Q4 2021 Gossamer Bio Inc Earnings Call
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Good day, and thank you for standing by and welcome to the Gossamer Bio Q4 earnings call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question during the session you.
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone keypad. And if you require any further assistance, you may press star 0. Without further ado, I would like to welcome your first speaker for today, Mr. Bryan Giraudo. Sir, the floor is yours.
I'll need to press star one on your telephone keypad and if you require any further assistance you May press star zero without further Ado I would like to welcome your first speaker for today, Mr. Brian Dorado, Sir the floor is yours.
Bryan Giraudo: Thank you, operator, and thank you all for joining us this afternoon. I am joined on today's call by Gossamer's co-founder, chairman, and chief executive officer, Faheem Hasnain, Gossamer's chief medical officer, Dr. Richard Aranda, and Gossamer's chief scientific officer, Dr. Laura Carter. Earlier today, Gossamer issued a press release announcing its year-end 2021 financial results and provided a corporate update. Please note that certain information discussed on the call is covered under the safe harbor provisions of the Private Securities Litigation Reform Act.
Thank you operator, and thank you all for joining US. This afternoon I'm joined on today's call by Gossamer co founder Chairman and Chief Executive Officer.
Chief Medical Officer, Dr. Richard Aranda, and Gossipers, Chief Scientific Officer, Dr. Laura Cart earlier.
Earlier today Gospeler issued a press release announcing its year end 2021 financial results and provide an update. Please note that certain information discussed on the call is covered under the safe Harbor provisions of the private Securities Litigation Reform Act, we caution listeners that during this call Gossamer management will be making forward looking statements actual results may differ.
Bryan Giraudo: We caution listeners that during this call, Gossamer management will be making forward-looking statements. However, actual results may differ materially from those data or implied by these forward-looking statements due to risks and uncertainties associated with the company's business.
Different materially from those stated or implied by these forward looking statements due to risks and uncertainties associated with the company's business.
Bryan Giraudo: These four local statements are qualified by the statements contained in Gossamer's news releases and SEC filings, including in the annual report on bone 10K in Southern Confinals. The conference also contains time-sensitive information that may be acted on only for a limited period of time. Our ability to meet our guidance, especially that related to timely initiation and completion of clinical studies, in addition to our ability to release results from our clinical trials in a timely manner, may be inversely affected by the ongoing COVID-19 pandemic. Gossamer Bio undertakes no obligation to revise or update any more forward-looking statements, reflect events, or circumstances, after the date of this conference call. Now, let us turn the call over to the evening.
These forward looking statements are qualified by the statements contained in <unk> news releases and SEC filings, including in the annual report on Form 10-K .
This conference call also contains time sensitive information that may be accurate only for a limited period of time, our ability to meet our guidance, especially that related to timely initiation and completion of clinical studies. In addition to our ability to release results Mark the trough in timely manner may be adversely affected by the ongoing COVID-19 pandemic.
Gossamer bio undertakes no obligation to revise or update any forward looking statements to reflect events or circumstances. After the date of this conference call now I'd like to turn the call over to Sidney.
Faheem Hasnain: Thank you. Thank you, Bryan, and thanks to everyone for joining us on this afternoon's call. In 2021, the year of execution for the Gossamer team, despite the challenges that the preceding two years have provided, we at Gossamer are excited and energized to enter 2022 with two upcoming proof-of-concept phase two readouts in ulcerative colitis and pulmonary arterial hypertension. Now, while these product candidates, Seralutinib and Gb004, target different indications, utilizing different And if approved, we believe both molecules hold treatment paradigm-shifting potential. First, let's start with GBO4.
Thank you, Brian and thanks to everyone for joining us on this afternoon's call.
2021 was the year of execution for the Gossamer team.
Like the challenges that the preceding two years have provided.
We at Gossamer are excited and energized to enter 2022 with two upcoming proof of concept phase two readouts in ulcerative colitis and pulmonary arterial hypertension.
Now while these product candidates Sarah Loopnet, Ben G. P O O four target different indications utilizing different approaches we viewed them both the like in the sense that they're using novel mechanisms to target populations that continue to be underserved and if approved we believe both molecules called treatment paradigm shifting potential.
First let's start with G B O for the.
Faheem Hasnain: The Phase II SHIFT-UC study is on track to read out Week 12 Primary Endpoint top-line results early in the second quarter of this year. And as a quick reminder, the SHIFT-UC study is a randomized, double-blind, placebo-controlled global clinical trial studying Gb004 in patients with active mild to moderate UC despite treatment with 5-ASA therapy. Patients were randomized in a one-to-one-to-one ratio between two doses of Gb004 in tablet form and placebo. The 12-week primary endpoint of this trial is clinical remission.
The phase two shift you see study is on track to read out week 12 primary endpoint top line results early in the second quarter of this year and as a quick reminder, the shift you see study is a randomized double blind placebo controlled global clinical trial studying G. D O O four in patients with active.
Mild to moderate UC, despite treatment with five assay therapy pace.
