Without further ado, I would like to welcome your first speaker for today, Mr. Bryan Giraudo. Sir, the floor is yours.
Thank you, operator, and thank you all for j oining 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. We caution listeners that during this call, Gossamer management will be making forward-looking statements. Actual results may differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business.
These forward-looking statements are qualified by the statements contained in Gossamer's news releases, SEC filings, including in the annual report on Form 10-K and subsequent filings. 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 from our clinical trials in a 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 Faheem. Faheem?
Thank you, Bryan, and thanks to everyone for joining us on this afternoon's call. 2021 was a 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 II readouts in ulcerative colitis and pulmonary arterial hypertension. Now, while these product candidates, seralutinib and GB004, target different indications utilizing different approaches, we view them both alike in the sense that they're using novel mechanisms to target populations that continue to be underserved. If approved, we believe both molecules hold treatment paradigm shifting potential. Now, first, let's start with GB004. 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.
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, 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 GB004 is distinct and may have a differentiated profile from the immunomodulatory or immunosuppressive mechanisms of approved IBD medications and those in late-stage development. GB004 is designed to be gut-targeted with higher intestinal exposure than systemic exposure, and clinical and pre-clinical data generated to date support this thesis.
By reducing local inflammation and potentially restoring intestinal epithelial barrier function and restitution through GB004's gut-targeted nature and preferential stabilization of HIF-1 alpha, we believe GB004 could improve outcomes for IBD patients. We believe this mechanism has potential as a standalone therapeutic as well as a combination therapy with other therapeutic mechanisms in IBD. 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 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, and of course, the Ukrainian people as a whole.
Above all else, we hope for their health and safety in this horrific situation. 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 to our 12-week primary endpoint. Understandably, communication into Ukraine has been challenging and we're continuing to monitor for impacts to our 36-week data set. Moving on to seralutinib, also known as GB002. Gossamer continues to enroll patients in its ongoing phase II TORREY study in patients with functional class II and III 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.
We're pleased to say that at this point, the wave of COVID-19 related to 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 TORREY study in the second half of this year. Of course, barring any further developments in the ongoing COVID-19 viral pandemic. Now once patients complete the blinded 24-week study period as part of the TORREY 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. To date, we continue to see a very high percentage of patients who have completed the 24-week study period elect to continue on to the open label extension, similar to the IMPRES study of imatinib and the PULSAR study of sotatercept.
If you recall, the IMPRES 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 IMPRES study occurred in the first eight weeks. We've been pleased to see that to date, the blinded discontinuation rate in the TORREY study has been more comparable to the more manageable discontinuation rate observed in the PULSAR study of sotatercept. Now, moving on from seralutinib, our CNS penetrant BTK inhibitor, GB5121, is expected to enter a global phase I-B/II clinical study in PCNSL CNS lymphoma patients 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 U.S. FDA. 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 financial results for the full year 2021. We ended the year with $325 million of cash and cash equivalents. 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 through the second half of 2023. 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 increase was primarily due to an increase of clinical trial and preclinical study costs associated with seralutinib, GB004, GB5121 and preclinical programs. This increase was partially offset by decreases in clinical trial and preclinical study costs related to GB001 and GB1275. 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 ending December 31st, 2021 was $56 million or $0.74 per share, compared to a net loss of $65 million or $1.05 per share 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 31st, 2020. 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.
That is noted, 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.
Hey, guys. Thanks for taking my questions today. I have a couple on the UC side since that's going to be your next upcoming catalyst. Just on the efficacy perspective, you know, we're pretty clear on what we should expect in terms of the placebo rate and also the efficacy rate, the clinical remission rates specifically. Can you just remind us how the histologic benefits associated with remission? It'll be great if you can help us to get a bit more color on how we can extrapolate early histologic benefit to remission later on. I have one more follow-up. Thank you.
I'll turn that question over to Richard Aranda, our Chief Medical Officer.
