Q3 2021 aTyr Pharma Inc Earnings Call
[music].
Good afternoon, ladies and gentlemen, and welcome to the <unk> Pharma third quarter 2021 conference call.
This time all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will be given at that time and to ask a question. During this session you will need to press star one on your telephone if you require any further assistance. Please press star zero and zero.
Reminder, this conference is being recorded for replay purposes.
It is now my pleasure to hand, the conference call over to Ashley Dunston, eight tires director of Investor Relations and corporate Communications. Mr. Johnson you may begin.
Thank you operator, and good afternoon, everyone. Thank you for joining us today to discuss <unk> third quarter 2021 operating results and corporate update we are joined today by Dr. Sanjay Shukla our <unk>.
President and CEO and Ms. Jill Broadfoot, our CFO on the call Sanjay will provide an update on our corporate strategy, including our clinical program for <unk> thousand 23, and our research and discovery programs in Europe, Helen Kim, including our preclinical program for <unk> 2008 time, Jill will review the financial results.
Financial positioning before handing it back to Sanjay to open the call up for any questions.
Before we begin I would like to remind everyone that except for statements of historical facts. The statements made by management and responses to questions. On this conference call are forward looking statements under the Safe Harbor provision of the private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ.
Materially from those in such forward looking statements. Please see the forward looking statement disclaimer in the company's press release issued this afternoon as well as the risk factors in the company's SEC filings and included in our most recent annual report on Form 10-K, and quarterly reports on Form 10-Q undue reliance should not be placed.
Forward looking statements, which speak only as of the date the army as facts and circumstances underlying these forward looking statements may change, except as required by law a tire pharma disclaims any obligation to update these forward looking statements to reflect future information events or circumstances, I will now turn the call over to Sanjay.
Thank you Ashley.
Good afternoon, everyone and thank you for joining us for our third quarter 2021 results conference call.
The third quarter was a major inflection point for a tire.
And which we demonstrated clinical proof of concept for <unk> 1923, or $19 23.
And that our novel trna synthetase biology platform has the potential to treat serious diseases.
The third.
Positive results reported from our phase <unk> study of $19 23, and always talk of doses.
Our initial interstitial lung disease or ILD indication.
Suggest that 1923 could be a transformative therapy for patients.
By reducing steroid burden, while also improving lung function and measures of sarcoidosis symptoms.
Since we reported these findings.
Had the opportunity to share them with many of the groups that played a key role in supporting us to get to this point <unk>.
Including the principal investigators.
<unk> pharmaceutical our partner for ILD in Japan.
The foundation for Taco doses research with whom we collaborated to conduct this study and even some target doses patients.
And in each case, the feedback has been outstanding.
This enthusiasm reinforces our confidence in the strength of the data.
And we are more excited than ever to proceed with the development of 1923.
We look forward to advancing 1923 to a registrational trial in pulmonary sarcoidosis next year.
Which will bring us one step closer to delivering a potential new treatment to sarcoidosis patients with clinically meaningful outcomes.
As we begin I will summarize a few highlights since we last spoke in August.
We announced positive results from a phase <unk> multiple ascending dose placebo controlled study of 19 to 23 and 37 patients with pulmonary sarcoidosis.
But in 'twenty, three was safe and well tolerated at all doses with no drug related serious adverse events.
Or signals of Immunogenicity.
Additionally, the study demonstrated consistent dose response for 1923 on key efficacy endpoints and improvements compared to placebo.
Including measures of steroid reduction lung function.
Tucker doses symptom measures in inflammatory biomarkers.
Furthermore, the clinical proof of concept data support the expansion.
The development of $19 23, and other forms of ILD.
Such as connective tissue disease related ILD and chronic hypersensitivity pneumonitis.
We announced the presentation of preclinical research at the 2021 society for immunotherapy of cancer annual meeting demonstrating the effects of EUR 28, 10, or 20 Aitken our lead anti European antibody in R&D candidates.
On tumor associated macrophages.
These data advance the understanding of 2008 and.
Mechanism of action and the process by which it may inhibit tumor progression and disrupt immune invasion.
These findings will help support the clinical development of 2010, including a planned phase one study in cancer next year.
We appointed industry veteran Dr. Robert Ashworth, as Vice President of regulatory Affairs.
And finally, we raised net proceeds of $86 million through the issuance of $10 8 million shares of common stock in September 2021 from a public offering.
With thrilled with all that we've accomplished thus far in 2021.
We're working diligently to finish the year strong and set ourselves up for a highly productive year in 2022.
Let's begin with our clinical program for 1923.
