Q2 2022 Uniqure NV Earnings Call
It's an OME mode. Add to the speaker's presentation, double your question, and answer session.
To ask a question during that session, you'll need to press star 11 on your phone.
Please be advised that today's conference is being recorded. And I would now like to hand the conference over to Ms. Maria Cantor, Chief Corporate Affairs Officer. Ms. Cantor, please go ahead.
Good morning and thank you for joining us.
This morning, UNICEF announced that it has postponed patient enrollment in the higher dose cohort of the Phase 1-2 clinical trial of AMG-130 in Huntington's disease based on reported two-star events at this dose.
We will discuss these events and provide an update on the program during this call.
Joining me for the Inventor events and webcast are Matt Kaffler-Star, our Chief Executive Officer.
and Dr. Ricardo de Melch, our President of Research and Development.
We'll be making forward-looking statements during this investor call. All statements other than those of historical facts are forward-looking statements.
They are based on management's beliefs and assumptions and on information available to management only as of the date of this conference call. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including the factors described under the heading Risk Factors in UNICURE's quarterly report on Form 10Q, filed today, August 8, 2022, and other securities filings.
Given these risks and uncertainties, investors should not place undue reliance on these towardlooking statements, and we assume no obligation to update these statements, even if new information becomes available in the future.
Now, let me introduce Mass Capista, unique yours to EL.
Thank you Maria and good morning everyone.
On June 23rd, we announced encouraging 12 month follow-up data from the low-dose cohort of our US Phase 1-2 study that showed AMD 130 was generally well tolerated with neurofilament light levels near baseline and tree-to-patients and meaningful lowering of mutant incoming strop enhanced formed of torrent engagement.
As announced in our press release this morning, in July , we were informed of two suspected, unexpected serious adverse reactions or suicides. In the Higher Dose Code Board of our Open Label, these ones be to clinical trial of AMG 130 in Europe .
Both of these patients, which were the first two patients dosed at a single clinical study, presented with localized inflammatory responses and other related symptoms within one to two weeks after their procedures.
A third patient who had previously been treated with a higher dose of AMT-130 in the U.S. in March of this year experienced severe headache and other related symptoms also shortly after their procedure. The patient was treated with a higher dose of AMT-130 in the U.S. in March of this year experienced severe headache and other related symptoms also shortly after their procedure
That event was initially deemed by the investigator as not related to AMG 130, but related to the procedure.
Upon further review and discussion with the clinical trials independent data safety monitoring board of DSMB, we have reclassified and reported that patient's reaction to have the issue start.
Importantly, these three patients are no longer hospitalized and have since fully or substantially recovered.
The DSMB does not view these events as a dose limiting toxicity and thus far in our investigation we have not yet identified the root cause of these events.
Nevertheless, we at the DSMV believe it is prudent to voluntarily and temporarily delay the enrollment and dosing of additional patients with a higher dose until we complete a comprehensive safety review in conjunction with our DSMV.
During that time, we will continue our investigation to consider potential risk mitigation plans.
We expected you this over the next 60 to 90 days.
This delayed does not apply to any future procedures at the low dose, but the remaining significant adverse events related to AMT 130 have been reported. The remaining significant adverse events related to AMT 130 have been reported.
That's far a total of 36 patients have been enrolled across our US and European clinical trials, including 26 patients treated with AMT 130 and 10 control patients.
Of those treated, 14 patients have received a higher dose with some having now been followed for up to one year.
An additional 12 patients have received a lower dose with some having now been followed for up to two years.
Over the course of our studies, the independent DSMB has conducted six separate tanky reviews and aside from these three events, no other suit SARS have been reported.
Would you not expect this to label how any impact on the data readouts in 2023?
In the US Phase 1-2 study, all 26 patients in the first two dose cohorts have been enrolled.
And the company continues to expect to present the 2022 year follow-up data in the second quarter of 2023.
And the European faith won't be studying.
Phase one, be two studying the six patient lower dose cohort is fully enrolled and the company continues to expect to present one year follow of data in 2023.
Four of nine patients in the European study have been enrolled in the higher dose cohort.
Before I hand the call over to Ricardo, I want to stress that patient safety and well-being will always be unique to your top priority. And we are committed to working with the DSMB to complete our investigation as soon as possible. The DSMB will be completed on investigation as soon as possible.
Now let me turn the call over to Ricardo.
Thanks, Math and good morning.
In mid-July, Unicron notified the health authorities of serious unexpected adverse events related to two subjects in Europe treated with the higher dose of AMP 130 at a single clinical site.
The first patient experienced onset of motor and other striatal symptoms within 12 days after the procedure.
Following admissions of a hospital and MRI was shown to show the intense T2-rated MRI signal along the tracks of the infusion and industrial item and audit, consistent with the GMA or Foreign Dermality of a healthy patients. The doctors, Doctors, they have slow patient and have shotgun IV in this case. In fact, your Law Sign into your psychologicalomental constraint will help you 80 ??? ones and of grain.
