NovaBridge Biosciences (NBP) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the I-Mab Lemzoparlimab Phase I Clinical Trial Data Update Conference Call. [Operator Instructions] Please note, this conference is being recorded today. I would now like to hand the conference over to the company's CFO. Please go ahead, sir.

Thank you, Rachel. Thank you. Hello, everyone. Good night, or good morning, depending on where you are. My name is Jielun Zhu, Chief Financial Officer of I-Mab. Thank you for your time joining this call. With me on the call today are Dr. Jingwu Zang, Founder and Honorary Chairman of I-Mab as well as Dr. Joan Shen, CEO of I-Mab. We plan to go through a deep dive analysis of the preliminary clinical efficacy results of lemzoparlimab, also known as TJC4, from its U.S. Phase I clinical trial for the treatment of relapsed or refractory solid tumors. The results are being presented this week at the 2020 Society for Immunotherapy of Cancer, SITC, annual meeting held virtually. The purpose of this call is to provide an expanded analysis of the clinical efficacy signals from the U.S. Phase I trial, which is not previously discussed. Now without further ado, I will hand over the call to our Chairman, Dr. Zang?

Thank you, Jielun. First of all, I would like to thank you all for joining this call today. On this call, We will provide you with an updated summary based on expanded analysis of Phase I clinical trial data on lemzoparlimab, our differentiated CD47 antibody. The data summary is already posted on I-Mab's website with a link that is indicated in our meeting announcement. Now without further ado, let me start to summarize the data of this single-agent dose escalation study in patients with advanced solid tumor. The study was conducted in U.S. clinical sites. The data can be summarized in 4 aspects. First, lemzoparlimab was well tolerated among all dose cohorts from 1 milligram per kilo up to 30 milligram per kilo. No DLT or severe hematologic toxicities were observed. We only observed a few cases of mild anemia, mostly Grade 1 anemia with the evidence of hemolysis. This well-tolerated safety profile is consistent with the key differentiation of lemzoparlimab that bonds minimally to red blood cells [indiscernible]. Second, lemzoparlimab accepted a favorable PK profile at mid or high doses. It did not show a single threat. We consider this an important clinical advantage as a single threat may influence clinical efficacy of the drug. Third, lemzoparlimab showed an expected receptor occupancy. It has reached maximum receptor occupancy at a 20-milligram per kilo and a 30-milligram per kilo. It is important to mention, unlike other CD47 antibodies, for example, Magrolimab from Forty Seven and [indiscernible] from Innovent and because of its minimum bonding to red blood cells, lemzoparlimab did not require priming dosing, which is considered another advantage in a clinical setting. Let me now summarize the efficacy data. As a single agent treatment, lemzoparlimab demonstrated a promising efficacy signal among 16 evaluable patients with advanced solid tumor. We observed one partial response, PR and a 3 stable disease SD. This PR is the case of advanced melanoma with a liver metastasis. The patient had a prior treatment with checkpoint antibodies for at least 6 months and progressed on treatment before entering our study. He remains on the treatment now and maintains as PR. The 3 SD patients are squamous carcinoma of the tongue, ovarian cancer and renal cell carcinoma. One of the SD patients, a stable patient, was originally determined as a PR and later was unconfirmed. It is also important to mention that many patients remain under treatments for a good duration. The longest is at 280 days on treatment. In conclusion, we are very excited that overall clinical trial results support the key differentiation of clinical advantages of lemzoparlimab in terms of drug safety and a favorable PK profile. Now the preliminary antitumor activity of lemzoparlimab as a single treatment agent is promising in our view. We are now continuing the study in the U.S. to combine lemzoparlimab with Merck's PD-1 antibody to evaluate safety and efficacy in patients with solid tumor and Roche's RITUXAN in patients with lymphoma. In addition, we are in the middle of a parallel clinical trial in China to focus on patients with AML and aMDS to evaluate safety, efficacy signal and the data expected early next year. Going forward, we will work together with AbbVie to facilitate the clinical development of the lemzoparlimab for AML and aMDS, as well as solid tumor both globally, by AbbVie and in China by I-Mab. We are very excited about the potential of lemzoparlimab as a differentiated CD47 antibody in this crowded space. Now thank you for your attention. We can now begin the Q&A session. Both Joan and myself are very happy to address questions that you might have.

Rachel, I think we are ready to take questions.

[Operator Instructions] Your first question comes from the line of Louise Chen of Cantor.

Congratulations on the additional data. First question I had for you is why do you think there wasn't a dose response on the anemia patients? Is it because it's just small numbers? And did the anemia lead to any drug discontinuation? And how was it treated with the patients? And then my second question for you is similar on the higher anti-drug antibody. Just saw more in the lower doses. Is there another explanation for this or once again, small patient numbers? And do these patients need to stop treatment or can they continue?

