Q4 2019 Earnings Call
Operator: Sciences and thank you for joining the Alpine Immune Sciences Board Quarter and Year-End 2019 Company Update Conference Call. All participants are now in a listen-only mode.
Gentlemen, thanks for joining alpine immune sciences fourth quarter and year end 2019 company update conference call.
All participants on nano listen only mode.
Operator: Following opening remarks, Alpine's management will open the lines for a question and answer period. Please be advised, this call is being recorded at the company's request, and a webcast of this call will be archived on the company's website for approximately two weeks. I would now like to introduce Courtney Dugan, Director of Investor Relations. Please go ahead.
Opening remarks Alliance management will open the line why shouldn't now.
Please be advised this call is being recorded at the company. This question and a webcast of this call will be archived on accomplished website for approximately two weeks I would now like to introduce coordinated in Investor Relations. Please go ahead.
Courtney Dugan: Thank you, Livia, and thank you everyone for joining us on today's call. This afternoon, we issued a press release announcing our corporate update and fourth quarter and year-end 2019 financial results. We also filed our annual reports on Form 10-K. Both documents can be found on the investor section of our website at alpineimmunesciences.com. Before we begin today's discussion, I'd like to note that certain matters discussed on today's conference call or answers that may be given to questions could constitute forward-looking statements, including but not limited to statements regarding the anticipated impact and timing of the COVID-19 pandemic on our business development plans and results of operations, as well as our preclinical and clinical development plans and the timing thereof. Expectations regarding the sufficiency of cash to fund operations, the timing of our publication of future clinical data, and expectations regarding our ongoing collaborations and potential future collaborations.
Thank you Libya and thank you everyone for joining us on today's call.
This afternoon, we issued a press release announcing our corporate update in fourth quarter and year end 2019 financial results.
We also filed our annual reports on form 10-K.
Both documents can be found on the Investor section of our web site at Alpine immune Sciences Dot com.
Before we begin today's discussion I'd like to note that certain matters discussed on today's conference calls or answers that maybe get into questions could constitute as forward looking statements, including but not limited to statements regarding the anticipated impact and timing of the coded 19 pandemic on our business development plans in a result.
With operations.
Our preclinical and clinical development plan and the timing thereof.
Expectations regarding the sufficiency of cash to fund operations.
The timing of art publication of future clinical data.
And expectations regarding our ongoing collaboration for potential future collaboration.
Courtney Dugan: Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC guidelines. Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward-looking statement. With that, I now turn the call over to Alpine's Chairman and Chief Executive Officer, Dr. Mitchell Gold.
Forward looking statements are subject to numerous risks and uncertainties many of which are beyond our control, including the risks and uncertainties described from time to time and our FCC filings.
However results may differ materially from those predicted on today's call.
We undertake no obligation to publicly update any forward looking statement.
With that let me now turn the call over to Alpine Chairman and Chief Executive Officer, Dr. Mitchell bulk.
Thanks. Good morning, Good afternoon, everyone. We hope that you and your families are shaping well.
Mitchell H. Gold: Thanks, Courtney. Good afternoon, everyone.
Mitchell H. Gold: We hope that you and your families are safe and well. With me on the call today are Stanford Peng, our President and Head of Research and Development, Paul Rickey, our Chief Financial Officer, and Remy Durand, our Senior Vice President of Business Development and Corporate Strategy. We look forward to sharing with you today our fourth quarter and year-end 2019 performance, as well as our clinical development plans for both ALPN-101 and ALPN-202 and the potential impact of the current COVID-19 situation. The Alpine team has made substantial progress over the last year.
With me on the call today are Stanford paying.
Our president and head of research and development, Paul Ricky Our Chief Financial Officer in Remy Duran, our senior Vice President business development and corporate strategy.
We look forward to sharing with you today, our fourth quarter and year end 2019 performance as well as our clinical development plans for both help you in one or one.
