Q3 2023 Arcus Biosciences Inc Earnings Call
Okay.
Thank you and welcome to the cool.
Speaker 1: Thank you and welcome to the call. Following prepared remarks from the company, we will open the call for questions. To ask a question, please press star 1 on your telephone keypad. To withdraw your question, press star 2. This call is being recorded and will be available on the investors section of the ARCUS website. I will now turn the meeting over to Pierre Yves, Head of Investor Relations and Strategy.
Following prepared remarks from the company, we will open the call for questions to ask a question. Please press star one on your telephone keypad to withdraw your question Press Star two.
This call is being recorded and will be available on the investors section of the ARCUS websites.
I will now turn the meeting over to Peter <unk> head of Investor Relations and strategy.
Hello, everyone and thank you for joining us on today's conference call to discuss <unk> third quarter 2023 financial results and pipeline updates, including todays presentation of data from our edge gastric trial at the Astro monthly Finery today, you will hear from Terry Rosen, Chief Executive Officer Dmitry.
Speaker 2: Hello everyone and thank you for joining us on today's conference call to discuss ARGUS's third quarter 2023 financial results and pipeline updates, including today's presentation of data from our EDGE-GAS for trial at the ASCO Monthly Fund area. Today, you will hear from Terry Rosen, Chief Executive Officer, Dimitri Nowton, Chief Medical Officer, Jennifer Jarrett, Chief Operating Officer, and Bob Gelt, Chief Financial Officer.
Chief Medical Officer, Jennifer Garrett, Chief operating Officer, and Bob <unk>, Chief Financial Officer for Q&A. We will also be joined by Ron Hi, Ed.
Speaker 2: for Q&A. We will also be joined by Juan Hayen, President and Head of Research.
Evident and head of research.
Speaker 2: I'd like to remind you that on this call, management will be making forward-looking statements, including statements about our cash runway, our investigational products, our expected clinical development milestones and timelines, and the potential market opportunity and drug-treatable population of any indications being pursued by our...
I'd like to remind you that on this call management will be making forward looking statements, including statements about our cash runway, our investigational products or expected clinical development milestones and timelines and the potential market opportunity and drug treatable population of any indications being pursued by our program.
Speaker 2: All statements, other than historical facts, involve risks and uncertainties that may cause our actual results to differ. Those risks and uncertainties are described in our most recent quarterly report on Form 10Q that has been filed with the SEC. We strongly encourage you to check out our website for more information on the
Statements other than historical facts involve risks and uncertainties that may cause our actual results to differ those risks and uncertainties are described in our most recent quarterly report on Form 10-Q that has been filed with the SEC. We strongly encourage you to review the filings for todays call. Please refer to our latest corporate deck, which can be found on the investor.
Speaker 2: For today's call, please refer to our latest corporate deck, which can be found on the investors section of our website. With that, I'll turn the call over to Terry.
Section of our website with that I'll turn the call over to Terry.
Speaker 3: Thank you very much, Pion. Thank you all for those who are on the line. This is the first quarterly earnings call we've had in some time. So, in addition to the DOMP to NILMAP data that was just presented at the plenary, we're also going to discuss our other upcoming data readout.
Thank you very much Pierre and thank you all for those who are on <unk>.
Hi.
This is the first quarterly earnings call we've had in some time.
In addition to the <unk> data that was just presented at <unk>. We're also going to discuss our other upcoming data readouts, specifically for <unk> 85 to one our potentially best in class hits, two alpha inhibitor equipment crews that are first in class small molecule CD 73 inhibitor, both of which will be sharing.
Speaker 3: specifically for AB521, our potentially best in class HIF2 alpha inhibitor, and quemin-clustat, our first in class small molecule CD73 inhibitor, both of which we'll be sharing data with you just in the next few months.
Data with you just in the next few months.
Speaker 3: So just a few hours ago, many of you likely watched Dr. Jan Giggion present initial data from our phase two study, Edge Gastric, from Domvanilumab and first-line metastatic upper GI adenocarcinoma.
Just a few hours ago, many of you likely watch Dr. Jamey Ian.
Initial data from our phase II study.
Predominant nuomi.
First line metastatic upper Gi Carcinomas.
Speaker 3: As a reminder, Dom is the only FC silent anti-tiget antibody in late-stage development. And we and our partner Gilead are pursuing a very broad development program that includes four phase three studies in non-small cell lung and upper GI cancer.
As a reminder is the only FC silent anti <unk> antibody and <unk>.
Late stage development, and we and our partner Gilead pursuing a very broad development program.
Four phase III studies in non small cell lung and upper Gi cancers.
Speaker 3: Today's data are extremely encouraging on all fronts. ORR for the PD-L1 high population clearly exceeded historical benchmarks in this setting.
Today's data are extremely encouraging on all fronts.
