Q2 2021 Alpine Immune Sciences Inc Earnings Call

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Good afternoon, ladies and gentlemen, thank you for joining the alpine immune sciences second quarter, 2021 financial results and corporate update conference call.

Operator: Good afternoon, ladies and gentlemen, and thank you for joining the Alpine Immune Sciences Second Quarter 2021 Financial Results and Corporate Update Conference Call. Currently, all participants are in a listen-only mode. Following management-prepared remarks, we will hold a question-and-answer session. To ask a question at the time, please press star followed by one on your touchtone telephone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this conference is being recorded on Tuesday, August 10, 2021. I would now like to introduce Alec Shariff, Director of Investor Relations and Corporate Development. Please go ahead.

All participants are in a listen only mode. Following management's prepared remarks, we will hold the question and answer session to ask the question at the time. Please press star followed by 1 on your attach don't telephone if anyone has difficulty hearing the coin France. Please press star zero for the operate.

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As a reminder, this conference being recorded Tuesday August 2021 I would now like the introduced all the carriers director Investor Relations and corporate development. Please go ahead.

Thank you Mary with me on today's call from the Alpine immune Sciences are executive Chairman and CEO, Dr. Mitchell Gold.

Alec Shariff: Thank you, Mary. With me on today's call from Alpine Immune Sciences are Executive Chairman and CEO Dr. Mitchell Gold, President and Head of Research and Development Dr. Stanford Peng, Chief Financial Officer Paul Rickey, and Chief Business Officer Dr. Remy Durand. This afternoon, Alpine Immune Sciences issued a press release announcing the company's second quarter 2021 financial results and corporate update. If you have not received this news release and would like to read it, or if you would simply like to be added to the company's distribution list, you can do both on the investor relations page of the company's website at www.alpineimmunesciences.com.

And the head of research and development, Dr. Sanford Payne, Chief Financial Officer, Paul Rickey, and Chief Business Officer, Dr. Remy Durant.

This afternoon Alpine immune sciences issued a press release announcing the Companys second quarter 2021 financial results and corporate update if.

If you have not received the news release and would like to read it or if you would simply like to be added to the company's distribution list you can do both on the Investor Relations page of the company's website at Www Dot Alpine immune sciences Dot com.

Alec Shariff: During the course of today's conference call, Alpine's management will make forward-looking statements, including, but not limited to, statements regarding the company's preclinical and clinical development plans and the timing thereof; expectations regarding the sufficiency of cash to fund operations, including any cash received from potential milestone payments under Alpine's collaboration.

During the course of today's conference call Alpine as management will make forward looking statements, including but not limited to.

Statements regarding the company's preclinical and clinical development plans and the timing thereof XP.

Expectations regarding the sufficiency of cash to fund operations, including any cash received from potential milestone payments under alpine of collaborations the.

Alec Shariff: The timing and publication of future clinical data. Expectations regarding Alpine's ongoing collaborations and potential future collaborations, including the anticipated strategic and financial benefits of the option and licensing agreement between Alpine and AbbVie for the development and commercialization of ALPN-101 or Kazikolsa. Alpine's ability to successfully develop its product candidates and achieve milestones under its collaboration with AbbVie and others, and the Financial and Business Outlook for Alpine. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties. The actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties.

Timing and publication of future clinical data.

Expectations regarding alpine ongoing collaborations and potential future collaborations, including the anticipated strategic and financial benefits of the option in licensing agreement between the alpine and Abbvie for the development and commercialization of a L. P N 1 O 1 or <unk>.

Sept Alper.

Alpine the ability to successfully develop its product candidates and achieve milestones under its collaboration with Abbvie and the others.

And the financial and business outlook for Alpine.

These forward looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties.

That could cause results to be different from these statements. Also include factors. The company describes in the section entitled risk factors in the Alpine the quarterly filing on form 10-Q for the period ended June 30th 'twenty, 'twenty, 1 and filed with the SEC on or about.

Alec Shariff: Factors that could cause results to be different from these statements also include factors the company describes in the section entitled risk factors in its quarterly filing on Form 10-Q for the period ended June 30, 2021, which will be filed with the SEC on or about August 10, 2021. Alpine cautions you not to place undue reliance on forward-looking statements and undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations.

August 10th 2021.

Alpine cautions you not to place undue reliance on forward looking statements and undertakes no duty or obligation to update any forward looking statements as a result of new information future events or changes in its expectations with that I will now turn the call over to Alpine executive Chairman and CEO.

Mitchell gold.

Thanks, Alan and welcome to our second quarter 2021 financial results Conference call.

We had of highly productive second quarter with substantial progress made across our portfolio.

We look to continue to build on our strong momentum and accelerate development of our pipeline of innovative therapies for patients living with cancer and autoimmune and inflammatory diseases.

The 4 Stanford provided the summary of the key updates for our 3 months of advanced programs.

I wanted to take a step back of highlight where the company sits today.

