Good day, Ladies and Gentlemen. Thank you for standing by. This is Tianyi Zhang, IR Head of I-Mab Biopharma. Thank you for joining the conference call today. Yesterday, I-Mab presented clinical data of lemzoparlimab in combination with rituximab in NHL patients at ASH Meeting. Today's conference, we will have the management team to give you more insights of the clinical data and the future development plan. Joining me today on the call from I-Mab's senior management team includes Dr. Jingwu Zang, Founder and Chairman of I-Mab, Dr. Joan Shen, CEO of I-Mab, and Mr. John Long, Chief Financial Officer of I-Mab. Today's conference call will be divided into two parts. First, the management team will give an in-depth overview of the clinical data, and it will be followed by a Q&A session.
Now, I'd like to turn the call to Dr. Jingwu Zang, Founder and Chairman of I-Mab, to share with you more details about the clinical trial.
Thank you, Tianyi. Thank you all for joining us today, for this call. Today on this call, we would like to use the opportunity to talk about the first part of the clinical data on our ongoing clinical trial of lemzoparlimab in combination with rituximab in patients with relapsing and refractory non-Hodgkin's lymphoma. Now, on slide three, I just want to refresh your memory to point out that lemzoparlimab is a highly differentiated CD47 antibody by design. At the molecular level, lemzoparlimab has a strong binding to various tumor cells and exhibits a strong antitumor activity. On the other hand, it has a minimum binding to red blood cells and does not cause hemolytic anemia.
At the clinical level, on the right side of this slide, it has demonstrated in multiple clinical trials conducted so far that lemzoparlimab has a clinical advantages, which are consistent with its molecular differentiation. In summary, there are four key differentiations. One is related to clinical safety of lemzoparlimab. So far, there are over 150 patients who have already dosed by lemzoparlimab and we have consistently seen a good safety profile and there's no hemolytic anemia. Now, because of the differentiation of the lemzoparlimab, unlike other CD47 antibodies, lemzoparlimab does not require priming dose. In all clinical trials we have conducted so far, no priming dose was required.
All the safety data, PK/PD data, and efficacy data are based on administration without priming dose. This is a very important point to mention, that it has advantages clinically. The third aspect of clinical differentiation is related to antigen sink effect. lemzoparlimab does not have an antigen sink effect because it has only minimum binding to red blood cells, so it does not cause antigen sink effect commonly seen by CD47 antibodies that have a strong binding to red blood cells. Last but not least, that is related to clinical activity. In our early studies, either with a monotherapy of lemzoparlimab or combo therapy of lemzoparlimab in combination with a PD-1 antibody in solid tumors, we have seen good clinical activity and good response to solid tumors.
Now, today, we're gonna talk about some more efficacy data related to lemzoparlimab in combination with rituximab in the treatment of relapsing and refractory non-Hodgkin's lymphoma. We're quite excited that lemzoparlimab has you know demonstrated its clinical differentiation, and with the multiple clinical trials ongoing, and we hope to obtain additional data to support further clinical studies, and most importantly, to support registrational trials sometime next year in China. Now, on slide four, the clinical data we are going to talk about today is from an ongoing clinical trial where lemzoparlimab is combined with rituximab to treat relapsing and refractory non-Hodgkin's lymphoma.
At this ASH meeting this week, we presented the detailed clinical data of a dose escalation part of the study conducted in the U.S. Today, we're gonna go through the detailed data and to give you a better view as to how lemzoparlimab functions in the clinical trial. Now, the study now has expanded to the dose expansion phase to include clinical sites in both U.S. and China, and we expect this trial will go much faster with more patients and more data generated. Additional data being matured, and we'll present a new data on the expansion phase early next year. Now on slide number five, here's the summary of the clinical data. On safety, we continue to see good safety profile.
In this trial again, lemzoparlimab is well-tolerated. I'd like to mention the safety profile observed results at priming dose and MTD was not reached. This is consistent with the safety profile we have seen so far from other parallel clinical trials. The second point is that in this study we were able to obtain biopsy samples from patients' tumor samples. We were able to analyze intratumoral drug distribution. This is important information because this will help us to assess how lemzoparlimab works and distributes in the system and how much the drug gets into the tumor because this is as you can imagine this is directly related to efficacy of lemzoparlimab.
