I-Mab (NASDAQ:IMAB) Q4 2021 Earnings Conference Call March 29, 2022 8:00 AM ET
Company Participants
Tyler Ehler – Senior Director of Investor Relations
Jingwu Zang – Founder, Chairman and Acting CEO
Andrew Zhu – President
John Long – Chief Financial Officer
Jielun Zhu – Chief Strategy Officer
Conference Call Participants
Kelly Shi – Jefferies
Louise Chen – Cantor
Joe Catanzaro – Piper
Andres Maldonado – HCW
Operator
Tyler Ehler
Good morning, ladies and gentlemen. Thank you all for standing by. And I’d like to welcome you all to the I-Mab Biopharma Full Year 2021 Financial Results and Business Update Conference Call. This is Tyler Ehler, I-Mab’s Senior Director of Investor Relations. At this time, all participants are in a listen-only mode. Later, 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, 2021, as well as an overview of our recent corporate highlights and upcoming milestones. The press release can be accessed on the Investors portion of our website at ir.i-mabbiopharma.com.
Joining me today on the call from I-Mab senior management team are Dr. Jingwu Zang, our Founder, Chairman and Acting CEO of I-Mab, Dr. Andrew Zhu, our President of I-Mab, Mr. John Long, CFO of I-Mab and Mr. Jielun Zhu, Chief Strategy Officer of I-Mab. Dr. Zhang will start by providing a high level overview of our recent achievements and upcoming milestones, followed by Dr. Andrew Zhu, who will provide an update on our R&D progress, and Mr. Zhu, who will provide an update on our commercialization capabilities. Mr. Long will then provide a summary of our financial results for the full year ended December 31, 2021 before we turn the call to the operator to take your questions.
Please note that today’s discussion will contain forward-looking statements relating to the company’s future performance and are intended to qualify for the 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 financial results is included in certain filings of the company with the Securities and Exchange Commission. The company does not undertake any obligation to update this forward-looking information, except as required by law.
We’ll also discuss specific non-GAAP financial measures for comparison purposes only during today’s call. Please see the financial results news release issued earlier today for a definition of non-GAAP financial measures and a reconciliation of GAAP to non-GAAP financial results.
With that, I’d like to turn the call over to Dr. Jingwu Zang, our Founder, Chairman and Acting CEO. Dr. Zhang, please go ahead.
Jingwu Zang
Thank you, Tyler. Thank you to everyone for joining us. It’s a pleasure to welcome all of you to our call today to discuss our business update and the financial results for the full year 2021
Now I must say 2021 was a dynamic year for I-Mab. We made remarkable progress in a short period of time and closed the year with stronger fundamentals than we have ever had before.
Firstly, on the top line development front, we met 20 key clinical milestones, including the successful completion of our registrational trial for felzartamab as our first – as our third-line therapy for multiple myeloma. We’re now in the process of submitting the BLA package in China.
We also achieved positive data readouts for two of our key assets, lemzoparlimab and uliledlimab, including the latest clinical data from our ongoing MDS trial, which will be discussed today in detail by Dr. Andrew Zhu.
As a result of the progress made in 2021 and the continued progress in 2022, we expect to advance our pipeline to include 3 of 4 registrational trials, 11 phase 2 clinical trials and 3 phase 1 clinical trials by the end of 2022.
Our pipeline has progressed to a completely different stage as compared to that at our IPO 2 years ago. It’s not only globally innovative with the potential best-in-class assets such as lemzoparlimab and uliledlimab but also advancing towards near term BLA and product launch within the next 3 years.
Secondly, on the corporate development front, in 2021, we entered into certain partnership deals, including the $350 million strategic commercial partnership with Jumpcan for eftansomatropin alfa, our long-acting growth hormone and a partnership with Roche Diagnostics. Now these partnership deals are critical to enrich our pipeline with the next generation of novel drug candidates in the preparation for our near term commercialization.
Now I would like to emphasize that we maintain a very strong cash position with $671 million cash on hand. On top of that, we will continue to receive expected milestone payments from the existing out-licensing deals, including the $2 billion deal with AbbVie, the Jumpcan deal and others. This has generated very significant cash flow. Combining the two, our cash is sufficient to fund our business operations through 2025 for about 3 years.
Now on the capital market front, our CFO, Mr. John Long, will address regulatory concerns facing ADR companies on today’s call. I just want to first say that we have seen positive signals that regulators from China and the U.S. are working towards a resolution.
But more importantly, John will tell you more updates on the active measures we have been taking to mitigate the potential risk by making necessary changes to switch to a U.S.-based auditors that are recognized by U.S. PCAOB, and there are successful examples with other ADR companies, so it can be done.
Thirdly, I’m very excited to tell you that our pipeline has advanced to a critical phase where we are approaching near term commercialization. This is a transformative step for I-Mab. Pending the finalization of an in-licensed pre-BLA product, we expect to file 4 BLAs followed by a product launch between 2022 and 2025.