When we founded the company over 6 years ago, we had a goal of targeting CD 28.

Alec Shariff: With that, I will now turn the call over to Alpine's Executive Chairman and CEO, Dr. Mitchell Gold. Thanks, Alex, and welcome to our second quarter 2021 financial results conference call. We had a highly productive second quarter with substantial progress made across our portfolio. We look to continue to build on our strong momentum and accelerate the development of our pipeline of innovative therapies for patients living with cancer and autoimmune and inflammatory diseases. Before Stanford provides a summary of the key updates for our three most advanced programs, I wanted to take a step back and highlight where the company stands today.

The key co stimulatory ligand on T cells is the therapeutic approach both of oncology and for autoimmune diseases.

In 2015, 80, 28 was seen as too risky of direct target given early experiences with the pace of narrow monoclonal antibody.

The near fatal cytokine storm.

But do you believe the biology was too compelling and believed we could successfully engineered approaches that we're both safe and effective.

That belief resulted in the development of the alpine 1 on 1 which we look first of all going forward by the generic name the cats, the coset or of Kathy.

Dual inhibitor of <unk> 28, and that goes for autoimmune and inflammatory diseases.

And alpine 2 of 2 a conditional see the 28 agonist in oncology.

Yesterday.

CD 28 came to the forefront and an all day Investor Conference hosted by Bernstein focused on how to target CD 28 and cancer.

Stanford along with the scientific leaders of 2 other companies and Mike current from MD Anderson presented on CD 28 is the therapeutic target.

We believe the data from the programs at Alpine will support the CD 28, as being of rational and effective targets both in oncology.

Mitchell H. Gold: When we founded the company over six years ago, we had a goal of targeting CD28, the key co-stimulatory ligand on T-cells, as a therapeutic approach both for oncology and for autoimmune disease. However, in 2015, CD28 was seen as too risky a direct target, given early experiences with occasional monoclonal antibody-mediated cytokine storms. We believe that biology was too compelling and believe we could successfully engineer approaches that were both safe and effective.

And in other diseases.

We are proud to have led to see the 28 torch back in 2015, and we look forward to continuing the carried across the finish line to help patients in need of new therapeutic approaches.

At the same time, we are strongly encouraged by the progress of our discovery platform beyond the 28 and the immunoglobulin superfamily.

The alpine 3 of 3 program for instance has demonstrated our ability to target the TNF superfamily as well.

It has shown promising preclinical data and we are particularly excited about this program.

Stanford will go into more detail on debt and review of our most recent clinical progress across the all of our development programs Stanford.

Thank you Mitch.

As Mitch mentioned 2021 continues to be an exciting and productive time for us.

Fortunately, we were particularly pleased to successfully initiated synergy the phase III study with mechanical stepped in lupus.

Mitchell H. Gold: Dapolese resulted in the development of Alpine 101, which we will refer to going forward by the generic name Akazococept or Akazia, a dual inhibitor of CD28 and IQOS for autoimmune and inflammatory diseases, and Alpine 202, a conditional CD28 agonist and oncologist Yesterday, CD28 came to the forefront in an all-day investment, hosted by Bernstein, focused on how to target CD28 in cancer Stanford, along with the scientific leaders of two other companies and Mike Curran from MD Anderson, presented on CD28 as a therapeutic target.

This is on international 24 week randomized double blind placebo controlled parallel arm study of approximately 130 participants with active disease.

The primary objectives include safety and Tolerability, but important efficacy assessments will include multiple traditional lupus disease activity endpoints, including suite of high end by lag as well as clinical biomarkers of disease activity, such as anti DNA complement levels.

Development activities for alpine true to our conditional CD 28 co stimulator in dual checkpoint inhibitor have also been particularly eventful.

We presented initial data from the ongoing dose escalation with monotherapy in advance of public and sees the need on 1 trial at <unk> in June.

The drug has been very well tolerated with the most remarkable adverse events, including great 1 or 2 immune related adverse events, particularly cutaneous as of the data cutoff date.

Particularly interesting even though the phenotypic changes were observed in circulating T cells, including markers of activation and proliferation increases and central memory T cells and reductions and T. Rex.

The findings were notable since they do not appear to have been reported previously in studies with combination of all of that is the living lab, suggesting a differentiated profile due to the C 28 mechanism of the drug.

Mitchell H. Gold: We believe the data from the programs at Alpine will support CB28 as being a rational and effective target both in oncology and in other immune diseases. We are proud to have lit the CD28 torch back in 2015, and we look forward to continuing to carry it across the finish line to help patients in need of new therapeutic approaches. At the same time, we are strongly encouraged by the progress of our discovery platform beyond CD28 and the immunoglobulin superfamily.

In addition, we are pleased to observe that the majority of participants derive clinical benefit as judged by the best response of stable disease or better. Despite the population consisting of heavily pre treated tumors that are traditionally considered not give me of logically responsive.

The majority of this reported experience was on the weekly dosing schedule now we plan to complete dose escalation on the Q3 week schedule and choose the dose specific.

