Q3 2021 Altimmune Inc Earnings Call
Yeah.
Operator: Good day, ladies and gentlemen, and welcome to the Autumune Inc. Q3 earnings conference call. At this time, our participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. If either you require operator assistance once more, please press Star, then Zero, or your touchtone telephone. As a reminder, this call may be recorded. I would now like to introduce your host for today's conference call, Will Brown, Chief Financial Officer of Autumnune. Will, you may begin.
Good day, ladies and gentlemen, and welcome to the afternoon, Inc. Q3 earnings Conference call. At this time all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time.
And once you require operator assistance. Please press Star then zero on your Touchtone telephone.
As a reminder, this call maybe recorded.
Now I'd like to introduce your host for today's conference call will Brown Chief Financial Officer of afternoon will you may begin.
William Wood: Thank you, operator, and good morning, everyone. Thank you for participating in Altamune's third quarter 2021 earnings conference call. Members of the Altamune team joining me on the call today are Vipengarg, our chief executive officer; Scott Roberts, our chief scientific officer; and Scott Harris, our chief medical officer. Following the prepared remarks, we will hold a question-and-answer session. A press release with our third quarter 2021 financial results was issued last night and can be found in the Investor Relations section of the company's website.
Thank you operator, and good morning, everyone. Thank you for participating and ultimate <unk> third quarter 2021 earnings conference call.
Members of the ultimate team joining me on the call today are vipin Garg, our Chief Executive Officer.
Scot Roberts, our Chief Scientific Officer, and Scott Harris, our Chief Medical Officer.
Following the prepared remarks, we will hold a question and answer session. A press release with our third quarter 2021 financial results was issued last night and can be found on the IR section of the company's website.
William Wood: Before we begin, I would like to remind everyone that remarks about future expectations, plans, and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimun cautions that these forward-looking statements are subject to risk and uncertainties that could cause actual results to differ materially from those indicated, including those related to COVID-19 and its impact on our business operations, clinical trials, and results of operations.
Before we begin I would like to remind everyone that remarks about future expectations plans and prospects constitute forward looking statements for purposes of Safe Harbor provisions under the private Securities Litigation Reform Act of 1095.
<unk> cautions that these forward looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated including those related to COVID-19, and its impact on our business operations clinical trials and results of operations.
William Wood: For discussion of some of the risks and factors that could affect the company's future results, please see the risk factors and other cautionary statements contained in the company's filings with the SEC. I would also direct you to read the forward-looking statement disclaimer in our earnings press release issued yesterday and now available on our website. Any statements made on this conference call speak only as of today's date, Wednesday, November 10th, 2021, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. As a reminder, this conference call is being recorded and will be available for audio replay on Altamine's website. With that, I will now turn the call over to Dr. Vipengarde, Chief Executive Officer of Altamian.
For a discussion of some of the risks and factors that could affect the company's future results. Please see the risk factors and other cautionary statements contained in the company's filings with the SEC.
I would also direct you to read the forward looking statement disclaimer in our earnings press release issued yesterday and now available on our website.
Any statements made on this conference call speak only as of today's date Wednesday November the 10th 2021, and the company does not undertake any obligation to update any of these forward looking statements to reflect events or circumstances that occur on or after today's date.
As a reminder, this conference call is being recorded and will be available for audio replay on our website with that I will now turn the call over to Dr. Vipin Garg, Chief Executive officer of Alchemy.
Thank you Bill and good morning, everyone.
We appreciate you joining us today for a discussion of our third quarter 2021 financial results and business update.
The third quarter has been a very productive time for the company as we reached several key milestones in the development stuff when we do tight.
We delivered on the 12 week phase one study results.
Vipin Garg: Thank you, Bill, and good morning, everyone. We appreciate you joining us today for a discussion of our third quarter 2021 financial results and business updates. The third quarter has been a very productive time for the company as we reached several key milestones in the development of PAMV Dutide. First, we delivered on the 12-week phase-1 study results in our trial in overweight and obese subjects. The data we generated exceeded our expectations, as we demonstrated double-digit weight loss in the 1.8 milligram arm, with favorable effects observed on blood pressure, serum lipids, and other measures.
Our trial in overweight and obese subjects.
The data we generated exceeded our expectations as we demonstrated double digit weight loss in the one eight milligram.
With favorable effects observed on blood pressure.
Lipids and other measures.
We believe we achieved a high watermark in weight loss given that dose titration whatnot was not used and there were no modifications to diet or physical activity.
Most other programs in this class of drugs must use dose titration.
That is gradually increase dose to maintain tolerability.
Those titration presents considerable challenges challenges for patient satisfaction and compliance and logistical challenges for time constrained primary care physicians, Josh with prescribing. These these therapies.
So it's highly encouraging that with straight dosing, we saw primarily mild Gi side effects with no study discontinuation due to adverse events.
The next key milestone will be met was the acceptance of our U S. Nash I N D for Pam we do died and the initiation of a 12 week phase one b naphtha deep clinical trial to explore them, we'd do tights effect on liver fat in this in the Nashville depopulation.
Vipin Garg: We believe we achieved a high watermark in weight loss, given that dose titration was not used, and there were no modifications to diet or physical activity. Most other programs in this class of drugs must use dose titration, that is, gradually increased doses to maintain tolerability. However, dose titration presents considerable challenges for patient satisfaction and compliance, and logistical challenges for time-constrained primary care physicians charged with prescribing these therapy.
We are highly encouraged at the prospects of this trial as we announced this morning. The results from an exploratory analysis that all of the patients with hepatic steatosis or fatty liver.
In the phase one trial that received one eight milligram.
Our two four milligram of <unk> died expedience reduction in liver fat to undetectable levels. After only six weeks of treatment.
These findings speak to the potency of <unk> tied both to induce weight loss.
And quickly move fat out of the liver.
Vipin Garg: So it's highly encouraging that with straight dosing, we saw primarily mild GI side effects, with no study discontinuations due to adverse events. The next key milestone we met was the acceptance of our U.S. Nash IND for pambidutide and the initiation of a 12-week phase 1B NAPLD clinical trial to explore Pembidutide's effect on liver fat in the NFLD population. We're highly encouraged by the prospects of this trial, as we announced this morning, the results from exploratory analysis that all of the patients with hepatic steatosis or fatty liver in the phase one trial that received 1.8 milligrams or 2.4 milligrams of pembidutide experienced a reduction in liver fat to undetectable levels after only six weeks of treatment.
We look forward with great anticipation to the results of the 12 week phase one b <unk> data, which are expected in the first half of next year.
Looking to the future we are diligently working to submit an IND for <unk> in obesity.
To enable a 48 week phase II trial, the study weight loss in obese subjects.
This is an important program for the company as patients with obesity are grossly underserved.
There is a tremendous market opportunity for effective therapies.
That safely induce meaningful weight loss and should future data continued to reflect our recent experience.
We believe that when we do died could be a highly effective tool to address the obesity epidemic.
Finally, we continue to execute on our phase II trial of Hep D cell in chronic hepatitis b with.
With clinical trial sites enrolling patients across North America and Europe.
We expect top line data from this study in the second half of next year.
And look forward to potentially exploring combination therapies.
Hep T cell with direct acting anti virals.
I am pleased that we have developed a pipeline that seeks to address such high value and significantly underserved indications as obesity Nash and chronic hepatitis b.
Our company's value has tremendous upside with these assets.
And we look forward to advancing our programs through the clinic.
