Shanghai Junshi Biosciences Co., Ltd. (CHRS) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to the Coherus and Junshi BioSciences post-ASCO investor event. [Operator Instructions] Please be advised that today's conference may be recorded. [Operator Instructions] I would now like to hand the conference over to your host, Chief Financial Officer, McDavid Stilwell. Please go ahead.

Thank you. Good afternoon, everyone. And on behalf of Coherus and our immuno-oncology partner, Junshi Biosciences, I want to welcome you to our conference call review toripalimab clinical data presented at ASCO and key elements of the ongoing toripalimab clinical development program. During the course of this conference call, we will -- we will refer to the slide deck that is posted now on the Events and Presentations page of the Investor Relations section of the Coherus website. Today's call includes forward-looking statements regarding Coherus' current expectations. These statements include, but are not limited to, our ability to advance toripalimab and other product candidates through development and registration as well as the potential timing for regulatory filings, data readouts and other milestones or catalysts; our ability to develop toripalimab for the treatment of nasopharyngeal carcinoma or other indications; and our ability to successfully commercialize toripalimab and other products in the future, all of which involve certain assumptions, risks and uncertainties that are beyond our control and could cause actual results to differ from these statements. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are discussed in documents that we file with the Securities and Exchange Commission, specifically in our quarterly report on Form 10-Q, for the quarter ended March 31, 2021, that we filed May 6, 2021, and our future periodic filings. The forward-looking statements stated today are made as of this date, and we undertake no duty to update such information, except as required under applicable law. With me today are Dr. Ruihua Xu, President and Professor at the Sun Yat-sen Cancer Center in Guangzhou, China; Dr. Sheng Yao, Senior Vice President of Junshi BioSciences and Executive Director of TopAlliance, Junshi BioSciences' U.S. subsidiary; Dr. Patricia Keegan, Chief Medical Officer of Junshi BioSciences and Top Alliance; and Denny Lanfear, Chief Executive Officer of Coherus. Today, Denny Lanfear will provide a brief overview of the Coherus Junshi BioSciences collaboration. Dr. Yao will then provide an introduction to certain elements of toripalimab's molecular characteristics. Dr. Xu will then review the clinical data from JUPITER-02, the Phase III study evaluating toripalimab as first-line treatment for metastatic or recurrent nasopharyngeal carcinoma. Dr. Keegan will discuss the broad pivotal clinical development program and regulatory strategy for toripalimab and Denny Lanfear will discuss possible toripalimab combination programs. And finally, we will take your questions. Again, before we get started, I want to remind everyone that during this conference call, we will refer to the slide deck that is posted on the Events and Presentations page of the Investor Relations section of the Coherus website. And I will now turn the call over to Denny, again on Slide 5.

Thank you, McDavid, and welcome all of you to our call today to discuss our partnership with Junshi BioSciences and the evolving data with toripalimab. Our relationship with Junshi BioSciences is a transformational strategic alliance, which launches Coherus into the rapidly growing immuno-oncology market. As you know, we acquired U.S. and Canadian rights to the anti-PD-1 antibody toripalimab. Junshi and Coherus have complementary strengths. Junshi is a high science company with extraordinary R&D capabilities. And Coherus, as you know, has excellent U.S. commercial expertise, particularly in oncology. The first BLA filing for nasopharyngeal carcinoma is underway with breakthrough therapy designation in mid-2021. There is potential, of course, for multiple additional toripalimab BLAs in the next 3 years, including lung cancer, and we'll discuss the timing of those subsequently. We believe there is long-term growth potential through PD-1 combinations, including Junshi BioSciences' anti-TIGIT antibody, the engineered IL-2 as well as other molecules. Slide 6, please. Toripalimab's pivotal development program spans across 19 studies and 12 tumor types. It includes head and neck cancer, such as the nasopharyngeal; lung cancer, both in non-small cell and small cell; breast cancer in triple-negative breast; gastrointestinal and so on. There are potential for multiple additional toripalimab supplemental BLAs, including lung cancer, over the next 12 to 24 months. Next slide. Now I would like to introduce my good partner and friend, Dr. Sheng Yao, who will talk to us more about the molecule itself, toripalimab. Dr. Yao?