923, as a potential first in class immuno modulator for severe inflammatory lung disease.
1923 is a novel <unk> FC fusion protein based on the naturally occurring splice variant of the lung enriched trna synthetase hardest fragment that downregulates aberrant immune responses in inflammatory disease states.
<unk> hundred 23 has been shown pre clinically to down regulate inflammatory cytokine and chemokine signaling and reduce inflammation and fibrosis.
<unk> is up regulated on key immune cells known to play a role in inflammation.
And as enriched in inflamed lung tissue.
923 by selectively to MRP, and therefore has the potential to normalize the immune system.
Serving to resolve inflammation and prevent progressive fibrosis.
Thereby stabilizing lung function and alleviating morbidity and mortality.
We're developing 1923 as a potential treatment for patients with ILD a group of rare immune mediated disorders that can cause progressive fibrosis of the lung.
Our initial ILD indication for 1923 is pulmonary sarcoidosis, a disease that is characterized by the formation of granulomas, where comps of immune cells in the lungs.
The formation of these granulomas driven by persistent aberrant inflammation.
If left untreated it can lead to irreversible scarring of fibrosis, and diminished lung function, which may lead to respiratory failure or the need for a lung transplant.
We estimate that there are approximately 200000 patients with pulmonary sarcoidosis and the U S alone although estimates do vary.
About half of all patients will require some form of systemic therapy.
And 30% of all patients will have chronic progressive disease despite available treatments.
The current set of care typically includes treating the informational or cortical steroids and other immunosuppressive therapy.
Can help manage inflammation and alleviate symptoms such as cough and shortness of breath.
However, they have no demonstrated efficacy on disease progression and can result in serious long term toxicity.
Additionally, many patients do not respond to currently available treatments.
There is a substantial need for a safer more effective treatment that could reduce or replace to requirement for chronic corticosteroids or other immunosuppressive therapy and prevent disease progression.
In September we reported positive results from a proof of concept study for 1923 in pulmonary sarcoidosis.
We wanted to take a few minutes to recap these outstanding findings.
In doing so we will also incorporate some of the commentary and feedback received.
From recent meetings held with study principal our studies principal investigators or pies, where we presented the results to obtain important insight regarding what they viewed to be the most impactful takeaways.
The phase <unk> study was a randomized double blind placebo controlled multiple ascending dose clinical trial, consisting of three cohorts testing doses of one three and five milligrams per kilogram of $19 23.
Or placebo.
Those intravenously every month for six months.
The study enrolled 37 histologically confirmed only started dosing patients. These.
These patients that are active and symptomatic disease at baseline and then were stably manage on the dose of corticosteroid treatment of greater than or equal to 10 milligrams per day.
The primary objective was to evaluate the safety Tolerability immunogenicity.
Pharmacokinetic profile of multiple doses of $19 23 compared to placebo.
Secondary objectives included assessment of the potential steroid sparing effects of 19 to 23.
In addition to other exploratory assessments of efficacy, including lung function by evaluating forced vital capacity or FCC.
Serum biomarkers.
<unk> related quality of life skills in pet imaging.
Because it was a small study it was up powered for statistical significance.
The trial included a forced steroid taper with patients daily steroid dose with paper to five milligrams or less stable dose of anywhere between 10% to 25 milligrams of prednisone biweekly.
And the study aimed to keep patients at a dose of five milligrams until study completion.
If the patient symptoms got worse, the Pi had the option to increase the patients dose of steroid largely based on clinical symptom worsening.
At the patient's symptoms remained stable at week 16.
Could attempt to titrate the patient completely off steroids.
At the end of the study we assessed steroid reduction in the 1923 versus placebo arms.
Now, let's recap some of the key findings.
To begin the study met its primary safety endpoint.
Monthly dosing of 19 to 23 was determined to be safe and well tolerated at all doses there.
There were no drug related serious adverse events and no signal of Immunogenicity.
These findings are consistent with previous studies of 1923 in patients and healthy volunteers and they reinforce <unk> favorable safety profile, a key part of $19 20 threes value proposition.
Considering current treatments typically have serious side effects and long term toxicity profile, let's talk of doses and other ILD.
In terms of the efficacy endpoints, perhaps one of the most remarkable findings with the improvement in lung function observed in patients who were treated with $19 23 compared to placebo.
Lung function is an important measure of disease in this patient population the.
The granulomas that form in the lungs of these patients can cause lung to become fibrotic, meaning they become stiff and make it more difficult to breathe.
<unk> is a measure of the volume of air Exhaled over one full breadth and is an objective measure of lung function in patients with ILD.
The greater the FCC the better the lung function.