And ill be intuitive and the potential impact of the current cobot 19 situation.
Yeah. My team has made substantial progress over the last year.
Mitchell H. Gold: Our most advanced program, ALPN 101, has successfully completed our phase one dose escalation study in healthy volunteers. ALPN 101 has exhibited favorable PK characteristics and is a highly potent molecule capable of inhibiting both T cell and humor responses in humans, as demonstrated in our pharmacodynamic assays.
Our most advanced program in one or one that's successfully completed our phase one dose escalation study in healthy volunteers.
LPN Wonder why has exhibited see real PK characteristics and is a highly potent molecule capable of having both.
T cell and tumor response in humans as demonstrated in our Pharmacodynamic assets.
Mitchell H. Gold: This is an important milestone for the company and we believe significantly enhances the developability of the program. We are planning a path forward for ALPN101 in both acute GVHD via our BALANCE study and potential other inflammatory diseases in need of a novel biologic approach. Our immuno-oncology program, ALPN-202, is a conditional CD28 agonist designed to activate a patient's own immune system to fight cancer. We are ready to enroll its first in human monotherapy trial, which we are calling NEON1. Both our BALANCE and NEON1 studies are now open for enrollment. However, as you might expect, it is difficult at this time to ascertain how rapidly enrollment may proceed based on the current COVID-19 situation. With that, I'll turn the call over to our President and Head of R&D, Stanford Peng, to provide an update on research and development.
This is an important milestone for the company and we believe significantly enhances the developed the ability of the program.
We're planning a path forward for MLP and one on one in both acute gvhd, we are balanced study to potential other inflammatory diseases in need of a novel biologic approach.
Are you immuno oncology program.
You are too is a conditional CD 28 agonist design asked me to patients own immune system to fight cancer.
We are ready to enrol, helping at your choose first in human monotherapy trial, which we are calling me on one.
Well as our balance and me on one studies are now opened for enrollment.
However, as you might expect it is difficult at this time to ascertain how rapidly enrollment may proceed based on the current coping 19 situation.
With that I'll turn the call over that president and head of R&D stand for pain to provide an update on research and development.
<unk>.
Thank you Mitch.
Over the past several months, we have indeed made several critical achievements for development programs.
Stanford Peng: Thank you, Mitch. Over the past several months, we have indeed made several critical achievements in our development program. AOPN 101 completed its first in-human study in adult healthy volunteers. The data from this study are still being finalized, but overall, ALPN 101 was well tolerated without evidence of cytokine storm or release. It exhibited well-behaved pharmacokinetics and pharmacodynamics, including on-target inhibition of immune functionality, such as antibody responses to KLH immunization. Antidrug antibodies were detected in this trial at a rate similar to other biologics and at generally low titers.
Okay and one on one completed its first in human study in adult healthy volunteers.
Data from this study are still being finalized the overall LP and one on one was well tolerated without evidence of cytokine storm or beliefs.
Exhibited well behaved pharmacokinetics and pharmacodynamics, including on target inhibition of immune functionality, such as antibody responses to kill HD meditation.
Anti drug antibodies were ticket in this trial at a rate similar to other biologics and it generally though tighter.
Based on these overall results, we anticipate therapeutic doses to be achieved with subcutaneous for intravenous dose is at two to four week intervals, which we plan to explore in one or more subsequent ethic true.
Some of these data were presented as part of an oral presentations at Ash in December 2019, and we plan to report further details after completion of final analyses later this year.
Balance or feed wouldn't be two study in acute steroid refractory Gvhd is currently open for enrollment we remain excited about this study because of the magnitude of the preclinical data supporting CLP and one on ones potential in this disease are particularly pleased to have recently been granted orphan designation by asking for this indication.
The balance study is an open label dose escalation and expansion study in patients who are refractory ore resistant the corticosteroids and will examine endpoints, including safety objective response rates and duration of responses as well as non relapse mortality in overall survival.