In this study, we have seen a strong penetration of drug distribution in biopsy tumors in tumor samples, you know, from treated patients. On average, we observed 80% and 90% of staining, which really represents a high level of drug distribution within the tumor mass. The third point is related to efficacy. Now, in this combination study, out of the seven evaluable heavily pretreated patients, we observed four CRs, one PR. ORR is 71%. We also observed two stable disease. Disease control rate is 100%.
This is quite encouraging because this is so far among all the studies, so far this represents really the best efficacy data, even though the patient number is still quite limited at this point. We'll continue this study expanding the patient population and hope to validate this data with more patients. Last but not least, with the accumulated data from this ongoing study, we hope we'll be in a position next year to initiate a registrational clinical study in China and to pave the way to get lemzoparlimab registered, potentially registered as a first CD47 antibody in China. At the same time, working with AbbVie to facilitate global registration.
Now, I'm gonna stop here to ask Dr. Shen, to take a deep dive into the detailed data and the critical part of the clinical data. Dr. Shen.
Thank you, Dr. Zhang. Here I will present more of the data which we already showed on the ASH meetings. In terms of this demographic information, as you can tell, overall, we enrolled nine patients, and all of them are NHL patients. On average, the age is about 61, with four females and five males and all white patients. The number of prior treatments on average is four lines, from 2-10. Then 33% of them are oxaliplatin refractory. The tumor types including DLBCL, MCL, and FL. This shows the treatment-related adverse events and which is also reported.
As Dr. Zhang mentioned earlier, we have over 150 patients dosed as of today with lemzoparlimab, and it consistently showed a very good safety profile, and as we have reported before. In this particular study, besides all the AE we have listed here, we only had one grade three anemia. This patient actually does not require the blood transfusion or discontinuation of the study, so he was able to tolerate this anemia and continue to be on the treatment. This further demonstrates the good safety profile and also validates our safety claim on the red blood cell sparing mechanism. Next. This further showed the transient anemia observed in both monotherapy and the rituximab combo treatment.
The monotherapy part has already been presented previously in the last year, and on the left side is the current study results. The blue lines are the hemoglobins, and then the red lines are the reticulocytes throughout the treatment. As you can tell, there is a transient reductions on the hemoglobin, especially the first cycle. It can gradually resume with the increase of reticulocytes. The average decrease on hemoglobin is around 14%, and then it's not related with the dose. This was resumed to pre-baseline or above baseline levels after continuing the treatment. Even this anemia observed does not show any hemolytic natures. All of these are continuing to support the previous claim that is, again, it's red blood cell sparing on the epitope. Next.
I want to continue to mention all these patients did not require priming dose. In clinical efficacy-wise, we had really observed a very exciting efficacy data from the patients populations. As I mentioned earlier, we have dosed nine patients. Seven of them are evaluable. Among these seven patients, we have four CRs, one PR, with ORR at 71%, and then two SDs. Disease control rates altogether is 100%. The durations of the response among these five responders is 61-236 days. As of today, there are still six patients who are still remaining on the study. The date of treatment is from 144-340 days, so it's almost a year.
The median time to initial response, about 50 days. You can tell from these studies and from these graphs here, the durations are continuing, and the patient continuing to benefit from the studies. These patients are including the rituximab refractory patients. Next. This is the image study shown in one of the DLBCL patients who have obtained CR after the treatment. The first part is transverse sections of the PET/CT, and you can tell from the image, the target lesions before and after treatments, that's very different. After treatment, it completely resolved. Lower part is an abdominal part, and then also disseminated lesions on the left side is completely resolved on the right side.
This showed this patient achieved the CR after 32 weeks of treatment. This patient is continuing on the treatment as of today. It is worth to mention this patient has been treated previously with the standard treatment with, you know, R-CHOP, RCVP, and also have been remained on rituximab for two years, which has relapsed afterwards. It was able to be treated and benefited from the current study. It is worth to mention, as Dr. Jingwu earlier stated, that to further demonstrate the tumor engagement of the lemzoparlimab and its penetration, the team worked very hard to be able to obtain the biopsies from the baseline and after treatment. Among seven patients, we obtained four samples.
This is very important to observe these changes before and after the treatment. You can tell the average penetrations after treatments showed is 80%-90% on the IHC stainings. Before that is you know plain and empty, but after the treatment, you can tell the staining is very strong. This further demonstrated lemzoparlimab was able to penetrate into the tissues, into the tumor sites, which as a result able to kill the tumor cells and the making another shrinkage of these lymphocytes. Yeah, lymph nodes. Sorry.
