IMAB - NASDAQ

Good morning to everyone and thank you for joining us this morning. Thank you all for standing by. And I'd like to take this opportunity to welcome you all to the I-Mab BioPharma Full Year 2022 Financial Results and Business Update Conference Call. This is Tyler Ehler here. I-Mab's Senior Director of Investor Relations. At this time, all participants are in a listen-only mode. At the end of this call, we'll conduct a Q&A session and instructions will follow at that time. Earlier today, we issued a press release providing a review of our financial results for the full year ended December 31, 2022, as well as an overview of our recent corporate highlights and upcoming milestones. The press release can be accessed on the Investor Relations tab on our website at ir.i-mabbiopharma.com. Joining me today on the call from I-Mab senior management team are Dr. Jingwu

Thank you, Tyler. It's a pleasure to welcome all of you to our call today. I want to take this opportunity to discuss our key business update and major progress in core asset development for the year ended December 31st, 2022. Since the start of 2022, the company faced multiple challenges, including, but not limited to geopolitical issues such as ADR delisting risks, macroeconomic factors, including interest rate hikes and COVID-19 pandemic. In response to these challenges, the company made several strategic efforts to reposition the overall business and prioritize its pipeline. These measures resulted in a streamlined corporate structure and workforce as well as focused development of five key assets, leading to a significant reduction in the cash burn rate in 2022 and beyond. These efforts have allowed us to achieve critical milestones for our prioritized pipeline and deliver near-term value. In terms of the ADR delisting risk, on December 15th, 2022, the PCAOB issued a report that vacated the previous determination and removed mainland China and Hong Kong from the list of jurisdiction where it is unable to inspect or investigate completely registered public accounting firms. For this reason, the company does not expect to be identified as a commission identified issuer under the HFCAA after it files the annual report on Form 20-F for the fiscal year 2022. This has removed a significant headwind the company faced in 2022. With the above mentioned strategic efforts on the pipeline development front in 2022, we achieved 13 key clinical milestones, including positive results, including positive data readouts for three of our key assets lemzoparlimab, uliledlimab and givastomig. Here we highlight the five key clinical assets that we have prioritized. These assets are novel, highly differentiated and among the frontrunners globally and all in China. First of all eftansomatropin alfa, a long-acting growth hormone. We completed enrollment of 168 patients for our Phase 3 trial in the first half of 2022. We expect to have a data readout in the second half of 2023, followed by subsequent BLA submission. In November 2021, we announced a commercial partnership with Jumpcan, a top 100 Chinese pharmaceutical company specialized in the pediatric space. Second, felzartamab, a differentiated CD38 antibody. In addition to the completed Phase 2 registration study, our Phase 3 study for second line multiple myeloma is on track despite the impact of COVID-19. Continue to make progress with the local manufacturing plan in preparation for BLA submission and seek a potential commercial partnership. Next, we have three key assets that I will discuss in more detail later. Lemzoparlimab, a differentiated CD47 antibody has reached the Phase 3 stage. Uliledlimab, a differentiated CD73 antibody and a global frontrunner, has demonstrated impressive antitumor activity, a non-small cell lung cancer in a Phase 2 trial. The clinical response is correlated with tumor CD73 expression. Next, givastomig, a Claudin18.2 4-1BB bispecific antibody with a favorable safety profile and single agent efficacy signal. I would like to start by highlighting our highly differentiated CD47 antibody lemzoparlimab, which has certainly attracted so much attention in the immuno-oncology field because of its leading position to be among the first CD47 antibody drugs potentially approved for hematological malignancies. I would like to remind you that lemzoparlimab is differentiated by design to avoid binding to red blood cells while maintaining strong antitumor activity. This differentiation includes the expected favorable safety profile with no priming dose required. Less RBC-mediated sink effect and compelling antitumor activity across several [Technical Difficulty]. This molecular differentiation has been validated preclinically and has translated into clinical advantages that are being validated. I should also add in September 2022 AbbVie and I-Mab entered into an amendment to the original license and collaboration agreement. As a result, both parties are continuing to collaborate on the global development of anti-CD47 antibody therapy. Here I want to highlight lemzoparlimab safety differentiation with clinical data. In a systemic safety data review of approximately 200 patients who are treated with lemzoparlimab either as monotherapy or in various combinations. We have seen a compelling safety profile today. Overall, the safety data from both the US and China studies continue to be favourable when administered without a priming dose regimen. MTD was not reached in any dose regimen. Mild TRAE in solid tumor and NHL. And we have seen a good safety profile in combination with Azacitidine in AML and MDS and no grade five hematological TRAE's have been reported. In the Phase 2 study in MDS, we have observed a favourable safety profile shown on the right. Of note this study enrolled more patients with worse baseline conditions than the comparable clinical trials conducted in Western countries due to the underlying disease that is heavily influenced by clinical practice in China. In this group, 74% of patients had grade three and above anemia, and 51% of the patients had grade three and above thrombocytopenia at baseline. The overall safety results showed that lemzoparlimab even without the priming dose was well tolerated in combination with azacitidine and the safety profile was comparable with that of azacitidine monotherapy. Next, I would like to highlight the clinical efficacy results presented at ESMO 2022. Of the 53 patients enrolled as of March 31st, 2022 for patients who began treatment six months or longer prior to the analysis, the overall response rate and complete response rate were 86.7% and 40% respectively. For those who began treatment four months or longer, the ORR was 86.2% with a CRR of 31%. I'm happy to share that the updated results from the most recent data analysis of 62 patients have demonstrated consistent clinical efficacy, including ORR and CRR, with no new safety signals