Denver Man Gets Gene Therapy to Restore Hearing

I think he means not exactly scientific reasons.
Really nice info ATELOS, it is encouraging especially for tinnitus patients who more or less do have remaining cells intact. Do you have any info on them tinnitus wise? Although I strongly believe they are interconnected, I don't know if they intent to use this on tinnitus patients, in trial phase I mean.

 

This is a transcription of the earnings call for Genvec. I've tried to pull out those potions relevant to CGF166.


Joe Pantginis - Roth Capital Partners

Hi guys good morning, thanks for taking the question. Couple of questions if you don’t mind. First maybe one for Doug, when we look at the CGF166 program, can you talk about the Phase 2 portion about the volume escalation, maybe can you remind us is this sort of looking at strictly volumes do the number of particles remain the same or does that change as well?

Douglas Brough - Chief Scientific Officer
Hi Joe, the volume goes up and the number of particles of vector go up with it. So the drug dose is basically being controlled by the volume going - increasing in that phase of the study.

Jim Lambert - Senior Director of Accounting & Finance, Corporate Controller and Treasurer
But to be clear the concentration of viral particles is not changing. So we deliver more drug by delivering more volumes.

Joe Pantginis - Roth Capital Partners
Got it, got it. Okay now that's helpful, thanks. And I guess, I don’t know how it gets here, since the first patients are in here and obviously you know you’re dealing with big pharma here and they’re taking a very thoughtful approach to this.

But the question I have ask to all the time is, do you have any information at this point with regard to potential news flow out of the program?

Douglas Swirsky - President and CEO
We're obviously not in a position to promise the sequence of events that may be ultimately revealed by Novartis here. So we don’t know what the news flow is going to be, we’re excited that we’re going to be entering Part B of the trial and Part A has been fully, fully dosed. But not sure what Novartis wants to do here in terms of disclosure.

I know it’s very material for our shareholders and we’re anxious for any news but the Novartis has a view here at this program can be very important for the long-term registration strategy for the compound and we don’t want to see a lot of excess news flow obviously that would compromise that.

So we would like more news, I think Novartis would prefer to keep things under wraps but they may end up putting some information out over time and we look forward to that.

Joe Pantginis - Roth Capital Partners
Sure and I guess since this is really to have a potential to be a transformational therapy, they would want to maintain the data for potential medical conference types of presentations as well.

So maybe if you could just switch to the underlying technology, I know Doug you spent a little time regarding the – these are obviously non-human adenoviruses maybe can you talk to the concept of the importance of neutralizing antibodies in humans.

I guess some data you've shown to-date has shown that the – you’ve seen less neutralizing antibodies, is it something that’s going to be important over time or does the trends and expression of the genes make the neutralizing antibodies less important?

Douglas Brough - Chief Scientific Officer
One of the limiting factors in clinical studies using adenovirus as molecular vaccine candidates has been the presence of existing or pre-existing immunity to the viral vector and its limited the overall performance once it’s delivered.

So I’m most excited about our new gorilla adenovirus vectors, which overcome that because they’ve not been seen as an entity in humans. So there is no pre-existing immunity to those and the human chronicle patient population going into.

The second part is that these vectors are actually showing greater performance characteristics than sort of the classic F5 in our preclinical animal models. And so we’re very excited to see and to move these forward into new clinical testing to see how well they perform in humans as well.

Joe Pantginis - Roth Capital Partners
That's helpful, thanks Doug. And then maybe one last question for Doug Swirsky, you obviously focus on RSV that's obviously a very important asset at the company. When you look at that asset and other potential assets, I know this is a bit of a sensitive topic because this is – this have to do with ongoing discussions but can you sort of portray how discussions have been progressing with some of your vaccine candidates?

Douglas Swirsky - President and CEO
Thanks Joe for the question, I think that all programs that we talked about today are important that we highlighted on the call and some programs that we didn’t talk about on today’s call I really believe that by taking a portfolio approach to how we’re managing the opportunities in front of us, so we’re in best position to create value for shareholders.

There is a number of ongoing conversations about a variety of assets and our goal is to we should get some additional things done this year but we can provide no assurance that things will get done on the timetable we expect.

But again the strategy is to move things forward with collaborations, that means we have an active business development effort. There is certain programs that are not yet mature enough to enter into discussions with potential collaborators but we’re very excited about EVD68 and we'll make our progress this year on very small budget.