Patients were randomized in a one to one to one ratio between two doses of G. D O four in tablet form and placebo.
Faheem Hasnain: Secondary endpoints include clinical response, histological remission, endoscopic improvement, and mucozal heal. Relevant safety and exploratory endpoints are also being assessed during the clinical trial. GPO4 is distinct and may have a differentiated profile from the immunomodulatory or immunosuppressive mechanisms of approved IBD medications and those in late stage development.
The 12 week primary endpoint of this trial is clinical remission and secondary endpoints include clinical response, histological remission endoscopic improvement and mucosal healing.
Relevant safety and exploratory endpoints are also being assessed during the clinical trial.
The G. P O four as distinct and May have a differentiated profile from the meter modular Tory are immunosuppressive mechanisms of approved IV D medications and those in late stage development G.
Faheem Hasnain: GbO4 is designed to be gut targeted with higher intestinal exposure than systemic exposure, and clinical and preclinical data generated to date support this feature. By reducing local inflammation and potentially restoring intestinal epithelial barrier function and restitution through GBO due to its gut-targeted nature and preferential stabilization of hip one out, we believe GBO4 could improve outcomes for IBD patients. We believe this mechanism has potential as a standalone therapeutic as well as in combination therapy with other therapeutic mechanisms in IBD.
G. B O. Four is designed to be got targeted with higher intestinal exposure than systemic exposure.
Clinical and preclinical data generated to date support this thesis.
By reducing local inflammation and potentially restoring intestinal filial barrier function and restitution through G. D. O force got targeted nature and preferential stabilization of hip one alpha we believe G. B O four could improve outcomes for IBD patients. We believe this mechanism has potential.
As a standalone therapeutics as well as a combination therapy with other therapeutic mechanisms in IBD.
Faheem Hasnain: Now, in addition to the week 12 primary endpoint coming early in the second quarter, in the fourth quarter of this year, the SHIFT-UC trial is also expected to read out week 36 treat-through endpoints in the fourth quarter. Now, as some of you may know, we have set a number of our sights and patience within the ongoing phase to shift the UC study in Ukraine and Russia. First and most importantly, our hearts go up to our Ukrainian patients, caregivers, investigators, study coordinators, and, of course, the Ukrainian people as a whole. Above all else, we hope for their health and safety in this horrific situation.
Now in addition to the week 12 primary endpoint coming early in the second quarter.
Fourth quarter. This year. The shift you see trial is also expected to read out week 36 treat through end points in the fourth quart.
Now as some of you may know, we had a number of our sites and patients within the ongoing phase II shift UC study in Ukraine and Russia.
First and most importantly, our hearts go out to our Ukrainian patients caregivers investigators study coordinators coordinators and of course, the Ukrainian people as a whole above all else, we hope for their health and safety in this horrific situation.
Faheem Hasnain: In terms of impact on our ongoing trials, Gossamer Bio's clinical operations team has been vigilant and proactive throughout the escalation of tensions and the tragic breakout of hostilities. We anticipate no impact on data for our 12-week primary end. Understandably, communication into Ukraine has been challenging, and we're continuing to monitor for impacts to our 36-week, I'm moving on to Sarah Lutnip, also known as GB002. Gossamer continues to enroll patients in its ongoing Phase 2 TORI study in patients with functional Class 2 and 3 PAH patients. As you may recall, the wave of COVID-19 related to the Delta variant in the late summer and fall of 2021 raised barriers to enrollment.
In terms of impact to our ongoing trials Gossamer bio's clinical operations team has been vigilant and proactive throughout the escalation of tensions and the tragic breakout of hostilities, we anticipate no impact on data. So our 12 week primary endpoint.
Understandably communication into Ukraine has been challenging and we're continuing to monitor or impacts to our 36 week data set.
Moving on to Sarah Loopnet also known as G D O O to.
Gossamer continues to enroll patients in its ongoing phase twos Tory study in patients with functional class II and three ph patients as you may recall the wave of COVID-19 related to the Delta variant in the late summer and fall of 2021 raised barriers to enrollment but.
Faheem Hasnain: But we're pleased to say that at this point, the wave of COVID-19 related to the Omicron variant has not significantly impacted patient enrollment. Today, we're able to reiterate our current guidance that we expect to read out top-line data from the ongoing TORI study in the second half of this year, barring any further developments in the ongoing COVID-19 viral pandemic.
But we're pleased to say that at this point the wave of COVID-19 related to omicron variant is not significantly impacted patient enrollment today, we're able to reiterate our current guidance that we expect to read out top line data from the ongoing Tory study in second half of this year.
Of course, barring any further developments in the ongoing COVID-19 virus pandemic.
Faheem Hasnain: Now, once patients complete the blinded 24-week study period as part of the TORI study, they are granted the option of enrolling into an open-label extension trial. This extension trial should allow us to generate valuable and elucidating long-term data in patients. We continue to see a very high percentage of patients who have completed the 24-week study period elect to continue onto the open-label extension, similar to the IMPRESS study of imatinib and the PULSAR study of cetator.