The specific dose regimen, preferably Q3 week 4 expansion cohorts hopefully by the end of this year.

For this program. We were also excited about entering a collaboration with Merck to study alpine <unk> in combination with samples of the Humana.

This is the neon 2 trial design is similar to neon 1 with an abbreviated dose escalation in separate expansion part of patient.

Patients with advanced malignancies that are either eligible for treatment with the PD, 1 inhibitor or otherwise have no standard therapeutic options.

Mitchell H. Gold: The Alpine 303 program, for instance, has demonstrated our ability to target the TNF superfamily as well. It has shown promising preclinical data, and we are particularly excited about this program. Stanford will go into more detail on this and review our most recent clinical progress across all of our development programs.

Although the addition of of PD, 1 inhibitor to alpine <unk> might seem redundant at first we have as the we've observed pre clinically that's such a combination can provide additional perhaps synergistic effects.

We attribute this to the ability of PD, 1 inhibitors to induce or up regulate PD L..1 expression on tumor and other immune cells, which in turn with potentiate. The PD Lone dependency 28 gross inventory activity of alpine 2 of <unk>.

The combination study also facilitates the study of alpine <unk> and immune responsive tumors in earlier lines of therapy, helping to expedite the overall clinical development plan.

Stanford Peng: Thank you, Mitch. As Mitch mentioned, 2021 will continue to be an exciting and productive time for us. Importantly, we were particularly pleased to successfully initiate Synergy, the Phase 2 study with Akazical Cept and Lupus. This is an international, 24-week, randomized, double-blind, placebo-controlled, parallel arm study of approximately 130 participants with active... Primary objectives include safety and tolerability, but important efficacy assessments will include multiple traditional lupus disease activity endpoints, including SLEDI and BILAG, as well as clinical biomarkers of disease activity, such as anti-DNA and compromised antibodies.

We were pleased to initiate the study as well this past June.

At the same time as Mitch mentioned, we are particularly enthusiastic about our third development candidate Alpine 3 of 3 of dual bass April B cell cytokine inhibitor, which we are developing for lupus and other b cell mediated diseases.

Our scientists received of basic Science award for their oral presentation on alpine 3 of 3 at the recent U R. E Congress, which included a presentation of alpine 3 of 3 superior potency and effectiveness in animal models <unk>.

Third the wild type Tacky FC fusion competitors.

The studies in non human primates demonstrated also superior of PK, PD, which may translate into superior efficacy <unk> of more convenient dosing regimen in humans.

We're currently completing clinic, enabling activities and continue to target initiation of a phase 1 study by the end of the year.

I'll now hand, the call over to our CFO, Paul Ricky's to discuss our financial results for the quarter Paul.

Thank you as Stanford mentioned in June we initiated our phase 2 synergy study as part of our Abbvie collaboration and achieved $45 million in pre option development milestones.

That deal provided an upfront payment to alpine last year of $60 million and we will have provided of $105 million cash in the first year of our collaborations.

There is still an additional $30 million in potential pre option development milestones as we progress on our calls the development plan and $730 million per option exercise the success based milestones plus royalties as part of the overall deal value.

Turning to our financial results for the fourth quarter Alpine as cash cash equivalents and marketable securities totaled $100.4 million as of June 32021, which does not include the $45 million and achieved abbvie milestones, which we expect to receive in the third quarter <unk>.

Stanford Peng: Development activities for Alpine 202, our conditional CD28 co-stimulator and dual checkpoint inhibitor, have also been particularly exciting. We presented initial data from the ongoing dose escalation with monotherapy and advanced NEON1 trial at ASCO in Japan. The drug has been very well tolerated, with the most remarkable adverse events including grade 1 or 2 immune-related adverse events, particularly cutaneous, as of the data cutoff today. Particularly interesting immunophenotypic changes were observed in circulating T-cells, including markers of activation and proliferation, increases in central memory T-cells, and reductions in Treg.

This compares to our cash balance of $115.4 million on March 31.2021.

Revenue recognized under our collaboration agreements was approximately $7.2 million in the second quarter of 2021 compared to approximately <unk> $7 million on the second quarter of last year the.

The increase was attributable to our revenue recognized under our at the agreement.

Research and development expenses were $14.6 million in the second quarter of 2021 compared to $7.1 million in the second quarter of last year the increase.

<unk>, primarily related to contract manufacturing and process development of our product candidates ongoing clinical trial activities direct research and personnel related expenses.

General and administrative expenses for the second quarter of 2021 were $3.3 million compared to $3.3 million on the second quarter of last year as well.

Alpine recorded a net loss of $11 million in the second quarter of 2021 compared to $9.9 million in the second quarter of 2020.

In terms of our cash runway, we expect that our cash on hand, combined with the $45 million and achieve milestones to be received in the third quarter and the potential $30 million in additional pre option exercise milestones under our collaboration with Abbvie is sufficient to fund alpine planned operations through 2023.