Treatment of steroids was initiated and tapered through a final dose 10 days later.
The subject is now fully oriented and has a non-focal neurologic exam, but still has subtle deficits in verbal fluency, memory, and attention relative to the pre-operative part of the preoperative exam.
Speak.
The second patient experienced vomiting and lead Inter premium pressure represented 12 days after the procedure.
Following admissions of the hospital, they seem to stand to have a happy regime. Your card out. Right. Your card out.
Excuse me, I'm sorry. If you don't mind going back in your remarks just a little bit because we were losing you on the audio just a bit. You were fading out so I apologize interrupting you. But if you can go back a little bit to reiterate and just for real clarity. Thank you.
Absolutely. So I apologize. Let me start again. So in mid-July, UNICURR notified the health authorities of serious, unexpected, suspect adverse events related to two subjects in Europe , treated with a higher dose of AM Q1 30 and a single clinical site.
The first patients experienced onset of motor and other spietal symptoms within 12 days after the procedure.
Following admission to the hospital, an MRI was performed that showed an enhanced T2-weighted MRI signal along the tracks of the inclusions and in the striatum and in the caudate consistent with edema or saline in the brain.
Treating to steroids was initiated and tapered to a file dose 10 days later.
The subject is not fully oriented and has a non-full mineral logic exam, but still has subtle deficits in the fluency, memory, and attention relative to its pre-operative state.
The second patient experienced vomiting and raised intracranial pressure that presented 12 days after the procedure.
Following it, this is a possible location to sound to have a happy beginning or a fixed moment. But the MRI did not show any of these to the G9's strides and all long retractive inclusions. A lumber puncture to remove 22% of the individual final fluid and the print data fully resolved. Yes.
Yeah, I'm sorry. You were cutting out again, and I just feel for the benefit of all of those listening into the call. The content of what you're sharing is so important that it may be better to have Matt provide your remark. And then we'll go through your NA session. And then we'll go through your NA session.
Again, I think that that's a matter for everyone listening and thank you. So we'll have Matt pick up from
Okay, yeah, we'll have everybody. So let me start off with the second piece of experience, vomiting and raised interprinial pressure around 12 days after the procedure.
Following admission to the hospital, a patient was found to have papal edema or optic dis swelling, but the MRI did not show any evidence of a d-mode in the stride number along the tracks.
A lumbar puncture to remove 20cc of cerebral spinal fluid with performance and the symptoms will be resolved leading to discharge.
The subject also received prophylactic antibiotic.
A subsequent review of the safety data from the previous treated patients identified a third patient.
who received the higher dose of AMT 130 in March of this year at U.S. State.
This patient had a serious adverse event that was initially deemed by the investigator to be related to the procedure and not AMT-130.
The patient was admitted to the hospital seven days after the procedure with severe headache and vomiting.
The patient was treated with NOG6 and discharged from the hospital, but returns to the hospital two days later with a recurrent headache. This time it treated it to a CFF week from a diagnostic one-board puncture conducted at the prior visit.
The patient was treated with a blood patch, which is a procedure by which blood is injected into the spinal canal to patch a hole through which cerebrospinal fluid is leaking.
The patient was then discharged from the hospital and is now fully recovered.
While the CAT scan taken on day seven did not reveal any abnormalities, an MRI taken on the patient's 14-day follow-up visit showed some edema or swelling in the striatum and the infusion tracts, which were largely resolved by the patient's 30-day follow-up visit.
Upon discussion with the DSMB following the events observed in the European study,
We have reclassified and reported this patient's events as the Sioux Star and reported to the authorities in the lead July .
And compliance with our study protocol, UNICU are as reported these events of all those incidents that have already been ? ?? ????. So of course I just hope to be Backing News in 10 News Medical day.
reviewed them in detail with our DSMB, and initiated a comprehensive investigation.
While our investigation is not yet complete, we have thus far found no evidence that these events are related to quality of the clinical lots of AMD 130 or the shipping and handling of the drug. There hasn't sound any evidence that they were related to anomalies in former sedable preparation of the surgical enhance.
As part of our investigation, you are also evaluating if there's any evidence that medical history of genetic predisposition may make some patients more susceptible to the information. We're susceptible to the information.
We will share the results of our investigations in a timely manner with regulators.
and with the medical and scientific community reparsable.
As all three events occurred within the first one to two weeks after the procedure, we believe that enhanced patient monitoring during this period has the potential to satisfactorily address any patient risk.
We have developed additional risk mitigation protocols including closer patient monitoring procedures and treatments.
which we are currently discussing with our DSMB.
The DSMB does not view these events as a dose-limiting toxicity. However, we in our DSMB believe it's prudent to temporarily pause additional patient dosing with the higher dose until we complete our safety review and investigation. And I've put the observation and risk mitigation plans in place.
We expect this will occur sometime in early fourth quarter.
It's important to note that the delay does not apply to any future administration of the low dose of AMC-1-3. 3. Thank you, everyone. Thank you.
