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spk00: Good morning, and welcome to the Vine Therapeutics conference call to discuss the third quarter 2021 financial results and corporate update. At this time, all participants are in a listen-only mode, and following the company's formal remarks, we will open the call for your questions. Please be advised that this call is being recorded at the company's request. I will now turn the call over to John Francis of LifeSci Advisors. Please go ahead.
spk04: Good morning, everyone, and thank you for joining us. Participating in this morning's call are Dave Domzalski, Vine's President and Chief Executive Officer, Tyler Zaranda, Vine's Chief Financial Officer, and Dr. Ian Stewart, the company's Chief Scientific Officer. Please note that there are slides to accompany Dr. Stewart's discussion. For those of you dialed into the phone lines, in order to access these slides, you will need to log on to the live webcast. The link can be found on the Investors and Media section of Vine's corporate website under Events and Presentation. Slide presentation and a replay of this conference call will be archived on the company's website. Before we begin formal remarks, let me remind you that some of the information in the press release issued this morning and on this conference call contain forward-looking statements that involve risks, uncertainties, and assumptions that are difficult to predict, including statements regarding Vine's development programs and future plans and prospects, as well as observations regarding ongoing operating expenses. These statements will include plans and expectations regarding strategic transactions, and the success, timing, and cost of clinical trials. Words that express and reflect optimism, satisfaction with current progress, prospects or projections, as well as words such as believe, intend, expect, plan, anticipate, and similar variations, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those contained in such statements. Several factors that could cause or contribute to such differences are described in detail in Vines Therapeutics filings with the SEC. These forward-looking statements speak only as of the date of today's press release and conference call, and the company undertakes no obligation to publicly update any forward-looking statements or supply new information regarding the circumstances after the date of this call. In addition, the financial portion of this call will include certain non-GAAP financial information. For additional disclosures relating to these non-GAAP financial measures, including a reconciliation to the most directly comparable gap measures, please see today's press release, which is posted on the investor relations section of our website. At this time, I would like to turn the call over to Dave Domzalski. Dave, please go ahead.
spk06: Thank you, John, and good morning to everyone. On our previous earnings call, we announced our transformational decision to refocus our efforts toward developing new and innovative therapies for the treatment of immunoinflammatory diseases. Today, one quarter later, I'm pleased to report that we've achieved a number of important milestones as we continue to advance our proprietary pipeline through a series of near-term, early-stage clinical catalysts over the next 12 to 18 months. Without question, the catalytic event driving this transformation has been the licensing of our bromodomain and extra-terminal, or BET, inhibitor platform, which we announced in August. As a reminder, the BET inhibitor platform provides Vine worldwide rights to a library of small molecule MCEs and a unique platform to develop both topical and oral BET inhibitor therapeutics for any indication. Because BET inhibitors have the ability to target multiple pro-inflammatory pathways, We believe this exciting new drug class could offer the opportunity for highly potent therapies. These therapies have the potential to address serious unmet medical needs with immunoinflammatory diseases. We are now poised to generate a series of exciting, data-driven milestones that we believe will unveil the significant therapeutic potential of these assets. Our focus will be to advance our lead topical bet inhibitor product candidate VYN201, into the clinic in 2022. VYN201 is a first-in-class pan-BD BET inhibitor that is designed to reduce inflammation while mitigating systemic drug exposure. VYN201 is being developed for topical applications, potentially including rare dermatoses where there is significant unmet need due to a lack of indicated treatment options. As many of you know, We recently announced positive data showing that BYN201 was able to significantly reduce several key pro-inflammatory cytokines