With that I will now turn the call over to Scott Harris to discuss our data and clinical plans Scott.
Vipin Garg: These findings speak to the potency of Pambidutide, both to induce weight loss and to quickly move fat out of the liver. We look forward with great anticipation to the results of the 12-week phase 1B NFLD data, which are expected in the first half of next year. Looking to the future, we are diligently working to submit an IND for Pambidutide in obesity to enable a 48-week phase-2 trial to study weight loss in obese subjects.
Thank you vipin and good morning, everyone.
First let me quickly recap our 12 week phase one.
Placebo controlled single single.
And multiple sending dose study of <unk> <unk>.
Study was conducted in Australia under a clinical trial application and enrolled otherwise healthy overweight and obese volunteers.
The SSD portion of the study enrolled 36 subjects in the <unk>.
MLG portion of all three cohorts at doses of 1218, and two four milligrams randomized 401 to drug or placebo weekly for 12 weeks.
Vipin Garg: This is an important program for the company as patients with obesity are grossly underserved. They have a tremendous market opportunity for effective therapies that safely induce meaningful weight loss, and should future data continue to reflect our recent experience, we believe that PAMVutide could be a highly effective tool to address obesity and related damage. Finally, we continue to execute on our phase two trial of hepticell in chronic hepatitis B, with clinical trial sites and rolling patients across North America and Europe.
The study did not employed dose titration.
Subjects, receiving the one eight milligram weekly dose achieved an absolute mean weight loss of 10, 3%.
Weeks of treatment with <unk>.
With a similar degree of weight loss of 9.0% at the two four milligram dose and four 9% at the one two milligram dose.
<unk> was well tolerated even in the absence of dose titration with no adverse events, leading to discontinuation and.
And predominantly mild adverse events.
Favorable trends were observed in secondary measures, including a 28% decrease in total and LDL cholesterol and a 38% decrease in triglycerides at the one eight milligram dose.
Mark I believe these changes occurred in only 12 weeks.
Glucose homeostasis as assessed by fasting plasma glucose and hemoglobin <unk> C was maintained and there was an improvement of insulin sensitivity.
Vipin Garg: We expect upline data from this study in the second half of next year and look forward to potentially exploring combination therapies of hefty cell with direct acting antiviral. I am pleased that we have developed a pipeline that seeks to address such high value and significantly underserved indications as obesity, Nash, and chronic hepatitis. Our company's value has tremendous upside with these assets, and we look forward to advancing our programs through the clinic. With that, I will now turn the call over to Scott Harris to discuss our data and clinical plans. Thank you, Viv.
First by the Homa IR.
Systolic and diastolic blood pressures also decreased in the absence of significant increases of heart rate.
We've also had the opportunity to perform an exploratory analysis of the MRI PFF data on liver fat content in the subset of subjects through the initial six weeks of treatment.
While the study enrollment criteria did not pre specify a minimum liver fat content and did enroll a number of subjects with <unk> hepatic steatosis or fatty liver.
Find as the liver fat content of greater than or equal to 5%.
To enable an early assessment of the effects of Covid do Todd on liver fat content.
Five subjects had baselines hepatic steatosis.
And received <unk> at one eight milligrams or two four milligrams and in each of these subjects.
Liver fat fell to undetected bull levels with only six weeks of treatment.
Scott Harris: Thank you, Vipin, and good morning, everyone. First, let me quickly recap our 12-week, Phase 1, placebo-controlled single and multiple acinidose study of penvedutide. The study was conducted in Australia under a clinical trial application and enrolled otherwise healthy overweight and obese volunteers. The SAD portion of the study enrolled 36 subjects, and the MAD portion enrolled three cohorts at doses of 1.2, 1.8, and 2.4 milligrams randomized 4 to 1 to drug or placebo weekly for 12 weeks.
Declining from levels as high as 19, 5%.
This represents a greater than 90% reduction in liver fat content.
While the subject numbers are small and the data is early the reductions in liver fat are amongst the largest seen in clinical trials to date.
As Vipin mentioned these data have increased our excitement for the 12 week phase <unk> study of subjects with nonalcoholic fatty liver disease or <unk> currently enrolling in the United States the.
<unk> expense the enrollment criteria used in the first in human study in Australia to include diabetic and older subjects.
We are optimistic that the reduction in liver fat content in the planned 12 week Napa <unk> study may parallel the impressive observations that we have already observed to date.
In clinical trials performed by other sponsors we see that high levels of liver fat reduction.
Scott Harris: Although the study did not employ dose titration, subjects receiving the 1.8 milligram weekly dose achieved an absolute mean weight loss of 10.3% at 12 weeks of treatment with Penvedutide, with a similar degree of weight loss of 9.0% at the 2.4 milligram dose and 4.9% at the 1.2 milligram dose. Penvedutide was well tolerated, even in the absence of dose titration, with no adverse events leading Favorable trends were observed in secondary measures, including a 28% decrease in total LDL cholesterol and a 38% decrease in triglycerides at the 1.8 milligram dose.
I've been highly predictive of Nash resolution and fibrosis improvement.
As previously announced we plan to file a second IND for <unk> in obesity that will create a parallel development path to our ongoing Nash development.
This study will be 48 weeks in duration and we expect to have topline data from a 24 week interim analysis in the fourth quarter of 2022 or the first quarter of 2023.
We are also considering a 12 week extension to the Afore mentioned phase <unk> <unk> study that will provide 24 week data on weight loss lipids and blood pressure control towards the middle of 2022.
In summary, dotard double digit levels of weight loss in 12 weeks.
Difficult reductions in liver fat content.
In the absence of the need for dose titration, all build our enthusiasm for the <unk> program.
And we look forward to sharing data from our ongoing trials in the near future.
I will now hand, the call over to will brown to give an update on our third quarter financial results.
Thank you Scott.
I will now provide a brief update on <unk> third quarter 2021 financial results more comprehensive information can be found in our Form 10-Q filed with the SEC last night.
Ultimately ended the third quarter of 'twenty, one with approximately $200 million of cash cash equivalents and short term investments representing a cash burn of approximately $18 million during the quarter. We continue to have sufficient cash to operate through 2023.
Scott Harris: Remarkably, these changes occurred in only 12 weeks. Glucose homeostasis as assessed by plasma glucose and hemoglobin A1C was maintained, and there was an improvement of insulin sensitivity as assessed by the Homa IR. Sistolic and diastolic blood pressures also decreased in the absence of significant increases in heart rate.
Turning to the income statement revenue in the third quarter was 158000 compared to $2 9 million last year.
<unk> revenue during the periods was primarily due to a decrease in revenue attributable to the T Covid program.
During the comparable period in 2020, we were performing a lot of activities in the phase one two trial of <unk> T. Covid, which was completed earlier. This year. We are currently collecting the related accounts receivable as the contract was completed during October.
Scott Harris: We've also had the opportunity to perform an exploratory analysis of the MRI PDFF data on liver fat content in the subset of subjects through the initial six weeks of treatment. While the study enrollment criteria did not prespecify a minimum liver fat content and did enroll a number of subjects with hepatic deatosis or fatty liver, defined as a liver fat content of greater than or equal to 5%, to enable an early assessment of the effects of penvedututide on liver fat content.
Research and development expenses were $29 2 million in the third quarter compared to $17 million in 2020.
The increase in R&D expense was primarily the result of add COVID-19 related development costs, including the expensing of payments made to <unk> for the construction of a manufacturing suite we continue.
To evaluate our strategic options with respect to that space.