Thank you, Denny. So I'm on Slide 8. So today, I'm going to give you a brief introduction of toripalimab, its mechanism of action as well as its unique features which we believe make it a differentiated anti-PD-1 among its class. Toripalimab is antihuman (sic) [ anti-PD-1 ] IgG4 monoclonal antibody with hinge mutation. It has unique CDR sequences, which recognize PD-1 molecule. We have resolved the clinical structure of toripalimab in contact with PD-1 extracellular domain. The results show that toripalimab interact with PD-1 through a differentiated domain on PD-1 surface, the FG loop. [ Among that ], it has the largest interacting interface with PD-1. It is a full blocker, which blocks both ligand and interaction. And moving on to Slide 9. Toripalimab during selection by design, we're looking for a strong block antibody. Shown on Slide 9 is a vehicle binding analysis. Toripalimab has a very unique feature of very slow disassociation. As you can see, the curve of disassociation is almost flat, which means one toripalimab binds to PD-1, it takes very long time to come off. It translates into a very high affinity to the PD-1 receptor. Now I'm moving to Slide 10. Like other PD-1, PD-L1 blockers, toripalimab completely blocks the interaction between PD-1 with ligands. However, it also simultaneously induced very strong internalization or under cytosis of the PD-1 receptor upon binding. So here, we use a flow cytometry fluorescent label toripalimab as well as a noncompeting PD-1 antibody to track both toripalimab as well as PD-1 in the assay format. As you can see on the last half, by combining the PD-1 target cell, toripalimab gets internalized into lysosome components within hours. As is shown by the fluorescent intensity in the lysosome compartment. Meanwhile, we track surface PD-1 by a noncompeting antibody. Consistently, we also see a surface reduction of PD-1. There are literature and studies reporting that with PD-1 highly expressed on T-cells, a suppressed T-cell function. Once if you remove T-cell -- PD-1 from T-cell surface or down-regulate PD-1 levels, it makes T-cell intrinsically better, which means it responds to antigen stimulation better. More importantly, this phenomenon is independent of ligand expression. So in our pivotal trial, so we're monitoring the PD-L1 expression closely as well as the clinical accuracy of toripalimab in both PD-L1 high as well as PD-L1 low tumor patient population. That including the first-line non-small cell lung cancer Phase III trial, first-line esophageal cancer cells as well as first line NPC trial, which you will hear next. Thank you.

Now advancing to the recap of the JUPITER-02 ASCO plenary presentation, I'll turn the call over to Dr. Xu, beginning on Slide 12. Dr. Xu?

So okay. Good afternoon. So dear colleagues, so I'm Ruihua Xu from Sun Yat-Sen University Cancer Center Guangzhou, China. So JUPITER-02 is the first international randomized placebo-controlled Phase III trial of toripalimab in combination with gemcitabine cisplatin for the first-line treatment of recurrent metastatic nasopharyngeal carcinoma. So we call the NPC. Next slide, please. So this is a background. As you know, NPC is endemic in Southern China and Southeast Asia. Right now, the standard care is cisplatin prior to gemcitabine so for this type of cancer. But there remains an unmet medical need to improve prognosis of prolonged survival in those patients. Toripalimab is the first anti-PD-1 monoantibody (sic) [ monoclonal antibody ] that was approved for the third-line treatment of NPC in China, with durable response and tolerable safety profile. So we designed this study to evaluate gemcitabine cisplatin regimen in combined with toripalimab or placebo as a first-line treatment in those patients. Next slide please. So this is a detailed study design. So the patient with primary metastatic or recurrent NPC were randomized one-to-one to receive either toripalimab or placebo plus the gemcitabine/cisplatin for up to 6 cycles followed by toripalimab or placebo as maintenance. So the primary endpoint is progression-free survival as assessed by a blinded independent review committee. The secondary endpoint include OS, PFS by the investigator, ORR, DoR and SOR. So we have 2 stratification factors like the recurrent versus the primary metastatic. The second is that ECOG performance status, 0 versus 1. So from November 2018 to October 2019, a total of 408 patients were screened in 35 sites in Mainland China, Taiwan and Singapore. And finally, 289 were randomized. Next slide, please.

Slide 15.