Now this near term product portfolio is focused on hematologic oncology with felzartamab, lemzoparlimab and our in-licensed product as a core product to cover multiple myeloma, leukemia and lymphoma.
Additionally, we expect that eftansomatropin alfa, our long-acting growth hormone, will become a major player in China growth hormone market for its product differentiation and convenience of use.
Now commercialization of this near term product portfolio is a critical step in I-Mab’s journey to transition from a global biotech to a specialty biopharma with global R&D, manufacturing and commercialization capabilities. It is expected that our current revenue stream from our licensing milestone payments will soon converge with our product sales revenue to generate significant cash flow for the company.
Therefore, a large part of our current corporate focus is really to prepare for the near term commercialization under leadership of Mr. Yifei Zhu, our Chief Commercial Officer.
Now looking ahead, 2022 is shaping up to be an even more exciting year for I-Mab. We continue to consolidate our position as a leading global biotech company in the immuno-oncology space and strive to transition into a global specialty biopharma. We are set to achieve a series of high impact and value-generating milestones and catalysts, which I will summarize for you at the end of this call.
Now with this quick overview, I would like to ask Andrew to take a deep dive into our key pipeline assets and provide our expectations for 2022. Andrew, over to you.
Andrew Zhu
Thank you, Jingwu. It is really my pleasure and privilege to speak with all of you today. The focus of my discussion will be on our pipeline development in terms of the recent progress and updates, as well as the near term prospect of our exciting pipeline.
With the progress made, it has become apparent that our pipeline is not only globally innovative but also advanced with 10 clinical assets that are either novel or highly differentiated.
Our first wave of innovation focuses on highly differentiated monoclonal antibody of best-in-class potential such as lemzoparlimab and uliledlimab which will have now entered Phase 2 and Phase 3 clinical trials by year-end.
The second wave innovation focusing on by specific antibodies are both first-in-class and best-in-class potential, such as L14B and CD4B are now in early stage clinical development. There will be more to come.
The pipeline is also advanced as felzartamab, lemzoparlimab and eftansomatropin alfa are either in registrational studies or have already reached the BLA stage. They will soon become the core products of our near term commercialization.
Today, I would like to take this opportunity to highlight seven key assets in our pipeline because they are value drivers. These assets are novel, highly differentiated and among the front runners globally or in China. I will go through each of them in more details.
I’d like to start by reviewing our highly differentiated CD47 antibody lemzoparlimab first. This has attracted so much attention in the immuno-oncology field because of this potential as a best-in-class CD47 antibody and its leading position among the first CD47 antibody drugs potentially to be approved for hematological malignancies. I would like to remind you that lemzo is differentiated by design to avoid binding to red blood cells, while maintaining strong anti-tumor activity. This molecule differentiation has been validated pre-clinically and has translated to clinical advantages that are being validated.
I-Mab’s priority for lemzo is to achieve its first registration of lemzoparlimab in its class in China and facilitate global development in close collaboration with AbbVie for global registration and commercialization.
To achieve this goal, five clinical studies of lemzo are ongoing in parallel, both in U.S. and China. We are running three clinical programs with lemzo in China, including NHL, AML, MDS and solid tumors. In addition, our global partner, AbbVie, is running two clinical programs globally.
Based on the clinical data being generated, we hope to initiate one or two registration trials with lemzoparlimab this year for MDS and potentially NHL. Recently, Gilead’s magrolimab has been put on clinical hold due to a SUSAR. As I mentioned earlier, lemzo is designed to avoid the hematological toxicities.
We recently conducted a systemic safety data review of 180 patients who were treated with lemzo in various combinations. Of these, over 70 patients with MDS or AML have been treated in combination therapy with acidity.
Overall, the safety data from both the U.S. and China studies continue to be favorable when administered without a priming dosing regimen, which is consistent with lemzo’s differentiation.
Among different combinations and across different indications, lemzoparlimab’s MTD was not reached in any dose regimens. As of today, the majority of TRAE in solid tumors and NHL were grade 1 or 2. In AML MDS, the safety profile as a monotherapy and in combination with ACA was favorable as expected and no Grade 5 hematological TEAEs have been reported.
We remain very encouraged by the therapeutic potential and safety profile of lemzoparlimab. This favorable safety profile with lemzo continue to build our confidence in rapidly moving this program forward to its registrational studies.
In terms of efficacy of lemzo, three clinical trials are summarized here with the MDS and the Phase 2 studies to be finalized. Efficacy signals have been detected at higher dose cohorts in monotherapy in patients with advanced and refractory solid tumors. In a smaller group of solid tumor patients who were previously treated with PD-1 therapy, both PR and SD were detected. Our ongoing Phase 2 studies with lemzo is combined with PD-1 therapy in solid tumors in both the U.S. and China will provide more efficacy data.
