Q3 2020 Gossamer Bio Inc Earnings Call

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On T. Penske earnings call.

This time all participants are in a listen only mode. After the speakers presentation, there will be a question and answer session.

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Operator: I would now like to hand the conference over to your moderator today, Mr. Bryan Giraudo, Chief Financial Officer. Thank you. Please go ahead, sir.

I would now like to have the conference over to your moderator today Mr., Brian Gerardo Chief Financial Officer. Thank you. Please go ahead Sir.

Bryan Giraudo: Thank you, Operator, and thank you all for joining us this afternoon. I am joined on today's call by Gossamer Bio's Co-Founder and Chief Executive Officer, Dr. Sheila Gujrati, as well as our Chief Scientific Officer, Dr. Louisa Salter-Schid. Earlier this afternoon, Gossamer Bio issued a press release announcing its financial results for the third quarter ended September 30, 2020, in addition to providing a corporate update. Please note that certain information discussed on the call today is covered under the Safe Harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Gossamer Management will be making forward-looking statements. However, actual results may differ materially from those stated or implied by these forward-looking statements due to the risks and uncertainties associated with the company's business.

Thank you operator, thank you all for joining us this afternoon I.

I'm joined on today's call by Gossamer Bio's, co founder and Chief Executive Officer, Dr., Shi liquids, Robbie as well as our Chief Scientific Officer, Dr. Luisa Salter said.

Earlier this afternoon Gossamer bio issued a press release announcing its financial results for the third quarter ended September 32020. In addition to providing a corporate update.

Please note that certain information discussed on the call today is covered under the Safe Harbor provisions of the private Securities Litigation Reform Act, we caution listeners that during this call gossamer amounts will be making forward looking statements.

Actual results may differ materially from those stated or implied by these forward looking statements due to the risks and uncertainties associated with the company's business.

Bryan Giraudo: These forward-looking statements are qualified by the statements contained in Gossamer's news releases and SEC filings, including in the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that may only be accurate for a limited period of time. Our ability to meet our guidance, especially that related to the 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 Sheila. Okay?

These forward looking statements are qualified by the statements contained in Gossipers news releases and SEC filings, including the annual report on form 10-K, and subsequent filings this.

This conference call also contains time sensitive information that may only be accurate for a limited period of time.

Our ability to meet our guidance, especially that related to the timely initiation and completion of clinical studies. In addition to our ability to release results from our clinical trials in a timely manner, maybe 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.

Now I would like to turn the call over to Sheila Q.

Sheila Gujrati: Thank you, Bryan, and good afternoon to everyone who is joining us on today's call. We appreciate you taking the time to hear about the progress Gossamer has made. Earlier this afternoon, Gossamer Bio was pleased to announce its financial results for the third quarter of 2020, in addition to several updates to the status of our pipeline of clinical product candidates. Gossamer Bio was founded as an innovative research and development engine to deliver value through the selection and development of a pipeline of multiple independent programs across the therapeutic areas of inflammation, immunology, and oncology.

Thank you, Brian and good afternoon to everyone, who is joining us on today's call. We appreciate you taking the time to hear about the progress gossamer his name.

Earlier. This afternoon Gossamer bio was please turn now to the financial results from the third quarter 2020. In addition to several updates to the status of our pipeline of clinical product candidates.

That's not buy it was founded as an innovative research and development engine to deliver value to the selection and development of a pipeline of multiple independent program across.

Across the therapeutic areas of inflammation, <unk> immunology and oncology.

Sheila Gujrati: This engine is centered around an experienced team with a history of successful and efficient execution in these closely related therapeutic areas. Each program is backed by rigorous preclinical and clinical work to understand and de-risk product candidates, focused on areas of high unmet need and a differentiated product profile that would be meaningful for patients. We are pleased to be advancing two independent molecules targeting two different indications into phase two trials. We are also excited to discuss new clinical data from our immuno-oncology candidate, GB1275, as it continues to progress through its Phase I-II trial in solid tumors. All told, the development progress from multiple candidates is a manifestation of Gossamer's purpose.

This engine is centered around an experienced team.

With a history of successful and efficient execution and these closely related therapeutic areas.

Each program is backed by rigorous preclinical and clinical work to understand and de risk the product candidates.

It's an area of high unmet need and a differentiated product profile that would be meaningful for patients.

We are pleased to be advancing two independent molecule targeting two different indications into phase two trials.

We're also excited to discuss new clinical data from our immuno oncology candidate she'd be 12 75 as it continues to progress through its phase one two trial in solid tumors.

All told development progress from multiple candidates is a manifestation of golf numerous purpose.

Sheila Gujrati: The continual and simultaneous advancement of multiple high-potential programs through the execution of the proper experiments to create value for shareholders. First, I will briefly review the status of GB001, our once-daily oral GP-2 antagonist for the treatment of moderate to severe asthma. In October, we read out the top-line results of our Phase II lead-leaded study. While the primary endpoint of asthma worsening was not met, TB-001 did demonstrate a consistent reduction of 32-35% in the proportion of patients exhibiting asthma worsening across all three active drug arms as compared to placebo. And in the key secondary endpoint of time-to-first asthma worsening, we saw statistically significant improvement in both the 20-milligram and the 60-milligram dose groups as compared to placebo. We are currently in the process of engaging with global regulatory authorities about these results and the path forward.

The continual and simultaneous advancement of multiple high potential programs through the execution of the a proper experiment to create value for shareholders.

First I will briefly review the status of GBC or zero, one our once daily oral DP two antagonist for the treatment of moderate to severe asthma.

In October we bought out the topline results of our phase to be leader study.

Well the primary endpoint of asthma worsening with not Matt do you view as your one did demonstrate a consistent reduction of 32% to 35% in the proportion of patients exhibiting asthma worsening across all three active drugs aren't as compared to placebo.

And then the key secondary endpoint of time to first asthma worsening we saw statistically significant improvement in both the 20 milligram and the 60 milligram dose group compared to placebo.

We're currently in the progress of engaging with global regulatory authorities about these results and the path forward.

Sheila Gujrati: We hope to have clarity from these discussions in the first half of next year, which will help inform potential partnerships and strategic alternatives. Since the end of the third quarter, we have activated two value-deriving, proof-of-concept Phase II clinical trials for our GB002 and GB004 programs, which I will touch upon before walking through the recent clinical data reported this week at FYSB from our oncology candidate GB1275. After that, Bryan will provide a financial update.

We hope to have clarity from these discussions in the first half of next year, which will help inform potential partnerships and strategic alternatives.

Since the end of the third quarter, we have activated to value driving proof of concept phase two clinical trials for our D. These years, you're at you and you'd be 004 programs, which I will touch upon before walking through the recent clinical data reported this week, it's just see from oncology candidate to be till 75.

After that Brian will provide a financial update.

Do you think there's your acute with an inhaled PDGF our receptor inhibitor for the treatment of pulmonary arterial hypertension or peach.

Sheila Gujrati: GP-002 is an inhaled PDGFR receptor inhibitor for the treatment of pulmonary arterial hypertension, or PAE. TB002 was designed to improve upon prior success observed with kinase inhibition in PAH by delivering a tyrosine kinase inhibitor with an optimized selectivity and potency profile directly to the site of disease by a convenient dry powder inhaler. TB002 is being studied on top of vasodilators with the hope of delivering a new standard of care that reverses pulmonary vascular remodeling and further improves patient outcomes.

Do you view as your kids are designed to improve upon prior success observed with kinase inhibition in P.H. by delivering a tyrosine kinase inhibitor with an optimized selectivity and potency profile directly to the site of disease by a convenient dry powder inhaler.

He was years, you're accused being studied on top of these though dilators with the hope of delivering a new standard of care that reverses pull many bumps every modeling and further improved patient outcomes.

Our ongoing two week phase one B study is meant to bridge the safety PK and PD results. We saw in our phase one studies in healthy volunteers to an initial experience in ph patients.

Sheila Gujrati: Our ongoing two-week Phase 1b study is meant to bridge the safety, PK, and PD results we saw in our Phase 1 studies in healthy volunteers to an initial experience in PH patients. While the two-week portion of the study is too short to evaluate changes in clinical endpoints, we have gathered important information on target engagement and biomarkers. These patients also have the option to roll onto a six-month open-label extension. We look forward to sharing the two-week data before the year ends at a GB002-focused investor event in December.

While the two big portion of the study is too short to evaluate changes in clinical endpoint, we have gathered in for important information on target engagement by markers.

Patients also have the option to roll onto a six month open label extension.

We look forward to sharing the two week data before year end added Gpcrs your acute focus investor event in December.

Sheila Gujrati: As a reminder, this study's conduct was interrupted earlier this year by the COVID-19 pandemic, and now that the trial has restarted, we have enrolled new patients into the study. We believe that Phase 1B inpatients helped inform us how a PH trial needs to be conducted during the COVID pandemic. And while unanticipated, the lessons learned here, in terms of protocol adjustments, operations, logistics, as well as the investigator and patient experience, are critical to moving this program forward in PAH. We are also excited to announce that we have activated multiple sites for our Phase 2 TORI study. We expect to begin enrollment in this trial in the fourth quarter.

As a reminder, this study conduct with interrupted earlier this year by the COVID-19 pandemic.

Now that the trial has restarted we have enrolled new patients onto the study.

We believe it stays won't be impatient helped inform us how the piece probably needs to be conducted during the club dependent Mick and.

And while unanticipated the lessons learned here in terms of protocol adjustments operations logistics as well as the investigator and patient experience are critical to moving this program forward in P.H.

We're also said he can now see we had activated multiple sites for the Tories study.

We expect to begin enrollment of this trial in the fourth quarter.

Sheila Gujrati: The TORI Phase II study is a 24-week, double-blind, placebo-controlled, multi-centered clinical study to evaluate the efficacy and safety of GB002 in functional Class II and III PH patients. This is an 80 patient study, and patients will be randomized evenly between the drug and placebo. The primary endpoint is change in pulmonary vascular resistance from baseline at week 24, and the key secondary endpoint for this trial will be change in six-minute walk test distance. We expect to be able to read out offline data from the Phase 2 Torrey Study in the first half of 2022, subject to further developments in the COVID-19 pandemic.

Detroit Phase two study is a 24 week double blind placebo controlled multi center clinical study to evaluate the efficacy and safety of GBC with your two and functional class two and three p. each patient.

This is an 80 patient study and patients will be randomized evenly between drug and placebo.