Stanford Peng: Based on these overall results, we anticipate therapeutic doses to be achieved with subcutaneous or intravenous doses at two to four-week intervals, which we plan to explore in one or more subsequent efficacy trials. Some of these data were presented as part of an oral presentation at ASH in December 2019, and we plan to report further details after completion of final analyses later this year. Balance, our Phase 1B2 study in acute steroid refractory GVHD is currently open for enrollment. We remain excited about this study because of the magnitude of the preclinical data supporting ALPN101's potential in this disease, and are particularly pleased to have recently been granted orphan designation by FDA for this indication. The BALANCE Study is an open-label, dose-escalation and expansion study in patients who are refractory or resistant to corticosteroids and will examine endpoints including safety, objective response rates, and duration of responses, as well as non-relapse mortality and overall survival. Importantly, dose escalation in this study begins at a dose level expected to have pharmacodynamic activity, 0.3 milligrams per kilogram
Importantly dose escalation in this study began a dose level expected to have pharmacodynamic activity 0.3 milligrams per kilogram.
At the same time, the rationale for exploring LP in one or one and other inflammatory diseases continues to expand.
Last year's American College of Rheumatology meeting, we presented preclinical disease model data supporting connective tissue diseases, like lupus and sjogren syndrome, as well as inflammatory conditions, such as rheumatoid in Psoriatic arthritis and.
Earlier this year, we presented data on inflammatory bowel disease at the Crohns and quite as Congress.
We had been scheduled to participate in a poster presentation with her collaborator Dr. Catherine pedal assistant professor of Ophthalmology at the University of Washington on preclinical data into the items at the association for research and vision and Ophthalmology annual meeting at that meeting husband temporarily postponed due to covert 19.
Nonetheless, along with our previously presented data in preclinical models at multiple sclerosis. These results suggest the potentially broad lifecycle for European one or one in multiple therapeutic areas.
Turning to LPM tool to we're pleased to have opened de on one phase one first in human open label dose escalation and expansion study and advanced malignancies.
Study will be done in patients who have failed available standard therapies, including checkpoint inhibitors went indicated.
The primary endpoint of the study involves safety, but this study will also assessed outcomes such as objective response rate. The recent responses progression free survival and overall survival.
Tissue based biomarker for patient selection based on the mechanism of action of European tool to what the explored during dose escalation and may be implemented during or before the expansion cohorts.
We recently presented some data on the biomarker assay in a poster at the United States and Canadian Academy of pathology and won't be.
Stanford Peng: At the same time, the rationale for exploring AOPN101 and other inflammatory diseases continues to expand. At last year's American College of Rheumatology meeting, we presented preclinical disease model data supporting connective tissue diseases like lupus and Sjogren's syndrome, as well as inflammatory arthritis conditions such as rheumatoid and psoriatic arthritis. And earlier this year, we presented data on inflammatory bowel disease at the Crohn's and Colitis Conference. We had been scheduled to participate in a poster presentation with our collaborator, Dr. Catherine Peppel, assistant professor of ophthalmology at the University of Washington, on Preclinical Data in Uveitis at the Association for Research in Vision and Ophthalmology Annual Meeting. But that meeting has been temporarily postponed due to COVID-19.
We therefore look forward to shortly having two active clinical programs in efficacy studies.
Looking forward to our pipeline, we have recently identified a novel PCL modulator develop the via our directed evolution platform, which would be applicable to serious inflammatory conditions, such as lupus or other b cell mediated diseases.
That's a preclinical data on this program matures, we look forward to presenting further details at an appropriate scientific forum later this year.
I will now hand, the call over to our CFO poor Vicki to discuss our financial results for the quarter.
Thank you Stanford.
At both mentioned Stanford mentioned, we anticipate advancing all LPN one on one an LP onto your too in the clinical trials throughout the current year.