But that's something eventually we would like to talk to collaborators about once we have some proof of principle information that we could share with them, in terms of RSV that's something that has been ready for partnership for some time and that's not lost on us that we've been discussing how to move that forward and we’re going to continue those discussions and hopefully at some point have the result, we can talk about it on the call such as this.

Joe Pantginis - Roth Capital Partners
Great, thanks a lot guys.

Douglas Swirsky - President and CEO
Thanks Joe.

Operator

[Operator Instructions] Our next question comes from the line of Reni Benjamin from H.C. Wainwright.

Reni Benjamin - H.C. Wainwright
Hi good morning guys, thanks for taking the questions and congratulations on the progress. I know Dr. Doug mentioned that October 2014 was when the first patient was treated and that a safety review, I believe you said a safety review is happening now.

Do you know when - I'm just trying to get a little bit more clarity, when was the last patient enrolled or when you think the safety review would be done and the second portion might start?

Douglas Swirsky - President and CEO
This is Doug Swirsky, I’ll take that question, Ren. We don’t know what we’re going to be able to say here other than Part A, we thought was significant to be completed and moving on to Part B I don’t know whether or not there will be any information that will flow in terms of specifically when the first patient is dosed under Part B.

I think it’s safe to say that the there has been an assessment after each patient of Part A and a feature of Part A of the study was a safety assessment following each patient. Whereas for Part B after they escalate the dose, there will be a safety assessment after that first patient and then they’ll treat two more followed by a safety assessment before the next escalation could occur.

So as of now, the safety assessments have obviously gone without issue and additional patients were dosed and therefore Part A is completed, we don’t have a lot of information to share right now about when Part B would be started or if or how much information we would be able to share.

I think that once we’re into Part B, we will make that clear in at some point in the future but we think the trial is proceeding as intended and absent news you can assume that the trial is continuing to improve and treat patients.

Reni Benjamin - H.C. Wainwright
Fair enough. With the patients that have been dosed in Part A are following – is the company following those patients out longer to test even at those doses if there has been any improvement in hearing or was it just purely safety and now really Part B and Part C are the more efficacy related parts?

Douglas Swirsky - President and CEO
Ren, one of the things we like about the trial design is that we went into the first patient, the very first patient received the dose that could be effective and that's obviously based on the preclinical animal model.

So the first dose which was 20 microliters and I think it’s five times ten to the eighth of viral particles for 10 ML, Doug can correct me if I’m wrong, but that dose we believe could be efficacious based on the preclinical model.

So but it’s the lowest dose we’re starting within the trial, those patients are being followed for both for safety as well as for efficacy and so I think subject to monthly efficacy assessments after they were treated.

Reni Benjamin - H.C. Wainwright
Okay. I think this one is for Dr. Doug, correct me if I’m wrong Doug, but how long based on the preclinical results might you I guess predict that you might see any sort of an efficacy signal for example how long do the sensory cells take to mature for the neuronal connections to take place, do you have any speculations?

Douglas Brough - Chief Scientific Officer
All of the animal model testing suggest after a couple of months and we were able to recover function either hearing function or balance function in animal models that we look down.

Reni Benjamin - H.C. Wainwright
Okay. And so is there – I mean a lot of times you can translate that directly into humans but have you and Novartis discussed or talked about how that could potentially translate or is this just unchartered territory?

Douglas Brough - Chief Scientific Officer
I don't think that we know exactly what’s going to happen here, so we don’t have an expectation either way, Doug do you want to add to that?

Douglas Swirsky - President and CEO
I think that you hit the target, we don’t know what will happen in a human both the guinea pig and mouse modeling that we've done, we have seen efficacy out of the couple of months no whether or not that gets better as we go longer or what we don’t know at this point even in the animal model. So it will be exciting to see new clinical results.

Douglas Brough - Chief Scientific Officer
Not everything is going to obviously translate equally between the animal studies and the human clinical studies and that’s why you obviously run the trial.

But there is a number of things to point you that give us optimism for that this could be an effective treatment for hearing loss and one obviously the animal models looks good but also we’ve been able to show that in human tissue we can regenerate these cells. So, we'll look forward to results from the trail, answering that key question.

