Good day, and thank you for standing by. Welcome to the fourth quarter and full year 2021 Coherus BioSciences earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance, please press star, then zero. I would now like to hand the conference over to your host today, McDavid Stilwell, Chief Financial Officer. Please go ahead, sir.
Thank you, operator. Good afternoon, everyone, and thank you for joining us. We issued our press release earlier announcing our 2021 fourth quarter and full-year results. This release can be found on the Coherus BioSciences website. Today's call includes forward-looking statements regarding Coherus's current expectations about future events. These statements include, but are not limited to, our ability to advance our product candidates through development and registration, the status of our product candidate clinical profile, our timing and ability to commercialize our products and product candidates in the future, our R&D and SG&A expense guidance for 2022 and our ability to meet the same, our projections about margin as well as our ability to draw down amounts under our new credit facility.
All of which involve substantial risks and uncertainties that are beyond our control and could cause actual results, performance or achievements to differ from the results, performance or achievements implied by the forward-looking statements. These statements are not guarantees of future performance and are subject to certain risks and uncertainties that are discussed in our press release that we issued today, as well as in the documents that we file with the Securities and Exchange Commission, including those in our annual report on Form 10-K and quarterly reports on Form 10-Q. The forward-looking statements provided on the call today are made as of this date, and we undertake no duty to update or revise any forward-looking statements. With me on today's call are Denny Lanfear, CEO of Coherus, Paul Reider, Chief Commercial Officer, and Theresa LaVallee, Chief Development Officer. I will now turn the call to Denny.
Thank you, McDavid, and thank you all for joining us this afternoon. Today, I'll describe how over the past year, we've delivered on our objective to transform Coherus into an innovative immuno-oncology company supported by income from a diversified portfolio of FDA-approved products. I'll begin today with a brief review of our achievements toward our strategic initiative in immuno-oncology, detailing the progress of our foundational asset, toripalimab, and of our preclinical and clinical-stage innovative combination agents. Then I'll review recent progress to grow and diversify our commercial portfolio. Now, with respect to our immuno-oncology programs, you may recall that in November, we announced the FDA-granted priority review for the BLA for toripalimab for the treatment of nasopharyngeal carcinoma, an indication with no FDA-approved cancer immunotherapy options and for which toripalimab has Breakthrough Therapy and Orphan Drug designation.
The BLA review is progressing well towards the target action date of April 30th , which is about 10 weeks from now. Toripalimab's clinical profile continues to strengthen across indications. In December, we announced that toripalimab plus chemotherapy demonstrated a statistically significant overall survival benefit in a pre-specified interim analysis of the CHOICE-01 clinical trial for the first-line treatment of advanced non-small cell lung cancer. This builds on other first-line indications in esophageal squamous cell carcinoma and nasopharyngeal carcinoma, where we have seen a robust benefit in both the progression-free survival and overall survival. We've also made progress with our clinical stage mid-stage IO asset strategy. In January, we initiated the process to exercise our option to license JS006, a TIGIT-targeted antibody developed by Junshi Biosciences, our partner, which they are evaluating in a study combination with toripalimab.
Dr. Theresa LaVallee, our new Chief Development Officer, will provide additional details about JS006 and our development plans for you in just a moment. Our immuno-oncology preclinical research and development team is proving to be highly productive. In January, we announced that we're advancing an internally generated pipeline of PD-1 combination candidates, and we expect to file the first IND in mid-2023. With toripalimab nearing its first potential approval, a TIGIT-targeted immune checkpoint blocker entering mid-stage development, and our in-house early-stage immuno-oncology candidates successfully advancing towards human clinical trials, Coherus is evolving into an innovative immuno-oncology company with a broad pipeline of product candidates and the potential to drive long-term growth over this decade. I'd now like to introduce Dr. Theresa LaVallee, our recently appointed Chief Development Officer, who brings more than 25 years of drug discovery and development experience and is recognized for her immuno-oncology expertise.
Most recently, Dr. LaVallee was Vice President of Translational Medicine and Regulatory Affairs at the Parker Institute for Cancer Immunotherapy, where she provided scientific leadership for the clinical strategy for development of novel immuno-oncology therapies and helped establish the institute's translational and regulatory organization. Prior to that, from 2008 to 2013, Dr. LaVallee was a member of the immuno-oncology team, developing checkpoint inhibitors and related diagnostics at MedImmune and AstraZeneca. Theresa.