Those far, no significant adverse events related to AMD 130 have been reported by any of the 12 patients treated with lower dose.
who have now been followed up for up to two years.
The DSRB has allowed us to continue enrolling at the lower dose of AMC130 for patients crossing over from the placebo group in the US study, which is expected to take place in the third quarter.
We're optimistic this matter can be resolved in timely manner and noticing the five remaining patients in the European higher dose cohort to be resumed.
I want you to reiterate, we do not expect that this will have any impact on previously guided data readouts in 2023.
With 36 patients enrolled to data across both clinical trials, we expect that have sufficient data to maintain our timelines for regulatory discussions and decisions regarding potential and organizational pathway. Biologian Organics
We also continue to be very encouraged by the 12-month update we provided in June on the patients in the lower dose cohort of the US study.
These data show neurofilament light chain levels in your baseline and lower than the Huntington protein level suggests of a meaningful target engagement.
We believe this goes as a potential for by benefits to patients suffering from Huntington's disease.
and we look forward to working with the HD community to develop a treatment for the devastating disease.
Now I'd like to open up the call for analyst questions, operator. Thank you.
Thank you sir.
As a reminder, to ask a question, you'll need to press star 1 1 on your phone. We ask that you please limit yourself to one question and one follow-up. And please stand by as we compile the Q&A roster.
One moment.
Our first question will come from
Paul Matisse of Stiko.
Sir, your line is open.
Hey, it's Alex on for Paul. Thanks for taking our question. I just wanted to ask, maybe share these updates with the FDA yet. What is your dialogue ban? And is there any risk to be put place in a clinical hole? Thanks.
Thank you.
Alright, this is Ricardo, can you hear me?
Yep. Okay, good. So, absolutely. So, right after we got these reports from the sites, we shared them with both the NMEA and the FDA, and so far we have heard nothing. So, we're on.
We have not been pleased as a monsoon for all any kind from the whole body of life.
Hey Ricardo.
Yeah, I think your audio is still muffled, but just to repeat it, all of these events have been shared with the appropriate regulatory agencies in accordance with our protocols and regulations, and we have not had any specific dialogue with them or outreach that we received.
All right, thank you.
Thank you.
One moment please for our next question.
question. Welcome from Joe Schwartz of SVD Securities. Your line is open.
Hi, this is Beth on for Joe. Thanks for taking our question. So I know you said that no clear root cause of these serious adverse events has been identified yet, but just curious what your initial hypothesis is on what could be driving it. Is there any sort of reason to believe that it could be associated with a degree of wild type hunting tin protein knockdown? And just the serious adverse events occurred so closely to the administration period. I'm curious if that could be playing any sort of role as well.
Yeah, I think that obviously we need to complete our investigation before we weigh in specifically on a hypothesis. But I will say that the proximity of these events, which have happened within days, the procedure, we just believe that it's probably unlikely that it's mechanism of action related and that it is probably something related to either the immune response or an inflammation associated with the product.
You have three patients who are no longer hospitalized. Two of the three patients have fully recovered. One of the patients has substantially recovered. I think there's some subtle deficits that are continuing to be monitored. And we have been doing the battery of follow-up tests, including neurofilament light. All of that information is going to be shared or is being shared with the data safety monitoring board. And we've imported the comprehensive investigation.
Great, thank you.
Thank you.
One moment please for our next question.
Our next question will come from Devjyad Tatapaya of Guggenheim Partners. Your line is open.
Just a couple of clarifications. What was the volume of administration between the low and the high dose? Is there any difference in the rate of infusion between the two doses?
And the volume, I think, is...
I think it's just the concentration. That is different. I don't know Ricardo if you have changed your audio, but I believe that's the case. And the rate of infusion I think is consistent with the low dose procedure as well.
Got it. Captain, can you hear me? Sorry. Yeah, I can hear you, Ricardo. Okay.
You can hear me so, yeah, so the volume is exactly the same at the load loss and the high dose.
It's basically a total of three mils.
Basically, the total of three mils.
in for both.
And the data transmission is exactly the same.
And did you measure neutralizing antibodies at baseline?
Yes, and none of the patients have neutralizing antibody.
Got it. Thank you so much.
Thank you. And again, one moment please for our next question.
Our next question will come from Joseph Tom of Cowan. Your line is open.
Hey there, good morning and thank you for taking my questions. It seems like the disease course or the response course are a little bit different in the European patients in the US and in that US patient had the CSF issue. So have you ruled out that this is potential position or administration error versus something like AMC 130? And then second, what do you expect to learn? I guess between now and that Q4 is an FD review. Thank you.
So we finished our investigation. It's probably difficult to rule anything out at this juncture. Having said that, there's been no specific evidence that we have found that's directly implicated the procedure or the way that the procedure has been done. And it's not clear if that's something that you will be able to identify. But... but...
