NovaBridge Biosciences (NBP) Earnings Call Transcript & Summary

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 include Dr. Jingwu Zhang, Founder and Chairman of I-Mab; Dr. Joan Shen, CEO of I-Mab; I-Mab; and Mr. John Long, Chief Financial Officer of I-Mab. Today's conference call will be divided into 2 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 Zhang, 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 refractory non-Hodgkin's lymphoma. Now on Slide 3, 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 bonding to various tumor cells and exhibits strong antitumor activity. On the other hand, there has a minimum bonding 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. So in summary, there are 4 key differentiations. One is related to the 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 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 and all the safety data, PK/PD data and efficacy data based on administration result priming dose. And this is a very important point to mention that has advantages clinically. The first aspect of clinical differentiation is related to side effect. Lemzoparlimab does not have a side effect because it has only minimum binding to red blood cells, so it does not cause side 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 monotherapy of lemzoparlimab or combo therapy of lemzoparlimab in combination with PD-1 antibody in solid tumors, we have seen good clinical activity and good response to solid tumors. Now today, we're going to talk about more efficacy data related to lemzoparlimab in combination with rituximab in the treatment of relapsing and refractory non-Hodgkin's lymphoma. So we are quite excited that lemzoparlimab has 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 4, 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 the dose escalation part of the study conducted in the U.S. Today, we're going to go through the detail of the 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. So additional data being matured, and we will presented a new data on the expansion phase probably next year. Now on Slide #5, here is the summary of the clinical data. On safety, we continue to see good safety profile. And in this trial, again, lemzoparlimab is well tolerated. And again, I'd like to mention the safety profile is observed without a priming dose, and MTD was not reached. And this is consistent with the safety profile we have seen so far from other parallel clinical trials. And 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. And this is an 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, the is directly related to efficacy of the lemzoparlimab. So in this study, we have seen a strong penetration of drug distribution in biopsy tumors, in tumor samples on treated patients. And average, we observed 80% and 90% of scanning which is -- really represents a high level of the drug distribution within the tumor mass. The third point is related to efficacy. Now in this combination study, out of 7 evaluable heavily pre-treated patients, we observed 4 CRs, 1 PR. So ORR is 71%. And we also observed 2 stable disease, so direct -- the disease control rate is 100%. And this is quite encouraging because this is so far, among all the studies so far, this represents, really, the best data -- efficacy data, even though the patient number is still quite limited at this point. And we have continued this study, expanding the patient population and hope to validate this data with more patients. Last but not least, with the accumulative data from this ongoing study, we hope we will be in a position next year to initiate a registrational clinical study in China 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 going to stop here to ask Dr. Shen to take a deep dive into the detail of the data and the critical part of the clinical data. Dr. Shen.

Thank you, Dr. Zang. Yes. Here I will present it more of the data, which we already showed on ASH meetings. So in terms of this demographic informations, as you can tell, overall, we enrolled at 9 patients, and all of them are NHL patients. And on average, age is about 61, with 4 females and 5 males. And all are white people -- white patients, and the number of prior treatments on average is 4 lines from 2 to 10. And then 33% of them are the rituximab refractory. And then the tumor types including DLBCL, MCL and FL, so next. And this showed the treatment-related adverse events, which is also reported. So as Dr. Zang 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 1 Grade 3 anemia. This patient actually does not require blood infusion or a discontinuation of the study so he was able to tolerate this anemia and continue to be on the treatment. So this further demonstrate the good safety profile also related to the -- validated our safety claim on the red blood cell sparing mechanism. Next. This further showed the transient anemia observed in both monotherapy and rituximab or 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 and especially the first cycle, but -- and it can gradually resumed with the increase of reticulocytes. The average decrease on hemoglobin is around 14%, and then these are not related with the dose. So this was resumed to the treatment -- baseline or above baseline levels after continuing the treatment. And even this anemic observed but does not show any hemolytic natures, so all of these are continuing to support the previous claim that is, again, is red blood cell sparing on epitope. Next. And also, I want to continue to mention all these patients did not require priming dose. And in clinical efficacy wise, we had really observed a very exciting efficacy and data from the patient populations. As I had mentioned earlier, we have dosed 9 patients, 7 of them are evaluable. So among these 7 patients, we have 4 CRs, 1 PR, with ORR rates of 71% and the 2 SDs, so disease control rates altogether is 100%. And then the durations of the response in -- among these 5 responders is 61 to 236 days. And as of today, there are still 6 patients who are still remaining on the study. So the date of treatment is from 144 to 340 days, so it's almost a year. So the median time to initial response about 50 days. So you can tell from these studies -- from these graphs here, the durations are continuing, then the patient continuing to benefit from the studies. And 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. This -- the first part is transactions of the PET CT and you can tell this -- from the image, the target lesions before and after treatment. It's very different, so after treatment is completely resolved. And lower part is abdominal part, and then also disseminated lesions on the left side is completely resolved on the right side. So this showed these patients achieved the CR after 32 weeks of treatment. And then this patient is continuing on the treatment up -- as of today. And also worth to mention, this patient has been treated previously with the standard treatment within R-CHOP, R-CVP, and also have been remained on rituximab for 2 years, which has relapsed afterwards. And it was able to be treated and benefited from the current study. Next. And it's worth mentioning, as Dr. Zang earlier stated, that to further demonstrate the tumor engagement of the lemzoparlimab and then it's penetration, the team worked very hard to be able to obtain the biopsy from the baseline and after treatment. Among 7 patients, we obtained 4 samples, so this is very important to observe these changes before and after the treatment. You can tell the average penetrations after treatment shown is 80% to 90% on the IHC stainings. So before that is plain and empty, but after the treatment, you can tell, the staining is very strong. So 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 making -- the shrinkage of this lymphocytes -- lymph nodes, sorry. So all the these demonstrated clinically, the patients are benefiting and safety-wise continue to show the benefit of non-red blood cell finding and minimal anemia, and as well as the overall benefit, and it is also validated by these strong penetrations in the tumor side. So this is the current presentations showed on ASH meetings, and I'll be referring back to Dr. Zang for summarizing this study.