Once patients complete the blind at 24 weeks study period as part of the Tory study. They are granted the option of enrolling into an open label extension trial.
This extension trial should allow us to generate valuable in elucidating long term data in patients.
To date, we continue to see a very high percentage of patients who have completed the 24 week study period elect to continue onto the open label extension.
Similar to the impress study of Imatinib and Pulsar study of Satanic set.
Faheem Hasnain: If you recall, the IMPRESS study was hindered by a very high discontinuation rate due to adverse events, with roughly one-third of patients in the imatinib arm dropping out prior to the 24-week primary end-of-life. The majority of these dropouts in the impress, Curtin, the first eight weeks. We've been pleased to see that, to date, the blinded discontinuation rate in the TORI study has been more comparable to the more manageable discontinuation rate observed in the PULSAR study of Cetatarsan.
If you recall the impress study was hindered by a very high discontinuation rate due to adverse events with roughly one third of patients in the imatinib arm dropping out prior to the 24 week primary endpoint. The majority of these dropouts in the impress study occurred in the first eight weeks.
We've been pleased to see that today are blinded discontinuation rate in the Tory study has been more comparable to the more manageable discontinuation rate observed in the pulsar study of the tattersall.
Faheem Hasnain: Now moving on from serolutinib, our CNS penetrant BTK inhibitor, GB5121, is expected to enter a global phase 1b slash 2 clinical study in PCNSL, CNS lymphoma patients, in the first half of this year. We previously announced on our prior earnings call that GB5121 had entered a clinical trial in healthy volunteers outside of the U.S. Since then, in the fourth quarter of 2021, we're happy to announce today that our IND application has been submitted to and accepted by the USFDA.
Now moving on from sterile Loopnet are CNS penetrant PTK inhibitor GB 50, 121 is expected to enter a global phase one b slash two clinical study in P. C. NFL CNS lymphoma patients the first half of this year.
We previously previously announced on our prior earnings call that GBP 50, 121 had entered a clinical trial in healthy volunteers outside of the U S.
Since then in the fourth quarter of 2021, we're happy to announce today that our R&D application has been submitted with and accepted by the U S. FDA.
Faheem Hasnain: Now with that, I'll hand it over to our CFO and COO, Bryan Giraudo, for a final update. Bryan. Thank you, Faheem. We will now review the year-end finance results for the full year 2020. We ended the year with $325 million in cash and cash equivalents.
And with that I'll hand over to our CFO and COO, Brian Gerardo for final update Brian . Thank you for him.
We will now review the yearend financial results for the full year 2021, we ended the year with $325 million of cash cash equivalents, we continued to maintain a robust balance sheet and anticipate our cash and cash equivalents.
Bryan Giraudo: We continue to maintain a robust balance sheet and anticipate our cash and cash equivalents plus the capital available to us in our debt facility will provide us sufficient capital resources in the second half of 2020. For the quarter ended December 31st, 2021, R&D expenses were $41 million compared to R&D expenses of $39 million for the same period in 2020. R&D expenses for the full year 2021 were $170 million, compared to $161 million for 2020.
The capital available to us and our debt facility will provide us sufficient capital resources in the second half of 2023 for.
Bryan Giraudo: The increase is primarily due to an increase in clinical trial and preclinical study costs associated with serolumib, Gb004, Gb5121, and preclinical protocols. This increase was partially offset by decreases in clinical trial and pre-colonical study costs related to GP001, as well 75. G&A expenses in the fourth quarter were $11 million, compared to $16 million for the same period in 2020. G&A expenses for the full year 2021 were $46 million, compared to $50 million for the full year of 2020. The net loss for the three months ended December 31, 2021 was 56 million, or 74 cents per share.
For the quarter ended December 31, 2021, R&D expenses were $41 million third to R&D expenses of 39 million for the same period in 2020.
R&D expenses for the full year, 2021, 470 million compared to $161 million for 2020.
The increase was primarily due to increased clinical trial and preclinical study costs associated with service G. B zero zero for GBP 121, and preclinical programs.
This increase was partially offset by decreases in clinical trial and frequent study costs related to <unk> 001, as well so Bob Gee.
G&A expenses in the fourth quarter were 11 million compared to 60 million for the same period in 2020 G&A expenses for the full year 2021 were 46 million compared to 50 million for the full year 2020.
The net loss for the three months ended December 31 2012.
Anyone with $56 million or 74 cents per share compared to a net loss of $65 million or dollar buyer.
Bryan Giraudo: Compared to a net loss of 65 million, or a dollar or five per share for the same period in 2020, that loss for the failure ended on December 31, 2021 was $234 million, or $3.13 per share, compared to a net loss of $243 million, or $3.55 per share for the full year ended December 31, 2020.
Sure for the same period in 2020.
The net loss for the full year.
Ended December 31, 2021 was $234 million or $3.13 per share compared to a net loss of 243 million or $3.55 per share for the full year ended December 31, 2000 plane.