In a recent clinical trial where lemzo is combined with rituximab for NHL, we observed encouraging clinical efficacy. Of seven evaluable patients, CR rate is 57% or 71% and DCR is 100%. We expect to report more data in the second half of 2022 and may potentially initiate a registration trial in patients with NHL in China, pending approval by the NMPA.
I’m now very excited to report to you the most recent preliminary clinical data on lemzoparlimab combination therapy with AZA for MDS. In a preliminary analysis of 47 newly diagnosed MDS patients on treatment for various durations, the preliminary data showed that the overall response and complete response rate in 22 MDS patients with median treatment duration of at least four months is comparable to that of magrolimab.
The complete data analysis is expected in June 2022 when all data are mature. We are very encouraged by the data and plan to present the full story at a selected scientific conference in the second half of 2022 and start a registration trial this year, pending approval by the NMPA.
Next, to uliledlimab, another global front runner that we are developing for solid tumors. As previously reported, uliledlimab is differentiated by design to avoid the hook effect.
In a recent study where patients with solid tumors were treated with uliledlimab in combination with the atezo, among 13 evaluable patients, ORR is 23% and DCR 46%. While the results are preliminary, they are very encouraging. We are conducting two Phase 2 clinical trials in both U.S. and China and hope to share the data as soon as available this year. I also want to mention that alongside planned data readouts this year, we continue to explore the global partnership opportunities.
Next is felzartamab, our most advanced asset. We have successfully completed the registration trial in China for felzartamab as a third-line treatment for multiple myeloma. Our study confirmed the efficacy of felzartamab with additional benefits such as shorter infusion time, lower infusion-related reaction rate and no severe infusion reaction. This allows the use of felzartamab in out-patient clinic setting. We plan to schedule a meeting with regulatory authorities and aim to file the BLA together with a local manufacturing firm.
In terms of the second line treatment of felzartamab in combination with lenalidomide for multiple myeloma, we have completed enrollment in our pivotal Phase 3 study and are waiting for the data to mature to support our BLA submission in 2023. We also expect to initiate a new clinical trial of felzartamab with lemzoparlimab as a potential first-line treatment for multiple myeloma.
Next is the eftansomatropin alfa or TJ101, our differentiated long-acting growth hormone as a weekly treatment versus the commonly used daily injections. Our registration Phase 3 TALLER trial is ongoing. We are on track to complete the target enrollment of 165 patients in Q2 2022 and are on track for BLA submission in late 2023.
In 2021, we entered into a strategic commercial partnership with Jumpcan to leverage Jumpcan’s vast commercial network as a commercial leader in the pediatric therapeutic area.
Our agreement includes upfront and potential milestone payment of US$315 million, as well as a 50-50 profit sharing or low double-digit royalties on revenues. This partnership represents one of China’s biopharma markets largest deals, which is a testament to the product’s potential, as well as to I-Mab’s development capabilities.
Another novel compound in our pipeline, TJ107 or efineptakin alfa is the world’s first and only clinical stage long-acting recombinant human interleukin-7. This asset is positioned as a monotherapy for the treatment of cancer patients with lymphopenia because of its unique properties of increasing tumor-attacking T cell numbers, and as a combination immunotherapy with PD-1 or PD-L1 antibody because of its potential synergism with PD-1/PDL-1 therapy. Currently, we’re conducting two Phase 2 clinical trials in China.
It is important to mention that Genexine’s clinical trials in the U.S. have provided some encouraging efficacy signals for both GBM as a monotherapy and triple-negative breast cancer as a combination therapy with pembrolizumab.
We are also developing enoblituzumab, a world’s leading humanized B7-H3 antibody as an immuno-oncology treatment agent. Enoblituzumab works through a unique dual mechanism and has exhibited the potential to treat multiple solid tumors.
Our partner, MacroGenics, has previously shown promising preliminary data in non-small cell – in squamous cell carcinoma of head and neck and non-small cell lung cancer. Currently, we are conducting a Phase 2 basket trial in combination with PD-1 in patients with selected solid tumors, including non-small cell lung cancer and urothelial carcinoma in China.
Our bispecific antibodies have made significant clinical progress as well. Of note, TJCD4B is a novel Claudin 18.2 and 4-1BB bispecific antibody, capable of binding to tumor cells expressing Claudin 18.2and stimulating intra-tumoral T cells by the 4-1BB arm, which is designed to become active only upon tumor engagement to avoid systemic toxicity. I-Mab recently received FDA Orphan Drug Designation status for CD4B for the treatment of gastric cancer, including cancer of gastroesophageal junction.
As one of the core assets in our highly innovative bispecific antibody pipeline, CD4B is currently undergoing Phase 1 clinical trials in both the U.S. and China in patients with advanced solid tumors.
In the ongoing dose-escalation study, CD4B was found to be safe and well tolerated at a dose up to 3 mg per kg weekly. While we advance the clinical development of this compound, we plan to share more data as they become available.