With our current cash on hand, we expect to have sufficient cash to support both development plans for at least the next 12 months into early 2021.
Now turning to financial results for the fourth quarter.
Cash cash equivalents and marketable securities totaled 40.9 million. After December 31st 2019, compared to 47 million as of September three in 2019.
Stanford Peng: Nonetheless, along with our previously presented data in preclinical models of multiple sclerosis, these results suggest a potentially broad life cycle for AOPN101 in multiple therapeutic areas. Turning to ALPN202, we are pleased to have opened NEON1, a Phase 1 first-in-human open-label dose escalation and expansion study in advanced malignancy. This study will be done in patients who have failed available standard therapies, including checkpoint inhibitors we're indicating. The primary endpoints of the study involve safety, but the study will also assess outcomes such as objective response rates, duration of responses, progression-free survival, and overall survival. A tissue-based biomarker for patient selection based on the mechanism of action of AOPN-202 will be explored during dose escalation and may be implemented during or before the expansion cohort.
Net loss for the corner was 6.1 million worth 33 cents per share. This was a decrease when compared to last year's fourth quarter loss of 11.1 million or 80 cents per share.
Revenue recognized under our Adaptimmune collaboration agreement with approximately 884000 in the fourth quarter 2019, we recognize no revenue on a fourth quarter of 2018.
Research and development expenses were 5.8 million in the fourth quarter 2019, compared to 8.9 million in the fourth quarter 2018.
The decrease was primarily due to the decrease in contract manufacturing and preclinical and research activities for our product candidates, partially offset by increased clinical trial expenses for alpine one on one.
General and administrative expenses were 2.1 million in the fourth quarter of 2019 compared to 2.5 million in the fourth quarter of 2018.
Decrease was primarily due to decreased legal and patent seems to support our intellectual property.
With that I will now turn over the call back over to match before opening the call for Q anyway.
Thanks, Paul.
As you heard from Stanford comments, we have made excellent progress on the company's programs and we're continuing active discussions with potential partners.
Stanford Peng: We recently presented some data on the biomarker assay in a poster at the United States and Canadian Academy of Pathology Annual Meeting. We therefore look forward to having two active clinical programs in efficacy studies. Looking forward to our pipeline, we have recently identified a novel B-cell modulator developed via our directed evolution platform, which would be applicable to serious inflammatory conditions such as lupus or other B-cell-mediated diseases. As the preclinical data on this program matures, we look forward to presenting further details at an appropriate scientific forum later this year. I will now hand the call over to our CFO, Paul Rickey, to discuss our financial results for the quarter.
We're now in the next phase of evolution for the company as we advance these novel molecules in patients who need it better therapeutic options.
Hi, This is a unique an unprecedented time in our country.
We remain focused on executing our strategy in advancing our programs to understand their potential benefit for patients in need better therapeutic treatment options.
This crisis has galvanize opted out fine in the industry as a whole and we feel a sense of purpose and developing therapeutics to help patients.
With that operator, we'll open the lines for queuing it.
Thank you. So it will now be conducting a question and answer session.
He would like just a question. Please press Star then to one key on your telephone keypad.
A combination killed will be indicate your line is into question Q.
You mean, a press the pound keep you like to most of your question from Tokyo.
Paul Rickey: Thank you, Stanford. As both Mitch and Stanford mentioned, we anticipate advancing both ALPN-101 and ALPN-202 into clinical trials throughout the current year. With our current cash on hand, we expect to have sufficient cash to support both development plans for at least the next 12 months into early 2021. Now, turning to financial resorts for the fourth quarter. Cash, cash equivalents, and marketable securities totaled $40.9 million as of December 31, 2019, compared to $47 million as of September 30, 2019. The net loss for the quarter was $6.1 million, or $0.33 per share. This was a decrease when compared to last year's fourth quarter loss of $11.1 million, or $0.80 per share. Revenue recognized under our ADAPT Immune Collaboration Agreement was approximately $884,000 in the fourth quarter of 2019.