Reni Benjamin - H.C. Wainwright
Right. I guess just another quick biology question. Do we know if the sensory cells can answer a lack of better word translate speech, will it be able to conduct - I guess conduct signal so that the brain can now translate those signal into speech. Are we, as a first step just trying to even partially restore any sort of sound?

Douglas Brough - Chief Scientific Officer
Ren, that’s a great question. At the core of any sound is just, as you are pointing out, just the ability to detect that particular frequency and whether that is the ability to understand a concern or whether that's just the ability to hear a noise makes a big difference in terms of how this therapy will work.

But also how both devices work and other treatment for hearing, so you are bringing up a great question and as we proceed, I would hope that we can have some answers to this as we go forward but at the very core you got to have some sensory cells to be able to pick up the sound.

Douglas Swirsky - President and CEO
Trail design has additional end points. So the primary end points, the change in pure tone audiometry or there is a number of other assessments here for hearing and balance function as well as tertiary end points for quality of life assessments.

Reni Benjamin - H.C. Wainwright
Got it. And then just one final question from me, Doug you mentioned that there are other programs that you really didn't talk about in the prepared remarks but I was wondering if you could maybe shed some light as to other things that might be happening in the background that, maybe too early to talk about in the prepared remarks but might be okay to answer in a question.

Douglas Brough - Chief Scientific Officer
Ren I think that we are going to let the news flow develop from those programs and something that we have talked about. Obviously we have a program against HSV, we have in malaria. We are looking at a number of things but the concept here and the strategy is consistent which is you want to keep the burn rate low and try to create a pipeline of opportunities through collaborations and everything we are doing is consistent with that.

So, I think additional news flow could be coming on some of - couple of those programs and some other things we haven’t talked about but we will wait till we have something specific to say about them rather than promise something and then wait for to happen.

Reni Benjamin - H.C. Wainwright
Got it. Congratulations and good luck in 2015.

Douglas Brough - Chief Scientific Officer
Thanks Ren.

Operator

Thank you. Our next question comes from the line of Julie Bickel from Boenning & Scattergood.

Julie Bickel - Boenning & Scattergood
Hi, thank you. My first questions is do you have any idea when the third patient was treated? Do you have a date for that when it was completed?

Douglas Brough - Chief Scientific Officer
We do, I don't think its particularly relevant - like I said, I think investors who are hungry for news flow from the program and we would love to be in a position to share as much as possible but I think that the assumption should be and we would have a duty to disclose or something went wrong.

The assumption is that the trial is continuing to go through safety assessments between cohorts to enroll patients in the trial to treat patients. We are up and running at the three centers and we will let the trials, sort of, unfold in a manner that's Novartis is comfortable speaking about the trials.

So the specific date when the patient is and therefore try to extrapolate when the fourth patient would be, I think ultimately the goal here is to do a quite a number of patients here we are not going to track the each specific one.

Julie Bickel - Boenning & Scattergood
So you have a date base but you just can’t tell me, right?

Douglas Brough - Chief Scientific Officer
We are choosing not to because we just don’t see that being beneficial to the program to provide that level of granularity.

Julie Bickel - Boenning & Scattergood
Okay. So going to the next phase of it, you talked about the first patient for each cohort after the first patient there will be safely review and then after each cohort. So I guess my question is, that just for the first cohort does it go first patient or first cohort and then safety review and then at the end of that one, and then forward to just at the end of each cohort or the first patient of every cohort gets a review after they are done because of the escalation.

Douglas Brough - Chief Scientific Officer
So I would think of it as the first part of the trial part A was patient analysis, and it was that step process. In this case it is going to be a one-two step. We are going to do – treat our new patient - treat a patient at the new dose, safety assessment and then do two more and then just do a full data set review from that cohort before considering escalating the dose.

And we don’t know how far those dose escalator again volume escalate before selecting the dose for - to go into part C of the trial which will enroll 20 patients as they're presented within option to upsize.

And so one of the reasons why I can't tell you exactly, when the trial is going to be completed is we don’t know how long part B is going to be, how many cohorts will eventually be enrolled and that will - lot of that will depend on what takes place in the assessment of the part B patients at the various doses.

Julie Bickel - Boenning & Scattergood
So regional cohort that will probably be a 1/2?

Douglas Brough - Chief Scientific Officer
That is the plan, that going to be a safety assessment after the first patient in each cohort followed by two more patients and then a full data set from that cohort before considering escalating.