The increases were offset by a decrease in the value of contingent consideration related to changes in the fair value of contingent consideration liability connected with the acquisition and development of <unk>.
As a reminder, we will have one last development milestone upon the dosing of the first patient in our phase two trial attempted to tad.
Scott Harris: Five subjects had baseline hepatic stiotosis and received pembadutide at 1.8 milligrams or 2.4 milligrams, and in each of these subjects, Liver Fat fell to undetectable levels with only six weeks of treatment, declining from levels as high as 19.5%. This represents a greater than 90% reduction in liver fat content.
This milestone is payable in shares of our stock and we estimate about 850000 shares when we meet that milestone.
General and administrative expenses remained consistent between the periods at $4 2 million in both the third quarter of 2021 and 2020.
Net loss for the three months ended September 32021 was $33 5 million or <unk> 81.
Net loss per share compared to $17 8 million or 54% net loss per share.
Scott Harris: While the subject numbers are small and the data is early, the reductions in liver fat are among the largest seen in clinical trials to date. As Vipa mentioned, these data have increased our excitement for the 12-week phase 1B study of subjects with non-alcoholic fatty liver disease or NAPLD currently enrolling in the United States. The Nathal D study expands the enrollment criteria used in the first human study in Australia to include diabetic and older subjects.
During 2020 the difference in the net loss is primarily attributable to the higher research and development expenses and a lower contract revenue.
I will now turn it back over to <unk> for his closing remarks.
Operator that concludes our formal remarks, and we would like to open the lines to take questions could you. Please instruct the audience on the Q&A procedure.
So ask a question you will need to press Star then the number one on your telephone keypad to withdraw your question press the pound key please standby, while we compile the Q&A roster.
Your first question comes from the line of Seamus Fernandez with Guggenheim.
Scott Harris: We are optimistic that the reduction in liver fat content in the Plan 12-week Napal D study may parallel the impressive observations that we have already observed to date. In clinical trials performed by other sponsors, we see that high levels of liver fat reduction have been highly predictive of Nash resolution and fibrosis improvement. As previously announced, we plan to file a second I&D for Pemvedutide and obesity that will create a parallel development path to our ongoing Nash development.
Yes.
Hey, Thanks for the question so.
Got it.
The first question really is what additional color can you provide us on these five patients.
The <unk>.
Uh huh.
Directional changes there.
Anything with regard to the.
The liver fat comparisons as we actually have looked at.
Other drugs in the Nash space, the FTF 21 class.
Appears to have rapid liberty fatty as well, which I think only the absolute best number matches up to what you guys are showing in these five patients. How confident are you that this is going to expand to the broader.
Scott Harris: This study will be 48 weeks in duration, and we expect to have top-line data from a 24-week interim analysis in the fourth quarter of 2022 or the first quarter of 2023. We are also considering a 12-week extension to the aforementioned Phase 1B NAPFOD study that would provide 24-week data on weight loss, lipids, and blood pressure control in the middle of 2022. In summary, double-digit levels of weight loss in 12 weeks, and significant reductions in liver fat content, in the absence of the need for dose titration, all build our enthusiasm for the PENVU-Type program, and we look forward to sharing data from our ongoing trials in the near future. I will now hand the call over to Will Brown to give an update on our third quarter financial results.
Array of patients and then separately a lot of investor concerns around <unk>, but you guys only had one patient that had an elevated alk <unk>.
A similar type patients and its own clinical study.
Maybe we can talk a little bit about the potential non.
Drug related <unk>.
That could be at play here.
Like rapid rapid Liberty fattening.
I guess, which is drug related but is obviously.
It may not be a direct effect of the drug but it may be defatigable liberate itself.
And then separately.
Rapid weight loss.
Which some of our thought leaders also comment Ken have associated.
Liver enzyme elevations that resulted in absolutely no damage whatsoever, and then those ltvs decline over time so.
William Wood: Thank you, Scott. I will now provide a brief update on Altamune's third quarter 2021 financial results. More comprehensive information can be found in our form 10Q filed with the SEC last night. Altamune ended the third quarter of 21 with approximately 200 million in cash, cash equivalents, and short-term investments, representing a cash burn of approximately $18 million during the quarter. We continue to have sufficient cash to operate through 2023. Turning to the income statement, revenue in the third quarter was $158,000 compared to $2.9 million last year. The change in revenue during the periods was primarily due to a decrease in revenue attributable to the T-COVID program.
Love to just kind of get.
A sense of your thoughts.
You continue to compile the data and the data evolve. Thanks.
Yes, Thanks <unk>.
Thanks for the question lots of questions that we'll try to answer them all.
Let me just start out by saying that we are very very encouraged with this data both.
The weight loss data and now the liver fat reduction data.
Yes. These are small numbers and this is early data, but it's very consistent every single subject.
That had baseline liver fat content of 5% and higher reached below the limit of detection on one eight and two four milligram dose. So the two most effective doses. So we'll talk more about it but as you know we're doing a much larger study in <unk> and really to US. This is a window into what we might see.
In that study so the potential of this drug both in obesity and weight loss.
And now in liver fat reduction seems really really good and that's what we're excited about we think we will have a drug here both for obesity not only for obesity, but also for Nash, but with that I'll turn it over to Scott Harris to top to provide you more color on the on these five subjects as well as talk about the Iot.
Vipin Garg: During the comparable period in 2020, we were performing a lot of activities in the Phase 1-2 trial of T-COVID, which was completed earlier this year. We are currently collecting the related accounts receivable as the contract was completed during October. Research and Development expenses were 29.2 million in the third quarter compared to 17 million in 2020. The increase in R&D expenses was primarily the result of AD COVID-related development costs, including the expensing of payments made to Lonza for the construction of a manufacturing suite.
Sure Good morning, Seamus so regarding the <unk> elevations none of these five subjects had any changes in the royalties and as we've said in the past ALC elevations are often sporadic and unexplained in studies, particularly in first in human studies and in fact as you've noted the frequently been ripped.
With other drugs.
We did report on the prior patient with the <unk> abnormalities I would finish that conversation to say that we had many patients in the trial with more dramatic changes in <unk> and also to your question about weight changes in weight as well, who did not experience <unk> abnormalities.
<unk> Ah subject dropped as liver fat content from 19, 5%.
To below the limit of detection without an <unk> elevation.
So we don't think that the data currently supports that hypothesis, but obviously more information as needed.
Regarding the comparison to other drugs.
It has to be emphasized the reduction of the <unk> to below the limit of detection is.
Vipin Garg: We continue to evaluate our strategic options with respect to that space. The increases were offset by a decrease in the value of contingent consideration related to changes in the fair value of contingent consideration liability connected with the acquisition and development of PINVAD. As a reminder, we will owe one last development milestone upon the dosing of the first patient in a phase two trial at Pimbedutides. This milestone is payable in shares of our stock, and we estimate that we will have about 850,000 shares when we meet that milestone.
Is unchartered territory.
Companies have not reported this in the past.
You've achieved a degree of liver fat reduction that has not been realized by other drug development programs, where the goal is merely to normalize the liver fat content of 5% or less.
The head of the imaging laboratory that perform the MLR IPD assess analysis, who has very extensive experience in these assessments.
<unk> says that the observed reduction in liver fat was among the largest he had seen so far if not the largest.
So I.
I would emphasize that while the study was small.
Im exploratory.
The pattern that we've seen.
It's a level of reduction in liver fat that has not been observed with previous compounds.
Great.
So quite.
Quite rapidly as well.