By decreasing steroid use it might be expected at RPC would decline.
And the placebo one milligram per kilogram treatment groups FEC remains stable or slightly decline.
But in the higher dose treatment groups patients had an improvement of two 8% and the three milligram per kilogram treatment group at three 3% and the five milligram per kilogram group, indicating that patients have their steroid dose substantially decrease received 1923 and there are lung function greatly improved compared to placebo.
The pie is viewed these results as very important findings from their perspective improvement of two 5% is considered clinically meaningful and comparable to what other studies in interstitial lung disease.
Have shown.
In addition, an amount of improvement is substantial might be expected in a year. So the degree and speed of these FTC percentage improvements demonstrated with 1923, particularly in the context of CRE paper and a short six months study were very impressive findings to these clinicians.
As we mentioned steroid reduction was one of the key assessments of efficacy included in the study.
All patients enrolled were stably manage of steroid in baseline steroid use was mostly balanced across treatment groups with the mean daily steroid dose ranging from 11% to 14 milligrams per day across the $19 23 and placebo groups.
Some patients. We're also taking background immuno modulator, which were permitted in this study.
While there was a slightly higher use of immuno modulators in the placebo group.
It did not impact our analysis.
Most patients were able to taper to five milligrams of steroids successfully.
Nearly all of the patients in the 1922 treatment groups were able to taper to five milligrams.
I'll only 75% of the patients on placebo were able to do so.
When you look at the average daily dose.
Saw relative reduction that overall reduction of steroid use in all of the 1923.
Groups compared to placebo.
Notably we saw some impressive activity in the five milligram per kilogram treatment group, where throughout the duration of the trial there was a 22% relative reduction of steroid dose compared to placebo demonstrating.
Demonstrating these patients disease could be managed with lower steroid doses by receiving 1923.
And when you look at the change from baseline overall for steroid dose patients were able to reduce their steroids by 58%.
From what they were on when they entered the study on average.
To put that in context, many <unk> have stated that for patients receiving baseline steroid doses of around 15 milligrams per day, and overall reduction of 50% or greater would be highly impactful to patients. If you also saw concomitant symptom improvement.
Upon reviewing the findings the pie.
We're very pleased to see an overall reduction greater than 50%.
That was maintained throughout the postpaid per period.
Finally, we had three patients were able to completely taper off steroids all in the five milligram per kilogram treatment group.
This was an outstanding finding and sets up $19 23, as a potential transformative steroid replacement therapy to.
To add to this what we heard from the Pis.
Is that there were additional patients who are well maintained at five milligrams of stiff steroid.
And in their opinion could have possibly tapered down further to zero milligrams.
In some instances patients did not want to try to taper to zero milligram, citing that they felt great at five milligrams.
We're very pleased with the findings of steroid reduction, which on their own show a dose response and a measure of drug activity.
But it is a steroid reduction combined with improvements in other efficacy endpoints like lung function and clinical symptoms, which confirm the potential of $19 23 to be a very impactful therapy.
Perhaps what made the biggest impression on the <unk> with a clinically meaningful symptom improvements. These.
These include quality of life assessments used for circuit OCD symptoms determined to measure how patients felt at baseline compared to the end of the study.
There were several validated symptom measures that we used in the study, including those for this meal or shortness of breath cough fatigue and sarcoidosis symptoms.
We assess the findings compared to a defined minimal clinically important difference for each of these indices and overall if the patient's symptoms improved remained stable or worsened.
The finding showed dose dependent clinically meaningful symptom improvement and the $19 23 treatment groups compared to placebo.
While patient symptom scores remain mostly stable and the one milligram per kilogram treatment group compared to placebo.
We saw a clinically meaningful improvement in nearly all symptom scores and the three milligram per kilogram treatment group.
And in the eyes of our experts drastic symptom improvement and the five milligram per kilogram treatment group.
And these results are really what to have our <unk> excited.
In their view. This is the only study in ILD to show substantial steroid reduction with meaningful symptom improvement.
Physicians know firsthand the high cost of chronic steroid use in these patients steroids.
Steroids are known to have side effects that can greatly impact patients quality of life as much as or even more so than the disease itself.
Quality of life compared to current treatment options as a high priority to patients living with sarcoidosis.
Many of the <unk> have stated that they prefer to prescribe the lowest amount of steroid as needed and in some cases, none if at all possible.
Yet if they must do so each and every milligram that can be regrouped reduced the predecessor in the near and long term.
Is extremely beneficial.
Finally, we will comment on some of the biomarker findings.
