To build a generational company that deliv9o$ers transformational benefits to patients. Our engineering approach delivers novel antibodies against validated targets that are optimized across half-life extension, improved formulation, and manufacturing. As a result, we were able to achieve higher exposures, which could lead to improved clinical outcomes while dramatically reducing dosing burden for patients. Our lead program, APG777, is initially advancing in atopic dermatitis as a potentially best-in-class monotherapy that is currently testing higher exposures of IL-13 inhibition during the first 16-week induction phase, with the potential for improved efficacy. Following induction, we are testing every three- to six-mo1nth maintenance dosing. With this program, we believe we can transform the $50 billion-plus atopic derm market from an every-two-week paradigm with Dupixent while also potentially improving efficacy. Based on new data we are sharing today, we believe we have a path to improve dosing even further to an annual paradigm.
Imagine a world where pat* ients would need to get just one annual dose. Beyond atopic derm, 777 has pipeline and a product potential, and we expect to advance in the asthma and eosinophilic esophagitis to start. Next, we are advancing a number of potential first-in-class combination approaches, starting with IL-13 and OX40 Ligand in atopic derm, again with the goal of bringing best-in-class dosing and efficacy for patients with atopic derm. Shortly after, we plan to extend this approach to asthma and COPD. Each and every one of our combination therapies is designed to offer the same pipeline and a product potential as our monotherapies, unlocking multiple expansion opportunities and blockbuster markets. Our ultimate goal is to launch each treatment with the convenience of one simple single injection.
We are well capitalized to reach a number of key near-term milestones, including our phase 2, part A top line, 16-week data for 777 in atopic derm, which, thanks to strong enrollment, we're excited to share that this data is now anticipated earlier than initially guided, with a new timeline expected for mid-2025. Our lead program, APG777, is currently in phase 2 for atopic dermatitis, with critical efficacy data expected mid-next year. We share an overlapping binding site with Lilly's Ebgliss and specifically block signaling in the same way as both Ebgliss and Sanofi's Dupixent. Beyond our ongoing 777 mono trial in atopic derm, we plan to launch trials in two expansion indications, starting with asthma, where we expect to initiate a phase 1b trial in the first half of next year, followed by a phase 2b trial in the second half.
Eosinophilic esophagitis is following shortly after, with a phase 2 expected to initiate in 2026. We recognize that the future of I and I rest in combinations, and our first combination study in atopic derm patients is expected to start next year, giving us another shot to achieve best-in-class efficacy while maintaining best-in-category dosing of every three months or even better. And we plan to run this study head-to-head with Dupixent, the market leader, and truly put our combo to the test. We believe that we will be the first to bring combinations of validated mechanisms to atopic derm, and we are just getting started. We plan to extend these combinations with potentially paradigm-shifting efficacy to asthma and COPD, where significant unmet need remains for these very large markets.
Today, we're excited to announce significant progress across our pipeline, starting with interim phase 1 data for 808, showing it is well tolerated with a PK profile that enables every two- or three-month dosing, which would be a significant improvement over Dupixent's every two-week dosing. This exceeded our expectations and gives us incredible optionality moving forward. For 777, updated 12-month SAD and 9-month MAD data continue to support a potential best-in-class profile, including a final half-life of 77 days. That is approximately three times better than Ebgliss and supports the every three- or six-month maintenance dosing we are currently testing. Updated biomarker data suggest we could go even further. A single dose of 777 led to near-complete inhibition of the pathway out to a full year, supporting the potential for annual dosing.
We've also made significant progress on our combo approaches, with preclinical proof of concept achieved for both our 777 and 990 combo in atopic derm, and our 777 and 333 combo in asthma and COPD. We also achieved co-formulation proof of concept for our 777 and 990 combo that could enable us to provide transformational efficacy in atopic dermatitis while maintaining best-in-category dosing. Apogee has the potential to transform the atopic dermatitis market. We are currently testing every three or six-month maintenance dosing, with a path to an annual dosing option for 777. This innovation alone would be completely transformational, but we also have three opportunities to improve efficacy outcomes for patients with atopic dermatitis. First, in the part A portion of our phase 2 study, we are testing 30%-40% higher exposures or drug levels of 777 compared to Ebgliss and induction.
Multiple pieces of evidence suggest these higher exposures could lead to better efficacy. The 16-week readout for this study is expected in mid-2025, followed by the 52-week maintenance portion of this study expected to read out in the first half of 2026. Second, in the part B portion of our phase 2 study, we will be testing even higher exposures than in part A to fully explore the potential of the IL-13 mechanism and ensure we do not leave any remaining efficacy on the table. The 16-week readout for part B is expected in the second half of 2026. Finally, in 2025, we plan to take forward the first rational combination approach in atopic dermatitis, where we'll be looking at combining the two orthogonal mechanisms with the greatest clinical validation, IL-13 and OX40L.
We expect to have initial results from this head-to-head trial with Dupixent in the second half of 2026. We have three opportunities for better efficacy in our pipeline in the next few years, with each approach having dosing that is expected to launch with up to 13 times fewer injection days than currently available treatments. Apogee is building a next-generation biotech with three waves of innovation over the coming years. Today's data continue to build our conviction that 777 could be a best-in-class treatment for atopic dermatitis, with the potential for both transformative dosing and better efficacy, an unprecedented advance that could translate into mega blockbuster status for 777 and the future more than $50 billion atopic derm market. Today's announcement that we've accelerated our anticipated phase 2 part A readout to mid-2025 brings us one step closer to that goal.
Beyond atopic derm, we believe 777 monotherapy has massive pipeline and a product potential with a path to leadership and over 10 potential expansion indications, many of which are blockbuster markets in their own right. Our vision includes building a franchise in atopic derm and other I and I conditions. We expect 777 to be followed by our combination approaches that could provide transformative efficacy while maintaining best-in-class dosing, with even greater pipeline and a product potential than our monotherapies, given the broader mechanisms being targeted. For the next section, I'll hand it over to Carl, our Chief Medical Officer, to cover several exciting clinical updates on our 777 and 808 programs.
Thanks, Michael, and good morning, everyone. I'm Carl Dambkowski, the Chief Medical Officer at Apogee, and this morning I'm excited to share our interim phase one results for APG808. Our interim data demonstrate the potential for best-in-class every two- to three-month dosing, a significant decrease compared to Dupixent, which is dosed every one- to two-week. APG808 was engineered to take the best of IL-4R alpha biology and Dupixent. APG808 has a similar mechanism and overlapping epitope to Dupixent, binding to IL-4R alpha in a similar manner. APG808 has femtomolar affinity for IL-4R alpha, which is an approximately 30-fold stronger affinity compared to Dupixent and could provide important advantages, including the potential to match Dupixent's activity at lower exposures. For the phase one APG808 trial, we set clear goals for what we needed to achieve in terms of safety, PK, and exposure targets for APG808.
In addition, we saw upside opportunity in looking at key biomarkers. Consistent with the IL-4 receptor alpha class, we tested doses up to 1200 milligrams and found the doses to be well tolerated based on initial data. On half-life, we observed a well-behaved PK profile across all cohorts. While our target was an at least 42-day half-life, we exceeded that with an approximately 55-day half-life when at or above target exposures. This is more than five times longer than Dupixent's half-life. The optimized PK profile demonstrated by APG808 is expected to enable up to every two-month dosing with modeled exposures comparable to Dupixent, exceeding our initial goal of every six-week dosing. In addition, we achieved a number of highly complementary supporting data for APG808.
These data include positive prolonged PD effects across the key target engagement biomarkers, pSTAT6, where we observed near-complete inhibition of pSTAT6 for three months above target exposures, which enabled the potential for even less frequent dosing at every three months. In addition, we saw deeper TARC reductions versus Dupixent, supporting APG808's robust activity in this study. The data we'll disclose today is from our ongoing phase 1 healthy volunteer study. We tested doses up to 1200 milligrams. This trial is fully enrolled with at least three months follow-up on all four cohorts, and today we will be presenting interim data on safety, PK, and biomarkers. Here you can see the baseline characteristics of participants in the study, which are in line with what you'd expect for a phase 1 study. Demographics were well balanced across cohorts.
APG808 has been well tolerated with a favorable safety profile across all cohorts, including doses up to 1,200 milligrams. The safety profile is in line with expectations for therapies targeting IL-4 receptor alpha, including Dupixent, which have a well-documented and benign safety profiles. AEs have been mild and generally unrelated to study drug. We've had only one SAE unrelated to study drug. We have seen only injection site reactions in three participants in this study. All have been mild and limited in duration. There have been no cases of conjunctivitis. APG808's PK profile has been favorable. The half-life of APG808 is approximately 55 days at or above target exposures, which is more than five times longer than Dupixent's published half-life of approximately nine days. The optimized PK profile demonstrated by APG808 is expected to enable an up to every two-month dosing regimen while maintaining exposures similar to Dupixent.
Here we have modeled exposures for an every two-month dosing regimen. As you can see, this regimen is expected to have exposures that are comparable to those of Dupixent while reducing the number of annual injection days to just six days per year versus 26 for Dupixent, a more than four-fold reduction in the number of injection days annually. In this study, APG808 showed an effect on two key biomarkers for IL-4 receptor alpha target engagement and pathway activation, which are PSTAT6 and TARC. PSTAT6 is the first downstream biomarker and a more sensitive biomarker of IL-4 receptor alpha pathway engagement. Therefore, it is a critical measure to demonstrate APG808's inhibition of this key inflammatory pathway. TARC is a key inflammatory biomarker that is robustly decreased with Dupixent treatment, enabling comparison to APG808.
In our phase 1 study, APG808 showed deep and sustained inhibition of both of these biomarkers, consistent with APG808's extended half-life. Our phase 1b in patients with asthma, which we'll discuss more later during this presentation, has the potential to further validate APG808's differentiated profile with initial FeNO data expected in the first half of 2025. FeNO is a biomarker of T2 inflammation in patients with respiratory disease. Here we see our pSTAT6 data from the clinic, where we saw that a single dose of APG808 led to near-complete and prolonged inhibition of pSTAT6 up to and including three months after dosing. As I mentioned earlier, we performed this assay by stimulating whole blood with IL-13. For the data shown here, we stimulated the levels of IL-13 nearly 300-fold those in the lung sputum of severe asthma patients, modeling some of the pathophysiology we'd expect in type two respiratory diseases.
This makes the robust durability observed out to three months with APG808 supportive of our ability to reach every two-month or even potentially every three-month dosing, consistent with APG808's five times longer half-life and 30 times greater affinity for IL-4 receptor alpha compared to Dupixent. For TARC, we have a clinical comparator from a non-head-to-head study in healthy volunteers, as Dupixent also looked at TARC changes after a single dose in their phase one healthy volunteer study. At similar single doses, APG808 shows greater depth of TARC reduction than Dupixent over eight weeks. So, for both PSTAT6 and TARC, two key inflammatory biomarkers for type two inflammatory diseases, we see deep and consistent responses after a single dose of APG808, including near-complete PSTAT6 inhibition for up to and including three months after dosing. With APG808, we set out to create an optimized antibody.
On the left-hand side, you can see the antibody attributes for APG808. APG808 targets IL-4 receptor alpha and binds to a clinically validated epitope that overlaps with Dupixent, but with much higher affinity, more than 30 times greater than that of Dupixent. Today, we have shown the translation of this antibody engineering approach into the clinic. On the right-hand side, you can see the clinical profile of APG808 is favorable. APG808's PK profile enables up to every two-month dosing with exposures comparable to Dupixent and a path to reach every three-month dosing based on the extended PD effect for pSTAT6. We will continue to examine the potential for APG808 based on this phase 1 healthy volunteer data in asthma patients.