Yes, let me take your first question. The anemia we observed in our clinical trial is mild. It's mostly Grade 1 anemia. So after the first dose, we typically see in some patients there was a drop of hemoglobin within about 10%. So it's a really mild drop. And this mild anemia did not require any treatment and did not have any clinical consequences as we know. It's quite clear. Now this mild anemia was also observed in our preclinical GLP tox study. And also in GLP tox study, in monkeys, we observed very similar phenomenon, which is also not dose independents, are not related to dose. And we think that perhaps this is an antibody bonding, some weak antibody bonding to red blood cells in some cases, and this could induce a slight decrease of the red blood cells. And this is how we view the data.

Yes. I just want to add Dr. Zang's comment. We've seen in the like old red blood cells, they typically are showing some [ efficacy ] signals like weaker. So I think those are the natural course of the depletion of those red blood cells. So we believe that's why there's only a certain part of it. That's why it's not dose dependent. And then maybe I just want to go for just the ADA questions you had raised. So in total, we only have 5 patients have been confirmed with ADA, but none of them had any impact on safety and the PK profile. Hope that answered the question?

Yes.

Okay, Rachel, let's take the next question.

Your next question comes from the line of Kelly Shi of Jefferies.

Can you please comment on if these 3 stable diseases are clinical and meaningful? Do you see a tumor regression? And to what extent, I assume the 1 PR and converted to -- I mean 1 initial PR, you probably have seen some tumor regression. And also how long have they been on the treatment individually? And also what are the current status of those 3 patients in stable disease? And lastly, do you see any potential for the tumor response continue to deepen if they are still on the trial?

So let me try. So for first thing -- the first question for the PR case, the patient was on NIVO for at least 4 cycles and we've confirmed progression of the image. And then the patient was on both NIVO and IPI for another -- this is another 2 or 3 cycles and then would confirm the progression again and then 2 cycles after and then the patient was on our drugs. So the image had 3 consecutive confirmation of this PR. So the patient stayed for the series of PR confirmation and then actually the trends of reductions continued with the third one. So that's how we think that -- so the patient later was PR [indiscernible] disease progression. But in terms of the other 3 disease -- stable disease, I can share with you. So the first one, the patient was 1 milligrams only and the patient actually who were on the studies for a pretty long duration and I can show you later. So the -- we stayed -- he stayed for 8 full cycles of treatment with 3 again confirmed stable disease and then so -- until progression after that. So the second patient who has ovarian cancer with metastasis to the lungs, and he shows on the 10-milligram per kilo cohort and then was also with the confirmed ASP for 2 scans, and then the patient continues to stay until the disease progression after that. And then the third SD was renal cell carcinoma patient with metastasis to the lungs. And this patient was on 30 milligrams per kilo and was heavily treated with chemo. And then also with the -- I just want to mention, this is only 1 PD-L1 expression with -- confirm that its low positive, less than 1%. So it had 2 scans confirmed SD. So after this patient discontinued on the treatment and after cycle 7 because it -- the data is still relatively new, so we didn't have the follow-on after this. So this is -- these are the 3 patients currently confirmed with SD.

Kelly, the comments I'd like to make, we were presently surprised to see 1 PR, 3 SD among 16 evaluable patients. Remember, this is a single agent treatment. If you look at the Forty Seven's data, published data, in there study, in patients with solid tumor, out of 44 patients, they observed 2 PR. So by comparison, we were pleasantly surprised to see the data. Now we are in the middle of a combination therapy to combine lemzoparlimab with a PD-1 antibody to further evaluate safety and efficacy signal of lemzoparlimab and we hope that in such a combination therapy, we might be able to have a better view on the clinical efficacy of our drug.

I also have a follow-up question. So one competitor program, ALX148, has recently showed in head and neck cancer, the addition of chemotherapy greatly improved the tumor response for their CD47 blocker and the KEYTRUDA combo. The ORR increased from 40% to 75% in second line, although in small sample size. I'm just curious, given the optimal safety of lemzoparlimab achieved so far, would you consider also adding chemo to KEYTRUDA combo regimen to leverage on the synergy between PD-1 and the chemo in the future, in the next phase of the study.

Yes. It's a great question. First of all, based on the safety profile and the PK profile of our drug, of lemzoparlimab, we have much room to maneuver in terms of combining not only with PD-1, PD-L1, but perhaps other small molecule drugs. So depending upon what cancer types, we do have flexibility in the future to consider how to combine lemzoparlimab with different either antibodies or small molecule drugs.

Yes, Kelly, I just want to add, I think you mentioned the tumor in head and neck. So in our data, one of the SD, after the patient with squamous cell carcinoma of the tongue and with metastasis to the lung, so he responded very well and have been worked on the treatment for full 8 cycles. So I think that's an encouraging tumor type and definitely, we will put that into consideration in terms of future combo treatment.

Operator, can you take the next question?

Your next question comes from the line of Joe Catanzaro of Piper Sandler.

Just thinking about the AML and MDS data you're expecting in early 2021 and maybe how we should think about the early safety profile we might see here based on what you've seen in solid tumors. And I guess I'm specifically thinking about AML and MDS patients maybe having underlying baseline cytopenias and whether there should be expectations for maybe higher rates or grades of anemia in this patient population. And then with the lemzoparlimab, pembrolizumab combo, can you just remind us the doses of lemzo that you're looking at in this combination and the tumor types you're enrolling, specifically, whether they're going to be PD-1 naive or PD-1 experienced patients and when we could expect initial data from those combination cohorts?