For the PD Lone high population clearly exceeded historical benchmarks in this setting.
Speaker 3: Ada in the overall patient population appears differentiated, particularly relative to the most contemporary phase three studies in this patient population. Ork's Keynote 859 and Dave Jean's Rationale 305. Most importantly, six months landmark PFS data for both the PD-L1 high and overall patient population appear to be quite differentiated from the benchmark.
Data in the overall patient population appears differentiated particularly relative to the most contemporary phase III studies in this patient population keynote 859, and <unk> genes rationale 305.
Most importantly, six month landmark PFS data for both the PD Lone high and overall patient population appear to be quite differentiated from benchmarks.
Speaker 3: These data are very supportive of our ongoing phase three study, STAR221, which is evaluating DOM in the same combination, same setting underlying today's data set.
These data are very supportive of our ongoing phase III study start $2 21, which is evaluating them in the <unk>.
Same combination same setting underlying todays dataset.
Speaker 3: STAR 221 is enrolling extraordinarily well. We expect that today's data will further enhance interest and actually accelerate recruitment in the study.
There are $2 21 is enrolling extraordinarily well and we expect that today's data will further enhanced interest and actually accelerate recruitment in this study.
Speaker 3: In addition to DOM, we continue to execute on the remainder of our pipeline, including our HIF-2 alpha and adenosine pathway program.
In addition to them, we continue to execute on the remainder of our pipeline, including our shift to alpha and adenosine pathway programs regarding.
Speaker 3: Regarding our hip 2 alpha inhibitor, AB 521, early next year we will be sharing detailed safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy data from the dose escalation portion of ARC20, which is a phase 1, 1B trial for AB 521.
Regarding our hip dwell for inhibitor 85 to one early next year, we will be sharing detailed safety.
Pharmacokinetics, pharmacodynamics and preliminary efficacy data from the dose escalation portion of our 'twenty, which is a phase <unk> trial for <unk> five to one.
Speaker 3: We're close to completing enrollment, in fact, of the dose expansion cohort that's evaluating 100 mg daily of AB521, the dose that we believe will hit the target substantially harder than the approved 120 mg dose of Merx Belzutifen.
We're close to completing enrollment in fact of the dose expansion cohort. That's evaluating 100 milligram daily of 85 to one the dose that we believe we'll hit the target substantially harder and the approved 120 milligram dose of <unk>.
Speaker 3: Most recent data sets for Belzudipan presented at ESMO continue to enhance our conviction around the opportunity for AB 521. Those data were just what we've been expecting for months, if not the past year.
<unk> most recent datasets for <unk> defense presented at ESMO continue to enhance our conviction around the opportunity for <unk> hundred one those data were just what we've been expecting for months if not the past year.
Speaker 3: Later in this call, we'll describe this program in much more detail.
Later in this call we will describe this program in much more detail.
Speaker 3: With respect to our adenosine programs, we'll discuss our ARC-8 trial evaluating our CE73 inhibitor, QEMLI. This is in combination with gemcitabine and apaquetaxel with or without our anti-PD-1 zimborella map in first-line pancreatic cancer.
With respect to our Denison programs, who will discuss our arcade trial evaluating our <unk> 73 inhibitor equivalent. This is in combination with Gemcitabine and Nab paclitaxel with or without our anti PD, one zimbra roadmap in first line pancreatic cancer.
Speaker 3: As you may recall, ARC-8 completed enrollment way back in November of 2021.
As you May recall <unk> completed enrollment way back in November of 2021.
Speaker 3: So the median follow-up with the most recent data cutoff exceeded 21 months.
So the median follow up the most recent data cutoff exceeded 21 months and we just now achieve the sufficient number of events for a mature median.
Speaker 3: and we just now achieved a sufficient number of events for mature, median, old estimates. These data show clear differentiation from contemporary benchmarks for gemabraxane in this setting, one with huge medical needs.
S estimate.
These data show a clear differentiation from contemporary benchmarks for Jimmy <unk> in this setting one of them was huge medical need.
Speaker 3: Furthermore, we've generated a rigorous synthetic control dataset for gemabraxane, which also shows very meaningful differentiation from our combinations here.
Furthermore, we've generated a rigorous synthetic control data set for <unk>, which also shows very meaningful differentiation from our combination therapy.
Speaker 3: We also continue to work tirelessly to advance new molecules into the clinic. We just initiated our phase one study for AB801, our highly selective adclone inhibitor, and we expect a selective development candidate with potential best in class properties for our KIT program for allergic diseases by year end. So I'll now turn the call over to Dimitri to describe in more detail the edge gastric data that were presented earlier today.
We also continue to work tirelessly to advance new molecules into the clinic.