To summarize, I-Mab has a powerful discovery engine with innovation in three waves. Most of the first wave of monoclonal antibody in POC and registration trials. The second wave of bispecific antibodies are in Phase 1 and preclinical studies. In addition, our third wave of even more innovative assets enabled by transformative technologies such as MRI technology, self-penetrating alphabody technology, locally activated per body technology and AI protein design technology are in preclinical stage and CMC stage.
The third wave of transformative molecules are in the discovery and preclinical stages and will reach an IND stage in 2023.
With that review, I will turn to Mr. Jielun Zhu to provide you with more insight into our commercial development.
Jielun Zhu
Thank you, Andrew. It’s a pleasure to be here with you all today to see you again. Following the update on our pipeline development given by Andrew, I will spend the next few minutes discussing with you our focus on the commercialization strategy, the progress and the few next steps.
On Page 18, you can see that our innovative and advanced pipeline will generate two waves of commercial portfolios. The first portfolio, which is a near-term product portfolio between 2023 and 2025 consists of felzartamab, lemzoparlimab eftansomatropin alfa and potentially another hematological oncology-focused pre-BLA product that is currently in late-stage negotiations to be licensed in.
By leveraging our product differentiation, the cost advantages from being a locally manufactured product and our commercial synergies, these three core products, when combined, will have the potential – will allow us to become a market leader in the hematological oncology area in China.
Additionally, our long-acting growth hormone, eftansomatropin alfa, is positioned to be a significant player in the growth hormone market in China, and that market is vast and fast-growing. With planned BLA filings, a large part of our corporate focus this year will be to prepare for the commercialization of our near term product portfolio.
We are building a commercial team which is being, currently as we speak, assembled to prepare for the market launch of these products to allow us to move quickly towards commercialization following the NMPA approval in China.
Additionally, in establishing a commercial partnership with, for example, Jumpcan in China for eftansomatropin alfa, we can rapidly gain market share among patients with pediatric growth hormone deficiency market, while focusing our internal commercial efforts on our core hematological oncology franchise.
These are some of the key steps we are taking to rapidly transition I-Mab to a specialized global biopharma and realize the commercial value of our key assets for our shareholders.
Now our longer term portfolio from 2026 to 2028, is focused instead on solid tumors. We have products like uliledlimab, efineptakin alfa, enoblituzumab and lemzoparlimab in this portfolio. These are potential drug candidates to bring innovative and more efficacious medicines to address unmet medical needs in the solid tumor space.
Next page, I will take a deeper dive into our near term product portfolio. Again, as I mentioned, this product portfolio consists of felzartamab in third-line and second-line multiple myeloma, lemzoparlimab in first-line MDS and second-line NHL, eftansomatropin alfa, long-acting growth hormone, in the pediatric growth hormone deficiency patients, as well as a novel late-stage hematological oncology therapy that we are planning to in-license, to round out and solidify our near term product portfolio in the hematological space.
We anticipate lemzoparlimab to be the first-in-class in the Chinese CD47 market, with internal estimates at 30% to 50% of the market share and peak sales potential of over US$1.1 billion.
In addition, felzartamab’s lower injection reaction rates and shorter infusion time for outpatient use, while potentially being the first locally manufactured CD38 antibody product, will position it well in the Chinese market with potentially over $260 million in peak sales potential.
Meanwhile, eftansomatropin alfa is the only pure protein-based long-acting growth hormone with the advantage of weekly versus daily use, which is the currently mainstay in China with no PEGs or chemical linkers and offers a stronger safety profile and compelling efficacy in a clinical setting. As a result, a conservative estimate gives 15% to 25% of the market share in China, with over $800 million in peak sales potential.
Lastly, we expect a potentially in-licensed first-in-class product for the Chinese market to bring a strong additional source of revenue. We expect these assets to provide a solid foundation in areas of high unmet medical needs with significant market potential as I-Mab commercializes and transitions to a global biopharma.
On page 20, on this slide, we will bring the market potential for the near term product portfolio together. Now according to reputable third-party analysis and some of our own internal estimates, the near term product portfolio that includes felzartamab, lemzoparlimab, eftansomatropin alfa and a potentially in-licensed pre-BLA product, has the potential to generate cumulative revenue in the range of $300 million to $400 million in the first 3 years, that is between 2023 and 2025, and revenue in the range of $1.3 billion to $1.6 billion between 2026 and 2028.
Meanwhile, the expected licensing income we have from existing BD deals, including the deal we have with AbbVie and also the deal we signed with Jumpcan last year, has the potential to bring in around $800 million to $850 million between 2023 and 2028.
We are very excited by the potential value of our pipeline and the potential these products can bring to the patients with high unmet medical needs, and then also the value to our shareholders.
