Q4 2023 Altimmune Inc Earnings Call
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Okay.
Good day, ladies and gentlemen, and welcome to the Altra Muni, Inc. Full year and fourth quarter 2023 financial results Conference call. At this time, all participants are in listen only mode.
Later, we will conduct a question answer session and instructions will follow at that time.
To ask a question during the session you will need to press star one one on your telephone.
This call is being recorded.
Your host for today's conference call Rich Eisenstadt, Chief Financial Officer of Ultimate Rich you may begin.
Thank you Michelle and good morning, everyone. Thank you for participating and ultimately full year and fourth quarter 2023 financial results and business update conference call members of the Ultimate team joining me on the call today are Vipin Garg, 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 press release with our lean mass preservation data and our full year and fourth quarter of 2023 financial results was issued this morning and can be found on the Investor Relations section of the company's website.
Before we begin I'd 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, Ottoman cautions that these forward looking statements are subject to risks and uncertainties that could cause actual results to <unk>.
For materially from those indicated for a discussion of some of the risks and factors that could affect the company's future results of operations. 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 press release issued this morning, and now available on our website any states.
<unk> made honest conference call speak only as of today's date Wednesday March 27th 2024, and a copy 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 up.
Variable for audio replay on Ottomans website with that I will now turn the call over to Dr. Vipin Garg, Chief Executive officer of <unk>.
Thank you rich and good morning, everyone.
We appreciate you joining us today for a discussion of our year end and fourth quarter of 2023 financial results and business update.
We are excited about the 2023 achievements with family do diet, our DLP, one glucagon dual receptor agonist, which is in development for the treatment of obesity and mash two important clinical indications.
Argument and achieved key milestones in the development of <unk> died last year include.
Including compelling positive data from our 48 week momentum phase II obesity trial.
The initiation of the impact biopsy, driven phase II B trial in Nash.
We're also extremely pleased with the results about body composition analysis from the momentum phase II obesity trial F&B due date.
Showing that 74, 5% of weight loss came from fat and only 25, 5% from lean mass.
Our Chief Medical Officer, Scott Harris will review these results in greater detail shortly.
Sure.
The momentum trial showed that subjects, receiving <unk> died had a mean weight loss of 15, 6% and over 30% of subjects achieved 20% or more weight loss on two four milligrams multifamily do died at week 48.
Along with robust reductions in BMI and serum lipids as well as improvements in blood pressure without imbalances imbalances in cardiac events and it demands are clinically meaningful increases in heart rate.
In addition.
The impressive in addition to the impressive body composition data further distinguishes <unk> from other compounds in development for the treatment of obesity.
Turning to our impact biopsy driven phase to be mass trial.
We're looking forward to announcing the top line 24 week results anticipated in the first quarter of 2025, we.
We are confident this trial will be successful considering the positive results from our 24 week phase <unk> trial of <unk> in subjects with <unk>.
We had a greater than 75% relative reduction in liver fat content was achieved at the one eight milligram and two four milligram doses at 24 weeks, along with robust reductions in LTE and <unk> one.
Both biomarkers of liver inflammation.
A recently completed a preclinical study demonstrating a direct anti fibrotic activity of Bambi do type provides evidence of a potential second mechanism for reducing fibrosis in mass patients.
With that.
I will now turn the call over to our Chief Medical Officer, Dr. Scott Harris to discuss our data and clinical plans Scott.
Thank you vipin and good morning, everyone.
First let me tell you about the compelling body composition analysis from the minimum trial, which showed that 74% of weight loss came from adequate tissue and only 25, 5% due to lean mass.
Bearable to the effects historically associated with diet and exercise programs.
These data are among the best results achieved with <unk> based obesity drugs.
With an increasing number of anti obesity candidates in development.
There is growing evidence emphasis on the type and quality of weight loss.
Where the ability to preserve lean body mass has been viewed as an important differentiator in the treatment of patients with obesity.
Excessive lean mass loss has been associated with negative outcomes, such as <unk> and bone fractures.
Especially in women and the elderly.
Additionally, we saw the participants momentum preferentially loss of visceral fat over subcutaneous fat an important result, as visceral fat <unk> fat content increases metabolic dysfunction, and it's highly associated with increased cardiovascular risk.
We expect to present, a complete analysis of these body composition data at an upcoming scientific meeting.
Keep in mind that these favorable body composition data only add to the improvements we observed in serum lipid profile, where up to 20% up to a 20% reduction in total cholesterol, 21% reduction in LDL cholesterol and.
Nearly 56.
Reduction in triglycerides were observed in momentum participants with elevated baseline serum lipids.
