NovaBridge Biosciences (NBP) Earnings Call Transcript & Summary

Thank you, operator, and thank you, everyone, for joining us today. Last night, after market close, we issued a press release announcing that we have successfully completed part 1 of our randomized double-blind clinical study of TJM2, our proprietary GM-CSF antibody in patients with cytokine release syndrome associated with severe COVID-19. The press release can be accessed on the investors portion of our website at http://i-mabbiopharma.com. Joining me today on the call from I-Mab's senior management team are Dr. Jingwu Zang, our Founder, Honorary Chairman and Director; and Dr. Joan Shen, our Chief Executive Officer and Director; and I am Jielun Zhu, the CFO of the company. Dr. Joan will provide background of the TJM2 clinical program, discuss the scientific rationale of inhibiting GM-CSF in severe COVID-19 patients and give an overview of the current study we're conducting. Dr. Shen will then share more details of the clinical trial design and the status, including preliminary findings from part 1 of the study, and we'll discuss our plan to move forward with part 2 of the study. We will then turn the call back over to the operator, so we may take some of your questions. Please note the discussion today will contain forward-looking statements relating to the company's future performance and are intended to qualify for safe harbor from liability as established by the U.S. Private Securities Litigation Reform Act. Such statements are not guarantees of future performance and are subject to certain risks and uncertainties, assumptions and other factors. Some of these risks are beyond the company's control and could cause actual results to differ materially from those mentioned in today's press release and this discussion. A general discussion of the risk factors that could affect I-Mab's business and the financial results is included in certain filings of the company with the Securities and Exchange Commission in the U.S. The company does not undertake any obligation to update this forward-looking information, except as required by law. Now I will turn the call over to Dr. Jingwu Zang, our Founder, honorary Chairman and Director. Dr. Zang, please go ahead.

Thank you, Jielun. Thank you all for joining us today. We are pleased to hold this call to discuss the successful completion of part 1 of ongoing randomized Phase Ib/II clinical trial with TJM2 to treat cytokine release syndrome associated with severe COVID-19 patients. As a reminder, TJM2 is our internally discovered neutralizing antibody against GM-CSF. It is positioned to treat autoimmune diseases and the cytokine release syndrome. Now the successful completion of part 1 of this study, which evaluated safety of TJM2 in this patient population marks an important advancement towards our goal of leveraging our robust scientific and R&D capabilities to develop potential treatments for severe condition caused by COVID-19 and also underscores I-Mab's commitment to science and innovation to deliver a global impact on human health. Importantly, our ongoing trial is one of the industry's first double-blind, randomized clinical trial of GM-CSF antibody in severe COVID-19 patients. We would like to use this milestone. We are reporting today to explain the rationale for employing TJM2 to treat severe COVID-19 disease, describe the design of this important study and give us an opportunity to answer any questions you might have on the clinical trial. Now please note, because the trial remains blinded, we will not be able to discuss the details of the safety or any efficacy results from the ongoing double-blind clinical trial. For background, GM-CSF is an important cytokine that plays a critical role in chronic inflammation and tissue destruction in autoimmune diseases. GM-CSF can polarize macrophages into the proinflammatory M1 phenotype and is known to induce an inflammatory cascade involving other inflammatory cytokines, such as TNF, IL-1, IL-6, IL-12 and IL-23. It's evident that GM-CSF plays a crucial role in the pathogenesis and disease progression of multiple autoimmune conditions. I want to remind you that prior to initiating the development of TJM2 to treat cytokine release syndrome associated with COVID-19, we had successfully completed a Phase I study in the U.S., in which TJM2 has shown favorable safety tolerability, PK/PD and a immunogenicity profile in healthy volunteers. While our goal was -- remains to develop TJM2 in rheumatoid arthritis and other autoimmune conditions, there's a strong scientific evidence to suggest that inhibiting GM-CSF may have a beneficial effect on patients with cytokine release syndrome or CRS associated with severe COVID-19, given its underlying mechanism of action. Now cytokine release syndrome is characterized by surge of high levels of circulating pro-inflammatory cytokines and is overreaction of the immune system, under the conditions, such as CAR-T therapy and COVID-19. Now recent data indicate that the common features among COVID-19 patients, particularly those severe patients includes lymphopenia, significantly elevated serum levels of pro-inflammatory cytokines. Moreover, it seems clear that recent published data indicates that severe COVID-19 has all the hallmarks of a cytokine storm caused by activated immune cells producing GM-CSF and IL-6. In one recent study, high concentrations of GM-CSF was found in the plasma of a severe and a critically ill COVID-19 patients, which account for approximately 20% of all patients, especially in those requiring intensive care. Now this cytokine -- this pro-inflammatory cytokines drive aberrant monocytes and lymphocyte activation, which, in turn, provoked more cytokines and chemokines resulting in cytokine stone, severe lung complications and mortality. Therefore, blocking GM-CSF by TJM2 can work upstream of the cytokine storm network to prevent a curved hyperinflammation and the immunopathology, which may be responsible for the severe anemia of COVID-19. Now given TJM2 blocks the cytokine release from the upstream of the cytokine cascade, this approach may have potential advantages over entire IL-6 antibodies, some of which are being investigated in COVID-19 by other sponsors. Now with this in mind, we swiftly initiated the development of TJM2 in March in the U.S. to help address this global pandemic. Now I would like to turn over to Dr. Shen to give you more details on this trial and some of the preliminary foundings from part 1 of the study. Dr. Shen?