<unk> initiated our phase one study for <unk> hundred one our highly selective exelon inhibitor and we expect to select the development candidate with potential best in class properties for a Kid program.
By year end.
So I'll now turn the call over to Dmitry to describe in more detail yet gastric data that were presented earlier today.
Speaker 4: Thank you, Terry. I'll start by directing our audience to slide nine of our updated corporate deck. The data presented today are from cohort A1 from our phase two ad gastric platform study, which is evaluating DOM-based combinations in both the first and second line setting. The A1 cohort is evaluating DOM plus SIM plus fall-fox chemotherapy in first-line gastric gastroesophageal junction and dysophageal ethanol carcinoma.
Thank you Terry.
By directing our audience to slide nine of our updated corporate deck. The data presented today are from cohort one from our phase two gastric platform study, which is evaluating <unk> based combinations in both the first and second line setting the Avon cohort is evaluating <unk> plus <unk> plus chemotherapy.
In first line gastric and gastroesophageal junction and esophageal adenocarcinoma.
Speaker 4: Staring mentioned earlier, this is the same setting we are evaluating in our phase tree.
Terry mentioned earlier this is the same setting and setting we are evaluating.
In our phase III study start two to one.
Speaker 4: This cohort was specifically designed to generate safety and efficacy data to support regulatory requirements for the initiation of STAR-221 in certain countries outside of the U.S.
This call. It was specifically designed to generate safety and efficacy data to support regulatory requirements for the initiation of start to two one in certain countries outside of the U S.
Turning to slide 11, we describe the baseline characteristics of this cohort 41 patients were enrolled in <unk> patients are included in the efficacy analysis.
Speaker 4: Turning to slide 11, we described the baseline characteristics of this cohort. 41 patients were enrolled and all patients are included in the efficacy analysis.
Speaker 4: The cohort enrolled a relatively diverse patient population from 20 different sites in the US, France, and South Korea. To love an even distribution of patients including ASIA versus the rest of the world, and 63% of patients had gastric cancer, 24 had junction tumors, and 12% is opagial, evidence.
Cohort enrolled a relatively diverse patient population from 20 different sites in the U S, France, and South Korea to US an even distribution of patients included in Asia versus the rest of the world and 63% of patients had gastric cancer 24 had junction tumors and 12% yourself with adenocarcinoma.
Speaker 4: PD-L1 status was evaluated using the TEP scoring methods with 24 patients having TEP less than five and 15 patients or 37% with a TEP greater than or equal.
PD Lone status was evaluated using the <unk>, scoring method with 24 patients having to have less than five and 15 patients or 37% with a greater than or equal to five two of the 41 patients included in the overall population did not have tumor samples attainable for PD lone testing.
Speaker 4: Two of the 41 patients included in the overall population did not have tumor samples available for PD-L1.
Speaker 4: Note that the CPS and TEP are two methods for PD-L1 assessment, and both are used in guest...
Note that the Cps and <unk> are two methods for PD Lone assessment and both are used in gastric cancer.
Speaker 4: We'll show you later in on this call some of these methods, sorry, that these methods have been high concordance. BMS and Merck have historically used CPS for their phase three studies of anti-PD-1 plus chemotherapy while Bay Gene is using TEP, including in the phase three gastric cancer trial, ------------------------------ height of candidates Techniquescrime
<unk> later on this call some of these methods sorry.
These measures have been high concordance.
Merck has historically used cps for that phase III studies of anti PD, one plus chemotherapy, while Beijing is using <unk>.
Including in the phase III gastric cancer trial rationale.
Speaker 4: Following slide is cracked the overall response rates of the data cut off of September 4, 2022.
The following slide describes the overall response rates of the data cutoff of September four 2023, and the tip high population, we observed sculpsure for a 73% confirmed overall response rate and an 80% best overall response rate. These results exceed historical phase III benchmarks for anti PD.
Speaker 4: In the depth high population, we observe a 73% confirmed overall response rate and an 80% vote kick LOL.
Speaker 4: these results exceed historical phase three benchmarks for anti-PD-1 and chemotherapy. For example, in checkmate 649 and keynote 859, the overall response rate was 60 or 61% for anti-PD-1 plus chemotherapy in the CPS high harms of the study. And in rationale 305, Beijing studying gastric cancer, which is the most contemporary phase three data set in the setting, there's a 50% overall response rate in the TAP-high
One in chemotherapy for example, the checkmate 609 in keynote <unk> 859. The overall response rate was $60 or 61% for anti PD, one plus chemotherapy in the Cps Hi arms of the study and innovation L 305, Beijing study in gastric cancer, which is the most contemporary phase III data set into <unk>.
Setting.
50% overall response rate and the <unk> high population.
Speaker 4: The overall population in S gastric, the confirmed overall response rate was 59%, which is very encouraging, particular given that approximately 60% of our patients are kept low, which is higher than the 40% PBL1 low patients in checkmate 649.