All of these demonstrated clinically the patients are benefiting and the safety-wise continue to show the benefit of non-RBC binding and minimal anemia and as well as the overall benefit, and then which is also validated by this strong penetrations in the tumor site. This is the current presentations showed on the ASH meetings, and now referring back to Dr. Zhang for summarizing this study.
Thank you, Joan. Now we are on slide number 12, and I'd just like to summarize that the I-Mab lemzoparlimab is a key clinical asset. It is at the critical stage of clinical development today. We and our partner, global partner, AbbVie, are running five parallel clinical programs in both U.S. and China, including two studies sponsored by AbbVie. Now just briefly summarize the key programs we're running related to lemzoparlimab. Firstly, regarding non-Hodgkin's lymphoma, we just talked about the first part of the clinical data, and we are now in the expansion phase. More data expected early next year, and we hope to, based on the data, potentially initiate a registrational study in patients with non-Hodgkin's lymphoma in 2022 in China.
Secondly, regarding AML MDS, we have an ongoing phase II clinical trial of lemzoparlimab in combination with AZA in patients with AML MDS. Early clinical data are also encouraging. We will complete all the patient enrollments this month and share the clinical data sometime next year. Our plan is to start hopefully a registrational clinical trial in patients with MDS in 2022 in China. Thirdly, regarding solid tumors, we have an expanded clinical trial of lemzoparlimab in combination with PD-1 antibody in U.S. We'll be in a position to present the clinical data early next year, 2022. Another phase II clinical trial with a basket clinical trial design to include lung cancer, ovarian cancer, and head and neck cancer has already started in China recruiting patients. More data will come in 2022.
To summarize, we have three data readout events for lemzoparlimab in 2022. The first data readouts is related to new data from the non-Hodgkin's lymphoma expansion study in 2022. The second data readouts is related to what I already mentioned, solid tumor data in combination with PD-1 antibody in early 2022. The third data readouts is related to our ongoing phase II clinical trial in patients with AML MDS with lemzoparlimab in combination with AZA. We expect to release the data in 2022.
In summary, with the good safety profile and the initial clinical advocacy, we'll be able to speed up the clinical development plan and aim to potentially initiate two registrational clinical trials in 2022. Our ambition is really to get lemzoparlimab registered as the first CD47 antibody drug in China and work together with AbbVie to facilitate global registration. I'd like to stop here and to see whether there are questions and both Joan and myself would be happy to address any questions you might have.
Thank you, Dr. Zhang and Dr. Shen, for the very comprehensive overview. Now we'll start the Q&A session. If you have questions, please use the Raise Your Hand function via Zoom, and we will unmute you and take questions in order. Our first question comes from Kelly Shi. Kelly, please.
Thank you. First, congrats on great progress and thank you for taking my questions. I have two. The first question is, how would you assess the potential of lemzoparlimab or like the entire CD47 drug class? They could eventually carve out a market share in non-Hodgkin's lymphoma, given the highly competitive landscape and also many new agents breaking into the space. My second question is, this is also many investors are actually curious about the U.S. SEC adopts amendments to finalize rules relating to the Holding Foreign Companies Accountable Act, that requires foreign companies to observe U.S. accounting rules and comply with information requests made by regulators. How will this impact the I-Mab? How do you mitigate the potential ADR risks? What is your dual listing plan and also timetable?
Thank you.
All right. Thank you, Kelly. Maybe I just say a few words about your first question and I will ask Dr. Shen, you know, to chip in to add her view on your first question. Your second question I will direct to John who is our CFO. He will be able to address this particular question. Now I just want to say although there are multiple agents being tested in non-Hodgkin's lymphoma, as you know, there's quite significant unmet medical needs with rituximab alone or in combination with a few other agents.
CD47 pathway, and, you know, this particular class of new agents, CD47 antibody, provides a powerful and novel pathway to work in combination with other agents to really provide an efficacious option for patients, you know, who suffer from refractory relapsing non-Hodgkin's lymphoma. Now, the data we shared today, again, is a demonstration that how a CD47 antibody can work effectively with a CD20 antibody to provide, you know, much better clinical efficacy, even though at this point, we have limited patients.
That really provides a direction for us to explore how CD47 pathway such a powerful validated pathway how it works with other agents in synergy to provide a efficacious solution for patients who failed other treatments you know as a combination therapy. Joan do you have anything to add?
