Good morning. My name is Yamo Ponce. I am the CEO of Aelix Oncology. After the usual disclaimers in Slide number 1 and some picture of us and our background in Slide number 2, Let's move to Slide number 3. ELI's Oncology is a clinical stage immuno oncology company that is focused in the CD47 pathway.
ELAS-one hundred and 48, our Phase 2 clinical candidate is a CD47 blocker that is designed to be used in combination. This design has shown in the clinic a very good tolerability profile that has enabled higher dosing. And in the clinic, this higher dosing has enabled greater efficacy. At this moment, we have clinical proof of principle, both in hematological and solid tumors. Our initial focus is on solid tumors, MDS and AML.
In addition to ELIJON-forty 8, we have a second compound that we call CIRPalpatrug that will be an R and D by the end of 2022. CA47 in the Slide number 4. CA47 as a target is highly expressed in tumor cells here on the left on red, but is also highly expressed in normal cells in black. Therefore, if we use CA47 as a tumor associated antigen, we may have problems with therapeutic window by destroying cancer cells could also be destroying normal cells. What makes CD47 interesting to me is its role as a checkpoint modulator.
Many anti cancer agents, for example, anti cancer antibodies bind cancer cells and provide what we call an ID missingal. In that context, cancer cells have regulates C47 that interact with SIRPalpha macrophages and other myeloid cells and sense what we call a done if missing now. So SIRPalpha is an inhibitory receptor on myeloid cell, is a checkpoint for myeloid cells. And the interaction with C47 and SIRPalpha limits activity of many anti cancer agents. 1 way to treat C47 as a target is making CA47 as a tumor associated time division.
And therefore, designing molecules that bind CA47 and at the same time provide the required positive signal, the EDM signal. This kind of molecules can have single agent activity because they block the non IME signal and at the same time they provide a required image signal. But the problem is that CR47 is also expressing normal cells. For example, red blood cells, platelets and neutrophils. And these approaches are showing the clinic cytopenias related to this approach.
This kind of molecules, therefore, they cannot be dosed high enough. And in the combination setting, where it requires to completely block the C47 C pathway, they cannot go high enough and completely block it and therefore cannot enable the full activity of the anti cancer drug. What we decided to do is design a C57 blocker that treated C57 only as a checkpoint modulator. We made a molecule that binds the strongly to CF57 and blocks interaction with XERPAFA, but does not have an active Fc. It is not able to interact with the gamma receptors.
And therefore it does not provide the required positive signal. Our approach will not have single agent activity. At the same time, because we don't provide a positive signal, despite our molecule will buy normal cells, it does not destroy normal cells. For example, we have proven that we do not have any dose related cytopenias in the clinic. In that situation, when we combine with anti cancer agent, we can dose very high, completely block CFOC 7 and CFAPFA and fully enabling the activity of the companion drug.
Next Slide number 7, you have a cartoon of ELISCOM-forty 8. Our C47 binding domain is what we call high affinity cilp alpha. That's the extracellular domain of SyprAlfa, the receptor for CA47 that has been affinity mature to bind CA47 with very high affinity, with picomolar affinity and is fused to a completely activated Fc that provides the same half life of an antibody, the same pharmacokinetics, but does not interact with FC gamma receptors. So therefore, it does not activate macrophages directly. Molecular weight is half on antibody.
So if we want to compare our dosing with antibody dosing, you have to multiply by 2. 10 mgs per kg of relazone 48 is equivalent to 20 mgs per kg of antibody in terms of binding sites. Also, the smaller molecular weight may enable better tumor penetration. As the molecule is currently active to human, monkey and mouse, so we can run syngeneic models and our technical models are more relevant of the clinical setting. And we have a complete antibody standard manufacturing process and very good stability.
In Slide number 8, you can see that in the combination setting, ELI-four 48 has higher activity than the competition molecules with active XCs. For example, in this example, we have cancer cells that express EGFR and human macrophages. We provide cetuximab that targets cancer cells, so provides the required positive signal and is the orange dot on the left. And then on top of that, we have a dose response of PLx-forty 8, valorimab and TTI-six 21 that we made in house based on public information. You can see that PLx-forty 8 with the highest affinity and the lowest effector function is the molecule that enhances more the activity of cetuximab in this combination setting.