 

We know about Rob Gerk, but were there also 2 other people that were dosed with this medicine that we don't know about? or am I reading that wrong about a third person? Do we know who they are?

 

Take this for what it's worth, but it looks like they have dosed all three in the first "safety" cohort.

http://2030something.me/jeffinkc/

 

Uncle Jeff is trying to get in on the next trial that they are having. Still not sure who the other two people are that got dosed?

 

Well, uncle Jeff may go into surgery by May. But he hasn't heard anything from the other girl he asked for. No info comes out I am afraid, just like our topic main character, Rob Gerk... We don't even know how he is, it is rumored that the therapy wasn't succesful.

 

I'm willing to bet that Novartis has some type of agreement with Rob Gerk where he cant comment much either way. Same goes for the other people that were dosed. All we can do right now is guess. Agreed from the couple of quotes he gave it seemed like it wasnt successful, but again we really dont know anything. I've been on his twitter page looking for an update but havent seen anything.

 

Could be that he has a kind of an NDA.
Otherwise he could influence the stock behavior of Genvec. At least we can speculate, that the drug didn't harm or gave dangetouse adverse reactions, otherwise they would't expand the trial.
There are also different dosages and he got the smallest....
The other blog of uncle jeff sounds a little strange to me...
So the only thing we can do is wait for released data from Genvec. If there is a positive result which is relevant, they won't keep it secret....

 

There is also the chance that if his high frequency charts are in the -100 db range and he picked up 10db or 20db and now sits at -90db or -80db that is not going to be noticeable at all. I remember reading the Genvec charts and didnt the lowest dosage reduce actually reduce hearing in the 4k range in the animal models? I really think they need to continue testing with the different dosages to see what works and what doesnt.
I'm sure Novartis is also experimenting further trying to figure out how to make it work better right now. I'm pretty sure they have this figured out, but might need to begin tweeking the drug to make the entire process more effective.
Tomytl, thats a good point. Any negative comments could derail Genvec stock. They are a very small company from what it looks like and I think their success is probably riding on this drug.

http://osp.od.nih.gov/sites/default/files/1_1260_CGF166_Klickstein.pdf
I found the chart I was looking for. Medium dose on page 12 makes 4k -4db. Only high dose saw an improvement. I'm really having trouble reading these charts because most of our hearing is in the 0-4k range and not at the super high frequencies.

 

Hi RB2014,

yes I also think, the outcomes won't be like a cure for hearing loss. It's more a proof of concept study.
So it's the first time, a clinical trial access the inner ear, in this case with virus-taxis.
If there is proof of just 1 hair cell bundle growing in the inner ear, it would be a huge success.
If it would work, I guess they have to tweek the therapy in many ways. But if Genvec could proof that they can
access the inner ear and do something positive, it's the start of a big range of therapies for the inner ear.
Parallel, the Draper Lab is doing research on a micro-pump to get some drugs in the inner ear...

I also found another reading about a possible optimisation of atoh1 therapy
http://journals.lww.com/thehearingj...ser_to_a_Gene_Therapy_for_Hearing_Loss.6.aspx

in this article it says:
Novartis has invested about $500 million and created a new division aimed at developing the first generation of Atoh1 therapies.





Let's hope there will some advance soon... but I guess, it will take some more years until it's widely applicable.

Greets Tom

 

Here I found an article from 2003 about the first experiments using Math1 (Atoh1)....It impressivly shows how press reflects the progress.
It took almost 12 years to bring this discovery to human trial...
On one side it's exciting on another side it shows the slooooowwww medical development...
http://www.futurepundit.com/archives/001328.html

 

Rob Gerk at 3 Months on Hearing Restoration Trial:

http://www.medicalnewsnetwork.org/N...Gerk at 3 Months on Hearing Restoration Trial

 

Thanks for sharing. Seems that there is small changes, but at least no harm to Rob!
I hope the best for him, that he has most benefit of this trial.

 

Thanks for the link. Its hard to find updates on the web for this stuff.
So it looks like he got his hearing back to "normal" after the first three months. I guess this means that it takes a while to recover from the surgery. If he scored better on the balance test then there is a good chance something good is happening inside his ear. I've read the tests are pretty thorough that they perform before and after so any benefit is really good news.