in both a preclinical model and in a human skin tissue model. Additionally, BYN201 demonstrated improvements in reducing fibrotic tissue mass and overall skin repair outcomes with no negative impact on healing time. These findings offer valuable insights into the evolving therapeutic profile of BYN201, suggesting that the drug may offer optimized efficacy and safety characteristics that could be highly differentiated. Our Chief Scientific Officer, Dr. Ian Stewart, will review the details from these studies later in the call. In parallel with these efforts, we have been working diligently with our partner, InfraDerm, on the development of the oral BET inhibitor, BYN202. BYN202 is an orally delivered, first-in-class bet inhibitor that is highly selective for bromodomain 2, or BD2, with the goal of having a more targeted anti-inflammatory effect with an improved benefit-risk profile as compared to other oral, non-selective bet inhibitors. Upon final candidate selection, we intend to commence an IND-enabling non-clinical safety program and enter the clinic. We are evaluating BYN202 for use in several potential indications within initial focus on autoimmune conditions. To further support our BET inhibitor programs, we recently formed our Scientific Advisory Board, which will provide an important source of external scientific and medical expertise as we expand our BET inhibitor R&D activities. The members of our scientific advisory board are world-renowned experts specializing in immunological and inflammatory diseases, and we are incredibly fortunate to have these distinguished scientists and clinicians to help guide our BET inhibitor and other development programs. Turning to FMX114, we are encouraged by the progress we are making for our most advanced drug candidates. In October, we announced the first patient had enrolled in our Phase 1B, 2A clinical trial that will assess the safety and efficacy of FMX114 gel versus vehicle gel in patients with mild to moderate atopic dermatitis. In light of the FDA's recent review of the oral JAK inhibitor class for the treatment of several systemic autoimmune diseases, we believe it's important to characterize the preliminary safety and pharmacokinetic profile of FMX114. The Phase 1b portion of the study will generate meaningful data as we advance the product into the Phase 2a portion for broader safety and efficacy evaluation. We currently expect top-line results from this study in the early part of the first quarter of next year. As a reminder, FMX114 is a proprietary topical combination formulation of tocacidinib, a Janus Kyanus inhibitor. and Fingolimod, a sphingosine 1 phosphate receptor modulator that is being evaluated for the treatment of mild to moderate atopic dermatitis. This program is an important part of our strategic transition to develop therapies for immunoinflammatory conditions. Atopic dermatitis is a chronic, pruritic inflammatory skin condition and is a multifactorial disease which supports our thesis that a multimodal therapeutic is the ideal approach to achieve optimal clinical outcomes for patients. FMX114 has been designed with intracellular and extracellular mechanism of actions to address both the source and cause of inflammation in atopic dermatitis. As a JAK inhibitor, topacitinib reduces inflammation by inhibiting the release of cytokines that promote inflammation in the skin. These cytokines negatively impact both skin barrier integrity and function, which are key components of the disease. FMX114's second component, Fingolimod, reduces inflammation by inhibiting the migration of inflammatory cells into the skin. Additionally, Fingolimod upregulates filaggrin, a protein, which plays an important role in supporting skin barrier recovery. If successfully developed, We believe FMX114 has the potential to be the first topical combination product for the treatment of atopic dermatitis. Now, I'd like to briefly touch on the planned sale of our topical minocycline franchise, which includes Amzeek, Zilxy, SCD105, which is our phase three ready combination product, and the underlying MST platform. These are excellent products. and the responses from patients and healthcare providers continues to be very positive. Amzeek and Zilksie have generated nearly 165,000 prescriptions combined through September of this year. As noted in this morning's press release, our Minocyclone franchise is a high-quality commercial platform that has significant value. We continue to make progress on the sale of this franchise, and we are encouraged by the level of interest we have received. We will provide additional updates as our current discussions continue to advance. With that, I'd now like to turn the call over to Tyler to cover the financials. Tyler?