But it is true that two of these particular two-source happened that at one clinical site and they were the first two procedures that were performed at that clinical site. So we'll continue to investigate that. But as I said to you know, there's no evidence that supports that thesis right now. Between now and the next data-taking monitoring board meeting, we're going to complete our investigation associated with reviewing all different aspects and we'll continue to investigate that.
and factors that can contribute to the root cause.
and will in addition have some further follow-up associated with.
14 patients in the high dose cohort. I'll just remind everybody that.
We have treated 14 patients in the high-dose cohort, and, you know, a level of those 14 patients have not reported any significant adverse events related to AMD 130 with follow-up up to one year. So all of that information will be compiled and pulled together for the DSMB as part of the review that we expect to have next month. The DSMB is part of the review that we expect to have next month.
Thank you very much.
Thank you. One moment please for our next question.
Our next question shall come from Salveen Richter of Goldman Sachs. You mind it open?
Hey, good morning, Mrs. Ores of the San Frisalve. Thanks for taking our questions. A few from us, so have any more procedures been performed at that same site in the EU, where the first two procedures were performed. And then you intend to message to the street after the SAC review and for two. And then, you know, what are kind of the exact evaluations that are going to be performed during the safety and obligation. And if you can.
with the Data Safety Monitoring Board.
And then third, as I mentioned, you know, there's...
various different factors and analyses that we'll be looking at. One of that we're going to continue to complete our investigation of the critical quality attributes of the product. As I said, there's nothing thus far that suggests that there's any CMC related issues or critical quality attributes.
but we want to finalize that analysis.
We will continue to review the pharmaceutical preparation and shipping and handling associated with the product. Again, there's no evidence that suggests that. There's additional data that will be accrued on follow-up visits. Again, remember that we have 26 patients that have been treated thus far that are doing quarterly follow-up visits. We will continue to review the pharmaceutical preparation and handling associated with the product. Again, there's additional data that will be accrued on follow-up visits. Again, there's additional data that will be accrued on follow-up visits. Again, remember that we have 26 patients that have been treated thus far that are doing quarterly follow-up visits.
In particular, in the high dose code, we're a number of those.
analyses are batched. So we will aggregate that data and review that data with the DSMD and we expect to do that over the course of the next 60 and 90 days.
Thank you. Thank you. I want moment for our next question.
Our next question shall come from Aliana Burrell of UBS. Your line is open.
Hi, this is Sarah on for Ali. Thanks for taking our question. As you're thinking about building out the pipeline beyond hemophilia and Huntington's, how are you thinking about potential business development there? Unless anyone's been studying hemophilia since last month, I'll be continuing my research and getting my
So the pipeline beyond honey and disease, I mean we're always looking at business development. Business development is something that is going to be part of our strategy. I think what we're committed to is being disciplined about business development and making sure that any transaction that we might consider is strategic that we believe can drive value for our shareholders.
So beyond that, it's not something that I can really comment on.
Okay, thanks.
Thank you.
Okay, one moment for the next question.
On the questions, we'll come from Daniel Bro, of Raven James. Your line is open.
Hey guys, this is Alex from Dr. Danielle. If there are any ways it could be related to the duration of the surgery, we're just kind of curious if there's any way that this could be rectified by the planned shortened surgical procedure. And then a quick follow up, several question on the control crossover. Was it ever an option for the patients or for you as a company to provide the low versus high dose for the placebo crossover patients to chose to crossover?
Yes, a question with respect to duration. Again, our investigation is incomplete yet, but I'll just remind. I mean, we've done 26 procedures. I mean, we've done 26 procedures. I mean, we've done 26 procedures.
that have been generally consistent in terms of duration. And this is the first three...
Seasores were events like this that we've seen.
So it's...
You know, our thesis is that it's probably not related to the duration of the procedure, but it's something that we'll continue to look at.
With respect to the crossover, it was an it's difficult to
It will be patients in the first-in-man study where they have the possibility of sham control unless they have the potential to cross over to treatment. The first-in-man study is the sham control of the first-in-man study The first-in-man study is the sham control The first-in-man study is the sham control
So I think that that was always something that I think was an option that was left open. Of course it became something that we have to establish safety.
So I think that now we can offer that and DSMB has evaluated the information and believes that that's something that we should provide to the patients that have the control.
If I could follow up, though, in terms of the crossover, I understand they could cross over, but in terms of, was that always an option of that they could receive the high dose and now that's off the table? Or was that going to be determined after the normal safety and efficacy data?
I don't think there was any specificity about exactly which dose they got. I think that that was something that would be determined based on the information that the DSMP had at the current time.
So the bottom line is there is an option for crossover patients to get the hind oats.
there is an option for crossover patients to get the hindos. So, don't worry.
But it will depend.
Gotcha. Thanks for the call.
Thank you. All right. Any questions?
Our next question shall come from Sammy Cohen of William Blair. Your line is open.
Hi there, thanks for taking my question. Based on the biomarker data from the low-dose cohort and now the two stars in the high-dose cohort, are you guys rethinking your development strategy for AMT130 at all? And in particular, are you reevaluating, possibly expanding the low-dose cohort?