The last slide in my section, page 21. I want to talk – say a few words about our manufacturing facility. To support the company’s rapidly growing and maturing pipeline, we have made very quick and rapid substantial progress in the construction of the — of our state-of-the-art GMP manufacturing facility in Hangzhou.
A process development lab in our Phase 1 GMP manufacturing facility is already operational to handle CMC project needs. Three times 2,000 liters production lines will become operational in about three months time, that is around June 2022, to produce clinical trial materials for I-Mab’s clinical studies around the world and also prepare for the local manufacturing needs for our key product, felzartamab.
The Phase 2 commercial production facility is being constructed as we speak to accommodate up to eight times 4,000 liters, commercial production lines and is on track to be completed by 2024, that is in 2 years time.
Now without much further ado, I will turn the floor to John, our CFO, to provide you with corporate and financial highlights of the company. John?
John Long
Thank you, Jielun. And thank you, everyone, for attending our call today. Next, I will provide you with an update on our 2021 key financial highlights.
First, let me review our financial results for the full year ended December 31, 2021. As of December 31, 2021, our cash and cash equivalents and short term investments amounted to total RMB4.3 billion or US$671 million compared with RMB4.8 billion as of December 31, 2020. For the full year 2021, our net revenues were RMB88 million or US$13.8 million compared with RMB1.543 billion for 2020.
While both periods included licensing and milestone payments from our strategic collaborations, 2021 fiscal year also included revenues from supplying our partners with clinical trial materials.
Now let me turn to R&D expenses. Our R&D expenses for 2021 were RMB1.213 billion or US$190 million compared with RMB985 million for 2020. The increase in R&D expenses was primarily due to the rapid advancement of our pipeline with more Phase 2 and Phase 3 clinical trials ongoing, especially for lemzoparlimab, uliledlimab, felzartamab and the eftansomatropin alfa.
Administrative expenses for the full year 2021 were RMB899 million or US$141 million compared with RMB402 million for 2020. The increase was primarily due to higher non-cash share-based compensation expenses and increased payroll expenses as we built out in preparation for product launch and commercialization.
We had several non-core and non-cash expenses booked in 2021. The share-based compensation expenses in R&D was RMB202 million or US$31.7 million. The share-based compensation expenses in administrative expenses was RMB407 million or US$63.8 million.
In 2021, we also booked RMB354 million or US$55.6 million equity loss from I-Mab Hangzhou, which is our affiliate company providing manufacturing services to I-Mab.
Non-GAAP adjusted net loss for our core business was RMB1.285 billion or US$202 million. I also want to highlight that our 2021 actual operating cash burn was about RMB1 billion or US$165 million.
Next, quite importantly, in light of the recent U.S., China regulatory concerns, we would like to reiterate that I-Mab has taken multiple proactive measures to address these concerns and risks.
First of all, the company has implemented additional business processes and control changes to meet the requirements outlined in the U.S. HFCAA. These measures include, subject to compliance with applicable rules and regulations, engaging an accounting firm that is subject to inspection by the PCAOB to prepare its audit report starting from 2022 fiscal year. Such compliance measures are expected to take effect in our 2022 annual report.
In addition, as previously disclosed, the company is also pursuing a new primary listing on the Main Board of Hong Kong Stock Exchange. We believe that the dual listing will offer our existing ADS holders the enhanced trading flexibility in addition to NASDAQ and complement our current investor base.
Recently, we have seen positive signals that U.S. and China regulators are working together on a solution to resolve the U.S. HFCA issue and ADR audit inspection requirements.
We are happy to note that the China Financial Stability and Development Committee came out in early March in support of Chinese companies listed overseas, with the Vice Premier, Liu He, stating that, “policies that are favorable to the market would be introduced.” So we are reasonably optimistic that a solution will be reached between the two countries and that the regulatory risk will be mitigated or reduced as the discussions and actions move forward.
It is also important to reiterate that the company maintains a strong cash balance with US$671 million at the end of 2021. Our current cash position, combined with expected incoming milestone payments from existing out-licensing deals and collaborations is going to further strengthen our cash balances and sufficient to support our key business activities through 2025.
This cash runway actually does not factor in additional cash upsides from potential new business payouts and new financing arrangements. We firmly believe that our cash position provides us with ample insurance and flexibility to support our R&D activities, expand our commercialization capabilities and ultimately transition us to a global specialty biopharmaceutical company over the next 3 years.
I will now turn the call back to Dr. Zang to summarize our upcoming milestones and catalyst.
Jingwu Zang
Thank you, John. Thank you, John. Now we are approaching the end of this call, let me just give you a brief forward-looking for 2022. I must say 2022 is already shaping up to be another exciting year. We are determined to focus our corporate priorities in the three value-driving areas to continue building even stronger fundamentals.
The first area is to deliver on the key pipeline milestones and catalysts. We aim to achieve 20 key clinical milestones, including the initiation of one or two registrational trials for lemzoparlimab and look forward to a set of five exciting clinical data readout events. These milestones are highly significant and impactful and are expected to drive the value of our pipeline.