All participants using speaker equipment, it may be necessary to pick up your handset before question just starkey.
One moment, please while we pull for questions.
Our first question coming from the line up CAD 10 touched on Piper Jaffray. Your line is open.
Great Hi, everybody, it's great to hear work I'm glad to hear <unk> doing well.
I wanted to get a trend.
[laughter] action.
Lending Sofia hope it.
But you know words when should we be expecting data is until it's too early to tell at this point I certainly appreciate that there's a lot on certain things.
Yeah, Yeah, Yeah, it's great to hear your voice as well I think what we can say as previously I think we thought we'd be up at their peak doses at the end of this year early part of next year and I think a lot of that's going to defend its on a how enrollment really proceeds with the with the cover 19 crisis, that's ongoing but Stanford you ended up you have anything you want to add onto that.
Yeah, we've not heard sites formally stopping are pausing or study in fact, there's only been enthusiasm can move forward, but that being said I think it won't be a few more months, perhaps one more quarter to kind of see where things settle out with regard to how how enrollment actually goes and how it affects.
Paul Rickey: We recognized no revenue in the 4th quarter of 2018. Research and development expenses were $5.8 million in the fourth quarter of 2019, compared to $8.9 million in the fourth quarter of 2018. This decrease was primarily due to the decrease in contract manufacturing and preclinical and research activities for our product candidates, partially offset by increased clinical trial expenses for Alpine 101. General and administrative expenses were $2.1 million in the fourth quarter of 2019 compared to $2.5 million in the fourth quarter of 2018.
The sites that are involved in our studies.
Okay, well keep though guys and thanks for the Hartford.
You too.
Yeah.
And our next question coming from July now smart, bringing back with Oppenheimer.
Please proceed with your question.
Hey, guys. Thanks for taking the questions and congrats on getting <unk> trials open for enrollment, especially given the current conditions.
Mitch <unk>, maybe you could give us a little bit more color on how many sites are open for each trial and whether or not that pin debit endemic has forced to do kind of change which clinical sites are being activated.
Yeah.
Yeah, you want to take down for both European went to one intuitive.
Yeah actually it has not changed her sites trashy because the sites that were interested before continues to be interested that being said we have heard that there had been delays at some sites with regard to for example, there I or higher be meeting timelines and so on so.
Paul Rickey: The decrease was primarily due to decreased legal and patent fees to support our intellectual property. With that, I will now turn the call back over to Mitch before opening the call for Q&A. Thanks, Paul. As you heard from Stanford's comments, we have made excellent progress on the company's program, and we're continuing active discussions with potential partners. We are now in the next phase of evolution for the company as we advance these novel molecules in patients in need of better therapeutic options. While this is a unique and unprecedented time in our country, We remain focused on executing our strategy and advancing our programs to understand their potential benefit for patients in need of better therapeutic treatment. This crisis has galvanized us and the industry as a whole. And we feel a sense of purpose, and Developing Therapeutics to Help Patients. With that, operator, we'll open the lines for Q&A.
I think what I'd like I'd like I, just mentioned I think well well need to a little bit more time to get it real handle on what impact its head. If some of these sites really can't move forward, but we're only hearing right now that they can continue so or kind of operating on fees on both sides that.
Well kinda navigate through the current situation.
And Sanford maybe you can offer some some qualitative observations on how little bit 19 is impacting allogeneic transplant.
Across the country or are they still happening or are they mostly being postponed due to lack of I see you space you know I'm not I'm not sure if it's a allogeneic transplant or kind of kind of on on hold in general or if they're still pursuing which is obviously relevant today.
The balance study.
Yeah, I think that we heard different messages, depending on how probably depending on the disease indications. So as you know allogeneic transplant are often Burger company required in certain settings. For example, some of the team is and we've not heard that those are necessarily going to be delayed in fact most.
