NovaBridge Biosciences (NBP) Earnings Call Transcript & Summary

Good afternoon, everyone. My name is Kelly Shi, one of the biotech equity analyst at Jefferies. Thank you for attending our virtual health care conference. We are very pleased to have Dr. Zang Jingwu, Founder and Director of I-Mab Biopharma joining us today for this fireside chat. I-Mab has made a tremendous progress since the IPO in early 2020, among which the first data from CD47 antibody and AbbVie partnership as well as the ASCO update of their CD73 combo have attracted great attention from investors. But [ for not ] missing a broad pipeline outside of these 2 IO candidates, I think we're going to start out with Dr. Zang give us an overview for I-Mab, what the milestones that company has made since the IPO, and what are the key learnings so far. Dr. Zang?

Thank you, Kelly. We have made remarkable progress in those 3 areas of business. The first area where major progress is made is related to the pipeline development. Since the IPO, we have achieved a number of major milestones for our key assets of top line value drivers. I can name a few here. TJC4, lemzoparlimab, a highly differentiated CD47 antibody, we completed Phase I clinical trial in the U.S. and demonstrated the key differentiation of our CD47, which led to a global partnership with AbbVie. TJD5, another exciting monoclonal antibody, our CD73 antibody, we completed recently Phase I clinical trial in the U.S. with very encouraging clinical results that are selected for presentation at an ASCO meeting next week. TJ202, our differentiated CD38 monoclonal antibody, we completed a registrational trial in China and are on track for BLA submission this year, which is the first BLA for the company. This is a very exciting moment. TJ101, our differentiated long-acting growth hormone, we started Phase III clinical trial early this year in China, which is a 165-patient trial. We aim to complete the patient enrollment very soon. Now another asset, TJ107, our long-acting interleukin-7 to treat cancers with lymphopenia, we initiated a Phase II clinical trial in China earlier this year and going to start another Phase II trial in China in the second half of this year. In addition, since the IPO, we have brought 3 new innovative assets, 1 monoclonal antibody, 2 bispecific antibodies to the clinical trial in the U.S. So as a result of the rapid progression of pipeline development, by the end of this year, we will have 16 clinical trials ongoing. 2/3 of them will be in late stage, either Phase III or Phase II, in both U.S. and China. So our top line is not only innovative and globally competitive but also very advanced, with 3 BLA submissions expected within the next 3 years. Now the second area where major progress is made is related to our BD and partnership activity. As a global biotech company with globally competitive assets, we are very active on the global BD and partnership front. We have done multiple BD deals since the IPO last year. The most visible global deal, of course, is the partnership with AbbVie on lemzoparlimab, our CD47 antibody. This deal is valued at close to $2 billion with the upfront and first milestone payments of $200 million. This is the largest cross-border out-licensing deal from China, has demonstrated our capability to develop innovative assets that are truly differentiated. For I-Mab, every partnership is not a chance. It's by design and driven by strategy. We're continuing to work on more deals with additional assets in our pipeline such as uliledlimab, our TJD5, and other novel assets that are being validated in clinical trials in the U.S. In addition, we are also working on a number of in-licensing opportunities to bring in late-stage assets or even globally marketed products to enrich our commercial portfolio. Now the third area I'd like to mention is the -- it's really related to building our manufacturing capability and commercialization capability. As you know, I-Mab has embarked on a journey to evolve from a clinical stage biotech today to a fully integrated global biopharma within the next 3 to 4 years. To this end, we have started to build our manufacturing facility in Hangzhou, China. Our pilot plant will be ready by 2022 to start producing clinical trial material for both U.S. and China studies. Our commercial production will be ready by the end of 2023 to prepare for commercialization of TJ202 in China. In addition, we are building our commercialization capability to prepare the planned product launch for TJ202 followed by a few others. So those are the -- very quickly, those are the major progress that has been made in these 3 major areas of our business.

It is a very exciting time for I-Mab. I also have a high-level question. So on the overall pipeline strategy and the business model, how is I-Mab differentiated from its peers? And also, how is I-Mab positioned in global biotech industry?

Yes. Firstly, our overall pipeline strategy is to focus on innovation. By innovation, we mean we only work on drug assets that have a first-in-class, best-in-class potential. The examples are TJC4 and TJD5. Those are highly differentiated monoclonal antibodies, and you will see more examples that are coming to play. That differentiates I-Mab from our peers in China and from many biotech companies around the world. Secondly, our pipelines are comprised of 2 portfolios. The global portfolio consists of internally discovered assets such as TJC4 and TJD5 to move rapidly for clinical proof-of-concept in the U.S. Now the China-focused portfolio is composed of in-licensed clinical assets that have a much less development risk to rapidly advance to registration in China. The examples are TJ202, our CD38 monoclonal antibody for multiple myeloma, which is expected for BLA submission this year, and TJ101 that is in Phase III clinical trial in China. So the 2 portfolios are complementary to each other to balance the risk, innovation and our accelerated time line for product launch. This is also unique among many different companies. I-Mab has been well recognized as one of the few top-tier innovative biotech companies in China, and our innovation is also well-known in the world. We are also one of the very few China-based biotech companies with extensive global operations and a global ambition.