This strengthens our view that <unk> has the ability to treat not only obesity, but it's key morbidities like cardiovascular disease and mash.
Recall that our momentum phase II obesity trial subjects, receiving two four milligrams pampers tide had a mean weight loss of 15, 6% and over 30% of the subjects achieved 20% or more weight loss at week 48.
What was equally exciting is that the two four milligram weight loss curve remained linear with no indication of plateauing at week 48.
Along with the previously mentioned effects on serum lipids.
<unk> also demonstrated improved <unk> and blood pressure within imbalances in cardiac events or arrhythmia is where clinically meaningful increases in heart rate.
Glucose homeostasis with maintain with no significant changes in fasting glucose or hemoglobin <unk> C.
Dr. Lu Roni lead investigator for the momentum trial will present the present the results of this trial in an upcoming scientific conference.
Now, let me talk about the impact biopsy, driven phase II B trial.
Approximately 190 subjects with <unk>.
Or without diabetes or being randomize, one to two to two to $1 two milligrams one eight milligrams.
Or one eight milligrams per ml <unk> placebo administered weekly for 24 weeks.
The key endpoints will be matched resolution of fibrosis improvement after 24 weeks of treatment with subjects followed for an additional 24 weeks for assessment of safety and additional biomarker responses in.
Enrollment is going well and we expect to have top line results of the impact trial in the first quarter of 2025.
We believe that the rapid rate of enrollment reflects the eagerness of match patients to achieve significant weight loss. In addition to treatment of their liver disease.
This past fall, we also reported that FDA granted fast track designation to <unk> for the treatment of match based on the robust and rapid reduction in liver fat content and biomarkers of fiber inflammation observed in our phase <unk> trial.
We look forward to working closely with the agency and the development of <unk> for this important indication.
Finally, turning to our phase II clinical trial of <unk> in chronic hepatitis b the.
The overall response in the recently completed trial was insufficient for further development. So we are stopping all further development.
With that I will now turn the call over to Dr. Scott Roberts, our Chief Scientific officer to discuss some recent preclinical findings Scott.
Thanks Scott.
Good morning, everyone.
I'd like to tell you about two studies that we've recently completed the.
The first represents an important developments related to the therapeutic mechanism a pivotal time for Nash.
We now have evidence for a direct anti fibrotic effect of <unk> tight and reducing liver fibrosis.
Preclinical model used chemical treatment to induce fibrosis as opposed to more typical Nash models based on obesity and high liver fat content.
The chemical model allows for the separation of direct anti fibrotic effects from the activity following potent defending of the liver by <unk>.
The data showed a significant 33% reduction in the amount of fibrosis. After only two weeks of heavy duty treatment and the presence of continued chemical exposure.
These data bolster bolster our optimism about obtaining a successful 24 week readout and the impact trial in the first quarter of 2025.
And a separate unrelated study, we demonstrated that pivot to tight treatments increase the efficiency of an important process call reverse cholesterol transport or RCT.
RCT is the process by which excess cholesterol is removed from tissues and eliminated from the body.
It is widely understood that LDL can cause the accumulation of cholesterol in the arteries, leading to atherosclerosis, an increased risk for cardiovascular events.
In this study we demonstrated that <unk> treatment was able to increase the amount of cholesterol eliminated by the liver by 300%, while lowering serum cholesterol levels cliff.
Clinically we have shown that <unk>, not only lowers serum LDL cholesterol by up to 21%, but also shifts the size of LDL particles towards larger particle sizes that cannot enter the vasculature is easily.
The demonstration of increased RCT activity together with the established reductions in serum lipids and liver fat support a potentially broad role.
For <unk> and improving cardiovascular risk in addition to its robust weight loss effects.
I will now hand, the call over to Richard Eisenstadt to give an update on our third quarter financial results rich.
Thank you Scott and good morning, everyone, it's actually our fourth quarter financial results.
For today's call I'll be providing a brief update on offerings full year on fourth quarter 2023 financial and operating results more comprehensive information will be available in our Form 10-K to be filed with the SEC later today Automd.
<unk> ended the fourth quarter of 2023 with approximately $198 million of cash cash equivalents and short term investments compared to $184 9 million at the end of 2022, we project that our existing cash funds us into the first half of 2026, which fully funds our impact trial mash.
Including the anticipated Q1, 2025 readout of top line 24 week biopsy data.
Turning to the income statement revenue was negligible in the fourth quarter and full year 2023, and 2022 any.
Any revenue reported during such periods was for indirect rate adjustments on a government contract that we were closing out.
Research and development expenses were $16 $9 million in the fourth quarter of 2023 compared to $19 2 million in the same period of 2022 proxy.