Faheem Hasnain: With that, I'll turn the call back over to Faheem for some closing comments before we open up for Q&A. Thanks, Bryan. Operator, please go ahead and open the line to questions. Status Note.
I'll turn the call back over to the heme for some closing comments before we open up for Q&A.
Thanks, Brian Operator, Please go ahead and open the line for questions.
Operator: At this time, if you have questions, please press star one. Again, that is star one to ask a question. We'll pause for just a moment to compile the Q&A roster. Our first question comes from the line of Bryan Chang. Please ask your question. Hey guys, thanks for taking my questions today. I have a couple on the UC size since that's going to be your next coming callus.
That has started sir at this time, if you have questions. Please press star one again that is star one to ask a question.
We'll pause for just a moment to compile the Q&A roster.
Our first question comes from the line of Brian Cheng. Please ask your question.
Faheem Hasnain: Just on the FSC perspective, you know, we're pretty clear on what we should expect in terms of the placebo rates and also the efficacy rates, the clinical remission rates specifically. Can you just remind us how the nostalgic benefits are associated with remission? It'll be great if we can help us to get a bit more color on how we can extrapolate early histologic benefits to remission later on. Have one more follow-up. Thank you. I'll turn that question over to Richard Aranda, our Chief Medical Officer. Yes. Thank you, Faheem.
Hey, guys. Thanks for taking my questions today.
On a new site and Stephane can be our next upcoming palace.
Just on the efficacy perspective, you know, we're pretty clear on what we ship back in terms that the placebo away and also the efficacy rates.
The clinical remission rates specifically.
Can you just remind us how they have a large benefit.
So with Covid.
Mission.
It'll be great. If we can if you can help us get a bit more color on how we can extrapolate early histologic benefit termination there on I have one more follow up thank you.
I'll I'll turn that question over to Richard Aranda, Our Chief Medical Officer.
Thank you for him.
Richard Aranda: Yeah, it's a challenging endeavor to predict early histologic results to later clinical responses. There have recently been several reviews in the literature that have specifically looked at that. Three reviews, for example, one was around Stellera, the other one was around the Varsity Study, and the third review was one of the Global Living Map and JAK inhibitor programs. And fundamentally, what they showed at the Early Time Point was different throughout those studies when they looked at histologic improvement and mucosal healing improvements early.
It's a it's a.
It's a challenging and.
Endeavour to predict early.
Histologic results. Two later later clinical responses.
There has been recently several reviews and in the literature that have specifically looked at that.
Three reviews for example, one was around the Atlanta. The other one was around the Boston study and the third with you.
It was one of the go live me Bath, and JAK inhibitor programs and based fundamentally what they showed is win at early time points, which were different without those studies when we looked at histologic improvement.
Richard Aranda: For example, at weeks four and eight in those studies, they seem to be associated with more robust clinical endpoints later in those studies. For example, the Stellera trial was week 44, and the gold limumab trial was six months, and the varsity trial was at week 52.
And mucosal healing improvement.
For example, what weeks for Nate in those studies they seem to be associated with Rome more robust clinical endpoints later and those studies for example, and this is the world's need for.
On the call.
And the math I think there was a <unk>.
Six months in the Washington trials at week 52.
So it's not a perfect relationship and it's not a perfect Association, but it's probably the best that we have that early histologic in particular, the mucosal healing changes.
Richard Aranda: So it's not a perfect relationship, and it's not a perfect association, but it's probably the best that we have, that early histologic and particularly mucosal healing changes can potentially reflect the more robust clinical and points later. Okay, thanks, Richard. And then one quick follow-up. So in terms of the background therapies that patients are allowed to be on during the SHIFT-UC study, how should we think about the level of background uses of 5-ASA and also, I assume, the intermittent use of steroids in these mild to moderate patients? And what guidance do you give to physicians on steroid use during the 12-week induction period?
Can potentially were flat.
The more robust clinical endpoints later.
Okay. Thanks, Richard and then one quick follow up so in terms of the background therapies that patients are allowed to be on during the study.
How should we think about the level of background here. It says five assay and also I assume into mezzanine USF steroids in the mild to moderate patients.
And what guidance are you capture the sessions on the steroid use.
During the 12 week induction period. Thank you.
Richard Aranda: Thank you. So Bryan, all patients will be on background five ASAs as they enter the trial. We anticipate anywhere from 20 to 40% could be on-concomitant with it, background cortical steroids. That seems to be the range if you look throughout the various studies.
So Brian all patients will be on background five assay as they entered the trial.
We anticipate anywhere from 20% to 40%.
Could be on concomitant back.
Background corticosteroids that seems to be the range.
Various studies.
Richard Aranda: During the first 12 weeks of the trial, patients are instructed not to change any of the background medications. Once they go beyond the 12 weeks, we do have a provision that they're able to taper the background steroids at the discretion of the patient and the investigator. Great. Thank you, Richard. Thanks for taking my question. Our next question comes from the line of Yasmin Rahimi. Your line is open.