So this is the result, the major finding of this study. A significant improvement in PFS was detected for toripalimab arm compared to the placebo arm. And the ratio was 0.53, and the p-value was significant statistical significance. The median PFS was 11.7 months versus 8 months. And I think there is a [ expected ] clinical minimal, 3.7 months improvement. 1 year PFS rate was almost 50% that compared with the control group, only 28%. Since the overall survival was not mature at the interim analysis, at 9 months of the interim analysis, we observed a 40% reduction in risk of death in toripalimab than the control arm. So if we look at the 2-year overall survival rate, so the 2 curves separate very well. Toripalimab is 77.8%, placebo only 63.3%. Next slide, please.

Slide 16.

Yes. Here is the subgroup, a [ pre-defined ] subgroup analysis. So you look at almost of the factors that we see an improvement in PFS. The cause was observed across all key sub-groups that if we look at those PD-L1 positive and negative patients can benefit from the combination very well. Next slide, please. So the result of the response rate and duration of response is here. So we see that toripalimab gemcitabine can reach very high response rate, 77.4%. That's very high response rate. And the control group of GP alone, 66.4% . And median duration is much longer in trial group, it's 10 months but the control was only 5.7 months. So that means combination, the IO, so prolonged the DOR very, very well. So the hazard ratio reached 0.5. Next, please.

Slide 18.

Next slide, please. Okay. Okay. Yes. This is an overview of the adverse events. So if we look at here, the group, seen are instance of all the advanced events (sic) [ adverse events ] we find. The grade 3 above AEs infusion reaction and the fatal AEs were found between the 2 arms quite similar. The most common AEs were like the myelosuppression, like the leukopenia, anemia, we -- as we know, so in the clinical experience, which were mainly attributed to the chemotherapy like the gemcitabine [ cisplatin ]. The incidence for immune-related adverse event such as hypothyroidism were higher in the toripalimab arm, which were expected and manageable for immunotherapy. So it is like not like a new AE, AR AE signal were found. Next slide, please. So this is a conclusion for the JUPITER-02 study from this first international trial. We can see the addition of toripalimab to gemcitabine and cisplatin regimen is a first-line treatment for nasopharyngeal carcinoma showed better PFS, OS than chemotherapy alone. The combination was safe and no new safety signal were found. This result support the use of toripalimab in combination with GP regimen as a new standard of care for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma. That ends the presentation. I would like to close here. Thank you. Thank you for your attention.

Thank you. And now we'll move to Dr. Patricia Keegan for an overview of the toripalimab development program.

Thank you. And hello to all. This first slide illustrates the breadth of the development program across multiple tumor types. Initially a large number of clinical trials looking at signal detection for clinical activity was conducted both as monotherapy and in combination with standard therapy where it was available and compared to historical controls to identify areas where toripalimab may show some strong clinical activity worthy of further development. And in fact, starting from the top of the slide and the top of the human figure, there was good clinical activity identified in nasopharyngeal carcinoma, based not only on its response rate, but most impressively on the duration of responses with the median duration of more than a year. Similar activity was seen in esophageal cancer, in lung cancer, in breast cancer and a variety of gastrointestinal malignancies, including squamous cell esophagus, preliminary data in gastric cancer, hepatobiliary cancers and hepatocellular cancer. In addition, activity has also been seen in patients with urothelial cancers and renal cell carcinoma as well as melanomas, neuroendocrine neoplasm and lymphoma. So based on this broad evaluation, a very large base preclinical development program was initiated in multiple common cancers. Next slide, please. And this shows the pivotal trials in the development program. As noted, some of the original signal detecting trials were actually expanded and made capable of supporting accelerated approvals in China and hopefully in the U.S., in some instances, for the treatment of second or greater line melanoma, nasopharyngeal carcinoma and urothelial cancer in China and our initial BLA submission, a rolling application, is looking at seeking accelerated approval based on the clinical activity in patients who have received prior platinum-based chemotherapy for nasopharyngeal carcinoma. In addition, there are quite a number of randomized clinical trials in the first-line setting, including in melanoma, nasopharyngeal cancer, as you've just heard, esophageal cancer, multiple hepatocellular cancers looking at the strategy of combining toripalimab with a VEGF inhibitor, both bevacizumab and Lenvatinib, looking at activity of toripalimab in combination with yet another VEGF inhibitor, axitinib in patients with mucosal melanoma, in combination with chemotherapy, both as first-line treatment of patients with non-small cell lung cancer, both squamous and nonsquamous, in combination with the platinum-based regimen as well as initial systemic platinum-based chemotherapy in patients with EGFR mutant tumors who are no longer responsive to EGFR tyrosine kinase inhibitors. In addition, there's a first-line trial in triple-negative breast cancer as well as in small cell lung cancer, renal cell carcinoma and urothelial cancers. As well as adjuvant trials in hepatocellular cancer, non-small cell lung cancer and squamous cell carcinoma of the esophagus. Next slide.