Approximately $11 $4 million of this total for the fourth quarter of 2023 were direct expenses for the conduct of our clinical programs, including $10 $3 million in direct cost but development.
Activities for <unk>, and $1 $1 million of direct costs related to development activities for <unk> T cell <unk>.
R&D expense in the fourth quarter of 2022 included $13 $4 million in direct expenses associated with the development of <unk> to tide and $1 $9 million of direct expenses related to hefty self development activities.
Research and development expenses were $65 $8 million in full year 2023, compared to $75 million in the prior year and full year 2023, we incurred $35 $8 million of direct costs associated with the impact of momentum trials for kind of a deep dive and six <unk>.
$6 million in direct costs associated with the hefty sell campaign.
General and administrative expenses were $4 $3 million and $3 $8 million in each of the fourth quarter 2023 and 2022.
For the full year 2023 general and administrative expenses were $18 1 million versus $17 $1 million for full year 2020 to the $1 million increase was primarily due to increased stock compensation expense as well as additional labor related costs in 2023.
And impairment loss on intangible asset of $12 $4 million was recognized during the fourth quarter of 2023 related to the acquired in process research and development or IP R&D asset associated with <unk> cel.
As previously discussed the overall response in the phase III trial is deemed to be insufficient to warrant further advancement in clinical trials and as a result, we have stopped any further development related to <unk> cel.
Our quarterly noncash operating expenses for the fourth quarter.
It was of 2023 was $15 $1 million, including the IP R&D write off our $2 $6 million for just the recurring expenses for the full year total noncash operating expenses was $23 8 million or $11 $3 million for just the nonrecurring items.
Or I'm, sorry for the recurring items I apologize.
Net loss for the three months ended December 31, 2023 was $31 $6 million or <unk> 54.
Net loss per share compared to net loss of $21 $7 million or <unk> 43, net loss per share for the <unk>.
Fourth quarter of 2022.
The increase in net loss in the quarter was primarily attributable to the $12 $4 million noncash impairment charge, partially offset by $2 $3 million lower research and development expenses net loss for the year ended December 31, 2023 was $88 4 million or $1 66 net loss per <unk>.
Sure compared to $84 7 million or $1 81 net loss per share for the year ended December 31, 2022, the increase in net loss for the year is primarily attributed to them.
To the noncash impairment charge, partially offset.
Offset by lower research and development expenses in 2023, and a $4 $5 million an increase in interest income.
Earned on our cash equivalents and short term investments.
I'll now turn the call back over to Vipin for his closing remarks.
Thank you rich.
Operator that concludes our formal remarks, we would like to open the line to take questions could you. Please instruct the audience on Q&A procedure.
Thank you as a reminder, if you'd like to ask a question. Please press star one.
If your question has been answered and you'd like to remove yourself from the queue. Please press star one again.
Our first question comes from Yasmin Rahimi with Piper Sandler Your line is open.
Good morning, Tim and thank you for all the updates.
First question that we have been getting.
Given the continued desirable product profile of <unk>.
A lot of investors would like to get a little bit more update on where you are with partnership discussions currently.
Number one.
Number two is have you had the opportunity to engage with the agency in regards to the phase three design for obesity in what would look like.
Then the third one how can we think you've shown really compelling lean mass preservation resolved at week 48, how could we think about the magnitude to be further improved overtime.
<unk>.
And patients and thank you for allowing me to ask the question.
Scott do you want to take the.
Questions first and I will come back to the partnering question. Okay. Jasmine. So I'll take your second and third questions and then we'll answer the partnering discussions. So our plan is to have a meeting with the agency in the second half of this year to discuss our phase three program in obesity.
At that time, we'll have.
Final conclusions about the design of the program in the trials.
But the template for this has been established with other programs and we think that we would have a similar development program in phase III.
Regarding the body composition data and the results that we saw week 48, yes. The results are compelling and among the best in class.
For <unk> agents and very similar to the.
Sure.
Percentage of lean mass scene with healthy weight loss with diet and exercise.
And this is what obesity experts are are emphasizing.
The lean loss down to avoid the comorbidities of loss, losing lean mass.
As you may be aware from the bariatric and weight loss literature.
The percentage of.
Of weight loss that is lean mass decreases over the course of time, so, whereas we were 25, 5% at week 48, there is potential to go to even lower numbers.
Objects were followed out to week six theaters with 72.
Great.
Yes, yes in terms of partnering discussions.
That is our partnering discussions we are having robust discussions with companies that are both scientific and technical in nature as well as business related discussions.
You can imagine each company has their own particular focus but theyre all appropriate.