Operator: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star, then the one key on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press the pound key if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key.
A number the investments we spoken to love insisted that are there shouldn't be a delayed because those are prioritized situations that their institutions.
That being said I would expect there to be some impact it's always hard to imagine that there won't be an impact subsumption, some way or perhaps on the order of.
Frequency or follow up visits or the intensity of them a threshold for requiring no subject to come back to the hospital for follow up and so long since there's a push toward as I'm sure you know toward trying to facilitate tele medicine or or remote sort of monitoring I think that's more likely the effect on clinical trial.
Operator: One moment, please, while we pull for questions. Our first question comes from the line of Ted Tenthouse, Bob Harper-Jeffrey. Your line is open. Great. Hi, everybody. It's great to hear your voice. I'm glad to hear everyone's doing well. Climbing.
Enrollment since anytime a new patient needs to be enrolled so what these be wade between the subject and the investigator and of course, the protocol is whether the any logistical considerations about could make interfere with the study processes.
Mitchell H. Gold: So NEON's open, but you know when we should be expecting data? Is it just too early to tell at this point? I certainly appreciate that there's a lot of uncertainty out there. Thanks.
Got it and maybe just so quick last one for Paul I don't want to leave them out of the conversation [laughter] I'm, just not just noticing that R&D spending, it's kinda sharply down versus third quarter and.
Mitchell H. Gold: Yeah, Ted, great to hear your voice as well. I think what we could say is, previously, I think we thought we'd be up at therapeutic doses at the end of this year, early part of next year, and I think a lot of that's going to depend just on how enrollment really progresses with the COVID-19 crisis that's ongoing. But Stanford, I don't know if you have anything you want to add to that.
You know I'm wondering if you can you know maybe maybe explain what's what's behind that and how we should be thinking about R&D spending in 2020.
Yeah, if we really look at R&D spending for 2019 and really the first three quarters.
We were.
Pretty much enrolling the alpine one on one healthy volunteer study over those first three quarters and really just kind of wrapping up and continuing following on our as we looked at kind of Q4, there and so that expense went down if you look at alpine two or two from up.
Stanford Peng: Yeah, we've not heard sites formally stopping or pausing our study. In fact, there's only been enthusiasm to move forward. But that being said, I think it will be a few more months, perhaps one more quarter, to kind of see where things settle out with regard to how enrollment actually goes and how it affects the sites that are involved in our study. Well, keep up the good work, guys, and thanks for all the hard work. You too, Ted.
CMC production perspective, we had a lot of costs in the first three quarters as well for that as we ramped up and then as you just heard on this call. We just now we're getting Oh, both studies opened for enrollment I'm here at the end of this quarter and so that's kind of really are indicative of what you're seeing from a Q4 R&D expense perspective.
All right. That's a that's very helpful. Thanks for taking questions and congrats.
Thanks, Mike.
And as a reminder, ladies and gentlemen, if you'd like to ask the question. Please press star one on your telephone keypad.
Operator: And our next question comes from the line of Mark Rickenback with Oppenheimer. Please proceed with your question. Hey guys, thanks for taking the questions and congrats on getting both trials open for enrollment, especially given the current conditions. Mitch, maybe you could give us a little bit more color on how many sites are open for each trial and whether or not the pandemic has forced you to kind of change which clinical sites are being activated.
Next question coming from July enough Wang Sealy with Ladenburg. Please proceed with your question.
Hi, Thanks for taking my questions I know a question specific oh upon two to <unk> no great stories started opened for enrollment.
You look at a can you try to the and it looks like it could be.
It was solid tumor and the lymphoma.
I'm supposed to close Crunch cities do you have a.
Stanford Peng: Stanford, do you want to take this for both ALPN 101 and ALPN 202?
The prioritization in solid tumor or lymphoma or you just it's there's no it's brendan based on.