Yeah. Thank you, Faheem. Yeah, it's a challenging endeavor to predict early histologic results to later clinical responses. There has been recently several reviews in the literature that have specifically looked at that. Three reviews, for example, one was around STELARA, the other one was around the Varsity study, and the third review was one of the golimumab and JAK inhibitor programs. Fundamentally what they showed is when at early time points, which were different throughout those studies when they looked at histologic improvement and mucosal healing improvements early, 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, in the STELARA it was week 44 and the golimumab, I think, was six months in the Varsity trial was at week 52. 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 endpoints later.
Okay. Thanks, Richard. Then, one quick follow-up. 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 intermittent use of steroids in these mild to moderate patients? What guidance do you give to physicians on the steroid use during the 12-week induction period? Thank you.
Brian, all patients will be on background 5-ASAs as they enter the trial. We anticipate anywhere from 20%-40% could be on concomitant background corticosteroids. That seems to be the range if you look throughout the various studies. 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 Yasmeen Rahimi. Your line is open.
Thank you so much. Thanks, team, for taking my question. Faheem, I really appreciate your commentary on that in the current TORREY 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? And then in regards to lower discontinuation rate, what discontinuation rates did you guys assume into the study? What type of discontinuation do you see at this junction? And then the third component is how many safety data monitoring committees has TORREY gone through? And that's basically it. Thanks so much for taking my questions.
Yeah, thanks for your questions. As it relates to the first question, we're not gonna be disclosing anything around 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 into 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. I think that kind of set a really good framework of reference for us. Richard, you wanna add anything else to that?
Yeah, no, I think we're seeing good retention and you know, it's as Faheem was mentioning, you know, the brackets around the IMPRES trial, which had a high rate, and our PULSAR study, which had a very low rate. We're much closer to the PULSAR, so it's very encouraging for us.
The DSMB, I think we've had a couple.
Two.
Two meetings. Yasmeen, does that cover it?
Yeah. That's it. Thank you.
Okay, thanks.
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 on GB004, if you'd be able to disclose the two doses that you're studying in the SHIFT-UC study. I know you said that both are higher than the 120 mg once a day. I was just wondering what they are and what the rationale was for using higher doses versus the phase I-B.
Joe, let Rich speak to the rationale. We have not disclosed it and won't disclose it. This, we are in the middle of enhancing our intellectual property position, and so would like to get that done before we come forth with those dose levels, which will be around the time of our data disclosure. Rich, rationale.
Yeah. I think the way I would frame it is, we were very encouraged with the 120 mg 28-day study in our phase I-B. That, I like to call it, provided us a floor of exposure, if you will. 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 hints of clinical activity. 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. Hence our phase II trial was designed with those two aspirations.
Okay. Kind of a similar question on GB5121. I was wondering if you could talk about the range of doses that you're studying in the phase I healthy volunteer study and how they relate to the dose range that you're anticipating could be efficacious. Are you looking for a strong safety profile with every dose you're assessing? 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?
Yeah. Joe, you're talking about our normal healthy volunteer study?
Yeah.
I think the good thing about BTKs is we have an opportunity to use a great target, a receptor occupancy assay to guide us. That's historically been done. Just to remind you, our profile is such that we believe we have superior CNS penetrance relative to what our systemic exposure is going to be. Utilizing a BTK receptor occupancy, we're able to model pretty you know good in a way that helps guide us our lower dose. We're gonna push the dose to you know achieve maximal receptor occupancy and then go above. You know, typically you go above 99%, at least in the systemic circulation, go above that and look for the safety within that context. That's our plan.
We're gonna start at a dose that gives us a assumed mid-range receptor occupancy, then escalate fairly rapidly with guidance there.
Very helpful. Thank you.
You are next, Carter Gould. Your line is open.
Great. Good afternoon. 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 my understanding is 36 weeks and then an additional 24 weeks. Has there been any consideration around maybe, you know, expanding that or lengthening it to just to get some longer term follow-up? Any thoughts there?