We have not made any decisions yet. It's a little too early for that. I think we want to complete our investigation and have our review with the DSMB. At that point in time, we'll be better informed to weigh in on how we might bring forth the product and how that might impact the dose that we move forward.
Okay, and then are there any changes in the timeline for conducting the procedures with the new surgical procedure?
Well, we wanted to complete dozing as a higher dose cohort. So that was something that we messaged in the due and crawl. That was really what we're focused on. So we're probably not going to be moving forward with the third dose cohort until we complete the enrollment of these remaining five patients. We think, again, this is something that's a decision that we'll be able to make in the next 50 to 90 days. So we think any impact on the third dose cohort will be minimal.
The other part that I'll mention is that again, the third dose cohort, it's not really a dillage cohort, it's a surgical adapted cohort where we're going to be mostly focused on understanding the feasibility and see if you can proceed here.
So we don't think that that impact is going to impact late state development in a material way at this juncture. So we have this juncture. So we have this juncture.
to impact late state development in a material way at this juncture. Great thing.
Thank you. And again, one moment for our next question.
Our next question will come from Robin Knozka and the code Dramino of Tuist. Your line is open.
Hi, this is Alex from Ferrobin. I just wanted to clarify, if the DSMB includes that the SAAs and Serbs were procedure related, would this third dose cohort with a different procedure just qualified to establish a new procedure that might be better, or would you need additional clinical trials? And would you apply that to the low dose cohort if you wanted to expand that trial and carried that forward?
Yeah, I, again, it's going to be difficult to hypothesize or to gesture about what might happen. I would say again that it's probably unlikely that it's... I would say again that it's probably unlikely that it's...
generic procedure related. We haven't seen any significant adverse events related to the M. K. 130 or the procedure in the entire low dose of 12 patients. We have seen the report from the M. K. 130 or the M. K. 130 or the M. K. 130 or the procedure in the entire low dose We have seen the report from the M. K. 130 or the
And there's 11 of the 14, the height of cohort we haven't seen in as well.
It might be something related to the specific procedure.
of that particular patient, but I think it's unlikely that there's some generic issue with the procedure itself given
The safety track record that we have over the last two years.
But any learnings that we get from this to the extent that they're applicable across the board, they certainly will be applied for the benefit of all patients. That would include risk mitigation or closer patient monitoring procedures.
Thank you.
Thank you.
One moment as we get our next question.
Up next we have Luca Isci of RBC Capital Market. Your line is open.
Oh great, thanks so much for taking my question. I noticed this was a couple of bit earlier, but can you just help us understand how adverse events are dichotomized as related to the procedure versus related to the actual drug? Is that a pretty clear code for is this more like a fine line that comes down to clinical judgment? So again, any call there will be great. And then in term of resuming the dose, what are your options here that you're contemplating in order to resolve these should hide those?
In addition to more frequent monitoring, what are the other levers that you can pull, how you think about potentially refining inclusion and exclusion criteria, are you considering maybe putting all patients on stereo for for last Italy? Any additional call there will be great. Thanks so much.
Yeah, so adverse events are really characterized by the investigator. So those events are documented and the specific investigator that is managing that patient really weighs in and attributes that to either the procedure or the product or unrelated to the best of their ability.
So it's really a judgment call that is really clinician directed.
It's also something that we would review with our data safety monitoring board and to take into opinion their evaluation and recommendations as well.
And then just remind me your second question. Yeah, what are your options going forward here to kind of solve the issues? You obviously talked about more frequent monitoring, but I was wondering if there's any other components here that you're contemplating.
Yeah, no, it's really, I mean, just as a reminder, all of these really happened in the first one to two weeks.
Right, so these are things that we can check in with patients on a daily basis. Before they're discharged from the hospital, we can do specific evaluations to make sure that they are meeting certain standards for discharge. There's the possibility that we can do, if there's anything abnormal or unusual, we can do additional MRI procedure.
And then if there are any symptoms of a diva or inflammation, we can look more rapidly, bring them in for, you know, and then press your steroid treatment. And then you press your steroid treatment. And then you press your steroid treatment.
So that's really what it is that we're focused on. If there's any reactions that happen quickly, we can identify those reactions and then get the patient treated.
And with that, we think we can...
substantially mitigate any risk to the patient.
You perhaps will thank for much.
Thank you. One moment please for our next question. Our next question will come from Christian Kluska of Cantor Fitzgerald. Your line is open.
Great everyone, good morning. Just to switch gears on, hema filio B, is there any color behind the decision that the review couldn't be done in Europe on an accelerated basis? And when in the US and Europe , do you and CSL bearing expect approval decisions to take place at this time? And then can you remind us of the near term milestone payment you are eligible for? Thank you.
Tomorrow I procedure and then if there are.
Any symptoms of.
Of a deal where inflammation, we can much more rapidly bring them in for some pressure steroid treatment. So that's really what it is that we're focused on.
Yeah, sure.