Because our molecule closely with mouse, we have been able to test safety mouse as well. In this experiment, we're comparing KLX-forty 8 with an inactive Fc with the same domain, the same binding domain of CF47, so with an active Fc, let's say ALX-three 77. You can see that a single dose of ALX-three 77 reduces red blood cells, platelets and white blood cells, while TRYOX-one hundred and 48 does not. This experiment proved to us that the cytopenias seen in the clinic by others are directly related to the active Fc and is not a target effect by binding CA47. We have proven in preclinical models that we can enhance anti cancer antibodies in xenograft models, for example, rituximab on the left.
And we can prove we have proven as well that we can enhance endpoint moderators in syngenegg models. In the right, combination with atezolizumab and PBL1 antibody, but we have also data with anti PD-one antibodies. In Slide 11, you can see with our PK profile that we have linear PK at doses of 3 mg per kg and higher. The combination of antibodies do not change the PK and the half life at the mix per kilogram higher is predicted about 30 days. On the right, you see target occupancy on T cells and you can see that we have full receptor occupancy across the dosing interval at 3 mg per kg weekly and higher.
In terms of safety, we have been able to dose very high in preclinical models up to 100 mgs per kg in non human primates as equivalent to 200 mgs per kg of antibody with no observable adverse events as a single agent in humans up to 30 minutes per kg every other week with no evidence of those appendicitopenias. And in combination, we have defined the Phase 2 recommended dose of 15 mgs per kg weekly, but in terms of exposure, because our T profile is good and we can dose higher, we have never reached a maximum tolerated dose. We can increase the dosing to extend the dosing interval. For example, if we combine with something that is dosed weekly, we can do 15 minutes per kilogram weekly or we can do 30 mls per kg every other week or 45 every 3 weeks, we are combining with pembrolizumab or 60 every 4 weeks, if we are combining with isacitidine that is stores monthly. So our safety profile allows a very flexible posting schedule, maintaining the same exposure.
On Slide 13, you see a high level description of our clinical program so far. We have tested ELISCO-forty 8 in head and neck squamous cell carcinoma in combination with KEYTRUDA and QVYSN with KEYTRUDA plus 552 plus platinum. And we have Fast Track designation for this indication. Now we're moving into a Phase II in first line, head and neck, less common cell carcinoma. In combination with KEYTRUDA and ArcelorMittal, and that are Phase II in combination with KEYTRUDA plus chemotherapy.
In gastric cancer, we have tested ELXCOM48 in the second line for patients that have failed Herceptin in the first line. In combination with Herceptin and in combination with Herceptin plus chemotherapy, we also have Fast Track designation for this indication and we are also moving into office to randomize potentially for accelerated approval. In collaboration with Zyneworks, we are testing helix-forty 8 with zamidatamab by a specific anti HER2 antibody in breast cancer and the Phase 1 should start shortly. In hematologic and malignancies, our focus is MDS and AML. In MDS, we are now in the middle of Phase 1 in combination with ericisitidine to start our Phase 2 this year and we're going to start our Phase 1 in AML also this year.
We have a very good proof of principle study in NHL in combination with rituximab, patients that have rituximab. And this is a study that allows us to compare ourselves with the data from others, CA-forty 7 blockers. And finally, we have a second program that I would discuss later. In terms of safety in humans, it has been very solid. The most common side effect is fatigue and some rash.
You can see that cytopenias like plateletidecrest or neutropenia is single digit percent and quite not frequent. And we have proven that it's not dose dependent. So this safety profile, it is really a best in class safety profile and allows us to combine with a multi agent cytotoxic chemotherapy, for example, in combination with Herceptin with chemotherapy or in combination of KEYTRUDA with chemotherapy. In terms of efficacy, at this moment, we have 5 independent combination studies and the 5 of them will results above the benchmark. The first 1 is for NHL's patients in combination of rituximab, patients that have rituximab already.
We don't have a very good benchmark for this indication. Here, this is probably in the range of 10%, but nobody has done a randomized study of rituximab in the second line or later after rituximab. But we can compare ourselves with maglutinibab, the similar patient population, the best response rate maglutinib had was 48% and we had a 70% response rate at our higher dose of 15 minutes per kg weekly. In second line, head and neck for patients that are checkpoint naive, so not treating with Keytruda and Tetris line, we had a 40% response rate With the benchmark for KEYNOTE-forty 8, the Phase 3 from Merck, benchmark is 15% and we also do double PFS and OS. In first line head and neck, now that KEYTRUDA is approved in the head and neck, we have combined with KEYTRUDA transchemotherapy.