The primary endpoint is change in pull me back their resistance from baseline at week 24, and the key secondary endpoint for this trial will be change in six minute walk test distance.

We expect to be able to read out top line data from the phase two Tory study in the first half of 2022 subject to further developments in the COVID-19 pandemic.

Sheila Gujrati: We are working closely with sites, investigators, and study coordinators surrounding the obstacles posed by COVID-19 with a focus on patient health, and we believe we have put in place protocols and procedures to help mitigate that risk. In response to the inbound interest we have received on the GB002 program from investors, clinicians, and patient advocacy groups over the past few months, we will host a GB002 PH-focused webinar in December. During the call, we plan to discuss the rationale for GB002 and PAH, initial results from our Phase 1b study, and give additional details on our Phase 2 study design, in addition to making some of our key external advisors available for Q&A. We hope you will join us on this call to learn more about the GB002 program. Please be on the lookout for details surrounding this virtual event in the coming weeks.

We are working closely with site investigators and study coordinators gerani be optical posed by 2019 with a focus on patient health and we believe we have put in place protocols and procedures to help mitigate that risk.

In response to the inbound interest we have received on the T.V.'s years. Your two program from investors clinician and patient advocacy group over the past few months, we will host a D.V. there as you go to page focus Webinars in December.

During the call we plan to discuss rationale for GBS years. Your acute P. H initial results from our phase one B study and give additional details on our phase two study design. In addition to making some of our key external advisors available Una.

We hope you will join US on this call to learn more about that you did you had your acute program. Please be on the look out for details surrounding this virtual event in the coming weeks.

Sheila Gujrati: Next, we will discuss our Oral Hippoanalysis Stabilizer, GB004, which is being developed for the treatment of inflammatory bowel disease. As a reminder, QB004 is an oral, gut-targeted therapy with a unique mechanism of action that is intended to address the high disease burden and impaired quality of life in patients with IBD. Unlike traditional anti-inflammatory approaches to IBD, GP004 is believed to promote the healing of the mucosa to achieve sustainable histologic, endoscopic, and clinical remission.

Next we will discuss our oral hits went out the stabilizer jeebies. There's your four which is being developed for the treatment of Islam try bowel disease.

As a reminder, Cupid years, therefore is an oral that targeted therapy with a unique mechanism of action that is intended to address the high disease burden in poor quality of life in patients with diabetes.

Unlike traditional anti inflammatory put aside the D. Do you view as your four is believed to promote the healing of the nekoosa did she sustainable histologic endoscopic and clinical remission.

Sheila Gujrati: GP004 has the potential to deliver meaningful patient benefit both as monotherapy and in combination with standard of care in patients across the disease continuum. We are so pleased to announce that we have begun dosing patients in the GB004 SHIFT-UC Phase 2 study in patients with active ulcerative colitis. The SHIPS-UC Phase 2 study is a randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy, safety, PK, and PD of GB004 in adult subjects with mild to moderate active ulcerative colitis.

You could use your four has the potential to deliver meaningful patient benefit both as a monotherapy and in combination with standard of care in patients across the disease can continue him.

You're so pleased to announce that we have begun dosing patients in a gpcrs. Your four ships you see phase two study in patients with active ulcerative colitis.

The shift you see phase two study is a randomized double blind placebo controlled multi center study to evaluate the efficacy safety PK and PD of Gpcrs your for the adult subjects with mild to moderate active ultraflex.

Sheila Gujrati: We expect to enroll about 195 UC patients who will be randomized evenly across two dose groups and placebos. The primary endpoint for this trial is the proportion of patients with clinical remission at week 12. Secondary endpoints include proportion of patients at week 12 with clinical response, histologic remission, endoscopic improvement, and mucosal healing. Patients will remain on background therapy, including 5 ASAs and steroids, throughout the trial. We expect to be able to read out top-line data from the Phase 2 SHIFT-UC study in the first half of 2022, subject to further developments in the COVID-19 viral pandemic. In line with what I mentioned previously regarding the TORI study in PAH, we are working closely with SHIFT-UC sites to mitigate potential COVID-19-related disruptions.

We expect to enroll about 195, you see patients who will be randomized evenly across two dose groups and placebo.

The primary endpoint for the trial its proportion of patients with clinical remission at week 12.

Secondary endpoints include proportion of patients at week 12 clinical response.

The logic that mission and just got big improvement and the coastal healing.

He will remain on background therapy, including by the state and steroids throughout the trial.

We expect to be able to read out top line data from the phase two shift you see steady in the first half of 2022 subject to further developments in it so the 19 barrel pandemic in.

In line with what I mentioned previously regarding Detroit study in P.H., we're working closely with should use these sites to mitigate potential COVID-19 related disruption.

Sheila Gujrati: Also, we believe there is a possibility that GB004's non-immunosuppressive mechanism may turn out to be a recruiting advantage in the recruitment of UC patients as compared to immunosuppressive therapies. We're commencing the Phase 2 induction study in UC after having completed a four-week Phase 1B trial in patients with active mild to moderate disease. In October at UEG Virtual Week 2020, Dr. Bill Sanborn of the University of California, San Diego presented these data following Gossamer's top-line announcement in May of this year.

Also we believe there is a possibility that you could do a drug for non immunosuppressive mechanism may turn out to be a recruiting advantage and the recruitment of you see patients as compared to immunosuppressive therapy.

We're commencing mistake to induction study in you see after having completed a four week phase one b trial in patients with active mild to moderate disease.

In October at UGI virtual weak 2020, Dr. Bill Sanborn at the University of California, San Diego presented these data following golf from a top line announcement in May of this year.

Sheila Gujrati: We received a great deal of interest and positive feedback from KOLs and investigators following Dr. Sanborn's presentation, which is available on the posters and publication section of our website and is enabling us to hit the ground running with our Phase 2 trial. And finally, we will turn to GB1275, our oral CD11B modulator being developed for the treatment of solid tumors. We have a couple of updates on our Phase 1-2 keynote A36 trial being shared at TIFSI this week. Dr. Johanna Bendel is presenting poster number 388, which details some of the GB1275 clinical results from the ongoing dose escalation portion of Keynote A36, both monotherapy and in combination with pembrolizumab. Dr. Wells Messerschmidt is presenting poster number 389, which describes the relevant clinical biomarker data, which is also from this ongoing Phase I-II study in advanced solid tumors.

We received a great deal of injury and positive feedback from kalo and investigator falling Docker Sandbars print presentation, which is available on the posters and publications section of our website and enabling us to hit the ground running with our phase two trial.

And finally, we will turn to GBP 12 75.

Our oral PD 11, B. modulator being developed for the treatment of solid tumors.

We have a couple of updates on our phase one to keynote <unk> 836 trial being shared its just see this week.

Dr. Johanna Bendel is presenting poster number three he was detailed some of that you'd be till 75 clinical results from the ongoing dose escalation portion of keynote 836 from.

Both monotherapy and in combination with Pembrolizumab.

Dr. Wells Messersmith is presenting poster number 389, which dot the guidance a relevant clinical biomarker data, which is also from this ongoing phase one two study in advanced solid tumors.

Enrolment in the dose escalation phase continues as no dose limiting toxicity has been observed.

Sheila Gujrati: Enrollment in the dose escalation phase continues, as no dose-limiting toxicity has been observed. Oral GB1275 has now been used to treat 40 patients at doses up to 1200 mg twice daily. Safety data suggest that GB1275, both alone and in combination with pembrolizumab, is well tolerated. Furthermore, despite being studied in tumor types that are known to be less responsive to checkpoint inhibitors, TB1275 has generated encouraging clinical and biological activity, especially in dose cohorts equal to or greater than 800 mg BID. In terms of clinical activity, 12 patients had an initial resistance assessment of stable disease with a median duration of treatment of 102.5 days. Among those 12 patients, prolonged stable disease, stable disease greater than 84 days was noted in seven patients who had microsatellite-stable colorectal metastatic carotid-persistent prostate cancer, triple negative breast cancer, and gastric cancer.

Oral G. B 12, 75 has now been used to treat 40 patients with doses up to 1200 milligram twice daily.

He did Jesse GB spoke 75, both alone and in combination with Pembrolizumab is well tolerated.

Oh, it's but have you been tumor types that are known to be less responsive to checkpoint inhibitor to be call 75 has generated encouraging clinical and biologic activity, especially in dose cohorts equal to or greater than 800 milligram be I'd.

In terms of clinical activity to all patients had an initial assessment as stable disease with a median duration of treatment of a hunger in 2.5 days.

Among those 12 patients prolonged stable disease stable disease grew to 84 days was noted in seven patients who had microsatellite stable colorectal metastatic castrate resistant prostate cancer.

Well negative breast cancer and gastric cancer three.

Sheila Gujrati: Three of these patients received monotherapy in regimen A, and four of these patients received combination therapy in regimen B. Importantly, five of the seven patients received doses greater than or equal to 800 milligram BID, suggesting increased clinical activity at higher doses. Staple disease was also observed in two of the combination therapy patients who had previously been treated and progressed with a checkpoint inhibitor.

Three of these patients received monotherapy in regimen aim and for these patients receive combination therapy in regimen beat.

Importantly, five to seven involved doses greater than or equal to 800 milligram be I'd, suggesting increased clinical activity at higher doses.

People disease was also observed into the combination therapy patients who had previously been treated and progressed with a checkpoint inhibitor.

We have seen one confirmed response in a patient with microsatellite stable colorectal cancer, who received 800 milligrams, if you'd be 12 75 B.I.D. in combination with Pembrolizumab.

Sheila Gujrati: We have seen one confirmed partial response in a patient with microsatellite-stable colorectal cancer who received 800 mg of CB1275BID in combination with pembrolizumab. That patient had previously received five lines of therapy and is continuing on steady treatment. Published preclinical work suggests that GB1275 works by disrupting immunosuppressive myeloid cell biology, which allows for more T cell infiltration and activation in tumors, potentially converting the tumor microenvironment to an inflamed phenotype. Our early biomarker findings support these aspects of GB1275's mechanism of action. Protein and gene signatures in blood show changes consistent with reduced myeloid-derived suppressor cells, which correlates with dose and pembrolizumab combination. Myeloderized suppressor cells also decrease in a dose-dependent manner after treatment with GB1275 or in combination with pembrolizumab. An increase in tumor-infiltrating T lymphocytes, or TILs, is observed in serial tumor biopsies following both the GB1275 monotherapy regimen as well as the combination therapy with pembrolizumab.