With respect to the interactions with EMA, that is being handled completely by CSL. What we have heard from CSL is that there was no specific issue that was identified in the review that led to the switching from accelerated to standard review, that this was simply just a bandwidth issue and for EMA, and as a result, that they needed some additional time for the review. But there was nothing specific. But there was nothing specific. But there was nothing specific.
Theres any reactions that happened quickly we can identify those reactions and then get the patient treated.
And with that we think we can.
Stanford, we mitigate any risk to the patients.
Super helpful. Thanks, so much.
Thank you.
One moment please for our next question.
Okay.
Next question will come from Christian <unk> of Cantor Fitzgerald. Your line is open.
When respect to the timing of approval, I think that again is something that CSL will have to provide. I think what we said is that we would now expect approval probably early next year, early in the first quarter of next year, that's based on the standard review. So that's what we would have.
Hey, everyone. Good morning, just to switch gears on hemophilia B is there any color behind the decision that the review can it be done in Europe on an accelerated basis.
When in the U S and Europe UN seasonal bearing expect approval decision to take place at this time and then can you remind us of the near term milestone payments you're eligible for thank you.
And then with respect to milestones, we have stated that there's $175 million that would be received upon commercial launch of the product in the United States and Europe .
Yes sure so.
With respect to that.
Interactions with EMA that is being handled completely by DSL, what we've what we have heard from Tfl is that there was no specific issue that was identified in the review.
And then there are additional milestones that are commercial related to certain net sales thresholds, as well as the product of the United States and Europe .
That led to the switching from accelerated to standard review that this was simply just a bandwidth issue.
And then there are additional milestones that are commercial related to certain net sales thresholds, as well as commercial launch in Japan.
And for for EMA and as a result that they needed. Some additional time for review, but there was nothing specific.
With respect to the timing of approval I think that again, it's something that CSL will have to provide I think what we've said is that.
Thank you.
Thank you.
One more for our next question.
We would now expect approval probably early next year.
Early in the first quarter of next year, that's based on the standard review.
Our next question will come from Duda Fromer of Credit Suisse. Your line is open. Yeah, thanks for taking the question. First, maybe you're following up on kind of the hypothesis that CMC are quality control and in handling of products could have potentially been an issue here. Would those have been the same for the EU and the US product would those have come from the same batch or potentially been handled the same way just by being conducted at different sites?
So that's that's what we would.
And then with respect to milestones.
We have stated that there is a $175 million.
That would be received upon commercial launch of the product in the United States and Europe .
And then there are additional milestones that are commercial related to certain net sales thresholds as well launch of the product in the United States and Europe .
Yes, precisely the analysis that we do, right, is that we just look to see if there's any lots and lots of differences in the critical quality attributes.
And then there are additional milestones that are commercial related to certain net sales thresholds as well as <unk>.
And based on that assessment, we do not believe that this is likely to be anything related to CMC.
Commercial launch in Japan.
Okay, and then just, you know, if we get in a situation where, you know, there was a dose limiting toxicity here, kind of, kind of, can you assess kind of how that would affect your confidence in the program if you were maybe only going forward with the load dose, maybe just remind us of your preclinical work and how the load dose could potentially confer a functional benefit. If, you know, we are going to be in a functional study at some point, ideally with at least the load dose.
Thank you.
Thank you.
Next question.
Our next question will come from Judah Frommer with credit Suisse. Your line is open.
Hi, Thanks for taking the question.
First maybe just following up on on kind of the hypothesis that CMC or quality control and handling of products could have potentially been an issue here with those have been the same for the EU and the U S product, where those have come from the same batch or potentially been handled the same way despite being.
Yeah, this doesn't impact my confidence in the program, honestly. I mean, the purpose of a dose.
Just finding study is exactly that to find the right dose.
Conducted at different sites.
Yeah.
We are really pleased with the data that we presented thus far from the first ten patients in the US study. We haven't seen any significant adverse events related to the low dose. We saw suppression of mutant protein in the cerebral spinal fluid that quite frankly was more meaningful than what we saw in the preclinical work. So that was over 50% suppression of mutant protein.
Yes.
Actually in the analysis that we do right and so we just look to see if theres any lots and lots of differences in any of the critical quality attributes.
And based on that assessment, we do not believe that there that this is.
Lightly to be anything related to CMC.
Okay.
And then just if we did end up in a situation, where there was a dose limiting toxicity here.
at 12 months, we've seen neurofilament light levels near baseline. So, we're really encouraged by that data. And even if there is a dose limiting toxicity, we'll obviously continue to follow patients that receive the low dose cohort, but we continue to be really pleased and encourage about that dose.
Can you assess kind of.
How that would affect your confidence in the program. If you were maybe only going forward with.
The low dose, maybe just remind us of your preclinical work and have a low dose could potentially confer functional benefit.
We are going to be in a functional study at some point ideally with at least the logos.
Yeah, just doesn't impact my confidence in the program honestly.
Thanks.
Thank you. Thank you.
I mean, the purpose of a dose.