We expect asthma data in the first half of 2025, including key FeNO data, where we have a goal of seeing similar maximal suppression of FeNO compared to Dupixent and other agents, but with prolonged durability supporting the potential for every two- or three-month dosing as discussed today. The healthy volunteer data from today and the asthma data first half of 2025 for APG808 will position us to follow the science and think about potential combinations with this program, especially where IL-4 biology is critical to the disease. Given the every three-month dosing is likely at the upper end of APG808's potential, we are currently prioritizing APG777 as a monotherapy and the backbone for our combination, including dermatology and respiratory combination due to its strong differentiated profile that is emerging for APG777 and the fact that IL-13 biology is the critical biology for our current indications.
We now discuss updated APG808 data, which includes the potential for annual dosing.
Interleukin-13, or IL-13, is a small protein known as a cytokine, which stimulates the immune system and is overactive in people with Type 2 inflammatory diseases like atopic dermatitis, asthma, and COPD. IL-13 signals the immune system by bringing together two receptors on the cell surface, IL-13 receptor alpha-1 and IL-4 receptor alpha, which starts an inflammatory process that leads to the signs and symptoms of diseases like atopic dermatitis, asthma, and COPD. APG777 is a monoclonal antibody being developed for atopic dermatitis and other chronic inflammatory diseases like asthma and COPD. APG777 works by binding and inhibiting the action of the inflammatory cytokine IL-13. By binding to IL-13, APG777 can prevent the IL-13 receptor alpha-1 and IL-4 receptor alpha from binding to each other and interrupt the inflammatory signal that leads to the signs and symptoms of inflammatory conditions.
Once inside the body, all antibodies and their bound targets are subject to degradation when they are internalized by cells. However, APG777 has been specifically designed to harness the power of the body's natural recycling mechanism for antibodies, allowing it to be returned to circulation where it can continue to work. As a result, APG777 has a half-life of 77 days, three to five times longer than a typical antibody. APG777, an optimized monoclonal antibody, may be administered two to four times per year compared to 13 to 26 injections with currently available antibodies due to its extended half-life. This dosing, along with the potential for improved clinical outcomes due to an optimized PK profile, could be transformational for patients with chronic inflammatory diseases.
I hope you enjoyed learning a little more about how APG777 was designed to be an optimized antibody. In March of this year, we presented interim data from the phase 1 healthy volunteer trial that exceeded all trial goals, including safety, PK, exposure, and PD targets. Today, we are excited to share additional follow-up data, including completion of follow-up from all SAD cohorts, which showed a best-in-class 77-day half-life, supporting our ongoing every three to six-month dosing in the maintenance setting of atopic dermatitis and PD data that further supports potentially even less frequent annual dosing with pSTAT6 inhibition for up to 12 months. Together, this PK profile supports our phase 2 dose regimen, which tests higher exposures in the induction setting of atopic dermatitis and best-in-class dosing in the maintenance setting of just two to four injections per year.
Due to strong enthusiasm from the atopic dermatitis community and Apogee's focus on operational excellence, enrollment has proceeded ahead of schedule, and we are excited to announce today that we expect to have our phase 2 16-week data in mid-2025, accelerated from our initial guidance of second half 2025. The data we'll discuss today is from our ongoing phase 1 healthy volunteer study with a SAD and a nested MAD design. In the SAD component, we have tested doses up to 1,200 milligrams, and in the MAD component, we have tested repeat doses of 300 milligrams. The SAD portion is complete with 12-month follow-up on all cohorts. The MAD portion is ongoing, and today we will present up to nine-month follow-up data. APG777 continues to be well tolerated with a favorable safety profile across all cohorts, including single doses of up to 1,200 milligrams.
The safety profile is in line with expectations for therapies targeting the IL-13 pathway, such as Ebgliss and Dupixent, which have well-documented and benign safety profiles. AEs have been mild and generally unrelated to study drug. There have been no SAEs and no dose-dependent AE trends. With final SAD data, APG777 demonstrated a best-in-class half-life of 77 days, in addition to dose proportionality and low variability. This optimized PK profile will enable our phase two dose regimen, which tests higher exposures in induction compared to Ebgliss with approximately 50% fewer injections and similar exposures in maintenance compared to Ebgliss with an up to 13-fold decrease in the number of injections per year. As previously released in this study, APG777 had an effect on the two most important biomarkers for IL-13 targeting in atopic dermatitis, which are pSTAT6 and TARC.
pSTAT6 is the first downstream biomarker and the most sensitive biomarker for IL-13 inhibition. Unique to the way this assay is run, we can use ex vivo stimulation with IL-13 to simulate disease conditions in the blood of healthy volunteers. TARC is an inflammatory biomarker in atopic dermatitis with good correlation to induction treatment efficacy. Unique to this biomarker, we have data from single doses of Dupixent in healthy volunteers through 12 weeks, which allow us to contextualize the APG777 data, especially as it relates to maximal pathway suppression. Updated pSTAT6 data through 12 months of treatment show a single dose can show near-complete inhibition for an entire year at the highest dose tested, 1,200 milligrams, and dose-dependent inhibition for the other doses out to six and nine months for 300 milligrams and 600 milligrams, respectively. We perform this assay by stimulating whole blood with IL-13.
We are stimulating with levels of IL-13 nearly 500-fold those of the levels seen in lesional skin of AD patients. So, in a way, we can recapitulate in these healthy volunteer blood samples some of the pathophysiology we would expect in atopic dermatitis. This makes the robust durability we observed out to 12 months from a single administration supportive of our current maintenance regimens of every three and six months, as well as provides us a potential path to an annual dosing regimen in the future. Uniquely, for our second biomarker, TARC, we have a clinical comparator from a non-head-to-head study in healthy volunteers, as Dupixent also looked at TARC changes after a single dose in their phase 1 healthy volunteer study.
At similar single doses, APG777 shows deeper inhibition of TARC compared to Dupixent and also shows prolonged inhibition out to 12 weeks when compared across the same time points. So, both pSTAT6 and TARC, the two most important biomarkers for IL-13 targeting in atopic dermatitis, show deep and sustained changes in response to a single dose of APG777, including near-complete pSTAT6 inhibition up to one year after a single dose, potentially supporting development of an annual regimen in the future. Multi-dose cohort data has been consistent with single cohort data for APG777. In multi-dose cohort two, where 300 milligram injections were given two weeks apart, similar to the timing of initial injections during our phase 2 trial, pSTAT6 showed near-complete inhibition up to and including six months after initial treatment, the longest available follow-up at time of data cut.
Further, TARC showed deep and prolonged inhibition out to six months after initial treatment, again the longest available follow-up at time of data cut. The additional data presented today, both pSTAT6 and biomarker data, continue to support our phase 2 goals for induction and maintenance. The goal of the APG777 phase 2 induction regimen is to provide 30%-40% higher exposures versus Ebgliss during the first 16 weeks of treatment, but with approximately half the number of injections. This goal is really based on three sources of evidence that support the hypothesis that higher exposures could lead to better efficacy. First, Ebgliss's phase 2b showed dose response that did not plateau and, importantly, did not show any dose AE relationship or exposure AE relationship.
Second, data from Ebgliss's EMA approval showed that lower body weight, which was associated with about 30% greater exposures, showed consistently greater efficacy across all key endpoints, including the most stringent endpoints of EASI-90 and IGA 0/1. And third, based on Ebgliss's exposure response model, we predict that better efficacy could be possible with higher exposures. In the maintenance setting, the goal is to equal Ebgliss's exposure since, in contrast to induction, higher maintenance exposure does not appear to provide additional benefits for patients. In maintenance for APG777, we will examine regimens of every three and six-month dosing, which are anticipated to have exposures that will at least equal those of Ebgliss while reducing the injection burden up to 13-fold compared to the current standard of care.
Our integrated phase 2 trial is ongoing now with an expected readout for the part A 16-week induction data in mid-2025, accelerated from our initial guidance of second half 2025 due to strong enthusiasm from the atopic dermatitis community and Apogee's continual focus on operational excellence. This readout will focus on the induction data from approximately 110 patients with an APG777 regimen that has 30%-40% greater exposures compared to Ebgliss. After part A finishes enrolling, the part B dose optimization portion of the study will begin enrollment, testing three dose regimens versus placebo. To continue to optimize APG777, this portion of the study will test one dose higher and one dose lower than the APG777 part A induction regimen, which will be maintained as the mid-dose in part B.
Our goal for the phase 2 trial of APG777 in atopic dermatitis is to ensure that we do not leave any efficacy on the table. Like in part A, after induction, all patients benefiting from treatment will have the option to continue to maintenance treatment, where patients will be re-randomized to every three or every six-month dosing regimens. This portion of the study will enroll approximately 280 patients, of which up to 20% will have had prior Dupixent experience. Based on recent Ebgliss data, these patients are expected to respond similarly to biologic naive patients. Therefore, the N has been reduced from our prior plans of 360 patients to 280 patients to further accelerate time to approval while maintaining greater than 90% power for primary and key secondary endpoints.
We believe this integrated phase 2 design will allow us to test APG777's potential, both in terms of the potential for greater efficacy in the induction period with an optimized dose regimen and maintenance dosing of just two to four times per year in up to 13-fold decrease compared to the standard of care. In this study, APG777 will have the opportunity to demonstrate its potential for both best-in-class efficacy and best-in-class dosing. We look forward to presenting this data now in mid-2025. Thanks, Carl. APG777 is the foundation of our plan to build a leading franchise in AD. The next step on that journey is our APG777 plus APG990 combination, which targets both IL-13 and OX40L for potentially broader inhibition of heterogeneous inflammatory pathways in AD. To tell us more about the importance of broader targeting of heterogeneous inflammation in atopic dermatitis, it is my pleasure to introduce Dr.
Emma Guttman-Yassky, an internationally renowned leader in dermatology and immunology. Dr. Gutman is Assistant Chair of the Department of Dermatology and the Waldman Professor of Dermatology and Immunology at the Icahn School of Medicine at Mount Sinai, New York. She also directs the Center for Excellence in Eczema and the Laboratory for Inflammatory Skin Diseases. Dr. Guttman's major research focus areas are atopic dermatitis and alopecia areata. Her research has transformed our understanding of the immunological mechanisms driving these disorders and paved the way for novel therapeutics. More recently, her research has expanded to other chronic skin conditions, including hand eczema, keloids, and ichthyosis. Dr. Gutman has received numerous prestigious awards, including the Quad AI Award for Scientific Innovation and the AAD Young Investigator Award.
She was elected as a member of the American Society for Clinical Investigation and the American Dermatological Society and is widely recognized as a leader in her field with over 400 peer-reviewed publications. It is a privilege to have Dr. Guttman-Yassky with us today. Her talk today will focus on the heterogeneity of atopic dermatitis and the potential for broad cytokine targeting to improve outcomes for patients. Hi, everyone. My name is Emma Guttman-Yassky, and I'm coming from New York City. And thank you so much for inviting me to speak here. And I'm going to speak on one of my favorite subjects, cytokine targeting for atopic dermatitis to address heterogeneity in patients. So, atopic dermatitis is the most common inflammatory skin disease, about 7% of the adults in the U.S., about 15% of the children, so a very sizable population.