Yes, Jingwu , I think I completely agree with you. This unique pathway provided the novel approaches for addressing the unmet needs, especially with this perfect safety profile, and we can open up for multiple combination treatments. For lymphoma in particular, it is even though there's a lot of, you know, currently, options and many new approaches is working on, but its uniqueness is no matter how well it responded to begin with, and it will, you know, many of the patients will suffer from recurrence. Once you recur and then it's harder to treat. There's always a fight against the recurrence and the refractories. You know, the physicians are constantly looking for new solutions.
We believe, as we have already explained, these new treatment options from very different angles to address the recurrence and relapse the patients, it's really needed regardless of other agents coming along. Yeah, I just want to add it. Thank you.
Okay, Kelly, I'll answer your second question regarding the SEC new rule. Actually, the Holding Foreign Companies Accountable Act has come into effect since January 1st , 2021. Under the SEC rule, it only adopts its amendments on disclosure and submission requirements. It is not a new thing in a sense. We noticed that the China and the U.S. regulators have been working together for a solution on this matter. As a matter of fact, as discussed by CSRC Chairman Yi Huiman last year, China's CSRC has already approved at least 14 U.S.-listed Chinese companies to provide all the working papers to PCAOB.
While this act and the new rule brings some jurisdictional risk to U.S.-listed Chinese companies, we do believe that the biotech sector, and in particular I-Mab, faces very little risk in this regard.
As far as we know, our I-Mab business does not relate to any national security matters, and there is no government official in our board or management team. We believe our business would least likely to be impacted. Nevertheless, to address concerns from some investors, we are proactively taking necessary actions to mitigate potential ADR uncertainties. For example, we are working with our auditors and advisors to pursue approval for provision of working paper to PCAOB. Last week, we also announced our plan of dual listing on the main board in Hong Kong. Next year, in 2022, we will accelerate our preparation for the Hong Kong dual listing. Once it's completed, the Hong Kong dual listing will offer our existing ADS holders more trading flexibility in addition to Nasdaq, and provide another platform to attract new and complementary investors.
Again, we are quite confident that with the measures we are taking, we are able to largely mitigate potential uncertainties related to IMAB ADSs. Thank you again for the question.
Thank you. Our next question comes from Joe Cantadaro. Joe, please.
Great. Thanks so much for hosting this and thanks for taking my question. Maybe just to follow up on Kelly's first question there, but get a little bit more specific. I'm wondering how you guys think these early data for lemzoparlimab in combination with rituximab compare specifically to other CD47 agents in combination with rituximab and in relapsed refractory non-Hodgkin's lymphoma on a safety efficacy basis. Maybe along those lines, I'm wondering if lemzoparlimab, given that it doesn't require priming dose, doesn't observe meaningful antigen sink effect, and can achieve target saturation much more quickly, whether there's possible opportunity for time to response to be meaningfully quicker than other agents. Thanks.
Thank you. Perhaps, Joan, would you like to address this question?
Yes. I'm trying. Okay. I think we are definitely observing what's happened with other studies with magrolimab earlier studies. There is a very similar study similar design in NHL patients with 22 patients enrolled. We have achieved 36% of CR rate while ours is 57%. They have ORR overall is 50% while we have 71%. The disease control rate is 64% when we have achieved 100%. On the other hand the other ALX148 reported CR rates of 18% and ORR of 55% and the disease control rate 73%.
Although the sample size are relatively small, but we are very, very pleased that, you know, our TJC4 data is comparable, actually numerically better, than magrolimab and ALX148. You know, relative efficacy-wise, we are very confident and we can achieve comparable or better results. In consideration of this, you know, safety profile and also the red blood cell sparing nature altogether with, like you mentioned earlier, without the sink effect, we believe our target engagement could be even quicker. Especially with the next years of more solid tumor data, we're hoping to demonstrate more of the efficacy data as well that continue to demonstrate the benefit in our safety profile. Yeah, I'm starting from here.
Thank you, Dr. Shen. Our next question comes from Carby. Carby, please.
Hi, everyone. This is Carby on for Louise and Tanner. This is a question from us. What are the key milestones for lemzoparlimab in 2022, and possibly beyond? Thank you so much.