For the overall population and as gastric to confirmed overall response rate was 59%, which is very encouraging, particularly given that approximately 60% of our patients are low which is higher than the 40% PD lone low patients and checkmate 649.
Speaker 4: The overall response rate in Merck's keynote 859 trial was 51.
The overall response rate in Merck's keynote 859 trial was 51%.
Speaker 4: But also note that we have seen two confirmed complete responses so far. The median duration of response has not been reached.
And also.
Note that we have seen two confirmed complete responses. So far the median duration of response has not been reached and given the time it takes to get to a complete response and the fact that many of our patients are still on treatment. The CR rate might go up over time.
Speaker 4: Given the time it takes to get to a complete response and the fact that many of our patients are still in treatment, the CR rate might go up over.
Speaker 4: We believe that the overall response rate results seen in F-Castre demonstrate the additive benefit that an anti-digit agent can provide above and beyond PD-1 and chemotherapy and opera GI.
We believe that the overall response rate was sold senior at Castlereagh demonstrate the additive benefit as an anti digit agent can provide above and beyond PD. One in chemotherapy PD, one excuse me and chemotherapy and opera Gi cancers on slide 13, we showed a waterfall plot and as you can see the vast majority of patients.
Speaker 4: In slide 13, we show the waterfall plot, and as you can see, the vast majority of patients experiences tumor volume reduction. Well, there is a difference in the overall response rates between the top high and low tumors you can see in the chart that we have observed very deep responses in both patients with high and low...
<unk> tumor volume reduction well there is a difference in the overall response rates between the tip high and low tumors you can see into chart that we have observed very deep responses in both patients with high and low expression.
Speaker 4: You can also see that in addition to the two complete responders, there are other patients with very significant tumor volume reductions that could convert to CROs over the next few
You can also seeded in addition to the two complete responders in our auto patients with very significant tumor volume reductions that could confer to crs overtime.
Speaker 4: The next slide shows the time on treatment by patient. You can see here that there are six patients, both with PD-L1 high and low status, who continue to have stable disease and remain on treatment.
The next slide shows the time on treatment by patient you can see here that there are six patients both with PD Lone high and low status will continue to have stable disease and remain on treatment.
Speaker 4: In slide 15, we show the overall response rate table again, but here we show the data using both the TEP and the CPS method. And as you can see, there is strong concordance between these two methods.
On slide 15, we show the overall response rate table again, but here we show the data using both to tip and the Cps method and as you can see there is strong concordance between these two methods.
Speaker 4: The next slide, slide 16, shows the Keppner-Mai occurs for progression free survival. Here we call out the Levmark 6-month BFS, which is mature in a trial with a minimum follow-up of 6 months for whole-p...
The next slide Slide 16 shows the Kaplan Meier curve for progression free survival.
We call out the landmark six months PFS, which is mature in a trial with a minimum follow up of six months for all patients. These data are extremely promising for both the high and low patient population, specifically, we observed a 77% in the overall population and a very impressive 93% in the tap HIFU.
Speaker 4: These data are extremely promising for both the high end of low patient population.
Speaker 4: Specifically, we observe a 77% in the overall population and a very impressive 93% in the doorstep high population for 6 months.
Appalachian for six month landmark PFS.
Speaker 4: Well, we recognize that these are small numbers. These six month PFS numbers compare very favorable to the benchmark phase three studies, which have been in the 50% to 60%.
We recognize that these are small numbers at the six month six month PFS numbers compare very favorable to the benchmark phase III studies, which have been into 50% to 60% range. You can see here in the curve that we have not reached the median PFS for either the tip higher overall population with a median follow up of eight.
One months given that the historical benchmarks have shown in PFS in the range of seven to seven five months. We believe these data put us on track to execute those benchmarks and importantly, a substantial number of specifically 24 out of 41 patients enrolled in our study continue to be on treatment at time of the day.
Speaker 4: Given that the historical benchmarks have shown a PFS in the range of seven to seven and a half months, we believe these data pull us on track to it.
Speaker 4: And importantly, a substantial number, specifically 24 out of 41 patients enrolled in our study, continue to be on treatment at time of the day that caught us.
<unk> cut off.
Speaker 4: Lastly, I will cover the safety and probability profile. We've seen so far in Hatskastrik. The most common treatment emergent at first offense, which are shown on slide 17, we're Nuntropinia, Norsia, and Anemia, which is very consistent with what we would expect from chemotherapy alone. In fact, the vast majority of grain free or higher truck related treatment emergent efforts events were contributed to chemotherapy, and only 12% were contributed to dormant.
Lastly, I will cover the safety and Tolerability profile, we've seen so far and hence gastric.