About 40% of these patients will have moderate to severe disease. Until recently, we really didn't have much to give them. Now we have treatments coming, but we still have an unmet need left to treat our patients, particularly for long-term disease control. However, the therapeutic drought is finally ending with new treatments coming to the market and others in clinical trials. Another important concept is the idea that the inflammation is more than skin deep in atopic dermatitis. So, if you have a red lesion on the surface, remember the patient may have systemic inflammation. That's particularly true in those patients that have significant body surface area involvement, particularly when it's more than 10% of their body. That's also documented by large population-based studies showing cardiovascular disease in patients with atopic dermatitis.
Remember that patients need systemic treatment when they have more than 10% of the body involved in atopic dermatitis. Importantly, the chronic inflammation in atopic dermatitis involves activated T cells. These are really central to the pathogenesis of atopic dermatitis. Of course, we are talking primarily of TH2 and TH22 with the IL-4, IL-13, IL-5, and IL-31 cytokines, but also IL-22 that is important to the hyperplasia of atopic dermatitis. Interferon gamma is important in chronic stages. In some instances, the TH17 pathway and IL-17 are also important in atopic dermatitis patients. Another important concept is that the disease is not a one-size-fits-all. It's highly heterogeneous and involves multiple immune pathways and cytokines based on the disease age of onset, duration, ethnicity, IgE, comorbidities, and many other factors.
So, we need to keep that in mind when we want to treat all our patients with atopic dermatitis successfully and not only a given subset. Now, importantly, we now have finally multiple treatments to treat patients with atopic dermatitis. So, we have tremendous advances, right? We have the TH2 pathway agents, dupilumab, and then the new IL-13 antagonist, tralokinumab, and now lebrikizumab. We have JAK inhibitors. But we know that now with the TH2 targeting agent, still clearance or almost clearance, so either EASI-90 or IGA 0/1 is usually achieved by up to 30% of patients. What does it tell us? That still the majority of our patients need something else, right, to really achieve that 100% disease control. And JAK inhibitors target more pathways. So, yes, they are more efficacious, but they have some safety concerns and they have black box warnings.
So, we need to keep that in mind too. So, we still have ways to go to really treat safely more of our patients with atopic dermatitis. And we know from real life that while dupilumab is a great treatment and the IL-13 antagonists are a great treatment, again, we don't have that 100% disease control in the majority of patients like we have in psoriasis, where with some treatments we now achieve EASI-100 in 80% of the patients. So, that's not the case yet in atopic dermatitis, where still we have full clearance only achieved in up to a third of our patients. Now, a new kid on the block is the OX40, OX40 ligand axis. This is a new exciting pathway in atopic dermatitis. And we have OX40 ligand on one hand and OX40 on the other hand and several new treatments targeting these.
Rocatinlimab is going after the receptor, after OX40 receptor, and Amlitelimab is going after OX40 ligand. And targeting this pathway is really important for targeting memory cells, memory T cells. What are these cells and why are they important? They are important because they harbor the memory, that delusional memory. So, basically, they are initiating again new lesions in patients. And it is important to target them when we think about the longevity of disease control because that may raise the idea of maybe targeting patients only a few times a year, every 12 weeks, every eight weeks. We do not know yet, but it's possible to spread a little bit the injections or giving a certain drug. And maybe after a while, we can maybe stop the treatment and not treat patients anymore. That's my own wishful thinking, but I think it may be possible.
Now let's review the phase 2 with amlitelimab that is an anti-OX40 ligand for patients with atopic dermatitis. Here we see nice data both at week 16 and week 24 with nice differentiation from placebo, not really a dose response, but really nice differentiation from placebo, both with rescue and without rescue. We also see this supported by the biomarker data, both the Th2 biomarker data, eosinophils, IL-13, and TARC, that's CCL17, that are in different directions from placebo, and also IL-22 that is also differentially expressed compared to placebo. This is also seen with rocatinlimab that targets OX40 both at week 16 and 24, very nice clear-cut data, again supported by nice biomarker work with CCL17, OX40 positive cells in blood, IgE, and IL-22. Now let's review another important concept, the concept of tape stripping. What is tape stripping?
In my lab, I helped develop this approach for inflammatory skin diseases, and tape stripping is based on the idea that we take a tiny tape and we apply it multiple times to the skin or different tapes we apply to the skin, and we collect these and collect the RNA from the tapes to really identify the molecular phenotype of a patient and of a skin disease, and then we compare between diseases, we compare with controls, we can compare between treatment arms before and after treatment, and so on, so this really, I think, is important in getting more patients to give samples because it's non-invasive or minimally invasive and allows us to sample the skin in patients in clinical trials and studies and learn about many patients and how the disease is correlated with their disease.
In this study, we compared head-to-head, actually, in the same patients' biopsies and tape strip data in lesional skin. Taking the bird's eye view, we already see that in tape strips, you really are able to identify many, many biomarkers. This is compared to controls that look familiar, right? You have IL-13 there, you have CCL17 there, you have OX40 there. So these are important key biomarkers of atopic dermatitis. You see more biomarkers, actually, compared to biopsies, where you do see maybe in higher magnitude. Here the size of the letter is compatible with the fold changes of difference compared to healthy controls. You do see that in biopsies, you see the S100s and IL-22 that are linked to hyperplasia front and center.
This is because these are a little bit lower in the epidermis, and we can detect them maybe better in biopsies. But they are still detected quite well also in tape strips. We can conclude that tape strips are a very good way to understand the phenotype of atopic dermatitis. Now let's review what different treatments are doing to different immune pathways. Both dupilumab and IL-13 antagonists are definitely targeting TH2, right? This is their bread and butter. This is what they need to target. This is also targeted by JAK inhibition with abrocitinib and also targeted by rocatinlimab. What ab okout targeting other immune pathways like TH17 and TH22? This is again targeted by dupilumab indirectly, of course targeted by abrocitinib and targeted also by rocatinlimab. What about TH1? TH1 is unique.
It is, of course, targeted by abrocitinib, targeted by rocatinlimab, but here dupilumab and TH2 targeting will not do anything, so dupilumab did not do anything to TH1 markers like interferon gamma, CXCL10, and sometimes when we need to target patients completely, we may need to also target the TH1 axis, so future treatments, I think, if we look into the future, what should future treatments do? They need to balance efficacy with safety, but they need a little bit deeper targeting. They need to target TH2, of course, that's the holy grail of atopic dermatitis and TH22, but potentially also to some extent TH1 and TH17 to really capture more of that disease phenotype in atopic dermatitis patients across the entire spectrum of our patients, so I think that will be the future, and with that, thank you so much for your attention. Thank you, Dr. Guttman-Yassky.
Good morning, everyone. I'm Becky Dvorak, Chief Development Officer at Apogee. I'm excited to present our preclinical data in support of our APG777 and APG990 combination program for treatment in atopic dermatitis. As Dr. Guttman-Yassky discussed today, atopic dermatitis is a heterogeneous T cell disease driven by type 1, 2, and 3 inflammation. T cell mediated type 2 inflammation is the central driver of atopic dermatitis characterized by increased levels of inflammatory mediators such as IL-13 and TARC. We have the potential to provide greater type 2 inhibition and better efficacy via higher exposures of APG777 in our ongoing phase 2 clinical trial. However, we know that type 1 and type 3 inflammation also contribute to atopic dermatitis, especially in specific subpopulations, as noted by Dr. Guttman-Yassky. Type 1 inflammation is characterized by increased interferon gamma levels, while type 3 can be characterized by release of IL-22.
Collectively, type 1, 2, and 3 immune activation manifest as chronic lesions, increased inflammation, barrier disruption, itch, and ehpidermal thickening. Clinical data for Dupixent and Ebgliss support that type 2 inflammation is the key driver of atopic dermatitis. While amlitelimab suppresses type 1, 2, and 3 inflammation, its clinical biomarker data show that inhibition is partial and amlitelimab has lower clinical efficacy versus Dupixent and Ebgliss. When we look at clinical data for both Dupixent and Ebgliss, the data support suppression of type 2 inflammation as the driver for clinical response. In contrast, JAK inhibitors, which effectively block and inhibit all types of inflammation, show the potential efficacy and strong clinical responses that can be achieved with broader inhibition. Unfortunately, the use of JAK inhibitors has safety considerations and are limited by a black box warning.
We believe APG777 and 990 could provide a significant combination benefit by broadening the inhibition profile to include not just type 2, but also type 1 and type 3 inhibition, potentially approaching JAK-like efficacy. The combination of APG777 and 990 has the potential for greater efficacy over monotherapy alone. APG777 and 990 combine two well-tolerated and effective mechanisms of action for potentially broad inhibition of type 1, 2, and 3 inflammation, similar to the broad inhibition profile observed for JAK inhibitors. However, unlike JAK inhibitors, the safety and tolerability profile for the APG777-990 combination is likely to be significantly better. As a brief reminder, both APG777 and APG990 monoclonal antibodies have been engineered for best-in-class properties against clinically validated targets. Both APG777 and 990 share an overlapping epitope and similar potency to lebrikizumab and amlitelimab respectively. Both antibodies are Fc engineered for extended half-life in vivo.
For APG777, updated phase 1 data announced today show a 77-day human half-life that is three times longer than lebrikizumab. Our preclinical data show an extended 26-day half-life for APG990 in non-human primates versus 21 days for amlitelimab. To explore the anticipated benefit of targeting type one, two, and three inflammation, we applied a preclinical model of allogeneic lymphocyte reactions, abbreviated here as ALR, which use primary human cells. We tested dupilumab and lebrikizumab, which are the active ingredients in Dupixent and Ebgliss, respectively. As expected, both agents mediate a deep type 2 inhibition as characterized by TARC levels. However, we do not see inhibition of the type one and type three inflammation markers interferon gamma and IL-22. For dupilumab, we observed a substantial increase in type three inflammation as measured by IL-22. We observed a similar trend for lebrikizumab, but to a lesser extent.
These findings are consistent with reports that some Dupixent-treated patients have elevated serum IL-22 and related side effects. While dupilumab and lebrikizumab show substantial type 2 inhibition, we know from JAK inhibitors that broad inhibition of type 1, 2, and 3 is important for maximizing efficacy. Amlitelimab targets OX40 ligand and has demonstrated broad inhibition of inflammatory biomarkers and was well tolerated in clinical studies. However, amlitelimab only partially inhibits type 2 inflammation, and that may explain its lower efficacy compared to Ebgliss and Dupixent, which more deeply inhibit type 2 inflammation. Our preclinical ALR studies affirm what has been observed with amlitelimab in the clinic, namely a broad inhibition profile with partial inhibition of type 2 inflammation versus lebrikizumab and dupilumab. This suggests combining OX40 ligand inhibition with deeper type 2 inhibition could provide greater clinical efficacy.
APG777 and APG990, a potentially first-in-class combination of IL-13 and OX40 ligand inhibitors, is designed to achieve both broad and deep inhibition that could translate to best-in-class clinical efficacy in atopic dermatitis. In our preclinical ALR model, we clearly demonstrate this potentially best-in-class profile with deep type 2 inhibition similar to lebrikizumab and dupilumab, while also inhibiting type 1 and type 3 inflammation markers at levels comparable to amlitelimab. In addition to the potential for best-in-class efficacy, our APG777-APG990 combination could also provide greater convenience for patients with the potential for every three-month dosing or less frequent dosing compared to every two or four weeks for approved monotherapies. Here we directly compare APG777 and APG990 to upadacitinib, the active ingredient in Rinvoq, the leading JAK inhibitor for atopic dermatitis.