Just finding study is exactly that to find the right dose.
And again, one moment for our next question.
We are really pleased with the data that we presented thus far from the first 10 patients in the U S study, we haven't seen any significant adverse events.
Our next question shall come from Yanan Zou of Wells Fargo. Your line is open.
Thanks for taking our questions. So I think in 2021, FDA convened an advisory committee meeting reviewing AAV gene therapy safety, and one of the topics was MRI abnormalities arising in patients who received intraparenchymal injections of AAV. So I'm wondering, you know, based on those, the information presented there...
Related to the low dose we saw suppression of mutant protein industry in the spinal fluid that quite frankly was more meaningful than what we saw.
And the preclinical work so that was over 50% suppression mutant protein.
At 12 months, we've seen neuro filament light levels near baseline.
So we're really encouraged by that by that data.
Even if there is a dose limiting toxicity.
How do you feel the cases you have been seeing, similar or different from those cases, for example, in terms of timing of onset and whether patients are symptomatic or not? Thank you. Yeah, I'm preparing to compare it against what was presented at the panel, but...
We will have to obviously continue to follow patients.
That have received the low dose cohort, but we continue to be really pleased and encouraged about that dose.
Thanks.
Thank you.
And again, we'll move on next question.
Our next question will come from Yun Zhong of Wells Fargo. Your line is open.
But, you know, as I say, these are pretty acute cases. All the patients have been treated, have either fully recovered or substantially recovered. The most important thing is obviously the clinical prognosis for these patients. We're still learning a lot around what we're actually seeing in the MRI, what is this related to. In some cases, is the drug working and it's not a bad thing.
Hi, Thanks for taking our questions.
So I think in 2021 FDA.
Convened.
Okay Advisory Committee meeting reviewing our AAV gene therapy safety and one of the topics was.
Roy abnormalities are rising in patients who received intra parenchymal injections of AAV.
So I'm wondering based on those.
But what is the best thing, obviously, if there's any safety implications for the patients, but the most important thing is that these patients can be treated. They can be monitored work closely and that they can recover. So that's really the most important thing that we're focused on, and so we're pleased in that regard. Thank you.
The information presented there.
So it is a bad thing, obviously, if there's any safety implications for the patients. But the most important thing is that these patients can be treated. They can be monitored work closely and that they can recover. So that's really the most important thing that we're focused on and so we're pleased in that regard. But if I may have a quick follow-up.
How do you feel your the cases that you have been seeing theme.
Similar or different from those cases for example in terms of timing of onset and whether patients are symptomatic or not thank you.
Yes, it's hard for me to compare it against what was presented at the panel but.
In the low-dose patients, have any of them been followed up with MRI, and whether are there any MRI findings in those patients? Of course, those will be non-symptomatic. Yeah, every single patient is followed up with an MRI. Those MRIs happen, I believe, quarterly.
But as I say.
These are pretty acute cases.
All the patients have been has been treated have either fully recovered or substantially recovered.
The most important thing is obviously the.
The clinical prognosis for these patients.
And, you know, I think what we reported at the time that we presented this data on the low-dose core patient is that there were no structural abnormalities on the MRI, but a full safety update will be provided when we present comprehensive data next year. We will only present comprehensive data next year.
Still learning a lot around what we're actually seeing in the MRI what is this related to.
In some cases is this drug working and it's not a bad thing but.
It is the best thing obviously, if there is any safety implications for the patients.
But the most important thing is that these patients can be treated they can be monitored more closely and.
Got it. Thank you very much.
Thank you. One moment for our next question.
And that.
They can recover right. So that's really the most important thing that we're focused on and so we're pleased in that regard.
Our next question will come from Young Zhang of BTIG. Your line is open.
Got it.
If I may have a quick follow up in the low dose patients.
Hi, I think very much for taking a question. And this is a follow up question on the load dose. Given the data like you said, Matt, expect exceeded your expectation. So I wonder how much effort and the time would you like to spend to figure out the high dose before deciding maybe load dose is the optimal dose to move forward. Thank you.
Have any of them been followed up with MRI and whether are there any MRI findings in those patient of course, those will be no symptomatic.
Yes.
The patient is followed up with an MRI.
Those MRI has happened I believe quarterly.
Yeah, I mean, you know, I'll remind everybody. So, you know, we have...
And.
I think what we reported at the time that we presented this data on the low dose cohort of patients is that there were no structural.
14 patients that have received treatment with the high dose.
Abnormalities on the MRI, but a full safety update will be provided when we present comprehensive data next year.
So, and there's remaining five patients in the European study that have not been treated thus far. And that's been the first two DOHS cohorts.
Got it thank you very much.
So I think we can follow the 14 patients that we've treated and have very robust data to I think evaluate the high dose and the low dose next year. So I'm not, I'm not totally concerned that we'll be spending a lot of energy or a lot of time evaluating this. I think to do you think that the DSMB continues to have problems.
Okay.
Thank you.
One moment for our next question.
Our next question will come from Yun Zhong of <unk>. Your line is open.