Thank you, Denny. It is exciting to join Coherus as the company gains momentum in its transition to an innovative immuno-oncology leader. I believe our broadening product portfolio with early, mid, and late-stage complementary IO products is well-positioned to clinically succeed in immuno-oncology. Commercially, our oncology-focused organization has proven that Coherus can be very successful in highly competitive fields. Coherus has both the in-house expertise and assets needed to support a successful transformation. Antibody development for PD-1 combinations and co-formulations requires world-class analytics, protein science, and bioinformatics capabilities. We have that at our Camarillo, California site, a 25,000 sq ft facility we moved into two years ago. On the development side, our clinical and regulatory teams have repeatedly demonstrated the ability to develop drugs that gain FDA approval.
Our scientific advisory board of recognized IO experts from academia and industry is actively involved in our target and moiety selection, playing a key role, for example, in selecting toripalimab from a due diligence review of more than 10 PD-1 product candidates, as well as vetting the TIGIT asset from Junshi. For Coherus, these investments are paying off. Toripalimab, our foundational immuno-oncology asset, is establishing an excellent safety and efficacy profile in the ongoing clinical trials. The toripalimab BLA for nasopharyngeal carcinoma, an unmet medical need with no approved immunotherapies, is under priority review by the FDA with an action date of April 30th. Denny mentioned earlier that toripalimab's clinical profile continues to strengthen across indications. Case in point, the positive progression-free survival and overall survival data from the JUPITER-06 study in esophageal squamous cell carcinoma, which showed a significant overall survival benefit even in low PD-L1 patients.
We have and will continue to engage the FDA on the potential for submission later this year of a supplemental BLA for toripalimab in combination with chemotherapy for first-line treatment of ESCC. Another important immune responsive tumor type is hepatocellular carcinoma, which also is highly prevalent in patients of Asian descent, and which the FDA has said could warrant regulatory flexibility for new PD-1. We are conducting two pivotal clinical trials evaluating toripalimab in HCC, including a front-line trial randomizing approximately 520 advanced HCC patients to lenvatinib and placebo versus lenvatinib plus toripalimab. In adjuvant therapy, we have a trial with approximately 400 HCC patients randomized to toripalimab or placebo following resection. Initial clinical data from these studies are expected later this year.
The February 10th ODAC meeting discussing the Innovent Lilly BLA for non-small cell lung cancer provided helpful insights into the FDA's expectations for sponsors seeking approval for PD-1 for indications with available immunotherapy options. We believe it is wise to fully engage with the FDA early and prior to submission decisions to fully understand their views. We are continuing to meet with the FDA frequently for toripalimab for multiple potential indications, and we'll discuss with them this year the pathway for toripalimab in combination with chemotherapy for first-line treatment of non-small cell lung cancer. Although there are FDA-approved checkpoint inhibitors for non-small cell lung cancer, new and more effective treatment options are needed as the majority of patients still die rapidly from this deadly disease.
We are focused on addressing unmet patient needs, so non-small cell lung cancer will be the first tumor type we pursue for the combination of toripalimab with JS006. We are excited about the development of this TIGIT antibody. TIGIT is emerging as an important checkpoint to enhance PD-1 antitumor immunity. After a decade of translational research with IO, the field understands better how PD-1 inhibitors work and why they have been foundational for IO treatment. Cancers trick attacking T-cells into shutting off prematurely. A subset of T-cells that exhibit stemness have the potential to be reactivated by the unique crosstalk between PD-1 and TIGIT pathways. All of this is consistent with the observed improved clinical activity with PD-1 and TIGIT inhibitors in the clinic, and specifically in non-small cell lung cancer.
In preclinical studies, JS006 has demonstrated excellent binding affinity and strong inhibition of the TIGIT pathway, as well as enhanced antitumor activity in combination with toripalimab in preclinical mouse models. A clinical study evaluating JS006 as monotherapy and in combination with toripalimab in patients with advanced solid tumors is ongoing. The IND for JS006 is open in the United States, and we are planning to advance JS006 in combination with toripalimab in a clinical trial in the U.S. later this year. Clinical data news flow will continue this year as results come in from trials evaluating toripalimab for first-line treatment of small cell lung cancer in two additional non-small cell lung cancer studies, one in the neoadjuvant setting, as well as a trial in patients with EGFR mutations who have failed prior TKI therapy. Also pivotal studies in triple-negative breast cancer, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma.
Depending on clinical outcomes and conversations with the FDA, these studies could lead to additional indications for toripalimab in the United States. I will now turn the call back to Denny.