<unk> comprehensive and differentiated profile. So overall, we are pleased that the scientific and business discussions to date, and we will update as things develop in the future.
Speaker Change: Thank you so much team I will jump back into the queue.
Thank you. Our next question comes from Seamus Fernandez with Guggenheim. Your line is open.
Hi, Thanks.
I appreciate the opportunity to ask questions here.
The partnering discussions.
Vipin, you mentioned scientific and <unk>.
Technical discussions, but also business discussions it seems to me. This is predominantly a business discussion at this point.
Just trying to better understand the commentary of differentiating.
Those two.
If there are scientific and technical discussions what are the scientific and technical debates that remain.
For Penn Madhu tied in the context of <unk>.
A obesity program and in the past on partnering <unk>.
Commented that.
Perhaps there would be a separation of.
The opportunity.
For obesity being.
Being with a partner, but perhaps having nash or Nash.
Move forward exclusively.
With.
<unk>.
Do you still believe that that is a realistic partnering discussion given the fact that we've now seen hints that trues appetite.
Has an opportunity potentially to impact fibrosis, and we have another competitor molecule and serve with you tide thats likely to present data in the near term.
With regard to their own potential fibrosis benefits in both programs have a very robust obesity program, either planned or well underway.
Yes. Thank you for that question say most days of Lockdown back there. So let me let me take one at a time and if I have not completely addressed to your questions. Please come back and repeat the remaining part.
Look in terms of discussions with partners.
As you can imagine that different companies have different focus, but everybody is appreciating the cardiovascular benefit of <unk> <unk> and that's what is driving these discussions it's old.
<unk> cardiovascular benefit all of the things we've been talking about in terms of the lipid profile the serum lipid the liver.
<unk> content and blood pressure. So all of these things combined we believe will have significant impact not just people, losing weight, but ultimately the cardiovascular outcomes. In these so lot of the discussions that are driven by that we're very encouraged because that's the value proposition that we think we bring to the table and people are getting it people are <unk>.
Shifting it and the question is is this an obesity partnership cardiovascular partnership our mass partnership or all of all of those combined together.
In terms of mash as you know we are moving forward with the with the program we will have our <unk>.
<unk> <unk> data in the <unk>.
First quarter of 2025 and that will drive that program further clear.
Clearly and mash, we are highly differentiated both in obesity and mastery of highly differentiated but in terms of other.
Glucagon program being that we have differentiated from that also and maybe Scott you can comment on that yes.
Yes, Seamus we're encouraged by the results with the other compounds and Vas you mentioned tours appetite and also serve as do Todd.
We believe that the effects seen with server do Todd or due to the booth regarding component and we would remind you that molecule is heavily biased to GOP, one away from glucagon and theres not as much glucagon in the molecules in our molecule, where we have one to one we feel so confident about the potency of our molecules that were actually willing.
To break from the pack and read out the endpoint of 24 weeks, the other compounds or reading at considerably longer periods of time.
Also with regards to serve with Utah, I'd remind you that the adverse event dropout rate in that trial was very very high. Despite the fact, they titrated for 20 weeks. So we don't think the Tolerability profile with our compound is comparable but we think that based on all of our biomarkers all of the data that we've journey.
Our rated up to date, we're going to have a very very potent readout and the confidence that we could actually read that out at 24 weeks rather than 48 weeks represents our confidence in the molecule.
Great and maybe just a follow up on <unk>.
The mash program can you just remind me the the doses my recollection was that the plan was to explore only up to the one eight milligram dose, but where we saw more meaningful weight loss.
The obesity program was at the two four milligram dose so just wanted to.
See where the sort of dose range is going and then you mentioned weight loss in match patients, but my recollection is that there was very limited weight loss.
In the <unk>.
<unk>.
Phase one b to.
Two program that you ran previously out to 12 weeks.
Just trying to get a better understanding because I.
My recollection is you explore the one eight milligram dose there but.
But we didn't see.
Much weight loss and that I guess was partially attributed to the patient population recruited but.
I'm, just trying to get a better understanding of how this space too will differ from your initial.
Phase one b two program. Thanks.
Right sure.
So we are seeing a different dose response curve.
For liver fat.
<unk> for weight loss with weight loss, we're seeing increasing weight loss with increasing doses of drug and in fact, we believe that if we were to go to even higher doses of <unk> in the future even greater weight loss would be achieve very happy with the weight loss that we've achieved in the obesity program, we think its very compelled.
Along with the other effects that <unk> described but we have the opportunity to go higher because the way the dose response curve and obesity continues as you go up.
When you get.