Slide 23.

Thank you. So this gives a little bit more details on our lung cancer development program. And as you can see, these are relatively large but well-controlled -- placebo-controlled clinical trials, evaluating traditional endpoints in non-small cell lung cancer. The first trial is evaluating a primary endpoint progression-free survival with key secondary endpoints of overall survival and response rate. In this first-line trial of non-small cell lung cancer, the interim analysis of the primary endpoint was statistically significant and had crossed the boundary. However, we elected to continue to follow the patients to wait until a more mature analysis of PFS was available and hopefully assume more mature analyses of overall survival. We also have clinical trials ongoing in neoadjuvant cancer, neoadjuvant non-small cell lung cancer. Again, it's an add-on to platinum-based chemotherapy, administered to both the neoadjuvant setting and following surgery, another round of chemotherapy, followed by maintenance treatment. And that trial is well accrued and expected to lead out next year. In addition, there is a clinical trial, as I mentioned, in EGFR mutant non-small cell lung cancer. In this instance, all nonsquamous carcinomas. And in addition to pemetrexed and cisplatinum (sic) [ cisplatin ], patients will receive either toripalimab or placebo. That terminal as well is expected to complete enrollment this year with a readout in 2022. And finally, there is a clinical common randomized clinical trial in patients with extensive stage small cell lung cancer of platinum-based -- platinum etoposide-based chemotherapy and patients are randomized to toripalimab or placebo. And the enrollment in this trial is complete, and we are awaiting readout of final data. Next slide. And in addition to this busy development program in lung cancer, we also have randomized trials ongoing in esophageal squamous cell carcinoma, again, add on to traditional platinum-based chemotherapy. We have a trial in triple-negative breast cancer, which is an add-on to paclitaxel first-line therapy. For hepatocellular carcinoma, the trial is randomizing patients to Lenvatinib placebo versus Lenvatinib plus [ toripalimab ] and in adjuvant therapy. It's a trial randomizing patients to toripalimab alone or placebo following reception. And again, all of these trials are expected to read out in the next 6 months to 1.5 years. Next slide, please. So as noted, this was the first domestic PD-1 blocking antibody approved in China, domestically manufactured PD-1 antibody approved in China under the name Tuoyi for the second-line treatment of patients with locally advanced or metastatic melanoma. This is followed this year, earlier this year, by 2 supplemental approvals: one in third-line treatment of recurrent or metastatic nasopharyngeal carcinoma; and the second for the second-line treatment of patients with advanced or metastatic urothelial carcinoma. All of these are accelerated approvals. And as you have seen, the confirmatory trials are ongoing or in the case of nasopharyngeal carcinoma, completed. Next slide, please. So there's an extensive safety database available for this antibody. This is based on 943 patients, but our safety database is now or approximately 1,200 to 1,300. As expected, the most common side effects that were predicted based on the mechanism of action of the molecule or immune-related adverse events. And as you can see, the incidence of immune-related adverse events were present, are similar to that observed with other drugs in the class, the most common in hypothyroidism, which is an easily managed toxicity as well as other immune-related endocrinopathies that are typically treated with [ F ] hormone replacement. The other toxicities of interest would be pneumonitis, which, while has a 2.5% incidence, in severe cases, were only 1%. And similarly, hepatitis, again, a little bit higher. This is an area where the incidents may be a little bit higher based on the number of patients evaluated in China, where there's also the issue of endemic hepatitis to deal with. But in general, the safety profile is very tolerable and very similar, and there were no unusual toxicities noted, either in the monotherapy program or in the program in combination with standard chemotherapy. Next slide, please. So in the U.S., we have -- we received breakthrough therapy designation based upon the second third line clinical trial in nasopharyngeal carcinoma and a rolling submission was initiated in March of this year, with hopefully potential approval by 2022 or sooner. And this waterfall plot provides insight into the data that supported the approval in China and showing the evidence of a good response rate, with very important durability, as I noted earlier. Of more than a year. Next slide. And the other activities planned for the next quarter or 2 will be to meet with the FDA to discuss submission of the results of the JUPITER-02 trial in first-line nasopharyngeal cancer as well as to discuss our plans for submission of future trials based on the randomized clinical trials in non-small cell lung cancer and esophageal squamous cell carcinoma. Next slide, please. Okay. And now I'd like to turn this back over to Mr. Lanfear.

