This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk07: Welcome to CJEN first quarter 2021 financial results conference call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. Please note, this event is being recorded. I would now like to turn the conference over to Peggy Pinkston, Senior Vice President of Investor Relations. Please go ahead.
spk00: Thank you, Operator, and good afternoon, everyone. I'd like to welcome all of you to CJIN's first quarter 2021 financial results conference call. This afternoon, we issued a press release with our results. The press release and supporting slides are available on our website in the investor section events and presentations page. Speakers on today's call will be Clay Segal, President and Chief Executive Officer, Chip Romp, Executive Vice President, Commercial U.S., Todd Simpson, Chief Financial Officer, and Roger Danzy, Chief Medical Officer. Following our prepared remarks, we'll open the line for questions. We aim to keep this call to one hour and to ask that you limit yourself to one question to give everyone an opportunity to participate in Q&A during our call today. Today's conference call will include forward-looking statements regarding future or anticipated events and results, including the company's 2021 financial outlook, anticipated product sales, revenues, costs and expenses, and potential clinical and regulatory milestones, including data readouts, regulatory submissions and approvals. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the difficulty in forecasting sales, revenues, and expenses, impacts related to the COVID-19 pandemic, and the uncertainty associated with the pharmaceutical development and regulatory approval process. More information about the risks and uncertainties faced by CJEN is contained under the caption risk factors, including the company's annual report on Form 10-K for the year end filed with the Securities and Exchange Commission and the company's subsequent reports filed with the SEC. And with that, I'll turn the call over to Clay.
spk11: Thank you, Peg, and good afternoon, everyone. Following a transformational 2020, we continue to make substantial progress in the evolution and global expansion of our business. We remain focused on investments to maximize the opportunity and value of our assets, fueling our ability to advance cancer care worldwide. We look forward to sharing key business, regulatory, and development progress on the call today. We reported record net product sales in the first quarter, representing 3% sequential quarterly growth and 52% growth over the first quarter of 2020. These results reflect rapid adoption of both Padset and 2Kaiza on top of strong sales of Etcetera's. Our financial strength is driven by product sales, as well as royalties and multiple strategic collaborations. We ended the quarter with $2.5 billion in cash and investments, which positions us to expand our programs, advance our research and development, and invest in our business. As we look ahead, we're focused on three strategic priorities to drive continued innovation and growth. Focusing on these key pillars will ensure our organization is aligned and empowered to deliver substantial benefit to shareholders, our employees, oncology health cancer patients. Our first strategic priority is to maximize the global potential of our three approved medicines through robust clinical development programs and exceptional commercial execution. I'll begin with Etcetera, a remarkable product that is the foundation of care in multiple CD30-expressing lymphomas. With six indications in the U.S., Etcetera serves as the basis of our core business. Etcetera is commercially available in 76 countries. Importantly, our partner Takeda continues to pursue additional approval for frontline Hodgkin lymphoma and peripheral T-cell lymphoma in its territories. We are committed to maximizing ETCETRUS' patient reach and are advancing a clinical development program in Hodgkin lymphoma and multiple other malignancies. Our global success with ETCETRUS is enabling us to continue investing in our pipeline in newer medications. Our next key product is PADSAT, a first-in-class ADC that has quickly become standard of care in previously treated metastatic neurofilial cancer. Locally advanced and metastatic urothelial cancer is an aggressive disease with poor survival, high associated healthcare costs, and limited treatment options. PatServe is the first drug to improve survival after patients have received a platinum chemotherapy and a checkpoint inhibitor. Since the beginning of 2021, we've made substantial progress with health authorities toward expanding the U.S. label and securing global approvals across America. Roger will share details about these activities during his remarks. We're also advancing two trials designed to redefine frontline treatment for metastatic neurofilial cancer patients globally with a focus on the combination of PADSEP and Keytruda. And we continue to make significant headway in exploring earlier stages of bladder cancers. In collaboration with Astellas and Merck, PAD-7 is being tested in two randomized Phase III trials in muscle-invasive bladder cancer patients, and we intend to initiate an exploratory study of PAD-7 in non-muscle-invasive bladder cancer. Our third key product is to customize a best-in-class HER2 tyrosine kinase inhibitor for HER2-positive metastatic breast cancer patients with and without brain metastasis. Tucaisa is now approved in 36 countries. In February, the European Commission approved Tucaisa in the EU, granted its marketing authorization in Great Britain. This is a significant milestone for patients in Europe who will, for the first time, have an approved medicine that has demonstrated a survival benefit for HER2-positive metastatic breast cancer after disease progression following two anti-HER2 treatment regimens. In anticipation of these approvals, over the past year, we've established affiliates in key European countries and built teams with deep industry experience. We recently launched Tecaisa in Germany, France, and Austria. We're pleased by the early uptake, physician feedback, and that Tecaisa has already been included in some key treatment guidelines given the strength of clinical evidence. Through our expanded European footprint, we are poised to execute upon another upcoming CHISA launches and collaborate with individual countries to maximize its ability, availability, and patient access. We are conducting a broad clinical development program design, including trials evaluating it in HER2-positive breast, colorectal, and gastric cancers, and in HER2 mutant tumors. Our second strategic priority is to advance our late-stage programs towards securing approvals for new products. One such asset is Tisodum abdodum, or TB. Earlier this month, FDA accepted for prior review our BLA seeking accelerated approval for TB with an action date of October 10th. The submission comprised data from the innovative 204 pivotal phase 2 trial, which was published in The Lancet Oncology. This is an important development in the treatment of cervical cancer, which remains one of the leading causes of cancer death in women globally. TB is positioned to be our fourth commercial product as we look to expand our portfolio further, and together with our partner, GenMab, we are preparing for its launch. Our third strategic priority is to advance our innovative early stage pipeline through continued leadership and innovation in antibody drug conjugates, internal R&D investments, and corporate development opportunities. Our earlier stage pipeline includes seven programs in clinical trials and multiple preclinical assets advancing toward INDs. I'm proud of the remarkable progress we've made in growing and evolving our business and assets to better meet the needs of cancer patients. Next, I'll turn the call over to Chip, who will discuss our commercial business. Then, Todd will provide an overview of our quarterly financial results. After that, Roger will detail our clinical development and pipeline progress.