Common treatment emergent adverse events, which are shown on slide 17, with neutropenia, nausea, and anemia, which is very consistent with what we would expect from chemotherapy alone. In fact, the vast majority of grade III or higher truck related treatment emergent adverse events were contributed to chemotherapy and only.
12% of our contributed to Dol more soon.
Speaker 4: No serious treatment emergence at FERSIFENDS were related to dolma.
No serious treatment emergent adverse events were related to <unk>.
Speaker 4: Of note, all infusion bladder reactions shown on slide 18 were deemed related to oxali.
Of note all infusion related reactions shown on slide 18 were deemed related to assembly platen overall.
Speaker 4: Overall the regiment was well tolerated with a similar AE profile to that expected from 4VOS Plus anti-pd
Overall regimen was well tolerated with a similar AE profile to that expected from full Fox plus anti PD one.
Speaker 4: These results add to the growing body of evidence supporting a potentially differentiated safety and tolerability profile for a dome relative to FC-enabled anti-digit...
These results add to the growing body of evidence supporting a potentially differentiated safety and tolerability profile for <unk> relative to <unk> enabled anti <unk> antibodies before I turn it over to Jim I wanted to spend a minute on some key elements of the design of our phase III study start two to one which is shown on slide number 20.
Speaker 4: Before I turn it over to Jen, I wanted to spend a minute on some key elements of the design of our phase three study, STAR221, which is shown on slide...
Speaker 4: first we are stratifying by temperature and 5 or less than 5 percent so this is well balanced between the two treatment arms. We are also closely monitoring the
First we are certifying by temp graded five or less than 5%. So this is well balanced between the two treatment arms. We are also closely monitoring the percentage of patients.
Speaker 4: who have tumors with a TEP score of more than 5% to ensure that the percentage of these patients in our study meets the pre-specified percentage per our statistical network.
Who have tumors with a <unk> score of more than 5% to ensure that the percentage of these patients in our study meets the pre specified percentage per our statistical analysis plan.
Speaker 4: Second, the study has dual primary endpoints of overall survival, one for the TEP more than 5%, and the other one for the ITT population. So we have two opportunities to win.
Second the study has dual primary endpoints of overall survival, one, Florida more than 5% and the other one for the ITT population. So we have two opportunities to win in this study.
Speaker 4: With that, I'll turn it over to Jen to talk about the market opportunity.
With that I'll turn it over to Jim to talk about the market opportunity for ticket.
Speaker 5: Thanks, Dimitri. I'd like to start by talking about the TIGET field overall. Our most recent feedback from KOL indicates a clear and growing data-driven enthusiasm for anti-TIGET is an innovative area.
Thanks, Dmitry I'd like to start by talking about potential <unk>.
Recent feedback from Kols and it takes a clear and growing data driven enthusiasm for anti <unk> is an innovative therapy. Following the release of data from the second interim analysis <unk> Lange, we engaged a third party to conduct a survey of 730 oncology kols regarding our sentiment.
Speaker 5: Following the release of data from the second interim analysis of Rocha Skyscraper 1, we engaged a third party to conduct a survey of seven to thirty oncology KOLs regarding their sentiment on the anti-tidgits. You can see these results on slide 35, bar and tester decks.
You can see these results on slide 35 for our Investor day, approximately 80% of respondents believe it is likely that Toronto classic heads out Russia anti PD, one combination will receive FDA approval. Additionally, based on data they've seen to date, 83% expect anti ticket to play a moderate.
Speaker 5: Approximately 80% of respondents believe it is likely that TORRGOS, Plessotezzo, Roche's anti-tiget and PDO1 combination will receive FDA approval. Additionally, based on data they've seen to date, 83% expect anti-tiget to play a moderate or larger role in the treatment of first-bind PDO1 high, not small cell phones.
Our larger role in the treatment of first line PD Lone high non small cell lung cancer.
Speaker 5: These survey results are telling. As the evidence on anti-tidgid accumulates, physicians are increasingly convinced of the potential for this mechanism to change the treatment paradigm in lunch.
These survey results on time.
Evidence on anti Angiogenic accumulate.
<unk> are increasingly convinced of the potential for this mechanism to change the treatment paradigm and lung cancer. Since we are combining them with the current standard of care chemo plus anti PD, one and adding almost no toxicity. This is a very easy value proposition for physicians today's results continue to demonstrate the potential for anti tamper.
Speaker 5: Since we are combining DOM with the current center of care, PMO plus the anti-PD1, and adding almost no toxicity, this is a very easy value problem.
Speaker 5: Today's results continue to demonstrate the potential for anti-TIGIT to improve outcomes and indications where anti-PD-1 is successful. As Terry mentioned, gastric, GE junction, and esophageal adenocarcinomas represent a $3 billion plus market opportunity.