Thank you, Theresa. It's great to have you on the team directing our mid to late stage IO development efforts. Now, let me briefly summarize our recent accomplishments with respect to our commercial stage portfolio and our goal to grow and diversify our commercial portfolio of FDA-approved products. As you may recall, in December, the FDA approved our second product, YUSIMRY, an adalimumab biosimilar. Paul will address our planning for this important launch in 2023 and some of the key issues we are considering to ensure that we reach our market share objectives. Pegfilgrastim market continues to be very important to us and has only about 50% biosimilar penetration in terms of presentation segment mix. We have had good success with additional presentation development to address all the segments.
In October, our UDENYCA on-body injector demonstrated pharmacokinetic and pharmacodynamic similarity in a randomized clinical trial, enabling the submission this year of a prior approval supplement to the UDENYCA BLA. If it is approved, we project that the 2023 launch of the UDENYCA on-body injector, which would compete directly with Neulasta Onpro, which would provide a second wave of growth for UDENYCA. UDENYCA in the prefilled syringe format continues to provide a significant source of funding for our pipeline investments and support upcoming commercial launches. Net sales of UDENYCA declined to $73 million in the fourth quarter within the context of increasingly competitive pegfilgrastim market. We anticipate UDENYCA net revenue in 2022 will decrease relative to the $327 million of net revenue generated in 2021.
Our strategy is to balance price and market share to optimize long-term revenues with the PFS format in 2022, and then gain significant share through accessing the untapped on-body segment in 2023. In October 2021, the FDA accepted for review the BLA for CIMERLI, our Lucentis biosimilar. Mid-cycle review meeting occurred recently, and the BLA is progressing well towards the target action date in August this year. As Paul will elaborate, we plan to launch CIMERLI in the second half of this year, assuming approval. We are also planning for the launch of toripalimab in NPC mid-year, further diversifying our product portfolio in 2022. These two launches in 2022 should be followed by the 2023 launches of YUSIMRY and the UDENYCA on-body injector, accelerating our revenue growth.
We expect these four new products to mark an inflection point for revenues, fueling top-line growth starting later this year. We expect growth to continue with the potential expansion of the toripalimab label and project longer-term growth with the JS006 toripalimab combination and our innovative IO pipeline that we discussed. I'll now turn the call over to Paul Reider, our Chief Commercial Officer, and Paul will review UDENYCA's fourth quarter performance and update you on the launch preparation for toripalimab, CIMERLI and YUSIMRY. Paul?
Thank you, Denny. As Denny indicated previously, UDENYCA net sales were $73 million in the fourth quarter, down 12% from the prior quarter. This was driven by a 4% decline in demand units, as well as continued price erosion due to intense competitive pressures in the pegfilgrastim prefilled syringe market. Our share declined slightly from 18% to 17.5% in the fourth quarter. Market share gains in the clinic segment were offset by declines in both 340B and non-340B hospitals. On a units basis, the overall pegfilgrastim market declined modestly in the fourth quarter, a period in which historically we've seen slight market growth. We expect to return to low single-digit market growth in 2022. Until COVID recedes more broadly, there will continue to be a short-term advantage favoring the originator's on-body device, which retains approximately 50% share of the overall market.
As Denny indicated, we expect UDENYCA's sales to grow again once we introduce our UDENYCA on-body injector next year, if approved. Our strategy is to balance price and market share, to optimize long-term revenues with the prefilled syringe (PFS) format in 2022, and then gain significant share through accessing the untapped on-body segment in 2023. Now I'd like to talk about commercializing our pipeline. We are preparing for the launch of three new brands in the next 18 months. Toripalimab, our PD-1 inhibitor for nasopharyngeal carcinoma, CIMERLI, our Lucentis biosimilar, and YUSIMRY, our Humira biosimilar. Regarding Toripalimab, nasopharyngeal carcinoma, or NPC, is a rare cancer where there are currently no PD-1 inhibitors approved for use by the FDA. Toripalimab not only has the potential to be the first and only PD-1 inhibitor indicated for this tumor type, but has the potential to also establish a new first-line standard of care.
Our oncology commercial capabilities have been built to scale, and the toripalimab launch effort will be efficiently integrated into our existing commercial infrastructure. Commercial launch preparations are proceeding on track. I'd also like to note that the NCCN guidelines for nasopharyngeal carcinoma recently added the JUPITER-02 study of toripalimab for the first-line treatment of NPC as a reference, which serves to validate the significance of this important clinical trial. Now with respect to CIMERLI, our FDA action date in August 2022 will allow us to launch into the $1.4 billion Lucentis market in the early stages of biosimilar market formation, and we look forward to competing in the retina therapeutic area.