During the first 12 weeks of the trial.
Patients.
Our instructed not to change any of the background medications once they go beyond the 12 weeks, we do have a provision that theyre able to taper.
The background steroids at the discretion of the patient at the investigator.
Great. Thank you Richard Thanks for taking my question.
Our next question comes from the line of Yes mean rahimi.
Your line is open.
Faheem Hasnain: Thank you so much. Thanks, Tim, for taking my question. Faheem, I really appreciate your commentary on that in the current TORI study, there's a high interest in patients rolling over into the open label. Is there an opportunity to maybe comment a little bit beyond that, like quantify it, like what percentage of patients are rolling over? And then, in regards to lower discontinuation rates, what discontinuation rates did you guys assume into the study? What type of discontinuation do you see at this junction?
Thank you so much thanks team for taking my question Faheem I really appreciate your commentary on that.
And the current Tory study, there's a high interest of patients rolling over into the open label.
Is there an opportunity to maybe comment a little bit beyond that like quantify it like what percentage of patients are rolling over.
In regards to lower discontinuation rate what discontinuation rates did you guys see them into the study.
What type of discontinuation due you see at this junction.
And then the third component is how many safety data monitoring committees.
Tweak has tweak Ontario.
And that's basically it so thanks, so much for taking my questions.
Faheem Hasnain: And then the third component is how many safety data monitoring committees has TORI gone through. And that's basically it. So thanks so much for taking my questions. Yeah, thanks. Thanks for your questions. As it relates to the first question, we're not going to be disclosing anything about enrollment or any of the specifics on that. That's kind of been our approach thus far. So we'll kind of just reiterate the fact that we're really pleased with the level of continued engagement that patients have with the OLE, and it's at a rate that we think is consistent, as we said with basically what we saw in the pulsar study, and I think that kind of sets a really good framework of reference for us, Richard. Would you like to add anything else to that?
Yeah. Thanks, Thanks for your questions as it relates to the first question, we're not going to be disclosing anything around enrollment or any of the any of the specifics on that that's kind of been our our approach. Thus far so we'll we'll kind of just reiterate.
Fact that we're really pleased with the level of continued engagement with patients have into the O N E and et cetera at a rate that we think.
Is consistent as we said with basically what we saw in the Pulsar study and I think that kind of set a really good framework of a preference for us Richard you want to add anything else to that.
Richard Aranda: Yeah, no, I think Yasmin, we're seeing good retention and, As Faheem was mentioning, the brackets around the IMPRESS trial, which had a high rate, and our PULSAR study, which had a very low rate, were much closer to the PULSAR. So it's very encouraging, and then the DSMB, I think we've had a couple, two, two me.
Yeah.
Thank you.
We're seeing good retention and.
No it's.
He was mentioning the brackets around the impress trial, which had a high rate.
Our pulsar study, which had a very low latency, we're much closer to the pulse ourselves with very encouraging for us.
And then the.
P. S M. B I think we've had a couple two two meetings.
Yes, I mean does that cover it yeah. That's it thank you.
Okay. Thanks.
Operator: Yasmin, did that cover it? Yeah, that's it. Thank you. Okay, I'll be back. Our next question comes from the line of Joseph Schwartz. Please ask your question. Hi, thanks very much and congratulations on all the progress. I was wondering, on GB004, if you'd be able to disclose the two doses that you're studying? shift UC study. I know you've said that both are higher than 120 milligrams once a day. I was just wondering what they are and what the rationale was for using higher doses versus phase one. Charlotte Rich, speak to the rationale, but we have not disclosed it; we'll disclose it.
Our next question comes from the line of Joseph Schwartz. Please ask your question.
Hi, Thanks, very much and congrats on all the progress.
I was wondering.
<unk> zero zero for a few.
<unk> be able to disclose the two doses that you're studying in the shift do you see study I know you've said that both are higher than the 120 milligrams. Once a day I was just wondering what they are and what the rationale was for using higher doses versus the phase one day.
Joel It rich.
Speak to the rationale, but we have not disclosed and won't disclose it.
Faheem Hasnain: We are in the middle of enhancing our intellectual property position, and so we'd like to get that done before we come forth with those levels, which will be around the time of our data disclosure but with a rich rationale. Yeah, I think the way I would frame it is that we were very encouraged by the 120 milligram 28-gauge study in our Phase 1B. That, I like to call it, provided us a floor of exposure, if you will, and within that floor of exposure, within the gut mucosa, as well as our plasma PK, we saw good signs of obvious biomarkers, histologic activity, and hints of clinical activity.
We are in the middle of enhancing our intellectual property position and so we'd like to get.
Get that done before we come forth with those dose levels, which.
We'll be around the time of our data disclosure, but rich rationale.
Yeah.
The way I would frame it is.
We were very encouraged with the 120 milligram 28 day study and our phase one be.
That I'd like to call. It provided us a floor of exposure, if you will and within that floor of exposure within the gut mucosa as well as our plasma PK. We saw good signs of obviously biomarkers.