Thank you very much, Dr. Keegan. Next slide. So what I'd like to do for you now is just take you to a little higher level of the overarching new oncology strategy that we're pursuing here at Coherus. So this includes both fast-follower and transformative assets, which are synergistic with toripalimab. On the far left of the screen, you see the PD-1 background toripalimab. As you know from our previous conversations, Coherus looked at over a dozen PD-1 opportunities globally, including looking very closely at the market leaders. Our criteria for selection were twofold. One, that we had a very potent and safe molecule. And I think as Dr. Keegan reviewed, that story is evolving very, very well for toripalimab. Secondarily, we wanted a PD-1, which was the subject of a both a broad and deep clinical development program. And as you can see, some 19 pivotal clinical trials are underway with toripalimab and we're very impressed at the breadth and the depth of the development program put in place by our partners at Junshi. And then lastly, we have also acquired an excellent partner with Junshi and are working together very, very fully. We are very pleased at the synergistic complementarity between the teams. Our strategy then is to first file and launch in NPC and then expand, as Dr. Keegan described, into these other monotherapies. We also intend to establish partnerships with other third parties who have a need for an excellent, highly efficacious, safe PD-1 to complement their other immunotherapy agents. We've had several incoming opportunities since we initiated the transaction. We also, of course, are pursuing fast-follower opportunities, and we will evaluate and partner our Junshi assets with these options. I'll disclose those a little more on the next slide. And importantly, we plan to co-formulate these fast-follower molecules with toripalimab. We're also pursuing both internal pipeline and some selective in-licensing. Good examples of these, for example, are the TIGIT and the engineered IL-2. We also take a look at what I would characterize as transformational assets as the third leg of the triad. These are opportunities which will afford a step change in cancer care, addressing the tumor microenvironment, myeloid cells, T-cell priming, et cetera. And for these, we are taking a look at both internal pipeline and selective in-licensing. You can expect us, as we move forward, very tissue and indication-focused with these opportunities. Next slide. Here is a summary of the options and negotiation rights in the Coherus-Junshi agreement, and particularly with respect to the fast-followers. Of course, you recall that we have included in this agreement options to clinically validate targets, JS006, anti-TIGIT. This immune inhibitory checkpoint limits anti-tumor response. This is now being validated by others in Phase III. It has a demonstrated synergy in combination with anti-PD-L1s. It's currently in Phase I. And then there's JS018, which is the engineered IL-2, a cytokine that helps effector T-cells proliferate and expand. Two other negotiation rights exist with the agreement. First is a clinically validated target that works synergistically with PD-1 in the activation and augmentation of anti-tumor immunity. And the second, a novel inventory molecule closely related to TIGIT that can independently inhibit anti-tumor response. This gives us a robust fast-follower pipeline. Next slide. Here we provide you, on the left panel, just a quick shot of the tumor microenvironment. Beyond the PD-1, toripalimab and the fast-forward combinations, we are investigating transformational approaches in the tumor microenvironment where step change in therapy may occur. This will include, for example, the potential for enhancing antigen presentation, T-cell priming, anti-T cell migration, infiltration into the tumor, expansion of T-cells through cytokines and overcoming T-cell exhaustion with immune checkpoint blockades. This is an area of -- the third leg of the triad, as we pointed out, and you'll be hearing more about this during our -or in this case, in Q4. Next slide. There's key catalysts coming up in the next 18 months for the Junshi-Coherus collaboration. Of course, ASCO with the first-line NPC data that we had the opportunity to review today. And also, in mid-2021, completion of the rolling BLA submission for second and third-line NPC. A little later on, as Dr. Keegan indicated, there'll be readouts in the clinical data, first line non-small cell and first-line esophageal, the Analyst Day and also significant conversations with FDA on regulatory pathways. In 2022, we see potential toripalimab approval for third line NPC in the first half. And a robust set of readouts across a number of indications, first-line for small cell lung cancer notably, neoadjuvant in non-small cell, non-small cell EGFR positives, first-line triple-negative breast, et cetera. So you'll be hearing from us on a very consistent and ongoing basis. We're very excited as these molecules then reach fruition, and all these studies start to read out between now and '22 with their attendant BLA submissions. Next slide. And with that, I will conclude our formal presentation, and then we'll move on to Q&A. McDavid?