Outcomes and indications where anti PD. One is successful as Terry mentioned gastric T junction and esophageal identic carcinoma represent a $3 billion plus market opportunity with approximately 25000 patients in the U S alone.
Speaker 5: with approximately 25,000 patients in the US alone in over 100,000 patients across the Q7.
100000 patients across 37 countries.
Speaker 5: Note that we are pursuing adenocarcinomas, a different histology than that which is being pursued by Roche and Beijin in their respective phase 3.
Note that we are pursuing identic carcinoma at different histology than that which is being pursued by Roche in Beijing and their respective phase III studies in fact, we in Gilead had the only anti Tianjin in phase three development for first line <unk> carcinoma, which is one of the fastest growing cancer types in the U S and western Europe.
Speaker 5: In fact, we in Gilead have the only anti-tidgid and phase three development for first-line upper GI adenocarcinomas, which is one of the fastest growing cancer types in the US.
Speaker 5: Many of you are aware that there is another class of agents being developed in gastric cancer, directed against clot in 18.2, which were also discussed in today's plenary.
Many of you are aware, but there is another class of agents think about in gastric cancer directed against cloud and $18. Two which are also discussed in today's plenary session. While the efficacy data are encouraging encouraging published literature estimate that only anywhere from 20% to 40% of patients are highest pressures are cloud and $18 two.
Speaker 5: While the efficacy data are encouraging, encouraging published literature estimates that only anywhere from 20 to 40% of patients are high expressors of cloud 18.2. And these molecules are associated with significant GI tuck.
These molecules are associated with significant Gi toxicity. We also expect it will take several years for cloud and 18 point, you're testing can be successfully rolled out with anti tis yet we believe we have the potential to achieve similar efficacy without the toxicity associated with anti <unk> and potentially avoid the need for any testing, allowing patients to go directly.
Speaker 5: We also expect it will take several years for quad and 18.2 testing to be successfully rolled out. With anti-tidget, we believe we have the potential to achieve similar efforts...
Speaker 5: without the toxicity associated with the anti-clotins and potentially avoid the need for any testing, allowing patients to go direct.
Sure.
Speaker 5: Today's dataset will support both study recruitment and regulatory filings for a combination, and we are moving aggressively to secure our position as first to market and best in class in the...
Today's dataset will support the steady recruitment and regular regulatory filings for a combination and we are moving aggressively to secure our position as first to market and best in class in this indication I'll now turn it back to Terry to discuss our hit to Alpha and Sydney 73 program. Thanks, very much Jim So first let me start.
Speaker 5: I'll now turn it back to Terry to discuss our H2 alpha in CD73.
Speaker 3: Thanks very much, Jim. So first, let me start by level setting a bit on hip to alpha.
Level setting a bit unhip two alpha.
Speaker 3: It's a transcription factor, it has no light and binding domain, and as a result, it's proven very difficult to create molecules that are high quality inhibitors, but also that have ideal drug properties against the target. That's why there are very few other HIF-2 alpha blockers in clinical development today.
It's a transcription factor has no ligand binding domain.
The result is proving very difficult to create molecules that are high quality inhibitors, but also that have ideal drug properties target. That's why there are very few other two alpha blockers in clinical development today.
Speaker 3: Belzudipan is the first and only HIP2 alpha inhibitor to be approved today. And it's only approved for BHL associated cancers, although Merck recently filed for Belzudipan's first approval in clear cell RCC.
<unk>, the first and only hit through Alpha inhibitor to be approved today and it's only improved for bho associated cancers, Although Merck recently filed for both <unk> first approval in clear cell RCC.
Speaker 3: Slide 47 of our corporate deck describes the value proposition for AB521. It's really pretty simple. The primary limitation of Bell's uniform is substantial. It's oral absorption saturates. It's dose of 120 milligrams. So what does that mean?
Slide 47 of our corporate deck describes the value proposition for 85 to one.
Really pretty simple the primary limitation of builds unifem is substantial.
Oral absorption saturates at a dose of 120 milligrams, so what does that mean.
Speaker 3: Even when higher doses of Belzutiphan are administered, systemic drug exposure does not meaningfully increase. In fact, it's very clear from the published data for Belzutiphan that the approved dose of 120 milligrams was chosen because doses beyond 120 milligrams did not result in meaningfully higher plasma levels. It said nothing to do with dose limiting target.
Even with higher doses of <unk> administered systemic drug exposure does not meaningfully increase.
In fact, it's very clear from the published data for both Unifem that the approved dose of 120 milligrams was chosen because doses beyond 120 milligrams did not result in meaningfully higher plasma levels.
Nothing to do with dose limiting toxicity.
Speaker 3: Merck in fact just released results for light spark 13 at Esmo, which evaluated doses of 120 milligrams versus 200 milligrams of Bell's on????iversaries in the?? average of 70??ato.