With that I will turn the call back over to Mitch.

Thanks, Paul.

Looking forward the upcoming milestones the Stanford mentioned, we plan to complete dose escalation for neon 1 on the Q3 week schedule and choose the specific dose regiment for our expansion cohorts.

We anticipate the initiation of our phase 1 first in human trial for alpine through 3 in the fourth quarter of this year.

Stanford Peng: These findings were notable since they do not appear to have been reported previously in studies with combination nivolumab and ipilimumab, suggesting a differentiated profile due to the C28 mechanism of the drug. In addition, we are pleased to observe that the majority of participants derived clinical benefit as judged by a best response of stable disease or better, despite the population consisting of heavily pretreated tumors that are traditionally considered not immuno The majority of this reported experience was on the weekly dosing schedule.

This will be the first clinical step towards establishing the potential best in class position for this program.

As a reminder.

<unk> 3 of 3 targets to be sales cytokines April and fat.

We are particularly excited about this program because these are well validated targets.

Inhibition of the cytokines associated with highly robust reproducible PD endpoints, even in healthy volunteers.

As a result, we anticipate that the findings of a phase 1 trial early next year.

Could be of significant inflection point for the company.

With that we'll now open the call for questions operator.

Thank you my day to answer the question you will need the cash bar line on your telephone.

Of all of your question first of bounty please standby, while we compile the Q&A of Washington.

Yeah.

Your first question comes from the line of Pat and Jeff from Piper Sandler Your line is open.

Stanford Peng: Now we plan to complete dose escalation on the Q3 week schedule and choose a specific dose regimen, preferably Q3 week for expansion cohorts, hopefully by the end of this year. For this program, we were also excited about entering a collaboration with Merck to study Alpine 202 in combination with embolizumab. This is the NEON-2 trial, whose design is similar to NEON-1, with an abbreviated dose escalation and separate expansion part, patients with advanced malignancies that are either eligible for treatment with the PD-1 inhibitor or otherwise have no standard therapeutic option.

Great. Thank you so much guys. Thanks for the update.

So 1 of them.

Just with respect to additional potential.

Studies of <unk>.

For 2 of them too.

What cancer types are really coming to the top.

It makes the most sense both in terms of combination.

But also.

So on.

Sure.

Monetary items.

On the therapy opportunities somewhat of the accelerated thanks, so much guidance.

Sandra do you want to take down in terms of what we're thinking for expansion studies.

Yeah sure I mean, we continue to think in a couple of different ways..1 is around tumor types that are.

Historically refractory to PD, 1 inhibitors or other checkpoint inhibitors.

Since the mechanism of <unk> hundred 2 is designed to overcome that resistance.

Well as also indications that havent historically immune responsive as 2 of <unk> is designed to be superior to at least checkpoint inhibitor monotherapy.

Stanford Peng: Although the addition of a PD-1 inhibitor to Alpine-202 might seem redundant at first, we have observed preclinically that such a combination can provide additional, perhaps synergistic effects. We attribute this to the ability of PD-1 inhibitors to induce or upregulate PD-L1 expression on tumor and other immune cells, which in turn would potentiate the PD-L1 dependent CD28 cosummatory activity of Alpine 202

I'd say those are things that we're continuing to analyze in terms of the data from the ongoing study.

And we'll be more prepared to.

To answer that in more specifics when we finished dose escalation.

Great.

So for.

Thanks.

Your next question comes from the line of Maury Speaker from Cowen Your line is open.

Great.

Last question about 2.2 but can you set expectations for the new on 1 data update later this year, what a successful of clients here.

Yes, Dan for you on that.

Sure I mean, as you know primary objectives in a dose escalation phase 1 are mostly safety tolerability. So a win for us establishing a dose regimen that will take into expansion cohorts. So.

No.

And I alluded to we've most of you have data that we've reported out with Q1 Q1 week regimen.

Stanford Peng: This combination study also facilitates the study of Alpine 202 and immune-responsive tumors in earlier lines of therapy, helping to expedite the overall clinical development. We were pleased to initiate this study as well this past summer. At the same time, as Mitch mentioned, we're particularly enthusiastic about our third development candidate, Alpine 303, a dual BAS-APRIL B-cell cytokine inhibitor that we are developing for lupus and other Our scientists received a Basic Science Award for their oral presentation on Alpine 303 at the recent U of R e-Congress, which included a presentation of Alpine 303's superior potency and effectiveness in animal models. Comparative Wild-Type Tachy-FC Fusion Comparator.

We're also evaluating of Q3 week regimen, which for various reasons could be advantageous both from the convenience standpoint, and perhaps also from.

Sparing T cell exhaustion as well so we'll be looking at that data carefully as that data emerges from from the escalation and then make a decision.

The only thing I might add on to that for us.

And this was highlighted in detail at the conference yesterday.

Focusing on the CD 28 is the therapeutic targeting oncology.

Is that everyone is really looking at why CD 28, so different than dual checkpoint blockade alone.