Yes, operator, please open the line for questions.

[Operator Instructions] Our first question comes from the line of Salim Syed of Mizuho.

Congrats on the initial data here from toripalimab. Maybe just one high-level one for me, if I can, and I don't know maybe who this is directed towards. But maybe, Denny, when we think about the toripalimab commercial strategy, right, obviously, Keytruda and Opdivo have been approved in multiple tumor types. And I imagine tori would ultimately be in a lesser amount, but it will also take some time. Just how do we think about in terms of reconciling here payers being able to say, okay, I like tori for this indication, but I'm really entrenched with Keytruda in Opdivo. Like how long do you need to wait before you see payers really take up tori in a substantive sort of fashion as you work through these indications?

Thanks for the questions, Salim. As you can see from the presentation, our current focus is to watch for the maturation of the data. We think that it's a little early. We haven't to be talking about -- chatting with payers just yet. I think that's really a function of how the data comes out, how the molecule performs. And we are very -- we think that it's very, very promising so far with this first-line data, particularly in nasopharyngeal. The other comment that I'd make to you is we view toripalimab really as the foundation stone of our immuno-oncology franchise. And we think that it's just an excellent PD-1 to be paired with a variety of immune-oncology agents, which are complementary, not just the TIGITs or the eIL-2s, but also those that come from others. And so we think that there's a very strong need for this type of [ monoclonal antibody ] in the environment. And we think that toripalimab is demonstrating potential for hospital differentiation. We look very closely at the future data readouts that come. But we -- I hope that's helpful for you, but we see it really is the foundation stone of our strategy.

Our next question comes from Mohit Bansal of Citigroup.

Great. And thanks for providing all this color and information here. Really helpful. Maybe one question on regulatory. If I understand correctly, do you plan to file on the basis of data generated so far in the U.S.? So data generated in China and Singapore, do you plan to file that way? And maybe question is directed towards Dr. Keegan. I mean, in your experience, how receptive is the FDA to have the data from non-U.S. territories, especially from China to -- which can -- which can be a basis for a regulatory approval.

Dr. Keegan, do you want to take that one?

Sure. So what I would say is in the field of oncology, we have rapidly, over the last 10 years, moved into an area where virtually, all trials have an international component to them. And the criteria that FDA would use to consider the trials are similar to what would be used in looking at clinical -- at all international clinical trials, which are the locations where the trial was done, do they have a similar standard of care for the disease? Is the disease is similar in nature, maybe not identical, as we've heard nasopharyngeal cancer has some -- there are some slight differences between the U.S. and China with regards to proportion of certain subtypes. But in general, and I think as we heard yesterday at the plenary session, the standard of care is the same, the treatment approach is the same, regardless of the histologic subtype and the behavior, the response to therapy is the same. So that I think in this instance, there shouldn't be much concern because of those strengths of both the trial and the similarity of the disease and the diagnostic and therapeutic modalities used for the disease internationally.

Our next question comes from Jason Gerberry of Bank of America.

I guess the first one, I'm just a little confused. So with the JUPITER-02 trial, what's the confidence that you can file on this data for first-line NPC? Is it sort of gated by having more mature OS data? Or is the uncertainty just not having had an FDA meeting yet. I was just sort of struck by the commentary from the discussion yesterday about calling it, I think, maybe practice changing. So just curious sort of what that maybe factor is. And then, Denny, just a follow-up question to your comment about business development and partnering here. I assume that what you mean by this is perhaps combination trials with other agents and sort of 50-50 cost-sharing of clinical trial spend, perhaps not encumbering the asset in any way, but more or less just thinking about partnership, that you could help defray the P&L burden from further studies.