identified. We are planning to present the updated data at a major scientific meeting in the second half in 2023. Here, I would like to summarize the key progress on lemzoparlimab. We have observed consistent and favorable safety profiles in more than 200 patients with hematologic and solid tumors treated with lemzoparlimab. Our Phase 2 MDS trial demonstrated a consistent efficacy trend, including ORR and CRR, with longer follow up time since the ESMO data presentation in September 2022. Lemzoparlimab in combination with azacitidine has obtained approval from the CDE to initiate a Phase 3 registrational trial for the first line treatment for patients with newly diagnosed higher risk MDS. Importantly, AbbVie and I-Mab entered into an amendment to the original licensing collaboration agreement. As a result, both parties are continuing to collaborate on the global development of anti-CD47 antibody therapy. Next, I'd like to turn to uliledlimab, another global frontrunner that we are developing with a focus on non-small cell lung cancer. As previously reported uliledlimab is differentiated by design to avoid the hook effect. So what is the hook effect? Simply put, the hook effect is characterized by an abnormal phenomena that a drug molecule paradoxically loses the effect at higher doses. As shown in the figure on the right side uliledlimab achieved complete enzymatic inhibition without the hook effect. In contrast, oleclumab could only achieve partial inhibition with hook effect with higher concentrations. Uliledlimab differentiation comes from a unique binding epitope at the C-terminals. We believe the differentiation give uliledlimab the potential to be best-in-class with an improved therapeutic window and more flexibility when combined with other antitumor drugs. We have observed robust efficacy data in Stage 4 non-small cell lung cancer with high CD73 expression and we are currently conducting focusing our efforts on a biomarker-guided pivotal trial in advanced non-small cell lung cancer in the second half of 2023. So on the left side of this slide is our PK study. It really demonstrated linear PK profiles at 5 mg per kg weekly or higher, indicating target saturation. A 30 mg per kg saturation and complete inhibition of CD73 activity were observed in human tumor biopsy samples. Studies of uliledlimab in combination with an anti-PD-1 or PD-L1 have shown treatment is safe and well tolerated with no dose limiting toxicities observed. Most treatment related adverse events were either grade one or grade two. Uliledlimab RP2D has been determined to be 30 mg per kg every three weeks in combination with toripalimab to 40 milligram every three weeks. This slide highlights the clinical experience of our US Phase 1 study of uliledlimab in combination with atezolizumab in patients with refractory solid tumors. About 13 efficacy evaluable patients, three responses were seen, including 1 PR with an overall response rate at 23% and the disease control rate at 46%. More importantly, shown on the right, all three responders were identified to exhibit higher expression of tumor 73, CD73 as compared to non-responders. This provides the initial indication that high CD73 expression may correlate with the clinical activity of uliledlimab. Here, I want to highlight the latest clinical development update on uliledlimab. As of December 2022, 70 patients had been enrolled in the Phase 2 study of uliledlimab in combination with toripalimab, a PD-1 antibody in Stage 4 non-small cell lung cancer patients. As a high level summary, at the time of the first data cut-off in March 2022, ORR was 26% and the DCR was 74% for the first 19 evaluable patients. Remarkably in patients with high CD73 expression defined of at least 35% expression level in tumor cells or immune cells. A much higher ORR was observed with a 57% ORR and DCR at 100%. Similar efficacy data in relation to CD73 expression were obtained in August 2022 with 32 evaluable patients and December 2022 with 45 evaluable patients showing a consistent trend of efficacy signal with an overall ORR greater than 30% in all patients and an ORR approximately 50% in CD73 high expression patients as compared to approximately 10% to 15% for those with CD73 low expression. The efficacy data continued to mature for ORR and PFS in 2023. Our data have demonstrated that higher clinical response of uliledlimab and PD-1 combination therapy correlated with high tumor CD73 expression in patients with advanced non-small cell lung cancer. I want to summarize the key development of uliledlimab on this slide. Uliledlimab is a differentiated CD73 antibody with best-in-class potential. It can achieve complete CD73 inhibition without the hook effect. Uliledlimab has a favorable safety profile and the combination of uliledlimab/toripalimab demonstrated robust anti-tumor activity in non-small cell lung cancer with the clinical responses correlating with CD73 expression. With regard to our further development plan for uliledlimab, a data readout for the 70 patients in our Phase 2 study is expected for ORR in the first half of 2023 and for PFS in the second half of 2023. The company plans to present the data at a major scientific venue in 2023 and further clinical development plan is being finalized to include a biomarker-guided pivotal trial of uliledlimab in combination with PD-1 therapy in Stage 4 non-small cell lung cancer in second half of 2023 in China. And a global study of uliledlimab in combination with a PD-1 therapy and chemo regimen in advanced non-small cell lung cancer. In parallel, a companion diagnostic kit is being developed with Wuxi Diagnostics and is on track for the planned studies. With the new data, the company has been actively engaging in a potential global partnership in sync with the planned global study. The last asset I'd like to touch on today is givastomig, our novel Claudin18.2 4-1BB bispecific antibody that has also made significant clinical progress. Givastomig is a novel bispecific antibody with one arm targeting Claudin18.2 and the other targeting 4-1BB through conditional or local activation. The key differentiation of givastomig is twofold. Firstly, it binds to tumors with a wide range of Claudin18.2 expression levels, including lower expression, as demonstrated on the right in pre-clinical models. Secondly, the 4-1BB arm of givastomig is designed to function upon local tumor engagement as a mechanism of conditional activation. This feature makes givastomig a unique T cell activator only localized at the tumor site without systemic toxicities. For example liver toxicity and systemic cytokine release, that are typically associated with 4-1BB. Here. I'd like to take a moment to highlight givastomig's unique differentiation compared to other Claudin18.2 target agents. The differentiated molecular design makes givastomig unique among Claudin18.2 target agents including ADC and zolbetuximab.