Our APG777-990 combination shows inhibition of type 1 and type 3 markers more similar to upadacitinib, with similar type 2 inhibition as lebrikizumab and dupilumab. In atopic dermatitis and other immune disorders, there is often chronic type 1 inflammation mediated in part by alarmins that we want to inhibit. However, type 1 inflammation can also be induced by viral antigens, which is important for the body's ability to fight off infection. One issue with JAK inhibitors is that they strongly inhibit type 1 inflammation non-selectively, blocking both chronic type 1 inflammation associated with atopic dermatitis and acute type 1 inflammation associated with antiviral immune responses. In our preclinical assays, we observed this non-selective type 1 inhibition by JAKs.
Upadacitinib, tested at the projected Cmax of the clinically relevant concentration, inhibits both alarmin-induced and viral antigen-induced type 1 responses as assessed by ALR and by a viral antigen T cell recall assay. In contrast, APG777-990 and amlitelimab selectively inhibit type 1 inflammation, blocking chronic type 1 inflammation driven by alarmins while preserving type 1 inflammatory response to viral antigens. The trends we observe in our preclinical experiments are consistent with clinical experience. JAK inhibitors carry a black box warning for infection risk, while amlitelimab, Ebgliss, and Dupixent have not shown issues with increased infection risk. This suggests that the APG777-990 combination could achieve broad inhibition of type 1, 2, and 3 inflammation while potentially avoiding the tolerability issues associated with JAK inhibitors.
In summary, our preclinical studies demonstrate that our APG777-990 combination achieves deeper and broader inhibition of type 1, 2, and 3 inflammation, which could translate into improved clinical responses in a wider patient population. Today, we are also excited to announce that we have established initial proof of concept for our 777-990 co-formulation, which could enable us to provide transformational efficacy in atopic dermatitis while maintaining best-in-class dosing. Co-formulations could enable potentially best-in-class efficacy while maintaining best-in-class dosing. We believe a co-formulation approach has several potential benefits relative to bispecific therapeutics. With half-life extension technology incorporated into each of our products, we believe the dosing frequency of three months or less frequent will offer a significant improvement over the other therapeutic options. An added benefit for co-formulation is the potential to investigate and optimize the dose level of each individual component to achieve the desired clinical result.
Like bispecific therapies, the co-formulation approach will allow convenient dosing administration with delivery by prefilled syringe and/or autoinjector presentations. Due to the relative ease of developability and the high yields associated with monoclonal antibody manufacture, a low cost of goods is expected. The co-formulation approach is not a new one, as you can see. There have been a significant number of approvals of these products in the last 20 years. Our goal with APG777-APG990 is to deliver both best-in-class clinical efficacy and dosing frequency in a convenient delivery format for patients. In our co-formulation studies, we are excited to report that we have demonstrated proof of concept results demonstrating that APG777 and APG990 are compatible with co-formulation, achieving the stability, injectability, product quality, and potency profiles that are compatible for use in prefilled syringes, important for providing a patient-convenient delivery presentation.
In our proof of concept studies, we have demonstrated that APG777 and 990 can be co-formulated at high concentrations greater than 150 mg/mL and encompassing a wide range of product ratios, providing future clinical dosing flexibility. Our proof of concept study results have demonstrated highly similar stability of the co-formulations relative to both APG777 and APG990 individually across all product attributes. In addition, due to the formulation development work performed, the viscosity of the co-formulations at all product ratios tested is at levels suitable for both prefilled syringe or autoinjector formats. We anticipate achieving injection times consistent with those of Dupixent in these formats. Our data demonstrate that our 777-990 co-formulations maintain similar product quality attribute profiles across various co-formulation ratios and relative to each of the individual components.
Here we show co-formulation potency data, a key product quality attribute as determined by two antigen binding affinities after accelerated storage condition exposure. As you can see, the results demonstrate that both APG777 and APG990 retain their target binding potency in the 50/50 co-formulation mixture when compared to their respective single-agent formulations. Similar results were achieved across all product attributes tested in our proof of concept study, giving us a high degree of confidence in co-formulation. With both preclinical proof of concept showing the APG777-990 combination potential for deeper and broader inhibition, as well as initial proof of concept for co-formulation, we believe the APG777-990 combination has the potential to deliver both transformational efficacy and best-in-category dosing for patients.
For the next section, I will hand it back to Christine, our Senior Vice President of Clinical Development, who will discuss our plans to bring APG777-990 into the clinic with our first trial expected to initiate in the first half of 2025. Thanks, Becky. Our path to developing the combination of APG777 and APG990 starts with understanding the profiles of each monotherapy component. Earlier today, Carl shared phase 1 data reaffirming APG777's potential for best-in-class dosing for the treatment of moderate to severe AD. APG777 is being evaluated in an ongoing phase 2 trial, and due to strong enrollment, we have updated our guidance for the week 16 top-line readout from the second half of 2025 to mid-2025. Concurrently, we are also evaluating the clinical profile of APG990 in healthy volunteers and its potential for combination with APG777.
Our phase one study evaluating APG990 in healthy volunteers is currently ongoing in Australia. This is a double-blind, placebo-controlled, single ascending dose trial evaluating five dose levels of APG990, a half-life extended antibody targeting OX40L, similar to amlitelimab. This study is enrolling and on track for a readout in the first half of 2025 to confirm APG990's potential for best-in-class dosing. With this study, we seek to confirm that APG990 has an acceptable safety and tolerability profile that enables its combination with APG777 in future studies. We also aim to establish a half-life of at least 21 days for APG990, and if realized, this optimized PK profile could enable us to determine dosing regimens that target sustained exposures similar to amlitelimab while prolonging the dosing interval.
Achieving a potentially best-in-class dosing regimen could make APG990 well-positioned for combination with APG777, which is currently being trialed with every three- to six-month dosing in the maintenance setting, with the potential for annual dosing based on today's 12-month data for 777. Assuming we can confirm APG990's safety and optimized PK profile and pending regulatory clearance, we plan to initiate Apogee's very first combination study. This will be a phase 1b study to evaluate the safety, PK, pharmacodynamic effect, and efficacy of the combination of APG777 and APG990, which target orthogonal mechanisms that are both clinically validated and well-tolerated in AD. We expect to initiate this study in 2025 and plan to randomize 50 to 75 patients with moderate to severe AD to either the combination of APG777 and APG990 or standard of care Dupixent.
We selected Dupixent as the comparator arm in this study as we believe that it is important to demonstrate that the combination could potentially deliver improved efficacy over currently available treatments. Efficacy readouts will be at week 16 and later time points. Our goal is that this phase 1b trial will demonstrate three things. First, that the combination of APG777 and APG990 has an acceptable safety and tolerability profile to progress to later stage trials. Second, that the combination shows broader pharmacodynamic effect on key AD biomarkers of types one, two, and three inflammation. And third, that the combination of APG777 and APG990 demonstrates a promising efficacy profile compared to standard of care Dupixent early in the clinical program prior to progression to later phase trials. We are very excited to initiate Apogee's first combination program in 2025.
We believe we have the potential to show improved clinical outcomes when taking an orthogonal approach with two of the most validated targets, IL-13 and OX40L, in patients with AD, while still minimizing the injection burden to every three-month dosing or better in the maintenance setting. For the next section, I'll pass it on to Amol, who will introduce you to our respiratory programs. As with our AD programs, we are aiming to develop best-in-class monotherapies that have the potential for dosing every three to six months, as well as combination programs with validated orthogonal mechanisms that could potentially improve the efficacy bar for patients with asthma and COPD. Thanks, Christine. As with atopic dermatitis, APG777 is central to our respiratory development plans as we recognize the important pathogenic role IL-13 plays in obstructive airway disease. We also appreciate 777's potential as part of a best-in-class combination for respiratory diseases.
We recently announced DC nomination for APG333, our extended half-life antibody targeting TSLP, or TSLP. This will enable our 777 and 333 combination for asthma and COPD. By targeting both IL-13 and TSLP, we believe there is opportunity to more broadly address key drivers of disease with the goal of breaking through the monotherapy efficacy ceiling. It is my pleasure now to introduce Professor Dave Singh, an internationally renowned respiratory expert who will share more about the importance of broader targeting in obstructive airway disease. Professor Singh is Professor of Clinical Pharmacology and Respiratory Medicine at the University of Manchester. His primary research focus is obstructive airway disease, where he has made seminal contributions to our understanding of asthma and COPD. These range from basic pharmacology studies to numerous interventional clinical trials that have led to the approval of novel therapeutics.
Professor Singh has received numerous prestigious awards, including the European Respiratory Society, or ERS, Gold Medal for his outstanding contributions to COPD. He is a member of the Scientific Committee of the Global Initiative for Chronic Obstructive Lung Disease, or GOLD, and was previously the chair of the ERS Airway Pharmacology Group. He is a fellow of the ERS and of the British Pharmacological Society. Professor Singh is widely regarded as a leader in his field. He has acted as principal investigator in over 400 clinical trials and has over 500 publications. It is a privilege to have Professor Singh with us today. His talk will focus on the role of alarmins and type 2 cytokines in obstructive airway disease and the potential for combined targeting of IL-13 and TSLP to improve outcomes for patients. Thanks, Amol.
I'm going to consider the role of alarmins and type 2 cytokines in obstructive airway diseases. In recent years, we've seen huge advances in the management and therapeutics of both asthma and COPD. But despite this, there remains clinically a huge unmet need. Asthma is an extremely common condition. It affects over 250 million people worldwide. And the day-to-day symptom control of asthma with our current management often is inadequate. Many people have daily and even nighttime symptoms, and this causes a poor quality of life. For COPD, it's the third most common cause of death worldwide. And one of the problems is that many COPD patients suffer with what we call exacerbations. These are sudden worsenings, often caused by infection or a change in the environmental condition. A sudden worsening of symptoms can lead to hospitalization, and there is a mortality associated with these exacerbations.
So there is a need for novel therapeutics to address these unmet needs. At the heart of the pathophysiology of both asthma and COPD is the airway epithelium. In a healthy person, the epithelium provides a barrier function and also maintains normal homeostasis. And part of this is achieved through strong epithelial cell junctions. People with asthma often have allergic sensitization and are susceptible to frequent viral infections. Both of these combine to weaken those junctions that form the strong barrier function. And this leads to inflammation below the epithelial layer. We call this subepithelial pathology, and it drives remodeling. COPD is different. It's caused by injury to the epithelium caused by particulate matter, often cigarette smoking. This injury leads to a response by the epithelial cells. These cells often become hyperplastic, and there's mucus hypersecretion.
So this is a different type of pathology where the epithelium itself is extremely abnormal. And another feature of pathology in COPD, which is markedly different from asthma, is alveolar destruction. We call this emphysema. So when you examine the airways of individuals with asthma and COPD, you can actually see these differences. In asthma, there is subepithelial pathology, for example, reticular basement membrane thickening and smooth muscle hyperplasia, whereas in COPD, there's more marked epithelial pathology, such as proliferation of cells and mucus gland hyperplasia. So given the importance of the epithelial layer in the pathophysiology of asthma and COPD, a great advance has been our understanding of the role of alarmins in propagating airway inflammation. This family of cytokines is released from epithelial cells after either activation or damage. These include interleukin 25, interleukin 33, and thymic stromal lymphopoietin.