 

I'm just hoping someone in the initial trial shows some hearing improvement. Hearing loss and tinnitus can be quite taxing on a person and if people could just see some hope for a real treatment for this affliction, it would certainly make the situation easier to bear. I would think that Novartis and Dr. Staecker have some reason/data to support treating people with long standing hearing loss, otherwise I don't think they would have pursued this trial. Thanks to everyone who has posted information and or provided information on this trial.

 

Same opinion. On the other side, it's a proof of concept study and there isn't the expectation to cure deafness with this treatment. It would be a success if they only could treat balance disorders, because this kind of cells are more likely responding in regeration to Atoh1 from what I have read. It would be spectacular if there would be a correct regrow of just one cell. This would also show, that there is a clever way to deposite drugs in the inner ear. But for sure, it needs much more tweaking before this drug is applicable to the masses.
Fascinating enough that 3 approaches aiming to solve a very complex problem
Gene Therapy (Atoh1)
Molecular Therapy ( Notch, LGR)
Stem Cell Therapy

I can't wait until one of the companies holding patents for Molecular Therapy enters clinical trial, but it's still some years away.

Let's hope for best results from the Novartis Trial to get some more knowledge about hearing loss.

 

I wonder what are the chances this may work one day and we get our old selfs back..

 

Nobody knows... another 10 years maybe?
Anyway, but like Dr. Hinrich Staecker said, to reach a clinical trial is a huge step. It's a Gene Therapy not just an injection of some drugs..
http://www.medicalnewsnetwork.org/N...ted For 1st Clinical Trial To Restore Hearing

 

I was tweeting with the person who has been posting the #jeffinkc updates on twitter and on her blog. Jeff will be getting the surgery on May 13 and she is not aware of any restrictions that will preclude her posting about how things go.

 

Thanks for sharing. First of all let's hope for a successful operation and that all goes well and ofcourse as much as possible hearing enhancement. It's very brave to join such an experiment.
Do you know which dose will be used? There are 6 different doses.
https://clinicaltrials.gov/ct2/show/NCT02132130

I guess, Rob Gerk got the 20uL.

 

Actually, chickens developed tinnitus but since they can regenerate their hair cells, tinnitus disappeared so this will be the cure for tinnitus, I'm assuming.

 

According to the GENVEC earnings call, this will be the 40 ul. They are also doing these sequentially, but I don't know the timing. I think there was six week between patients in the first cohort. My impression from the earnings call was also that GENVEC would be much less open about the trial going forward, and that further info would only be released at the discretion of Norvartis.

 

Yes looks like... It's difficult to say what's going on, if they got results they expected or if everything not working in the case of hearing restoration or balance improvement.
Also many factors can play together, maybe it also depends how the hair cells has been killed in patience, due to
viruses, noise or ototoxic drugs.
I also find that for a clinical trial they are very much in the press. Usually it's not the case. If they could publish positive results, I guess the GENVEC Stock would explode....From this case, I'm not sure if they are allwoed to publish results on the fly... it would distort the market ....

 

I recall the CEO stating, well before the trial at one of these investor conferences that were available online, that they did not expect the first cohort to show any hearing improvement. I think you are absolutely right that from hear on out that the financial considerations of Big Pharma and stock manipulation will have a lot to do with what information is public. These seems to go against what #jeffinkc is saying, but there is lot a money involved in this. In some ways that makes me feel more positive than if a university were involved.

 

I think this will only be a cure for tinnitus if your tinnitus is caused by hearing loss. Anyone that has tinnitus and perfect hearing I dont think will benefit.

It does seem that these tests are being done quickly though so this is very good news. If the therapy proves successful I remember reading that it could be 5 years when it becomes mainstream. Again, not a cure for hearing loss, but someone with profound hearing goes to moderate.

 

Most people have perfect hearing with hidden hearing loss.

 

when we will know if this man restored hearing, and what is happening, will the virus as all the previous attempt cause cancer (from 1 year to 10 years)

 

that is because there no audiometry that mesure full hearing spectrum 16- 16000

 

Results are expected in 2017, this is what the clincaltrials.gov says.
The viruses used in this trial have been used in other trials before and they seem to be safe.
Gene Therapy has developed a lot since the first trails causing problems. It's like a come back
of this technology.

 

well still 1970 was far away, but they still are not sure will he get cancer. @Silvio Sabo can you explain how it goes with virus and genes therapy and will these new hair hearing cells have any effect at all, or they will just stand there without any use at all