And maybe just provide a little bit more color on the novelty study.
Vipin Garg: General and administrative expenses remain consistent between the periods at 4.2 million in both the third quarter of 2021 and 2020. The net loss for the three months ended September 30th, 2021 was 33.5 million or 81 cents net loss per share compared to 17.8 million or 54 cents net loss per share during 2020. The difference in the net loss is primarily attributable to the higher research and development expenses and the lower contract revenue. I will now turn it back over to Vippen for his closing remarks.
Study can you just help us.
What are the what are the thresholds for enrollments.
As it relates to liver fat content.
And.
I assume for simplicity reasons.
Biopsies are likely not going to be included in this phase one study.
But just wanted to get a little bit more color on the enrollment criteria.
For that study and the pace of enrollment that you anticipate.
As a result of the <unk>.
More.
Maybe restrictive criteria. Thanks.
Thanks for the question Seamus well if anything the enrollment criteria are less restrictive than they were in the phase one study and will include a wide variety of patients now.
The threshold for liver fat and that study is 10% that's the cutoff that's been used by most sponsors.
And as you mentioned that will not be a biopsy. In this study. This is a noninvasive study based on liver fat content.
Operator: Operator, that concludes our formal remarks, and we would like to open the lines to take questions. Could you please instruct the audience on the Q&A procedure? So ask a question; you wouldn't need to suppress it
But I would emphasize that this population will now include older subjects as well as subjects with diabetes and we actually expect the pace of enrollment to be very rapid.
Great well I'll jump back into queue congrats on.
Some really intriguing data.
Operator: So to ask a question, you would need to press star, then the number one on your telephone keypad. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster.
Looking forward to.
The next dataset.
From from your Phase <unk>.
Thank you.
Your next question comes from the line of Es. Meanwhile, Hanmi with Piper Sandler.
Hi team. Thank you so much for taking my question and congrats on the great data that you shared with that.
Seamus Christopher Fernandez: Thanks for the question. So, you know, guys, the first question really is, what additional color can you provide us on these five patients, you know, the ALT's, you know, directional changes there, anything with regard to the liver fat comparisons. As we actually have looked at other drugs in the Nash space, the FDF21 class, you know, appears to have rapid liver defatting as well, which, you know, I think only the absolute best number matches up to what you guys are showing in these five patients.
I have a number of very short questions.
And then I'll just go one by one the first question directly to unit.
What was the average weight loss that was observed in the Si piece really bought.
<unk>.
Accurate actions I'd like to start there.
Right.
The.
Average weight loss that I have for you is at week six I would imagine that.
The numbers that we told would be approximately double that although I don't have that number in front of me and the average weight loss from these subjects was with a range of weight loss was between.
Three one and four 7% so the average the average weight loss was approximately 4%.
Seamus Christopher Fernandez: How confident are you that this is going to expand to a broader array of patients? And then separately, you know, a lot of investor concerns around ALTs, but you guys only had one patient that had an elevated ALT. Maybe we can talk a little bit about, you know, the potential non-drug-related mechanisms that could be at play here, like rapid liver defatting, you know, which is drug-related but, obviously, may not be a direct effect of the drug, but it may be the defatting of the liver itself. And then separately, you know, rapid weight loss, which some of our thought leaders also comment on, can have associated liver enzyme elevations that result in absolutely no river damage.
Thank you.
Then again again, just one that was at week six so it was <unk> 12.
Thank you second question is was there any other MRI PFS analysis done at an earlier point I'm trying to understand.
We're already at the plateau, 90%, but sort of what the curve looks like in terms of the slow.
If you could just comment on that.
Two more questions.
Thanks, Yes, so the way. The study was conducted there was a baseline MRI <unk> and.
In week six and then week 12, we don't have the week 12 data here so.
So we don't have a slope other than to be able to tell you what happened at baseline and at week six.
Thank you. The next question I think for us and a lot of our clients are just really understand the translation weight loss between overweight population voices and Apple population that you will be enrolling in year one.
So.
When we look at the data from other Phillip one contract.
We noticed is that the presence of being an apple patient does not impact the degree of with Mark, but what does impacted is the presence of diabetes. So I would like you to maybe explain to us.
Vipin Garg: Yeah, thanks, Seamus, thanks for the question. There are lots of questions there, but we'll try to answer them all.
Scott Harris: Let me just start out by saying that we're very, very encouraged by this data, both the weight loss data and now the liver fat reduction data. Yes, these are small numbers, and this is early data, but it's very consistent. Every single subject that had baseline liver fat content of 5% and higher reached below the limit of detection on 1.8 and 2.4 milligram doses, so the two most effective doses. So we'll talk more about it, but as you know, we're doing a much larger study in FLD, and really, to us, this is a window into what we might see in that study.
Should we be expecting weight loss rates that we saw in obese population to be similar to that household population, specifically, but now called non diabetic and then the second thing is what do we know about Gi Tolerability based on historical data when we go from <unk>.
These populations in asphalt.
Thank you for the question, Yes, I mean, so you are correct.
Studies with drugs and other mechanisms.
Have shown approximately a 30% lower weight loss with diabetics. So our prospective plan in this study is to read on weight loss in both the non diabetics in the population and the diabetics and stratify enrollment in that manner. Because it is an important covariate and the amount of weight loss that will be achieved.
Although not in the amount of liver fat reduction.
So that's to your first point.
Regarding the adverse events.
We do not feel that there will be any difference in the adverse event profile going forward because of the inclusion of other patients. Its been said by experts in the field the diabetics actually realized lower adverse events. The non diabetics also recognize that as we go from <unk>.
Scott Harris: So the potential of this drug, both in obesity, in weight loss, and now in liver fat reduction, seems really, really good, and that's what we are excited about. We think we will have a drug here for obesity, not only for obesity, but also for Nash. With that, I'll turn it over to Scott Harris to talk, to provide you with more color on these five subjects as well as talk about the ALT. Good morning.
Just wanted to phase two in general because of the change of the way. The studies are conducted adverse events dropped between phase one where you have intensive monitoring.
<unk> in patients in phase II, So I would say that as we move from the phase one study to the phase <unk> study that we'll actually see no worse than the adverse events that we have if not an improvement.
Yeah.
Thank you team credit clarity I'll jump back in they can.
Your next question comes from the line of Lisa <unk> with Evercore ISI.
Hi, Thanks, most of my questions have been answered, but I guess I'll just kind of.
Scott Harris: Sure. Good morning, Seamus.
Scott Harris: So, regarding the ALT elevations, none of these five subjects had any changes in their ALTs. And as we've said in the past, ALT elevations are often sporadic and unexplained in studies, particularly first in human studies, and, in fact, as you've noted, they've frequently been reported with other drugs.
Breath off.
The last series of questions can you just comment on the effect of age I know these patients more.
<unk>.
Younger than perhaps.
Future studies will be and just wanting to understand.
Stan.
The fact of age on weight loss and also <unk>.
Scott Harris: We did report on the prior patient with ALT abnormalities. I would finish that conversation by saying that we had many patients in the trial with more dramatic changes than MRI PDFF. And also, to your question about weight, changes in weight as well who did not experience ALT abnormalities, including a subject who dropped his liver fat content from 19.5 percent to below the limit of detection without an ALT elevation. So we don't think that the data currently supports that hypothesis, but obviously, more information is needed. Regarding the comparison to other drugs, it has to be emphasized that the reduction of the MRI PDFF to below the limit of detection is uncharted territory, and companies have not reported this in the past.