Histologic activity and and hence a clinical activity. So if you consider that as a foundation our idea as perhaps we would amplify.
Faheem Hasnain: So if you consider that as a foundation, our idea is perhaps we would amplify the signal that we saw there by dosing higher to increase the exposure within the gut and also treating longer, and hence our Phase II trial was designed with those two aspirations. Okay, um, and then kind of a similar question on GB 5121.
The signal that we saw there by dosing hire to increase the exposure within the gut and also treating longer and hence our phase two trial was designed with those two.
Aspirations.
Faheem Hasnain: I was wondering if you could talk about the range of doses that you're studying in the phase one healthy volunteer study and how they relate to the dose range that you're anticipating could be efficacious. And are you looking for a strong safety profile with every dose you're assessing? Or are you doing, as is often done in some oncology studies, where you push the higher end of the dose range in order to find the maximum tolerated dose?
Okay.
And then kind of a similar question on GB 50 121.
I was wondering if you could talk about the range of doses that you're studying in the phase one healthy volunteer.
Study and how they relate to the dose range that you're.
Anticipating could be efficacious and are you.
Are you looking for a strong safety profile with every dose you're assessing or are you doing.
This is often done in some oncology studies, where you.
Push the higher end of the dose range in order to find the maximum tolerated dose.
Faheem Hasnain: Joe, you're talking about our normal, healthy volunteer study? Yeah. Yeah, I think the good thing about BTKs is we have an opportunity to use a great target of receptor occupancy assay to guide us, and that's historically been done.
Joe you are talking about our normal healthy volunteer study yes.
Yeah.
Yeah.
I think the.
The good thing about BT case is we have an opportunity to use a great target a receptor occupancy assay to guide us and that's historically been done and are just to remind you our profile is such that.
Faheem Hasnain: And our profile is such that we believe we have superior CNS penetrance relative to what our systemic exposure is going to be. And so utilizing BTK receptor occupancy, we're able to model pretty well in a way that helps guide us to our lower dose. And we're going to push the dose to achieve maximal receptor occupancy and then go above, you know, typically you go above 99%, at least in the systemic circulation, and go go above that and look for safety within that context.
We believe we have superior CNS penetrance relative to what our systemic exposure is going to be and so utilizing.
Our BK receptor occupancy.
We're able to model pretty.
Pretty good.
Way that helps guidance, our lower dose and we're going to push the dose to achieve maximal receptor occupancy.
And then go above more typically you go above 99% at least.
And the systemic circulation go well above that and look for.
The safety within that.
Context.
Faheem Hasnain: So that's our plan we're going to use. Start out with a dose that gives us an assumed mid-range receptor occupancy, then escalate fairly rapidly with guidance. Very helpful. Thank you. You are next, Carter Gould. Your line is open. Great. Good afternoon.
That's our plan. We're then a huge start at a dose that gives us a assumed mid range receptor occupancy then dose escalate.
With our guidance.
Very helpful. Thank you.
You are next Carter Gould your line is open.
Operator: Thanks for taking the question. Maybe to start, in terms of the SHIFT-UC top line, can you just comment about what you expect to disclose in the press release? Are you committing to sharing any quantitative disclosures around clinical remission? And then separately, as I understand the open-label extension of SHIFT-UC is, only 24 weeks, so minus the next 36 weeks and then an additional 24 weeks.
Great. Good afternoon, thanks for taking the question.
Maybe to start in terms of the the shift you see top line can you just comment about what you expect to disclose in the press release are you committing to sharing any quantitative disclosures around clinical remission and then.
Separately.
As I understand the the open label extension a shift you see is 'twenty only 24 weeks. So my understanding is 36 weeks and then an additional 24 weeks has there been any consideration around maybe.
Faheem Hasnain: There's been any consideration around spanning that or lengthening it to just get some longer term follow-up? Any thoughts there?
Turning out or lengthening it to just to get some longer term follow up.
Any thoughts there.
Faheem Hasnain: Thank you. Thanks, Carter. We'll be fairly robust in our disclosure, certainly around the primary and secondary endpoints and a key biomarker doubt that we have at the time. So, as in the past, and certainly as Faheem and Richard did going back to recess, you should expect fairly transparent conversation as far as the, well, the alternative. Yeah, I just want to clarify that our 36, from week 12 to week 36, is still double-blind, if you will.
Thanks.
We'll be fairly robust in our disclosure.
Starting around the primary and secondary endpoints and key.
Key biomarker data that we have at the time so.
As in the past and certainly as.
The human Richard did going back to receptors, you should expect a fairly transparent conversation as far as the OLED alternative yeah. Just wanted to clarify are.
The 36 week from week 12 week 36 is still a.
Double blinded if you will so just wanted to clarify that the patients. After week 12 stay on their allocation of their original randomization, assuming they don't worsen or need to roll over into the open label and then the open label extend out to <unk>.