70, plus five plus percent liver fat reduction at the one eight milligram dose is really very little place to go further with the two four milligram dose in the dose response. So that's the way the trial was design looking at the 1.2 and one eight milligram doses.
We always have the opportunity to either one in phase III that is always that possibility that exist for us, but right now in the phase II design, we're going to be looking only at the one two and $1 eight milligram doses.
Great. Thanks, I'll drop back in the queue.
Thank you. Our next question comes from Roger song with Jefferies. Your line is open.
Speaker Change: Great.
Thanks for sharing the new data.
And taking our questions. So another question related to the partnership may be a little bit more specific.
Can you, let us know how much discussion is contingent upon this more detailed.
Face shield <unk> momentum data at the words your phase II Nash data.
Yeah.
Kind of are coming.
And.
Just remind us the discussion is calm.
Combination.
Both program moving forward or.
Speaker Change: Different partner.
A different setup.
Certain program.
Yes.
Yeah, Matt Thanks, Roger I would say the good news is that most of our partnership discussions are actually focused on on both obesity and Nash program. Most of the players that are looking at Ben We do died.
Are interested in both because they are very related indications that you can imagine so it's going to be hard to separate them anyway, but in terms of.
Developing and commercializing a product it's a very similar pathway. So so the good news is that most of our partnership discussions are focused on both of those programs. So we think ultimately our ideal partner would be in a multinational player that has that has the ability to develop both obi.
City, and mash and commercializing both of these in and really take this program forward in parallel.
So we're in we're in good shape from that perspective, the partners are clearly getting the message in terms of the value proposition the differentiation that.
And we do that brings and therefore, we're very excited about those discussions.
Got it thank you.
Another.
Mechanistic question. So it seems very compelling this muscle preservation, which is very interesting.
How do you think about and with the tech can be differentiated.
We're maintaining all the weight rebound kind of back into it yet given you are more or less all yield additional liver lipid targeting versus.
<unk>.
Hi, Paul Caloric mechanism.
Yes.
Yes, that's a great question, Roger Scott do you want to take that.
Yes.
Roger we feel that every time, we generate data, we're showing there really incredible differentiating effects of glucagon.
Compared to other mechanisms so we're very familiar with.
Speaker Change: <unk> and <unk>.
And those drugs have very nice effects on weight loss and they also have other benefits that have been seen in clinical trials that are ongoing or soon to be completed.
Glucagon brings a whole different dimension here.
That's extremely valuable for not only achieving weight loss, but maintaining weight loss healthy weight loss and having long term effects on cardiovascular outcomes.
So we really think in that sense glucagon as a game changer, we've seen as you've mentioned the effects in serum lipids and liver fat.
And now on top of that we're seeing a very potent effects on preserving lean body mass as people lose weight.
This has been a very.
Important point of differentiation in discussion.
And the obesity.
Circle for the last two years.
Because now people are turning away from the absolute amount of weight loss to the quality of the weight loss and thats important, especially for long term maintenance. So the ability to hit a certain number of acutely doesn't really matter if someone stops the drug and regains the weight or regains the way thats, mainly fad or not lean.
So we think this could be an incredibly important mechanism for maintenance.
As you know there was some suggestion in the obesity data at the two four milligram dose.
The weight loss was continuing in an aggressive manner.
At 48 weeks, we think this could also represent a fundamental effect of glucagon on.
Intermediary metabolism and energy expenditure that could continue in the future basically changing the metabolic balance and having in that score.
Real differentiation from the <unk> and the <unk>.
We don't have that data at this point it certainly would be of great interest to study this going forward and it's something that we are strongly considering in our phase III program.
The other thing I would add is this preservation of lean mass has important implications for continued weight loss and for maintaining that in the weight loss, because I think everybody appreciates that because of the sheer amount of muscle.
That people have it.
It represents.
<unk> share of where calories are spent so by maintaining more lean mass more muscle we maintained more of an engine to burn those calories and to reduce weight.
Excellent. Thank you.
Thank you. Our next question comes from Lisa <unk> with Evercore. Your line is open.
Hi, I think most of my questions have been answered, but maybe if you could give us a little more.
I guess color on some of the kind of feedback you're getting from potential partners as it relates to dose and phase III strategy.
And and just wanted to confirm that your plan is to wait for a partner before proceeding into phase III for obesity.
Yes, Thanks, Lisa I mean as you can imagine.
Partners are looking to differentiate going forward I mean, if you are a third or fourth or fifth company launching a drug in the obesity space the idea of having yet another <unk> not even at <unk> Gi.
Without defense <unk>, and it's going to be difficult. So therefore, we believe having the mechanism. Adding addition of the glucagon mechanism is very attractive.