That piece would have previously the C. Five lines of therapy, and it's continuing on study treatment.

Published preclinical work suggest that you'd be 12, 75 works by disrupting immunosuppressive myeloid cell biology, which allows for more T cell infiltration and activation and tumor potentially converting the tumor micro environment to an inflamed phenotype.

Our early biomarker findings support these aspects that you'd be 12 75 mechanism of action.

Protein and gene signatures and blood should change is consistent with reduced myeloid derived suppressor cells, which correlates with Joe's and Pembrolizumab combination.

My like you're right. The press yourself also decreased and dose dependent manner atrophy and that would you be 12 75 or in combination with pembrolizumab.

An increase in tumor infiltrating T lymphocytes or Tils is observed in serial tumor biopsies selling both the GB 12, 75, monotherapy regimen as well as a combination therapy with pembrolizumab.

He positive T cells also increased with combination treatment.

We now plan to further characterize GB 12, 75 in an expansion cohort of up to 40 patients evaluating the recommended phase two dose at GBP 12, 75 in combination with Pembrolizumab we.

We will continue to report out clinical data from this ongoing trial in 2021.

Sheila Gujrati: CD8 positive T-cells also increased with combination treatment. We next plan to further characterize GB1275 in an expansion cohort of up to 40 patients evaluating the recommended phase 2 dose of GB1275 in combination with pembrolizumab. We will continue to report out clinical data from this ongoing trial in 2021. Please feel free to view these posters in their entirety on our website.

Please feel free to do these posters in their entirety on our web site. The presentations from doctors Bendel messersmith can be accessed on the 60 website as part of the city virtual conference.

With that I will hand, it over to Gossamer Barrios, Chief Financial Officer, Brian Gerardo for Finance Lucky Friday.

Brian.

Thank you Sheila we will now review the financial results for the third quarter of 2020, we're.

We ended the quarter with $555.4 million of cash and cash equivalents, we anticipate our cash cash equivalents and marketable securities along with access to our debt facility will provide us sufficient capital resources to fund operations and capital expenditures into the second half of 2023.

Sheila Gujrati: The presentations from Drs. Bendell and Mr. Smith can be accessed on the ATSISI website as part of the ATSISI virtual conference. With that, I will hand it over to Gossamer Bio's Chief Financial Officer, Bryan Giraudo, for a financial update.

Research and development expenses in the third quarter of 2020 were approximately 41.8 million as compared to R&D expenses of 40.1 million for the same period in 2019 gene <unk> expenses were 11.4 million in the third quarter as compared to G. and expenses of 9.8 million for the same period in 2019.

Bryan Giraudo: Thank you, Sheila. We will now review the financial results for the third quarter of 2012. We ended the quarter with $555.4 million in cash and cash equivalents.

Bryan Giraudo: We anticipate our cash, cash equivalents, and marketable securities, along with access to our debt facility, will provide us sufficient capital resources to fund operations and capital expenditures into the second half of 2023. Research and development expenses in the third quarter of 2020 were approximately $41.8 million, as compared to R&D expenses of $40.1 million for the same period of 2019. G&A expenses were $11.4 million in the third quarter, as compared to G&A expenses of $9.8 million for the same period in 2019. Our net loss for the quarter was $57.8 million, equating to $0.80 per share.

Our net loss for the quarter was $57.8 million equating to 80 cents per share.

For the same period in 2019, we reported a net loss of 48.5 million, which equated to 80 cents a share. The increase was primarily attributable to an increase in interest expense of $4 million a decrease in investment income of 1.7 million was.

With that I will turn the call back over to Sheila to offer some closing comments before we open the line up for Q1 at June.

Thank you Brian.

It's been an exceptionally busy quarter and year gossamer, especially as we advance multiple clinical and research programs during the call the pandemic.

I want to extend my personal appreciation to our patients physicians and partners, who have helped us achieve the activation of golf in this third and fourth phase two trials to date.

Sheila Gujrati: For the same period of 2019, we reported a net loss of $48.5 million, which equated to $0.80 a share. The increase was primarily attributable to an increase in interest expense of $4 million and a decrease in investment income of $1.7 million. With that, I will turn the call back over to Sheila to offer some closing comments before we open the line up for Q&A. Thank you, Bryan. It has been an exceptionally busy quarter and year at Gossamer, especially as we advance multiple clinical and research programs during the COVID pandemic. I want to extend my personal appreciation to our patients, physicians, and partners who have helped us achieve the activation of Gossamer's third and fourth Phase II trials to date. I would also like to extend my sincerest gratitude to the Gossamer team, who continue to bring their best selves and go beyond what is possible during these unprecedented times. With that, I will now turn the call over to the operator for questions. Operator?

I would also like to extend my sincerest gratitude to the Gossamer team, who continue to bring their best selves and go beyond possible. During these unprecedented times.

With that I will now turn the call over to the operator for questions.

Operator.

Thank you so much ladies and gentleman often asked one question and answer session.

Ask a question. Please press star one on your telephone if you wish to cancel your request you May press the founder Hashed. Please stand by while we compile documenting roster.

Your first question comes from the line of tighten their plans are.

Your line is now open.

Hey, guys. Good afternoon for taking the questions or football in GB users are two and a few age.

Data coming up.

Understand that it's more potent and selective about that but I guess im specifically interested in ratio of long exposure given the route of delivery can you. Just I guess has there been any data in terms of ratio of long exposure was about it but you can speak to and you know how much higher.

Sure you think Oh, Gee reserves or two could be when we see the data.

And then on can you just confirm what we see.

Operator: Thank you so much. Ladies and gentlemen, we will open it up for a question and answer session. If you wish to ask a question, please press star 1 on your telephone. If you wish to cancel your request, you may press the pound or hash key.

Implant patients and did you mention a six week well the use of possible, we could see data from that as well.

Great I'll start and then I'll ask a movie that I thought you said, our chief scientific officer to add any anything she would like so yes I'm in terms, we do have a several fold higher exposure in the lung to plasma and Ah you know, we we have done more care characterization of this preclinically.

Operator: Please stand by while we compile the Q&A rock. Your first question comes from the line of Tyler Vandenberg. Your line is now open.

Tyler Vandenberg: Hey guys, good afternoon. Thanks for taking the questions. I had a couple on GB002 and the PAH data coming up. I understand that it's more potent and selective than imatinib, but I guess I'm specifically interested in the ratio of lung exposure given the route of delivery. Can you just, I guess, has there been any data in terms of the ratio of lung exposure with imatinib that you could speak to and, you know, how much higher you think GB002 could be when we see the data? And then on, can you just confirm, will we see data from, Did you mention a six-week OLE? Is it possible we could see data from that as well?

As well as in our normal healthy volunteer study in terms of measuring purple.

PK and then in our P.H. phase one B trial.

It's important to understand that we designed as a molecule specifically that to have low systemic PK concentration because clearly what we saw with the prior and Matt and his experience and the clinical phase two and three P.H. trial was really substantial issues around safety and tolerability today.

If you have high I imagine you have a PK levels that hit again, a number of Chinese is that they were having a significant number of adverse events serious adverse events, including Gi side effects as well as damages, Ben and CNS subdural hematoma. So.

Sheila Gujrati: I'll start, and then I'll ask Louisa Saldesit, our Chief Scientific Officer, to add anything she would like. So, yes, we do have a several-fold higher exposure in the lungs to plasma. And, you know, we have done more characterization of this pre-clinically as well as in our normal healthy volunteer study in terms of measuring peripheral PK, and then in our PH Phase 1b trial. It's important to understand that we designed this molecule specifically to have low systemic PK concentrations because clearly, what we saw with the prior imatinib experience in the clinical Phase 2 and 3 PH trials were really substantial issues around safety and to So if you have high imatinib PK levels that hit, again, a number of kinases, that they have a significant number of adverse events, serious adverse events, including GI side effects, as well as edematous events, and CNS subdural hematomas. So, this was really critical that we would be able to ensure, again, low PK levels systemically in the periphery And so, GB002 is rapidly cleared and never reaches high levels systemically. So, what you see are low levels from a CMAX perspective, but then rapid clearance.

So this is really critical that we would be able to ensure again low PK level systemically in the periphery and so gpcrs, you're too is rapidly cleared and never reach as high level systemically. So what you see are low levels from the Cmax perspective, and then Bob Mclaren and we've shown this NR.

Norm healthy volunteer trials and were confirming that profile in our in the P.H. population. So that's a really critical component to this profile where are you getting want very substantial long exposures, but right at you know again manageable systemic exposures to really improve upon the safety and tolerability.

So and so that's that's critical and so you know well continue to discuss that and I think we can touch upon that in our Webinars December to go into more details on that.

Regarding the phase one big screens again as I mentioned, the two week study Oh, we do have a six month allele available for these patients or eight we had patients in that in the early part of this year, but because of Koubei. They had to come out because we had to pause that they really the contact at <unk>.

Louisa Salter-Schid: And we've shown this in our normal healthy volunteer trials, and we're confirming that profile in the pH population. So, that's a really critical component to this profile, where you, again, want very substantial lung exposures but very, again, manageable systemic exposures to really improve safety and tolerability. So that's critical, and so we'll continue to discuss that, and I think we can touch upon that in our webinar in December to go into more details on that. Regarding the Phase 1B experience, again, as I mentioned, this is a two-week study. We do have a six-month OLE available for these patients. Fortunately, we had patients in that OLE in the early part of this year, but because of COVID, they had to come out because we had to pause the conduct of the study given the total shutdown at the sites, especially for the pH-treating centers.

Study given the total shutdown at the sites, especially for the P.H. treating centers. So we will mainly be focused on two week data in December so again focused on PK safety tolerability target engagement and Biomarkers.

And could you discuss the perfect.

With that let me did you have anything to add.

[noise], yes at your I think you pretty much covered but I think one other thing is in it is not only just the exposure, but it's also the duration that's really deals you'd have to have a high retention on top of it is and because of that we have actually sustained exposure in.

The line up for a long period of time, so it's not just the PK distribution, but he's also so the way that you know to buys on target and we have data from the PD endpoints such as the MPR to another they're really cool fund this prolonged PD.

Louisa Salter-Schid: So we will mainly be focused on two-week data in December. So again, focus on PK, safety tolerability, target engagement, and biomarkers, and continue to discuss the program. With that, Louis, did you have anything else to add? Yes, I think you pretty much covered it, but I think one other thing is not only just the exposure, but it also is the duration that really 002 has a high retention on target, and because of that, we have actually sustained exposure in the lungs for a long period of time.

