Good morning. This is Bruce Steel, Chief Executive Officer of Equillium. We appreciate you joining us today for our Analyst and Investor Day presentation, featuring Dr. Arash Mostaghimi. We're very pleased to have Dr. Mostaghimi joining us today. We will be discussing some forward-looking topics. We would like to refer you to our filings for further details on our forward-looking statements. Next slide, please, Stephen. The agenda today, we will be providing a brief pipeline overview, as well as our recent partnership with Ono Pharmaceutical. And then we'll focus on our multi-cytokine platform and development candidates, with a specific focus on EQ101, our first-in-class trispecific peptide inhibitor of IL-2, IL-9, and IL-15. This will be presented by Dr. Stephen Connelly, our Co-founder and Chief Scientific Officer.
We will follow that with a more detailed discussion on our clinical program of EQ101, targeting alopecia areata. That'll be presented by Dr. Maple Fung, our Chief Medical Officer. And then we will engage in a discussion with Dr. Arash Mostaghimi. We're again very pleased to have him joining us today. He is Associate Professor of Dermatology at Harvard Medical School and Director of the Department of Dermatology at Brigham and Women's Hospital. We'll then provide some closing remarks and also offer some time for a Q&A session. So again, we appreciate everybody's time today in joining us for these updates. Quick snapshot of Equillium and recent highlights. We currently have three different drugs and four different clinical studies. We have itolizumab, our foundational asset, that we recently partnered with Ono Pharmaceutical.
We'll provide you some more details on that partnership in a moment. And then, of course, our multi-cytokine inhibitors with both EQ101, our IL-2, 9, and 15 program, as well as EQ102, our IL-15 and 21 program currently in clinical development. And we'll provide you some more details on the overall operating runway of the company and upcoming milestones around all of these programs. As it relates to our overall pipeline, shown here, is the full pipeline view. Again, the multi-cytokine programs are wholly owned and itolizumab, as mentioned, has recently been partnered with Ono Pharmaceutical. In terms of some details on this strategic partnership, in December of last year, we entered into... next slide, please, Stephen. sorry.
Yeah, in terms of the, the Ono partnership, in December of last year, we entered into the strategic partnership with Ono. This is an option agreement where Ono has the right to acquire Equillium's rights to itolizumab. We have two data deliverables that will trigger that option period. One is the top-line data from our ongoing EQUALISE study of itolizumab in lupus nephritis. The second is our interim data from our ongoing phase 3 study of itolizumab in acute GVHD. This is the EQUATOR study. In terms of the transaction details, we received approximately $38 million of payments related to closing, including upfronts and a retroactive reimbursement of R&D. If Ono does opt into the program, we will receive an exercise payment of JPY 5 billion. That's approximately $35 million based on exchange rates at the time of our last filing.
Then we also are eligible to receive over $100 million in milestone payments related to clinical, regulatory, and first commercial sale events. Very importantly, Ono has committed to fully funding the entirety of our R&D program for itolizumab. The quarterly budget is approximately $8 million, and that funding will continue through their option exercise period. Obviously, with this, relationship in place, this has dramatically reduced our overall operating burn and significantly extended our operating runway. Next slide, please, Stephen. With that, I'd like to turn it over to, Dr. Stephen Connelly, to take you through the multi-cytokine platform and our therapeutic candidates. Steph?
Thanks, Bruce, and thank you to everyone joining the live webcast this morning. So let's get started with discussing cytokines. And I'm sure you're all aware cytokines are small signaling molecules, are responsible and critical for immune responses in both physiological and disease states. However, there's a complex relationship with the signaling of cytokines because you can have both overlapping signals as well as synergistic signaling, which presents a unique development challenge when thinking about designing therapeutics, what I like to call the multi-cytokine problem. And from a signaling perspective, this complexity comes from the use of upstream shared receptor signaling hubs. A good example of this would be the IL-4 alpha hub, with the targets such as Dupixent or downstream divergent kinase cascades, and examples of this comes from the JAK inhibitor class.
Now, when we think about these challenges for cytokine signaling, we can focus here on the left-hand side with the monoclonal antibodies. These are very effective at neutralizing a single cytokine by either sequestering the cytokine or blocking its binding to the receptor and abrogating all of the downstream signaling associated with that single cytokine. Now, the problem with this is it's likely too narrow when we think about complex autoimmune or inflammatory disease, where more than one pro-inflammatory cytokine plays a role. So then the field turned to inside the cells and targeting the JAK kinase pathway. So these JAK inhibitors can inhibit 50+ cytokines and all, including the JAK-STAT pathway intracellularly. Now, the problem with this is probably 3, 4, 5 of these cytokines are pathological, whereas 45+ of these cytokines are physiological.
So we have a lot of on and off-target toxicities and safety liabilities associated with the JAK inhibitor class. Now, the other challenge is that the JAK-STAT pathway is really only one of three potential pathways cytokines can signal. So although they may vary broadly in the number of cytokines they can target, they're still actually somewhat narrow internally at abrogating the cytokine signaling pathways. So an optimal therapeutic approach would be one where you can inhibit the right combination of cytokines, optimal in their therapeutic effect by balancing both the potent activity of these along with potential toxicities. So we acquired Bioniz in early 2022 for the multi-cytokine platform, a platform that originated at the National Institutes of Health in the lab of Tom Waldmann.
This is a platform that allows us to uniquely target upstream shared receptors to selectively modulate multiple cytokine pathways in a single novel product. This is a very modular, flexible platform, allows us to generate a number of different therapeutics with intravenous subQ or oral delivery. These can be modified to give you different therapeutic profiles for tissue targeting and, distribution. We have broad IP covering the platform, methods of treatment and composition of matter. Now, I know this is a little bit of a complex diagram, but let's talk for a minute just what shared receptor hubs are. These are important signaling hubs, shown here in the green, the shared receptors, and then the private receptors shown in blue. You can see a relationship of multiple pro-inflammatory cytokines through these shared receptor hubs.
It's important to note that in any given biologic function, multiple cytokines, often signaling through shared receptors, contribute to this. So for example, on the gamma c receptor, we have 3 pro-inflammatory cytokines that control CD4, CD8, NK, and B cells, that in combination or redundant to each other, play an important role in the activation, proliferation, and activity of those cells. We also have an allergy for skin, gut, lung, a number of common, common receptors, such as the IL-4 alpha or IL-7, that contribute to allergy in those different tissue systems. From the GP130 family, we have IL-6 and IL-11 that control fibrosis, and we also have IL-27 and IL-35 that are important for controlling inflammation. On the IL-10 beta family, we have IL-10 and IL-22 that in synergy, contrast to each other, can actually control wound healing and tissue regeneration.
And then IL-28 alpha, beta, and IL-29, that in concert with each other, control pathogen and antiviral responses. So this is important because if we think about shared receptor hubs, they offer an opportunity for us to modulate biology more effectively. And from the multi-cytokine platform, we have multi-cytokine activators. These are engineered proteins that engage multiple signaling pathways in a single molecule to modulate biological function. And then we have the multi-cytokine inhibitors that are engineered peptides or proteins that can block multiple signaling pathways in a single molecule to more effectively modulate biological function. So let's take a moment and focus in on the gamma c receptor, which is the first cytokine signaling hub that Equillium is targeting. Now, the gamma c cytokine signaling hub is critically important for modulating T, NK, and B cell activity.