Particularly to new players getting into the obesity space because again.
Differentiation is going to be the key to commercially to successfully launch.
Product and obesity space going forward. So we are really very encouraged by the fact that that's what partners are focusing on Scott.
Scott talked about the quality of weight loss that is becoming very important components of our conversations because again.
If youre looking longer term the conversation is now going to shift from just losing weight. Initially whatever 48 72 weeks. So how do you maintain that weight loss and what is the maintenance schedule than what's the quality of weight loss at that point. So I think on both of those fronts, we bring a very differentiated approach.
A very differentiated products. So we are very encouraged by those discussions, particularly.
By the fact that the partners that actually getting it and focusing on it.
And how are they thinking about your kt's titration schedule I know, you're only doing that for the highest dose or doses that you have there any interest in the low dose.
What is the thinking on kind of your dosing approach and how much of a differentiating feature is no dose titration or might you actually consider dose titrated to even improve tolerability more.
Yes, it's actually a very important feature, particularly the fact that all three doses that we are talking to them.
At one point to one point, David and <unk> for their own active doses, even at $1 two milligram some of our patients, losing 20% or more of their body weight and many patients are losing 10% or more.
<unk> two milligram has a very active dose for many patients out there.
The idea is that we can have to re dose it will take three dosage forward in phase III approval for all three of them and for doctors then they can they have the option. They can stop the patient at the lowest dose at 1.2 and by the way the Tolerability Das.
Just like placebo at 152 milligrams, so really no dose titration required they can start with that dose see how much weight. This patient is losing and then if they need to lose more weight. They can go to one eight and eventually to even two four so thats really.
People are really appreciating that differentiation because that simplifies the whole dosing schedule, particularly as this market moves into primary care.
Speaker Change: Doctors don't want to have to deal with dose titration, but that's.
It's a very important differentiating feature of <unk> Scott.
Yes.
He's a prescription is extremely important physicians don't have the time to monitor patients through titration to give it to physician extenders or to hire them to spend money on that and also.
With each.
Escalation many times you have to get approval from insurance companies to escalate.
And all of these titration schemes with other drugs, who are starting on drugs that are not on approved or effective which are not approved or unnecessarily effective doses.
Patients here would start on the one two milligram dose Liza and Thats, an active dose and that will be an approved dose which is the tolerability similar to placebo and I think for primary care to have a mean of 10% weight loss and the 48 weeks and longer with longer therapy with all the benefits is a real win but we also offer the <unk>.
Option of going to higher doses in patients who want to lose more weight.
Great. Thank you so much.
Thank you. Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is open.
I guess, maybe partnerships, obviously been a huge focus but as you think about timelines or kind of goals for the management team. I guess is there anything you can share with respect to when you would hope to have something established and then.
Maybe if you could comment on whether you'd like to have something in place by the time you get to phase through conversations with the FDA later this year.
And the other question that we had was just how many patients are included in this body composition analysis and is that something you've looked at Empire. So I was just curious how.
How many patients and how Robert Bosch side data Center.
Yes.
<unk> 100, 606 subjects participated in the study and we have baseline and week 48 data on 70 patients and.
We've looked at the data it's statistical significance, it's extremely high so we really feel that this is quality data and we look forward to presenting them in greater detail at a scientific meeting later this year.
Thanks.
And Colin in terms of the timeline.
Those of US who have done deals.
It's very difficult to to sort of lay out a timeline, but our focus has been always to have a partner in place before we start phase III towards the second half in the second half of this year.
Would be nice to have a partner alongside with US when we have our end of phase II meeting. It is not critical because it's pretty standard at the end of phase II meeting for a photo DCD program. So we're very comfortable.
Having that conversation with the FDA, but it will be nice to have a partner alongside with us and we'll see if that's going to be possible.
Okay. Thank you.
Thank you. Our next question comes from my ankle Pantani with B Riley Your line is open.
Good morning team, thanks for taking our questions and appreciate the comprehensive update here in just a few more of the site.
He has taken a good follow up.
Got it.
As flagged normalization data out to 79%, which is a little bit higher than what you saw in that study with the with the sample size and I assume it's a pooled analysis from those.
Those levels could you please clarify that.
Well.
The body the liver fat data mining comes to the body composition study right. So patients MRI scans and they've got the MRP DFS when liver was being scanned.
So.
We are seeing.
A very high rate of liver normals that normalization. We think this is very.
Very.
Very similar to what we saw in patients and therefore, <unk> study, who started with much higher levels liver liver fat.
Main liver fat and the math will deep study was about 22% to 23% and in this study was about 5%. So the barrier for normalization was less.