Great. Thank you.

Yeah, great. Thanks, Louise So I think we were going to look for I cant really presenting a substantial amount of preclinical.

Data and and for the calculation that we've done with our milestone to really show how we think it's truly best in class and the right way the REIT molecule for for ph patients.

Particularly.

Your next question comes from don't line up until Sept, Swartz, John Hynes now.

Louisa Salter-Schid: So, it's not just the PK distribution, but it's also the way that 002 binds to target, and we have data from PD endpoints, such as BMPR2 and others, that really confirm this prolonged PD. Great, thank you. Yeah, great. Thanks, Luisa.

Hey, guys. How are you doing thanks for taking my question.

I wanted to ask one on.

There are two to start.

I have to do with some.

Some comments I think I heard you say.

About how you might be able to look at so.

From the ongoing phase one.

Sheila Gujrati: So I think we're going to look forward to really presenting a substantial amount of preclinical data and further characterization that we've done with our molecule to really show how we think it's truly the best in class and the right molecule for PH patients, particularly. Your next question comes from the line of Joseph Schwartz. Your line is now open. Hey guys, how are you doing?

And.

So.

Potential due to bridge off of.

You've seen.

Healthy volunteers.

Stan I was just wondering.

That was accurate if you could expound on that and then.

[laughter] that these are dilator per se you know.

At what point would you hope [laughter] signal what would that signal.

Joseph Patrick Schwartz: Thanks for taking my question. Um, I also wanted to ask one on, uh, GP002 to start, and that... It has to do with some comments I think I heard you say about how you might be able to look at some data from the ongoing Phase 1B patients, and I was just wondering if that was accurate, if you could expound on that, and then, since this isn't a vasodilator per se, at what point would you hope to see a signal, and what would that signal be in terms of, you know, P. This is an interesting time.

In terms of.

Oh.

[laughter] marker.

How are you thinking about you know what.

[laughter].

[noise] Yeah, Great I think my point, we're really.

Judge of that we have a pretty substantial phase one experience. When you look at our essay D. Our multiple ascending dose study in normal healthy volunteers across a range of doses and now with the theme on being Peach patients. So the totality of the clinical experience. We have to date is is it.

Great for where we are in the stage of development I think we're taking all the right that.

An extra never going with the right design for the phase two trial. So I think what we'll be sharing a in December really it's the totality of our phase one experience and so that's that's what I was mentioning in terms of being able to bridge.

Sheila Gujrati: Yeah, great. I think my points were really, Joseph, that we have a pretty substantial phase one experience. When you look at our SAD, our Multiple Ascending Dose Studies, in normal healthy volunteers across a range of doses, and now with the Phase 1 B and PH patients, so the totality of the clinical experience we have to date is great for where we are in the stage of development. I think we're taking all the right steps to make sure that we're going with the right design for the Phase 2 trial. So, I think what we'll be sharing in December is really the totality of our Phase 1 experience. And so, that's what I was mentioning in terms of being able to bridge and look at not only what we have generated in terms of data from the PH patients in the Phase 1 B study, but also bridging that information back to normal healthy volunteers and seeing consistency in PK exposures and the like. I think that was the point I was making.

Look at not only what we generated in terms of data from the teach patients in the phase one b, but also the bridging that information back to normal demand tears and seeing consistency in peak exposures and the like I think that's a that was the point I was making.

And then secondly on your second question on you know time points for efficacy read out they think.

In temp typically score for P. D. You know our hope would be we could follow some patients over time and be able to look at changes and peripheral clinical disease biomarkers, such as pro BNP levels as well as potential changes on imaging, which is echocardiogram.

If you're asking me about timing if you look at some of the mountain of data you know they were able to see effect you know really even in that 12 week timeframe, but of course, our phase two study is a 24 week study.

Sheila Gujrati: And secondly, on your question about time points for efficacy readouts, I think typically for PD, you know, our hope would be that we could follow some patients over time and be able to look at changes in peripheral clinical disease biomarkers, such as pro-BMP levels, as well as potential changes on imaging, such as an echocardiogram. If you're asking me about timing, if you look at some of the imatinib data, you know, they were able to see effects, you know, really even in that 12-week timeframe. But, of course, our Phase 2 study is a 24-week study. And so, that's looking at PBR.

That's that's and that's looking at PBR, so and will be off the lucky in imaging and somebody systemic markers as well for clinical diseases. Both biomarkers I think it'll be a pretty robust data set coming out of the phase two a and again. Unfortunately, just because of the coated pandemic, you know really impacted or ability to have the <unk>. The.

A more robust stays on big spring, we were hoping for but nonetheless, we think we got very informative and impactful data for the program.

[noise] cool <unk> town.

Sheila Gujrati: So, and we'll also be looking at imaging and some of these systemic markers, as well, for clinical disease, as well as biomarkers. So, I think it'll be a pretty robust data set coming out of Phase 2. And again, unfortunately, just because of the COVID pandemic really impacted our ability to have the more robust Phase 1 B-experience we were hoping for. But, you know, nonetheless, we think we got very informative and impactful data for the program. Cool, we'll stay tuned. So then, on GB001, I was wondering if you could give us your thoughts or expectations for when we might meet.

Then on your reserves are one I was wondering if you know.

Bob.

[noise] expectations.

[noise] forward to learning about what Biomarkers.

Well our associated.

So first of all.

Are we to trial.

Yeah, I think that.

For US is I think we're shooting towards that first half of next year to be able to to kind of get the budgetary feedback. We're seeking you know we have to schedule. These meetings and the C. diff.

Divisions that deal with Cove, it and other therapeutics that are out there being studied in this in the call that patient population. So we're very mindful of that but our hope is that we're going to get that regulatory you know feedback and angle you know look forward to presenting more the detailed data in our plan forward in that.

Sheila Gujrati: We're able to look forward to learning about what biomarkers you've found are associated with a better response and the lead of Trump. Yeah, I think that for us, I think we're shooting towards the first half of next year to be able to kind of get the regulatory feedback we're seeking. You know, we have to schedule these meetings, and these are the same divisions that deal with COVID and other therapeutics that are out there being studied in the COVID patient population. So we're very mindful of that, but our hope is that we're going to get that regulatory feedback, and then we'll, you know, look forward to presenting more of the detailed data in our plan forward in that first half. Sounds good, thanks. Your next question comes from the line of Jeff Mecham. Your line is now open. Hey guys, thanks for checking the question. I had a couple.

First half.

Sounds good thanks.

Your next question comes from the line of traffic me Kim Caroline how often.

Hey, guys. Thanks for taking the question.

I had a couple I'm. The first one is on old too.

<unk> population the P.H. that you feel like you could maximize the differences in PBR resistance I guess, maybe those not well controlled on on combo therapy for example.

And what types of effect size Hsulin would you say that you you're aiming for in the study just as a proof of concept as you sort of get the.

Prepare for a a larger study and I had one follow up on the old one.

Yeah, that's really exactly they're picking publishing were going after Jeff were looking at patients who continued to have higher P.B. yards, and <unk> disease burden and symptomatology, despite being on at least two classes of being the dilator therapies, if not three classes of either donnelley to therapy.

Jeff Mecham: The first one is on O2. Is there a population in PEH that you feel like you could maximize the differences in PBR resistance? I guess maybe those not well controlled on combo therapy, for example? And then what types of effects size, Sheila, would you say that you're aiming for in the study just as a proof of concept as you sort of get the idea ready for a larger study? And I have one follow-up on 001. Yeah.

So they are onshore functional class two and three patients.

We had you know again pretty substantial disease burden.

And they are on background therapy. So we're adding on to it. So I think we're really enriching for kind of a higher disease activity population, which we think is the right population to be studying in this phase two trial. So I think that you know very very compelling unmet need.

In terms of effect size you know if you look at the data from the mountain and from the impress trial.

Sheila Gujrati: That's really exactly the patient population we're going after, Jeff. We're looking at patients who continue to have higher PVRs and disease burden and symptoms despite being on at least two classes of vasodilator therapy, if not three classes of vasodilator therapy. So they are functional class two and three patients with, again, a pretty substantial disease burden, and they are on background therapies that we're adding on to. So I think we're really enriching for kind of a higher disease activity population, which we think is the right population to be studying in this phase two trial. And I think that's, you know, a very, very compelling unmet need.

They saw about a 32% reduction in a PDR like 30% to 32% as well as improvement through about 30% improvement in six minute walk distance now that was done a while ago. You know in terms of when the study was conducted and you'll have to pick those patients were and then they were also on.

You are through cost of living the dilator therapy. So that's similar that was also an add on study design to those other classes of therapy. So that's that's really helpful to know that they saw that level of improvement despite being added on to visa Dilators and I think that's again very compelling rationale for our program and so I think you know obviously that that.

Sheila Gujrati: In terms of effect size, you know, if you look at the data from Imatinib from their IMPRESS trial, they saw about a 32% reduction in PVR, like 30 to 32%, as well as improvement, about a 30% improvement in six-minute walk distance. Now, that was done a while ago, you know, in terms of when that study was conducted, you know, how sick those patients were, and then they were also on two or three classes of vasodilator therapy, so that's similar. That was also an add-on study design to those other classes of therapy, so that's really helpful to know that they saw that level of improvement despite being added on to vasodilators, and I think that's, again, a very compelling rationale for our program.

Would be terrific to to be able to show that type of similar efficacy again. The question is how much are patients improved since then with their level of disease control and so you know where we're going to be you know talking thinking more about that in talking more about that as we get our study off the ground.

Gotcha, Okay. That's helpful. Sheila and then maybe.

Maybe one for you or for Brian I know, you're still getting feedback on Oh, one on next steps but.

When you think about strategic options here or partnering or is it a parallel process or do you have to have absolute clarity on phase.

Phase three design as a sort of a first step to negotiations. Thank you.

Yeah, I would say both right because I mean, you reengage in discussions it's of course, a very critical piece for us to understand what is the regulatory and development path forward right. So I think those are obviously very natural.

Sheila Gujrati: So I think, obviously, it would be terrific to be able to show that type of similar efficacy. But again, the question is, how much have patients improved since then with their level of disease control? So, you know, we're going to be, you know, talking, thinking more about that, and talking more about that as we get our study off the ground. Gotcha. Okay, that's helpful, Sheila. And then maybe one for you or for Bryan.