From a high level takeaway, we saw that when removing steroid and adding 1923 patient biomarker levels were controlled in a dose dependent manner compared to placebo and this is aligned to what we saw.
Clinically in other studies.
This concludes the same inflammatory cytokines and key markers of sarcoidosis that we saw impacted by $19 23, and our preclinical lung inflammation models and a previous clinical study we conducted in patients with COVID-19 pneumonia.
We expect to go into more detail of these findings at an upcoming medical conference.
The results of this study support the advancement of $19 23 to the next stage of clinical development and we expect to initiate a registrational trial in pulmonary sarcoidosis next year.
We anticipate meeting with regulators, including the U S food and drug administration very shortly to discuss these data.
And subsequent clinical development and path to registration for 1923.
Proposal <unk> doses.
As part of our regulatory efforts, we appointed Dr. Bob Robert Ashwin.
As vice President of regulatory Affairs.
Dr. <unk> is an industry veteran with more than 35 years of regulatory and drug development expertise expertise, including a track record of contributing to the FDA approval of more than 12, new drugs across a broad range of categories and disease indications.
In addition to mapping out our regulatory strategy since we reported the results we've been preparing for next steps for 1923 in many other ways as.
As we mentioned we conducted an investigator meeting to present, the findings and obtain valuable feedback that will contribute to trial design for the next study.
We also presented the findings to our partner <unk> to help determine the optimal ways in which they will be able to participate in the next study. In addition to their development efforts of 1923 for ILD in Japan.
While our current focus for 1923 is on the public because on pulmonary sarcoidosis and planning for the next study in that indication the.
The mechanism of action translational work and clinical data for 1923 combined with the overlapping disease pathology across ILD strongly suggests the 1923 could have potential in other indications as well.
There are more than 200 types of IOP that can cause fibrosis or scarring of lung tissue.
Primarily driven by aberrant immune response to an inhaled exposure or other insult.
The four main types that make up roughly 80% of the population.
These include connective tissue disease related ILD.
We're in lung manifestations are secondary to autoimmune diseases, such as systemic sclerosis.
Chronic hypersensitivity pneumonitis, which results from an exaggerated immune response to environmental antigens.
In idiopathic pulmonary fibrosis, the prototypical fibrotic lung disease.
We estimate there are over 500000 patients.
Currently living with ILD in the United States and over 3 million patients globally.
Like sarcoidosis all of these diseases have limited standard of care with substantial morbidity and mortality.
Outcomes for these patients remain poor despite current treatment options with median survival as low as three years in certain cases.
Scarring of the lung can occur in upwards of 20% of patients across all forms of ILD.
Standard of care outside of IPF is treatment with immuno module toy therapy similar to those used in sarcoidosis.
And like Sarcoidosis. These treatments have limited clinical evidence of efficacy and are associated with significant long term toxicity.
When you think about some of these opportunities that we may be able to explore we think we have a transformative therapy in 1923 with an addressable multibillion dollar market.
While we've been focused on advancing our 1923 clinical program. We've also progressed our preclinical pipeline.
Which includes the development of anti <unk> antibodies for cancer and inflammation.
We've discussed in detail the clinical proof of concept for 1923.
What's also very exciting about this data is that it validated and ERP to 1923 binding partner as a target.
A broad receptor screen for $19 23 led us to this very selective receptor.
We believe it is a compelling therapeutic target in a number of diseases.
These areas in addition to inflammation, including oncology.
As <unk> is well established as playing a role in various disease states. We utilize our in house antibody engineering capabilities to develop a panel of blocking antibodies to selectively target distinct domains of this untapped target include.
Including those interacting with some of forums that Jeff and certain <unk>, such as CCL 'twenty one.
When it comes to cancer and our pizza is up regulated on a variety of solid tumors and it's particularly enriched in highly aggressive tumors with expression linked to worsened patient outcomes in several cancers, which may include drug resistance to current therapies, such as chemotherapy or targeted agents.
<unk> is also highly expressed on key immune cells implicated in regulating cancer progression, including tumor associated macrophages and myeloid derived suppressor cells among others.
Antibodies that can selectively block different aspects of MRP two signaling pathways may have therapeutic potential in these aggressive cancers.
<unk> is implicated.
One of the antibodies, we developed 28 <unk> is a fully humanized monoclonal antibody that specifically and functionally blocks the interaction between <unk> and VEGF.
This is our lead anti <unk> antibody, an IND candidate in preclinical development for cancer.
The rollout of <unk> in Veg F signaling in the tumor microenvironment and its potential importance and the progression of certain aggressive cancers is becoming increasingly validated.
We have generated a body of compelling preclinical data in both human derived in animal models, demonstrating 28, tenths blocking ability and tumor inhibitory effects.