Got it got it Scott.
A related question I have on that.
Body composition data.
<unk> used here.
Got it if I had that in my base.
Additionally approaches like next Bud Bud.
It could be helpful to also compare against what we have for semi and did the other day.
I believe in our holdings in that dividend could be presented in the future.
Part of the protocol.
Well MRI is the preferred technique for body composition, we think that there are many experts things that Texas is not a good surrogate.
For the specificity and sensitivity of MRI. So thats a technique we relied on for this study.
Okay understood and then on the in fact Nash trial execution.
Any color you can provide on pace of enrollment and if you'd expect later in the year.
Doing a placebo controlled study could be impacted now that and approve Nash therapy on the market.
Did the prior commentary you had that some of the approved drug fluids that showing more there now is that that I think affect that than we've seen before.
On the Nash trial execution through the course of the this shouldnt be a battle.
So enrollment in the trial is going quite well and the feedback we get from.
Investigators and their subjects is that they prefer to come into their trial.
Speaker Change: Because patients can lose weight, so faced with the possibility of choosing amongst different trials available to them and community. We're seeing patients come into our trial because this trial offers weight loss and also potent effects.
We believe that that reflects the commercial potential of the drug when these drugs are being offered were seeing RASK mineral recently being approved.
But there is no weight loss associated with that and we think head to head, we're going to do extremely well in that regard.
Regarding the other benefits of the drug.
Remind you that we're seeing.
Class, leading effects on liver fat reduction and other biomarkers of inflammation, which is going to allow us to actually read out and differentiate from the pack in this area by reading out on fibrosis improvement in 24 weeks and we think that we can do that.
But you know repeatedly the effects of glucagon here.
<unk> being shown to be very differentiating and very valuable, especially with regards to the quality of the changes that are being seen especially in the weight loss front and we look forward to generating more data in the future and Scott you may want to talk about direct anti fibrotic effect that we're seeing for sure but actually before I get there I just want.
It too.
No.
Reaffirm that.
We are in the sweet spot when it comes to mesh we are in the sweet spot.
Scott just talked about.
And also the FGF 20 ones are doing great jobs on on directly acting on the liver, but theres no way loss associated with those.
With drugs like <unk> appetite.
They're hitting mass resolution, but delivered <unk> of <unk>.
<unk> <unk>, our <unk> IP is just not that great.
That's why we believe.
The fibrosis endpoint wasn't here. So here, we have a direct acting agent that can DFAST deliver very quickly and control inflammation very quickly, but we also have the weight loss and you don't find those two qualities and the competitors that are that are out there.
As far as the direct anti fibrotic effect, we think that the data we talked about here today.
Our exciting and really offer a second mechanism that could certainly push things along for <unk>, III, which is our intent to that population and our.
It is the population in our <unk> study, but also may have implications for late stage.
Fibrosis at four for example, so we're continuing to look at that and try to understand the mechanisms by which this is occurring but we're excited about the data and we think that it certainly adds to the value of heavy duty from ash.
And just maybe staying with you Scott final question on that.
Any clinical anti Fibrotic study data unit forward, I think 32% level payroll in less than two weeks.
In the same extent and then getting extended.
The ingredient and good and drugs.
Can you comment on what you've seen and then also lastly, an update on the <unk>.
Formulation of <unk> I believe you assume that the Bloom technology.
Is there any early buy to reinstate annualizing that you can talk about a deal that type format and thanks again for taking our questions.
Sure absolutely so as far as.
In parallel with other drugs, there's really not a lot out there for mass drugs that have really looked at this non <unk> non obese models. So it's been difficult to really keep our deep adding deliver and that's why we're getting anti fibrotic effects or is there some direct activity.
I will mention that <unk>. For example has done the same sort of study that we've done very similar and we see comparable effects on the amount of fibrosis reduction and as you know Lance trip R&R is certainly.
Demonstrating anti fibrotic effects in the clinic and is currently in phase III testing. So there's not a lot out there, but I think that that's an important.
Touch point, there with them.
Any data.
As far as the oral formulation, we are making good progress there when we look at the levels of <unk> that are.
Speaker Change: Detected in the in vivo studies, we're seeing a significant fraction of what we.
Achieve clinically for example at the one eight or two four milligram dose we know what those levels are and in these dogs were able to achieve a significant fraction of that and so we feel we're on the right Road here, we still have two different approaches that we're evaluating and both of them look promising so I think that.
Those that effort is looking good and we hope to report that we will putting one of those candidates into development.
Development by the end of the year.
Thank you.
Thank you. Our next question comes from Jonathan London with JMP. Your line is open.