Thank you, Joan. Now, we are on Slide #12. And I'd just like to summarize that at I-Mab, lemzoparlimab is a key clinical asset. It is at a critical stage of clinical development today. We and our partner, global partner, AbbVie, are running 5 parallel clinical programs in both U.S. and China, including 2 studies sponsored by AbbVie. Now just briefly summarize the programs where -- 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, we hope to 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 enrollment 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 expanded clinical trial of lemzoparlimab in combination with PD-1 antibody in the 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 neck cancer has already started in China, recruiting patients. So more data will come in 2022. So to summarize, we have 3 data readout events for lemzoparlimab in 2022. The first part -- the first data readout is related to new data from the non-Hodgkin's lymphoma expansion study in 2022. The second data readout is related to what I already mentioned, solid tumor data in combination with PD-1 antibody in early 2022. And then the third data readout 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. So in summary, with the good safety profile and the initial clinical efficacy, we'll be able to speed up the clinical development plan and aim to potentially initiate 2 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. So I'd like to stop here and to see whether there are questions, and both Joan and myself will be happy to address any questions you might have.

Thank you, Dr. Zang and Dr. Shen for the very comprehensive overview. Now we will start the Q&A session. [Operator Instructions]. So our first question comes from Kelly Shi. Kelly, please.

First, I'll congrats on great progress. I have 2. The first question is how do you assess the potential of lemzoparlimab or the entire CD47 drug class? Either they could eventually carve out market share in non-Hodgkin lymphoma given the highly competitive landscape, and also many new agents breaking into the space. And my second question is, there is also many investors 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 I-Mab, and how do you mitigate the potential ADR risks? And what is your deal listing plan and also time table?

All right. Thank you, Kelly. Maybe I'll just say a few words about your first question, and I will ask Dr. Shen to chip in to add her view on your first question. And 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. So CD47 pathway, and this particular class of new agents CD47 antibody, provides a powerful and novel pathway to work in combination with other agents to really provide a efficacious option for patients who suffer from refractory relapsing non-Hodgkin's lymphoma. Now our data today we shared -- the data we shared today, again, is a demonstration that how a CD47 antibody can work effectively with CD20 antibody to provide much better clinical efficacy even though at this point, we have limited patients. But 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 as a combination therapy. So Joan, do you have anything to add?

Yes, I do. 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 treatment. So for lymphoma, in particular, it is -- even though there's a lot of currently options and the many new approaches it's working on. But its uniqueness is no matter how well it responded to begin with, and it will -- many of the minimal patients will suffer from recurrence. Once you reoccur and then it's harder to treat, so there's always a fight against the recurrence and the refractories. So the physicians are constantly looking for new solutions. But we believe, as we have already explained, that these new treatment options from very different angles to address the recurrence and relapse the patients is really needed regardless of other agents coming along. Yes, I just want to add it.

Okay. Kelly, I'll answer your second question regarding the SEC new rule. Actually, the Holding Foreign Company Accountable Act has come into effect since January 1, 2021. Under the SEC rule only adopts its amendments, on disclosure and some mission requirements. So it's 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 disclosed by CSRC Chairman, Yi Huiman, last year, China CSRC has already approved with least 14 U.S. listed Chinese companies to provide all the working papers to PCAOB. While this act under the new rule brings some jurisdiction group risk to U.S.-listed Chinese companies, we do believe that the biotech sector, and in particular, I-Mab, but this is very little risk in this regard. As far as we know, I-Mab's business does not relate to any national security matters, and there is no government issue nor 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 these potential ADR uncertainties. For example, we are working with our auditors and advisers to pursue approval for provision of working paper to PCAOB. And last week, we also announced our planned 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 ADRs 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 I-Mab's ADRs. Thank you for the question.

Thank you. Our next question comes from Joe Catanzaro. Joe, please.

Great. Thanks so much for hosting this. Maybe just a follow up on Kelly's first question there, but get a little bit more specific. I'm wondering how you guys think the 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? And maybe along those lines, I'm wondering if lemzoparlimab, given that it doesn't require a priming dose, doesn't observe meaningful antigens sink and achieve target saturation much quickly, whether there's possible opportunity for time to response to be meaningfully quicker than other agents?