We continue to investigate 2000 eighteen's mechanism of action and the potential ways in which this novel antibody may confer some of the anti tumor effects that we've seen.
Recent data announced just this week at city adds to a growing body of knowledge of these antibodies mechanism of action.
The research details the effects of 28% on tumor associated macrophages or <unk>.
Differentiated from human Triple negative breast.
Breast cancer tumor cells.
It is well known that Tam suppress T cell activity.
All of that player and important role and mounting an immune response to kill cancer cells.
<unk> also play an important role in the induction of epithelium.
<unk> transition or Emt, a process that is of great importance and regulating tumor growth progression and metastatic cascade.
As well as being implicated in tumor of ageing of the immune system.
Furthermore, these highly suppressive Tam express high levels of MRP too.
Treatment with 28, <unk> was shown to decrease the suppressive capabilities of Tam against T cells compared to untreated attempts.
Furthermore, <unk> treated with 28 10 showed a decrease in <unk> gene expression, which is a master trends scripture factor regulating emt.
These results suggest that 28, 10 may be able to treat cancer by targeting tumor immune avoidance mechanisms as well as regulating emt.
These findings demonstrate for the first time modulation of key cells associated with suppressing T cell mediated anti tumor responses in the tumor microenvironment.
As a result of treatment with 28 10.
These data advance our understanding of 28 <unk> mechanism of action and the process by which it may inhibit tumor progression and disrupt immune invasion, suggesting the ways in which 2008 to 10, maybe a potentially effective anti cancer agent.
And these findings will help support the clinical development of <unk> 28 <unk>.
Including as I mentioned, a phase a planned phase one study in cancer next year.
Finally today, we want to emphasize the magnitude of what the recent clinical proof of concept for 1923 means for our trna synthetase biology platform, which is the foundation for our science and our approach to drug development.
We have shown that we can effectively take a trna synthetase and its biological pathway and translate it into an innovative therapy with the potential to improve outcomes for patients.
In essence, we are well on our way to fulfilling our mission of creating a new class of medicines.
Our first case as evidenced from the data from 19 to 23 comes from cars the synthetase driving our lead clinical program.
That has shown promise for comments, our doses, but has great potential for other <unk> as well.
And through <unk>, we have found it compelling and largely untapped novel targeted <unk>, which also forms the backbone of our lead preclinical program with 28.
And two additional <unk> targeting antibody with implications for cancer and inflammation.
As a reminder, there are 20 trna synthetase gene families.
<unk> intellectual property portfolio covers protein.
Derivatives from all of these with over 300 protein compositions patented.
The results for 1923 of our major step forward in unlocking the potential and promise of this novel Biology platform.
I will now turn it over to our Chief Financial Officer, Jill Broadfoot to review our financial results.
Thank you Sanjay cash cash equivalents and investments as of September 32021 were $116 4 million.
This includes net proceeds of approximately $80 6 million.
Public offering in September.
We received strong support from several of our existing shareholders and also generated interest and demand from high quality institutions, who are newcomers to HII.
Research and development expenses were $5 1 million for the third quarter of 2021, which consisted primarily of expenses related to 1923, 28, 10, and our discovery program.
And administrative expenses were $2 6 million for the third quarter 2021.
Common shares outstanding were $27 8 million and fully diluted shares were $29 6 million as of September 32021.
With our updated cash progression clean balance sheet and support from several high quality long term focused investors. We're in the strongest position that the company has been in quite some time and allows us to move the company forward the combination of capital and clinical proof of concept data in hand.
Essentially to drive meaningful value for the company.
Now I'd like to turn the call back over to Sanjay before we open it up to Q&A.
Thanks, Joe.
Well, our recent clinical readout represents.
Years of hard work.
<unk> intense dedication to developing and advancing our trna synthetase biology platform.
To one that can generate new therapeutic targets.
And from which we can develop a potential new class of medicines.
While we're very excited and encouraged by these recent results for 1923, we're even more excited.
For what is still yet to come.
So with that we appreciate your interest continued support at this time, Jill and I will be happy to take your questions.
And as a reminder to ask a question you will need to press star one on your telephone again that is star one.
And our first question is from Kennan Mackay.
RBC capital markets. Your line is now open.
Hi, Thanks for taking my question and congrats on a really transformative quarter.
Two questions maybe first.
I would imagine the data from 19 to 23 in pulmonary sarcoidosis.
To your point sparked a huge amount of interest.
Just thinking about this asset and some of the other indications that are are there any.
Thoughts around potentially partnering this asset.
So.