It signals through six cytokines: IL-2, 4, 7, 9, 15, and 21. You can see here the gray common gamma chain and then the private chains colored individually. Now, what's important to note is that IL-2 and IL-15 of this signaling hub actually have overlapping signaling activities on cytotoxic CD8 cells. Whereas if you block IL-2, IL-15 can actually compensate and vice versa, highlighting the importance of blocking both of these cytokines. And you also have IL-15 and IL-21, where there's synergy between these two cytokines that drives a very activated and pro-inflammatory pathogenic phenotype of CD8 and NK cells. We'll talk a little bit more about these in due course. But one thing that's really important of our therapeutic lineup is that IL-15 sits central to this. Now, IL-15 is an apex pro-inflammatory cytokine.
It actually initiates pro-inflammatory cascades, preceding expression of early molecules such as TNF alpha and other cytokines. It plays a critical role in pathogenic organ-specific autoimmune disorders, stimulates the generation of NK, NKT, gamma delta, ILC, and memory CD8 cells that we see driving a number of autoimmune and inflammatory pathogenesis. There's been diverse approaches in the development to block IL-15, shown on the left-hand side here from a review in 2019 by Thomas Waldmann. You can see that there are intracellular approaches through JAK kinases and a number of extracellular approaches targeting either the receptor or the soluble cytokine. But really, the point of this is to highlight that IL-15 is a critically important cytokine driving autoimmune and inflammatory disease. So how does one generate these multi-cytokine inhibitors?
On the left-hand side, what you're looking at here is the IL-2 receptor complex, showing just the beta and gamma subunits, the common gamma chain shown in gray and the private receptor shown in purple. Now, all of the six cytokines that bind to the common gamma chain are four helical bundles made up of the A, B, C, and D helix. And what you can see is that helices A, B, and C interact with a private chain, and helices D interacts solely with the common gamma chain. And each of these different cytokines, the common gamma chain, accepts that helix in slightly different orientations. But if you were to overlay those different cytokines and the D helix, you'll see a number of similar or dissimilar amino acids that play a role in the binding to the common gamma chain.
By generating and screening proprietary composite sequences, we can generate these engineered multi-cytokine inhibitors that allow us to block a number of cytokines while releasing the others. This engineered cytokine inhibitor can then be fused, pegylated, lipidated, fused to a Fc. It can be stapled. It can be added to monoclonal antibodies to generate these optimized multi-cytokine inhibitor therapeutics. Specifically how these work from a mechanistic perspective is shown here on the left. These common receptors, shown in gray, have their private receptors shown in the different colors, and the cytokines bind to the private receptors at high affinity and then dimerize at lower affinity with the shared receptor.
And when you have a multi-cytokine inhibitor that's engineered and designed to bind to the common gamma chain in pockets that are selective for certain cytokines, you can inhibit the dimerization of select cytokines, here shown as A, D, and F. Whereas the multi-cytokine is not very effective at inhibiting the other three cytokines, B, C, and E. So let's talk about the multi-cytokine inhibitor advantage. So we've talked about the limitations of monoclonal antibodies and JAK inhibitors. But the multi-cytokine inhibitors have a number of advantages. They can target undruggable sites not possible with monoclonal antibodies or small molecules. They're optimized in their targeting. They can tackle multiple cytokines, allowing them to be not too narrow, but certainly not too broad either. And this increased selectivity over things like the JAK inhibitor class can afford you a better safety profile.
That being able to inhibit cytokine signaling at a receptor level also allows us to inhibit all three of those downstream pathways associated with cytokine signaling. So we've got a number of different molecules in development at Equillium. We have EQ101, which is currently phase 2, 3 ready. It's a peptide pegylated to inhibit IL-2, 9, and 15, that can be taken forward in cutaneous T-cell lymphoma and a number of different dermatology indications, as well as rheumatoid arthritis, myositis or interstitial lung disease. Now, this is available as an IV with subQ in development. We also have EQ102 in a phase 1 normal healthy volunteer study that inhibits IL-15 and 21. Also, a pegylated peptide administered as subQ, currently being moved forward in celiac disease, but could have potential utility in IBD, type 1 diabetes, lupus, or other hepatic diseases.
Now, the platform allows us to flexibly generate novel molecules with different tissue targeting profiles, and EQ302 is a great illustration of this. A preclinical molecule inhibiting IL-15 and 21, that's been stabilized as a peptide for oral delivery and local acting activity. So this really will change the way we can deliver these multi-cytokine inhibitors. And then the EQ400 series, that is actually an activator program that allows us to go after multiple pro-inflammatory cytokines that synergize to generate activated T-cells for the purpose of oncology or vaccine adjuvants. So moving forward, let's talk about and focus on EQ101, this first-in-class tri-specific inhibitor of IL-2, 9, and 15. So IL-2, 9, and 15 has been translated from the preclinical data into humans. Now, IL-2, 9, and 15 are important cytokines for CD8 and NK cells, whereas IL-9 is important for the inflammation in skin.
And as I pointed out earlier, the relationship specifically between IL-2 and IL-15 makes it very important to tackle both of these cytokines as opposed to one individually. The pegylated peptide, based on the D-helix, has been shown to be very selective at inhibiting IL-2, IL-9, and IL-15 and forgoing inhibition of others, as well as also being effective at modulating all of the downstream pathways associated with cytokine signaling. It's administered currently as a low volume IV push, with a subcutaneous formulation currently in development. Now, from a modeling perspective, this has been extensively studied. In the early days, coming out of the NIH, it was tested against ruxolitinib in multiple lymphoproliferative and leukemic T-cell lines, and more recently tested against ruxolitinib in a mouse model of immune-mediated hair loss or alopecia areata.
We've got significant clinical experience with this molecule of over 100 subjects dosed, and it's demonstrated a very safe, tolerable profile to date, and also achieved proof of concept in treating refractory cutaneous T-cell lymphoma patients. So let's highlight one of the advantages we feel we get with targeting the pro-inflammatory cytokines at the receptor level. So what you're looking at here is the IL-2 complex with IL-2 bound. Now, this will trigger all of the downstream signaling pathways, as shown here in this Western blot when you add IL-2. You see phosphorylation of the STAT through the JAK-STAT pathway, phosphorylation of ERK and PI3K.
Now, when you add ruxolitinib, a JAK-STAT inhibitor, you of course see an inhibition of the phosphorylation of STAT 3, 1, and 5, but you still see phosphorylation of ERK and PI3K, showing that it doesn't fully suppress all of the downstream cytokine signaling. Now, contrasted with that, if you're able to inhibit the binding of IL-2 to its receptor complex, you can see on the right-hand side the ability to inhibit STAT 1, 3, and 5, but also PI3K and ERK signaling, showing that it's more complete in its ability to modulate those pro-inflammatory signals. As I pointed out earlier, with its generation at its origins at the NIH, some of the early studies were actually in leukemia and lymphoproliferative T-cell lines that led Bioniz Therapeutics to test this molecule in cutaneous T-cell lymphomas.