Cost of fat in the liver and if that would have any impact and if you could just comment a little bit on what the age of these patients five patients where were you at looked at liver fat.
Right.
So.
It's Ben.
<unk> and other studies as well as our studies, we did an analysis of that.
Which we presented but it's also been discussed in the step programs.
There is no effect of Asia in weight loss and if there is any effect there is a higher level of weight loss as you get older age so translating from a younger population in this phase one study to the next study or studies that we'll be doing if anything based on that information, we will be seeing more weight loss.
There has also been no effective age on.
To the degree of fatty liver reduction that's reported in other programs.
Average age of this cohort was similar with these five patients with similar to the general cohort that we reported on earlier.
Thanks.
Your next question comes from the line of John Walden with JMP Securities.
Hey, good morning, and thanks for taking the questions I was hoping can you just remind us what doses you're studying in the Napoli study how many patients are in that one as well as how many patients are in the.
Scott Harris: We've achieved a degree of liver fat reduction that has not been realized by other drug development programs, where the goal is merely to normalize the liver fat content to 5% or less. The head of the imaging laboratory that performed the MRI PDSS analysis, who has very extensive experience in these assessments, advised us that the observed reduction in liver fat was among the largest he had seen so far, if not the largest.
The DDI study.
Well. Thank you John so we're going to be taking.
Three doses into the natural <unk> study 1218, and two four milligrams there'll be 72 subjects in that study that means 18 per each of the arms and also includes the placebo arm.
The DDI study will be 36 subjects.
Got it.
The liver meeting coming up this weekend.
I am not sure if you had a chance to take a look at this yet, but it's an interesting analysis for semi glu Todd.
Scott Harris: So, you know, I would emphasize that while the study was small and exploratory, the pattern that we've seen is a level of reduction in liver fat that has not been observed with previous compound great, and also quite rapid as well. And maybe just to provide a little bit more color on the NAPLD study, can you just help us understand what the, are there, what are the thresholds for enrollment as it relates to liver fat content?
They found that 69% of the histologic improvement was due to weight loss.
So im wondering kind of your thoughts on that analysis and then also what you might expect with a direct acting glucagon effects with.
Thank you Paul.
Right.
Well.
We would agree with that.
Interpretation, but recognize that with some a glue Todd.
It has no direct effects on the liver so we didn't realize entirely on weight loss.
In a similar analysis on hemoglobin <unk> C. At one year that they performed in their step program.
The majority of the hemoglobin <unk> dropped that they had was not due to the increase in effect that is the stimulatory effect with <unk>, one and insulin secretion, which did give better acute diabetic control in the first three weeks.
Scott Harris: And, you know, I assume, for simplicity reasons, that biopsies are likely not going to be included in this phase one study, but just wanted to get a little bit more color on the enrollment criteria for that study and the pace of enrollment that you anticipate as a result of the more, you know, maybe restrictive criteria. Thanks. Well, thanks for the question, Seamus.
<unk> 52 weeks the majority of the drop in the hemoglobin <unk> was due to the weight loss, so that paralysed, what you've just said about the effects.
Yes.
On.
On histologic improvement now as you've all heard mentioned this is a direct effect of glucagon here.
On the liver.
Which is different from <unk>, which differentiates <unk> from GOP one mechanisms magnetite.
So we believe that there is an opportunity for even greater weight greater.
That reduction as well as greater weight loss.
With the additive glucagon agonism, so we agree with your assessment.
Interesting color, thanks, again for taking the questions.
Seamus Christopher Fernandez: Well, if anything, the enrollment criteria are less restrictive than they were in the phase one study and will include a wider variety of patients. For instance, the threshold for liver fat in that study is 10%. That's the cutoff that's been used by most sponsors. And, as you mentioned, there will not be a biopsy in this study. This is a non-invasive study based on liver fat content. But I would emphasize that this population will now include older subjects, as well as subjects with diabetes, and we actually expect the pace of enrollment to be very rapid. Great, well, I'll jump back in the queue, congrats on some really intriguing data, looking forward to the next dataset from your Phase 1B.
Youre welcome.
Your next question comes from the line of Manny Tommy with B Riley Securities.
Good morning, Dean Congrats on the progress and thanks for taking our question so.
Maybe if I can just quickly ask a follow up on the <unk>.
Absolute study and disc of bidding.
Baseline.
Six of the Phase <unk> study that we talked about.
What are the expectation sort of differences that you may have on the baseline LDL levels that the Napoli study would have I think you had about.
Somewhere between <unk> and the obese.
Healthy volunteer.
Volunteer study and just trying to understand.
What might be the difference in kinetics that you may observe <unk> LD.
Given now that we have a good idea on what you have on Bds F&B clause as we think about the naphtha study.
Yasmeen Rahimi: Your next question comes from the line of Yasmin Rahmi with Piper Sandler. Hi, team, thank you so much for taking my questions and congratulations on the great new data that you shared with us. I have a number of very short, tailored questions for you. I'm going to just go one by one. The first question directed to you is, what was the average weight loss that was observed in these five patients that really got a great lower fat reduction? So let's start there.
Mike I'm going to try to answer the question Im not sure I fully understand that so please.
<unk>, if I don't answer your question completely.
In the <unk>.
Phase one study that was recently completed we're allowed we allowed up to two fold elevation.
We have a very similar.
Very similar cutoff in the upcoming study.
Sure I understand your question about the kinetics could you please elaborate on that.
Yes.
Just based on your ESG data from the Phase one study.
Scott Harris: Right. The average weight loss that I have for you is at week six. I would imagine that the numbers that we tell would be approximately double that, although I don't have that number in front of me. And the average weight loss in these subjects was, well, the range of weight loss was between 3.1 and 4.7%. So the average weight, the average weight loss was approximately 4%.
Not seeing.
It's kind of like except for that one.
And normally we are not seeing.
Significant loading for example.
Generally not fleet studies, you would want to see that.
Dropped.
With liberal side and.
And we at Loews, So should we should we be expecting that as you.
Scott Harris: Thank you. And then again, Yasmin, that was at week six, so it doubled in 12.
Going to the naphthalene diabetic and non diabetic study just curious.
I understand.
Expect to recognize.
Yasmeen Rahimi: Thank you. The second question directed to you is, was there any other MRI PDFF analysis done at an earlier point? I'm trying to understand, I mean, we're already at the plateau of 90%, but sort of what the curve looks like in terms of the slow. If you could just comment on that, and then I have two more short questions.
In this study that we recruited because these patients in general.
Not an Apple D population.
We're not going to see or have the opportunity to look at ALC dropping that I was in the phase one study, but specifically recruiting people.
Where we're going to be having a pharmacologic effect on liver fat, which was driving the ALC, we should see that reduction in the upcoming Apple <unk> study.
Understood and then on the lower dose one dose level Scott did we have any patients did with.
Scott Harris: Yeah, thanks, Yasmin. So the way the study was conducted, there was a baseline MRI PDFF at week six and then week 12. We don't have the week 12 data yet, so we don't have a slope other than to be able to tell you what happened at baseline and at week six.
Elevated liver fat just curious what what.
What would the findings if any on the <unk> with that dose.
Right.
<unk> had.
Two patients at the one two milligram dose who had elevated liver fat.
One with 19% in one with 11% approximately.
Yasmeen Rahimi: Thank you. The next question, I think for us, and a lot of our clients are asking us to just really understand the translation of weight loss between an overweight population versus the NAPL population that you will be enrolling in your 1B. So when we look at the data from other Glyp1 constructs, what we notice is that the presence of being an apple patient does not impact the degree of weight loss, but what does impact it is the presence of diabetes.