Thank you, Dr. Zang. So as Dr. Zang already mentioned, this is a study industry-wise, like first GM-CSF that is with randomization of double-blind and placebo-controlled. So we intended to make it to 2 parts to ensure we understand the safety well in these special populations. So which is why we had the 2 parts. The first part has 3 dose arms, 3-milligram per kilo and 6-milligram per kilo and placebo. Of course, here is the standard treatment. So after 8 patients on each cohort, we have completed 24 patients, which is where we are in discussions with you all. So altogether, the second part is about to initiate after the first part of completion and also the DMC recommendations to make decision -- after making a decision of the safety profile for the first part. So altogether, we'll have 144 patients. Those patients are at the age of 18 or above across between those arms. So we are all -- the patients are given single injections. The primary safety endpoint is the incidence of treatment-emergent adverse events after 30 days and after the drug administration. And the primary efficacy endpoint is the proportion of participants experiencing deterioration in clinical status from baseline to Day 14 versus placebo. So we started the study since early April after the clearance of IND by U.S. FDA or -- and after the clearance -- the approval by the central IRB. So we have completed the 24 patients few weeks ago. And last week, we had the data monitoring committee, DMC, to have the review of the data, which, at this moment, as Dr. Zang already mentioned, was focusing on assessing the patient safety and the overall conduct of the study. Without any major safety concerns on those randomization treatment in 3 arms, the DMC concluded after carefully review the whole data package that the I-Mab can commence the part 2 of the study as planned. This indicates that TJM2 is safe and well tolerated with severe COVID-19 patients. The DMC also endorsed a few protocol amendments, including increasing the doses of -- the dose of 3-milligram per kilo to 6-milligram per kilo for single infusion. This make the 3 dose arms as 6 and placebo, indicating the safety profile, it's very acceptable in the higher dose as well. And also DMC endorsed broadening a few other inclusion criterias. This also gives us more confidence because of the safety profile showed so far. So altogether, we had 16 treatment-emergent adverse events. Most of them were infections or transient liver enzyme elevation. Just keep that in mind, this is blinded data, including the placebo arm. We also had 8 subjects reporting 11 SAEs and 4 deaths. So among the 4 fatal cases, 2 were assessed as definitely not related and 2 others were assessed as unlikely related. So all the SAEs at this moment are all assessed as unrelated or unlikely related. So most of them were respiratory failure or infection. So with the DMC's recommendation, we are now proceeding to move on to the next part of the study, while continue communicating with FDA in parallel. So we're looking forward to continue the progress of this study and plan to provide the next update, which we anticipate it will include FX results at a time when we complete the Part 2 studies later this year. So with that, I would like to turn the call back to our operator, so we can go ahead and take your questions. Operator?

[Operator Instructions] The first question we have is from Fei Zheng from Crédit Suisse.

I have 2 questions. One -- the first question is, I noticed that some companies are actually using the IL-6 antibody to treat the COVID-19 patients. I'm just wondering, since we have the IL-7 antibody, why are we not choosing this pathway instead of we are choosing the M2 as our treatment? And my second question is, if we succeed in the part 2 of this study, what's our plan to move to the next step?