I think that we have to get information on Brian do you want to provide any commentary yeah I would guess that thanks for the question. Jeff I think there are practical challenges that you are while we have ideas around what a phase three program could look like.

Really hard to engaging in substantive discussions until we let regulators way in that obviously has a direct read through to the investment that any partner would have to make in phase three and then what the really potential commercial presentation could be so you know it is a little bit of a chicken in the egg conversation and working diligently to be able.

Sheila Gujrati: I know you're still getting feedback on 001 on next steps, but, you know, when you think about strategic options here or partnering, is it a parallel process? Or do you have to have absolute clarity on, you know, phase three design as sort of a first step to negotiations? Thank you. Yeah, I would say both, right?

To get those answers because right now the only real reference point the strategic market has as to what a phase three was a DP two antagonist looks like is what our friends at Novartis did and so we're obviously trying to see if we can have a more streamlined and efficient plants, but until we have regulators weighing on that it's really hard.

Sheila Gujrati: Because, I mean, we engage in discussions. It's, of course, a very critical piece for us to understand what the regulatory and development path forward is, right? So, I think those are obviously very natural things that we have to get information on. Bryan, do you want to provide any commentary? Yeah, I would.

To talk about what that could financial as well as.

Infrastructure commitment or any partner would have to make.

Okay. Thanks, guys.

Thanks.

Bryan Giraudo: Thanks for the question, Jeff. I think, you know, our practical challenge is that, while we have ideas around what a phase three program could look like, it's really hard to engage in substantive discussions until we let regulators weigh in. That obviously has a direct read-through to the investment that any partner would have to make in phase three, and then what the potential commercial presentation could be. So, you know, it is a little bit of a chicken and egg conversation, and we're working diligently to be able to get those answers. Because right now, the only real reference point the strategic market has as to what a phase three with a DP2 antagonist looks like is what our friends at Novartis did. And so, we're obviously trying to see if we can have, you know, a more streamlined and efficient plan. But until we have regulators weigh in on that, it's really hard to talk about what that financial as well as infrastructure commitment any partner would have. Okay, thanks guys. Thanks, Jeff.

Your next question comes from the line of Josh Schimmer. Your line is now.

Thanks for taking the question I got on a road to communicate when we might be able to get a first look to effect on reported hurt pressure.

Specifically it was up you measure to the most frequently are set to have to wait for phase two and a friend I might have missed it but I in your prepared remarks, but how should we think about operating expenses going forward.

Yes, the job.

Yeah, so pulmonary bathroom resistance and that you really be the data comes from right heart catheterization and it is really the primary endpoint of our phase two trial. So that's again the 24 week endpoint for phase two and so that will be definitely when that will be robustly characterize and so on that.

That's when you should plan to see that from the phase one b you that that that is more around again clinical biomarkers disease activity by <unk>.

That potential Echograph echocardiographic imaging, but not really you know him dynamic data.

And then go ahead Bryan operating expenses.

Jeff Mecham: Thanks. Your next question comes from the line of Josh Schimmer. Your line is now open.

Yes, so Josh we said as we said in my remarks that you know all the capital available to Gossamer takes us into the second half of 2023.

Josh Schimmer: Thanks for taking the question again on OO2. Can you indicate when we might be able to get a first look at the effect on right-sided heart pressure and PBR specifically? Is that being measured in Phase 1B, or is that going to have to wait for Phase 2? And Bryan, I might have missed it, but in your prepared remarks, how should we think about operating expenses going forward? Yes, the job of, yes.

I'm cautious to give greater guidance than that just because you know as we are kicking off these two important phase two trials against the backdrop of the depend demick, it's still too early for us to make predictions on enrollment timelines and then and thus cost, but we do feel very good based upon the totality of.

Sheila Gujrati: Yeah, so pulmonary vascular resistance, and the data comes from right heart catheterization, is really the primary endpoint of our phase two trial. So that's, again, the 24-week endpoint for phase two. And so that'll be, that's really when that will be robustly characterized. And so that's when you should plan to see it. From phase 1b, you know, that is more around, again, clinical biomarkers, disease activity biomarkers, and potential echocardiographic imaging, but not really, you know, hemodynamic data. And then go ahead, Bryan, on operating expenses.

The book of work shall we say that we're doing it gossamer that the capital we have takes us well to the back half of 2023.

Thank you.

Your next question comes from the line of optical your line is now open.

Great. Thanks. Good afternoon. Thanks for taking the questions I guess first maybe to come back to the Sears or two I I know you guys have been engaging with a lot of okay wells and I'm just trying to understand the landscape I I. Appreciate you guys bring it up the mountain it you.

You know experience in phase two but I guess, when you think about sort of the the hurdle for clinical meaningfulness on either in terms of PBR six minute walk distance, how do you think about that and in this population kind of what's what's the I guess like a bunch of them sort of floor and what you need to see and then maybe on 12 75.

Sheila Gujrati: Yeah. So, Josh, as I said in my remarks, all the capital available to Gossamer takes us into the second half of 2023. I'm cautious to give greater guidance than that just because, you know, as we are kicking off these two important phase two trials against the backdrop of the pandemic, it's still too early for us to make predictions on enrollment timelines and, thus, costs. But we do feel very good based upon the totality of the book of work, shall we say, that we're doing at Gossamer that the capital we have takes us well into Your next question comes from the line of Carter Gould. Your line is now open.

The poster talked it do you know sort of delineated for.

For 50% to 75% reduction on.

On M.D. assays can you maybe just help put that in context, and if there's if theres a target or there's some sort of you know.

Total you guys are looking to ticket you know to to reach and you know just kind of help thinking about some of the biomarker data. Thank you.

Sure.

Uh huh.

Yes, I think you know does it feel like it's your first question really gets to the unmet need of what we're trying to achieve here. So.

Yeah, just as a reminder.

Everyone knows there are these three causes a day the dilator therapy that had been approved and P. Asian better you know predominately use a functional class two three and four and most patients are start off in a combination regimen. You know usually you know with some type of P. Five DRA type in <unk>.

Carter Lewis Gould: Great. Thanks. Good afternoon.

Sheila Gujrati: Thanks for taking the questions. I guess first, maybe to come back to 002. I know you guys have been engaging with a lot of KOLs and trying to understand the landscape. I appreciate you guys bringing up the Imatinib experience in Phase 2, but I guess when you think about sort of the hurl for clinical meaningfulness, either in terms of PVR, or six-minute walk distance, how do you think about that in this population? Kind of, you know, what's the, I guess, for lack of a better term, sort of floor on what you need to see. And then maybe on 1275, the poster talked, you know, sort of delineated, about 50 to 75 percent reduction on MDSCs. Can you just help put that in context, and if there's a target or there's some sort of hurdle you guys are looking to reach, and just kind of help think about some of that biomarker data? Thank you. Sure.

You know tyco combination.

I.

You know then probably like ones are added obviously and you know depending on how severe the patient has can be add on even earlier in the disease state.

Then there really are no other approved treatment option you know beyond the two cost of either dilator therapies. So for those patients who have a continues into mythology continued deterioration in their functional status and real impairment on the human dynamics, leading to right heart failure.

And morbidity and mortality you know with the highway to mortality and there's a 50% to 75% mortality rate for patients who are functional class three and four who are you know controlled are continuing to progress, which as you know really rivals any oncology indication decisions.

Decisions have no available therapy suburban.

So we're really looking to add on to these classes. If there you know to be neither doctors and see if we can just it really show any functional improvement.

As measured by six minute walk distance, which is obviously very clinically important because we need to see that functional improvement any objective parameter of looking at human dynamic improvement is obviously very important and critical especially at the stage of development for us to get the type of information. That's why we put this is our primary endpoint for the phase two trial.

Sheila Gujrati: Yes, I think, you know, your first question really gets to the unmet need of what we're trying to achieve here. So, just as a reminder, everyone knows there are these three classes of vasodilator therapies that have been improved in PAH and that are predominantly used as functional classes 2, 3, and 4. And most patients are started off in a combination regimen, usually with some type of PD5ERA type coat combination, and then process cyclines are added, obviously, depending on how severe the patient is, could be added on even earlier in the disease state. And then there really are no other approved treatment options beyond those three classes of vasodilators. So for those patients who have continued symptoms, continued deterioration in their functional status, and real impairment of the hemodynamics, leading to right heart failure and morbidity and mortality, you know, with a high rate of mortality. And there's a 50 to 75 percent mortality rate for patients who are in functional class three and four who aren't These patients have no available therapy.

We will also be measuring our impact on functional improvement as well.

So that's really you know where you know what were looking so that we can answer the question about you know what's the level of improvement we want to see you know I would argue on what we're hearing from our commitments as they would obviously like to see any level of improvement here because you know just being able to add on to these be the data later in the <unk>, that's just pick a population and show.

Improvement and he's outcome measures will be very meaningful because there just aren't any available treatment option.

Having said that you all know that Acceleron is attached or stuff is moving forward in this population as well, which is terrific that they could potentially be affording a another another.

Another type of treatment for these patients and just to remind you all see that isn't injection that given every three weeks and in person because of the human logic monitoring this but our commercial presentation for good years. Your two is really designed to be a very convenient dry powder jewelry that patients can carry around with them and really be.

Able to live a normal life, while having the PPI I'm just similar to what asthmatic patients do they're also very familiar with it you know different types of inhaler device.

Before they had a pretty bulky nebulizer type system now that they've had to take up to four times a day.

Sheila Gujrati: So we're really looking to add on to these classes if they're doing these vasodilators and see if we can just, you know, really show any functional improvement, as measured by six-minute walk distance, which is obviously very clinically important because we need to see that functional improvement. And the objective parameter of looking at hemodynamic improvement is obviously very important and critical, especially at this stage of development, for us to get that type of information. That's why we put this as our primary endpoint for the Phase II trial, but we will also be measuring our impact on functional improvement as well. So that's really, you know, where we're looking.

So now with yeah type a type a D.V. I presentation, and they're moving more to depuy very favorably received its a presentation and a delivery system that is highly appreciated by the team in the community.

So I think that you know again, showing really any improvement on functional symptomatology improvement will be will be considered very very.

Very favorably given that there's really a lack of treatment options for these patients.

The movie.

Moving on to 12, 75, I mean, I'll, let luis to comment on this as well I mean, I think we've seen preclinically our ability to really disrupt.

My like cell biology that means we've shown in preclinical tumor is the reduction of myeloid derived suppressor cells population book granular Citic Enanta Citic as well is a tumor infiltrating macrophages are tumor associated macrophages or time.