These alarmins cause a broad range of inflammation, promoting type 2 responses and also encompassing non-type 2 responses. Focusing on the role of thymic stromal lymphopoietin, TSLP, it cultivates type 2 responses through promoting the interaction between dendritic cells and T helper II cells. Then there's a secretion of cytokines involved in type 2 T2 responses. TSLP also interacts with ILC2 cells. These are innate lymphoid cells, again involved in type 2 responses. There's the release of cytokines, T2 cytokines, which, among other actions, cause smooth muscle dysfunction. TSLP also activates innate immune cells, and these include macrophages and neutrophils that contribute to pathophysiology. Alarmins, including TSLP, can be viewed as upstream master regulators of inflammation, controlling a broad range of inflammatory processes. I've mentioned type 2 cytokines. These include interleukin 4, interleukin 5, and interleukin 13.
Interleukin 4 promotes IgE production from B cells and also the activation of T helper II cells. One of the major actions of interleukin 5 is eosinophil maturation and differentiation. Interleukin 13 is a particularly important cytokine in T2 inflammation. It plays a role in smooth muscle constriction and hyperplasia. It also promotes mucus hypersecretion and is involved in airway remodeling. So this is one of the key cytokines amongst this portfolio of type 2 cytokines. Given the role of upstream alarmins and type 2 cytokines, there have been clinical trials in asthma of monoclonal antibodies which interfere with the actions of these mediators. For example, dupilumab, which blocks the action of both interleukin 4 and 13, has shown prevention of exacerbations in moderate to severe asthma patients, those who have blood eosinophil counts above 150 cells per microliter.
Those with lower counts, there was no prevention of exacerbations, showing that this is a treatment targeted at patients with type 2 inflammation. In contrast, targeting TSLP with tezepelumab has a broader action. Not only does it have an effect above 150 eosinophils per microliter, there's also a benefit below this. And the effect of tezepelumab at higher eosinophil counts was greater. Given these positive findings in asthma, these monoclonal antibodies have also been tested in COPD. Dupilumab was investigated in two phase 3 studies, which were both positive for the primary endpoint of exacerbation rate reduction in COPD patients with eosinophil counts above 300 cells per microliter, with an effect size above 30% exacerbation rate reduction. In a phase 2 study of tezepelumab, the primary analysis population, which was broad and not restricted by eosinophil counts, was a 17% exacerbation rate reduction.
But in predefined analyses, the effect size was greater at higher counts. So above 150 cells per microliter, the effect was above 30% exacerbation prevention. So here again, we see potentially a broader effect of interfering with an upstream alarmin. Blood eosinophil counts have been used to identify patients with type 2 inflammation, and there has been some concern that blood eosinophil counts can change from day to day, going above or below the thresholds that I've mentioned. For me, this is a natural dynamic flux that we see in human inflammatory diseases. Inflammation, when present, is never static. The way I think about it is that when you see a high count, it's a signal. It gives you an idea that an individual has a susceptibility to develop eosinophilic or type 2 inflammation. Another biomarker of type 2 inflammation is the measurement of exhaled nitric oxide in breath.
Interleukin 13 is a key driver of the enzyme inducible nitric oxide synthase, and this drives nitric oxide production. Eosinophils are released when there are high levels of interleukin 5, and interleukin 5 is promoted by the alarmins, so you can see different pathways leading to the overexpression of these two type 2 biomarkers. In both asthma and COPD, there is an overall correlation between the levels of these biomarkers, and yet, on an individual basis, some patients, presumably with more interleukin 13-driven inflammation, have higher nitric oxide levels, and other patients, presumably with more interleukin 5-driven inflammation, have higher eosinophil levels. These biomarkers can be used to select patients for appropriate biologics or measure the effects of these treatments, and tezepelumab, being more upstream and able to interfere both with eosinophilic and interleukin 13 signaling, decreases the levels of both of these biomarkers.
Dupilumab, being more downstream and more specific for IL-4 and IL-13 signaling, only interferes with reducing exhaled nitric oxide levels. So there's great promise for using anti-alarmin treatments and treatments directed against interleukin 13, given the importance of both of these cytokines in airway inflammation in both asthma and COPD. TSLP, being upstream, mediates a broad range of inflammatory processes, including non-type 2 and type 2 processes, and that includes interleukin 13. But there are other drivers of interleukin 13 production, including the other alarmins. Interleukin 13 is one of the key cytokines involved in airway inflammation, given its different roles in pathophysiology. As a combination, it makes a lot of sense to combine the broad upstream activities of TSLP, interfering with TSLP, with agents that block interleukin 13. Thank you for listening. Thank you, Professor Singh. Good morning, everyone.
I'm Lucas Döllinger, and I'm the Vice President of Research and Translational Medicine here at Apogee. Today, it's my privilege to talk about the combination of APG777 and APG333, and particularly our preclinical data in support of combination benefit over monotherapy. As we've heard from Professor Singh, alarmins and type 2 cytokines are key drivers of obstructive airway diseases. Alarmins such as TSLP act primarily on the immune system and drive central inflammation. This includes the production of type 2 as well as non-type 2 cytokines. It is important to note that type 2 cytokines, which also includes IL-13, can directly contribute to obstructive airway diseases. They act primarily in the periphery, driving local airway responses such as smooth muscle cell activation and epithelial dysfunction. Most of the approved biologics for asthma target either alarmins such as TSLP or type 2 cytokines such as interleukin 5.
They are also emerging as potential treatments for eosinophilic COPD. However, clinical data demonstrate that efficacy has unfortunately hit a ceiling. Despite the development of new treatments against novel targets, we have seen very little improvement in clinical efficacy, which leaves a significant unmet need for our patients. APG777 and APG333 inhibit IL-13 and TSLP, therefore targeting two well-tolerated and clinically validated mechanisms. APG777 is designed to address local, and APG333 is designed to address central drivers of obstructive airway diseases. Our combination of APG777 and APG333 has the potential to break through the efficacy ceiling observed with monotherapies. As a brief reminder, both APG777 and APG333 are engineered for best-in-class properties against validated mechanisms. They share an overlapping epitope and similar potency as lebrikizumab and tezepelumab. Both molecules are Fc engineered for an extended half-life.
For APG777, we announced updated phase 1 data today showing a 77-day human half-life that is three times longer than that of lebrikizumab. Our preclinical NHP PK studies demonstrated a 24-day half-life for APG333 compared to an 11-day half-life for tezepelumab. Today, I'm excited to present preclinical data demonstrating the potentially best-in-class combinatory profile for our APG777 and APG333 combination. This combination is designed to more broadly address both central inflammation and local airway responses compared to monotherapy. To explore the anticipated combination benefit on central inflammation, we applied our preclinical model of allogeneic lymphocyte reactions, abbreviated here as ALR, which uses primary human cells. In these ALR assays, our combination of APG777 and APG333 achieves deep inhibition of type 2 cytokines such as IL-5. These play a key role in respiratory disease by promoting recruitment of inflammatory cells like eosinophils into the airways.
The combination of APG777 and APG333 demonstrates the ability to block sources of central inflammation. It surpasses type 2-only inhibitors like lebrikizumab and dupilumab while retaining similar in vitro activity as tezepelumab. The combination of APG777 and APG333 also inhibits non-type 2 inflammation that may contribute to obstructive airway diseases. For example, in this ALR assay, we show that the combination of APG777 and APG333 inhibits TNF-alpha, which is elevated in COPD patients. The combination demonstrates a similar effect on non-type 2 inflammation as tezepelumab, while lebrikizumab and dupilumab do not inhibit non-type 2 cytokines. However, the inhibition of non-type 2 inflammation may be important for clinical efficacy in broader populations. Tezspire is the only biologic approved for uncontrolled asthma without type 2 biomarker requirements, while Dupixent's label is limited to certain subpopulations.
Next, we evaluated the effect of APG777 and APG333 combinations on bronchial smooth muscle cells isolated from COPD patients. Bronchial smooth muscle cells, or BSMCs, play a key role in driving hallmark symptoms of obstructive airway diseases. IL-13 can activate BSMCs, leading to bronchoconstriction, airway hyperreactivity, and release of pro-inflammatory factors. Our APG777 and APG333 combination demonstrated in vitro blockage of IL-13 and inhibition of BSMC activation measured through periostin release. As expected, the determined inhibition for our combination was similar to lebrikizumab and dupilumab, whereas tezepelumab had a weak inhibitory effect on periostin. As Professor Singh highlighted in his talk, the loss of epithelial barrier integrity is a fundamental driver of asthma and COPD. The barrier loss amplifies inflammation by enabling deeper penetration of allergens, viruses, bacteria, and other harmful particles that further damage the epithelium.
This is setting up a pro-inflammatory feedback loop that drives the progression of asthma and COPD. We therefore also evaluated the effect of our APG777 and APG333 combination on preventing epithelial barrier loss in a COPD patient-derived air-liquid interface lung tissue model. IL-13 promotes local airway epithelial dysfunction, including the loss of barrier integrity and release of pro-inflammatory factors, which is recapitulated in our model. The combination of APG777 and APG333 protects barrier integrity as measured by transepithelial electric resistance, or TEER. As expected, we again determined similar in vitro activity of lebrikizumab and dupilumab and superiority over tezepelumab. On this slide, we show representative images of our COPD patient-derived air-liquid interface lung tissue model with the epithelial cells stained in pink.
In the upper left, we can appreciate that the unstimulated tissue model maintains a tight barrier with little to no disruption of the uniform layer of the epithelial cells. The remaining images are from this tissue model following stimulation with recombinant human TSLP or IL-13, which mirrors the pro-inflammatory environment in the lungs of COPD patients. As expected, the control antibody has little effect, and we observe significant disruption of the epithelial layer. Tezepelumab has a limited effect and appears similar to the control, which is consistent with the results of the TEER measurements shown on the previous slide. The combination of APG777 and APG333, however, appears similar to the unstimulated control, demonstrating its ability to prevent barrier integrity loss similar to lebrikizumab and dupilumab.
In summary, we clearly demonstrated in our preclinical models that the combination of APG777 and APG333 has the potential for best-in-class efficacy in obstructive airway diseases. APG777 and APG333 combines tezepelumab's ability to block inflammation centrally as well as lebrikizumab's and dupilumab's ability to address local airway responses. In addition to the potential for best-in-class efficacy, the combination of APG777 and APG333 could also provide greater convenience for patients with the potential for every three-month dosing or less frequent compared to every two or four weeks for approved monotherapies. In summary, the data I have presented today demonstrate the potential combination benefit of APG777 and APG333 to more broadly address the key drivers of obstructive airway diseases. APG777 inhibits IL-13 that drives bronchial smooth muscle cell activation and epithelial barrier loss.
As we've shown in our BSMC stimulation assay as well as the COPD patient-derived air-liquid interface model, APG777 has the potential to block these effects of IL-13. APG333 inhibits TSLP, which together with IL-13 drives central inflammation including type 2 and non-type 2 cytokine responses. As shown in our ALR assay, APG777 and APG333 in combination can effectively inhibit this key source of inflammation observed in obstructive airway diseases. There is clinical proof of concept for our approach through lunsekimig, a bispecific nanobody targeting IL-13 and TSLP. Recent data from a phase 1b biomarker study in patients with mild asthma suggested the potential for an additive effect on fractional exhaled nitric oxide, also known as FeNO, which is a key biomarker for type 2 inflammation in asthma and COPD.