Now, cutaneous T-cell lymphoma is an indolent chronic cancer that causes patch plaque disease and tumors on the skin. This disease is known to be driven by IL-2, IL-9, and IL-15 in terms of pro-inflammatory cytokines that drive the aberrant activity of these T cells. What's also known is blocking IL-2 or IL-15 alone was ineffective at treating large granular lymphocytic leukemia or adult T-cell lymphoma when done individually. The need to block both of these was very clear. The model you're seeing below is a mouse model of adult T-cell leukemia, and you can see the control animals there. You see a lot of fluorescence for the tumor growing in these animals.
And when you treat with EQ101 at 40 mg per kg IV BIW for 4 weeks, or ruxolitinib provided as a continuous administration at 50 mg per kg per day, that's very effective at suppressing the tumor growth. Now, it's perhaps more easy to see here, the fluorescence of the tumors. We can see large amount of tumor growth with the PBS-treated animals and very little growth of the EQ101 and ruxolitinib-treated animals. Now, what I really want to illustrate from this animal model is that you can inhibit 3 cytokines and get very, very specific, selective and potent inhibition of tumor growth without the need to go for a pan-JAK approach, inhibiting over 50+ cytokines. So specificity can still draw all of the efficacy in those molecules. Now, historical studies to date for EQ101, it's been through over 100 subjects to date.
There was two phase I studies, a SAD and a MAD, conducted at various different dose levels, and then a proof of concept study, phase I/II, in patients with LGLL or CTCL, and we'll talk a little bit about that proof of concept data. But just to quickly summarize the experience to date in normal healthy volunteers, this was observed to be safe and well tolerated, no DLT, no clinically significant lab abnormalities, no AEs greater than Grade 3. The most common AEs seen in the SAD were headache, with about 17%, and in the MAD, sore throat and headache, headache in about 16%. We saw dose proportional PK and PD with a half-life of approximately five days.
And we also saw that multiple doses of EQ101, dosed at 1.5 mg/kg or longer, actually led to prolonged PD effects exceeding 7 days, suggesting every week or every other week dosing was available. And no detectable anti-drug antibodies or neutralization was detected in those patients. So let's switch gears and talk about the phase I proof of concept study in CTCL patients. This was a study in LGLL and CTCL patients. I'm just gonna describe here the CTCL portion of this. These were CTCL patients who were heavily pre-treated, so refractory to a median of 5 prior systemic treatments. In this study, which looked at a number of different doses before expanding a 2 mg/kg range, and you can see at the bottom there, a 4-week treatment followed by a 3-month extension.
Actually, in the long-term extension study, many patients were dosed with this drug beyond 70 weeks. Now, what we observed was dose-dependent PK/PD. It was observed to be well tolerated, safe, no drug-related SAEs or no clinically significant lab abnormalities. And we saw dose-dependent reductions in IL-2 and IL-15-dependent cells, alongside a concurrent improvement in what's called the Modified Severity Weighted Assessment Tool. Think of that like a PASI score for the oncology field, looking in patients with patch plaque tumors. And it was 2 mg/kg that was chosen for dose expansion based upon these PK/PD studies.
So when we think about understanding the efficacy of this study, perhaps it's best to contrast this to what we call the MAVERICK phase III trial, which evaluated mogamulizumab, which is an approved therapeutic, versus vorinostat, a non-specific HDAC inhibitor, in a large phase III study, and that allows us to sort of benchmark where we land with EQ101. When we look at CTCL Stage IB/II patients, shown in the graph and the pictures below, mogamulizumab scored an mSWAT of about 28%, and vorinostat about 19%. But in the heavily pre-treated patients treated with EQ101, we saw an mSWAT of 42.1%. Even if you were to discount this a little bit for the smaller numbers or cross-trial comparisons, that's a very compelling mSWAT to achieve in these patients.
You can actually see below the improvement of these skin tumors and patch plaque lesions in these patients that continue to improve beyond week 16. As I pointed out, many of these patients continued to be treated for beyond 70 weeks. Now, CTCL is still a disease of high medical need, very expensive therapeutics, very poorly tolerated therapeutics. This was ready for a phase III study prior to Equillium's acquisition of Bioniz in 2022. To sort of wrap up this first part of the clinical and translational section, 100 patients have been dosed, safe, well-tolerated profile observed, compelling clinical activity observed in patients treated with EQ101 with CTCL. It's an attractive target product profile for treatments in CTCL patients, with not only very good efficacy and durability, but also a very compelling safety profile observed.
The FDA had largely given concurrence on moving forward with a phase 3 study, but we've decided to pivot at the point of acquiring Bioniz to take EQ101 into medical dermatology, such as alopecia areata, vitiligo, or atopic dermatitis, where we think it's a more proximal and rapid way for us to create value in the franchise. So let's talk about that franchise. EQ101 is very well suited in terms of its cytokine inhibition profile to tackle a number of dermatological diseases. We've shown already proof of concept achieved in cutaneous T-cell lymphoma patients in that phase 2 study. We recently initiated an alopecia areata study, really having our eyes set on an alternative or substitute for JAK inhibition in this patient population.
Should this be successful, we could think about expansions into vitiligo, where JAK inhibitors and anti-IL-15 approaches have been, or are being tested, as well as subsets of atopic dermatitis that still remain refractory to current approaches, or to displace drugs that we believe are, are less effective or less well-tolerated in this patient population. So really, a multi-billion dollar market opportunity for EQ101 in medical dermatology that really can lead us to have a therapy, therapy that has a safer, more tolerable long-term profile. So in alopecia areata, let's just talk quickly about the underlying immune pathogenesis. So simplified here, quite heavily, in the center, you can see CD4, CD8, and NK cells. These are three very important cells that are driving destruction of the hair follicle. When these cells are activated, they release interferon gamma that binds to the hair follicle and causes destruction.
In turn, those hair follicles can release IL-15, that further activates the CD8 cells. Now, on the far left-hand side, we can see three cytokines that are very important for driving the activation, proliferation, and activity of these cells: IL-2, IL-9, and IL-15, that have all been well-studied and well-validated from transcriptomic profiles and human data. So by blocking these cytokines that are activating these cells, we hope to very, very effectively dampen this cycle of destruction between the cells and the hair follicle and allow the systemic inflammation to be reduced and hair to regrow over time. Now, we've shown some model data of leukemia and lymphoproliferative cells, but here I wanted to share with you some data in a model of immune-mediated hair loss in mice. Now, this is a model where you take animals, you inject to them activated human cells.
That causes a lot of dermal inflammation of CD8 NK cells, that causes destruction of hair follicles, and then the mice become bald. And then at that point, with large amounts of inflammation, you intervene with either EQ101 at 2 mg/kg IV twice a week, or ruxolitinib at 30 mg/kg twice a day. And what you can see as the time goes on through day 21, is very quick damping of the immune response and restoration of hair in the animals treated with EQ101. You don't see as an impressive result with ruxolitinib, although by day 21, those animals are starting to regain hair. So pictures of animals aside, 'cause that can be a little subjective, let's focus on the right-hand side. These graphs show you the cumulative levels of CD8 cells with the cytotoxic marker NKG2D.
This is an activation marker of activated cells causing destruction of skin follicles, and other tissues. Now, in the PBS treated group, we see a lot of those activated cells. In ruxolitinib-treated animals, we see about a 50% reduction, but we see over 90% reduction when treated with EQ101. And this may harken back to what I pointed out earlier, is that by abrogating the cytokine signaling at the receptor level, inhibits all three of the downstream cytokine signaling pathways. Whereas you may still get some level of inflammation that's creeping through and leaking through those orthogonal pathways in the ruxolitinib-treated animals. So by going after these three cytokines, we believe this is a more safe, selective approach to modulating the pro-inflammatory signals, but one that also could be potentially more potent long term. So at this stage, I'd like to hand it over to Dr.