Stanford Peng: Yeah, actually, it has not changed our site strategy, because the sites that were interested before continue to be interested. That being said, we have heard that there have been delays at some sites with regard to, for example, their IRB meeting timelines, and so on. So I think, like I just mentioned, we'll need a little bit more time to get a real handle on what impact it's had if some of these sites really can't move forward, but we're only hearing right now that they can continue. So we're kind of operating on faith on both sides that we will kind of navigate through the current situation.
The patient enrollment and the second question is if you look at those are those ranges starting from zero point and using the one who couldn't give me a group of people Quinn, it's quite a wide range. So any color on how many dose levels you will.
You will test for the phase one trial.
Great Lindsay I like Stanford take that you might take the first part of it works lymphomas versus solid tumors and our enriched for the trial.
Yeah. So in terms of the indications, we actually don't have a particular preference although as I'm sure. You know most phase one units tend to be weighted toward solid tumors. So we expect that majority of the patients will be solid tumors.
And to be honest I think our intent is to consider is liquid tumors like lymphoma more de expansion phase. So the way we set the protocol up this way so that if we could get at least a few patients during escalation just because some experienced with a drug that would help us feel comfortable moving into.
Stanford Peng: And Stanford, maybe you can offer some qualitative observations on how COVID-19 is impacting allogeneic transplants across the country. Are they still happening, or are they mostly being postponed due to lack of ICU space? You know, I'm not sure if allogeneic transplants are kind of on hold in general or if they're still proceeding, which is obviously relevant to the balance study. Yeah, I think we've heard different messages, probably depending on the disease indication. So, as you know, allogeneic transplants are often urgently required in certain settings, for example, some leukemias, and we've not heard that those are necessarily going to be delayed. In fact, a number of the investigators we've spoken to have insisted that there shouldn't be a delay because those are prioritized situations at their institution.
From a another heme malignancies. This if that's of interest and the expansion phase but to be clear. We expect most of the tumors to be solid just given the nature of most phase one units.
With regard to dose regimen yep Yep, so with regard to their dose regimen you know the its written is pretty.
Broadly in order to allow a pretty high dose at the 20 milligrams per kilogram, but we don't really expected need to go with that high as you know that's a pretty large amount of drug and our modeling. So you may recall that about a year ago, we published a PK PD modeling where the therapeutic dose.
Anticipated is around 0.1 to 0.3 makes for keurig.
Stanford Peng: That being said, I would expect there to be some impact. It's hard to imagine that there won't be an impact in some way, perhaps on the order of frequency of follow-up visits or the intensity of them, the threshold for requiring those patients to come back to the hospital for follow-up, and so on, since there's a push toward, as I'm sure you know, trying to facilitate telemedicine or remote care. [inaudible] Got it. And maybe just a quick last one for Paul. I don't want to leave him out of the conversation, but just noticing that R&D spending is kind of sharply down versus the third quarter. And, you know, I'm wondering if you could maybe explain what's behind that and how we should be thinking about R&D spending in 2020.
So for that for this study we haven't accelerate titration design, where we get out of that very low dose really quite quickly I'm using single subject cohorts. We so if the modeling turns out to be correct will be at from a clinically active dose is actually pretty soon and may not need to go that high but but the trolls written with high.
Doses, mostly to accommodate any flexibility or optionality. If we did want to keep a continuing to escalate to get better experience of safety and exposure I'm kind of drugs.
[noise] I didn't see we're starting with a single patient dose escalation cohort and once the region. So I wasn't then just because the classic sweep luxury.
Yes, that's right.
Got it okay, great six months my questions.
Exactly.
And there are no further questions at this time.
Oh.
One just skewed up would you like me to it picked up question.