Can you just help us understand sort of what that could look like.
Then.
Just thinking about the potential registrational path in pulmonary sarcoidosis, you've mentioned starting the potential Registrational trial next year I'm, just wondering from a registrational perspective.
Endpoints, we should be.
Considering.
For an approval trial, thanks, and congrats again.
Thanks, Kevin.
<unk> so certainly are.
Our data is being viewed as.
Probably the well maybe the best sarcoidosis data.
Really produced in the last 15 years.
I think the fact that we are the only.
Therapy that has been able to frankly reduce steroids and see this magnitude of clinical improvement.
Is garnering a lot of interest not only from experts, but as you can imagine from.
Partners as well it is something that we can't.
Can't comment too much about with regards to partnering activities, we're going to do what's right here to make sure that we continue to drive value for this program.
As Youre aware biotech companies like us can sometimes do that on our own and sometimes we can do that through partners.
It makes sense for us and shareholders.
We may pursue those kinds of.
Of options, but at this point, we are really bullish on the.
The data our findings we have a really.
The strong wind behind us at this point with regards to the endpoints, which was your second question.
The endpoints that.
We looked at.
Hitting on really all of the key endpoints steroid reduction.
We see improvement and also the.
Rather large symptom improvement gives us really really great options. When we talk to the regulators, we know theres guidance from the FCA talking about how symptoms and meaningful outcomes like that are really important for new therapies. We also know that there is other guidance, saying, we need better therapies when the standard of cares.
Toxic.
And this.
The environment that we're in with ILD. We've also demonstrated that that could also be effective strategy.
Then the FCC improvement, we saw as I mentioned more than two 5% is viewed as.
Significant in the eyes of the clinicians.
To see $2 83, 3% and our highest dose this is better.
And very competitive too as I mentioned the types of therapies that have been approved for ILD.
IPF, mostly.
So we have great options here.
The Delta that we have.
And Delta of improvement gives us a lot of ability to carefully craft a trial and hit a P value in a in a large registrational trial.
So I will say that stay tuned with regards to these endpoints.
We have three very very good options to discuss with the FDA.
And I do think that.
We are in an extremely favorable position.
To argue for any of these and really work closely with them with the FDA for example to determine what do they think is the most important.
When you talk about patients and providers, they really want to see symptom improvement and they want to see that improvement while at the same time, removing steroid and as I said, we're really the only therapy, that's been able to do that thus far in ILD.
And our next question is from Sheila.
Sheila.
Capital partner your line is now open.
Yeah. Good morning, Thanks for taking my question.
I just have a couple of quick ones. The first one is just about 1923 days in the prepared remarks, you noted certain legal quorum.
We plan to actually start the phase III study alongside you all would that be a little better raw rating for them or is it.
The possible to start with.
And then you asked and then expand into that their attorneys just kind of wondering if that could impact the timing of the study in terms of waiting for that and then the second question is just about totally Tom just wanted to get a sense of what needs to be completed for the RMB. One is some things that are under consideration in terms of the garrison.
But indications how you're thinking through that and then the last but are you watching alongside kols to kind of decide how to move forward.
Right.
Thanks Vic.
Certainly with your first question around cure and Theres no delay there's no waiting if anything.
I'd like to get started tomorrow, probably.
As you as you.
Are aware of.
Our current trial had some impacts with regards to <unk>.
Covid.
In the middle of the trial that we were able to battle through.
And get the trial enrolled.
Julien themselves have completed the necessary work that allows them to join our trial immediately so we will be looking to launch at the same time.
With with cure in here in a trial together so.
So really no delays.
Related to that that that partnership Youre second question was around 28 to 10 I would say right now we're in the final stages of.
Honing in on.
The indication.
Or at least the phenotype of indications to look for.
In the trial next year.
We've see.
<unk> seen a lot of excellent data over the last two years with 28 10, we pointed to efficacy in triple negative breast cancer lung cancer with <unk>.
Really completing I would say now the.
Indication selection process, but what you can also appreciate.
Is.
Many early cancer trials also sometimes take a basket approach, where they look at specific environments.
For example, where <unk> might be highly enriched so it could be across multiple solid tumors.
And we are right now working very closely with.
Key opinion leaders in Europe, Poland Biology.
Also those who have more of a cancer biology focus.
Recent data.
Around our mechanism at city, obviously is going to.
Really inform us also looking at that tumor microenvironment. So much in the same way that we develop 1923, we are taking a very curated carefully crafted approach to advancing 28 10 doing it by being data driven.
And I really like the setup here for 2810.
Two potentially.
Yes.