The drops there were.
27% and 70% for remainder of about 48%, so the effects, where they're very comparable to other drugs, but not as robust as the reductions at one eight and $2 four where in each of those arms, the reductions were greater than 90% and to below the limit of detection.
Wow, that's amazing and then on the indie package with obesity just reminders.
How this is different than the Nash IND.
What goes into it.
Just curious.
So the heavy lifting <unk> was done by the National IMD, because thats, where the major parts of the <unk> were presented things like the manufacturing.
Yasmeen Rahimi: So I would like you to maybe explain to us, you know, should we be expecting weight loss rates that we saw in the obese population to be similar to the Nassol population, specifically the NAPL non-diabics? And then the second thing is, what do we know about GI tolerability based on historical data when we go from an obese population to NACO?
Toxicology.
And also some of the early clinical data now the emphasis of the obesity R&D will mainly be clinical.
And we will provide the first study to be conducted under the IND. That's a requirement of the IMD and we'll update with any additional data from the phase one study and from our chronic tox, so which will be completed before the study.
Scott Harris: Thank you for the question, Yasmin. So you're correct that studies with drugs and other mechanisms have shown approximately a 30% lower weight loss with diabetic patients. So our prospective plan in this study is to read out the amount of weight loss in both the non-diabetics in the population and the diabetics and stratify enrollment in that manner because it is an important covariate in the amount of weight loss that will be achieved, although not in the amount of liver fat reduction. So that's my first point.
So really it's a smaller IMD.
Oriented mainly towards the clinical development program with some additional uplift dates.
But the heavy lifting was done with the Nash IND submission in August and as you know it cleared in September.
Great and the final question.
Hep C in HBV.
No I understand.
Based on the data second half of next year.
I'm just curious how you might be thinking of.
This is being deployed as a combination I think you commented on this being used with the data.
But.
It's becoming clear that at least not in AI and AR.
Scott Harris: Regarding adverse events, we do not feel that there will be any difference in the adverse event profile going forward because of the inclusion of other patients. It's been said by experts in the field that diabetics actually experience lower adverse events than non-diabetics. Also, recognize that as we go from phase one to phase two, in general, because of the change in the way the studies are conducted, adverse events drop between phase one, where you have intensive monitoring, often inpatient, and phase two. So I would say that as we move from the phase one study to the phase one B, NAPLD study, we will actually see no worse than the adverse events that we have, if not improvement.
Look as sort of what you need in the.
The buttons are in immuno stimulation.
Is becoming increasingly clear so you might be in <unk>.
Sweet spot there.
Part of <unk>.
Thinking about this more strategically as you look to be bought.
The combination for developing functional geared for HBV.
Yes, my uncle I'm going to have Scott Roberts on the line I'm going to ask Scott to answer that question Scott.
Thanks for that question I mean, you hit the nail on the head Thats exactly how we see this.
<unk>.
Thinking is to create a window with even lower levels of surface antigen than are currently encountered with with new treated patients alone and that would provide a better feel.
<unk> for the immunotherapy to stimulate the T cell response so.
Liisa Ann Bayko: Thank you, team, for the clar, and I'll jump back in the neck here. Your next question comes from the line of Lisa Baker with Evoire, I-S-I. Hi, thanks. Most of my questions have been answered, but I guess I'll just kind of riff off the last series of questions. Can you just comment on the effect of age? I know these patients were slightly younger than perhaps future studies will be and just wanting to understand what you know about the fact of age on weight loss and also loss of fat in the liver and if that would have any impact, and if you could just comment a little bit on what the age of these patients these five patients were where you looked at liver fat, thank you.
As you know the RNA AI approaches mean to do that it's not really clear if theyre doing that well and we're certainly not doing it for a long term, but they can create that window of opportunity for <unk> to work better. So that's how we're thinking about that then.
I think.
That there is a lot of potential and approach.
Thanks for taking our questions.
Your next question comes from the line of Patrick <unk> with HC Wainwright.
Hi, Thanks, Good morning, I just have a couple of follow up questions. The first one is on Nash I am just curious based on your discussions with regulators in Europe, and North America, how likely or unlikely do you think are kind of a change in the regulatory endpoints as they currently exist for potential approval of Nash compounds, how likely or unlikely that chain.
Scott Harris: has been shown in other studies, as well as in our studies; we did an analysis of that, which we presented, but it's also been discussed in the step program. There is no effect of age on weight loss, and if there is any effect, there's a higher level of weight loss as you get to older age. So translating from our younger population in this phase one study to the next study or studies that we'll be doing, if anything based on that information, we'll be seeing more weight loss.
Or is it more likely just kind of stay how it is for the foreseeable future.
Thanks for the question Patrick it's extremely important.
<unk>.
I'm not aware of any public announcements that FDA or EMA.
We will be revising the guidance is.
For Nash approval, I think that Theres, a great deal of talk.
They should change and perhaps have to change to veer towards noninvasive assessments.
Scott Harris: There's also been no effect of age on the degree of fatty liver reduction that's reported in other programs. The average age of this cohort was similar, and these five patients were similar to the general cohort that we reported on earlier.
Steer away from the liver biopsy, but I can't give you any further guidance myself.
As to the likelihood of either of those regulatory bodies, making a change and when it would occur.
Got it and then just on T cell on the Phase II program can you remind US is this study powered to demonstrate a certain reduction in surface antigen or what would what would you need to see this data gives you confidence.
Jonathan Patrick Wolleben: Your next question goes to the line John Wolbin with JMP Securities.
Jonathan Patrick Wolleben: Hey, good morning, and thanks for taking the questions. So, but can you just remind us what doses you're studying in the Naffold study, how many patients are in that one, as well as how many patients are in the DDI study?
<unk> does not.
In immuno stimulatory.
Combined with another.
Return on a direct acting antiviral.
So the study has two key endpoints. The primary endpoint is a one log reduction in surface antigen and the study is powered to show the but another key endpoint is the clearance of the surface antigen and we think that that should be achievable as well, but we don't have our power.
Scott Harris: Thank you, John. So we're going to be taking three doses into the NAPLD study, 1.2, 1.8, and 2.4 milligrams. There will be 72 subjects in that study, that means 18 per each of the arms, and then also includes a placebo arm. And the DDI study will have 36 subjects.
We ended towards the.
The approval endpoint will be the clearance of the antigen, probably although that discussion with the agency has not taken place.
Clearly to get.
Reductions is extremely meaningful as we move forward, especially in combination therapies with partners.
Jonathan Patrick Wolleben: Got it. And with the liver meeting coming up this weekend, I'm not sure if you've had a chance to take a look at this yet, but I saw an interesting analysis for stem of gluteide, where they found that 69% of the histologic improvement was due to weight loss. So I'm wondering, kind of your thoughts on that analysis, and then also what you might expect with a direct acting glucagon effect with Pe
Got it and then just one last one just in terms of.
Central collaboration on time bead retired how are you thinking about that.
They're kind of R. R.
Turning to development on which you would look for collaboration partner how far along he brings program on your own.
Yes, Patrick Thank you for the question I mean, as we have said.
Previously we are well positioned to take the program through the next phases of trials here with.
Without funded to do that our goal is to.
Really increase the value of this asset with each study. So thats why we are planning multiple different studies to really.