Retinal specialist opinion leaders have expressed positive receptivity to Coherus entering this market, and our documented track record of success in oncology gives them confidence that Coherus understands the dynamics of the buy-and-bill market, and that we will deliver a safe and effective alternative to Lucentis, along with a compelling value proposition. Similar to our playbook with UDENYCA, we plan to launch a biosimilar education campaign to the retina community in the second quarter. We've also completed our account segmentation work and intend to launch with a focused and dedicated ophthalmology sales team, while at the same time leveraging our commercial organization's existing key account, market access, and patient support capabilities. Now on to YUSIMRY. We're preparing for the launch in July 2023.
Humira has been the top-selling drug in the United States with net sales of $17 billion in 2021, and we look forward to competing in this market. While we expect significant competition, our commercial goal is to achieve at peak at least 10% share of the overall adalimumab market. We believe payers will drive biosimilar adalimumab adoption and have completed extensive market research with national and regional payers as well as PBMs. The insights gleaned from this research confirm that Coherus can and expects to deliver on all of the payers' critical expectations.
These include a competitive price that delivers value to key stakeholders, robust and reliable supply with high-quality manufacturing, a non-stinging citrate-free formulation, prefilled syringe and autoinjector presentations with high-gauge needles that are comparable to the reference product and that are comfortable, reliable, and easy for patients to use, robust patient support services to facilitate access and to address patient out-of-pocket costs. Also according to our research, interchangeability was regarded as a nice-to-have attribute, but not essential, since payers already have the mechanisms to drive product selection based on their formularies and utilization management tools that they use routinely today in multiple product categories. To meet these expectations, Coherus has previously invested in large-scale manufacturing and expects to be well-positioned to compete on supply guarantees and price. We will have quality prefilled syringe and autoinjector presentations.
Our YUSIMRY device uses a 29-gauge needle comparable to the originator's, and we also will use our proprietary non-stinging citrate-free formulation. In addition, through Coherus Complete, which is our patient and provider services that are considered best in class among the pegfilgrastim class today, we have an established and high-touch service offering to facilitate access and affordability. Some large competitors may position their adalimumab biosimilar within a portfolio offering to payers. Coherus, by contrast, will have a singular focus on competing successfully in the adalimumab market without the constraints of trying to minimize the collateral impacts of price erosion on a portfolio of premium-priced branded products. Our interest is in seeing the overall adalimumab market become as large as possible. We believe this is also in the best interest of payers and patients.
In short, we are confident we can deliver a compelling overall value proposition and expect results consistent with our market share forecast with YUSIMRY. I'll now turn the call to McDavid for a review of the quarter's financial results.
Thank you, Paul. The details of our financial results are in the press release, so I'll focus now on a few highlights. For the fourth quarter and full year 2021, we reported net losses of $46 million and $287 million, respectively, on a GAAP basis. Cash used in operating activities was $52 million for the fourth quarter and $37 million for the full year 2021. As detailed earlier in the call, net revenue was $73 million for the quarter and $327 million for the year. This is a decrease for both periods, reflecting lower unit volumes and lower net realized price. Wholesaler inventory remained within the normal range at year-end. Cost of sales was $12 million for the quarter and $58 million for the year, resulting in gross margins of 84% and 82% respectively.
Recall that in the first quarter of 2021, we depleted the inventory manufactured and expensed prior to approval. Since then, per-unit acquisition costs are fully reflected within COGS. Accordingly, cost of goods as a percentage of net revenues has increased since 2020. In the long run, starting in 2024, we expect UDENYCA prefilled syringe gross margins to return to 90% or higher as we realize the benefits of a significant manufacturing process improvement and also royalty expiration. Research and development expenses were $51 million for the quarter and $363 million for the year.
This is an increase over 2020 and includes the $136 million upfront payments to Junshi for the toripalimab license, as well as costs to advance our late-stage pipeline, activities such as regulatory affairs and manufacturing scale-up for YUSIMRY, clinical development and BLA filings for toripalimab, a clinical trial for the UDENYCA on-body injector, as well as the ongoing three-way PK study evaluating CHS-305, the Avastin biosimilar. Selling, general, and administrative expenses were $50 million for the quarter and $170 million for the year, an increase that was primarily driven by higher UDENYCA commercialization activities as well as stock-based compensation expense. We ended the year with $417 million in cash and cash equivalents.
Recall that subsequent to year-end, we entered into a credit facility agreement with Pharmakon Advisors for a $300 million term loan payable across four tranches. We drew the first $100 million tranche at closing and simultaneously paid off a $75 million term loan. Prior to April 1st, we plan to draw a second $100 million tranche and simultaneously pay off the convertible notes that come due at the end of March. Two additional tranches of $50 million each will become available to us upon the FDA approval of toripalimab and of YUSIMRY.