spk02: Thanks, Dave, and good morning, everyone. Revenues in the third quarter of 2021 totaled $4.1 million and consisted of $4 million of product sales from Amzeek and Zilksie and $0.1 million of royalty revenue. Our third quarter 2021 GAAP net loss was $21.3 million, or 41 cents per share. When excluding $2.4 million of stock-based compensation expense, our third quarter 2021 adjusted net loss was $18.9 million, or 36 cents per share. For the third quarter 2021, adjusted operating expenses were $18.4 million, including adjusted SG&A expenses of $11.9 million and adjusted R&D expenses of $6.5 million. The third quarter adjusted operating expenses of $18.4 million were $1.9 million lower than the second quarter of 2021, reflecting our focus on cost control and resource prioritization. As we continue to transition our focus and spend toward developing our pipeline, we expect to further reduce our adjusted operating expenses to a range of $10 to $15 million in the fourth quarter of 2021, excluding the one-time $4 million milestone payment related to the exercise of the license agreement for the oral BET inhibitor BYN202. Based on our current plans to conduct a Phase 2B trial for FMX114, assuming positive results in the Phase 2A trial, and to progress both BYN201 and BYN202 into the clinic in 2022, we anticipate that our adjusted operating expenses will be approximately $10 million per quarter next year. Now turning to our balance sheet, Our cash position as of September 30th was approximately $53 million. We believe that this cash will be sufficient to fund our operations through the second quarter of 2022. This projection does not take into account any potential proceeds from the sale of the Topical Minocyclone franchise, new business development transactions, or additional financing activities. Finally, our shares outstanding at September 30th, 2021 totaled 53.5 million shares. For additional information regarding our third quarter results and prior period comparisons, please refer to today's earnings release in our Form 10-Q filed with the SEC. With that, I will turn the call over to Ian, who will go through the progress we've made with our BET inhibitor program.
spk03: Thanks, Tyler. I'd like to start by providing a brief progress update on our BET inhibitor programs, which includes VYN-201 and VYN-202 that we are introducing today as the inhibit platform. I will then present a few slides covering recently announced preclinical data for VYN201, our topical pan-bromo domain BET inhibitor project. As a reminder, today's slide presentation is being presented via our live webcast, and these slides can also be found in our corporate presentation available on our website under the investor relations section. Beginning with VYN201, we have selected our topical formulation for this pan-BET inhibitor and have already generated significant stage-appropriate product characterization and stability information to support its development. In this past quarter, we have initiated the prerequisite preclinical safety program to support the product's regulatory submissions. I'm pleased to report that both formulation development and preclinical safety programs are progressing well to date. Moving now to VYN202, our bromodomain 2 selective oral bet inhibitor project, The lead optimization work is progressing well with our partner, Infoderm, to identify potential development candidates for this program. Infoderm have produced several drug-like NCE candidates with potential class-leading potency and BD2 selectivity. Work is continuing to further characterize these molecules and adding new molecules to the platform of several hundred BET inhibitor examples. As Dave outlined earlier, We recently announced the formation of our Scientific Advisory Board, and we convened our first meeting last month with a sustained group of advisors. In brief, there was broad agreement and interest from the Scientific Advisory Board members on the utility of the BET inhibitor platform across the respective specialties and enthusiasm for its first-in-class potential. Turning back to VYM 201. We recently announced new data from two preclinical studies demonstrating the potential of VYM201 as a highly potent anti-inflammatory therapy for the treatment of various dermatoses with high unmet need. Slide three presents data from a common mouse model of Th17-mediated inflammation. The differentiation and activity of Th17 immune cells drive inflammation in several autoimmune diseases, and are of particular relevance to rare skin diseases we are currently investigating with VYN201. In this model, docile-dipelatated mice will be topically treated with a Mixamod once daily for seven days to induce a Th17 inflammatory dermal phenotype. Following this induction phase, VYN201 was applied once daily at several concentrations and compared