Jason, thanks. I'll take the second question first, then I'll leave your first question with respect to the system of a first-line NPC data and potential filing strategy to Dr. Keegan. With respect to your question, my point was that I think being recognized that toripalimab is an excellent PD-1 with strong efficacy and as Dr. Keegan pointed out, a very strong safety record accumulating. So there's definitely a need in the commercial environment for such a PD-1 to be coupled with other assets, complementary IO assets, as you point out. We have not had certain commercial conversations around cost-sharing as these things go. But we would be open to a variety of constructs. There might be situations where we simply provide a drug and so on. But I think we would pursue opportunities which would broaden the use of toripalimab in combination with other agents. And I think that others are approaching us now for those types of arrangements. And we're happy to give you further updates as that evolves. Dr. Keegan, you want to address the first-line NPC question?

Sure. And we have had preliminary meetings with the agency prior to the full results being available and certainly this more recent update. But I think the agency has shown a willingness, even in first-line cancers, to consider the strength of the data on progression-free survival, both the magnitude of the treatment effect as well as any other supportive information such as the higher response rate and the near doubling of the duration of response and the safety profile, and look at that as a package and not always require a demonstration of improvement in overall survival. However, I think in this particular situation, we're in a happy position of having a very strong trend in the survival data. And I think that as a total package, although we haven't met with the agency on this entire package as it's been presented at the point of recession, I think that there's a likelihood that they would look favorably on this type of data on this data package.

Our next question comes from Georgi Yordanov of Cowen.

Congratulations on the impressive data. So just a couple on our end. You have previously discussed the potential anti-PD-1 market opportunity reaching $30 billion by 2026. So given the multiple competitors in this space, and we're seeing a lot more collaborations with Chinese assets and other international assets, I was wondering if those estimates included any pricing discounts? And then the second one a little more on the science. Given the mechanism of action of tori leading to receptor internalization, do you expect any differentiated efficacy in certain tumor types compared to other PD-1s in development or approved PD-1s?

Thank you, Georgi. I'll let Dr. Yao take the issue of the mechanism of action and potential differentiation, and then I'll follow-up with your second question about the size of the market and so on. Sheng, do you want to take that one?

Sure. Yes. Thank you, Denny. Thanks for the question. So we believe internalization is one unique aspect, at least for tori. And we are, as I mentioned, we're closely monitoring our pivotal trials, the metastases in both tumor PD-L1 positive high or PD-L1 low population. And historically, we know drugs of this class will favor patients with PD-L1 high. But so far, at least the story for NPC data, patient will benefit from tori chemotherapy regardless of PD-L1 expression. We have seen this with our second, third line NPC monotherapy as well. So this is somewhere we would like to monitor closely and the new results will emerge first-line [ nasopharyngeal cancer ] as well as our first-line squamous esophageal cancer there.

And then with respect to the market size, I would make 2 points. First of all, as I've said a couple of times already today, that we think that toripalimab really is an excellent molecule to partner with if you have novel complementary immuno-oncology molecules. And not just others, but also, for example, the anti-TIGIT that our colleagues here at Junshi are developing and the engineered IL-2. So secondarily, there's other folks that are showing up, and we intend to promote very broad uptake of toripalimab in the commercial environment, irrespective of price. I think we've talked on our last call about how we expect to take 10% or more of any particular market that we entered, and we would put toripalimab at PD-1 in that market also. And I think that as time evolves, you'll see our strategy focused on that objective. Hope that helps.

[Operator Instructions] Our next question comes from Greg Gilbert of Truist Securities.

I have a couple. First, Dr. Keegan, going back to what you said about using data from China and elsewhere for U.S. filings. To take this a step further, could you end up with a label similar to those of Keytruda and Opdivo in the larger patient populations in theory without doing any of those studies in the U.S., if it's not ethical to do so in the U.S.? I just want to understand to what degree you might end up, over time, copying large elements of others' labels, not just operating around the edges and getting to certain smaller populations first? And then I have a follow-up.