We are introducing full year 2022 guidance for R&D and SG&A expenses of $415 million-$450 million, not including the $35 million upfront fee to Junshi Biosciences we expect to pay later in the first quarter for rights of JS006 or the $25 million milestone payment that will become due on approval of toripalimab for NPC. This guidance range includes approximately $55 million-$60 million in non-cash stock-based compensation expense. Let me provide some additional color on these anticipated operating expenses, much of which is investment that will convert back to cash quickly with a high IRR. This year, we will spend approximately $50 million manufacturing inventory for new product launches. You'll recall that one lesson from our successful UDENYCA launch is that going to market with ample supply is a critical success factor.
Recall that low-cost inventory manufactured and expensed prior to FDA approval subsequently delivers P&L benefit in the form of lower COGS. Another $40 million-$50 million of operating expense this year will fund completion of development of additional presentations of products we expect to introduce over the next two years, as well as manufacturing scale-up projects that will deliver ongoing benefits in the form of significantly lower cost of goods. Finally, on the investor relations front, we will present and host investor meetings in March at two conferences, the Cowen conference and also the Barclays conference. We are planning to host the Coherus Analyst Day event in late March in New York City, hopefully in person. I will now turn the call back to Denny for closing remarks.
Thank you, McDavid. A year ago, we told you that our vision for Coherus was to become an innovative immuno-oncology company with commercial IO assets, promising clinical-stage programs, a novel in-house preclinical pipeline. With the potential approval of toripalimab in April, the initiation of a clinical trial evaluating TIGIT in combination with toripalimab later this year, and the advancement of the first of our in-house IO assets towards IND, we are delivering on this vision that we laid out to investors a year ago. The levers of success are now in our own hands. I am proud of the execution of my team and confident that we will fulfill the promise of our strategy. On the commercial side, we are uniquely positioned to launch multiple new products in the next 18 months.
With these launches, the total addressable market opportunity of our product portfolio will increase tenfold from about $2.5 billion to more than $25 billion. Our commercial opportunity will continue to expand as additional toripalimab indications are added and as our immuno-oncology pipeline candidates advance to commercialization. This growing product portfolio will fund our continued growth in immuno-oncology through the end of this decade. Operator, we're ready for the questions.
Thank you. If you have a question at this time, please press star then one on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Our first question comes from the line of Salim Syed with Mizuho. Your line is open. Please go ahead.
Hey, good afternoon, guys. Thanks so much for the color. A couple from me, if I can. One on toripalimab. I would like to understand a little bit more about the strategy here in lung post an assumed NPC approval late April, specifically the prospects of getting toripalimab listed as a category 2B medication on NCCN guidelines and the prospects of a subsequent Medicare reimbursement off-label uptake in lung. Or do you really think you'll need an additional trial in lung that's head-to-head versus a PD-1 and how those costs would be allocated or shared?
And then the second question is on the UDENYCA guidance for 2022. Denny, I appreciate that revenues will be lower than 2021. How are you thinking about ASP declines in 2022, 2021, by my math, had roughly about a 20%-30% ASP decline. This is now the fourth year post-launch. Should we be thinking about that moderating in 2022? With COVID cases largely declining here and Onpro still having 50% of the pegfilgrastim market, just maybe you could speak about qualitative here, your views on units, please. Thanks so much.
Thank you for that, Salim. I would ask that follow-on questioners limit themselves to one question then so we can work through. If your question is not answered, we're happy to go through. Let me direct the question of the non-small cell regulatory strategy that you posed to Dr. LaVallee. Theresa, do you wanna answer that one?
Yeah. Thanks, Denny. Thanks for the question. I mean, for non-small cell lung cancer, we haven't had any meetings with the FDA since the ODAC, and look forward to discussing the path forward with them and continue to be impressed with the data. I think for the overall tone of how the FDA is reviewing these data, they've kind of given some bookends between the NPC indication and non-small cell lung cancer. Our strategy is to have frequent and often conversations with them and align on the packages.
Thank you, Theresa. Any additional comment with respect to the endpoints of our study or other aspects to Salim's question?
The endpoints that we have are for overall survival with a pre-specified secondary endpoint and was part of the statistical analysis plan, which was designed to meet FDA filings.
Thank you. Thank you for that. I think your second question, Salim, was with respect to second half of the year sales or 2022 sales. Paul, can you offer Salim any additional color on what we see for UDENYCA through the rest of this year?