Sheila Gujrati: So, you know, we can answer the question about, you know, what's the level of improvement we want to see? You know, I would argue, and what we're hearing from our clinicians is that they would obviously like to see any level of improvement here because, you know, just being able to add on to these vasodilators in such a sick population and show improvement in these outcome measures will be very meaningful because there just aren't any available treatment options. Having said that, you all know that Exceleron and Cetatorcept are moving forward in this population as well, which is terrific because they could potentially be affording another type of treatment for these patients. And just to remind you, obviously, that is an injection that's given every three weeks in person because of the hematologic monitoring. Our commercial presentation for GB002 is really designed to be a very convenient dry powder inhaler that patients can carry around with them and really be able to live a normal life while having this DPI, just similar to what asthmatic patients do.

And the increase and the T cell populations, which is so critical for efficacy the increase in tumor infiltrating lymphocytes and at the gate called the T cell. So weve seen pre clinically. So it's really you know that the combination of being able to reduce the immunosuppressive burden both by blocking the recruitment and migration of these cells into.

You the tumor themselves, but all and also we polarizing them from an M. Two immunosuppressive monotype to an M. One immunostimulatory phenotypes and then showing the resulting increase in the T cell biology to be able to then translate into kind of fun and so I think when you look at the totality of our biometric marker data when you see the reduction in energy.

Yes, he sells a grant book a book that the purple compartment book modest it again granule city in the monotherapy as well as the combination arms, especially if you look at the granular citic and geographies.

Sheila Gujrati: They're also very familiar with different types of inhaler devices. Before, they had pretty bulky nebulizer-type systems that they had to take up to four times a day. So now with a type of DPI presentation, and they're moving more to DPI, it's very favorably received.

As well that's what we're seeing on inappropriate on the proteomics and the transcript will make that lose it can speak more to you and then looking at the tumor biopsies himself and seeing the influx of tils in the influx of PV cells.

And until you see in monetary patients as well as combination therapy patients for the CD eight we're seeing it in the limited samples we have in the combination treated patients I think that's what we're trying to get to your question of what level and do you see or you know myeloid cell population targeting we have to get used to kind of show the increase in.

Sheila Gujrati: And it's a presentation and a delivery system that is highly appreciated by the PA treatment community. So I think that, again, showing really any improvement in functional symptomatology and improvement will be considered very favorably, given that there's really a lack of treatment options for these patients. [inaudible] Moving on to 1275, I mean, I'll let Louisa comment on this as well.

T lymphocytes I mean, I think that's a great question I don't know if we have enough data to answer that but let me turn it over to Luisa to get her you know more informed opinions about about these matters.

Yes, absolutely. So that is the question put out there that people have grappled with what you know and basically what I think most people, including US have land that is it has to be going down in the right direction and he has to be beyond just a significant so there is significant so it's not just a.

Sheila Gujrati: I mean, I think we've seen preclinically our ability to really disrupt myeloid cell biology. That means in preclinical tumors the reduction of myeloid-derived suppressor cell populations, both granulocytic and monocytic, as well as tumor-infiltrating macrophages or tumor-associated macrophages or TAMs, and the increase in T-cell populations, which is so critical for efficacy So you see an increase in tumor-infiltrating lymphocytes and CD8 positive T-cells. We've seen this preclinically.

Ill now pass it observation, but sheilas point, well I think that other folks and as including have really beautiful Dean is do we have that proteomics biomarkers that go with it. That's it you see such a significant change in cytokine in chemo kind.

We do and that is really that you whiting backing the biology and then it Sheila mentioned at the end of the day in that to me is all about the T cells, specifically the C.D.A. and are you seeing any increase in C.D.A. into most infiltration and and we are so I think is this a tally up the data rather than a specific number.

Sheila Gujrati: So it's really, you know, the combination of being able to reduce that immunosuppressive burden, both by blocking the recruitment and migration of these cells into the tumors themselves, and also repolarizing them from an M2 immunosuppressive phenotype to an M1 immunosimilatory phenotype, and then showing the resultant increase in the T-cell biology to be able to then translate into clinical response. And so I think when you look at the totality of our biomarker data, when you see the reduction in MDSC cells, both in the peripheral compartment, both monocytic and granulocytic, in the monotherapy, as well as the combination arms, especially if you look at the granulocytic MDSCs, as well as what we're seeing in the periphery on the proteomics and the transcriptome mix that Louisa can speak more to.

But that number just has to be you know consistent you know that <unk> for us to know that is not just a fluke.

And that's I think what everybody else is doing with these M.D.S.C. modulating therapies.

Yeah, and I would just add it's getting back to the clinical data as well you know this it's been very reassuring to us that we're seeing these biomarker changes again looking at the periphery looking at the cells themselves looking at the proteins looking at the gene expression for myeloid derived gene a as well as inflammatory.

Sheila Gujrati: And then looking at the tumor biopsies themselves and seeing this influx of TILs and this influx of CD8 cells in the TILs you see in monotherapy patients as well as combination therapy patients for the CD8. And we're seeing it in the limited samples we have in the combination treated patients. I think that's what we're trying to get to. Your question of what level of MDSC or myeloid cell population targeting we have to get to to kind of show the increase in T lymphocytes, I mean, I think that's a great question. I don't know if we have enough data to answer that, but let me turn it over to Louisa to get her more informed opinion on these matters.

Switching to be look at interferon type responses and then the tumor themselves and you know in the few patients we've been able to get a biopsy, which had been a really great effort from our team I want to thank our team could not been easy during the call. The pandemic actually get a paired biopsies I think you know that's been incredibly productive and fruitful for us to be.

Good to see that you know we are seeing an influx of pills and cdeight positive T cells, which are getting really critical for the mechanism and validation of that biologic activity and then see the clinical activity just to remind everyone. I mean, you guys know that these are very sick patients in most patients are coming in you know all have at least two line.

Louisa Salter-Schid: Yes, absolutely. So that is a question for all therapies that people have grappled with: what is enough? And basically, what I think most people, including us, have landed on is that it has to be going down in the right direction, and it has to be beyond just, you know, significant. So there is significance, so it's not just a haphazard observation.

The therapy, many of them have five or greater prior lines of therapy across very difficult to treat tumor types that have not shown good responses either you know mostly secondary with the checkpoint inhibitors and also the primary reason to checkpoint inhibitors as we've seen with patients who've been treated with Cpis. It had about a two month duration of response prior and the law.

I know, we're seeing you know responses in combination. So I think that you know terms at least stable disease I should say I think that it's really encouraging to have you know again five of the seven prolonged stable disease at the 800 milligram or greater including a you know again a confirmed PR the point a given just the phase one experience we're in.

Louisa Salter-Schid: But as Sheila points out, what other folks, and us included, have really zeroed in on is do we have then proteomics biomarkers that go with it, that you see a significant change in cytokines, in chemokines, which we do, and that is really that you are impacting the biology. And then, as Sheila mentioned, at the end of the day, the tumor is all about the T cells, specifically the CD8, and are you seeing an increase in CD8 in tumors, or infiltration, and we are. So I think it's the totality of the data rather than a specific number.

We find really encouraging and that's been about 16 evaluable patients. So if you're saying you know five out of 16, you know that's really I think encouraging information for.

Your next question comes from the line of Am on Millen.

Your line is now open.

Louisa Salter-Schid: That number just has to be, you know, consistent enough for us to know that it's not just, And that's, I think, what everybody else is doing with this MDS-C modulating therapy. Yeah, and I would just add, getting back to the clinical data as well, so this has been very reassuring to us that we're seeing these biomarker changes. Again, looking at the periphery, looking at the cells themselves, looking at the proteins, looking at the gene expressions for myeloid-derived genes, as well as inflammatory genes, if you look at interferon-type responses, and then the tumors themselves.

Hi, Thanks for taking the question so turning to TV. There's there are four and you see I mean, given some of the physician feedback from the rethink kind of phase one data can you just speak to why that really cofelice essentially exciting positions and this mild to moderate setting and where it could fit into the evolving commercial landscape and and then just in terms of potential future combination work are there anything I can I can again that you think would be logical.

Yeah, I think it's just the excitement really is such a differentiated mechanism. So as I mentioned on the call. It's really not that typical immunosuppressant and there are a number of you know effective therapies of course most of them are biologics, but also some orals that.

Sheila Gujrati: And, you know, in the few patients we've been able to get biopsies, which has been a really great effort from our team. I want to thank our team because it's not been easy during the COVID pandemic to actually get paired biopsies. I think, you know, it's been incredibly productive and fruitful for us to be able to see that we are seeing this influx of TILs and CD8 positive T cells, which are, again, really critical for the mechanism and validation of that biological activity. And then to see the clinical activity, just to remind everyone, I mean, you guys know this, that these are very sick patients. You know, most patients who come in all have at least two lines of therapy.

Entering into the marketplace, we have the jobs that are approved.

The S&P a receptor modulator denim odd a you know had very exciting phase three data and I think others will you know potentially be entering the space, but those are really focused on targeting the immune system. This this type of therapy is it's actually a therapy that clinicians have been looking for.

Both in terms of the differentiated mechanism focused on Epicel your barrier function in repair and integrity of the mucosal lining in being able to heal that they the mucosa into got for these IBT patients that have had a disrupted epithelial lining mislead that further information and continued.

Kind of a disease symptomatology and severity I'm sitting that's really very exciting from you again, a depression mechanism that could be used alone it, especially in earlier stages of disease as well as in companies and some other immune suppressant hopefully in a safe and synergistic manner as well the ability then to take that and to target.

Sheila Gujrati: Many of them have five or greater prior lines of therapy across very difficult-to-treat tumor types that have not shown good responses, either, you know, mostly secondary resistance to checkpoint inhibitors and also primary resistance to checkpoint inhibitors, as we've seen with patients who were treated with CPIs and had, you know, about a two-month duration of response prior and then lost that. And then we're seeing responses in combination.

A earlier population in terms of really that more moderate disease, especially by they and steroids failure patients who have not progressed on to moderate to severe disease. At this point because right now it's a pretty big leap of faith for patients to have to go from there five eight days and steroids and maybe some other.

Sheila Gujrati: So, I think that, you know, in terms of stable disease, I should say, I think that is really encouraging. So, to have, you know, again, five of the seven prolonged stable disease at the 800 milligram or greater, including, you know, again, a confirmed PR at this point, given just the phase one experience we're in, is really encouraging. And that's in about 16 valuable patients. So, if you're seeing, you know, five out of 16, that's really, I think, encouraging information for us. Your next question comes from the line of Emma Miller. Your line is now open.