There the benchmark is 36% and with a very small number of patients, only 4, we had 75% associated last year. We're going to update this study by the end of this year with 13 of 14 patients total. In second line gastric cancer, patient that have failed Perceptin in the first line, we know that Herceptin in the second line does not add anything. That has been shown in a prospective Phase 2 study that bactaxol plus Herceptin had the same response rate and OS as bactaxol alone. In the second line, EL-forty 8 plus Herceptin has a 21%, which is very significant.
And then if we put this doublet, this active doublet in what is standard of care, XERRAMZA, paclitaxel, we got ATTO-sixteen next year at 64% response rate, where the benchmark is at 28%. And we're going to update this study July 3 at ESMOGI. Now we're going to go to a little more detail to each 1 of the studies. The first 1 is ALX-one hundred and 48 parituximab in combination of rituximab in NHL. In this case, rituximab binds C to anti cancer cells and bind Fc gamma receptor macrophages providing the required positive signal and ALX-forty 8 releases the brakes binding CA47.
In the Slide number 17, you can see that at 10 migs per kick we had a 41% response rate and at 15 mgs per kg weekly, we had a 70% response rate and this increase of response rate is statistically significant. What's interesting is that both doses will have full receptor occupancy in the periphery. So they tell us that to completely block CA47 in the placement matter, in the tumor, we need to reach more than 100% receptor occupancy in the periphery. We have to have excess of antibody above the 100% receptor occupancy in blood. You can see in Slide number 18, the spider plots and the waterfall plots for this trial.
And you can see that we have responses, both in indolent and aggressive lymphoma and we have PRs and CRs and very long directional response. And this is statistically significantly better at 15 minutes per kg compared with 10 minutes per kg. The next study is Slide 19 is gastric cancer, second line, patients that have failed Herceptin in the first line. In this case Herceptin by HER2 on cancer cells and provides a positive signal and the IL-forty 8 again releases the mix. The first study we did was CLX plus Herceptin alone in the 2nd line where we know that Herceptin by itself does not add anything and we have a 21% response rate.
From there, we went to the 2nd line on top of the standard of care in Slide 21, and you can see that we had associates last year 64% response rate, which is very significant when the benchmark is 28% from the TRAINBOVE study. We are going to update this study by the end of July at ESMO GI, beginning of July. And from that, we're moving into a randomized Phase 2 study in combination with Herceptin and zaparitaxel. There could be potential for registration. Another study that we have done is in head and neck in combination with KEYTRUDA.
Here the mechanism is slightly different in Slide number 23. Serpalfase are suppressed in dendritic cells and CA47 immediate dendritic cells. By blocking CA47, we activate dendritic cells, dendritic cells can present antigen to T cells and then T cells get activated and when we unleash them with their own checkpoint with a PD-one blocker, these T cells can kill cancer cells. So basically in this case, we are helping the tumor microenvironment to create or activate T cells. We do have a very good benchmark for this study in Slide 24.
We know in the second line, patients are checkpoint naive. These are 15% response rate. And in the first line, with Keytruda alone is 17% and KEYTRUDA plus chemotherapy is 36%. Now our first study that was second line before K2 that was approved in the first line, we had 10 patients that were checkpoint naive and 10 patients that are checkpoint experienced. If we focus on the patients that are checkpoint naive in blue, you can see that 4 out of 10 that responded with a 40% respond rate that compares very well to the expected 15% in this line and also we doubled the PFS and OS.
And you can see that we have responses in patients with very low PD-one scores. For example, the 5th patient from the right is a CPS score of 0. From that, we went to 1st line, now that pembrolizumab is approved in the 1st line on top of KEYTRUDA plus chemotherapy. As of last year, we only had 4 patients, both of those 4, 3 responded, 1 CR and 2 PRs and 1 of them was a CPL score of 0. So again, very promising data and we're going to update this study by the end of the year with more patients something like 13, 14 patients.
From that, we are moving into 2 Phase 2 studies in the first line, 1 in combination with KEYTRUDA and 1 in combination with KEYTRUDA chemotherapy, both are randomized and both are substrate for potentially accelerated approval. We have already dosed the presentation in the TOP study in the ALX basket. And shortly, we expect to dose the bottom 1 ALS basketulina as chemotherapy. And finally, another mechanism that we're exploring is in combination with isacitidine in MDS. In that case, isacitidine ab regulates a molecule called calreticulin on cancer cells, calreticulin binds a receptor or macrophage is called LRP and provides the required positive signal.