Maple Fung, our Chief Medical Officer, to walk you through some of the clinical data and introduce Dr. Mostaghimi to discuss the alopecia areata landscape. Maple.
Thanks, Stephen. Today I'm going to review our ongoing alopecia areata study, as well as share what we've learned about treatments for alopecia areata before getting to the highlight of today's presentation, and that's really chatting with Dr. Mostaghimi, our alopecia expert. This first slide shows our phase 2 study design. We at Equillium are conducting this open-label, single-arm phase 2 study of EQ101 in subjects with moderate to severe alopecia areata. This study design might be familiar to you, as it's similar to those that you might be familiar with from other similar products in different phases in this stage of development. We targeted studying approximately 30 subjects with at least 35% scalp hair loss, or as defined by that SALT score of 35.
This current episode of hair loss had to be at least 6 months in duration, but no more than 7 years. Enrollment has now been completed, and so there are no longer patients in the screening period, but the subjects are all now in the treatment period and beyond, where we are dosing subjects with EQ101 every week, at 2 milligrams per kilogram with an IV bolus push for 24 weeks, followed by that follow-up period. The objective of the study is really to assess the safety and tolerability of EQ101 in alopecia areata subjects, but then establish some biologic activity through efficacy, pharmacokinetic, and pharmacodynamic markers. Following this study, we could then perform a dose selection study. The next slide highlights some key attributes from the recently completed phase 3 programs of ritlecitinib, baricitinib, and deuruxolitinib.
Clearly, it's been a great advancement for alopecia areata patients, but this also has given us a lot of learnings on how to best conduct future alopecia areata studies as well. First, I'd like to highlight the really low placebo rates of hair regrowth in these trials. They're really no more than 9% and more likely closer to the 5%-6% in terms of hair regrowth in the placebo arms of these large phase 3 programs. Second, we also like to note really the 40%-50% hair regrowth that has been seen in these trials, knowing that that is in the over 24- to 36-week timeframe. So this is really, you know, what, you know, patients and physicians may be looking to achieve with additional treatment options.
So this next slide reminds us from the baricitinib studies, and this has recently been published, I believe, in the British Journal of Dermatology that hair regrowth and speed might be dependent on the severity of the disease. On the left is the 2-milligram dose for baricitinib, and on the right, the 4-milligram dose. And those with the very severe disease, which was defined in this trial as a baseline SALT score of greater than 95% or greater than 95% hair loss, they had slower ability to... And it may take, and they have a lower success rate in reaching those SALT scores of less than 20, compared with those patients that have severe disease, even of that SALT score, 50-94, or that 50%-94% hair loss.
Truly, the effects of treatment may take beyond 52 weeks even to fully reach their full effect. So the next slide has a lot of information on it, but we wanted to highlight some of the key late-stage assets in the alopecia areata pipeline. The 2 recent approvals are on the far left, and then following by the resubmitted deuruxolitinib program, followed by other phase 3 and phase 2 programs that are in development. I'll know there's a lot of words and words here, but I'm just gonna highlight some key features across the different programs here. Really, we see high degrees of similarity in terms of the study designs.
When we look over on the right-hand side with the phase 2 programs, you'll see that the SALT scores for eligibility had to be at least 25 across the programs, and they are both placebo-controlled as well as a number of open-label study designs. The endpoints for these phase 2 proof of concept studies tend to look at % change in the SALT at about the 24-week mark. Also, when we look at the dosing towards the bottom of the slide here, we'll see that most of the JAK inhibitors are oral, but there are a number of new drugs that are subcutaneously dosed as well. Again, just really focusing on the fact that on the left-hand side of the slide, and in later stage development, they're predominantly JAK inhibitors that are in development.
That leads to my final slide, where we highlight some current concerns in the alopecia areata treatment landscape. Alopecia areata is a chronic, lifelong disease, unfortunately, which affects young men and women. The Spherix Global Insights recently conducted a survey of greater than 100 dermatologists, who up to nearly 80% reported that there's an extremely high unmet medical need to treat alopecia areata. Here in the middle panel, you'll see that the majority of them also were very concerned about the safety of oral JAK inhibitors in their alopecia areata patients, likely in part due to this black box warning, which you'll see on the right-hand side, that warns of serious infections, malignancy, hematopoietic disturbances, as well as cardiovascular events.
And so with that, I'd like to, in order to join the discussion today about alopecia areata clinical landscapes and treatments, I'd like to welcome Dr. Arash Mostaghimi. Dr. Mostaghimi is an associate professor of dermatology at the Harvard Medical School. As you've heard before, he's Director of Inpatient Consultation Services at the Department of Dermatology at the Brigham and Women's Hospital, and he has long been a proponent for alopecia areata patients and treatments, participating in many clinical trials with extensive publications in this area. Welcome, Dr. Mostaghimi.
Thanks so much for having me, Maple.
Dr. Mostaghimi, before we tackle some questions on the alopecia areata treatments, unmet needs, and thoughts on EQ101 in development, can you provide the audience a bit more detail on your background, as well as a clinical overview of alopecia areata?
Sure, absolutely. So my interest in alopecia areata comes not only from my work as a clinician and researcher, but also, I'm a parent of a daughter with alopecia areata. My daughter developed alopecia universalis at age five, which began my interest in this field, and it's been remarkable to see the growth and progress that's been made over the years. So alopecia areata is a fascinating disease. It's really a disease of inflammation of the hair bulb. So, you know, when we look at eczema, we look at psoriasis, we see that the skin is red from the inflammation. In alopecia areata, you also have profound inflammation, but it's deep, it's under the skin. It's right at the base of the hair.
So what happens is the hair weakens, it falls out, and then the inflammation remains and keeps the hair from regrowing. So one of the major differences between alopecia areata and these other conditions is that because the inflammation is deeper, often a lot of our topical treatments don't penetrate sufficiently into the skin to reach the inflammation. So our reliance is on either systemic agents, such as the ones that were described earlier by you and Stephen. Or for more mild to moderate disease, we actually rely a lot on injections. So we commonly will have people come in on a monthly basis, where they'll receive steroid injections to their scalp. This is painful, it's difficult. You know, COVID has shown us how difficult it is to get somebody to get one injection once for a vaccine.
These are patients coming in for 20 injections into their scalp every 4-6 weeks. You can imagine how difficult it is for adolescents and children, who really are traumatized by it. It's the same treatment we've had for the last 50 years. So I'm excited that we're finally able to talk about new options.
Thanks, Dr. Mostaghimi. So with that, we can go ahead and move to the first question. So how are you treating patients with alopecia areata? If you could talk about... a little bit about how different severities impact that treatment, and what treatments do patients prefer, as well as what patients might physicians prefer?
Yeah. So the way that we can think about alopecia areata, there's kind of two different approaches toward severity. One is the severity that's defined in clinical trials, where really patients with 50% or more hair loss is defined as severe. When I think about that, I think about, you know, show me 45% of your hair that you'd be willing to lose and not consider having a severe disease, right? So in clinical practice, a lot of the severity is not just based on amount of hair loss, but also how much it impacts the patient. Also, non-scalp hair loss, such as eyebrows and eyelashes, are really important and can really change the way that one looks.