And I think what we're thinking of the PD perspective with alpine to of 2 is very different and we're going to obviously get some information out of the knee on 1 trial on that regard we presented some of that debt ESCO.

He is going to be a much more robust data set is the move that forward.

Got it and I just have 1 question on the synergy of study in Lupus just curious what do you anticipate the timeline for enrollment to be.

Yes.

Yeah.

Yes, we expect that the take at least at least the year, although that's something we're continuing to evaluate with the changes in the pandemic situation and how that will affect.

Our operation So I think.

We're cautiously.

The only thing that now.

Okay.

And just for clarity purposes on our plan is 1 thing is the <unk>.

Planning on completing the.

Dose escalation in defining our expansion cohorts by the end of the year, obviously, we looked at present debt at a scientific conference going forward, whether that's the end of this year or sometime next year as the conference schedule out debt when it'll be presented.

Paul Rickey: Studies in non-human primates also demonstrated superior PKPD, which may translate into superior efficacy and or a more convenient dosing regimen. We're currently completing clinic-enabling activities and continue to target initiation of a Phase I study by the end of the year. I'll now hand the call over to our CFO, Paul Rickey, to discuss our financial results for the quarter. Thank you.

Okay, great. Thank you very much for taking my questions sure.

Next question comes from the line of Mark Layton back from Oppenheimer. Your line is open.

Hey, guys good afternoon, and thanks for taking the questions.

Just with regards to upcoming clinical presentations.

Can you give us a sense for when we might see initial data from from me on 2 dose escalation and also can we expect to see healthy volunteer data from the alpine 3 or 3 in the first half of next year.

Paul Rickey: As Stanford mentioned, in June, we initiated our Phase II Synergy Study as part of our AbbVie collaboration and achieved $45 million in pre-option development milestones. That deal provided an upfront payment to Alpine last year of $60 million, and we'll have provided $105 million in cash in the first year of our collaboration. There is still an additional $30 million in potential pre-option development milestones as we progress with our ACASI development plan, and $730 million for option exercise and success-based milestones plus royalties as part of the overall deal value.

Yeah, well I'll take the second question first American that I'm sure of Stanford is going to want to comment.

Comment on the first part so in terms of alpine 3 of 3 obviously, we have a lot of enthusiasm for that.

As I mentioned in my prepared remarks, these are well validated targets in the.

The healthy volunteer trial is going to give us some very instructive endpoints in terms of the impact that we're having a 90 G and IBM.

We anticipate that we'll start that trial in Q4 in the report data on that probably sometime in the first half of next year.

It will come in relatively quickly.

In terms of the ITU standards, you want to talk about debt a little bit.

Sure I mean.

Sure.

Hopefully by the first half of next year I would say, but again, we're just getting started with that trial. So.

I think we will have to get a better estimate of the operation of position of recruitment and so on.

The more likely in a couple of months so assuming all goes as planned.

We could potentially get through that just as quickly as we did with me on 1.

Because it is an abbreviated dose escalation compared to the on 1 but as I said the.

Paul Rickey: Turning to our financial results for the fourth quarter, Alpine's cash, cash equivalents, and marketable securities totaled $100.4 million as of June 30, 2021, which does not include the $45 million in achieved AbbVie milestones, which we expect to receive in the third quarter. This compares to our cash balance of $115.4 million on March 31, 2021. Revenue recognized under our collaboration agreements was approximately $7.2 million in the second quarter of 2021 compared to approximately $0.7 million in the second quarter of last year.

Operational aspect.

Shifting and we just want to acknowledge that.

Understood and just with respect to the healthy volunteer study of tier 3 are there any particular PD markers or kind of the efficacy signals in the healthy volunteer population, but that you really need to see before justifying moving this program forward into a phase III study in lupus or or other.

Their autoimmune indications.

Yes, yes, yes, it's pretty well documented.

I guess the nowadays if you will debt the April on cytokines play a role in B cell.

Population development as well as immune globulins accretion or the production of circulating immune clause on so with.

With prior Wild type Tacky FC fusions that are in the clinic before Theyre actually published the healthy volunteer data that are consistent with each other is showing that.

Youre getting approximately 10% to 20% reductions in Iga and <unk> with the single dose. So we are going to be targeting at least that amount to be able to know what.

The dose levels of 303 or dose regimens of 3 of 3 would be predicted to be at least be able to match that and then also hopefully exceed the.

Paul Rickey: The increase was attributable to revenue recognized under our AFI agreement. Research and development expenses were $14.6 million in the second quarter of 2021 compared to $7.1 million in the second quarter of last year. The increase primarily related to contract manufacturing and process development of our product candidates, ongoing clinical trial activities, direct research, and personnel-related expenses. General and administrative expenses for the second quarter of 2021 were $3.3 million compared to $3.3 million in the second quarter of last year as well. Alpine recorded a net loss of $11 million in the second quarter of 2021, compared to $9.9 million in the second quarter of 2020.