Our next real real opportunity at a tire in particular because of what we're learning around <unk> and some of those aspects around terms and emt that I discussed.
And congrats on the cargo.
Thanks.
And our next question is from <unk> <unk> of Jones trading your line is open.
Hi, Thanks for taking my questions. So firstly on the trial design for 1923.
In terms of the potential primary endpoint for registration trials, where does your preference between steroid reduction FCC and symptoms.
I am trying to understand it is among the three which endpoint do you think has the least risk.
And secondly on development.
<unk> development plans for other R&D.
Any details on timing.
Sure Dan.
The gating factors.
Scott Thank you.
Okay, you broke up a little bit there for cloud in the second half, but I think I got it. So the first the first question is around preference.
Yes.
Honestly, we've been this is a situation where I think for me as a clinician I look at symptoms and I'll also look at the magnitude of improvement we saw.
And our symptom scores.
Is really something that I think jumps off the page.
So that gives us a lot of room.
If we want to actually power study.
And hit a minimal Clint.
Clinically important difference there so a lot of opportunity with symptoms and symptom improvement.
We also have to look at regulatory precedents that IPF drugs have been approved based on FCC.
We have that also because we've hit a threshold.
In a very short study.
Threshold that I think would be also dramatic to see two 5% over the course of the year, we're seeing north of 3%.
Six months, so two very very good options there with regard to steroid reduction. We also are hitting a threshold that is really important but we have to understand that.
There isn't necessarily as much precedent when you look at steroid reduction as an endpoint compared to MPC.
And if you think about steroid reduction versus symptoms.
Patients and providers.
Really want to see that symptom benefit not just not just a steroid reduction without that so.
Maybe that gives you an idea of the lean here, but again, we have three really good options here to have a informed discussion with the FDA and worldwide regulators, but I would say right now the <unk>.
In terms of the area that we really really like.
About potentially pushing that forward.
Symptom improvement.
Second question was I think it really around the <unk> filing is that for <unk>.
Sorry. The same question is on the plans for other ILD indications CHL other IV.
Yes.
You gave us on the timing for moving forward.
What are the gating factors for a potential trial starts right now.
Yes, I mean, we are game ready to be able to move into some of the ILD indications, but we want to make sure that we <unk>.
Focus and get sarcoidosis in that trial launch and running well first.
At the same time as Youre aware, we produced really good efficacy data in animal models for example in scleroderma ILD, so with our current data being now starting to be.
Talked about and consumed by more pulmonologists in other areas.
We are getting interest and a lot of interest in connective tissue disease.
Pneumonitis, even IPF because IPF you still have quite a bit of inflammation that patients have trouble with.
On top of Pirfenidone or Nintendo So there's no short shortage of interest for US we just want to remain focused move.
Move our core value.
A core value here at sarcoidosis, but I do think that it would.
We will be able to quickly jump into other indications right now I would say stay tuned about another IND.
In the work for.
Another another non sarcoidosis ILD, but.
I want to make sure that we get tugboats is launched.
Crisply and executed well first.
And then we can get into those other indications.
Thank you.
And our next question is from Yale Jen of Laidlaw <unk> co. Your line is open.
Sure.
Good evening and thanks for taking the question.
My first question is that I know that you mentioned.
Earlier in terms of alpha.
Okay.
Ah 90.
Okay.
The drug could be potentially partnering opportunity.
But still giving the more patient size or more limited.
Reach for the physicians.
Something that you can also potentially marketed.
<unk> itself and.
We'll be the thought if thats the potential routes you have to take any thoughts on that and any comment on that.
Yes, Thanks, Joe.
Have the capabilities and the.
We've already demonstrated the ability to execute and move really really difficult indication forward. So I have no doubt.
We could actually move this forward and.
And market and commercialize.
Doug ourselves.
We were really the world leader I would say right now.
Non IPF.
In our non IPF therapy here, so we have.
Entirely the focus and mindset to take this forward ourselves.
At all times with partnering do you have to just sort of way.
Some of those.
The way that interest you have to.
Listen.
Those sorts of.
For Reyes towards us.
Say that Dave.
Never been hotter if you will obviously data like this is going to generate a tremendous amount of interest.
So you can look at those companies that are in the respiratory space.
This is <unk>.
Extremely attractive opportunity having worked in those sort of large organizations prior to a tire.
This is <unk>.
Built very very well to be a late stage asset really for anybody in because it has that transformation transformative potential I think.
Any commercial team would also look at this as a potential type of game changer for their franchise there but.
Thinking about how we want to move forward. We know that this is an extremely valuable asset and we are prepared to.
To really take it all the way here.