So the goal in alopecia areata is to get somebody to the point where they can present themselves comfortably as themselves, and not either feel the individual psychological ramifications of the disease, but also not to receive stigma on the basis of having this condition. So the majority of patients, as we talked about before, we're gonna have limited disease. So this is about 95% of folks. And by limited, I mean that they're not at the most severe 50% in a phenotype. The prevalence over one's life is 1%-2%. The incidence, rather, over one's life is 1%-2%, so it's a fairly common disease. But the majority of patients only have one or two spots that will go away on their own. They'll resolve automatically.
For another group of patients, they'll continue to have more chronic disease, either with relapsing, patches, or that they will extend and continue to have, more extensive disease, such as the people, in this, in the studies that we've mentioned. Now, the struggle is that with the first round of drugs for this indication, the JAK inhibitors, you know, to maintain a risk-benefit ratio, they really focus on people with the most, severe phenotypes, so patients that had, all or almost all of their hair loss, or at least 50%. So the majority of the people in the trials that were reviewed, really tended towards, chronic disease with substantial hair loss.
But there's a large number of people who are in that middle range, in that sort of 20%-50% range, which would not be considered a success in trials. Success in trials is below 20%. Or, but they don't qualify for the trial, so there's a load of a no-man zone there. And that represents a tremendous need in this field because, as mentioned before, injectable steroids are still the mainstay of treatments. Oral prednisone is an option, but not something that you can do long term. Other drugs, such as cyclosporine or methotrexate, old, you know, calcineurin inhibitors or antimetabolites, have successes that are really in the 10%-15% range, but with a tremendous amount of side effects.
So really, Maple, what we're left with is, we really have to move towards these new JAK inhibitors and move towards them early because they're not, you know, displacing effective treatments. They're really entering a void where there really previously weren't very many efficacious treatments.
That's very helpful, Dr. Mostaghimi. Do you wanna talk a little bit about what treatments patients prefer then?
So when patients are deciding what treatments they want, they're really looking at three things, and it's pretty consistently these top three things, although the order may be a little bit different on the patient. First, it's clear they want their hair back, right? So hair regrowth, in terms of both extent and quality of hair, is super important for them. Secondly, they want to know that the drug they're taking is going to be safe, right? So they're often risk-averse. These are not patients like atopic dermatitis, where they're itching all the time, getting infected, things along those lines. This is a lot of psychosocial impact. So a lot of patients, while they want to feel better, don't wanna take a tremendous physiological risk on that basis.
The third thing is durability of results. So basically, once you get your hair, how long does it last? So unlike, let's say, a flare in atopic dermatitis or psoriasis, so let's say that you get a little bit of a flare, you get a little bit itchy, you scratch a little bit, you move from there. In conditions with such as alopecia areata, if you get a flare, you may lose some hair. That might be 12 inches of hair. Even if your hair starts coming back and starts growing, it may take, you know, six to 12 months, up to 2 years, to get yourself looking and feeling the way that you did before. So that can often be challenging. The result is, as you see in this graph, there's profound dissatisfaction with current therapies.
Up to 70% of people saying that they're not satisfied with the current therapeutics, and there's a lot of alternative medication used. So there really is a tremendous need for additional therapeutics.
Great, thank you. And how about physicians? What types of treatments do you prefer in patients?
So as a specialist and expert in alopecia, I'm comfortable with using JAK inhibitors, but that's not something that is shared by a lot of my colleagues. You know, dermatology has been spoiled by the success we've had with the biologics that have been developed for psoriasis and the ones that have been developed for eczema. So these are really highly, highly efficacious medications that precisely target the key and core pathways in these diseases. Whereas in alopecia areata, we're left with sort of these broad inhibition, the way that Stephen outlined in his presentation on mechanism of action. The net result is that we're not exactly sure what to make of the net immunosuppression in these folks, right?
Not just from an immune status, but there's also a fairly ubiquitous expression of JAK proteins throughout the whole body. And other risks, such as, thrombosis and the other things you saw in the black box warning, are real risks that dermatologists are often uncomfortable not only exposing patients to, but even in discussing with patients. So the need for ongoing lab monitoring, these other potential risks, makes it challenging for a lot of dermatologists. And adoption has not, it's climbing, but it's not where it needs to be.
Well, that makes sense. Thanks, Dr. Mostaghimi. I think the other question we had was about the time it takes to see hair regrowth and the timing. Is that an issue for patients?
Yeah, so as I mentioned before, you know, you have those, those three main things that patients are looking for, you know, efficacy, safety, and durability. Velocity of improvement and how fast things get better is also super important. You know, patients want their hair immediately. But if given an option between something that is safer and more durable in response versus something that might work more quickly but has a questionable side effect profile, I think the majority of patients would prefer that safety profile. As I tell my patients, "You know, it's a marathon, it's not a sprint. The goal is to get your hair back, the goal is to maintain your hair.
The goal is to get you looking and feeling the way that you want. If it takes a little bit longer to get there, as long as we can get you there and maintain you there, that's the most important thing.
Great. Great, very helpful. I guess before we move on to unmet needs, just the last question on treatment here is that when you decide to, you know, at what point do you make a decision to change treatment options? Is there a specific time period in which you're waiting to see certain results?
... Yeah, so this is something that is critical when talking to patients. So the best way to think about the JAK inhibitors is that they're a tremendous move forward for the field of alopecia areata. In the same way that Enbrel was a tremendous move forward for patients with psoriasis. But our hope is that much like Enbrel, you know, although it was a major move forward, we come up with much better treatments down the road, which is what we're discussing in this conference today. The part of the issue is that these drugs work very slowly, so you may need at least 6-9 months of therapy before you can make a decision as to whether or not these drugs are working or not.
You presented data that went all the way out to 52 weeks, so beyond sort of the 24 and 36 weeks, that was the primary endpoint of these trials. There's even data now that's suggesting that up to 104 weeks, some patients are still regrowing hair and not where they want to be. So it's a very, very, very slow process. Even to say that you were not successful, let alone not successful in terms of not reaching your goal, but not even beginning to get towards that, it takes about 6-9 months minimum, really, to be able to get there. So this is very different than, you know, atopic dermatitis, where we tell patients, you know, "In a week, your itch is going to get better.
In two months, nobody will know you ever had this disease. So we're—we have a long ways to go.
Great. Thank you, Dr. Mostaghimi. So now, we'll kind of switch gears related to, does there remain an unmet need in the treatment of alopecia areata with the approval of JAK inhibitors? And are there concerns about long-term use?
Absolutely. So the reality is that about a third of patients will get to where they want with JAK inhibitors, which is awesome for those patients, but that means there's two-thirds of patients with severe disease who really don't respond to that. And remember, the outcome in this trial, when they're considered a success, is SALT less than 20, which means they go from having over 50% hair loss, a SALT of over 50, to having less than 20% hair loss. Now, while some of those patients may have a complete head of hair, there's a lot of patients that have 10, 15, 20% of hair loss, which can still really impact the way that you look and the way that you need to style your hair.