These type of PD outcomes.

Super helpful. Okay. Thank you for taking the questions and congrats on the progress.

Thanks, Mike.

Your last question comes from the line of Joe <unk> from H C. Wainwright. Your line is open.

Hey, guys. Good afternoon, thanks for taking the question.

1 of the start on CD 28 concept. Obviously this is the molecule that's been around for a long time and I guess all of <unk>.

Frame my question in the following manner. When you look at Io and Io approaches. There's always an underlying are percolating concept of being concerned about immune related adverse events. So Mitch I'll use the phrase you used earlier with regard to the rational targeting of alpine too low too do you think that help.

<unk> reduced the risk for IR, aes, especially as you're getting to the point, where youre looking to choose your regimen your final regimen.

Yeah, let's stay up on talk a little bit on dosing, but it was really exciting about this.

This conference that we participated in yesterday was the everyone acknowledged that there was a lot of fear and going after you see the 20 I don't think anyone doubted that it was going to be powerful from a biologic perspective.

But your early experience with antibodies that are targeted I think made.

It made a lot of people kind of stay away from it we felt like whenever you see of biology that powerful do you want to find ways to engineer around it and obviously us.

Mitchell H. Gold: In terms of our cash runway, we expect that our cash on hand, combined with the $45 million in achieved milestones to be received in the third quarter, and the potential $30 million in additional pre-option exercise milestones under our collaboration with AbbVie, is sufficient to fund Alpine's planned operations through 2023. With that, I will turn the call back over to Mitch. Thanks, Paul.

<unk> is obviously working in the space.

We're pretty excited about what we're seeing and it's clearly a differentiator from what youre seeing with checkpoint therapies alone.

Sam you want to take the second part of the question.

Yes, let me make sure I maybe to clarify are you you mean, the concerns about adding 2008 on top of checkpoint inhibition for adverse events is that does that.

Just to your question, yes, but not necessarily just for 2 O 2 specifically, but in general when you have much more of immune activation versus checkpoint inhibition alone and that the targeting aspect of the molecule has the potential to reduce any potential <unk>, yes, yes.

Mitchell H. Gold: I am looking forward to upcoming milestones. As Stanford mentioned, we plan to complete dose escalation for NEON1 on the Q3 week schedule and choose a specific dose regimen for our expansion cohort. We anticipate the initiation of our Phase 1 first-in-human trial for Alpine 303 in the fourth quarter of this year. This will be the first clinical step towards establishing a potential best-in-class position for this program. As a reminder, Alpine 303 targets two B-cell cytokines, APRIL and BAP.

I guess on that regard for the design of 202, we've been actually quite pleased that how well the drug has been tolerated.

Despite the many concerns.

Even our own team had in design of the molecule that we wanted to make sure that it was controlled CD 28 activation in the tumor microenvironment and so on so from that perspective, it's been pretty reassuring to see the progress so far in the clinic.

That being said what we've reported out has been primarily the lower doses. So were quite eager to see how things go as we go to higher doses with the drug.

But another way to look at it though is that the checkpoints primarily seem to work through 2008. So PD 1 works by inhibiting the <unk> 2008 signaling seasonally for works by primarily by.

Being of decoy receptor for the C 20, <unk> see the ADC 6 so they're really taking the breaks obviously the 28 and.

Mitchell H. Gold: We are particularly excited about this program because these are well-validated targets. Inhibition of these cytokines is associated with highly robust, reproducible PDM points, even in healthy volunteers. As a result, we anticipate that the findings of our Phase 1 trial early next year could be a significant inflection point for the company. Operator?

2 of 2 provides like.

On active signaling or the gas so to speak on <unk> 28.

It's also possible that we're not necessarily going to amplify it exceedingly so in terms of excess of physiology, but rather potentiate the effects.

And the in the tumor space of.

Sure.

Potentially the desired effects on T cells into the tumor space.

Got it no I appreciate that and then just quickly on 303, you obviously gave some extra color already.

Just curious what other type of PD markers, you might be looking for beyond the immunoglobulins, because I think like you said, even though its a healthy volunteer study I think there could be some important read throughs.

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Ted Pantoff from Piper Sandler. Your line is open.

I actually forgot to cash or mentioned also the visa on circulating T cell populations, we do expect to see changes in circulating b cell populations because that's also been.

Ah suggested are demonstrated by the mechanism of action and other prior molecule. So we'll be looking at the combination of flow cytometry for B cell subpopulations as well as circulating IGF.

Ted Pantoff: Great. Thank you so much. Hi guys. Thanks for the update. So I want to get a sense only with respect to additional potential.

Got it thank you very much guys.

Joe.

This concludes fitbit Q&A portion of the call I will now turn the call back over to the telcos, who will make the few closing remarks.

Ted Pantoff: 4202. You know, what cancer types are really coming to the top and making the most sense both in...