Faheem Hasnain: So I just want to clarify that patients after week 12 stay on their allocation in their original randomization, assuming they don't worsen and need to roll over into the open label, and then the open label extends out to, we've got these 28 weeks. And you know, once again, we'll look at our top-line results and decide on next steps if the open label should be extended. Our next question comes from the line of Patrick Trucchio. Please ask your question. Thanks, Good afternoon.
One eight.
You know once again, well, we'll look at our topline results and decide on next steps.
The label should be extended.
Thank you.
Our next question comes from the line of Patrick Tracheal. Please ask your question.
Faheem Hasnain: The first question is just regarding serolutinib. So, in the primary endpoint of change in PBR from baseline at week 24, I think in the past, you've discussed an expectation of an approximate 20% improvement relative to placebo. I'm wondering if that remains the expectation.
Thanks. Good afternoon. The first question is just regarding Sara.
So on the primary endpoint of change in PBR from baseline at week 24, I think in the past you have discussed an expectation of an approximate 20% improvement relative to placebo I'm wondering if that remains the expectation and secondly in addition to safety and Tolerability can you discuss what additional data.
Data points, you'll be looking to hit to give confidence to move the program, Florida Phase III.
Faheem Hasnain: And secondly, in addition to safety and tolerability, can you discuss what additional data points you'll be looking to hit to give confidence to move the program forward to phase three? Yeah, just to clarify. The guidance we're giving is between an 18% to 32% improvement from baseline in PVR, not necessarily the treatment effect from placebo. And that's based on looking at the totality of the data from the IMPRESS trial as well as the recent Sultatercept, where the PVR changes bracketed those endpoints and seemed to be clinically meaningful.
Yes, just just to clarify.
The guidance, we're giving.
Is between 18% to 32% improvement from baseline and NPV are not necessarily a treatment effect.
The bow.
What where.
And that's based on looking at the totality of the data from the impress trial is.
So todd or something where the PBR changes bracketed those those endpoints.
Seem to be clinically meaningful.
Faheem Hasnain: Obviously, in addition to PBR, the other premise we have for the inhaled route of administration is a good safety profile, and that's the other key component that we will be evaluating. We are, we'll be looking at six. 6-Minute Walk, but we're not powered for that.
Obviously in addition to the PBR. The other premise we have for the inhaled route of administration as a as a good safety profile and that's the other key component that we will be evaluating.
We are we'll be looking at.
Six.
Faheem Hasnain: Yet, hopefully, we will see good trends, and we will do the other standard biomarker, NT ProBMP, as a measure of right heart function. Yeah, that's helpful. And then can you describe for us what the clinical development path for serolutinib could look like if, you know, the promising data are just described, or is there an opportunity for an accelerated approval pathway? Yeah, I would say that, you know, Pat, first and foremost, we want to get through the TORI study. And with that data, have the right conversations with regulators.
Six minute walk, but we're not powered for that yet hopefully we won't see the trends.
And we will do the other standard biomarker NT Pro BNP.
As a measure of right heart function.
Yeah. That's helpful. And then can you describe for us what the clinical development path for start of alerting them could look like if if you see the promising data has just described or is there an opportunity for an accelerated approval pathway.
I would say that Pat first and foremost we want to get through Tory study.
Faheem Hasnain: And obviously, we will push as hard as we can for the most efficient phase three clinical plan. You know, we know that patients are desperate for new options. And we want to be able to, Bush, as hard as we can, but really, to have any comments before we spend time with regulators, we'll just keep dreaming.
And with that data have the right conversations.
With regulators and obviously.
We will.
Bush as our we get as hard as we can for the most efficient phase III clinical plan, we know the patients.
Are desperate for new options.
We want to be able to.
Push as hard as we can but really to have any comments before we spent time with the regulators would just be premature.
Faheem Hasnain: Yep. Thank you very much. Your next question comes from the line of David Holland. Your line is open. Hi, thanks for taking the questions. I just had two, one each on UC and PAH.
Yep.
Thank you very much.
Your next question comes from that comes from the line of David Holland.
Your line is open.
Faheem Hasnain: So maybe first, for you know, UC, can we make any inferences on the expectations for the week 36 responses based on what we see at week 12? And maybe, you know, considering some of the other molecules and other trials which have used a treat through design? Yeah, I, one expectation is that we could see an incremental sort of better treatment effect as we treat longer. That's, that's something that we experienced, for example, on Osanamod when we worked on that program. Bob.
Hi, Thanks for taking the questions I just had I had two one each on UC and PIH. So maybe first for you you see are we.
Can we make any inferences on the expectations for the week 36 responses based on what we see at week 12, and maybe considering some of the other molecules and other trials, which have used a treat through design.
Yeah.
There's clearly.
Potentially one expectation is that we could see.
Incremental sort of.
More better treatment effect as we treat longer that's not something that we experienced for example on those on a model when we work on that program.
Faheem Hasnain: So, and then, you know, we also have the opportunity to look at some degree of maintenance, of as well as, you know, patients at week 12, who have a certain response, do they maintain that response as they continue into week 30? at two time points, for example. So at the end of the day, it will give us a hint of the ability of the team to, you know, maintain the response. Okay, thanks. That's helpful.