Hey, good morning, and thanks for taking the questions.
Couple of thoughts on the body composition study I was wondering if you could give some context for how what youre seeing what kind of a <unk> compares to <unk> in terms of appetite and if you'd expect to see similar changes with other dual and triple agonist that include glucagon or if this is.
Specific to <unk>. Thanks.
Yes, thanks, Jonathan.
So.
In the same analysis remind you that we were at 25, 5% some are glued Titus at 40%.
Compared to some of Glu, Todd, we're clearly preserving more lean mass.
Within the <unk> prescribing information.
The higher rate of bone fractures in women and the elderly as highlighted we believe that thats associated with the lean mass loss and emphasizes the importance of preserving lean mass as people lose weight and to get as close to the.
Ratio scene.
With.
Diet and exercise, which is about 25% and we've achieved that.
The <unk> data has only been presented in abstract form it's a bit difficult to see the exact number but we believe it is at about 26%.
So clearly we're in that class of the leading drugs in this space.
<unk> reported out a lean ratio in other words, how much lean was being loss compared to body weight of about 37% to 38% and a recent trial now we believe that the effects that we're seeing are being driven by glucagon. We would point out that we believe that we have more glucagon in a molecule than regulatory.
Through time, and that's why we're differentiating on the body composition. So we think the more who's done the better in a variety of areas, including reduction of lipids reduction of liver fat and now better preservation of lean mass.
Thank you.
Last question comes from Patrick <unk> with HC Wainwright Your line is open.
Thanks. Good morning, just first a clarification on the lean mass data I'm wondering if the.
The lean mass preservation and body composition compared across dose levels of <unk> tighter and so it was consistent across the doses and then separately I'm wondering if the updated preclinical or clinical data reported today has impacted the way youre thinking about a potential phase III program in obesity in terms of trial design, such as dosing titration.
Our endpoints and separately can you tell us how the data reported today would be expected to read through to the impact program.
Thanks, Patrick I guess also.
So.
Total loss ratio that we quarter to 25% 25, 5% was the same in all dose groups.
So you achieve that ratio, regardless of the dose of 25%, 25%, 25% at all three doses.
The data on body composition, clearly has to be thinking make us think about incorporating this into a phase III design.
The largest change that we've made in the program. So far has been allowed dose reduction, which we think is going to remarkably improve the tolerability of the compound of the program in phase III, we certainly have the optionality.
To look at.
Longer titration, so that's not a decision thats been made yet with a partner, but that is something that we could consider there is felt to be value. There. Our current position is that we do not feel into longer dose titrate, we think as vipin mentioned, especially at the one two milligram dose it is differentiating for other.
<unk> against other compounds, particularly.
For primary care.
But is the opportunity.
<unk> in the future program.
Go to higher doses, if we chose all the evidence suggests as we would get higher weight loss, but I want to emphasize that we are very happy with the fixed 15, 6% weight loss that we achieved at 48 weeks getting even longer larger with longer durations of treatment the.
The endpoints in these studies are pretty much established by the FDA at least for the non diabetes diabetes trial.
This is Dave we actually do.
We actually look to see if we will do a study that includes body composition, we have other options to look at it as well that we can detail in the future.
Speaker Change: In terms of the match program I think.
We've always had confidence in our ability to differentiate against the.
The other drugs in mesh.
Everyone has mentioned the anti fibrotic potential of curious appetite and server due time, we think that based on the glucagon content of the molecule, we're going to get even better effects youll be able to demonstrate that potency by getting statistical significance at 24 weeks of treatment rather than 48 weeks of treatment the <unk>.
Anti fibrotic data that Scott described on the call also increases our confidence that we're going to hit the fibrosis endpoint, because we are not only moving fibrosis by reducing liver fat, where having a direct anti fibrotic effect, which is very important as well.
Yes, just only one thing I would add to that in terms of looking at the phase III plans.
As you know for phase III is going to need thousands of patients, particularly for our safety database. So that gives us the opportunity to actually have multiple patient population that we can test. We can we can study under the phase III program, particularly given the differentiation of <unk> for instance, we might be able to have it.
Relation looking at high serum lipids and showed that benefit and try to get that on the label. So that's those are the kind of discussions and considerations that we're going through in terms of how we designed the phase III program.
Great. Thanks, so much.
Thank you. This concludes the question and answer session I'd like to turn the call back over to the Sungard for any closing remarks.
Thank you everyone for participating today, we appreciate this opportunity to share our results and outlook with you and thank you for your continued interest have a nice day.
Speaker Change: Thank you for your participation. This does conclude the program you may now disconnect good day.
Okay.
Okay.
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