To further advance the pipeline development, we expect to initiate eight clinical trials in 2022 and five IND submissions or approvals in both the U.S. and China. But at end of 2022, our pipeline will have advanced to include three or four registrational trials, 11 Phase 2 clinical trials, three Phase 1 clinical trials and a step closer towards near term commercialization.
Now the second area I’d like to mention is to deliver on the key corporate milestones, including out-licensing BD deals for uliledlimab and possibly our bispecific antibodies.
As I mentioned earlier, we are also working on finalizing the deal for a pre-BLA product to enrich our near term product portfolio. Last but not least, we are moving fast to build our capabilities and prepare the company for the near term commercialization.
So going forward, revenue generation will be a corporate focus of the company, by combining the cash flow from the existing cumulative milestone payments with the near term sales revenue expected in the next few years, to bring the company to a stronger financial position.
So with that, I would like to end this call and thank you all for your participation and your continued support. Tyler, over to you.
Question-and-Answer Session
Operator
A – Tyler Ehler
Thank you, too, Dr. Zang, and thank you to Dr. Zhu, to Jielun and to John for all their updates and their insights today. Next, we’ll begin our Q&A session. [Operator Instructions] Our first question comes from Kelly Shi at Jefferies. Kelly, could you please unmute yourself.
Kelly Shi
Can you hear me?
Jingwu Zang
Yes.
Tyler Ehler
Yes.
Kelly Shi
Okay, great. Thank you for taking my questions. And congrats on the progress. I believe this is the first time we have heard a mention [ph] data from lemzoparlimab in combination with azacitidine. We mentioned that response rate is comparable to magro in MDS. I’m wondering, are you referring to the data sets that 90% ORR and 40% complete response rate of magro and aza combo in front-line MDS? And also, could you please provide more commentaries regarding the safety differentiation you have observed to date?
And then lastly, would you be able to provide more specific timetables for the key data readouts for lemzo program? Thank you.
Jingwu Zang
Thank you, Kelly. Yeah, for your questions, I’d like to ask Andrew to elaborate. Andrew?
Andrew Zhu
Thank you, Jingwu. Thank you, Kelly, for your very, very insightful questions. You’re right. You know, Gilead definitely reported the magrolimab efficacy data in 2020 ASCO meeting, where they actually described the efficacy of magrolimab in combination with azacitidine for first-line MDS treatment. In their report of 33 patients who were treated for about four months duration, ORR was around 90%, CR rate was about 40%.
So we look at our preliminary data with first-line MDS. You know, we have actually found that a combination of lemzoparlimab and AZA in this cohort of 22 patients who were treated for at least four months duration, the ORR and CR rates in our cohort was actually comparable to that of the magrolimab data.
And also, we do actually have a better safety profile. I think what I mean by that is, really, we did not see any unexpected safety signal. And also, we did not see Grade 5 hematological TEAE.
And so we’re very encouraged by the preliminary data. And obviously, we’re eager to disclose the data when the data is more mature. And hopefully, we’ll present this one in a selected scientific congress.
I want to just reiterate that our molecule is truly differentiated by design. This is actually through a very vigorous antibody screening for a very highly selective binding site to a unique epitope.
This epitope is really the center piece of our IP because this is actually hidden on the red blood cells but exposed on tumor cells. Thus, this will allow us to separate tumor cells from red blood cells.
The preclinical and clinical data have actually supported the differentiation, that it has a very strong anti-tumor activity, while minimizing the effect on red blood cells. We do hope that this one actually has the potential to become the best-in-class CD47 antibody.
As I said, based on the Phase 2 data, we are planning to initiate a Phase 3 registration trial using lemzo in combination with azacitidine in first-line MDS in China this year. We do believe, you know, by combined a good safety profile and also encouraging you know, efficacy signal, without the need for priming, and also with the fact that magrolimab is being on hold, hopefully, we can accelerate our clinical trial development program. So hopefully, we can position lemzo as perhaps the first approved CD47 products, this will be very exciting.
With regard to the upcoming milestones, definitely, we plan to push our trial as fast as we can. And also, we are planning to release the top line data of lemzo in combination with AZA in AML/MDS soon. And hopefully, the full data will be presented at a scientific congress, either at ESMO or ASH.
We’re also planning to present the data for lemzo in combination with rituximab in NHL, likely at ASH. And also lastly, the lemzo in combination with pembrolizumab in solid tumors at another conference, likely SITC. Thank you, Kelly.
Tyler Ehler
Thank you, Kelly. And our next question comes from Louise Chen at Cantor. Louise, please go ahead.
Louise Chen
Thank you for taking my question and congratulations on all the progress in the second half of the year. So just curious how you plan to deal with the regulatory risks associated with the HFCAA. And also, could you please follow up on your current dual listing progress? Thank you.