Yes, well, maybe I can take the first question. We're running a parallel clinical trial in China, focusing on AML, MDS. Now we are at 30-milligram per kilo, the highest dose. Now once we finish those cohorts, we'll be able to summarize all the data. Although we don't have a complete data analysis at this point, our impression is that the data are largely consistent with those described in the U.S. study. Joan, could you...

Yes, I just want to elaborate a little bit more. Even though AML, MDS, you would say it's a hematologic disease, more susceptible to anemia, however, we didn't change any regimens because of the confidence of the safety profile. So we still go without priming dosing strategies, and we just continue to those cohort escalations. And then so in China, slightly different, we go with single agent to complete that dose escalation like Dr. Zang mentioned, which should be early next year. Beyond that, we will do combo with AZA as 5F9 did to demonstrate further of this combo evaluations. And of course, moving forward, we will have other potential collaborations with our collaborators AbbVie for any further combo treatments in that area.

I'm just wondering if -- yes, the second -- my second question around the lemzo/pembrolizumab study.

You mean, that solid tumor study, right? So currently, we are in combination treatment in U.S. for solid tumors. Once we have all the dose escalation data, which should be also complete in early next year, we will expand the cohort to look into the tumor types, 2 or 3 tumor types, which you had higher expression of receptors as well as the clinical signals we've seen in cohort expansions. And then we will be able to determine the tumor type to continue to explore the indications. And on the other hand, we have conducted the joint studies with lymphoma, both in U.S. and China, to look into the combo treatment with CD20 as mentioned earlier.

Yes, if you were referring to the dose, we are combining with PD-1 with lemzoparlimab at 20 milligram per kilo and at 30 milligram per kilo.

Yes.

Rachel, next question?

Your next question comes from the line of [indiscernible].

Very exciting, the safety profile; and really interesting, the response in the CPI refractory melanoma. Just wondering, some of the other tumor types have even higher CD47 expression, either based your data or others or preclinical data? Are you expecting CD47 expression to be an important prognostic market for response or not?

Yes, well, this is really a good question. And we think based on our study and all published studies, we think that it is important to have a high expression of CD47 in order to have a better efficacy. So our approach to solid tumor is threefold. One is that through a translational medicine study with academic groups or clinical groups in China and elsewhere. We have been analyzing the level of CD47 among various types of solid tumor. It's very clear. Some of the solid tumors expressed very high level of CD47. Others the levels were low. So that will give you really a good indication as to what solid tumor types you want to focus on. Now the second approach we use is to look at our data, single-agent treatment, and now we're doing combo. And the data will help us to judge what solid tumor types we want to focus on, to have a better chance of success. And then third is -- it's willing to look at the -- our competitors' data and based on information from different sources, we might have a better -- we might be in a better position to determine what solid tumors we want to focus on.

All right. Yes, great. Go ahead.

I'm sorry, maybe I just want to elaborate a little more. So we currently plan for expansion cohort is IO-filled, our lung's most -- cell lung cancer planter and IO-naive, ovarian. But we will adjust it, like Dr. Zang mentioned, based on the efficacy observing the combo.

Congratulations. Very exciting initial clinical data in an important field.

Rachel, so given the timing, I think, we have time for one more question and then we'll wrap up. Okay?

All right. Your last question comes from the line of [ Omar Habachi ] from [indiscernible].

So very simple question. When do you think that you will be able to start Phase II, please?

Yes, so we have -- as Dr. Zang mentioned, we have 2 programs, both in U.S. and China. So there are 2 Phase II programs. So for phase -- for U.S. solid tumor studies, we expect it to start it Phase II, so-called. Also those cohort expansion in the mid of next year. And then so after we completed those cohort expansion -- our cohort escalation with combo 20 and 30. And in China, we also, around that time, we will -- starting the Phase II treatment of AML and MDS with the AZA combos mid of next year.

Okay. That's a great timing. So we're at 9 a.m. Eastern and 10:00 p.m. here in China. Thank you again, everyone, for your time today participating in this call. As you can see, what we discussed on the call today are very interesting and highly differentiated data as far as monotherapy anti-CD47 molecules in solid tumors go. Now we are more convinced than ever that with the favorable safety profile, lack of need for priming dose and lack of antigen zinc effect, as well as encouraging efficacy signals we're seeing with 1 confirmed PR and 3 SDs, we are very convinced that lemzoparlimab has the best-in-class potential among the various competitive CD47 blockers globally. We appreciate your attention too and focus on this promising and highly differentiated asset. We look forward to connecting with you again in the near future on our next data release on lemzoparlimab and other significant catalysts for I-Mab. Thank you. And good night or good day.

Ladies and gentlemen, that does conclude our conference for today. Thank you for participating. You may now all disconnect.