to both vehicle and to the class one super potent glucocorticoid steroid, clobetasol propionate cream 0.05% over a seven-day treatment period. Topical imicromod was also applied once daily during the treatment period. The graph on the left of the slide presents percent change in composite inflammatory severity score of erythema and scaling severity for the treatment group over seven days treatment period. Over the concentration range 0.001% to 0.1%, we observed a dose-dependent improvement in clinical signs of inflammation with VYN201 treated animals, culminating in a 94% reduction in clinical signs for VYN201 0.1% compared to vehicle at the end of treatment. Further, VYN201 0.1% was found to be comparable have a comparable positive impact on reducing clinical signs of inflammation when compared to the colperazole product, indicative of a marked anti-inflammatory effect. Moving to tolerability. The plot on the right of this slide presents mean change in animal body weights during the treatment phase. Change in body weight is used as an indicator of general tolerance to treatment. Here we compare body weight changes between VYN201 0.1%, vehicle, clobetazole cream, and a healthy control animal group shown here in green. Animals treated with VYN201 0.1% continued to gain weight throughout the treatment phase in a similar manner to the healthy control animals and was well tolerated. However, animals treated with clobetazole experienced a 17% mean reduction in body weight throughout the treatment period compared to VON201 0.1% treated animals. This is attributable to the negative impact glucocorticoid steroids have on the endocrine system by causing hormonal imbalances that impact metabolism. Slide four presents the impact of VON201 in reducing the expression of key cytokines that drive TH17 mediated inflammation. It should be noted that all of the cytokines presented here play a contributory role in T17 cell differentiation and inflammatory response in several autoimmune diseases. In this study, we observed a strong correlation between cytokine reduction and resolution of clinical signs of inflammation that I presented in the previous slide. Further, we observed a dose-dependent reduction in all six cytokines culminating in a maximum effect at the VYN201 0.1% dose. Slide five presents typical examples of photography at the end of this treatment. The left photograph is of an animal treated with VYN201 vehicle. As you can clearly see, there is still significant inflammation, redness, and scaling present. The central photograph is an animal treated with VYN201 0.1%. The clinical signs of inflammation and scaling have greatly subsided with this animal presenting as a more normal clinical phenotype at the end of treatment with no evidence of dermal intolerance to treatment. The animal treated with probetazole cream has experienced a significant reduction in clinical signs of dermal inflammation. However, the skin presents with marked dermal toxicity with clear evidence of fine and deep wrinkling translucency, and lack of elasticity. Although clearly undesirable, these phenomena are expected based on well-known skin toxicities from topically applied glucocorticoid steroid treatment. Slide six presents with effect of VYN-201 on inhibiting the release of key inflammatory cytokines from human skin tissue in comparison with the JAK-1-2 inhibitor ruxolinib, and the glucocorticoid steroid betamethasone. This ex vivo assay uses harvested human skin tissue that has been stimulated to produce a TH17 inflammatory phenotype where the impact of VYN201 on the release of several TH17 cytokines was evaluated in comparison to untreated controls. In these examples, cytokine release was inhibited by greater than 95% relative to the untreated control. And in this graphed example of interleukin-17, the effect of VYN201 was demonstrated to be statistically superior to both active comparators. This confirms the findings from the preclinical model I presented earlier and demonstrates the potent inflammatory, inhibitory potential of VYN201 for the treatment of diseases driven by TH17 immunology. Now we move to the most recent announcement relating to the evaluation of VOIN 201 and the preclinical model of skin healing. Although diverse in etiology, neutrophilic dermatoses commonly present as ulcers or readily compromised pustules or blisters in the skin. This requires rapid intervention to halt further tissue destruction and allow innate skin repair mechanisms to facilitate lesion healing and closure. As such, it's important to show that any potential treatment for these diseases does not interfere with these processes. So the primary objective of this study was to demonstrate that our topical VYN201 product would not delay skin tissue healing. In this model, two identical incisions were made on either side