Thank you operator welcome your request for upcoming meetings with our team. Please feel free to reach out the Alex if you like the schedule some time with us with that like the thank you all for participating on today's call and have a great day.

Stanford Peng: Science, both in terms of combination, but also potentially, even if so, monotherapy opportunities that might be accelerated. Thanks so much.

Yeah.

This concludes today's conference call. Thank you all for your participation you may now disconnect.

Stanford Peng: Thanks, Ted. Stanford, do you want to take that in terms of what we're thinking for our expansion studies? Yeah, sure. I mean, we continue to think in a couple of different ways. One is around tumor types that are historically refractory to PD-1 inhibitors or other checkpoint inhibitors since the mechanism of 202 is designed to overcome that resistance, as well as indications that have been historically immune responsive, as 202 is designed to be superior to at least checkpoint inhibitor monotherapy. You know, I'd say those are things that we're continuing to analyze in terms of the data from the ongoing study, and we'll be more prepared to answer that in more specifics when we finish those escalations.

Yeah.

[music].

Good day.

[music].

Yes.

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Operator: Great. Excellent. Thanks, Stanford.

Marty Speaker: Your next question comes from the line of Marty Speaker from Golan. Your line is open.

Stanford Peng: Great. I want to ask a question about 202. Can you set expectations for the Neon1 data update later this year? What does success look like?

Okay.

Sure.

Yes.

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Stanford Peng: Sure. I mean, you know, as you know, the primary objectives in dose escalation phase 1 are mostly safety tolerability. So a win for us is establishing a dose regimen that we'll take into expansion cohorts. So, as I alluded to, you know, we mostly have data that we've reported out with the Q1 week regimen. We're also evaluating a Q3 week regimen, which for various reasons could be advantageous both from a convenience standpoint and perhaps also from sparing T-cell exhaustion as well.

Yes.

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Stanford Peng: So we'll be looking at that data carefully as that data emerges from the escalation, and then The only thing I might add to that, Boris, and this was highlighted in detail at the conference yesterday, focusing on CD28 as a therapeutic target in oncology, is that, you know, everyone's really looking at why CD28's so different than dual checkpoint blockade alone. And I think, you know, what we're seeing from a PD perspective with Alpine 202 is very different, and we're going to obviously get some information out of the NEON1 trial in that regard. We presented some of that data at ESCO.

Okay.

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Yes.

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Stanford Peng: Got it. And I just have one question on the Synergy Study in lupus. Just curious, what do you anticipate the timeline for enrollment to be? Yeah, Stanford. You want to talk about that?

Stanford Peng: Yeah, we expect that to take at least at least a year, although, you know, that's something we're continuing to evaluate with the changes in the pandemic situation and how that

Stanford Peng: and how that will affect them.

Stanford Peng: So I think we're cautiously, you know, evaluating that now. And just for clarification purposes, our plan is that, you know, we plan on completing dose escalation and defining our expansion cohorts by the end of the year. Obviously, we'd look to present it at a scientific conference going forward, you know, whether that's the end of this year or, you know, sometime next year, as the conference schedule allows, that'll be presented. Great, thank you very much for taking the time to be with us today.

Operator: The next question comes from the line of Mark Badenbeck from Oppenheimer. Your line is open. Hey guys.

Mark Badenbeck: Hey, guys. Good afternoon, and thanks for taking the questions. Just with regard to upcoming clinical presentations, can you give us a sense for when we might see initial data from NEON-2 dose escalation? And also, can we expect to see healthy volunteer data from Alpine 303 in the first half of next year? Yeah, I'll take the second question first, Mark, and then I'm sure Stanford's going to want to comment on the first part.

Mitchell H. Gold: So, in terms of Alpine 303, obviously, we have a lot of enthusiasm for that. As I mentioned in my prepared remarks, these are well-validated targets, and I think the Healthy Volunteer Trial is going to give us some very instructive endpoints in terms of the impact that we're having on IgG and IgM. You know, we anticipate that we'll start that trial in Q4, and we'll report data on that probably sometime in the first half of next year.

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Mitchell H. Gold: So, it'll come in relatively quickly. In terms of NEON 2, Stanford, do you want to talk about that a little bit? Sure. I mean, hopefully, by the first half of next year, I would say, but again, you know, we're just getting started with that trial. So, I think we'll have to get a better estimate of the operationalization of recruitment and so on, more likely in a couple of months. So, assuming all goes as planned, we could potentially get through that just as quickly as we did with NEON1, because it is an abbreviated definition.

Stanford Peng: As I said, it's an abbreviated dose escalation compared to NEON-1, but as I said, the operational aspect of it.

Stanford Peng: Tests are shifting, and we just want to acknowledge that. Okay.

Stanford Peng: And just with respect to the healthy volunteer study of 383, are there any particular PD markers or kind of efficacy signals in a healthy volunteer population that you really need to see before justifying moving this program forward into a phase two study in lupus or other autoimmune indications? Yeah, yeah, it's pretty well documented and, I guess, validates, if you will, that the APRIL and BASC cytokines play a role in B-cell population development as well as immunoglobulin secretion or the production of circulating immunoglobulin.