So again, going back to the analogy with Enbrel, you know, those PASI 30, PASI 50 outcomes, which are considered great with Enbrel, now the new drugs blow that out of the water. So we're hoping that we are really thinking about SALT less than 10, SALT less than 5. So if you look at for this slide here, for 100 patients with alopecia areata, about 10 of them will have that severe AA, defined as greater than 50%, and about half of them, with the current treatments, will have a successful treatment, defined as SALT less than 20. That really means that there's 95% of the population that doesn't have new and effective treatments, even a...
Not only the other 5 out of the 100 that have severe AA, but also patients that will have significant hair loss that's less than 50%, that really are impacted but don't qualify for the current medications. You asked me also, Maple, about long-term side effects. I think that's really the million-dollar question for this drug. The reality is that we don't know what the long-term side effects are. We do know that there's some laboratory abnormalities, some increased risk of infection, and then idiopathic rates of thrombosis that we've seen in the data we have across all JAK inhibitors right now, which can be really challenging to talk to patients about. This is not something. The thrombotic risk is not something that you can monitor and adjust the medicine up or down.
It's something that either happens to you or doesn't happen to you, and when it does happen to you, it can be incredibly life-threatening and dangerous. The other thing that we don't know is, you know, what if you're on these medications for 5 years, 10 years, 15 years? The data from JAK inhibitors shows that if you're on the medication, it works. And if you stop the medication or dose reduce, so when baricitinib, going from 4 milligrams to either 2 milligrams or off, leads to reduction in that, in those gains, where about 80% of people who were successful will lose their hair again. So only 1 out of 5 folks are going to be able to maintain that, their hair once coming off the medication.
And we don't know which of those out of the five, we don't know which one that person is going to be. When I give this medication to patients and we treat them, the idea is really, this is a long-term treatment until something better comes along, and we can replace it. Or that we have a better sense that the safety of this is improved.
Great, thank you for that. Oh, so what are dermatologists looking for then?
So dermatologists are looking for really what, what we have in psoriasis and eczema, which is a, a targeted therapy, that really, impacts the parts of the immune system that are necessary and sufficient to cause this, disease. The idea, is a little bit like, Goldilocks and the Three Bears, right? If you, if you block everything, that's too much. If you don't block enough, you may not get the hair back. We wanna kind of get a sense of, well, what, what's just right? And I think that's what we're, that's what we're seeking. So if, if the ability to have a targeted treatment that has good efficacy, good durability of treatment, and a, strong safety profile, would be ideal.
Is there anything in development that you think is promising, Dr. Mostaghimi?
... I think looking across that slide of development that you showed before, you know, a lot of JAK inhibitors are on that slide. They may have slight differences in terms of efficacy or safety between JAK inhibitors, but ultimately, the concerns that we're discussing are really a class effect. So while it's always nice to have additional options, it's not going to be a dramatic advance to have a new JAK inhibitor on the market. What's most compelling, I think, is the specific targeted treatments, ones that are looking at specific cytokines, blocking specific pathways from that regard. And there are a couple options in addition to Colina's molecule on that list that you showed.
Great. Thank you very much. So for our final question here, can you share your thoughts on EQ101's mechanism of action and its potential use in alopecia areata patients, and what are you hoping to observe in this ongoing study of ours?
Yeah. So something that's really fascinating about alopecia areata is that unlike, let's say, psoriasis, right? Psoriasis, if you look at affected versus unaffected skin, there's 1,000 genes that are expressed differently. It looks like almost all of these go through the pathway of IL-17. When you block them, you can retain the rest of the immune system and really have profound efficacy. We haven't identified that yet in alopecia areata. So we know that IL-2, IL-15, and IL-9 are critical to the pathogenesis of this disease. We know that cyclosporine, which is a very toxic drug when used on a short-term basis, can regrow hair.
We know that as Stephen's demonstrated, the interferon pathway basically cycles with the increased production of IL-15, propagating this disease and leading to continued inflammation, suggesting that IL-15 blockage, which has not only been shown in animals, but in humans as well, may lead to regrowth. And then, of course, IL-9 has broad inflammatory expression in the skin. So that combination, the idea that I don't have to just throw one dart, but I get three chances at hitting the target, is super valuable and useful and an exciting component of this specific medication. The other thing that we don't know yet about this disease is whether or not patients are the same from an inflammatory basis.
We don't know how heterogeneous they are. So it may be that each of these molecules in different amounts and different components is perpetuating disease in patients. That two patients, let's say, that have a severe phenotype may actually have different specific natures to their inflammation and hitting that's causing it. So hitting multiple cytokines simultaneously in a manner that maintains the rest of the immune system intact seems exciting from that standpoint. What we're looking for in this study, I think, is just a question of, does hair grow in humans, right? And that could be eyebrow hair, it could be eyelash hair, it could be, it could be scalp hair.
And are we beginning to get that regrowth in folks who previously didn't have that hair, who are among the hardest and most refractory to treat, the most refractory to current treatments? Are we maintaining the safety profile that was seen across all the other trials for this medication? The speed, I think, is less important. I think that there may be a function of dosing or other specifics that need to be adjusted. But ultimately, we're trying to get to the point where we can tell patients, "Hey, if you use this medication, it will work. It'll work over the long term. It'll be safe for you to use, and we're confident in its efficacy and safety.
Great. Thanks, Dr. Mostaghimi. Just a last question here. Is there a specific attribute of EQ101 that gives you reason to believe it will demonstrate a signal?
I think specifically that IL-15 blockage. IL-15 really seems to be uniquely involved in this pathway, not only the development, but also the propagation and maintenance of alopecia areata. So I'm particularly excited in that component of the three cytokines that are being targeted by this drug.
Well, thank you, Dr. Mostaghimi. So, just to wrap up, do you have any final thoughts then on our discussion today?
I think it's important for us to note that we're really in the very early innings of this disease, that having the first two FDA-approved medications that are both in the same class for this disease is a profound step forward and something that's very meaningful for patients. But in the same way that the story of psoriasis began with Enbrel and Humira and didn't end there, that it really behooves us to look for better options. Not only better from a side effect profile, safety profile, but also we're really not there yet with the long-term efficacy. So I'm really excited that additional attention is being paid to new mechanisms of action for this condition.
All right. Well, thank you so much, Dr. Mostaghimi, for those insightful comments, and we look forward to the Q&A. Dr. Mostaghimi is going to stay on for additional Q&A. For right now, we're gonna turn it back to Bruce Steel, our Chief Executive Officer here at Equillium.
Yes. Thank you both for that enlightening discussion. So, coming back to sort of the upcoming milestones and forecast, and again, to revisit, our mission as a company is to develop highly impactful novel therapeutics to treat a range of severe autoimmune and inflammatory diseases. In most of the cases, particularly with the indications we're pursuing, there are few, and in some cases, no drugs currently approved for these severe diseases. So we're very pleased and fortunate to have this opportunity to be working currently on three novel programs that we hope can bring significant improvements to patient outcomes and quality of life. With EQ101, as discussed here, we expect to have some initial data on the ongoing alopecia areata study before the end of the year.
Importantly, followed by our top-line data, with guidance currently expected for mid-year 2024 next year. With EQ102, we're currently in our SAD/MAD study and do plan to provide an update on this portion of the study prior to the end of the year, with a view that EQ102 and/or its follow-on program EQ302, which we just released some information on this morning, could be very well targeted for patients with celiac disease. Again, an indication or, or a disease area with no approved drugs currently on the market. And itolizumab, we do plan to have a significant update on the EQUALISE study in lupus nephritis. We will be presenting posters at both ASN and ACR in November. We do hope you will tune into that.