While early, these phase 1b data suggest that the combined targeting of IL-13 and TSLP may achieve greater efficacy not previously seen by single-target therapies. We therefore evaluated the combination of APG777 and APG333 head-to-head against lunsekimig in our preclinical models. Our data demonstrate a similar inhibition of Type 2 and non-Type 2 inflammation. However, our combination of two half-life-extended full-length IgG1s could provide a significant improvement on dosing compared to the nanobody Lunsekimig. Lunsekimig has reported serum half-life of approximately 10 days in humans and is expected to be dosed every two to four weeks. In contrast, based on available PK data and modeling, the combination of APG777 and APG333 has the potential for every three-month dosing or even better. This means that our combination of APG777 and APG333 could have three to 12 times fewer annual injections compared to luLunsekimig.
Lunsekimig is currently being tested in a phase 2 trial for allergic asthma patients. Data are expected later this year. Lunsekimig is also currently being tested in a phase 2 trial in high-risk mild to moderate asthma patients where there is a significant unmet need and no approved biologics. We look forward to the data and being able to follow the science. For the next section, I will hand it off to Amol, our VP of Clinical Development, who will share more about our respiratory clinical development plans. Lucas, thank you. We recognize the potential of APG777 to treat obstructive airway disease. By blocking IL-13 signaling mediated by IL-4 alpha receptor and IL-13 alpha-1 receptor, 777 inhibits important downstream inflammation driven by IL-13. Professor Singh described some of those effects. 777 could be the first agent to hit this pathogenic target with every three- to six-month dosing.
We are excited about advancing it as the cornerstone of our respiratory program, both as a monotherapy as well as the foundational piece of combination therapy, so we're building our respiratory program in two waves. First, by demonstrating the value of our molecules as monotherapies. We then expect to advance a potential best-in-class combination. Near term, phase 1b studies for 808, 777, and 333 will lay the groundwork in terms of providing initial safety and proof of concept in asthma prior to initiating combination clinical trials. We are also thrilled to continue building out our 777 franchise by initiating a phase 2b trial of 777 monotherapy in asthma. This, we know, is a critical step towards bringing additional options to patients suffering with comorbid atopic dermatitis and asthma. Last month, we shared the exciting news that we selected a development candidate, APG333, targeting TSLP.
This is the same mechanism as tezepelumab, as Lucas described. We anticipate initiating a phase 1 study of 333 in healthy volunteers by the end of this year and expect to share those data in the second half of 2025. This will be a double-blind, placebo-controlled, single ascending dose trial evaluating four dose levels of 333. The first objective of this trial is to confirm that 3333 has an acceptable safety and tolerability profile, allowing potential combination with 777 in future respiratory studies. Additionally, we aim to establish a half-life of approximately 60 days. If realized, this optimized PK profile will enable us to determine dosing regimens that target sustained exposures that are similar to tezepelumab while prolonging the dosing interval to a more favorable every three months or potentially less frequent regimen, further positioning 333 well for combination with 777.
Given the promising early data of tezepelumab and COPD, as described by Professor Singh, and the differentiated broad population it is approved for in asthma, we are delighted to announce we expect to bring 333 into the clinic in the coming weeks. Carl spoke earlier today about our ongoing phase 1b trial of 808 in asthma. We expect to initiate similar studies of 777 and 3333 in 2025. These trials seek to confirm initial safety of 777 and 3333 in an asthmatic patient population and to provide early proof of concept by demonstrating suppression of fractional exhaled nitric oxide, or FeNO, a key biomarker of inflammation in the airway, as Professor Singh noted earlier. In asthma, decreases in FeNO are associated with improvements in lung function and decreased risks of exacerbations.
Importantly, we aim in these trials not just to show competitive suppression of FeNO, but also durability of that suppression consistent with the extended half-lives of our molecules. Doing so will provide further support to advance combination trials of 777 and 333 in respiratory disease. We have built our portfolio with the objective of developing best-in-class monotherapies to enable optimal respiratory strategies. As an allergist and clinical immunologist, I have seen firsthand how biologics can dramatically improve the lives of patients suffering with uncontrolled obstructive airway disease. The introduction of these therapies has been life-changing for so many patients. We know, though, that two unmet needs remain. First, we appreciate the impact that frequent injections have on patients and families. With every three- to six-month dosing, 777 alone and in combination with 333 has the potential to offer a differentiated dosing regimen.
It is our hope that reducing not just the physical injection burden, but also that stress of frequently having to think about arranging the next injection meaningfully improves the patient experience. Second, there is that important efficacy bar. There are patients still who have an inadequate or incomplete response from blocking a single ligand or receptor. The combination approach, hitting both IL-13 and TSLP, has the potential to deepen these responses. We're incredibly excited at Apogee to be leading this charge of bringing transformational medicines to patients and families. I'll now hand it over to Jeff, our Chief Commercial Officer. Thanks, Amol. Clearly, combination products are the future of the AD markets due to the potential for transformational efficacy and dosing. But today, I want to focus on our lead program, APG777 as a monotherapy.
It is a pipeline and a product with the potential to transform each of the largest INI markets with differentiated dosing and potentially higher efficacy. 777 could disrupt the atopic dermatitis market first. There are three key drivers for why 777 could be the largest biologic launch this decade. First, the sheer size of the INI markets we are addressing. Second, the lack of biologic penetration versus other key INI markets. You can see how the more mature markets have approximately 25%-60% biologic penetration, and finally, third, the fact that we're testing 777 to be differentiated with, at a minimum, every three- to six-month dosing and potentially even annual dosing, as well as higher exposures that could lead to enhanced efficacy.
We anticipate launching into a unique opportunity of market size, lack of biologic penetration, and unmet need, not only in atopic dermatitis, but also in asthma and COPD, which are the next markets that we will be addressing. Focusing on the enormous opportunity for 777 in atopic dermatitis, there are three key insights from the dermatology biologic market that highlight 777's massive potential in AD. First, as you look at the plaque psoriasis market in gray, it is clear that these are not winner-take-all markets. Later entrants with differentiated dosing have become the clear market leaders. Skyrizi, at the bottom right of the slide, is a perfect example. Despite being the 11th biologic to launch in psoriasis, Skyrizi became the market leader only three years after launch.
Second, a single product launch in AD has outpaced the entire $25 billion plaque psoriasis biologics market and is on track to be a $50-plus billion market, with each market share point representing a billion dollars in top-line sales. Third, with only single-digit biologic penetration in what is set to become the largest INI market, we expect a much faster ramp in atopic dermatitis. 777 has the potential of quickly disrupting this market. The evolution of the psoriasis market teaches us how the atopic dermatitis treatment landscape could develop. Enbrel and Humira got it started. Both dosed frequently with moderate efficacy. Then came the IL-17 class, Cosentyx and Taltz, which raised the efficacy bar. At this point, you could have argued that the landscape was crowded, no more treatments were needed. We already had multiple topicals, five biologics, and an oral Otezla that launched in 2014.
But Skyrizi is just a few years into launch and on a trajectory to do nearly $12 billion in peak net sales in plaque psoriasis alone, despite being one of the latest launches. This is primarily due to its dosing advantage. Finally, Bimzelx has recently launched with an impressive trajectory, and that's from a small company. As you can see, psoriasis has eight blockbuster biologics, with six products expected to do north of $2 billion each in net sales in 2024. This is all in a market that has only about one-third the number of moderate to severe patients as atopic dermatitis. By contrast, this is where atopic dermatitis treatments are today, the veritable definition of white space. Dupixent and Ebgliss show the best efficacy of the class, but they're dosed every two to four weeks and with massive space for improvement in both efficacy and dosing.
It is clear this is an unsatisfied market looking for new treatment options. In fact, Dupixent, the market leader, has about half of the patients discontinuing by end of year two, and that's based on real-world evidence. Apogee has the potential to meet this unmet need and transform the AD market. We are currently testing every three or six-month maintenance dosing and believe there is a path to an annual dosing option for 777. Patients and their dermatologists and allergists tell us this innovation alone would be completely transformational for them. But we also have three opportunities to improve efficacy outcomes for patients with atopic dermatitis. First, in the Part A portion of our phase two study reading out mid-2025, we are testing approximately 30%-40% higher exposures or drug levels of 777 compared to Ebgliss.
Multiple pieces of evidence suggest these higher exposure rates could lead to better efficacy. Second, in the Part B portion of our phase two study, we will be testing even higher exposures than in Part A to fully explore the potential of the IL-13 mechanism and ensure we do not leave any remaining efficacy on the table. And finally, in 2025, we plan to take the first combination approach in atopic dermatitis forward, where we'll be combining two mechanisms with the greatest clinical validation, IL-13 and OX40 ligand. Given the conviction we have in this strategy and the differentiation we believe it needs to demonstrate, we are testing out of the gate versus the market leader, Dupixent.
So we have three opportunities for better efficacy in our pipeline in the next few years, and each approach having dosing that is expected to launch with up to 13 times fewer injection days than currently available treatments. The level of commercial launch success is always dependent upon three factors. Does it meet an unmet need for patients? Do physicians see value in the product for their patients, and are they inclined to prescribe? And will payers give patients access to the new product? We've done quite a bit of blinded market research where each group was given baseline information that 777 was only as efficacious and safe as Dupixent, but with an every three-month maintenance dosing regimen. Not only do patients prefer the 777 profile to other available products with equal efficacy, but 94% said they will take action to be treated with 777.
Physicians said that with just equal efficacy and safety and a Q3-month dosing schedule, on average, they would prescribe 777 for 92% of their biologic naive patients. What's more, physicians see such value in 777, they would expect 57% of current biologic patients to switch to 777. And finally, payers have been clear that with this innovative dosing schedule and similar net pricing, they would support equal access to Dupixent as a first-line biologic. With overwhelming early support of patients, physicians, and payers, if 777 can deliver on its promise, we believe it will be set up for both early and sustained success. Beyond atopic dermatitis, we are going after potential blockbuster expansion indications, including respiratory, GI, and additional dermatology disease states.
Evidence supports 777's mechanism in treating numerous conditions driven by Type 2 inflammation across these therapeutic areas, and we see an opportunity to leverage a phase 2 dose in each therapeutic area to have the option to expand directly to phase 3 trials in the most attractive expansion indications, a potentially expedited path to pipeline into product status for 777. 777 could disrupt these large AD markets with new dosing options that patients desire while driving toward better efficacy for biologic naive patients, as well as patients that are unsatisfied with current treatment options. Finally, as any successful commercial biotech knows, eventually, competition will come and look to improve upon your monotherapies.
That is why we are rapidly advancing our combination approaches just behind our 777 mono and will look to improve upon our own therapies, constantly striving to bring better options to patients who deserve the best disease control that we can provide. For the next section, I'll hand it back to Michael, our CEO, to give a few closing remarks and walk you through our upcoming milestones. Thank you, Jeff. As you can see, 2024 was a transformative year for Apogee, and we have several exciting milestones on the horizon in the coming months. Over the past year, we've made remarkable progress, moving our lead program into a phase 2 trial while advancing our second, third, and soon fourth programs into the clinic. Today, we announced positive clinical data for our lead program, demonstrating a 77-day half-life, three to five times that of on-market competitors.