Great. And turning to the pipeline, let's start with I-Mab's CD73 antibody, uliledlimab. It recently made headlines on ASCO abstract release day. Can you remind us the data details and why those results could be interpreted as impressive? And also, at the ASCO meeting, what additional information will be available to investors?

Yes. Thank you, Kelly. It's a Phase I dose-escalation study where TJD5, our CD73 antibody now called uliledlimab, is evaluated as a monotherapy run-in and followed by combination with Roche's PD-L1 antibody in patients with advanced solid tumors. Now firstly, the data showed that TJD5, our CD73 antibody, has a good safety profile. The drug reached full receptor occupancy at 10-milligram per kilo. So now we know the effective dose level to move forward. Now it is also important to mention that our study demonstrated the differentiated property of TJD5. That is, TJD5 does not have the hook effect that is commonly seen with other CD73 antibodies. And this is really a clinical, meaningful differentiation because it allows the drug to take its effect according to predicted PK/PD relationship. So we don't have the challenges as other companies do with a different CD73 antibody. Now secondly, we are very encouraged to see efficacy signal even in this limited Phase I clinical trial. To be more specific, we observed 1 CR, 2 PR and 3 SD among 13 evaluable patients with advanced cancers. Now the patient with a complete response has ovarian cancer that is usually not sensitive to PD-L1 treatment alone. The patient has been under treatment for 17 months. One patient with PR, partial response has previously failed repeated checkpoint therapies, and those are significant information. As compared to [ others ] in similar clinical setting, for example, a similar Phase I combination clinical trial with PD-L1 antibody and TJ antibody, this level of ORR observed in our study is significant and very encouraging. Now the other important observation from the clinical study is the correlation between the higher co-expression of PD-L1 and CD73 in the tumor samples and the clinical response of the patients, and this is very striking. All patients with the higher co-expression of PD-L1 and CD73 in their tumor samples happen to be the clinical responders. And this is exciting because we may now have a handle on this, and we may use PD-L1 and CD73 as the potential biomarkers to select the right cancer patients who are suitable for the combination therapy for a better probability of success. In addition to the continued clinical study in U.S. and China, we have an ongoing Phase II clinical trial of TJD5 in combination with PD-1 antibody for lung cancer and a few other selected cancers. So these well-designed clinical studies will hopefully pave the way for a registrational study to be started soon.

I see. So it seems that all this biopsy data and biomarker studies point to this -- the responses you have seen with CD73 antibody is very specific, which set a good stage for the future combo studies. So my question is, what makes CD73 standing out as a good PD-1 and PD-L1 combo partner? Are you also thinking about other combo strategies centered on this key component in the adenosine signaling?

Yes. Yes, it's a good question. A combination of CD73 with PD-1 or PD-L1 antibodies, it's quite obvious according to the mechanism of action, right? But we are also exploring the possibility to combine our CD73 with other targeted therapies, small molecule drugs, in order to create synergy with other treatments to potentially offer a better efficacy. So this is something we are planning. Most likely in the second half of this year, we may submit R&D application in China to start a clinical trial to combine our CD73 with targeted therapy.

What are the next steps for CD73 in the U.S. and China in details? And also, when can we expect the next data from this program?

Yes. So TJD5, uliledlimab, is one of the leading CD73 antibodies under development globally and has the potential to become the first-in-class CD73 antibody drug in China. Now there's 3 points to this question. In the U.S., with the completion of Phase I clinical study, we are now planning a Phase II clinical trial hopefully to start in the second half of this year. One of the focus indications is ovarian cancer because we have seen some of the efficacy signals in our previous studies. Now in China, we have started a Phase II clinical trial to combine our CD73 with a PD-1 antibody. One of the focus indications is lung cancer that has failed other treatments. So we hope to share more clinical data as we advance with the proof-of-concept clinical trials in both U.S. and China.

Great. And let's turn to CD47. And this is remaining a very popular topic in the IO space. And I wonder, following the first data and every deal from last year, what are the key learnings so far? And would you like to summarize to investors? And also, give us update on the ongoing trials in your broad CD47 program.