Yeah. Thanks for your question, Salim. Yeah. You know, I think it's reasonable to expect continued price declines in this market, you know, throughout 2022 as it's becoming increasingly competitive. You know, I think if you look at our ASPs, you know, we've been averaging mid-single digits over the last three quarters. Our strategy has really been to balance price and market share, you know, as we look to optimize longer-term revenues for UDENYCA. In 2022, it's gonna be within the context of the prefilled syringe segment.
We're gonna be ready to go with the launch of an on-body device in 2023, if approved, you know, to go after that remaining 50% of the Onpro market that's, you know, I think just been able to entrench itself through the persistence of COVID. You know, that's what we're thinking.
Hope that answers your question, Salim. We'll be happy to loop back with you, if we have a little more follow-ons to that. Operator, can we have that next question?
Our next question comes from the line of Ken Cacciatore with Cowen. Your line is open. Please go ahead.
Hello, Ken.
Ken, your line might be on mute. Okay. We'll move to our next question, which is Georgi Yordanov with Cowen and Company. Your line is open. Please go ahead.
Hey, guys. Thank you so much for taking our questions. We're gonna limit to one. On the recently announced partnership for the TIGIT asset, could you maybe talk about how do you see it being differentiated from the more advanced TIGIT antibodies that are in later stages of development out there? And then you mentioned your intentions to run trials here in the U.S. in combination with toripalimab and in monotherapies. Could you remind us of the expected R&D costs for that associated with that development and what percentage of that you're responsible for?
Now let me take the last part first with respect to cost, and then I'll let Theresa describe our strategy around the TIGIT. With respect to cost, you may recall that the agreement with Junshi limits our shared clinical cost to $25 million per year per product. That is the same for toripalimab as it is for the opted-in products which TIGIT JS006 is one. We presume that this will be done under the auspices of the Joint Steering Committee of the partnership and subject to those caps. Now, if there's additional work that we wanna do outside of that may be some additional things that is not paid for through the partnership, and then Junshi has the opportunity to opt back into that data later.
Given that this asset, however, will be developed internationally, globally, across all markets, it's probably safe to assume that this will be primarily developed through the Joint Steering Committee of the partnership. With respect to TIGIT development, potential differentiation, and our strategy of going into line, Theresa, would you like to make a few comments on that?
Yeah. I think the data we've seen from our partner, Junshi, on the TIGIT antibody is that it has significant potency in preclinical models. We look to develop it in tumor types such as non-small cell lung cancer, obviously to establish proof of principle in combination with toripalimab with a translational strategy to really understand where we see activity and non-activity to advance it with urgency.
The only other additional color I would provide with respect to the TIGIT is we have developed co-formulated approaches to the product, which would be single vial. Operator, we're ready for the next call.
Our next question comes from the line of Chris Schott with JP Morgan. Your line is open. Please go ahead.
Great. Thanks so much. I'm gonna slip one and a half questions in. Just coming back to the toripalimab discussion earlier, would you run a U.S.-based head-to-head study in non-small cell lung cancer if the FDA required it, or is that kind of a non-starter as you think about, I know you still need to meet with the FDA, but if that's what they're asking for, is that something that makes sense for Coherus or not? And my core question was, coming back to biosimilar Humira. I think there's been a lot of debate about how much volume AbbVie is gonna be able to contract here and how many biosimilars each payer is gonna cover. So can you just elaborate a little bit more on how you think that plays out as you look out to 2023 and beyond?
Do you think it's gonna be in a situation where there's multiple biosimilars, and it's kind of a jump ball, and it's about commercial execution, or do you expect the payers to kinda focus in on, like, one or two biosimilars? Do you expect that AbbVie is gonna be able to retain a sizable portion of the market, or do you expect that a lot of the volume in this space is gonna be available to the biosimilar players? Thanks so much.
Thanks. Thank you for your one and a half. I think you had one and a quarter questions there, Chris, but that's okay. I'm gonna let Paul first address the YUSIMRY, you know, Humira biosimilar question for you, and then we'll loop back on toripalimab. Paul?
Yeah, thanks for your question. You know, at the time of our launch in July 2023, you know, we will expect to be one of a number of biosimilars entering the market at that same time. What we'll be prepared to do at that same time is to bring, you know, a value proposition, you know, that includes those factors that I mentioned in my prepared remarks. A very competitive price, substantial supply guarantees, and all of the prefilled syringe and autoinjector types of presentations. The citrate-free formulation will be another differentiator. I think what we expect to happen is, you know, we're gonna through our payer segmentation not look at them all as a one size fits all, but to fit their particular objectives based on their plans, their covered lives, and their businesses.