Jingwu Zang
Thank you, Louise. Yeah, I just want to say a few things, and then I will ask John, our CFO, to elaborate on the details. So our position is that we are quite optimistic that this potential risk can be mediated by the actions that we are taking at this time.
We’re working hard on the two main actions, one is to switch our current auditors to an auditor that is recognized by PCAOB and meets all the necessary requirements by the SEC. And as I mentioned earlier, there are successful examples by other companies, our peer companies, so it can be done.
And the other action we are taking is to accelerate a dual listing process for Hong Kong Exchange. So maybe, John, you can elaborate more on the details.
John Long
Sure. Thank you for the question, Louise. Like most of you, we are closely monitoring the negotiations between U.S. and China regulators and are also following the practice from our peer companies in China ADR sector.
In addition to that, the company has taken proactive actions to mitigate the potential risk. We have actually started the process to evaluate the feasibility in terms of changing principal auditor in the U.S. based on our own situation and assess necessary requirements according to SEC and the PCAOB guidelines.
Specifically, we have already engaged professional firms to support our assessment in this regard, including review and analysis from regulatory, legal, operation and internal control perspectives, in order to meet the regulatory requirements from both China and U.S. on all the information provision and disclosure.
In terms of timetable, we are working closely with our counsels, aiming to complete the process by the end of 2022. Of course, it’s subject to compliance with all applicable regulations and the laws from both countries.
At the same time, as Dr. Zang just mentioned, we are accelerating our dual primary listing project. We are hopeful that the capital market conditions would improve in second half of this year and we would complete the listing process and offer our ADS holders the risk mitigation alternative. Thanks.
Tyler Ehler
Thank you, John. Thank you, Dr. Zang. Thank you, Louise, for your question. Our next question comes from Joe Catanzaro with Piper. Joe, please go ahead.
Joe Catanzaro
Hey, guys. Thanks for taking my question and congrats on all the progress here. Maybe one for me on the pipeline. For the Phase 2 uliledlimab data expected at ASCO, maybe can you speak to some of the high level details on this data set? Such as how many patients, what tumor types will be the focus? And whether you’ve been able to look at the CD73/PD-L1 dual biomarker in this trial?
And then maybe as a follow up, what are your current expectations around the potential to execute on a global licensing collaboration for this program? Thanks.
Jingwu Zang
Thank you, Joe. Well, maybe, Andrew, could you elaborate on that question?
Andrew Zhu
Yes, sure. Thank you, Joe, for that question. You’re right. We did actually submit an abstract for this year’s ASCO. This is a Phase 2 trial with our uliledlimab in combination with toripalimab, an approved PD-1 antibody in China in patients with advanced solid tumors. And for this data set, we have a very comprehensive safety analysis for over 90 patients. And also, we will report the efficacy data in over 40 evaluable patients.
In addition, as you suggested, we definitely plan to analyze the potential biomarker correlation with clinical efficacy, including CD73, PD-L1 expression and also some other biomarkers. And with regard to the patient population, this is mainly dealing with non-small cell lung cancer with different treatment modalities.
Your second question has to do with generating more clinical data. So hopefully, we can secure a global business deal. So on this front, we are continuing our clinical development program so that we can generate more robust data for uliledlimab.
This includes our ongoing efforts in the states, where we have a Phase 2 clinical trial program of uliledlimab in combination with atezo in patients with ovarian cancer and also other solid tumors.
And as you know that AstraZeneca released their randomized Phase II COAST trial testing CD73 with their PD-L1 antibody at ESMO last year, showing quite impressive efficacy signal in non-small cell lung cancer, in this case, mainly Stage 3 following combined chemo-radiation.
So they have actually entered the Phase 3 trial with 1,000 patients. We are very encouraged by the published data. And also, we hope we – our ongoing efforts will generate additional data with uliledlimab as well.
And also, last year ASCO, we already published some compelling clinical data with our 73 antibody and showing our products highly differentiated advantage, including the property avoiding the so-called hook effect that’s shared by many CD73 antibodies. We have demonstrated uliledlimab has a very favorable PK/PD relationship and also some preliminary efficacy signal.
So we do hope, as the field continues and also as our data is more mature, we can continue the clinical development, as well as to support our potential BD transaction. Thank you, Joe.
Jingwu Zang
Joe, I’d also like to add that CD73 as a drug class is still relatively early and it’s not as mature as a CD47. So it’s quite natural for companies, they want to see more data. So uliledlimab is a very attractive CD73 antibody because it’s differentiated. It’s also globally competitive.
So we hope that the new data being generated will facilitate our ongoing discussion with the big pharma groups for a global partnership deal. And we are actually in discussion with two or three big pharma groups. Like I said, the more data, Phase 2 data, will help to facilitate.
Tyler Ehler
Thank you, Dr. Zang, and thank you, Dr. Zhu, for that comprehensive response. And thank you, Joe, for the question. Our next question comes from Andres Maldonado at HCW. Andres, please go ahead.