Paul Rickey: Yeah, if we really look at R&D spending for 2019, pretty much enrolling the Alpine 101 Healthy Volunteer Study over those first three quarters and really just kind of wrapping up and continuing following on as we looked at kind of Q4 there, that expense went down. If you look at Alpine 202 from a CMC production perspective, we had a lot of costs in the first three quarters as well for that as we ramped up. And then, as you just heard on this call, we just now are getting both studies open for enrollment here at the end of this quarter. And so that's kind of really indicative of what you're seeing from a Q4 R&D expense perspective.
Oh coming from the line off Larry you mentioned.
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I'm showing no further questions at this time I would like to turn the floor back over to Dr. Cohen for closing comments.
Thank you. Thank you thank everyone for joining us today and I Hope you all stay healthy we look forward to give you updates in the future. Thanks very much operator.
Ladies and gentlemen doesn't teleconference for today. Thank you for your participation you may now disconnect.
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Operator: Alright, that's pretty helpful. Thanks for taking the questions and congratulations. Thanks, Mark.
Operator: And as a reminder, ladies and gentlemen, if you'd like to ask a question, please press the star 1 on your telephone keypad. Now our next question comes from the line of Wang Zili with Lettenberg. Please proceed with your question. Hi, thanks for taking my questions. I have a question specifically about Alpine 202. I think there's now a great story starting open for enrollment.
Stanford Peng: I look at connecticut.gov, and it looks like it's going to be both solid tumor and lymphoma. So the first question is, do you have a prioritization for solid tumor or lymphoma, or is it random based on patient enrollment? And the second question is, if you look at the dose range, starting from 0.001 to 20 mg per kg, it's quite a wide range. So any color on how many dose levels you will test for the Phase 1 trial.
Stanford Peng: Great. Lindsay, I'd like Stanford to take that. Stanford, do you want to take the first part of it where it's lymphomas versus solid tumors and how enriched for the trial?
Stanford Peng: Yes, so in terms of the indications, we actually don't have a particular preference, although as I'm sure you know, most phase one units tend to be weighted toward solid tumors. So we expect that the majority of the patients will have solid tumors. And to be honest, I think our intent is to consider liquid tumors like lymphoma more in the expansion phase. So the way we set the protocol up this way so that if we could get at least a few patients during escalation, just to get some experience with the drug, that would help us feel comfortable moving into lymphoma and other hemopoietic diseases if that's of interest in the expansion phase. But to be clear, we expect most of the tumors to be solid, just given the nature of most phase one tumors.
Stanford Peng: With regard to the dose regimen, it's written pretty broadly in order to allow a pretty high dose, up to 20 mg per kg, but we don't really expect to need to go that high. As you know, that's a pretty large amount of drug. And our modeling, so you may recall that about a year ago, we published PKPD modeling where the therapeutic dose anticipated is around 0.1 to 0.3 mg per kg. So, for this study, we have an accelerated titration design where we get out of that very low dose really quite quickly using single-subject cohorts. So, if the modeling turns out to be correct, we'll be at pharmacodynamically active doses actually pretty soon and may not need to go that high, but the trial is written with high doses mostly to accommodate any flexibility or optionality if we did want to keep continuing to escalate to get better experience of safety and exposure from the drug. We started with a single patient post-escalation cohort, and once we reach certain levels, then you start Yes, that's right. Okay, great. Thanks a lot for answering my questions.
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Operator: D.
Operator: Institute
Mitchell H. Gold: And there are no further questions at this time. One just queued up, would you like me to take that question? Coming from the line of Larry Litton. I'm not showing any further questions at this time. I would like to turn the floor back over to Dr. Gold for closing comments.
Operator: Thank you. I'd like to thank everyone for joining us today, and I hope you all stay healthy. We look forward to giving you updates in the future. Thanks very much, operator.
Operator: Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may all disconnect.
Operator: Physicist, Dr. James Tumlin, Michael Ulz, Jonathan Barratt, James Tumlin, Robert Driscoll, Remy Durand, Gao Chen, Alpine Immune; Michael Ulz, Robert Driscoll, Remy Durand, Gao Chen