We also announced positive interim clinical data for our 808 program, demonstrating potential for every two-to-three-month dosing. Finally, our vision is to create a next-gen biotech that refuses to stop at good enough and constantly seeks to improve the therapeutic options we are delivering to patients, delivering multiple waves of innovation for the conditions we look to treat. With our lead program, we now have a path to annual dosing, and today's preclinical proof of concept data for our combination approaches demonstrate our potential to deliver potentially paradigm-shifting efficacy while maintaining best-in-category dosing. We are excited to put the combo to test out of the gate and plan to kick off a head-to-head trial with Dupixent in the coming year. Looking ahead, 2025 is set to be a pivotal year of readouts for Apogee.
Today, based on strong enrollment, we accelerated our readout guidance for Part A of the 777 phase 2 trial, which we now expect to deliver proof of concept data in atopic derm patients in mid-2025. Additionally, in the first half of 2025, we also plan to read out the first data for 808 in asthmatic patients. The third clinical readout in 2025 will also be in the first half, our phase 1 healthy volunteer data for our 990 program, which we hope will confirm a tolerable safety profile to enable future combination trials and establish the PK profile of this optimized molecule. With our TSLP program, 333, set to dose by the end of this year, we expect to read out phase 1 data for it as well next year.
Over the next two years, we will have eight clinical data readouts that we believe will prove out our potential to disrupt the largest markets in INI. This wraps up our presentation for today. Before we end this session, we at Apogee want to express our deepest gratitude to the patients participating in our clinical studies. We know you are waiting for better therapies, and we couldn't make this progress happen without you. On behalf of the entire Apogee team, thank you for joining us today. We will now open up our call for analyst Q&A. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster, and our first question comes from Seamus Fernandez with Guggenheim Securities.
Your line is open. Oh, great. Thanks for the questions and congrats on all the progress and rapid development advances. The first question is, can you just give us a sense of how the healthy volunteer data for Dupixent actually translated to the actual moderate to severe atopic dermatitis population as it relates to biomarkers? I think that's an interesting question as it relates to the healthy volunteer comparisons that you offered up. And then the second question is just as it relates to the TARC biomarker versus STAT6. I think you've positioned the TARC biomarker as an induction, a very valid induction biomarker. But why does it sort of matter more for STAT6 suppression over time versus that induction biomarker dynamic? Thanks so much. Thanks, Seamus. Appreciate the questions. Great ones. I'll hand it off to Carl for the first question, but also to elaborate on the second.
Just briefly on TARC, there's a lot of different inputs that go into TARC, right? Downstream of IL-13, IL-4, there's STAT6, there's STAT3, a number of different pieces of the inflammatory cascade. So TARC is kind of the most studied and directional one, and we do see traditionally tracks the most with induction efficacy. So we're following the literature there. Whereas STAT6, it's a newer, very sensitive measure, which we think is helpful in kind of keeping the inflammatory cascade tamped down over time. So more sensitive to monitor the ongoing inflammation, which is why we love the data that we're seeing out to a year with almost full suppression of pSTAT6 after that single dose giving us a potential path to annual dosing. But I'll hand it off to Carl to comment more on that and also the 808 and Dupixent phase 1 read-through to atopic derm trials.
Yeah, great. Thanks, Michael, and thanks for the question, right? I think on your first question, the translation of the Dupixent healthy volunteer data to moderate-to-severe atopic dermatitis, I think, since it's an N of one, we only have that, but we know the change in TARC that we saw with Dupixent in healthy volunteers, the maximal change very similar to what we've seen with both APG777 and APG808, but obviously, especially with APG777, we see that prolonged change both in single dose and multi-dose over time, which we think is extremely encouraging. As Michael said, what we really know about TARC is that, yeah, I guess two things. One is that it's correlated really well with AD severity, and it's also been shown to be correlated with induction responses with Dupixent, but with other drugs as well.
We do think that the comparison, while a non-head-to-head trial comparison, we think is extremely encouraging for APG777. Then on the second question, the difference between TARC and pSTAT6, I think a key piece of thinking about them as different stages in atopic dermatitis or correlating better to different stages in atopic dermatitis is when you really think back to what the disease state is for both induction and maintenance. In induction, right, we're trying to get patients with atopic dermatitis that are really in a hot inflammatory state, right? They're itchy, they have red lesions. We're trying to get that under control. As Michael said, right, TARC has a lot of inputs into it in terms of inflammation.
In that induction stage, and this is one of the reasons we're testing higher exposures there compared to lebrikizumab, we're really trying to get all that inflammation under control. Once patients become responders in the maintenance setting, we're kind of trying to put up a barrier so that inflammation cycles don't increase over time. We don't have flares. We're trying to control kind of a baseline of very little disease or no disease at all, and so pSTAT6 is a really sensitive marker for atopic dermatitis. We think it's a really nice marker long-term there and obviously extremely encouraged by the APG777 data showing up to a year inhibition of pSTAT6 after a single administration. Great. Thank you, guys. I'll drop back in the queue. Thank you. Our next question comes from Akash Tewari with Jefferies. Your line is open. Hey, thanks so much for hosting this event.
I had a few questions on the Rinvoq versus Dupixent head-to-head study level up that recently reported in atopic derm. So number one, do you think an IL-13/OX40L combo could show responses on more stringent endpoints like EASI-90 of 10% or more versus Dupixent like we saw with Rinvoq? Number two, there was some early evidence that using a titration protocol of 15 mg to 30 mg for Rinvoq decreased the rate of serious AEs to a rate that was pretty similar to Dupixent. Could Apogee take a similar approach to avoid a possibility of a black box warning? And then lastly, for Dr. Guttman, have those results increased your use of Rinvoq versus Dupixent in AD, or has changed the bar in any way for Apogee's combo approach in your view? Thank you. Thanks, Akash. Good questions. And unfortunately, we don't have Dr.
Guttman in the room with us, but we will ask her and pass along what she says to your third question. With regards to the ability to see efficacy or more stringent endpoints first and foremost with the combo, I think that actually with our mono, we're looking for that as well, right? When we go back to the exposure response analysis that exists for 777 from their approval documents, you see that not just on EASI-75, but more so against the more stringent endpoints of IGA 0/1 and EASI-90, you saw a very nice exposure response increase for lebrikizumab at those higher exposures. So in our ongoing phase 2, which will now read out middle of next year, given the strong enrollment, we will actually see if that can also lead to improved response on those more stringent endpoints.
Of course, with the combo, we think that, right, not only could we get a greater breadth of patient responses, but also a greater depth. I think, as Dr. Guttman noted in her remarks, right, compared to psoriasis, atopic derm, while there are finally some therapies, only a third of patients are really getting to the kind of clearance that you see in 90% of psoriasis patients. So a big therapeutic gap. And then finally, on your point about the titration that was seen with the JAK studies, right, we don't expect a black box warning given the very safe therapies that we're advancing here.
So of course, with JAKs, you have, right, not only the black box warning and the discussion to give to patients, making it secondary to any biologics, but you also have pretty onerous labs that you have to follow, which just aren't that straightforward for a dermatologist given how heavy their workflow is. So when we look at OX40 ligand and, right, the very significant and long-term safety data that now exists from Amlitelimab, and we combine that very clean profile with the very clean profile for IL-13, we, at least at this point, right, and of course, we'll have to do the studies to prove this out in the clinic, would not expect there to be a risk of a black box given how clean those monoclonal antibodies are. Thanks so much. Thank you. And our next question comes from Alex Thompson with Stifel. Your line is open.
Hey, great. Thanks for taking our questions. Appreciate the discussion today. Maybe on the combinations, particularly with 777 and 990, can you talk about sort of how you're thinking about specific dosing relative to one another in the phase 1b, whether it's going to be one-to-one or something different, and how you're going to get to sort of that optimization? And then for the potential with annual dosing with 777, can you talk about how you might potentially be able to study that in the future? Thanks. Yeah. Thanks, Alex. I'll hand it off to Carl to hit on one and two. Yeah, sounds great. Thanks for the question.
I think first, the dosing question related to 777 and 990, I think one of the big advantages of the approach that we're taking in terms of co-formulation and not a bispecific is we have the opportunity to make sure that we target both IL-13 and OX40L in this case, the right amount, right? Often with a bispecific, you're forced into one-to-one targeting, which might not be optimal for a variety of reasons. Here, we'll be able to really follow the science and make sure that we get that ratio of targeting correct to really maximize benefit-risk in this case, right? That might be two-to-one or three-to-one or four-to-one, right? It might be some other ratio than one-to-one, and we'll uniquely be able to do that with our combination approach overall.
Exactly what that looks like, I think more to come later, especially with the 990 healthy volunteer data in the first half of next year. We'll not only be able to talk about the 990 data in and of itself, but we'll also have more on this combination, and I think especially related to what the optimal level of targeting is for both APG777 and 990. On the second question related to annual dosing of 777, as you guys well know, at this point in time, we're testing every three- to six-month dosing in the phase two trial that's ongoing right now. Transformative for the space where AD drugs, Dupixent and lebrikizumab, are dosed every two weeks and every four weeks at the outer end, right? So huge change in terms of injection burden for patients overall.
I think the pSTAT6 data really encourages us that there's a path towards annual dosing and something that we'll definitely explore in the development of this product overall and would really be something, I think, for AD diseases in general that hasn't been seen yet, and we're excited to be on the forefront of that discovery and development. Thank you. Our next question comes from Tyler Van Buren with TD Cowen. Your line is open. Hey, guys. That was a great first R&D day presentation, and congrats on all the progress. I have a couple for you. So I'm excited to see the part A data for 777 in the middle of next year that you just referred to, given the strong pSTAT6 data.
But for the phase 2 part B portion testing higher exposures, can you give us a sense of how much higher those exposures are expected to be relative to part A or perhaps relative to the top quartile of exposures with lebrikizumab and what that would imply for clinical responses when we see the data? And the second question is, it's bold to run a head-to-head versus Dupixent, and it signifies your confidence, but given the 777 monotherapy can stand on its own, how do you see it and the 777/990 combo coexisting in the marketplace? Or in other words, what patients would be more appropriate for one versus the other? Great. Thanks, Tyler. I'll hand it off to Carl to touch on the first question, and then I'll start on the second before letting our Jeff weigh in. Yeah, great. Thank you for the question.
We're really excited, I think, first to have moved in the part A 16-week induction data where we're testing 30%-40% greater exposures than lebrikizumab and delivering that data now mid-next year. In making sure that we didn't leave any efficacy on the table, right, we want to walk away from this phase 2 study knowing that we have maximized benefit for patients overall. To that end, we're testing higher exposures, as you pointed out, in the part B compared to the part A, and a similar increase that what we did in the part A. In the part A, 30%-40% greater exposures than lebrikizumab. In the part B, our high dose will have a similar increase in exposures compared to our part A dose.
We haven't seen anything with this target in increasing exposures based on the lebrikizumab data that suggests higher exposures would lead to any increased safety risk. So our goal here is really to maximize efficacy and maximize benefit for patients in that study when possible. Yep. And then to the second question around, right, how we think about the combo relative to our 777 mono long-term, right? So we feel our 777 monotherapy has the potential to be, right, that mega blockbuster, that $10 billion-plus drug which establishes kind of our presence in atopic derm, asthma, and related conditions over time. And then when we think about who we want to be when we grow up, right, we look at the generational companies, and those are the Vertexes, the Gileads.