Andres Maldonado
Yeah. Thanks for taking my questions. And I reiterate my congratulations on the progress thus far. So my first question is, outside of increasing the manufacturing capabilities, how is your commercialization efforts expected to further evolve in the upcoming year?
And then on the bookkeeping side of things, could you maybe provide additional details on the cash burn rate? And any expected revenue milestone payments we should be on the lookout for? Thank you very much.
Jingwu Zang
All right. Thank you. Thank you, Andres. Maybe the first question, I would like to ask Jielun to elaborate. Jielun?
Jielun Zhu
Sure. Thanks, Dr. Zang. Hey, Andres. Yeah, just quickly on your question about commercialization. As I mentioned during the presentation, we have a near term product portfolio which includes lemzoparlimab, CD47, felzartamab, CD38, eftansomatropin, which is our long-acting growth hormone, and one pre-BLA product that we’re working to in-license for Chinese – for the Chinese market.
So we expect to file BLA or launch these products in the 2023 to 2025 time frame, so basically, the next 3 years. And that’s also the critical time period for us to transition into a commercial stage biopharma.
The hematological oncology. These products in the hematologic oncology area, based on these three backbone products will be very competitive in China to cover three major oncology indications, namely multiple myeloma, leukemia and lymphoma. And all these three indications combined will take almost the overwhelming majority of all the heme-onc patients in China.
In addition, eftansomatropin, our long-acting growth hormone, is expected to become a fairly sizable blockbuster drug in the Chinese market on its own, given all the technical differentiation we talked about and also the fact that our partner – our commercial partner, Jumpcan, is a very experienced pediatric commercial company in China.
We are actually rapidly building our commercial team under the leadership of our – Chief Commercial Officer, Mr. Yifei Zhu. We aim to cover around 200 to 250 major hospitals in China, and that represents 70% to 80% of all the hematological oncology patients in China. And we are also working on adding these products to the reimbursement list in China as soon as possible.
Lastly, I think in terms of estimates, we estimate that for the first 3 years, for the next 3 years, between 2023 and 2025, we would be in a position to generate product sales revenue in the range of $300 million to $400 million. These sales revenues are expected to increase significantly between 2026 and 2028, basically the following 3 years, when our near term product portfolio converges with our expected solid tumor portfolio. So we expect to see exponentially growing sales revenue in the following 3 years. So I hope these answer your question.
Jingwu Zang
John, could you elaborate on Andres’ second question?
John Long
Sure. Thank you, Andrew, for the question. As we reported in the slides before, the company had $671 million cash and cash equivalent at the end of ’21. On top of that, we now expect to receive over $250 million cash between 2022 and 2025 from multiple out-licensing deals, including existing AbbVie and Jumpcan deals that we have successfully completed over the past few years.
With regards to current cash burn. Our actual operating cash burn for 2021 was US$ 165 million, and we expect to manage operating cash burn between $180 million to $220 million for 2022 and 2023.
Again, with the cash balance in bank and the expected incoming milestone payments from the existing deals, we are confident that our cash position is sufficient to support our business operations for at least 3 years. Thank you.
Tyler Ehler
Thank you, John, and thank you, Jielun. And thank you, Andres, for your question. We’ll take one last question before we wrap up. Next question comes from Yingqi Peng [ph] at UBS. Yingqi, please go ahead.
Unidentified Analyst
Yes. Many thanks for taking my question. I have a question regarding to TJ202. So what is the latest update on TJ202’s BLA submission in China? Could you please explain the difference in declaring it as an imported product compared to a domestic product for BLA submission? And when do you expect the BLA filing to be completed? Thanks.
Jingwu Zang
All right. Thank you. So I’m happy to take this question. Now in 2021, we successfully completed this registrational trial for felzartamab for third-line multiple myeloma. The results are good, met both the primary, secondary endpoints and also demonstrated its advantage with a shorter infusion time and lower injection reaction rate, allowing felzartamab to be used in the outpatient setting, so this is all good.
Now there’s a slight delay in submitting the BLA package. The reasons are two-fold. On the one hand, we are in discussion with the China CDE in light of a new CDE policy for conditional approval. So we’re communicating with the CDE on that.
On the other hand, we wanted to submit a different BLA package with a localized manufacturing plan embedded to significantly reduce the cost of goods, making felzartamab the only locally made CD38 product, to be commercially more competitive.
So we are putting all this information together, and this is also supported by the Hangzhou local government for the local manufacturing. So through active communication with the CDE, we hope to submit a new BLA package very soon this year in 2022.
Tyler Ehler
Thank you, Dr. Zang. And thank you, everyone, for dialing in today. If there are any more questions, please contact your local IR representative. And thank you again for everyone’s time.
Jingwu Zang
Thank you.
John Long
Thank you.
Andrew Zhu
Thank you all.
Jingwu Zang
Thank you.
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