Thank you, Andrew. Let me turn to review our financial results for the full year ended December 31st, 2022. As of December 31st, 2022, our cash and cash equivalents and short-term investments were RMB3.5 billion or US$514 million compared with RMB4.3 billion or US$671 as of December 31st, 2021. I-Mab's strong cash balance is expected to provide the company with adequate funding to support its key business operations over the next three years. Total revenue for the full year of 2022 were RMB-221.6 million or US$32.1 million compared with RMB88 million for the full year of 2021. The decrease in 2022 net revenue was primarily due to a one-off accounting treatment of US$48 million recorded in the second half 2022, following the amendment to the original licensing and collaboration agreement with AbbVie in August 2022. Further details can be found in our annual financial results. The decrease was partially offset by the revenue of RMB92.6 million or US$30.4 million from licensing and collaboration arrangements and the supply of pipeline products. Now let me turn to the R&D expenses. Research and development expenses for the full year of 2022 were RMB904.9 million or US$131 million compared with RMB1.2 billion for the full year of 2021. The decrease was primarily due to the reduced demand for pipeline products as the company prepared to procure the sufficient stock for the pipeline products in 2021 and a lower share-based compensation expenses. Administrative expenses for the full year of 2022 were RMB720 million or US$104.4 million compared with RMB899 million for the full year of 2021. The decrease was primarily due to lower share-based compensation expenses in relation to the management personnel and optimized control of operation and administrative expenses. Net other expenses for the full year of 2022 were RMB126.6 million or US$18.4 million compared with net other income of RMB83.2 million for the full year of 2021. The change was primarily caused by unrealized exchange losses due to fluctuation in the exchange rate of RMB against the US dollars in 2022. I would like to reiterate that -- we maintain a strong cash position of US$514 million that we held at the end of 2022. Our current cash position combined with potential upcoming milestone payments from the previous out-licensing deals and the collaborations is expected to further strengthen our cash reserves. This has been largely achieved by our move to focus on five key clinical assets in our pipeline through our reprioritization effort in mid-2022. We also streamlined our corporate structure. This has also been included in streamlining our workforce through a headcount optimization that was in line with the reprioritization of our pipeline reduction in our overall operating expenses and corporate structure. With this we have implemented cost initiatives that we intend to maintain committed as we were determined to maintain operational efficiency and a very lean operational budget. Overall, this represents about a 20% reduction in cost in 2022. We -- expected to further reduce in 2023 as we continue to focus on where we can deliver the most important value to our shareholders. In closing, our current strong cash position will provide us with ample flexibility to support our R&D activities in the next three years. With that, I would now like to turn the call back to Tyler and begin our Q&A sessions. Tyler?