Those are the ones that refuse to stop at good enough, and they know that either they could come with a better drug to come frontline to go broader and deeper in efficacy, or they could let competition do it. We don't want to let competition do it. We want to cannibalize our own markets and bring combos, right? We know that combos, innovators are headed, and we want to be the ones to replace our own therapies and provide something even better for patients. Jeff, anything to add? Yeah. Just briefly, Tyler, I think first and foremost, we're going to be laser-focused on launching 777 monotherapy in AD. That's first. We think that clearly, as you saw in the presentation, both patients and physicians are excited about 777. It is a disruptor in and of itself.
We think that we can grab quite a bit of market share early on and also expand that market. So that's what we're focused on. However, in time, we fully expect where we can raise the ceiling of efficacy even further with co-formulation. We fully expect that revenues will, in time, begin to shift toward the combination. When you look at what we're bringing forward, this is a long-term play. So we're going to be able to have impact in the AD space for years to come. Thank you. And our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Thank you. Good afternoon. Just two questions for me here. One is on your maybe just confidence of FeNO and endpoint and whether you will also be looking at FEV1 with regard to the 808 monotherapy study and the 777 and 333 study.
And then as we look to your dataset next year from the phase 2 16-week induction data in AD, could you just frame the likelihood that over that period of time, we could see improvement on efficacy over standard of care? Thank you. Yep. Thanks, Salveen. Great questions. I'll hand it to Carl for the first, and then I'll jump in for the second. Yeah. Great. Appreciate the question. I think that a couple of things about FeNO has been a really good biomarker, especially for type 2 inflammation in obstructive respiratory diseases. So we have a lot of confidence that it'll help us compare to not only Dupi but other treatments in this space as we look towards getting increasing confidence on how to select doses for APG808 for potentially future programs.
The other important aspect of it too, while maximal change in FeNO, I think, will help us compare to other products in the space, the thing that I think is most important almost for that is the durability of effect that we see with FeNO. And I think that will help us show the potential for APG808 overall. And as we look to other asthma trials in our portfolio, both for APG777 and APG333, we'll look for similar readouts. We are collecting FEV1 in that trial, and obviously, we'll look at that across our asthma trials and in the future COPD trials. It's a much more noisy endpoint, and so in the small n's might be more difficult to see a clear differentiation over time.
Then to your second question of the accelerated part A readout now coming middle of next year, I might reframe it a little bit, which is what's likely that we will see increased efficacy either via the part A or the part B or the combination all coming over the next two years, improved efficacy while maintaining that best-in-category dosing. I think the likelihood there is that's a very high likelihood, right? Especially when we think about the combo and the data that we put forward today, right? Incredibly rational approach supported by clinical data that we're applying those clinical principles to our atopic derm combo approach. I think with the part A, right, you've seen the evidence. I think everyone can look as well, right? Very strong reason to believe that improved efficacy could be achieved via higher exposures.
The strongest there, of course, the phase 2b that Dermira ran when they had lebrikizumab and both the EMA and FDA documents for lebrikizumab showing that there, right, an exposure response exists with the EMA really quantifying that to the greatest extent. And we are testing the 30% to 40% higher exposures, which approximate that low body weight subgroup in the part A, which is reading out next year. I think all that data suggests that it's the experiment that needs to be run. We're testing it. All the market research we show is based off of similar efficacy and safety and only improved dosing. So I think over the next two years, three shots at better efficacy.
Our first shot we're taking next year, which we think there is, again, very strong rationale to be testing what we're testing, but we'll have to wait and see for the data. Thank you. Our next question comes from Charlie Yang with Bank of America. Your line is now open. Great. Congrats on all the progress, and thanks for taking the question. I have two questions and one clarification, please. My first question is regarding your IND for the co-formulation 777 and 990. Just what's the dosing for that co-formulation, and how do you think in that kind of head-to-head versus the other agents out there? And how would that translate into kind of potential kind of safety profile? Do you think that there could be incremental adverse events from the combination that may have to be considered? And second, just regarding kind of what's the future plan for APG808?
I mean, I know kind of you're looking to have data readout in the phase 1b asthma, but I'm just wondering, just based on the plan that you're presenting, I'm just wondering, is there just given the co-formulation availability down the road, is there actually a pathway for the 808 in the future? And in terms of my clarification question is for the dosing for the APG777 phase 2 maintenance arm, can you just clarify what's the dosing for that? Is that the same mid-dose that's tested in the part A induction setting? Thank you. Great. So, to clarify, I'll go in reverse order. So the part B mid-dose is the same as the part A dose. So yes, Claire, you're correct in your question there. With regards to 808 and the path forward, we have remarkable data with 808, right?
It exceeded all of our expectations, and we couldn't have asked for a better fully optimized half-life extended IL-4 receptor alpha antibody. When we stack up the target product profile, and especially via a combination of 808 with 777, right, 777 has the potential to go out three, six months, even annual. So we are prioritizing 777 as a monotherapy and as our combination backbone for now, right? I think that we will have 808 data coming next year, which will show us the potential path forward, and we'll be able to respond to that data as well as emerging data from the field. If we ever see that IL-4 biology is something that can't be replicated with IL-13, which we haven't seen yet, if anything, IL-13 looks to be the primary culprit across all the disease states that we're seeing in all the trials.
But we'll have 808 there and ready, and we'll look forward to understanding the prolonged potential PD effect of it next year. And for the ALR assay, I'll hand it off to Carl. Yeah. So great question on the ALR assay. And what we've tried to do in designing those experiments is really make sure that we're coming out with data that is going to be relevant for our clinical programs overall. And I'll hit on two points there that I think are as important as one, just the design of the assay overall, where we're combining two different healthy volunteer donor pairs to get the biggest immune response we can from the assay. And therefore, the data we're showing from it is supposed to really replicate something that we'd see in a more physiologic sense.
And then to that end as well, we're trying to use physiologically or clinically relevant levels of each drug to help us show what responses we might get in the clinic too. For the monoclonal antibodies, we're using exposures that are similar to the C troughs of those. For Rinvoq, we're actually using exposures that are closer to the Cmax of it. So if anything, we're maybe discounting what we would get from the monoclonal antibodies and the combination overall compared to that for Rinvoq. And then on the second piece of the question for the combination data related to safety, I think when you look at the viral versus alarmin challenge data versus Rinvoq, I think that's one of the really important aspects of our preclinical package that we've put together.
And specifically, when you look at the viral challenge aspect of it, right, the combination of 777 and 990 really showed little change, meaning it didn't really dampen the immune insignal there. And that's what we actually want to see versus Rinvoq, which across both the alarmins and the viral antigen challenge, right, almost decreased that type 1 inflammatory signal to zero but didn't really separate out in terms of the type of trigger. And we don't want to dampen that viral trigger too much because that's something we still want these patients in the future to really have intact responses to those external causes that are unrelated to the immunologic disease. Great. Thank you. Thank you. And our next question comes from David Nierengarten with Wedbush Securities. Your line is open. Hey, thanks for taking the question.
I was wondering just if there was any other data you're waiting for if we missed it to take a look at the 12-month dose interval, and then on the commercial side, did you test that question on your preference for annual dosing and if there was any other price, maybe a pricing premium associated with different intervals of dosing versus parity to Dupi? Thanks. Yep. So for your first question, so that we're really now just waiting for clinical data from the phase two trial, right? I think the six-month maintenance dosing as well as the three-month maintenance dosing will help to, right, validate that we can reach much longer dose intervals, and then we see the annual dosing as a, right, a lifecycle management piece, so unlikely that we would have it at launch versus in the coming years after launch.
So we'll have a whole host of additional data, especially from just the maintenance studies that we're running with the, right, the single injection, especially at six months, that will further inform our ability to not really what annual dose to or whether annual dose is possible, but what dose to pursue to achieve annual dosing. So more to come there. And then, Jeff, do you want to speak to kind of how we view annual dosing from a commercial perspective? Sure. Hello, David. Thanks for the question. So first of all, we've done market research looking at obviously the three-month maintenance dosing that we spoke about, 94% of patients wanting that. We did, in fact, have questions in that third-party research looking at what patients would prefer around three versus six months.
You did have another 12% of patients that said, "I would absolutely rather even have further out, six months for sure." So we do know that when you look at plaque psoriasis, the further out that they have been able to go, three months has driven the market that way. What we want is we want optionality for patients. Patients and physicians both want that. They expect that as we continue to bring out new innovation for them in the AD space and others. And so the annual dosing will continue to increase adherence through both compliance and persistency, all of which are important to payers as well. And in this case, we get to see for both patients and physicians in the first 16 weeks the response to the product prior to moving to a three, six, or potentially 12-month dose. Did you test pricing premium versus parity? Yeah.
So we are evaluating all of those things right now. I think you probably saw that Ebgliss, moving from two weeks with Dupixent to two to four weeks with Ebgliss, came out with a minimum of a 30% price increase versus Dupixent in the first year. So we believe that HEOR, health economics and outcomes research, will help to tell that story as we see the adherence rates and things like that. So there's a potential for that, but we are not in a position to speak to that today. Yeah. And I'll just add, when we look at Dupixent's a great drug, right, amazing outcomes. Within two years, though, 50% of patients have fallen off Dupixent, right? Penetration of the market significantly lags as well into the pediatric population.
So, right, when we talk to patients and physicians and payers even who don't like patients coming off therapy as it hurts their bottom line, right, we hear a real yearning for improved compliance and adherence. And we know historically that longer dosing gets you that. So I think there's a lot of excitement. And as Jeff said, too early to comment on pricing, but we're optimistic and excited about what we're pushing forward because we do think it is transformational. Thanks. Thank you. And our final question comes from Julian Harrison with BTIG. Your line is open. Good morning. This is Rayon for Julian. Congrats on all the progress, and thank you for taking our question. Just a couple for us. First, how should we be thinking about the introduction of co-formulations into the pipeline?
Would the FDA require additional phase 2 work on the co-formulations before the combination programs enter pivotal development? And then I have a follow-up, if I may. Yep. Good questions. And welcome to follow up as well. I'll hand it to Carl to talk through how we're thinking about the co-formulation. Yeah. In terms of the clinical path there, I think that thanks to the manufacturing team and their thoughtfulness early on with our development, both the individual monotherapies as well as a look towards the future in terms of co-formulation and co-development, I think we'll be well positioned to enter the co-formulation at a stage of development that leads to no necessary repeated work in terms of clinical studies in our path towards BLA.
When we look down the line, I think it's too early to comment exactly where that will happen, but I think we've had really the foresight or the team here has had the foresight to do that work early so we can enable that early enough in development as we move forward, and I think there's also a lot of precedent in the space for this now and early on, right, for J&J and AbbVie and Lilly as well as multiple products in the obesity space that are also doing this too. So I think relative to where we were five years ago or so in terms of development path forward with formulation, there's a lot of people setting the path forward for this, and I think we'll take advantage of their learnings along the way. Got it. Thank you.
For the follow-up, we were curious about whether there are any specific combination precedents in atopic dermatitis, asthma, or COPD that you could point to that are informing your current development strategies. Yeah. No, so it was a great question. And I think we're really leading the space there in terms of the disease area specifically, in terms of atopic dermatitis, asthma, and COPD. We do see others in the IBD space now doing it, AbbVie and J&J both doing it in IBD. But I think an exciting piece is that we are really the first pursuing this approach in atopic dermatitis and asthma. And it's an approach that's going to allow us to really maximize benefit for patients. And I think it's great to be in a unique position to do that. Great. Thank you. Congrats again. Thank you. This concludes our question-and-answer session and today's conference call.
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