To deliver the value proposition that, depending upon the control level of the plan, might be a single biosimilar and a rapid conversion away from the innovator. Or in the short term of launch, you know, Humira plus YUSIMRY, in which case it'll be a slower transition over time. Either way, we'll have, you know, a portfolio of the value proposition that will meet their needs, and we will expect to be, you know, one of the most compelling high volume, low cost providers at the time of commercialization midyear. We expect to do very well.
The other point I would make with respect to that, Chris, is we think with the number of competitors in the market, there's going to be tremendous cost pressure all around. We would be surprised if AbbVie, you know, two or three years into the market, did not have a relatively small share of that market as opposed to a majority greater than 50% share. We think they'd probably get down to the, you know, 20%-25% type of share gain.
With respect to your question on toripalimab and the potential regulatory pathway there in line, we believe it's probably prudent for us not to preempt our conversations, you know, that we haven't had yet with the FDA. As Theresa said, we haven't really had a chance to interact with FDA post the ODAC, and we look forward to doing that. We're convinced that we have a very high-quality molecule that's demonstrating significant efficacy and safety across a number of indications, including lung. We're very enthusiastic about talking to the FDA about that. You know, we really think it's probably not prudent to talk about what sort of studies they might require and when and other types of things.
That being said, though, we are planning on moving into lung with the TIGIT asset in conjunction with toripalimab, and you'll be hearing more of that later in her prepared remarks. Theresa, of course, talked about that and how we are gonna move in towards the end of this year. Stay tuned on that one.
Thank you.
Thanks, Chris.
Our next question comes from the line of Balaji Prasad with Barclays. Your line is open. Please go ahead.
Thank you. Hi, good evening, everyone. Firstly, getting back to biosimilar Humira, can you qualify better the non-stinging citrate-free formulation and what kind of an advantage it provides to you? Also probably importantly, do you expect to be the only citrate-free formulation on the market next year? One, and two, if you can just also quantify with your clinical trials, with the multiple trials going on with $417 million in cash, if you need to prioritize your clinical trials, what will be the top one or two ones that are going to advance next year? Thank you.
Thank you, Balaji. Let me first address the issue of the formulation. It's very important from the viewpoint of patient comfort upon injection that the formulation does not sting, that it's not unduly uncomfortable. There's anecdotal data that patients found the previous low concentration formulation of AbbVie very uncomfortable because it does have citrate. Several years ago, when we approached the Humira biosimilar, which was CHS-1420 at that time, we developed a proprietary non-stinging citrate-free formulation. Now, I won't speak for others, but I think this is very, very important from the viewpoint of patient comfort and being able to penetrate the markets, as Paul said.
Now, with respect to the clinical trials in 2022 and various costs and guides, as McDavid pointed out to you, there are significant spends on matters such as manufacturing. One of the ways that we succeeded with UDENYCA, and you may recall, is we stockpiled 300,000 syringes prior to launch at significant manufacturing expense. It was $25 million or $35 million when we did it. However, I think that served us very, very well post-launch. We were able to do supply guarantees and did very well in that market while others were not able to do so. I think that was one of the reasons why we achieved in excess of a 20% market share in that market. We think that very same formula applies here, for example, with Humira.
We have gone to large scale. We've made those investments. We will be prepared, for example, for fierce competition and price that we have to. We think that we wanna be the team that has the inventory and the supply guarantees to be able to go in the market for that. That's where I think some significant parts of our spend go. On the other hand, we think that's very wise. As McDavid indicated in his remarks, that pays back later. That goes, you know, into costs. It's expense now, but that gives you an advantage, and there's a significant IRR. Hope that answers your question.
Thank you. Our next question comes from the line of Jason Gerberry with Bank of America. Your line is open. Please go ahead.
Hey, guys. Thanks for taking my question. Mine's on the NPC US market opportunity. Can you just talk a little bit about your expectations here with this? Do you expect it to be used more front line with the chemo combination or second line monotherapy? How many of these patients are really addressable? Is it gonna be hard to find these patients because it's a pretty small population? It seems like there's a pretty big swing factor if you're front line versus second line. I think the interim PFS was 12 months for front line, but I think in, like, second line, it was much, much shorter. Just trying to get a sense if you can kind of frame the key parameters of an oncology forecast.
Thanks, thanks for the question on that. Of course, we expect to get front line with NPC. I'll let Paul fill in the rest of your question with respect to the market size and so on. Paul?
Thanks for your question, Jason. As a rare cancer, you know, the data suggests that, you know, there's a couple thousand patients treated with NPC annually, and about a third of those patients, you know, are cycled through in the first-line setting. We expect, if approved, to be the first and only PD-1 antibody approved for NPC, including first-line, you know, that's where we believe we have the potential to establish a new standard of care. Really, in combination with chemotherapy plus toripalimab, it'll be the standard of care in front-line patients. The patients who are treated with chemotherapy only in first-line, it's likely they're gonna progress.