Thank you. This is Jingwu Zhang again. I must say, you know, CD47 is one of the most promising targets in immuno-oncology, and we put a lot of resources to make sure that we will effectively advance this key clinical asset in clinical trials. Currently, as I mentioned, we are running three parallel clinical programs, non-Hodgkin's lymphoma, AML, MDS, and solid tumors. Our global partner, AbbVie, is running two global clinical programs to focus on AML, MDS in combination with their BCL-2 inhibitor and
On multiple myeloma with CD38 monoclonal antibody. Those are very exciting programs. We expect next year, 2022, is going to be an exciting year for lemzoparlimab because we will have a series of key clinical milestones to come out to realize in 2022. I can quickly mention the four key clinical milestones. One is additional data from our ongoing dose expansion study on non-Hodgkin's lymphoma. We'll have additional data to report in 2022. Second, we will have new data coming from our ongoing phase II clinical trial in patients with HR-MDS. We hope to report this phase II data in 2022.
Thirdly, we will report, early next year, clinical data from our ongoing clinical trial in solid tumor in combination with PD-1 antibody. Those are the three data readout events we expect to report next year. The fourth clinical milestone is really based on the progress of lemzoparlimab in multiple clinical trials. As we accumulate more clinical data, safety data, efficacy data, we hope we'll be in a position to initiate one or two registrational clinical trials in China to pave the way, you know, for lemzoparlimab to get registered as the first CD47 antibody in China. We will work with our global partner, AbbVie, to facilitate global registration of lemzoparlimab.
Thank you, Dr. Zhang. Due to time limitation, I think we will take one last question. Our last question comes from Andres Maldonado from H.C. Wainwright.
Great. Thanks for taking my questions. I guess my first question is, regarding combinations with lemzoparlimab with pembrolizumab in solid tumors. Could you give us some additional color on what you need to see in order to classify a positive outcome for that program? Lastly, could you provide an update on, uliledlimab's clinical development in the United States and in China, particularly in regards to how your thinking on partnership has evolved over time? Thank you very much.
Yeah, thank you for the question. Maybe I can take your second question first, and I let Joan address your first question or first part of the question. So uliledlimab CD73 antibody is another exciting asset. Our CD73 antibody uliledlimab is globally competitive. We are among the top two or top three global CD73 antibodies in clinical development. And you have seen recently phase II clinical data from AstraZeneca. The data are quite encouraging. Now, for our program, we're running parallel two clinical phase II clinical trials. One is in the U.S., we just started that clinical trial. The other clinical trial is ongoing, a phase II clinical trial ongoing in China.
So far, combining all the clinical studies, we have dosed about 100 patients already. The data are being matured. We hope that next year we'll be in a position to report more data to you. CD73 antibody, where you know in both phase II clinical trials, we will focus on selected tumor types, lung cancer, ovarian cancer, and a few others. Based on you know our own preclinical data, clinical data and other companies' data, and that give us some good idea and some direction as to how going forward we will increase the probability of success by focusing on the selected tumors.
At the same time, as we already talked about in the past, we are continuing working with our big pharma groups for global partnership. We're getting some level of details, you know, in the negotiation phase, how we're gonna work together in terms of clinical developments, commercialization, manufacturing. We hope that early next year, sometime next year, we'll be able to close the deal. This is an exciting program, has really attracted a lot of attention from the big pharma groups. We are continuing to make sure we will strike a best deal for this exciting asset. Thank you.
Okay, maybe I'll just elaborate a few regarding the first part of the questions, how to define the success with this lemzoparlimab in combination with Keytruda. As Dr. Zhang mentioned, we are exploring in both U.S. and China in a basket trial design fashion to look at this unmet needs in the particular tumor areas with the translational work showing the high expressions of CD47 in combination with the current PD-1, in particularly Keytruda, to show Keytruda or other PD-1 if it can address the unmet needs. For example, the success will be, you know, defined as either it can improve the current unmet needs, for example, ovarian cancer we all know is not responded very well to PD-1 or PD-L1.
For like lung cancers also, the overall response rate is not greater than 20%, for single treatment arm. We wanted it to demonstrate this combo can overcome the hurdles, either treatment naive patients or high and low expression of PD-1, PD-L1 to look at the potential of this high expression of CD47 in combination with the PD checkpoint inhibitors. Overall, since checkpoint inhibitors largely applied for different tumor types, and we have been aware what is the current treatment magnitude. By defining success, we should be able to address with the current basket trial design, see if it can reach the clinical benefit, in terms of comparing with what existing checkpoint alone can achieve.
Next year, as Dr. Zhang mentioned, earlier next year, we should be able to show some clinical data from the U.S. studies, which is the solid tumor, in combination with Keytruda. Thanks.
Thank you, Dr. Zhang and Dr. Shen. Thank you everyone for joining our meeting today. If you have any further questions, please feel free to reach out to our IR team. I wish you all a good day, and you may disconnect now.
Thank you.