Merck in fact, just release results for light spark 13 at ESMO, which evaluated doses of 120 milligram versus 200 milligrams of <unk>.
Speaker 3: No surprises. They concluded that there was no difference in RR between these two doses than that the results support their dose selection of 120 milligrams for their trial.
No surprises they concluded that there was no difference in or are between these two doses from the results support the dose selection of 120 milligrams for their trials. However.
Speaker 3: However, it's super important to know that they made no mention of whether they were achieving higher levels of drug exposure with the 200 milligram dose, and they did not share any PK or PD data for this study.
Super important to note, but they made no mention of whether they were achieving higher levels of drug exposure with the 200 milligram dose.
Not sure any PK or PD data for this study.
Speaker 3: So consistent with the previous literature, we just view this as more evidence of Bell's utipans PK and PV limitations in the ability and ability in fact to achieve meaningfully greater plasma concentrations with doses that are above 120 milligrams. Our fundamental thesis going into this program.
Consistent with previous literature, we just view this as more evidence builds <unk> PK and PD limitations and the ability inability in fact to achieve meaningfully greater plasma concentrations with doses that are above 120 milligrams, our fundamental thesis going into this program.
Speaker 3: The primary objective of our HIF2-alpha program then was to create a molecule without this pharmacokinetic liability enabling us to hit the target harder.
The primary objective of our half two Alpha program, then was to create a molecule without this pharmacokinetic liability, enabling us to hit the target hurdle.
Speaker 3: In a Phase 1B study in second line clear cell RCC, belzudifan demonstrated an ORR of about 25%, and approximately half of these responses were not achieved until six months or more of treatment.
The phase <unk> study in second line clear cell RCC, those unifem demonstrated in or about 25% approximately half of these responses were not achieved until six months or more of treatment.
Speaker 3: These ORR data were essentially recapitulated in the Phase III Light Spark O5 study, which showed a 22% ORR for Bell's Zootivan versus 3.5% for ever-alignments in a 5.6-month medium-PFS.
Our our data where essentially recapitulated in the phase III <unk> study, which showed a 22% or for bill <unk> versus three 5% forever.
Ever alignments and a five six month median PFS.
Speaker 3: While these results are actually quite encouraging, we believe they show clearly room for improvement. And with AB521, we could observe a higher response rate, deeper responses, or faster response kinetics, all of which should translate into longer PFS.
While these results are actually quite encouraging we believe they show clearly room for improvement and with 85 to one recruit observe a higher response rate deeper responses for faster response kinetics, all of which should translate into longer PFS.
Speaker 3: In our Healthy Volunteer Study, we demonstrated that AB521 has an ideal profile, including dose proportional pharmacokinetics. That's important. Dose proportional pharmacokinetics is the huge differentiator.
And our healthy volunteer study, we demonstrated that <unk> five to one as an ideal profile, including dose proportional pharmacokinetics. That's important dose proportional pharmacokinetics is the huge differentiator here in our dose escalation study in patients we replicated the pharmacokinetics that we observe.
Speaker 3: In our dose escalation study in patients, we replicated the pharmacokinetics that we observed in healthy volunteers and now have dosed up to a daily dose of 100 milligrams, which we believe has the potential to achieve at least three times higher levels of AB521 than those equivalent to the approved dose of Belzutafan. Importantly, and this is a key finding, we have not seen any dose-limiting toxicity.
Served in healthy volunteers and now have dosed up to a daily dose of 100 milligrams, which we believe has the potential to achieve at least three times higher levels of 85 to one when those equivalent to the approved dose of Bill Sudafed.
Importantly, and this is this is Keith.
Finding we have not seen any dose limiting toxicities. So based on these data we have initiated our 30 patient expansion cohort at a dose of 100 milligrams daily in clear cell RCC patients.
Speaker 3: So based on these data, we've initiated our 30 patient expansion cohort in a dose of 100 milligrams daily in clear cell RCC patients.
Speaker 3: There's been a great deal of investigator enthusiasm around the study. In fact, the cohort is almost fully enrolled.
Great deal of investigator enthusiasm around this study and in fact, the cohort is almost fully enrolled.
Speaker 3: Early next year, we're very excited to have the opportunity to present PK pharmacodynamic safety data as well as the initial efficacy data from the 12 patients in the dose escalation portion of the study.
Early next year, we're very excited to have the opportunity to present PK Pharmacodynamic safety data as well as the initial efficacy data from the 12 patients in dose escalation portion of the study.
Speaker 3: approximately half of these patients have RCC in all were treated at a dose of 50 milligrams or 100 milligrams daily So both of these doses are pharmacologically relevant
Approximately half of these patients have RCC and all were introduced at a dose of 50 milligrams or 100 milligrams daily. So both of these doses are pharmacologically relevant.
