first  spend your time getting to know your people  

1:03:26because it would be it’s it’s a dependency  that can’t be skipped over so we’re here  

1:03:34and with that before i give it to you tom i  just want to say thank you to the panelists   and thank you to bayer rossi for for inviting  me to do this i really this is a this is a  

1:03:42talk i’m going to forward to a lot of people and  strongly urge them to listen to over to you tom

1:03:49brilliant thank you very much mike  and thanks to you all for sharing   these great insights and being really  generous with your time today on behalf  

1:03:56of bayerasi and marcus evans webinars we’d  just like to thank you all for joining us   and do hope you’ll be listening in at our next  event take care and have a good rest of your day

1:04:16you