Sure you know generic humanist immunosuppressant therapy that are commonly used to a biologic or to really put an immune suppressant oral that has the risk of infection the risk of malignancies and other monitoring that maybe required. So it's a really big jump and leap of faith and Billy patients anchors and would prefer to have another.

Therapy that could be in the in that gap to be able to use a such a GB. They're there for so I think it's way again that pre biologic that pre moderate severe positioning as well as the differentiated mechanism that is resonating so powerfully and so and they are so excited about this type of approach.

Emma Miller: Hi, thanks for taking the question. So turning to GB004 and UC, given some of the physician feedback from the recently presented phase one data, can you just speak to why the early profile is so potentially exciting to physicians in this mild to moderate setting and where it could fit into the evolving commercial landscape? And then just in terms of potential future combination work, are there any specific mechanisms that you think would be logical? Yeah, I think it's just the excitement that really is such a differentiated mechanism.

Which makes really tremendous sense, we look at the biology of the disease area.

So I think that's really what we're focused on addressing a win with our trial design with the shift you see study to really capitalize on what we understand about the mechanism and who are the best patients to benefit and then I want to have Louisa and add her thoughts on this as well because we've been doing a lot of work on the mechanism and then and we could talk.

The combination approaches to.

Yes. So we do we have really spend some time because as Sheila mentioned this is really a new mechanism of action is so complimentary to a immunomodulators that are out there a standard of care.

Sheila Gujrati: So, as I mentioned on the call, it's really not that typical immunosuppressant. And there are a number of, you know, effective therapies. Of course, most of them are biologics, but also some orals that are entering the marketplace. We have the JAKs that are approved.

So we have got a lot of data about the translational endpoints, we organize and coal cultures as valid the in vivo models, as and and including patient samples and and really we are seeing that the that seanergy not just not just compliments.

Sheila Gujrati: I think the S1P receptor modulator, Xanamod, had very exciting phase three data, and I think others will, you know, potentially be entering the space, but those are really focused on targeting the immune system. This type of therapy is actually a therapy that clinicians have been looking for, both in terms of the differentiated mechanism focused on epithelial barrier function and repair, and the integrity of the mucosal lining and being able to heal the mucosa in the gut for these IBD patients that have had a disrupted epithelial lining, which leads to further inflammation and continued disease symptomatology and severity.

Sorry, but also Seanergy you know lots of quite a few and points. When you combine a lead to a specific therapies up dead, including the JAK inhibitors is valid anti TNF, so more to come and we will absolutely do share the data, but I think you know not surprisingly we are seeing very good.

Synergy between these two approaches.

Great. Thank you very much.

Yeah.

Your next question comes from the line.

David Wong.

Your line is now open.

Hey, guys. Good afternoon. Thanks for fitting me in so I just had.

Sheila Gujrati: So, I think that's really very exciting from, you know, again, a differentiated mechanism that could be used alone, especially in earlier stages of disease, as well as in combination with some other immunosuppressants, hopefully in a safe and synergistic manner, as well as the ability then to take that and to target a earlier population in terms of really that more moderate disease, especially 5A phase and steroid failure patients who have not progressed on to moderate to severe disease at this point, because right now it's a pretty big leap of faith for patients to have to go from their 5A phase and steroids and maybe some other, you know, generic immunosuppressant therapies that are commonly used to a biologic or to a really potent immunosuppressant oral that has the risk of infections, the risk of malignancies, and other monitoring that may be required. So, it's a really big jump and leap of faith, and really patients and clinicians would prefer to have another therapy that could be in that gap to be able to use, such as a GB004.

Two questions one on T.H. and then one for all three plays so well.

The P.H. I suppose at Acceleron with other SEC.

Supportive phase two trial, that's looking at cardiopulmonary exercise testing and really looking at peak oxygen consumption is that you know is that something that you would ever be interested in pursuing for two and these big haven't got it though.

Would be for me, Dave are additive to the drugs profile.

Yeah, No that's very obviously very interesting study and you.

You know, we applaud them for taking those types of measurements. We had discussed this extensively with our investigators.

Investigators as well we have not built in that type of detailed and rigorous you know in terms of intensive I should say and assessments in two on some of these are our trial and our phase two study specifically I think you know what they think we're focused on there we think the most relevant endpoints at this stage.

The development in terms of looking the pulmonary doctor visits and.

Sheila Gujrati: So, I think it's really, again, that pre-biologic, that pre-moderate to severe positioning, as well as the differentiated mechanism that is responding so powerfully, and they're so excited about this type of approach, which makes really tremendous sense when you look at the biology of the disease area. And so, I think that's really what we're focused on addressing with our trial design, with the SHIFT-UC study, to really capitalize on what we understand about the mechanism and who are the best patients to benefit. And I want to have Louisa add her thoughts on this, as well, because we've been doing a lot of work on the mechanism, and then we could talk about, you know, the combination approaches, too.

And the measurement on the Hema dynamic grandmother, as well as right heart function.

Function.

And that's again through again, the right path data that we'll be getting involved echocardiogram imaging to really assess ejection fraction. So I think those are you know some of the areas that we think we think that where that's the most relevant for for where we are the other biomarkers that were assessing again around.

Pro BNP loved the marker, but her screen it.

You know.

Would be off the very important it'd be in PR too to really think about the mechanism in greater depth. I think is important but those are things that we are looking at potentially doing.

Overtime in support of studies, we are looking at some other imaging modalities and I think I will be very exciting to hence you try to get at what's happening in the vascular structure, you know and be a really in the vessels themselves in the lung and so those are things that we look forward to.

Louisa Salter-Schid: Yes, so we have really spent some time because, as Sheila mentioned, this is really the mechanism of action that is self-complementary to the immunomodulators that are out there as standard of care. So we have gathered a lot of data, both on translational endpoints with organoids and co-cultures, as well as in vivo models, including patient samples. And really, we are seeing that synergy, not just complementary, but also synergy in quite a few endpoints when you combine it with specific therapies out there, including the JAK inhibitors as well as anti-TNFs. So more to come, and we will absolutely share the data, but I think, you know, not surprisingly, we are seeing very good synergy between these two approaches. Great, thank you very much. Your next question comes from the line of David Huang. Your line is now open.

Nothing again at our Webinars in December and I think those are some other novel techniques that imaging that will be employing in our program. As you know we have decided are probably the best at this time.

Got it great and then just on ulcerative colitis.

I know that some of the S. One p. receptor modulators are interested in moving.

Earlier into the treatment paradigm and so for example, I see that trend.

TRASM odd as a phase two trial.

David Huang: Hey, guys. Good afternoon. Thanks for fitting me in. So, I just had two questions, one on PAH and then one on ulcerative colitis. So, for PAH, I know that Acceleron with the Pratercept has a supportive Phase II trial that's looking at cardiopulmonary exercise testing and really looking at peak oxygen consumption. Is that, you know, is that something that you would ever be interested in pursuing for OO2?

Her occasions, I think they're going from Mayo score four to six endoscopic score of at least one.

Does that you know is that a patient population that overlaps with yours rolling in your phase two or you know would you guys be different or maybe even earlier.

In the treatment paradigm.

I would say that that would be an overlapping 80 population and you know if you look at the totality of the male stores in the end of the scores.

Sheila Gujrati: And, you know, do you think having that info would be informative or additive to the drug profile? Yeah, no, that's obviously a very interesting study, and we applaud them for taking those types of measurements. We have discussed this extensively with our investigators as well. However, we have not built in that type of detailed and rigorous, in terms of intensive, I should say, assessments into some of these trials in our phase two study specifically. I think we're focused on, what we think are, the most relevant endpoints at this stage of development, in terms of looking at pulmonary vascular resistance and the test measurement on the hemodynamic parameters, as well as right heart function. And that's, again, through the Reinhardt CAF data that we'll be getting, as well as echocardiogram imaging to really assess ejection fraction.

You know I think the question will just be you.

What is the profile for you know I've got you know Charles in my long term and you obviously know the Pope up or down a lot. You know you know, we know denim not very well having developed the drug. So I think that we know that the safety and other liabilities or you know around monitoring for that therapy and while we think it's a great therapy I think there will.

B, you know maybe potential challenges and in their uptake given some of the you know 50, I believe the day that drug and the treating clinicians will have to deal with wood. That's one p. class I think the question is over time well be liabilities be for any S&P modulator, you know completing their large development programs that we have to see that and then.

How how can they move up into that the treatment algorithm. So I think that will be a question in terms of how it's positioned and how that will be used.

Sheila Gujrati: So I think those are, you know, some of the areas that we think that we are most relevant for where we are. The other biomarkers that we're assessing, again, around pro-BMP levels, the marker Reinhardt strain, and, you know, would be also very important in BMPR2 to really think about the mechanism in greater depth, I think, is important, but those are things that we are looking at potentially doing, you know, over time in support of studies. We are looking at some other imaging modalities that I think will be very exciting to potentially try to get at what's happening in the vascular structure, you know, and really in the vessels themselves in the lung.

By the clinical community and how we've received by patients.

No. There is something around just significant lymphocyte reduction, which is which can be scary to clinicians, especially because they have had to deal with PML rent with tysabri I'm, obviously, they've gotten a lot more comfortable with that within Ti vo with a better lose them out looking at you know album for me to seven targeting therapies I'm, having said that it's always.

You know a rest in terms of thinking about potential infection risk. When you have you know really <unk> you know reduce the number circulating peripheral lymphocytes. So I think those things are real and well always have to be managed by clinicians and we thought about for patients. So the question is how will that profile in.

Sheila Gujrati: So those are things that we look forward to discussing, again, at our webinar in December. And I think those are some other novel techniques of imaging that we'll be employing in our program, which, you know, we have decided are probably the best at this time. Got it, great.

Here, the ability to be treated to be and to be really using that mild to moderate population versus a therapy that doesn't have that type of immune system. The fact and potential infection risk over time. So I think those are some of the things that we think about when we think about these other therapies and how they want it you want to try to move up and to the earlier a line that there.