We've got the data in later lines of therapy that we'll you know we'll expect to pick them up later lines. We wanna get these patients treated front line. So there's not a lot of them, Jason, but you know we you know looking at our data with about 1,500 HCPs that we see are using PD-1s for NPC, and they account for over half of the patient volume. We've got Significant overlap with our current, you know, UDENYCA base. We'll have high overlap, very synergistic at the time of launch to drive share voice in the, in the toripalimab, NPC story there. The fact that the data's already been, you know, widely, presented by ASCO Plenary in 2021. The study was published in Nature Medicine last year, and of course, now NCCN guidelines have added it, you know, provides a real tailwind for us going into, potential launch here.
Jason, the other thing we would add here, of course, we'll also get second and third line, and so we're going to pursue NPC quite holistically and we, as Paul indicated, you know, we think we have a very strong case therapeutically with the ASCO Plenary Session and Nature Medicine and so forth. After we get the approval under our belts and we get into the market for a few months, I think your question's fair game with respect to forecasts and so on. We'll be happy to loop back to you.
Can you just remind me in the frontline setting what the PFS was? And when you say 1/3 cycle through first line, so basically of 2,000, only a third of them make it to second line. Was that the point? Or only a third of 2,000 ultimately get treated in the frontline setting?
Theresa, do you wanna grab that one?
Yeah. The PFS in first-line was 11.7 months, with a one-year PFS of 49%.
Yeah, Jason. Of the 2,000 patients treated annually, about a third get treated in the first-line setting.
Okay. All right. Thanks so much.
Thanks, Jason.
Thank you. Our next question comes from the line of Douglas Tsao with H.C. Wainwright. Your line is open. Please go ahead.
Now added sort of your own internal R&D capabilities, discovery, and IO. I'm just curious h ow it's been.
Oh, forgive me, Doug. I think we missed the first part of your question. Could you restart?
Oh, yeah, sorry. You've now started your sort of own internal discovery efforts in IO, it sounds. I'm just curious, as you sort of add to your own capabilities, you know, how do you see your vision for growing the business, you know, versus business development? Obviously, you're gonna be launching a number of products. Your cash flow should be quite significant. Do you have a sort of bias towards now focusing on sort of internally developed assets versus ones that you might wanna acquire? As that cash flow comes in, do you potentially think about you know, business development and M&A more aggressively? Thank you.
That's a great question, Doug. It's very important to us that we have a portfolio that's balanced across all three stages of development, preclinical, early stage development, mid-stage development, represented by, for example, the TIGIT toripalimab combination, and then late stage, of course, with the potential approval of toripalimab. I'll let Theresa LaVallee talk a little bit about our early stage development efforts. To cut to the chase and answer your question directly, we certainly would be open for business development opportunities with IO. There's a lot of opportunities out there, and we have a number of folks who approach us from time to time with various assets. We haven't locked in on anything so far, but we continue to look at them. Theresa LaVallee, you wanna say a few things about our early-stage pipeline?
I think having recently joined, one of the things that really attracted me to Coherus was the people and the talent, in addition to having great assets. What surprised me was how strong the science was and the preclinical aspects and looking at the early pipeline and how well it's been put together and really targeting important aspects of the tumor microenvironment that, you know, the field is really going after broadly. To think about, you know, we have starting on the T cell with you have to have a PD-1, so toripalimab is an excellent molecule. Then coming in with the TIGIT as an important way to really get the T cell activated and have that antitumor immunity. If you have a suppressed microenvironment, an active T cell still is hindered.
I think the portfolio, really looking at that, is gonna be exciting. As we advance the stages, I mean, I'm really looking forward to getting an in-house IND next year and starting an in-house clinical trial.
The other comment I would offer you, Doug, is we will be covering our in-house assets in more detail at our investor meeting. I think McDavid indicated it's going to be around the end of March in New York. We'll bring out some of the key personnel as we're working on this and explain the mechanism of action, a few things that we're doing, so I think you'd find it interesting.
Okay, great. Look forward to the event.
Thank you, Doug.
Thank you. I'm showing no further questions at this time, and I would like to turn the conference back over to Denny Lanfear for any further remarks.
Thank you. We wanna thank you all for joining us today for our end of the year and our fourth quarter conference call. We look forward to seeing you at the upcoming conferences at Cowen and so forth. We also look forward to talking to you in more detail at our investor day event end of March. Thank you.
This concludes today's conference call. Thank you for participating. You may now disconnect.