This will be a very robust update, with a prelude to the type of data we'll be delivering to Ono early in the new year. We have brought in that guidance that we expect to deliver the LN top-line data to Ono early in the new year. To then be followed by the interim data from the EQUATOR study in GVHD, our Phase 3 program for acute GVHD, expected during the course of 2024. Based on the timelines and current enrollment in the EQUATOR study, we do expect both that data deliverable and Ono's option exercise period to occur during the course of 2024. So with that, I think, we will open this up to any Q&A for Dr. Mostaghimi and/or our team.
If you would like to ask a question, simply click on the Raise Hand button at the bottom of the screen. Once you have been invited to, please unmute yourself and begin with your question. If you are dialed in, please press star nine to raise hand and star six to unmute. For those watching on the webcast, you may submit questions through the Ask a Question tab in the top right of the video player. Our first question comes from Catherine Novack with Jones Trading. Catherine, please unmute yourself and ask your question.
Oh, hi, can you hear me?
We can, Catherine . Go ahead.
Okay, great. I guess my first question is actually on the oral peptide delivery technology that you released this morning. You know, it's very interesting. How do you expect to validate this clinically? Do you see a commercial proposition for using this technology to generate partnerships, you know, in addition to using it on your own molecules?
Yes, so, a couple questions in that question, Catherine, and, I'll welcome, Stephen to maybe join in on the response. I think first is, you know, a significant portion of the acquisition of Bioniz was not only the, clinical development programs, including EQ101, which had already been through 90 subjects at the time of the acquisition. With readiness to quickly move into, the alopecia areata study, as well as an open IND for phase 2/3 development in cutaneous T-cell lymphoma, where that initial proof of concept was completed. But also, the underlying platform, technology, which included, the concept of taking, these peptides, and aiming to deliver them in alternative routes of administration over and above the, sub-Q or IV routes that were already established with EQ101 and EQ102.
So clearly, in indications that are chronic, and particularly those, say, in the GI tract, where you may be able to deliver your targeted agent directly where it's needed, oral delivery would be a very attractive route of administration. But let Stephen also add a little bit of context here.
Yeah. Thanks, Bruce. You know, I think one of the really interesting things about this platform and the fact that we're working off natural molecules or fragments thereof, is that they can be modified to bind to antibodies. They can be modified to attach to Fcs. They can be delivered orally, systemically, maybe even topically or inhaled as well. The small fragment that we're talking about here for EQ302 is about 20 amino acids, that's then been screened and optimized and hydrocarbon stapled. That's done a number of really interesting things to the molecule that we've shown in these sort of early proof of concept studies, is it allows us to get very good GI stability, permeability, and translation of that molecule working locally, acting in quite aggressive animal models of GI inflammation.
Now, when we think about the utility of this to something like celiac disease, where those aggressive CD8 cells are essentially just behind that first layer of cells in the gut lumen. So what we have now is a molecule that we could administer orally, that could be locally acting and very, very effective at suppressing the activity of those cells. Now, the same technology of stapling could be applied to other molecules, such as EQ101, that could then perhaps be unpegylated and then used, orally and/or potentially topically to certain diseases as well. So I think this just, you know, does a number of things. First, it highlights the ability to modify these molecules to give you better drug-like properties, so we call second-generation molecules, more targeted in that approach.
But you highlighted another really important part, which was a strategic priority for Equillium, which was by being able to tap this platform and be able to target these shared receptors in a way that I think is unique and proprietary to Equillium, and then generate these molecules, it really allows us to open up the opportunity to partner these molecules for different indications, different markets, et cetera. And that's something that really further de-risks the company, because it allows us to, in these more sort of fiscally frugal environments, to become more self-sufficient on our platform, on our partnerships, to be able to create value for shareholders without having to tap capital markets.
... Yeah, and, obviously, during the course of the last year, we've demonstrated, I, I'd say, a pretty robust business development capability, with a lot of focus on strategic, partnering, with, you know, 2022, being a very important year for us, including, you know, closing on the acquisition of Bioniz in the early part of the year and then, recruiting Ono into our strategic partnership. And as Stephen highlights, in these periods and cycles that we as an industry go through, where the capital waxes and wanes, and this is an extended period where, the equity capital markets have been extraordinarily challenging. Having this type of flexibility as well as capability, on board, and active, I, I think is quite important as we think about, capitalizing the business and, and programs.
So yeah, we're pretty active on the strategic BD front on an ongoing basis.
Great. And, and just one more on the timeline of EQ101. So previously... You mentioned earlier doing a dose optimization study following the prior, the alopecia areata study. And then you've also talked about a subcutaneous formulation. So do we be thinking about, after these data, you know, a dose optimization and potential bridging study for subcutaneous? Or, you know, how should we be thinking about the development progress of EQ101 going forward?
Yeah, good, good, good question, Kathryn. So, you know, generally, assuming we feel that we've seen the program has continued to demonstrate favorable safety and tolerability in a new patient setting here with patients with alopecia areata and sufficient signal in this initial evaluation of the program in these patients, then we would plan to move ahead with a phase 2/3 development program. We obviously don't want to provide a lot of details on something that's a little bit premature at this point, but generally, I think we'd likely want to test probably another dose level.
We would also be expecting to move from the current IV push into a sub Q delivery formulation, which is, you know, well underway obviously, given that we would look to turn things around quickly, following the top-line data, if we, you know, do get conviction that this overall approach could be differentiated for this patient setting.
Got it. That's very helpful. Thank you for taking my question.
Yeah. Thank you, Kathryn. Appreciate you joining us today.
Our next question comes from Raghuram Selvaraju with H.C. Wainwright. How might the dose vary between various medical dermatology indications for EQ101, and how might that differ from the oncology dose? What are the implications on both safety and efficacy?
I can go ahead and take that one, if that works. So, great question. And clearly, we're still continuing to learn more about EQ101. I mean, we're fortunate that the package that came to us when we acquired Bioniz and those products had a great safety profile, and early efficacy for sure in that cutaneous T-cell lymphoma. I think, you know, but since we've acquired that, you know, our team internally is continuing to work on, you know, pharmacodynamic type of markers to understand better, you know, what dose should be used in both indications. And so we're certainly awaiting anxiously the data from our alopecia areata study, and we'll have a close look at that and compare it to the CTCL data to understand what doses might be needed in either of those indications.
Again, very fortunate that the range of doses that had been administered in the trials to date have been pretty well tolerated and quite safe. So we have a nice range to work amongst.
Our next question comes from Thomas Smith with SVB Leerink. Please unmute yourself and ask your question.
Hey, guys. Good afternoon. Can you hear me okay?
We can, Tom. Go ahead.
Okay, great. Yeah, thanks for putting together this event, and thanks for taking our question. Yes, first for the Equillium team. You mentioned that you've completed enrollment in the EQ101 alopecia study. Congrats on that. I was wondering if you could comment with a bit more detail on the baseline characteristics of the patients that you've enrolled and how that compares versus the baricitinib and the deuruxolitinib population, and how should we think about the differences in patient populations when it comes to interpreting the initial results from the EQ101 study?