Yeah. Thanks, Carter. We'll be fairly robust in our disclosure, certainly around the primary and secondary endpoints and key biomarker data that we have at the time. As in the past and certainly as Faheem and Richard did, going back to the Receptos, you should expect a fairly transparent conversation. As far as the OLE alternative-
Yeah, I just wanna clarify. The 36-week from week 12 to week 36 is still double-blinded, if you will. Just wanna clarify that. The patients after week 12 stay on their allocation of their original randomization, assuming they don't worsen and need to roll over into the open-label. The open-label extends out to, I believe at least 28 weeks. You know, once again, we'll look at our top-line results and decide on next steps if the open-label should be extended.
Thank you.
Our next question comes from the line of Patrick Trucchio. Please ask your question.
Thanks. Good afternoon. The first question is just regarding seralutinib. In the primary endpoint of change in PVR 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. 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 III?
Yeah. Just to clarify, the guidance we're giving is between 18%-32% improvement from baseline in PVR, not necessarily a treatment effect from placebo. That's based on looking at the totality of the data from the IMPRES trial and the recent sotatercept, where the PVR changes bracketed those endpoints and seem to be clinically meaningful. Obviously in addition to PVR, 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'll be looking at a six-minute walk, but we're not powered for that yet.
Hopefully, we will see good trends, and we will do the other standard biomarker NT-proBNP as a measure of right heart function.
Yeah, that's helpful. Can you describe for us what the clinical development path for seralutinib could look like if you see, you know, the promising data as just described? Or is there an opportunity for an accelerated approval pathway?
I would say that, you know, Pat, first and foremost, we wanna get through the TORREY study, and with that data, have the right conversations with regulators. Obviously, we will push as hard we can, as hard as we can for the most efficient phase III clinical plan. You know, we know that patients are desperate for new options, and we wanna be able to push as hard as we can. Really, to have any comments before we spend time with the regulators would just be premature.
Yep. Thank you very much.
Your next question comes from the line of David Hoang. Your line is open.
Hi. Thanks for taking the questions. I had two, one each on UC and PAH. Maybe first for you know UC. You know, 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, you know, there's clearly potentially one expectation is that we could see incremental sort of more better treatment effect as we treat longer. You know, that's something that we experienced, for example, on ozanimod when we worked on that program. We also have the opportunity to look at some degree of maintenance as well as patients at week 12, if they have a certain response, do they maintain that response as they continue into week 36? Looking at 2 time points, for example. At the end of the day, it'll give us a hint of the ability of GB004 to maintain a response.
Okay. Thanks. That's helpful. On PAH, you know, just in terms of how you think about the total addressable market for seralutinib. I know that, for example, Merck, when they had their acquisition of Acceleron, they discussed in their presentation some, you know, some numbers around market sizing and opportunity for sotatercept. I'm just wondering if you think that's comparable or, you know, if there are any patients that you would or would not include in the seralutinib opportunity that might not overlap with sotatercept.
Yeah. I think it's appropriate to look at it as kind of, you know, our view is pretty consistent with the way sotatercept has been described in the addressable market. I don't 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. I just have one on seralutinib. Could you explain how exactly the dose titration protocol works for TORREY, and thus far, like, roughly what proportion of patients are making it onto the 90 mg dose?
Yeah. We start patients out at 60 mg twice a day, and during the first two to three weeks of the trial, they rapidly dose-escalate up to 90 mg twice a day. They're able to dose de-escalate if, in the opinion of the investigator, and obviously the tolerability profile of the patient, beyond once they reach the 90. What was the second part of your question, please? Could you repeat that?
Just roughly what portion of patients have made it onto or stayed on the 90 mg dose?
It's, as we were alluding to, very high as patients are rolling over into the open label. I think that's reassuring since we see high rollover, and the dose there is also 90 mg 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. Bryan Giraudo.
Actually, this is Faheem Hasnain, and I just wanna thank everyone who joined us today. I also wanna give heartfelt thanks to the team here at Gossamer. We have a group of incredibly dedicated and passionate professionals. The team has made really fantastic progress. 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. Thank you again everybody for joining us.
Thank you again for participation. This concludes today's conference call. You may now disconnect.