That's our mindset at this point.
Okay, Great. That's very helpful. And then maybe one more short question, which is bad debt.
I assume the next step.
If you need to speak with agency and carve up.
Yes.
Understanding data thoughts and to carve up the pivotal registration trial design.
Do you guys have a timeline in terms of when that meeting might take place or would that be in the fourth quarter or more likely in the first half or first quarter next year and thanks.
We're moving as quickly as possible as I said, we've been quite busy the last say couple of weeks here with.
Talking to investigators from around the world.
I will say stay tuned.
Working very very quickly here to get with the FDA.
Because we do want to start this trial quickly next year patients can't afford to wait there's a lot of interest to move into a phase III trial from sites clinicians around the world I'd say, we're probably up to 50 to 60 centers that want to commit now to entering into our trial. So the excitement is there we're in.
Not going to slow down our regulatory efforts and we will be meeting with the FDA as quickly as possible.
Okay, Great and again congrats on the very same.
Just know that transformative.
Quarters.
Thank you Joe.
And our next question is from Joseph Bank, Dennis <unk> of H C. Wainwright. Your line is open.
Good afternoon, everyone, ladies and when you add ons like Joe and thank you for taking the questions.
With regards to the data.
Thank you for shedding the feedback of the investigators and I was wondering I know this is a small study, but as you look at baseline conducted each day.
How does that any biomarkers that could potentially predict on EMEA duration.
<unk>.
Okay.
That's a great question, a predictive biomarker of progression is something to advance all of the experts have been searching for worldwide.
Region to region, you may have a biomarker that.
Individual or.
A group of experts may favor more than others.
We'll say that what we tried to do when we looked at our biomarker panel is taken into account everybody's favorite.
What im really encouraged by is we see consistency, regardless of which biomarker people like the most.
We're controlling all of them.
We're doing a great job with regards to.
For example, controlling IL six.
Again, I don't want to go into too many details about each individual biomarker, we have a very important.
Abstract in a publication that wed like to get out so I do have to do it to save a little bit of powder for I think what would be a major medical journal, but but the point the key takeaway here is when you look at.
The cytokines that we've looked at previously.
<unk> TNF interferon gamma MCP one.
IP 10.
These are these are the markers that we followed years ago in our animal studies that the drug seem to impact. These are the markers that were highly up regulated in say COVID-19 pneumonia patients that making 23 did a a substantial job of knocking down and I think what youre going to find is the same.
Findings in this study. So this is why <unk> spends a lot of time really understanding mechanism and we talk a lot about biology and mechanism that we derisk things as early as possible. So that when we do have clinical results. While they were not seeing the kind of results with 1923 program has produced so.
I'd say stay tuned for that and Daniela.
But.
I'd, probably refer to you to our recent Trs publication, which if you take a look at the box and whisker plots from those COVID-19 pneumonia patients we're going to have a similar kind of presentation hopefully at a medical major medical conference.
That will.
Show that consistency again now in sarcoidosis patients.
Got it. Thank you and thank you for that and with regards to the potential I think discussion I'll try and answer.
Again, you have Andy sharing your thoughts on the endpoint, but can you give us a sense of do you.
Its size and duration of the trial.
Yes, that's a great question. So when you look at for example, the magnitude of our effects in say la.
<unk> symptoms improving along symptoms, we can basically model that if we wanted to power a trial to see.
A significant signal for example in symptoms what would the trial look like right now ballpark.
As we've said previously we're looking at about 200 patients.
We've always thought that that would be kind of the ballpark.
Yes.
Ahead of data now that we have the data.
We feel even more confident that we're going to be able to plan for a well powered trial with numbers around there again, it's all dependent on interactions with the agency. So I cant say definitively until we finish that but I will say that we're looking at a trial somewhere in that ballpark of around 200 patients.
<unk>.
From a duration standpoint, this was a six month study.
There is a suggestion that if we run a longer study we may see even more worsening in placebo. So I do think to see a potentially larger effect and certainly a more durable effect.
We'll be looking at a longer trial and right now we will be discussion discussing somewhere between a nine to 12 month trial with with the ex with the regulators. So again thats dependent on what the caveat this dependent on that those interactions, but right now those are our draft our draft plans here.
Got it thank you very much.
And our next question is from <unk> Zhang of Oppenheimer. Your line is open.
Hello, everyone. This is Eric I think already prototypes today.
Congrats on all the progress and thank you for the question I'll just share from us.
Could you give us an update or any.
Color on the upcoming milestones from children, especially after carrying yarn.
Discussions with them.
Just on the timing of those are developed bank regulatory and in the future.