Yeah, Tom, so excellent questions. And obviously, in this presentation today, we provided, I think, some insights into, those different patient populations, you know, the very severe versus severe. In our initial data update on the program, later this year, we will provide, a full breakdown of the patient segmentation, is our expectation. And, and obviously, the, you know, very severe patients are, demonstrably harder to treat, compared to, the less severe patients, based on, you know, predecessor, data from the JAK inhibitors. So, you know, this is the type of information we plan to elaborate on, on that upcoming initial, data that we'll provide later this year.
I, you know, I can add, we do have a significant number of patients that fit the very severe criteria. You know, in terms of starting this initial study, those patients were pretty queued up, again, indicating that, you know, the high unmet medical need there. But we will have a blend of patients across the spectrum.
... Got it. That's helpful. Thank you, Bruce. And then, one for Dr. Mostaghimi. Thanks for the overview and your insights here. I was just wondering if we could push you a little bit to put some numbers around the signal that you'd like to see in this proof-of-concept study for EQ101. What would be a promising SALT score improvement for this type of study, first in patient data?
Yeah. So I think I would break down the regrowth into a couple of categories. If somebody regrew eyebrows and eyelashes, even by itself, that's such a leading indicator of additional success, that even with minimal scalp score, a scalp hair regrowth, that would be a wonderful sign. Beyond that, sort of a clinically meaningful difference in terms of SALT score on the scalp for an individual patient is a shift of about 20-30 points. So if you're beginning to see that sort of regrowth, even if it does not achieve SALT less than 20, but it means that that patient is on their way and towards that regrowth.
But ultimately, really for proof of concept, given the extremely low placebo rates, and this is something that we've evaluated across many trials, that really, if you have significant hair disease, hair loss, you're not going to have spontaneous improvement. Any signal with regards to a meaningful change in hair growth would be a positive sign. The things I mentioned before would be ideal, but any sort of positive signal for terminal hair growth in a patient that hasn't had it for a long period of time would be a great sign.
Got it.
Yeah, yeah, Tom-
That's really helpful. Thanks for taking the question.
Yeah, yeah, Tom, just to maybe, you know, kind of follow on to that. So again, we're, we're testing a single dose. This may not be the optimal dose for this patient setting. And, you know, I, I think we want to see, you know, a, a good, good evidence of some drug activity again, against that very low, background rate of patients, you know, not spontaneously growing hair on a, on a placebo arm from the other studies. To then take forward, and, and really test the, the, the dose level, in the next set of studies. But we do, you know, we do feel that from a, you know, overall target product profile, we, we clearly want this drug to be competitive with the, recently approved, JAK inhibitors.
That's in the context of not only their efficacy, but their longer-term safety and tolerability profile. You know, recognizing that, you know, black box warnings for non-life-threatening, albeit, you know, severe disease here, with that type of profile, maybe is not the most optimal way to, you know, chronically to treat a chronic illness. So, you know, we're pretty, I'd say, optimistic about the mechanistic targeting and where we, you know, hope our drug can end up from an overall target product profile compared to certainly the existing programs.
Got it. That makes sense. Thanks, Bruce. And thanks, team, for putting this together.
Yeah. Thank you for joining us today, Tom.
Our next question comes from Roger Song with Jefferies. Please unmute yourself and ask your question.
Great. Thanks for the event and, very informative, presentation. A few quick questions. The first one maybe follow up on Tom's question earlier. Just curious, outside of the background, baseline disease severity, any other factors can, kind of sway how we interpret the data, for, you know, phase 2, in terms of compare across, different trials? Any other, factors will be able to, impact the final results for the efficacy?
I could probably start and see if Dr. Mostaghimi has anything else to add. Again, we're learning a lot from the ongoing trials and the trials that have recently been completed. So besides severity of disease, something else that's being looked at is the length of duration of that episode, and maybe even duration of the disease. Dr. Mostaghimi, is there anything else that we should be keeping a close eye on then, when we're interpreting our results in terms of baseline characteristics?
No, I think the two things that have been consistently demonstrated is that the more severe disease you have and the longer you've had it, particularly with perhaps a steep cutoff at the four-year point, it leads to harder to treat disease, both measured by the amount of resolution of hair, but also the length of time it takes to get there. Given, I think it's very difficult to compare across trials. There's very different characteristics of the patients that are within the trials. Even with the existing JAK inhibitor trials, it's very hard to compare directly between the two, given the variation in demographics and the variation in outcomes.
But I think we can contextualize some of the challenges on the basis of those two main factors, extent and duration.
Excellent. Thank you. And in terms of the dosing, understanding, you will do the further dose optimization in the phase, in the next phase of the study. But just curious, for your current CTCL study, do you see any dose dependence in terms of maybe PD or the efficacy from the trials? And also, maybe just to remind us, what's the rationale to keep the 2 mg per kg for the CTCL and also for the alopecia as well? Thank you.
... Sure, and perhaps I can take this one, and Maple, you know, chime in if I miss anything. So in the CTCL study, we saw dose-dependent decreases in IL-2 and IL-15-dependent cells, things like CD8, central memories, NKs, et cetera. And that started to plateau out at about 4 mg. So the jump between 2 and 4 mg wasn't huge, and that's actually part of the rationale why the 2 mg per kg was taken forward. Now, there are a number of things we can think about when dose optimizing. Of course, these are two different diseases, so one chooses a dose as a rationale to start, but then you continue to learn, and you continue to test from there. As a signal finding study, we think 2 mg per kg should generate a signal.
Now, it may not generate an optimal signal. We'll have to have a look at the data when that comes out, and different levers one could think about pulling is you could increase the dose but also extend the regimen. You could increase the dose and potentially move the regimen out longer. To talk about instead of weekly dosing like it is now, you could go to biweekly. And actually, that was certainly seen with the pharmacodynamic markers in the CTCL sub-subjects and normal healthy volunteers, which is at the higher doses, the PD certainly extended much longer. So there are different ways to think about dose optimizing, but I think from a signal detection perspective, you know, we got 90% of our bang for our buck in the CTCL study at 2 mg per kg.
So it made sense, given that's where most of the data collected to date from the dose expansion in CTCL, and as I pointed out, many of those patients dosed beyond 70 weeks, is to sort of start there in alopecia areata patients. And in the next study, one could think about changing the dose or increasing the dose, but moving the regimen as a way to sort of think about optimizing signals there. Now, of course, one is happening in the body across patients, CTCL patients, it's patch plaque disease across the surface of the body, whereas in alopecia areata, that drug has to get into sort of immune-privileged spaces like the hair follicle.
So there are always things that you should be mindful of, but when you carry one dose forward from one indication to another, there are other things at play that may lead to that being either too much or too little drug. But you must start somewhere, and 2 mgs per kg is what we believe would be a very, reasonable, suitable place to start with the alopecia areata study.
Got it. Thanks. That's very helpful. That's it from us. We have run out of time for any additional questions. Additional questions can be directed to the company directly. Thank you.
Yeah. In closing, we'd like to thank everybody who joined today to hear the updates on Equillium, with the focus on EQ-101 and our efforts in alopecia areata. And then again, a special thanks to Dr. Mostaghimi for joining us today. If there are any follow-up questions or comments, please feel free to reach out to us. You can find our information on our company website at equilliumbio.com. Thank you very much.