And then again blocking EL-forty 8 unleashes macrophages to eat MDS cells. Magrolumab, the KILIAM molecule had very significant responses in this indication in this combination. You can see on the table on the left, the maglorumab in combination with azacitidine had a 42% CR rate when the benchmark by isacitidine alone is 17%. So very meaningful responses for patients. As a monotherapy in the middle, margolimab did not show much with a 0% CR.
Despite the responses are really good, at the same time, makolumab does have significant thrombocytopenia, neutropenia and anemia. And cytopenias are important for MDS patients. Many of them will die of complications due to cytopenias. So we want to do here is make a molecule in Lesson 48 that will provide the same or better response rates to magolumab, but with better safety profile. We have shown in preclinical models that isacitidine enhances scarleticulin and that the IL-forty 8 enhances activity of fezocitidine in fibrosis assays in the Slide number 30.
We have shown also in the clinical models of leukemia that EL-four 48 can enhance activity of viscosapyridine in Slide 31. And now in Slide 32, the clinical trial that we are performing. We are now in the middle of Phase 1, dose escalating to prove the safety of iragination 48 in combination with azacitidine and from that we're going to move into a randomized Phase 2 that could be substrate associated approval. Finally, this is a summary for ELX-forty 8. We have shown that ELX-forty 8 has a very good safety profile that enables a combination with a wide range of patients, allows higher dosing and a small molecular weight may facilitate their tumor penetration.
We have clinical proof of principle both in hematological and solid tumors. And the IL-forty 8 is the only CA47 blocker to show an encouraging data in solid tumors so far. In terms of milestones for the rest of the year, well, as I said, we are going to disclose the data from the vascular cancer Phase 1 combination of chemotherapy at ESMO GI. And for the head and neck, the Phase 1 will be disclosed in second half of the year. We just initiated the Phase 2 for head and neck and shortly we will initiate the Phase 1 with daratumumab in breast in combination with and collaboration with Zymeworks.
In the second half of the year, we are going to start the Phase 2 for gastric cancer in combination with Herceptin. We are going to start the Phase 1 in AML. And by the end of the year, we expect to disclose data for MDS in combination with isratidin and initiate the Phase 2. The results from the Phase 1 from AML should be coming Q1 of next year. And now with a few minutes I have left, I have a very quick introduction to our 2nd compound, our CIRPalpha track.
We are really specialized in the CA-forty 7 CIRPalpha hardware and we understand the biology very well. CIRPalpha is expressed in dendritic cells, which are very important to activate T cells and other group main orchestrates of the immune system. So we have done in collaboration with another company, Tarek Telepetic, Tarek Therapeutics. It's an anti-three part antibody conjugated to a TLR9 agonist antibody, TLR9 agonist molecule, CPG. This molecule will bind dendritic cells and activate them directly.
And these syndicated cells will be able to activate in the tumor microenvironment. What's interesting of this molecule is that can be dosed systemically. CPGs, the Pilar agonists have a very good clinical validation from companies like CheckMate, but they have to be dosed systemically. Here we are dosing them systemically and could be using this molecule in multiple indications. We have shown in the clinical models in Slide 36 that we can activate dendritic cells, human dendritic cells and that we have a very strong activity in syngeneic models, for example on the right and then CT26 just to doses produce full tumor regression.
And in MC38, on Slide 37, we have proven that we provide a long term memory of immunogenicity, memory of efficacy. So mouse that had been treated with cipapar track and produced complete regression. When we are challenged again with MC38, the tumor does not grow, while the naive mouse, all the mouse, the tumor grow. Slide 38, the differentiation between EL-one 48 and Cipantha drug. ELH-forty 8 is an antagonistic molecule that is designed to maximize activity of a wider rate of anti cancer agents by blocking the CA-forty 7 milloid checkpoint.
The removal of the CA-forty 7 divisional kidney signal requires full blockade of the pathway. On the bottom, cepalpa drug is an agonistic molecule that directly creates genetic cells and initiates a coordinated innate and adaptive immune response against cancer. In the case of agonistic molecules, constant blockade is not required. So in terms of positioning, we think about the ELIS-forty 8 to go on top of the standard of care. And we think about the SIPA after standard of care when standard of care fails.
Finally, in Slide 39, our financial information. As of March 31, 2021, we have €429, 000, 000 in the bank. This is expected runway through 2024 and that's enough to finish all the test tours that I just described. Thank you for your attention.