Sheila Gujrati: And then just on ulcerative colitis. I know that some of the S1P receptor modulators are interested in moving, you know, earlier into the treatment paradigm, and so, for example, I've seen that, you know, at TRASIMOD as a phase 2 trial, in moderate patients, I think they're going from Mayo score 4 to 6, endoscopic score of at least 1. Now, is that, you know, a patient population that overlaps with who you're enrolling in your phase 2, or, you know, would you guys be different or maybe even earlier in the treatment paradigm? I would say that that would be an overlapping disease population, you know, if you look at the totality of the Mayo scores and the endoscopic scores, you know, I think the question will just be, you know, what is the profile for, you know, I've got, you know, atrazumab long-term, and we obviously know the profile for odanamide very well, having developed the drug.

Beep.

So that's one thing and then the second thing is you know somebody go to oral coming in I don't really view them. It's so much competition. These could be great again complement terriers synergistic combinations breath. So for us to have really powerful oral oral combinations I think will be great for patients and because we are such a.

With orbital mechanism you know and we think we should be able to combine safely with these other therapies also you know to to really focus on that we are got targeted so we have a very limited systemic okay. We have a lot of you know really focused on colonic exposure I.

I think that those would be very good for us to be able to mechanism that we could potentially combined with its loses mentioning we just started our work on the common age.

And again have oral combination it put this for patients is critical you know no one therapy is going to cure it.

Sheila Gujrati: So, you know, I think that we know that, you know, the safety and other liabilities are, you know, around monitoring for that therapy, and while we think it's a great therapy, I think there will be, you know, maybe potential challenges in their uptake given some of those safety liabilities of that drug, and those treating clinicians will have to deal with S1P class. I think the question is, over time, what will the liabilities be for any S1P modulator, you know, completing their large development programs?

And also to quite a station or you really any patient with any auto immune disease is going to be a combination approach. So for us to figure out the best way to abstain combination regimens over time I think it's also important as we develop our therapy, that's a individual therapies.

Got it thanks for the insights and taking my questions.

[noise]. Your next question comes from the line of Patrick Chao. Your line is now open.

Sorry.

Good afternoon, just a few follow ups on the GBS or is your four I'm sooner weve seen a shift in recent years in terms of regulatory guidance and endpoint trial would be with the prefering through the measuring a colder healing. It's confirmed by this logic analysis on it.

Sheila Gujrati: We'd have to see that, and then how can they move up in the treatment algorithm? So, I think that'll be a question in terms of how it's positioned and how it will be used by the clinical community, and how it will be received by patients. You know, there is something around just significant lymphocyte reductions, which can be scary to clinicians, especially because they have had to deal with PML risk with Tysabri. Obviously, they've gotten a lot more comfortable with that, with Intivio, with Avetaluzumab, looking at, you know, Alpha-4, Beta-7 targeting therapies. Having said that, that's always, you know, a risk in terms of thinking about potential infection risks when you have, you know, really, you know, reduced the number of circulating peripheral lymphocytes.

Validated PURELL measures. So you know I'm sure you see enrolling I'm wondering how we should view the endpoints in our median you see particularly.

And with this mild in much more moderate patient population and do you believe the endpoints regulatory bar is still shifting or is it fairly stable as we look ahead to an eventual update in the ship you see study and then a few problems.

Yes, great question.

You know for alternate Collider, it's I would say there's been of course, a lot or by the dialogue on just pop or anything but it does seem to be able then for example, crohns disease, which I think is still you know an evolving area and has additional challenges I think the importance of clinical remission, it's still very relevant.

Got it so that is looking at Lilly than Mayo score, primarily looking at again, not only signs and symptoms, primarily stool frequency macdill bleeding, but looking at the endoscopic improvement and looking in endoscopic remission to really be able to you know be counted as as that clinical emitter and so I think there's a lot of you know confidence in.

Sheila Gujrati: So, I think those things are real and will always have to be managed by clinicians and always thought about for patients. So, the question is how will that profile impair the ability to be treated and to be really used in that mild to moderate population versus a therapy that doesn't have a type of immune system effect and potential infection risk over time. So, I think those are some of the things that we think about when we think about these other therapies and how they want to, you know, want to try to move up into the earlier lines of therapy. So, that's one thing.

I'm pleased I think the higher bar is mucosal healing and it really gets to you know as our medically that live act like the saying has spoken to many of you on the phone here the tissue with issues, though would you say that a lotta gossamer and though we believe that greatly because it. It is very true that if you can.

Sheila Gujrati: And then the second thing is, you know, some of these other orals coming in. I don't really view them as so much competition; this could be great, again, complementary or synergistic combinations for us. So for us to have really powerful oral-oral combinations, I think will be great for patients. And because we have such a methodical mechanism, you know, and we think we should be able to combine safely with these other therapies, also, you know, to really focus on that we are gut targeted. So we have a very limited systemic PA. We have a lot of, you know, really focused on colonic exposure. I think that those would be very good for us to be able to, you know, mechanisms that we could potentially combine with, as Louisa was mentioning, we just started our work on the combination.

His show that clearly that histologic remission and on top of the clinical remission and really get to mucosal healing. That's just such a meaningful endpoint. So if you can show resolution of inflammation and again as we define logic or Mitch and it's very very detailed you have to have again really absence of neutrophils.

And other inflammatory cell types in multiple layers of the chronic tissue. So you've got to get to that high hurdle mucosal healing endpoint is is again I think it is definitely a higher bar and it's something that we'll we'll be measuring very closely it's where we show. It's all really the best data coming out of our phase one b.

And so we're going to measure that in our phase two trial, but I do think the approvable endpoint of the clinical remission is I feel very solid and so I don't think that's going to shift a.

Sheila Gujrati: And again, oral combination approaches for patients is critical. You know, no one therapy is going to cure an ulcerative colitis patient or really any patient with any autoimmune disease. It's going to be a combination approach. So for us to figure out the best way to have safe combination regimens over time, I think it is also important as we develop our therapies as individual therapies.

Dramatically during our development program it could be wrong, but I think having clinical remission as your primary endpoint and then looking at histologic remission as a very important secondary endpoint and then mucosal healing as well as important secondary endpoints to characterize your efficacy and getting at that the ability to have sustained long term remission.

Patrick Ralph Trucchio: Thanks for the insights and taking my questions. Your next question comes from the line of Patrick Trucchio. Your line is now open. Thanks. Good afternoon.

And we'll be very important to the regulators and will also be very answering to treating clinicians into peak.

Sheila Gujrati: Just a few follow-ups on GB004. So, you know, we've seen this shift in recent years in terms of regulatory guidance and endpoints for IBD with the preference for the measuring of mucosal healing as confirmed by histologic analysis and validated PRO measures. So, you know, with SHIFT-UC enrolling, I'm wondering how we should view the endpoints in IBD and UC, particularly with this mild and more moderate patient population, and do you believe the endpoints and regulatory bar are still shifting, or is it fairly stable as we look ahead to an eventual update in the SHIFT-UC study? And then I have a few follow-ups. Yeah, those are great questions.

Got it and then just regarding control movement for Crohns disease.

Would the plan be to wait for the outcome from shifts you see before moving ahead in crohns disease, or <unk> or what would determine if the reserve for moves are in crohns.

That's currently that the thinking.

That we have plans for it for Crohns disease, and believe a you know based on rationale the scientific rationale that it will work in Crohns disease.

Yes, I think right now you know are there are lead indications ulcerative colitis and based on the data we see there and as we get more experience, where you know, we'll we'll be moving Crohns board.

Sheila Gujrati: You know, for ulcerative colitis, I would say there has been, of course, a lot of regulatory dialogue on the proper endpoints, but it does seem to be more stable than, for example, Crohn's disease, which I think is still an evolving area and has additional challenges. I think the importance of clinical remission is still very relevant, so that is looking at really the Mayo score primarily, looking at, again, not only signs and symptoms, primarily stool frequency and rectal bleeding, but looking at endoscopic improvement and looking at endoscopic remission to really be able to be counted as that clinical remitter. And so I think there's a lot of, you know, confidence in that endpoint.

That's helpful. Thank you very much.

Thanks, Patrick.

[noise] once again in order to ask a question. Please press star one on your telephone.

[noise] there are no further questions at this time, Sir you may continue.

Thank you so much particular time and asking US all these great questions around our portfolio. So pleased to be able to speak to you all and looking forward to hopefully seeing you at the Webinars in December and I'm more discussions become so thank you again bye.

Sheila Gujrati: I think the higher bar is mucosal healing, and it really gets to, you know, as our medical leader at Levac likes to say, and I've spoken to many of you on the phone here, the tissue is the issue. So we do say that a lot at Gossamer, and we believe that greatly because it is very true that if you can show that histologic remission on top of the clinical remission and really get to mucosal healing, that's such a meaningful endpoint. So if you can show resolution of inflammation, and again, as we define histologic remission, it's very, very detailed. You have to have, again, a really absence of neutrophils and other inflammatory cell types in multiple layers of the colonic tissue.

Ladies and gentlemen that does conclude today's conference call. Thank you for participating you may now.

<unk>.

[music].

Sheila Gujrati: And so to be able to get to that high hurdle mucosal healing endpoint is, again, I think is, you know, definitely a higher bar. And it's something that we'll be measuring very closely. It's where we saw really the best data coming out of our Phase 1B trial, and so we're going to measure that in our Phase 2 trial. But I do think the provable endpoint of clinical remission is, I feel, very solid. And so I don't think that's going to shift dramatically during our development program. I could be wrong,

[noise] Oh.

[music].

Sheila Gujrati: But I think having clinical remission as your primary endpoint, and then looking at histologic remission as a very important secondary endpoint, and then mucosal healing as an important secondary endpoint to characterize your efficacy and getting at that ability to have sustained long-term remission will be very important to the regulators. It will also be very important to treating clinicians and to patients. Got it. And then just regarding potential movement to Crohn's disease, would the plan be to wait for the outcome from shift UC before moving ahead with Crohn's disease? Or what would determine if 004 moves ahead in Crohn's? That's currently the thinking that we have plans for Crohn's disease and believe, you know, based on rationale, the scientific rationale, that it will work in Crohn's disease. Yeah, but I think right now, you know, our lead indication is ulcerative colitis, and based on the data we see there and as we get more experience, we'll be moving Crohn's forward.

Sheila Gujrati: That's helpful. Thank you very much. Thanks, Patrick. Once again, in order to ask a question, please press star 1 on your telephone. There are no further questions at this time, sir; you may continue. Thank you so much for taking the time and asking us all these great questions about our portfolio. I am so pleased to speak to you all today and looking forward to hopefully seeing you at the webinar in December and for more discussions to come. And with that, ladies and gentlemen, that does conclude today's conference call. Thank you for participating.