of the flank of hairless mice under anesthesia. Three treatment groups were treated topically once daily with either VYN201 vehicle or a hydroalcoholic gel control that is known to delay lesion healing enclosure. The graph on the left presents global external lesion healing score by treatment day. The global external lesion healing score is a composite score comprising of lesion length, width, degree of swelling, and overall lesion visibility. It was anticipated that VOIN 201 1% would perform similarly to Viacona's model, and therefore confirming that the BET inhibitor active ingredient would not impact on the time for lesion healing and closure, unlike the hydroalcoholic gel control. As early as treatment day five, there is a statistically significant improvement in lesion healing score for VOIN 201 1% compared to the hydroalcoholic gel, and this continues for the remainder of the treatment period. The mean time to heal for VOIN2011% and vehicle was 15.5 days, whereas the mean time to heal for the hydroalcoholic gel was approximately five days later. Based upon these results, VOIN2011% does not appear to negatively impact skin repair mechanisms. Moving to the graph on the right. This data represents the extent of fibrotic mass formed during the healing at the end of the treatment period. Excessive fibrotic tissue deposits in a healing lesion frequently results in a poor aesthetic outcome of the resultant scar. Fibrotic tissue mass was assessed on a four-point severity scale. Findings from this study show that both vehicle and hydroalcoholic gel treatments resulted in a moderate amount of fibrotic tissue being identified in the lesion bed after the lesions had healed. However, in comparison, there was a much lower presence of fibrotic tissue mass in the VYN 201 1% treatment group, which is indicative of the anti-fibrotic mechanism of action for bed inhibitors. This slide presents typical examples of photography at the end of the treatment. The left photograph is of an animal treated with VYN 201 vehicle. As you can see, there is residual swelling, and the scars are still clearly visible. The central photograph is of an animal treated with VYN 201 1%. There is little evidence of residual swelling, and the lesions are flatter and less distinct in comparison with the other treatment groups. On the right, animals treated with hydrochloric gel have clearly definable scars with significant residual swelling and scabbing still present. In conclusion, we are very satisfied with the preliminary data we have generated with VYN201. VYN201 significantly reduces the expression of several key pro-inflammatory cytokines relevant to TH17-mediated autoimmune diseases and has demonstrated improvement in reducing fibrotic tissue mass and overall skin repair outcomes. These initial data validate our earlier belief of the broad utility and attractiveness of this platform in addressing dysregular immune activity in several serious autoimmune diseases. We continue to work diligently to generate additional data on bed inhibitor pharmacology and epigenetics. The prerequisite IND enabling nonclinical safety program is underway, and we intend to enter VOIN 201 into the clinic in 2022. We look forward to providing additional updates as the program progresses. With that, I will now pass the call back to Dave. Dave?
spk06: Thanks, Ian. We're very excited about the future direction of the company, and we are quickly building momentum across our pipeline of novel and highly differentiated candidates, each with the opportunity to address significant unmet medical need in immunoinflammatory diseases. As I've previously mentioned, We intend to leverage our existing development capabilities and strong network of discovery and preclinical science partners to develop products and advance a series of truly innovative new medicines through the clinic. Our key priorities are to complete the divestiture of the minocycline franchise and advance the pipeline. Over the next 12 to 18 months, we anticipate multiple milestones and early stage development catalysts for our programs. As we move toward 2022, creating shareholder value remains front and center for our company, and we look forward to providing further updates on our progress. This concludes our prepared remarks. I will now turn the call back to the operator and open the call for questions. Thanks.
spk00: Thank you. We will now begin the question and answer session. To join the question queue, you may press star, then 1 on your telephone keypad. You will hear a tone acknowledging your request. If you are using a speakerphone, please pick up your handset before pressing any keys. To withdraw your question, please press star, then two. We will pause for a moment as callers join the queue. The first question comes from David Amsalem with Piper Sandler. Please go ahead.