Well, thank you for your question. Maybe I can take the first question and leave the second one to Dr. Shen to address. Your first question, you're right that in our pipeline, we have both IL-6 blocker and GM-CSF blocker antibodies. Okay. Now the reason why we choose TJM2, which is GM-CSF antibody for the treatment of cytokine release syndrome associated with COVID-19 is twofolds. Okay. First of all, comparing to IL-6 targeting GM-CSF has certain advantages, which may translate to better clinical efficacy and perhaps safety. Now in terms of how you're going to understand the advantages of TJM2. I think I can give you 2 aspects to consider. One is that in terms of the mechanism of action, GM-CSF works upstream in the pro-inflammatory cytokine network, okay? It sits above IL-6. So targeting GM-CSF not only inhibits IL-6 but also other inflammatory cytokines that will play -- that also play an important role in cytokine release syndrome. And this is a very important factor to consider. And for IL-6 antibody, you only inhibited -- you only inhibit IL-6. Now with GM-CSF antibody you inhibit not only IL-6 but also other pro-inflammatory cytokines that are associated with cytokine release syndrome associated with COVID-19, okay? So that's the first aspect to consider which is very important. Secondly, there are preliminary clinical data indicating that GM-CSF antibody has a preventive effect on cytokine release syndrome as compared to IL-6. It also has a lower infection rate as compared to that of IL-6. This is also very important to consider because in COVID-19 patients, they are already in a severe disease situation and facing challenges with multiple infections. We don't want to add agents that can cause more infections, so GM-CSF has advantages in this regard. So putting together, those are the certain advantages of TJM2 over IL-6 antibodies. And that's the reason why we'll focus on TJM2, but not our IL-6 blocker. Dr. Shen, could you -- second question.

Yes. I'll continue the second half of the question. So in terms of what we will do after we complete the second part of the study. As you are aware, this study was closely working -- the result of working with our regulators in the United States. So we'll be communicating with the ongoing and then the intended plan was that upon the completion of the study, we will go to FDA for potential registrational path discussion depending on robustness of this result. And then so far, we believe this is a potential possibility because of the urgent needs of the patients and also the ongoing safety data and efficacy as long as we support it, and we should be able to quickly make it available. And in fact, the company is accelerating the manufacturing process as well to ensure besides we have enough drug supply for clinical trials ongoing. We will also make it available to the public, if we were being accelerated for registration. Hope that answered your question.

The next question we have is from Kelly Shi from Jefferies.

This is Kelly from Jefferies. Congrats on the progress. It was mentioned that in the press release, the DMC endorsed a protocol change, including broadening the inclusion criteria and dosing our patients at a higher dose of 6 milligrams per kilo of TJM2. I was wondering what triggered the protocol change. And do you anticipate any impact on efficacy readout and also enrollment pace? And the second question is, what is the estimated time line to get data from part 2 of the study? And also, like, are you going to talk to the regulatory agency immediately after the part 2 of the data available? Or you will actually start a dialogue in the middle of the part 2 study?

Thank you, Kelly, for the question. So for the first part of the question, we talked about increasing the dose cohort -- dose from 3 milligrams to 6. Based on the -- our continued discussion, we know in our earlier study like Dr. Zang has mentioned in the United States, we had dosed healthy volunteers up to 10 milligrams in a single dose. And now we are giving the 2 doses, not knowing the safety profile, if 6 milligrams is safe enough. So our intention is giving the higher dose to ensure patients adequately treated because this is only single shot. But before we fully understand its safety profile of 6 milligrams, so we gave the 3 milligrams to really compare what is a safety profile looks like. So now with the completion of first part and with this conclusion, that means the 6 milligram is safe to proceed as well. So with the limited number of sample size, we -- also with the potential to give the patient maximum benefit, we -- this is why we roll over the 3 milligrams to 6 milligrams altogether, with the DMC's endorsement. That's one thing. Secondly, some of the inclusion criterias, for example, COPD, those patients already have a compromised regulatory function, we were not very comfortable at the beginning to enroll those patients. When the -- COVID-19 is mostly targeting on the respiratory areas. So however, with the good safety profile we completed so far, and then we didn't have any, at least trace of safety concerns because of the CD status. That is why this is also endorsed by DMC. So that will enable us to expand the patient pool to give them all -- the more patients, the potential benefit. So keep in mind, most of the patients who had severe cases are compromised with other complications, including respiratory situations like COPD or of elderly. So if we exclude that, that means we had more limited patient numbers or limited outreach. So that is why we feel at this moment, we wanted to give more patients the opportunity. So did that answer your question?

Yes. And do you anticipate any impact on the enrollment pay because I assume like if you broadened criteria -- inclusion criteria, it should accelerate the enrollment? And the second is, do you expect that this will have some impact on efficacy? But I think the part 1 is actually focusing on safety, probably you will not be able to tell at the moment, unless...