Scott Harris: Well, we would agree with that interpretation but recognize that with semaglutide, it has no direct effects on the liver, so it relies entirely on weight loss. In a similar analysis on hemoglobin A1C at one year that they performed in their step program, the majority of the hemoglobin A1C drop that they had was not due to the incretin effect, that is, the stimulatory effect of JLP1 on insulin secretion, which did give better acute diabetic control in the first few weeks.
<unk> had a very compelling package Jim ultimately we think this is ed.
Asset that we will have a partner and what stage I can't tell you exactly right now, but we are marching towards that goal and making making good progress.
Perfect. Thank you very much.
Yes.
As a reminder to ask a question you will need to press Star then the number one on your telephone.
Joining a question press the pound key please standby, while we compile the Q&A roster.
Your next question is a follow up question from the line of Lisa <unk> with Evercore ISI.
Hi, this is kind of relates to what we talked about earlier with baseline at that level, but I know future trials are going to be looking at patients with at least 10%.
Scott Harris: At 52 weeks, the majority of the drop in hemoglobin A1C was due to weight loss. So that paralyzes what you've just said about the effects of weight loss on, um, histologic improvement. Now, as you mentioned, there's a direct effect of glucagon here on the liver, which is different from somaglotide and which differentiates Pemvedutod from GL-1 mechanisms, semagletide. So we believe that there's an opportunity for even greater fat reduction, as well as greater weight loss, with the additive glucagon agonism. So we agree with your assessment.
Liver fat as I cut off.
Can you maybe.
That higher thresholds.
<unk> outcome.
Patients with higher baseline levels of liver fat.
We can expect to see the same more elastic how much more difficult is it to reduce liver fat from the higher baseline.
Yes.
I would phrase the question is the positive the higher deliver the greater the opportunity for the percent reduction.
As we saw.
In the program the data that we presented at Liza.
We had a patients with patients with up to 19, 5% liver fat.
Jonathan Patrick Wolleben: Interesting caller. Thanks again for taking the questions.
Not only dropped their liver fat content.
Mayank Mamtani: Your next question comes from the line of May and Nick, Mam Tommy, with B. Riley Securities.
By substantial amounts.
Not only did we normalized liver fat to 5%, we actually dropped that 19% in just six weeks.
Mayank Mamtani: Good morning team, congratulations on the progress and thanks for taking our question. So maybe if I could just quickly ask a follow-up question on the NAFER study and just compare the baseline characteristics of the Phase 1 Obes study that we talked about, what are the expectation sort of differences that you may have on the, you know, the baseline ALT levels that the Nafel study would have? I think you had about somewhere between 20 to 30 and the OB's healthy volunteer study and just trying to understand, you know, what might be the difference in kinetics that you may observe on ALT, given now that, you know, we have a good idea of what you have on PDFF and weight loss as we think about the NAFRT study.
To below the limit of detection.
These are.
This is unchartered territory drugs have not done this before so we think that the opportunity to expand that.
The change in seeing even greater change.
Is even higher so in moving to a 10% population I think the opportunity to duplicate. These changes are great and see really unprecedented changes in liver.
Okay. Thank you and just.
Really helpful and then just may.
You may have addressed this already but were any of those five patients one of the five patients with that.
Elevated L T.
No.
The patient with the elevated <unk> Lisa.
Had a liver fat content of baseline of three 7% and that patient drop below the limit of detection. So that patient was not included in the analysis that we just provided but I would also emphasize the patience that we've reported on with much greater reductions.
Scott Harris: Mike, I'm going to try to answer the question. I don't really fully understand it, so please chime in if I don't answer your question completely. Um, in the phase one study that was recently completed, we allowed up to two-fold elevation. And we'll have a very similar cutoff in the upcoming study. And I'm not really sure I understand your question about kinetics. Could you please elaborate on that a bit, so I can?
<unk> in liver fat content as I, just mentioned from 19, 5% to below quantitative another 117% below quantitation and I could go through the serious here did not repeat did not have <unk> drop.
Drops triangulation excuse me elevations so.
No.
Consequently, although that might've been.
The framework for initial Conjecturing a hypothesis generating the.
The data that we have that we're reporting now does not confirm.
A relationship between the drop in liver fat and the <unk> elevation.
Understood. Thank you and then just one more question.
Mayank Mamtani: answer it yeah, so we just based on your ALT data from the phase one study, and we are not seeing, you know, it's kind of like, except for that one anomaly, we're not seeing, you know, a significant loading, for example, but generally, in NAFEL studies, you would want to see that your ALT drop along with liver fat and weight loss, so should we be expecting that as you go to the NAF Just just curious.
Moving forward are you going to include diabetics in your studies.
Sure.
Maybe you can describe the impact of diabetes on weight loss.
Yes, so as we talked about earlier traditionally in drug development programs diabetics have lost.
Less weight over the course of the trial the non diabetics typically about 30% less so based on that.
And our Napa <unk> study.
We will be stratified subjects.
Scott Harris: I understand. Yeah, we should expect that. You know, recognize that in the study that we recruited because these patients, in general, were not an AFLD population. We're not going to see or have the opportunity to look at ALT dropping as I was in the phase one study, but specifically recruiting people where we're going to be having a pharmacologic effect on liver fat, which is driving the ALT, we should see that reduction in the upcoming NAPL D.
12 week NAFL study that we've recently launched Lisa restarting following subjects by the presence or absence of diabetes at baseline and analyzing the weight loss separately.
The phase II study that we will be conducting and launching next year. We are enrolling non diabetics. So that it'll be a pure look at that population in the weight loss in that population and as I mentioned before should we conduct the 12 week extension to the <unk> study will have 24 week data on weight loss in both non diabetic.
<unk> and diabetics and probably around the middle of next year.
Okay and then just.
Scott Harris: I understood and then on the lower dose 1.2mig dose level Scott, did we have any patients there with elevated liver fat? Just curious what you know about what were the findings, if any, on the MRI PDFs for that dose level.
Is there a certain proportion of diabetics that you wanted to have in the settings understanding is trying to find them, but do you expect it to be like a third cut off of 50% and is there some.
Number.
Alright.
To say it will be a 3rd% to 50% is probably an initial good estimate.
Okay.
Thank you.
Scott Harris: Right. We had two patients at the 1.2 milligram dose who had elevated liver fat, one with 19% and one with 11%, approximately. The drops there were 27% and 70% for a mean of about 48%. So the effects were very comparable to other drugs, but not as robust as the reductions at 1.8 and 2.4%. were in each of those arms. The reductions were greater than 90% and below the limit of detection.
Welcome.
At this time there are no further questions.
Thank you everyone for participating today, we appreciate the opportunity to share our results and outlook with you and thank you for your continued interest have a nice day.
Ladies and gentlemen. This concludes today's conference call. Thank you you may now disconnect.
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Scott Harris: Wow, that's amazing. And then on the IND package for obesity, just remind us how this is different than the Nash IND, just what goes into it. I'm just curious.
Scott Harris: So the heavy lifting was done by Nash I&D because that's where the major parts of the I&D were presented, things like the manufacturing, the toxicology, and also some of the early clinical data. Now, the emphasis of the obesity ID will mainly be clinical, and we will provide the first study to be conducted under the I&D, that's a requirement of the I&D, and we'll update it with any additional data from the phase one study and from our chronic talks, which will be completed before that study.
Scott Harris: So, really, it's a smaller I&D, oriented mainly towards the clinical development program with some additional update dates. But the heavy lifting was done with the Nash I&D submission in August, and as you know, it cleared in September.