spk01: Hey, thanks. So, just had a few, starting with 201 and 202, and this is kind of a high-level question, but I thought it's important to ask. I mean, just given the underlying mechanism of these compounds, do you have a sense for what specific indications you think would be most appropriate for both 201 and 202. I know that's early, but wanted to just, you know, hear your thoughts on this sort of white space area. And to the extent that you move forward with both, should we think about sort of the topical being used in sort of a more mild to moderate disease setting and the oral being used in a more moderate to severe sort of disease setting as we see with other classes like, for instance, the JAK inhibitors. So just help us understand your thought process there. And then for 114, just understanding, knowing what we know about the JAK inhibitors, I guess the question here is from a safety tolerability perspective, not just that, but also from an efficacy perspective, given the nature of the market, what do you have to really see to make a go, no-go decision after you get your data next year? Thanks.
spk06: Hey, David. Dave, you were breaking up a bit. If I can summarize, you just tell me if this is what you're looking for. I think it was for 201 and 202 for our BEV platform, where the initial indications could potentially be. It's obviously early. We have some thoughts on that. The second question, I believe, was whether or not we would take the topical into more mild to moderate disease states versus moderate to severe, and the third question I've I believe you were looking for clarity on perhaps 114 relative to what's going on in a Jack class, but if you could confirm or let me know if it was something else.
spk01: Yeah, no, that's exactly right. Yeah, sorry for the bad connection.
spk06: Why don't we start with the Jack program and how we view our product. So I don't know, you want to provide some color on?
spk05: you know, how we see the benefits and the advantages of FMX114. Sure.
spk03: Hi, David. So, in relation to 114 and how we see it, obviously, differentiating relative to others in this space, and obviously, the recently approved topical JAK inhibitor from Insight. So, Dave kind of covered also in the prepared remarks. We do see this as the key benefits here being a multimodal impact on the disease state itself. The TOF-7 of the JAK inhibitor itself we know obviously can have exquisite impact on down-regulating key cytokines that drive inflammation in the skin and atopic dermatitis. But also we see great utility in actually preventing some of these auto-reactive lymphocytes, these key immune cells, from moving into the skin in the first place where they actually unload the majority of these pro-inflammatory cytokines that drive the disease. So this is where Fingolimod comes in. Fingolimod itself has the potential to inhibit and retain these autoreactive lymphocytes in the lymph nodes and therefore prevent those cells moving into the skin in the first place. So this is the extracellular mechanism that Dave talked about in the prepared remarks. But what we've also found, and others have found, is that Fingolimod itself has the potential to upregulate a key skin structure protein called filaggrin. that actually is really important in maintaining the epithelia in the skin, the epidermis. Now, we know that atopic dermatitis is really a disease state where the epidermis is effectively missing. So the ability to prospectively support recovery of the epidermis as the anti-inflammatory effects of the treatments are working is a key component. That's how we see it being quite differentiated away from any of the other topical portals, whether it be a JAK inhibitor or others who certainly don't have that potential. I hope that answers your question on that.