Speaker 3: The safety data support our view that the enhanced target coverage by AB 521, relative to that obtained by Belzudiband, does not result in increased safety liability.
Safety data support our view that the enhanced target coverage by <unk>, 5% to one relative to that obtained by Bill's Nurofen does not result in increased safety liability.
Speaker 3: We also expect to present data from the expansion cohort next year.
We also expect to present data from the expansion cohort next year.
Speaker 3: We're progressing the molecule rapidly and expect to start a phase II TKI combination study in second line clear cell RCC by year end with the goal of getting a phase III study for AB521 as quickly as possible.
We're progressing the molecule rapidly and expect to start a phase <unk> combination study in second line clear cell RCC by year end with the goal of getting a phase III study for <unk> five to one as quickly as possible.
Speaker 3: So now I'm going to shift over to our gate. Really excited to talk about this study, our Phase 1-1D study that's evaluating quamilite in first-line metastatic pancreatic cancer.
So now let me shift over to our gate really excited to talk about this study our phase one <unk> study.
Adding <unk> in first line metastatic pancreatic cancer.
Speaker 3: Quemely is a highly thick selective and extraordinarily potent small molecule inhibitor of C-73.
<unk> is a highly selective and extraordinarily potent small molecule inhibitor of <unk> 73.
Speaker 3: Keep differentiator of quenle compared to the most advanced CDC 73 antibody in clinical development is that it blocks both the membrane bomb and the soluble forms of CDC 73 enabling it to achieve complete inhibition of the enzymatic activity. This is a huge...
Key differentiator quickly compared to the most advanced CD 73 antibody in clinical development.
Did it blocks, both the membrane bound and the soluble forms of CD 73, enabling us to achieve complete inhibition of the <unk>. This is a huge difference because CD 73 is readily shed from cells, resulting in significant levels of soluble <unk>.
Speaker 3: because CD73 is readily shed from cells, resulting in significant levels of soluble CD73.
73.
Speaker 3: So, in contrast, the most advanced CD73 antibody is only partially effective in inhibiting the enzymatic activity of either membrane-bound or soluble CD73. So, I think an important concept here is that although they share the same target, CD73, QMLE is highly differentiated by its mechanism of action, which as I said, enables it to fully inhibit both forms of the enzyme.
In contrast, the most advanced <unk> antibody is only partially effective at inhibiting the enzymatic activity of either membrane bound score soluble CD 73. So I think an important concept here is that although this year the same target CD 73, when we as highly.
Differentiated by its mechanism of action, which as I said enables us to fully inhibit both forms of the enzyme.
Speaker 3: We also believe that small molecules make penetrate tumors better than an antibody.
We also believe the small molecule may penetrate tumors better than an antibody tanker.
Speaker 3: Pancreatic tumors are notorious for being very fibrotic. What is fibrotic? Think about it like scar-like tissue. This makes it hard for drugs to infiltrate the tumor, and therefore a small molecule approach may be particularly advantageous in the setting.
Pancreatic tumors are notorious for being very fibrotic oils fibrotic makes us think about like skylake tissue. This makes it hard for drugs to infiltrate the tumor and therefore, a small molecule approach may be particularly had been patients in this setting.
Speaker 3: We chose pancreatic cancer as the first indication for QEMLI because its tumor type is associated with extremely high CD73 levels and in fact high CD73 expression has been shown to result in poor overall survival outcomes in patients.
We chose pancreatic cancer as the first indication frequently because this tumor type is associated with extremely high CD 73 levels and in fact, ICD 73 expression has been shown to result in poor overall survival outcomes in patients.
Speaker 3: Slide 42 highlights the design of our case. We enrolled approximately 30 patients evaluating 100 milligrams of QEMLI plus ZIM plus gemabraxane in the dose escalation and expansion portions of the study.
Slide 42 highlights to design a market.
We enrolled approximately 30 patients evaluated 100 milligrams of <unk>, plus <unk>, plus <unk> and the dose escalation and expansion portions of the study.
Speaker 3: Subsequently, we enrolled the randomized portion of the study, and this highlights the design of our case. We enrolled approximately 30 patients evaluating 100 milligrams of QEMLI plus ZIM plus gemabraxane in the dose escalation and expansion portions of the study.
Subsequently, we enrolled the randomized portion of the study and then.
Highlights design of market we're in.
Enrolled approximately 30 patients evaluated 100 milligrams of <unk>, plus <unk>, plus <unk> and the dose escalation and expansion portions of the study.
Speaker 3: Subsequently, we enrolled the randomized portion of the study, and this evaluated injuring our measure of graphs per percent to 40% to 5% in 2020.
Sequentially, we enrolled the randomized portion of the study and this evaluated <unk> plus <unk>.