Scott Roberts: Great. And my final question on HEPT and HV, you know, I understand we are a little away from the data for the second half of next year. I'm just curious how you might be thinking of, you know, this being deployed as a combination. I think you commented on this being used with a DAA. But, you know, it's becoming clear that at least an RNAI and a nuke are sort of what you need, and the importance of an immunostimilant is becoming increasingly clear.
Scott Roberts: So, you might be in a sweet spot there. So, have you thought of thinking about this more strategically as you look to, you know, be part of a potent combination for developing functional gear for HP?
Scott Roberts: Yeah, my, I'm gonna, I have Scott Roberts on the line. I'm gonna ask Scott to answer that question, Scott. Hey, Monk, and thanks for that question.
Scott Roberts: I mean, you've hit the nail on the head. That's exactly how we see this. The thinking is to create a window with even lower levels of surface antigen than are currently encountered with new treated patients alone, and that would provide a better field for the immunotherapy to stimulate the T-cell response. So, you know, as you know, the RNA approaches mean to do that. It's not really clear if they're doing that well, and they're certainly not doing it for the long term, but they can create that window of opportunity for a hefty cell to work better. So that's how we're thinking about it. And, you know, we think that there's a lot of potential in that approach.
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Mayank Mamtani: Thanks for taking our questions.
Patrick Ralph Trucchio: Your next question comes from the line of Patrick Truccio with H.C. Wayne Wright.
Patrick Ralph Trucchio: Thanks, good morning. I just have a couple of follow-up questions. The first one's about Nash.
Patrick Ralph Trucchio: I'm just curious, based on your discussions with regulators in Europe and North America, how likely or unlikely do you think a change in the regulatory endpoints as they currently exist for potential approval of Nash compounds will be, or is it more likely to kind of stay as it is for the foreseeable future? Thanks for the question, Patrick. It's extremely important. I'm not aware of any public announcements that FDA or EMA will be revising their guidances for Nash approval. I think that there's a great deal of talk that they should change and perhaps have to change, to veer toward non-invasive assessments and steer away from liver biopsy.
Patrick Ralph Trucchio: But I can't give you any further guidance myself as to the likelihood of either those regulatory bodies making a change and when it would occur. Got it. And then just on Hepticell in the Phase 2 program, can you remind us, is this study powered to demonstrate a certain reduction in surface antigen, or what would you need to see in this data to give you confidence that it can act as that, you know, potent immunostimulatory to combine with another, you know, with a direct acting antiviral? Right.
Scott Harris: So the study has two key endpoints. The primary endpoint is a one-log reduction in surface antigen, and the study is powered to show that. But another key endpoint is the clearance of the surface antigen, and we think that that should be achievable as well, but we don't have our power oriented toward that. The approval endpoint will probably be the clearance of the antigen, although that discussion with the agency has not taken place.
Scott Harris: Clearly, to get reductions is extremely meaningful as we move forward, especially in combination therapies with partners. Got it. And then just one last one, just in terms of potential collaboration on 10-Budetud, how are you thinking about that? Is there, you know, kind of a point in development at which you would look for a collaboration partner, or how far along can you bring this program on your own?
Vipin Garg: Yes, Patrick, thank you for the question. I mean, as we have said previously, you know, we are well positioned to take the program through the next phases of trials here. You know, we're well-funded to do that. Our goal is to really increase the value of this asset with each study, so that's why we are planning, you know, multiple different studies to really gather a very compelling package. Ultimately, we think this is an asset that we will have a partner at what stage. I can't tell you exactly right now, but we are marching towards that goal and making good progress. Perfect.
Patrick Ralph Trucchio: Perfect. Thank you very much. As a reminder to ask a question, you will need to press the star key, then the number one on your telephone. To withdraw your question, press the Pound Key. Please stand by while we compile the Q&A roster.
Operator: Your next question is a follow-up question from the line of Lisa Beiko with Evercore ISI. Hi, this just kind of relates to what we talked about earlier with the baseline fat level, but I know future trials are going to be looking at patients with at least 10% liver fat as a cutoff. Can you maybe, That higher threshold could impact outcome, you know, for patients with higher baseline levels of liver fat, would you expect to see the same more or less? How much more difficult is it to reduce liver fat from a higher baseline? Thank you. I would phrase it this way:
Liisa Ann Bayko: I would phrase the question positively, the higher the liver fat, the greater the opportunity for a percent reduction, as we saw in the program, the data that we presented, Lisa. We had patients with up to 19.5% liver fat who not only dropped their liver fat content by substantial amounts. Not only do we normalize liver fat to 5%, but we actually dropped that 19% in just six weeks, to below the limit of detection. This is uncharted territory.
Liisa Ann Bayko: Drugs have not done this before, so we think that the opportunity to expand to change and see even greater change is even higher. So in moving to a 10% population, I think the opportunity to duplicate these changes is great and to see really unprecedented changes.
Scott Harris: Okay, thank you. And just, and that's really helpful. And then just, um, may have addressed this already, but were any of those five patients, the one of the five patients with the elevated ALT? No.
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Scott Harris: No. The patient with the elevated ALT, Lisa, had a liver fat content of baseline at 3.7%, and that patient dropped below the limit of detection. So that patient was not included in the analysis that we just provided, but I would also emphasize patients that we've reported on with much greater reductions in liver fat content, as I just mentioned from 19 and a half percent to below quantitation. Another one, 17 percent below quantitation, I could go through the series here, did not, repeat, not have ALT drops.
Scott Harris: Excuse me, elevations. So consequently, although that might have been the framework for initial conjecturing of hypothesis-generating, the data that we have that we're reporting now does not confirm a relationship between the drop in liver fat and the ALT elevation.
Scott Harris: And then just one more question, you know, moving forward, I'm going to include diabetics in your studies, and you know, maybe you can describe the impact of diabetes on weight loss for us.
Scott Harris: Yeah, so as we talked about earlier, traditionally, in drug development programs, diabetics have lost less weight over the course of a trial than non-diabetics, typically about 30% less. So based on that, in our NAFLE study, we will be stratifying subjects, That's the 12-week NAPLD study that we've recently launched, Lisa, with stratifying subjects by the presence or absence of diabetes at baseline and analyzing the weight loss separately. In the Phase 2 study that we'll be conducting and launching next year, we are enrolling non-diabetics, so that'll be a pure look at that population and the weight loss in that population. And as I mentioned before, should we conduct the 12-week extension to the NAPLD study, we'll have 24-week data on weight loss in both non-diabetics and diabetics, probably around the middle of next year.
Liisa Ann Bayko: Okay, and then just Is there a certain proportion of diabetics that you want to have in the studies, understanding that you're stratifying them, but do you expect it to be like, you know, a third, or you cut off 50%? Is there some, Number
Scott Harris: Right. I mean, I think that to say it'll be a third to 50% is probably a good initial estimate.
Operator: At this time, there are no further questions.
Vipin Garg: Thank you, everyone, for participating today. We appreciate the opportunity to share our results and outlook with you, and thank you for your continued interest. Have a nice day. Ladies and gentlemen, this concludes today's conference call. Thank you.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you. You may now disconnect.
Operator: Bres. Then and I'm gonna go ahead. I'm going to go ahead. I'm going to be in, and I'm going to be. Oh, me.
Operator: I'm not going to be there, and so on the I'm going to go. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, and Thank you.
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Operator: Thank you. Thank you. Thank you, and so on the Thank you.
Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, and so on the same. Thank you.