spk06: Yeah, I'll just add, too. Obviously, we're in the middle of our 1B component of this phase, 1B2A study for 1.14. The 1B component will provide meaningful PK data, which obviously would be helpful, especially in light of the recent class labeling around JAK inhibitors. You know, we have It certainly appears that even though it's class label for all JAKs, that this is really focusing, or the view from the FDA was focusing primarily on systemic JAKs. Dermatologists who are the prescriber of these products, they're used to seeing these types of labels. And we feel, obviously, very good about the prospects of this product, assuming it gets all the way through the clinic. And we hope to have, obviously, the top line results in the early part of the first quarter of next year, the PK data we should have before the end of the year. So we're quite bullish on the prospects of this program. I think on the 201, 202, bed inhibitor programs, As we outlined, we're very early in the development of both of these programs. The preclinical data we've seen so far for 201, you know, we're quite enthusiastic, quite pleased with. We're going to continue to take this molecule through a battery of additional animal models and biomarker studies that are ongoing. We're doing the prerequisite tox work for 201 now. There seems to be a significant level of enthusiasm from our scientific ad board and the general scientific community. We think that this program gives us a lot of utility. It's a lot of flexibility for where this product can go. We've talked about some of the more rare skin disease arenas. We've mentioned some, pyoderma gangrenosa and others. We're going to hold off on putting a you know, a line to stand on where we're exactly going to take it. We're really excited about where it could go. I think there's several different arenas. Ultimately, we want to develop products that address unmet needs for patients, and we think that this platform could do that. So you can anticipate that. I wouldn't characterize it, David, as being mild to moderate versus moderate to severe. Ultimately, the data is going to drive where we go, but I think as we've shown, as Ian showed today, There's a potent anti-inflammatory effect from this inhibitor platform, and we think that gives us a lot of flexibility in where we could take this particular product. I think when it comes to 202, as we mentioned last quarter, I would envision we'd be looking at some of the more broader INI indications, again, without specifically locking in on a particular disease. We've talked about, and our ad board saw that it could have potential in RA. It could have potential for IVD Crohn's, MS. Obviously, there's been work done in various oncology settings. Myeloproliferative disease is one. Now, whether or not we would go there ourselves is yet to be determined. But again, I think that the utility of this platform is quite significant. So we're eager to advance both these programs, and as it gets further down the line, we'll obviously be able to lock in on specifically where we take these programs for its first indication, both for the topical VETI as well as the oral VETI upon completion of final candidate selection. So hopefully that helps, David. Yeah, that does.
spk01: Thank you.
spk06: You got it.
spk00: The next question comes from Louise Chen with Cantor Fitzgerald. Please go ahead.
spk07: Hi. Good morning, everyone. This is Patrick Carvey in Philly. We have a few questions here. First, what is the breakdown of product sales? How much of it was coming from Amnit? How much was it from Celsius? We're interested in tracking the progress of these products. Second, I had the phase one B28 POC data for 114. Can you remind us how we should interpret the data once they come out? And lastly, on 201, on the presentation, there's a lot of promising images of the mouse model compared to vehicles, steroid, alcoholic gel, and you also included ex vivo analysis against a JAK inhibitor. So just want to see if you have done the same mouse model testing against a JAK and see the comparison. If so, what are the takeaways there? Thank you so much.
spk02: Yeah, sure. Good morning, Carby. This is Tyler. I'll take the first question on the breakdown of sales. So for the quarter, we had $4 million of product sales for Amzeek and Zilksy. We have not historically disclosed the breakdown and haven't provided guidance on what the split between products is. What I can point you to is if you take a look at the script data, just from a relative proportion, you know, that can give you a general direction, but at this point in time, we're not going to break the products down.
spk05: Ian, you want to talk about the 1B28, 1B214? Sure.
spk03: Hey, Kirby. So, yeah, the primary endpoint will be change in atopic dermatitis severity index. So, maybe just back up to the design itself. So, the Phase 1B patients will be, six patients will be treated for two weeks. There, as Dave said earlier, we're primarily evaluating, obviously, and pharmacokinetic information. The Phase II A portion of the study is four weeks with an additional two weeks open-label study. Same endpoints there. So, as I said, we're looking to report the data kind of in the early part of Q1 next year. And then I think, Carver, your question was on comparator information in the animal models for the bet inhibitor, topical bet inhibitor. We haven't done that yet, although that is certainly something we will be focusing on. We traditionally use glucocorticoid steroids as a control, but it's certainly something that will start to grow as we start to hone in on indications later.
spk07: Okay, great.
spk00: Thank you so much.
spk06: Thanks, Barb.
spk00: Once again, if you have a question, please press star, then 1. The next question comes from Patrick Dolezal with LifeSci Capital. Please go ahead.
spk08: Hi, thanks for taking the questions. So for the BET inhibitors, as a class, just curious what safety effects have emerged clinically and what gives you confidence that these may be averted by a topical approach in the case of 201 and the selective BD2 approach in the case of 202? And then just perhaps if you could detail the items outstanding to IND submission for each of those, that would be helpful. Thanks.