Thank you. Perhaps Joan, would you like to address this question?

Yes. I'll try. 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 initial patients with the number of 22 patients enrolled. We have achieved 36% of CR rate, while we're -- ours is 57%. And then they have ORR overall is 50%, while we have 71%. And then the disease control rate is 64% when we have achieved 100%. So on the other hand, the other ALX148 reported CR rates of 18%, an ORR rate of 55% and the disease control rate, 73%. So although the sample sizes are relatively small, but we are very, very pleased that in our TJC4 data is comparable, actually numerically better than magrolimab and ALX148. So relatively, efficacy-wise, we are very confident that we can achieve comparable or better results in consider of the safety profile and also the red blood cells sparing nature altogether with -- like you mentioned earlier, without the sink effect, we believe the target engagement could be even quicker. And especially with the next years of more solid tumor data, we are hoping to demonstrate more of the -- of the efficacy data as well as continue to demonstrate the benefit in our safety profile. So yes, I'm stopping from here.

Thank you, Dr. Shen. Our next question comes from Carvey.

This is Carvey on for Louise from Cantor. Just a question from us. What are our key milestones for lemzoparlimab in 2022 and possibly beyond?

Thank you. This is Jingwu again. I must say CD47 is one 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 assets in clinical trials. So currently, as I mentioned, we are running 3 parallel clinical programs: non-Hodgkin's lymphoma, AML/MDS and solid tumors. And our global partner, AbbVie, is running 2 global clinical programs to focus on AML/MDS in combination with their BCL-2 inhibitor, and on multiple myeloma with CD38 monoclonal antibody. So those are very exciting programs, and 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. So I can quickly mention there are 4 key clinical milestones. One is additional data from our ongoing dose expansion study on non-Hodgkin's lymphoma, so we have additional data to report in 2022. Second, we will have a new data coming from our ongoing Phase II clinical trial in patients with AML/MDS. We hope to report this Phase II data in 2022. Thirdly, we will -- early next year, we will report clinical data from our ongoing clinical trial in solid tumor in combination with PD-1 antibody. So those are the 3 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 will be in a position to initiate 1 or 2 registrational clinical trials in China to pave the way for lemzoparlimab to get registered as a first CD47 antibody in China. And we will work with our global partner, AbbVie, to facilitate global registration of lemzoparlimab.

Thank you, Dr. Zang. Due to time limitation, I think we will take one last question. Our last question comes from Andrew from HCW.

I guess my first question is regarding combinations with lemzoparlimab with pembro in solid tumors, could you give us some additional color what you need to see in order to classify a positive outcome for that program? And then lastly, could you provide an update on uliledlimab's clinical development in the United States and in China, particularly in regards to how you're thinking and partnership has evolved over time.

Yes. Thank you for the question. Maybe I can take your second question first, and I'll 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're among the top 2 or top 3 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 are running parallel 2 clinical -- Phase II clinical trials. One is in the U.S., we just started that clinical trial, and the other clinical trials ongoing -- a Phase II clinical trial ongoing in China. And so far, combining all the clinical studies, we have those 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. So CD73 antibody, where in both Phase II clinical trials, we will focus on selected tumor types. Lung cancer, ovarian cancer and a few others, and based on our own preclinical data, clinical data and other companies' data. And that gave us some good ideas and some direction as to how, going forward, we will increase the probability of success by focusing on 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 in the negotiation phase how we're going to work together in terms of clinical development, commercialization, manufacturing. We hope that early next year -- sometime next year, we'll be able to close the deal. And this is an exciting program, has really attracted a lot of attention from the big pharma groups. And we'll continue to make sure we will strike a best deal for this exciting asset. Thank you.

Okay. So 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. Zang mentioned, we are exploring in both U.S. and China in a basket trial design fashion to look at these unmet needs in the particular, in tumor areas, with the translational work showing the high expressions of CD47 in combination with the current on PD-1, and particularly KEYTRUDA, to show -- KEYTRUDA or other PD-1 to show if we can address the unmet needs. For example, the success will be 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. And then for like lung cancer is also, the overall response rate is not greater than 20% for single treatment alone. So we wanted to demonstrate that this combo can overcome the hurdles either treatment-naive patients or high and low expression of PD-L1 to look at the potential of this high expression of CD47 in combination with the checkpoint inhibitors. So overall, since checkpoint inhibitors largely applied for different tumor types, and we have been aware what is the current treatment magnitude. So by defining success, we should be able to address what's the current basket trial design. See if we can reach the clinical benefit in terms of comparing with what existing checkpoint alone can achieve. So next year, as Dr. Zang mentioned, earlier next year, so we should be able to show some clinical datas from the U.S. studies, which is the solid tumor in combination with KEYTRUDA.

Thank you Dr, Zang and Dr. Shen, and thank you, everyone, for joining our meeting today. If you have any further questions, please feel free to reach out to our IR team. Wish you all have a good day, and you may disconnect now.

Thank you.

Thank you.