Stanford Peng: So, with prior wild-type tachy-SC fusions that have been in the clinic before, they've actually published healthy volunteer data that are consistent with each other showing that you get approximately 10 to 20 percent reductions in IgA and IgM with a single dose. So, we're going to be targeting at least that amount to be able to know what dose levels of 303 or dose regimens of 303 would be predicted to be at least able to match that and then also, hopefully, exceed those types of PD outcomes. That's super helpful. Okay. Thank you for taking the questions and congratulations on the progress.

Operator: Your last question comes from the line of Joe Pantginis from...

Joseph Pantginis: Hey guys, good afternoon. Thanks for taking the question. I want to start with the CD28 concept. Obviously, this is a molecule that's been around for a long time, and I guess I'll frame my question in the following manner. When you look at I.O. and I.O.

Joseph Pantginis: Approaches, there's always an underlying or percolating concept of, you know, being concerned about immune-related abnormalities. So Mitch, I'll use a phrase you used earlier with regard to the rational targeting of Alpine 202. Do you think that helps reduce the risk for IRAEs, especially as you're getting to the point where you're looking to choose your regimen, your final regimen? You guys at Stanford talked a little bit about dosing, but what was really exciting about this conference that we participated in yesterday was that everyone acknowledged that there was a lot of fear in going after CD20.

Joseph Pantginis: I don't think anyone doubted that it was going to be powerful from a biological perspective, but the early experience with antibodies that it targeted made a lot of people kind of stay away from it. We felt like whenever you see biology that's that powerful, you want to find ways to engineer around it. And obviously, us.

Mitchell H. Gold: Regeneron's obviously working in this space. We're pretty excited about what we're seeing, and it's clearly differentiated from what you're seeing with checkpoint therapies alone. Stanford, do you wanna take the second part of that question?

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Stanford Peng: Yeah, I want to make sure, maybe to clarify, you mean the concerns about adding 28 on top of checkpoint inhibition for adverse events, is that the gist of your question? Yeah, but not necessarily just for 202 specifically, but in general when you have much more immune activation versus checkpoint inhibition alone, and that, you know, the targeting aspect of the molecule has the potential to reduce any potential IR. Yeah, yeah, I mean, you know, we, I guess in that regard for the design of 202, we've been actually quite pleased at how well the drug has been tolerated, you know, despite the many concerns that, you know, even our own team had in the design of the molecule that we wanted to make sure that it was controlled CD28 activation in the tumor microenvironment and so on.

Stanford Peng: So, from that perspective, it's been pretty reassuring to see the progress so far in the clinic. That being said, what we've reported out has been primarily at lower doses, so we're quite eager to see how things go as we go to higher doses with the drug. But another way to look at it, though, is that the checkpoints primarily seem to work through 28, you know, so PD-1 works by inhibiting CD28 signaling.

Stanford Peng: CTLA-4 works primarily by being a decoy receptor for the CD28 ligands, CD80, and CD6, so they're really taking the brakes off of CD28, and 202 provides, like, you know, an active signaling or the gas, so to speak, on CD28. So, it's also possible that we're not necessarily going to amplify it exceedingly so in terms of excess physiology but rather potentiate the effects in the tumor space, you know, potentially the desired effects on T-cells in the tumor space.

Stanford Peng: No, I appreciate that. And then just quickly on 303, you obviously gave some extra color already. I was just curious what other type of PD markers you might be looking for beyond the immune system. Because I think, like you said, even though it's a healthy volunteer.

Stanford Peng: Yeah, I actually forgot to catch or mention the B-cell, circulating B-cell populations. We do expect to see changes in circulating B-cell populations because that's also been suggested or demonstrated by the mechanism of action and other prior molecules. So we'll be looking at a combination of flow cytometry for B-cell subpopulations as well as circulating IgE. Okay. Thank you very much.

Operator: This concludes the Q&A portion of the call. I will now turn the call back over to Mitchell Gold, who will make a few closing remarks. Thank you, App Grader.

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Mitchell H. Gold: Thank you, Operator. We welcome your requests for upcoming meetings with our team. Please feel free to reach out to Alex if you would like to schedule some time with us. With that said, I'd like to thank you all for participating in today's call and have a great day.

Operator: This concludes today's conference call. Thank you all for your participation. You may now disconnect.

Operator: [inaudible] ??? ??? ??? ??? ??? ??? ??? ??? ??? Dr. James Tumlin, Robert Driscoll, Robert Driscoll, Alpine Immune, Dr. Michael Ulz, Dr. Michael Tumlin, Alpine Immune, Dr. Michael Tumlin, Alpine Immune, Dr. Michael Tumlin, ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? and others. ?? ?? ?? ?? ?? ?? ?? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?? ?? ?? ?? ?? ?? ?? ?? Thank you for watching and please Like, Subscribe, & Comment on where to head to next!