Right. So we -- yes. Yes, thank you. That's a good point. So however, since we had -- our efficacy is looking at the patients deterioration to comparing how we can prevent or alleviate their severity of the symptoms. So even though they had a baseline situation compromised with some of those respiratory conditions, as long as they are able to retain or improve upon the medical -- upon this treatment. We believe that is all the benefit we should look into. So before we fully understand exactly what patients start to benefit the most, we believe we should expand it to the larger population. That's how we feel we should do and also regulatories actually encourage us to do. So that's one of the reasons. And -- yes. So to continue the second part of the question, that is a very good question. So we -- and when we should start the conversation with regulators. I think first, as I mentioned earlier, it is ongoing. So actually, yesterday, we received like a call from FDA say, well, they wanted us to give them the status reports. They even gave us the table to build it up. So they are very -- paying attention to this study. And we also, of course, will continue. I think as this DMC result is part of reports. However, to prepare the potential restriction, as you can tell, we definitely need to start the communications before we finish the study to fully prepared in case we need to accelerate it. So there's many opportunities or potential. However, all of them needs to be like well prepared beforehand. So that's a very good reminder. Thank you.

And this is Jingwu. Maybe I'll just add one more point on top of what Dr. Shen already explained. For us, it's a positive sign related to this mono change of protocol to switch low dose 3-milligram per kilo now to 6-milligram per kilo. It's a positive sign. And it's also a positive sign that DMC allows broadening of the selection criteria because based on the safety data, now they are much less concerned with the safety and also this will help us to accelerate our patient recruitment, and this is very helpful in this pandemic situation. I just want to add a point.

And if I may, can I ask a question on CD47 antibody TJC4. The safety differentiation should allow a variety of combo strategies. So besides the pembro combo in solid tumors through the collaboration with Merck, and also the rituximab combo in lymphoma in collaboration with Roche. Are you also considering other strategic partners to further expand the CD47 program leverage on the combo strategies?

Yes, that's a very good question. We are considering this. There are 2 areas we can consider how to combo with other treatment agents to increase treatment efficacy. Now on the -- on AML, MDS, we can think about combining our CD47 with agents like BCL-2 or small molecules like the AZA to increase efficacy in patients with AML MDS. For solid tumors, in addition to PD-1 or lymphoma in addition to CD20, we could combine with other existing treatment agents, for example, Avastin and a few other options we have to combine the agents that already have shown some efficacy and is a part of the standard of care to increase the efficacy of the treatment. So there are multiple options we can consider to combine with the existing treatment agents to increase efficacy, if you will.

Thank you very much for providing your view, and we are looking forward to the first readout of CD47.

The next question we have is from Zhao Bing from China Renaissance.

And I had 2 questions related to the COVID-19. And the first one is it seems that the TJM2 is targeting the COVID-19 patients. So if the COVID-19 are under controllable, so do you think it would be -- affected your patient recruitment for the later clinical trial? And the second one is, I'm interesting to know the clinical trial progress on some of the current assets, I say, CD47, is that -- we noticed that CD47 is doing clinical trial currently in U.S. and would be -- would this trial -- would the progress will be affected by COVID-19?

Okay. So let me try to answer your questions. Thank you. So we are aware of this epidemic data in the United States as well. And also, as you -- the FDA laid out in the new guidance, so they actually encourage to migrate the sites to where the patients are in -- for this COVID-19. So we had -- that is why in our first part, we have 8 sites. In second part, we expanded to 15 sites. So this gives us a lot of flexibilities to give them more enrollment to the site where the pandemic is still in kind of hard hit. We also are closely watching this epidemic data like modeling, where and when the states or the city will hit the peak. So in that case, we believe this 15 sites currently will be able to give us the patient numbers we had planned here. In case there are needs for moving to the other places where our sites are not located. We also have a backup plan to include more sites to -- in -- for completing this part of the enrollment. So this is one. For your second part of the question, if other programs has been affected, for example, CD47. And so far, we believe it's a very minimal impact we had. At first, we -- you've seen the Phase I studies, we don't expect a large number of patient recruitment. Secondly, our major sites were in -- not in central cities like in New York or Chicago. So we were able to divide or diversify our patient from most sites, for example, Indiana or some Kansas. Currently -- so CD47 is being enrolling smoothly. We are currently about complete 20-milligram per kilo cohort, and then we'll move to the last cohort, which is 30 milligram very soon. So so far, we're pretty -- in good shape in terms of enrollment for CD47.

Thank you. Ladies and gentlemen, I would like to advise you that this now concludes our conference call. Thank you, everybody, for joining. You may now disconnect your lines. Thank you.

Thank you.

Thank you.