Thank you, Richard and thank you Dr.

Thank you, Tyler, and thank you for taking my questions. My first question is, has I-Mab been able to resolve its delisting risks fully and also have follow-up. Thanks.

Yeah. Hey, Kelly, thank you for your question. I think most of the delisting risk has been mitigated by our -- working with our current auditor through the PCAOB new rules. So our delisting risk has been largely mitigated throughout last year.

Thanks. And also regarding the Phase 2 trial of CD73 antibody in Stage 4 non-small cell lung cancer. You updated 70 patients has been enrolled by the end of last year. I'm curious, could you share more information regarding the patient baseline characteristics regarding PD-L1 expression level and also prior PD-1 treatment? Are they like refractory or relapsed from any PD-1 other PD-1 agents? Thank you.

Yeah, let me take that question. So, Kelly, as I indicated in my presentation, the data that I presented, the one with 70 patient cohort that's specifically targeting the treatment naive Stage 4 non-small cell lung cancer. So they are definitely naive to all the treatments, including PD-1. And so our date, yeah.

Sorry. Go ahead.

You have a follow-up question?

No, sorry. Go ahead. I'm okay with that.

Yeah. So basically, I think, you know, our study exclusively look at that particular population, you know, for our activity and also tolerability in our Phase 2 trial.

Okay. Thank you.

Thank you, Kelly. And I'm showing Joe Catanzaro. Joe, please go ahead.

Hey, guys. Hopefully you can hear me okay. Maybe just one quick one from me on givastomig. I know you touched on this a bit in the prepared remarks, but the Claudin18.2 space is obviously become highly competitive. So maybe for two questions around this. First, how do you think about the data that we've seen for zolbetuximab and the implications around Claudin18.2 as a target? And then second, given the competitiveness with a lot of different modalities, how do you think givastomig is positioned here? Thanks.

Yeah. So, Joe, great question. I think with the data from SPOTLIGHT and GLOW, you know, two Phase 3 trials in the first line metastatic gastric cancer space. With the addition of zolbetuximab to the standard chemo backbone both studies, you know, convincingly demonstrated the improved benefit. And I think, you know, clearly we have validated Claudin being a relevant therapeutic target in gastric cancer. So I think that part, you know, I personally feel that, you know, there's absolutely no argument. I think anti- Claudin18.2 antibody has a role. This will definitely benefit patients with metastatic gastric cancer. But also, as you know, both trials select patients based on Claudin18.2 expression. And the criteria they use is actually two plus, plus three plus of at least 75%. So you can imagine, I think, if you look at this population very carefully, this probably will be applicable for about 30% of the patients with high Claudin18.2 expression. So my feeling is that, you know, I think zolbetuximab will define -- will have the role in certain patients. And also for those who have low PD-L1 expression. This may become the major target therapy in combination with chemo. But having said that, you know, we also feel strongly that givastomig has a very, very unique position in a very Claudin, you know, Claudin18.2 therapeutic target space in gastric and potentially maybe in other tumor types. Because, you know, the unique molecular design really allow this molecule to cover a wider population with different levels of Claudin18.2 expression. In particular the lower Claudin18.2 expression. And we demonstrated that in preclinical models, you know, clearly it behaves favorably with more robust antitumor activity in comparison with other Claudin18.2 target antibody. Our ongoing Phase 1 trial also gives us the initial confidence that, you know, we definitely have seen antitumor activity in Claudin18.2 low expression patients are granted. Our trial is still actually just ongoing. It's a Phase 1 study, but nevertheless, we are encouraged by the early efficacy signal. On the other side of the spectrum is really the safety profile with our unique modular design. As I indicated in my presentation, our molecule will only become active when the molecule is engaged with the tumor-associated antigen, in this case, Claudin18.2 positive tumor cells. In this case, the 4-1BB will get activated. So in this way it's actually spares the systemic toxicity, including hepatic and also cytokine release syndrome. And this is actually commonly seen with other T cell engager modalities including 4-1BB based. So we think our molecule also has the added advantage even for those with high Claudin18.2 population, because it may potentially have the potential to be combined with a standard first line. For example FOLFOX/PD-1 based combo and also for other tumor types. We definitely have the potential to explore the combination of our drug with other combination chemotherapy in other tumor types. And lastly, as you know, there is actually the so-called class specific side effects associated with Claudin18.2 target agents because the GI toxicity is actually very remarkable. You know, nausea, vomiting is commonly observed, and some of them could be actually incredibly challenging to manage. And in our trial, we only observed very mild gastrointestinal toxicity, in particular, nausea, vomiting, which we think, you know, offers the advantage to be better tolerated, you know, in gastric cancer patients. So we definitely would like to further explore, you know, givastomig development, either as a single agent, as we're doing right now, but also in combination down the road. Thank you, Joe.