spk03: Hey, Patrick. I see him. So as you know, the majority of benhibitors in development are pan-BD, so they bind to BD1 and BD2. They're orally available, and they are primarily for oncology indications, although there's one in the cardiovascular space. So why do we think ours are differentiated from there? I think we'll start with what the types of adverse events you can typically see for an orally available PanBD inhibitor. They tend to be things like thrombocytopenias, gastrointestinal toxicities, emesis, vomiting, that kind of thing, flushing. Moving to 201, so topical, but inherently we have assumed we'll have a reduced systemic exposure there. But I think primarily we actually have factored in a metabolic liability into the molecule itself as part of the design principles from medicinal chemistry. So what that effectively means is that any 201 that is systemically exposed by the topical route will be rapidly cleared by the liver and inactivated. So that's a way where it's like a one-two punch there, one go topical and one induce this soft drug approach where we're specifically and consciously introducing a metabolic liability. On 202, the way we're addressing the pan-BD toxicity question is that there's certainly evolving information from others and with our own data that if you selectively bind to BD2, you tend to have an improved safety profile in general terms. Secondarily, it appears that the majority of pro-inflammatory signaling or genes that are activated, pro-inflammatory genes that are activated tend to be driven mostly through BD2. rather than BD1. BD1 has been implicated in driving the activation of genes, a lot of housekeeping genes. The work that Infoderm have done today I covered off in the prepared marks. We have exquisitely potent and highly, highly selective BD2 selected components already. Of course, we're developing additional work as goes on there. So I think that we are really addressing that from two components through the two projects. One is about a metabolic liability. and going topical with 201 and 202 going for a very selective BD2 inhibitor.
spk08: That's helpful. And just one follow-up. The preclinical data on composite inflammation severity in this mouse inflammation model looks solid, you know, very comparable to steroids. Just curious, should we be thinking about the magnitude of effect observed here or more so just that it's directionally favorable? And then as it relates to the biomarker data, are there any biomarkers in particular that are known to be pathogenic in a given disease state or are giving you excitement about future clinical development?
spk03: Yeah. So, just on your last point there, the fact that we have significant impact in pretty much all cytokines that drive TA17 immunology is particularly exciting. You saw from the slide there, we were, I mean, obviously, we are significantly down regularly in IL-17, IL-6, and others. So, again, this speaks to the broad applicability as an anti-inflammatory agent. Secondarily, you know, we were effectively equipotent to a class one superpotent steroid, which is quite rare for certainly newer generation of anti-inflammatory agents. So, I think to your earlier question, you should think about the potential having that super potent anti-inflammatory effect, but without the specific liabilities you would tend to see for long-term use of glucocorticoid steroids.
spk06: Yeah, I'll just piggyback on this, Patrick. Clobetazole, as Ian outlined, is a super potent steroid. That's That's a far cry from the over-the-counter hydrocortisone steroids that are out there. It's deemed a class one, and there's a reason why it's called a super potent steroid, because it's just that. And the fact that we, again, obviously this is early data, preclinical data, but the fact that we saw that level of response in line with what you see from clovidazole, super potent steroid, yet initial tolerance, tolerability data being very positive and encouraging just gives us a lot of enthusiasm about the prospects of obviously this molecule and this program for the entire platform.
spk08: Great. Thanks so much. Of course. Of course.
spk00: This concludes the question and answer session. I would now like to turn the conference back over to management for any closing remarks.
spk06: Well, thank you, operator, and thanks to everyone that took time out of your schedules to join this call. We look forward to continuing to provide an update on the progress of our business, and we wish everyone an enjoyable holiday season that's coming up over the course of the next few weeks.
spk05: We look forward to speaking with everyone soon. Thanks, and have a great rest of the week.
spk00: This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.
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