So and then we also have the opportunity to look at some degree of maintenance.
As well as.
Patients at week 12.
<unk> have a certain response that they maintain that response.
We continue until week 36 looking out to two time points. For example, so at the end of the day, it'll it'll give us a hint of the ability of.
<unk> or Jim.
Maintain our response.
Faheem Hasnain: And then on PAH, you know, just in terms of how you think about the total addressable market for serolutinib, I know that, for example, Merck, when they had their acquisition of Accelon, they discussed in their presentation some, you know, some numbers around market sizing and opportunity for citatricep. I'm just wondering if that's comparable or, you know, if there are any patients that you would or would not include in the serolutinib opportunity that might not overlap with citatricep. Yeah, I think it's appropriate to look at it as kind of, you know, our view is pretty consistent with the way it's done. Sid Hattersept has been described in the Addressable Market.
Okay. Thanks, that's helpful and then on a P H.
Just in terms of how you think about the total addressable market for several loot nib I know that for example, Merck when they had their acquisition of Exceleron. They discussed in our presentation from some numbers around market sizing and opportunity for <unk> and I'm. Just wondering if you think that's comparable or if there were any patients that you would or.
It would not include.
Indeed in the sterile loot nib opportunity that might not overlap with Patterson.
Yeah, I think I think it's appropriate to look at it as kind of our view is pretty consistent with the way.
So Todd receptor has been described in the addressable market. So.
Faheem Hasnain: I think that we've got any significant deviations [inaudible] Okay, thanks a lot for taking my question. Once again, as a reminder, if you have questions, please press star one. Our next question comes from the line of Gavin Clark Gartner. Your line is open. Hey, thanks for taking the question. So I just have one on Sarah Lutinib.
I think that we've got any significant deviation from that.
Got it thanks, a lot for taking my questions.
Once again as a reminder, if you have questions. Please press star one.
Our next question comes from the line of Gavin Clark Gartner.
Your line is open.
Hey, Thanks for taking the question. So I just had one on thorough loopnet could you explain how exactly the dose titration protocol works for Tory and thus far like roughly what proportion of patients are making it onto the 90 make dose.
Faheem Hasnain: Could you explain how exactly the dose titration protocol works for Tori and, thus far, roughly what proportion of patients we're starting them on the 90 mg dose? Yeah, we start patients out at 60 milligrams twice a day, and during the first two weeks, the first two to three weeks of the trial, they rapidly escalate up to 90 milligrams twice a day. They're able to dose deescalate. In the opinion of the investigator and, obviously, the tolerability profile of the patient, they're able to dose deescalate once they reach the 90s.
Yes.
We started patient salad at 60 milligrams twice a day and they during the first two weeks.
Pursued it and said the trial they rapidly dose escalate up to 90 milligrams twice a day theyre able to dose escalate.
In the opinion of the investigator and obviously the Tolerability profile.
Of the patient, they're able to dose escalate.
Once they reach the 90.
Sure.
Faheem Hasnain: Will the second part of your question, please, could you repeat that? Just roughly what the portion of patients have made it on to or stayed on with the 90-mig those It's as we were alluding to, Very, very high as patients are rolling over into the open label.
What was second part of your question. Please could you repeat that.
Just roughly what proportion of patients have made it onto restate on the 90 to make those.
It's as we were alluding to.
Richard Aranda: So I think that's reassuring since we see high rollover and the dose there is also 90 milligrams twice a day and it's being very well tolerated. Got it. Thanks. Once again, if you have questions, please press star 1. We have no further questions at this time. I will now turn the call over back to Mr. Bryan Giraudo.
Very very high as patients are.
Rolling over into the open label so.
I think that's reassuring since we see high rollover.
And.
The dose there is also a 90 milligrams twice a day that it's being very well tolerated.
Got it thanks.
Once again, if you have questions. Please press star one.
We have no further questions at this time I will now turn the call over back to Mr. Brian Jurado.
Faheem Hasnain: Actually, this is Faheem Hasnain. I just want to thank everyone who joined us today. I also want to give a heartfelt thanks to the team here at Gossamer. We have a group of incredibly dedicated and passionate professionals, and the team has made really fantastic progress. So I just would like to thank everybody that's involved with these programs. We're honored to share our progress with you as we move our gaze forward towards an exciting 2022. So, thank you again, everybody, for joining us. Thank you again for your participation. This concludes today's conference call. You may now disconnect. [music]
Actually this faheem hasnain I just want to thank everyone, who joined US today I also want to give a heartfelt. Thanks to the team here at Gossamer, we have a group of incredibly dedicated and passionate professionals.
And the team has made really fantastic progress. So I just would like to thank everybody.
That's involved with these programs we're honored to share our progress with you as we move our gaze forward towards an exciting 2022 so thank you again everybody for joining us.
Thank you again for participation. This concludes today's conference call you may now disconnect.
Okay.
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Yeah.
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Yes.
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Okay.