I would say that there is precedent for clinical trials being conducted outside the U.S., which, based on the available therapy in that region, would be ethical to conduct, but not in the U.S., given the alternative therapy available. So that if the study was conducted in China that mirrored, say, some of the studies previously conducted with Keytruda and with and nivolumab, that those studies would still be as valid as the original pembrolizumab and nivolumab studies. And as long as the other criteria that I mentioned before, similarity of the disease in the population, similarity of the treatment and management of that disease to the U.S. population, that those data should support a U.S. -- I mean, basically, a demonstration of efficacy.

So it sounds like you expect labeling language that could be almost the same, if not the same, as some of the existing products in certain cases. Is that fair?

I think if the studies were similar, labeling could look similar. It's always a little difficult to comment on specific labeling language without having a particular study in front of you. But I think similar trials would likely have similar language and labeling. I think that's a true statement.

And in Slide 28 when you folks discussed the filing strategy and that you plan to meet with the FDA to discuss clinical data. I assume that's a general comment that sort of ties to each time you have data to talk about, you will talk about it as opposed to some overarching strategic FDA meeting you plan to have soon. Is that correct?

Right. I think we want to discuss and focus on clinical trials and data. In some instances, it might be also to talk about the general trial designed before the data are available. We did do that for the JUPITER-02 study and had a conversation about the trial design and its ability to obtain the data necessary to support an approval. And I think in some instances, it will probably be a mix. Some of these studies are reading out so soon that we may come in with clinical data. Other ones we probably would like to initiate discussions about trials that may be ongoing or planned and have the conversation about trial design. So it likely would be a mix.

Great. And then my other one, perhaps for Denny, you've probably seen comments from Merck and Bristol and maybe others about their plans to co-formulate their PD-1s with other IO agents essentially in one product. Do you see that as a life cycle management game? Or do you plan to pursue co-formulations as a strategy as well? And have you discussed that with your partner?

Yes. Thank you for that. Yes, actually, that's on one of the slides that posted. What I would say is that co-formulation is analytically and scientifically a bit challenging. One of the strengths of Coherus and one of the core competencies that we put in place while pursuing biosimilars is very strong analytical capability, particularly around mass spec. When you co-formulate in one vial, for example, you have to track all the degradation of products for 2 products. And at the same time, simultaneously. So I think that it becomes analytically and in a protein chemistry sense as somewhat complex. But that complexity, I think, is something that Coherus is in an excellent position to handle given our virtuosity in terms of addressing these things with biosimilarity.

Our next question comes from Balaji Prasad of Barclays. .

Just a couple from me. Denny, congratulations again. Firstly, on one of the slides, you called out that the mechanism does not rely on PD-L1 expression. Can you comment about the advantages that it brings both in development and in future commercialization? And secondly, can you also give any feedback that you had real-time today from ASCO after the plenary session?

Well, with respect to the plenary session, I believe the primary feedback is that there's a new standard of care for in treating NPC in first line. I think this is perceived, obviously, as very, very strong data at ASCO, I think, it can reasonably be viewed as the fear of our peers. In terms of things, there's a lot of papers to select from, and we're very honored that they would select ours. With respect to the mechanism of action in terms of the scientific presentation provided by my good friend, Sheng Yao here, we think that it is unique and is unique by insight on the PD-1 receptor with the FG loop. We're going to see how the data reads out across these various tumors and cancers with the ongoing study. So stay tuned for that. But we think that it's very, very interesting, and we think it's very promising. And just how that reads commercially, will, I think, is yet to be determined.

If I could just have a follow-up. Can you remind us of the -- could you just remind what contents of clinical data have gone into the rolling BLA that was initiated early on?

Okay. Dr. Keegan, do you want to comment on that contents of the rolling BLA?

Right. So the first component of our BLA was actually the nonclinical data, and the clinical data is hopefully going to be going in soon. The last components will be the CMC and the clinical pharmacology section. And we hope to get this rolled in by July.

Thank you. At this time, I'd like to turn the call back over for closing remarks. .

Thank you, everybody, for joining us today. And I want to give a special thanks to Dr. Xu for being with us. I know it's very early for you in China. Thank you very much. Dr. Keegan, Dr. Yao, we appreciate this opportunity to work together on a successful post ASCO event. Thank you. Good night.

Thank you, all. Bye-bye.

Thank you. Thank you.

Good bye.

Bye-bye.

Goodbye.

This concludes today's conference call. Thank you for participating. You may now disconnect.