Thank you, Dr.

Hi. Thank you. Hi. Thanks for taking my question. So do you have any concerns regarding the toxicity of 4-1BB agonists? These features have prevented high target engagement in past programs. So can we expect more results from this dose escalation study? Thank you.

Yeah. I think Louise I'll take your question. Again, it's a very, very important question when it comes to the tolerability, the safety of any bispecific antibody particularly comes to the T cell engager modality. I think as I was trying to answer to Joe's question earlier, I did mention that our bispecific design is unique in a sense that we can only induce 4-1BB activation upon Claudin18.2 engagement at the tumor site. So for this reason, we actually spare the systemic toxicity commonly associated with 4-1BB and also other agonist treatment. So in that sense, the toxicity concern associated with other 4-1BB antibody or actually other T cell engager including CD3 based, definitely we actually have a very favorable safety profile as shown in our Phase 1 ongoing Phase 1 trial. Because, you know, we're not actually seeing the systemic toxicity, including hepatic toxicity, cytokine release syndrome and also the added bonus for our bispecific is that our GI toxicity also is on the mild side.

Thank you, Dr.

Hi, guys. Thanks for taking my question. Quick one from me. Could you provide additional color on how we should be thinking about your expected cash burn rate in 2023? And a quick follow-up to that is obviously you've been focusing on the four highlighted programs from your prepared remarks. So just curious from a timing wise and a financial perspective, where do you expect to feel comfortable and bringing in additional assets to the clinic in the future? Thank you.

Yeah. Let me thank you for your question, Joe. And let me start with the financial the burn rate question and Andrew can answer the pipeline question. So with this regard, as we have mentioned, that in 2022, we actually spent a lot of time actually optimizing our cost structure is mostly. So first of all, we actually focus on the five key assets and second, really optimizing the organizational structure. So this year we further going to reduce the overall cost as we just mentioned in the call that our expected current net burn rate for 2023 is expected to be in the range of US$130 million to US$140 million. This will further optimize our operational structure, so that our cash position can retain us at least for an additional three years or more years of cash operations. So given that we have other pipeline products that Andrew will discuss to develop and we really focus on our key assets.

Yeah. So I think Andres it's a very, very important question for the R&D operation. I think a few things that I would like to share with you. As you know that I-Mab actually has a very, very innovative discovery engine. We actually produce quite a lot of innovative assets internally, but also for reasons that we discussed today. We've been actually really trying to focus on the key assets that we can actually generate more value, you know, move the program to the next level faster, but also realize the value of these assets hopefully earlier so that, you know, the company will benefit, the shareholders will benefit, or more importantly, patients will benefit from this strategy. But having said that, we never stop looking at innovative assets from outside. It's just, you know, right now with the current situation, our bar is higher. You know, we definitely want to take a more critical look when it comes to, you know, the licensing efforts from outside. But this, you know, this is a dynamic process. Clearly we are aiming to also generate additional cash flow with our BD deal. So I think clearly, you know, we will reassess the strategy as we proceed with the new year in 2023. But right now, you know, we definitely want to make sure we focus on the internal assets. But definitely we will actually look at the key assets that potentially have value and also have potential market more critically. This is our current position.

Thank you, Dr.