Yes. So our CD73 antibody, lemzoparlimab, is internally discovered and developed in highly differentiated CD47 antibody. So it's made by design to avoid severe anemia, commonly seen with other clinical stage CD47 antibodies around the world, while maintain strong antitumor activity. This is really the key differentiation of our CD73 antibody, lemzoparlimab. Now this differentiation is demonstrated in our Phase I clinical trial in the U.S. with our priming dosing condition, the other CD47 usually required. Other clinical advantages of lemzoparlimab includes avoidance of adverse sink effect that is also commonly seen with other CD73 antibodies that bond strongly to red blood cells. In addition, we are very encouraged by the clinical activity of lemzoparlimab in our clinical trial as a monotherapy in patients with advanced solid tumors. The clinical results were presented at several occasions last year, including SITC. Now we are working together with AbbVie to rapidly advance multiple clinical programs in hematologic malignancies, solid tumors in U.S. and China, aiming for registration as the first CD47 antibody drug in China. And now we believe that we have a safer and a potent CD47 antibody. And we are putting all the resources behind us to move very quickly with our CD47 antibody in the clinic.

Great. And you also mentioned the CD38 antibody and the long-acting growth hormone. And I just want to double-check, are the time lines actually remain intact regarding the NDA submission and top line report from CD38 antibody and also the pivotal trial of long-acting growth hormone?

Yes. TJ202, felzartamab, our CD38 antibody, we have 2 registrational trials in China. Now the first registrational trial -- both registrational trials are on track. Now the first registrational trial, the third-line treatment, is on track for BLA submission in fourth quarter this year, as we promised. We are quite excited by this upcoming milestone. Our commercialization team has been working hard to get the company prepared for the product launch, and we also believe that our CD38 antibody has significant advantages over our competitor's drug. Now for long-acting growth hormone, TJ101, we initiated a Phase III clinical trial early this year, and we are on track in patient recruitment. And we are doing our best to complete patient enrollment in the early 2022.

Lastly, we would like to hear your thoughts, Dr. Zang. What are the key value drivers from a pipeline perspective at this moment? And what should investors be looking to in the next 6 to 12 months regarding the milestones and also key data events?

Yes. Thank you, Kelly. So 2021, this year, is really a catalyst-rich year for I-Mab. We expect to have double-digit development milestones, and some of them have already been achieved in the first half of this year, as we promised. Here are some critical milestones that are considered to be the pipeline value drivers. Now the first set of key milestones are related to BLA submission and the data readouts, and they're very critical. Now the first one is for TJ202 registrational trial. We will have top line data in the third quarter of this year, which will lead to BLA submission in fourth quarter this year for TJ202, our CD38 monoclonal antibody. And this is absolutely important milestone for the company. Now for lemzoparlimab, CD47 antibody, we have a non-Hodgkin's lymphoma study in combination with rituximab. We expect data readouts in fourth quarter this year or latest, first quarter next year. For lemzoparlimab solid tumor study with KEYTRUDA, we expect data readouts in fourth quarter this year. This is a Phase Ib or Phase IIa study. Now for our CD73 antibody, uliledlimab, we will present our Phase I data, as I mentioned earlier, at ASCO in June. And last but not least, for plonmarlimab, our TJM2 GM-CSF monoclonal antibody in Phase II clinical trial in the U.S., we will conduct a interim analysis in June or July this year and decide how to move forward. Now the second set of key milestones are related to clinical development milestones. There are several key development milestones for TJ101, our long-acting growth hormone in Phase III clinical trial. We achieved, as I mentioned earlier, first patient dosing early this year, and the enrollment is on track. For TJ107, our long-acting interleukin-7 in a Phase II clinical trial in patients with GBM, we achieved first patient dosing early this year. And again, this study is on track. Also for TJ107, we will initiate a new Phase II combination clinical trial with KEYTRUDA in patients with triple-negative breast cancer based on Genexine's global data. This study will start in the second half of this year. Now there are 2 development milestones for TJD5, our CD73 antibody. The combination study with PD-1 in China, we achieved first patient dosing, and the trial is on track. The combination with PD-L1 study in the U.S., we will start a new clinical trial in patients with solid tumor in the U.S. in the second half of this year. And then for lemzoparlimab AML/MDS trial, we achieved the first patient in early this year, and the study is on track. And then for TJ202 second-line registrational trial, we will complete the study by the fourth quarter this year. And we will be preparing for BLA submission in 2022. So this is going to be the second BLA submission for TJ202. Last but not least, we have brought 1 new monoclonal antibody, TJ210, and 2 new bispecific antibodies, PD-L1/4-1BB and Claudin 18.2/4-1BB to the clinic early this year. So our innovative pipeline continues to grow with new assets moving into clinical trials, and we will keep the excitement going.

There are really a lot ongoing on all fronts. We will watch very closely to the news flow from I-Mab in the rest of 2021. And we are only together for a very short-term period, not enough to go over every exciting news from I-Mab. Unfortunately, we have to wrap up our session here. Thanks again, Dr. Zang, for spending time with us. Looking forward to ASCO update on your CD73 antibody program. And thanks, everyone, online for attending our session.

Thank you, Kelly.