Hi.
So very much for taking my question and this is a follow up question on the low dose.
Given the data like you said met exceeded your expectations. So I wonder how much effort and time would you like to spend to figure out the higher dose before deciding maybe low dose is the optimal dose to move forward. Thank you.
When we do our safety review, we always have the possibility of contemplating treating those remaining patients with a low dose.
But as I said, we'll cross-epverage when we have that discussion and provide an update after that time.
Yes.
I'll remind everybody so.
We have.
14 patients that have received treatment with the high dose.
And there is a remaining five patients in the European study.
Thank you.
One moment please for the next question.
That have not been treated thus far this isn't the first two dose cohorts.
So I.
I mean, we can follow the 14 patients that we've treated and have very robust data to I think evaluate.
And we have a follow-up question from the devjit of Guggenheim Partners. You're not in the open.
Hey, thanks for that. So a clarification, is the EU segment enrolling subjects with similar disease stage and correct vitamin volume as the United States? Vitamin volume as the United States?
The high notes from the low dose next year so.
I'm not terribly concerned that we'll be spending a lot of energy a lot of time.
Yes!
Valuation of this I think to the extent that.
Got it. And do you have a sense where the NFL lines up in these patients? I know it's early, but given the US patient to have a SAE back in March, do you have a sense of where NFL lines up in these patients with SAEs versus those who have not experienced this? See you next time.
The SMB continues to have pause when we do our safety review, we always have the possibility of contemplating treating those remaining patients with a low dose.
But as I said, well, we'll cross that bridge.
We have that discussion and provide an update after that time.
Yeah, what I say is that we're not providing any of that specific details.
But the information is being reviewed by the Data Safety Monitoring Board.
And thank you.
One moment please for the next question.
Thank you.
Thank you. One moment please.
And we have a follow up question from <unk>.
<unk> partners your line is open.
Okay. Thanks for that.
And we have a follow-up from Luca of RBC Capital Market. Your line is open.
The clarification is the EU segment enrolling subjects with similar disease stage and go to <unk>.
<unk> volume as the United States.
Oh great, I'll be quick. Just going back on the Hemophilia B delay in Europe . Is this related to the companion diagnostic or how should you think about that? Thanks so much.
Yes.
Got it and do you have a sense, where the NFL lines up in these patients I know it's early.
No, I've had that before. There's no specific issue that was cited by the European authorities related to this at all. So this is not like there's a specific issue that they've identified and feel they need more time to review that specific issue. It's just the bandwidth.
But.
Given the U S patients who had.
Back in March.
Do you have a sense of where NFL lines up in these patients with SaaS versus those who have not experienced in NSE.
Yes.
What I'll say is that we're not providing any specific details.
issue with the agency that they feel they just need more time to complete the review.
issue with the agency that they feel they just need more time to complete the review. Thanks so much.
But but the information is being reviewed by 580 safety monitoring board.
Better thank you.
Thank you.
Thank you.
And I'm seeing no further questions in the queue. I would now like to turn the conference back to Matt Cavendish for closing remarks.
One moment please.
Yes.
Thank you, operator. In summary, we remain confident in the potential of AMG-130 and Huntington disease. Continue to be very encouraged by the data we recently presented. We hope to resume higher dose enrollment with minimal delay. And do not expect any impact to the previously guided data readout for next year. Thank you.
And we have a follow up from Luca RBC capital market. Your line is open.
Great I'll be quick just circling back on the hemophilia B a delay in Europe .
Is this related to the companion diagnostic or how should we think about that thanks. So much.
No.
As mentioned earlier, patient safety will always be our top priority, and I'd like to express my gratitude to patients, their families, and physicians who have been part of our clinical trial to date for their trust in us and their dedication to pursuing new treatment options.
I would add to that that before there is there is no specific issue that was cited by.
By the European authorities related to this at all so this is not like there is a specific issue that we've identified and feel they need more time to review that specific issue with just a bandwidth.
Thank you for attending this call and we look forward to providing further updates as soon as possible. Thank you.
The issue with the agency that they feel they just need more time to complete the review.
Thank you. This concludes today's conference call. Thank you all for participating. You may now disconess and have a pleasant day.
Thanks, so much okay.
Thank you.
And I'm seeing no further questions in the queue I would now like to turn the conference back to Matt Kevin to Sal for closing remarks.
Thank you operator in summary, we remain confident in the potential of AMG 130 in Huntington's disease continue to be very encouraged by the data. We recently presented we hope to resume higher dose enrollment with minimal delay.
Any impact of the previously guided data Readouts for next year.
As mentioned earlier patient safety will always be our top priority and I'd like to express my gratitude for patients their families and physicians, who have been part of our clinical trials of <unk> for their trust in us and their dedication to pursue revenue treatment options. Thank.
Thank you for attending this call and we look forward to providing further update as soon as possible. Thank you.
Thank you. This concludes today's conference call. Thank you all for participating you may now disconnect and have a pleasant day.
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