spk13: Chip? Thanks, Clay. Our three approved products are important first-in-class or best-in-class medicines that have been embraced by oncologists and patients. We believe that each of the brands have blockbuster potential, and we continue to invest in our commercial capabilities to ensure we can maximize the opportunity to gain future approvals and label expansions. We are engaging with our customers through multiple channels and are pleased that most of our sales representatives have been able to safely return to making face-to-face calls. At Cetra Sales, we're $163 million, a 1% decline versus Q1 2020. The COVID-19 pandemic continues to impact Hodgkin lymphoma diagnosis, but we are seeing early signs of recovery. And despite this headwind, we've maintained share in our frontline indications. We are monitoring these trends, and it is our expectation that diagnosis rates will return to historic norms. We continue to message the landmark five-year Echelon 1 progression-free survival data in frontline Hodgkin lymphoma. We are encouraged by the favorable reaction to the data we received during recent market research with physicians. Moving on to PADSEV, first quarter sales were $70 million, double the first quarter of 2020. We are pleased with our quarterly growth after a strong launch. Our efforts continue to focus on promoting the full breadth of the PADSEV label. The locally advanced metastatic urothelial cancer marketplace is rapidly changing. and we are confident that PADSEV is well-positioned this year for continued growth as the market evolves. Our sales representatives have been proactive in educating healthcare providers on our label update, and customer sentiment remains positive on PADSEV's risk-benefit profile. Transitioning to Tecasa, first quarter sales were $70 million, an increase of 14% over last quarter. These results are in line with our expectations, given the challenging Q1 patient co-pay dynamics of oral oncolytics. We continue to gain market share in both patients with and without brain metastasis. Tecaisa provides an overall survival benefit for patients with and without brain meds, and we are confident that we can continue to drive share gains for all patients. Tecaisa is now the most utilized product in second and later lines for HER2-positive breast cancer patients with brain meds. And finally, we are very pleased to receive a priority review for TB. A brand team is in place, and we are working closely with our co-promotion partner, GenMed. We will be ready for a launch ahead of the October 10th PDUCA date. If approved, this would be an important new drug for women with metastatic cervical cancer, and we look forward to adding it to the proven C-Gen commercial model. Now, I'll hand over to Todd.
spk17: Great. Thanks, Chip. And thanks to everyone for joining us on the call this afternoon. Our financial results for the first quarter reflects significant progress across the business. I'll briefly summarize our financial results for the quarter, which are in line with our expectations for the full year. Total revenues were $332 million in the first quarter of 2021. This included net product sales of $303 million from Etcetera's Pad 7 to Kaisa, representing growth of 52% over the first quarter of 2020. Growth in product sales is driven by the continued strong uptake of Pad 7 to Kaisa since their launches in the U.S., Royalty revenues in the first quarter of 2021 increased to $27 million compared to $20 million in the first quarter of 2020. This growth reflects royalties earned on increasing sales of Etcetera by Cicada, as well as royalties on sales of Polo V by Roche and BlendRep by GSK. Collaboration revenues were $2 million in the first quarter of 2021 compared to $16 million in the first quarter of last year, As discussed when we gave our 2021 financial guidance, collaboration revenues are primarily driven by progress-dependent milestone payments from our collaborators, which causes quarterly variations in revenue. In the future, we expect collaboration revenues to reflect the profit share from Stellis from sales of PADSEV in its territories. Cost of sales in the first quarter of 2021 increased to $64 million. This included product cost of sales and royalties for each of our three brands, the PADSEV profit share of $33 million to Astellas, as well as non-cash amortization of acquired technology costs for Takaida. R&D expenses increased to $230 million in the first quarter of 2021. This reflects continued investment across our pipeline to drive progress of our late and early stage pipeline. SG&A expenses increased to $160 million in the first quarter of 2021. This reflects commercialization efforts related to the launches of Pad 7 Takais in the U.S., as well as investments to support the launch of Takais in Europe. We ended the first quarter with $2.5 billion in cash and investments, and we have no debt. This positions us strongly to advance our plans in 2021 and beyond. And lastly, our financial guidance for 2021 is unchanged. With that, I'll now turn the call over to Roger.
spk02: Thank you, Todd, and good afternoon, everyone. I'm happy to share today key R&D activities for our approved medicines as well as our pipeline programs. I'll start today with PADSIP. As a reminder, PADSIP has accelerated approval in the United States for metastatic urothelial cancer patients who have previously received both platinum-based chemotherapy and a checkpoint inhibitor. The randomized Phase III EV301 trial, which compared PADSIP to chemotherapy in the setting, demonstrated a clinically meaningful and statistically significant 30% reduction in the risk of death among patients who received PADSET. These data were presented at ASCO-GU and simultaneously published in the New England Journal of Medicine. The EV301 data were also submitted to FDA in a supplemental BLA under the real-time oncology review and Orbis programs. And this month, the application was accepted for priority review with a producer date of August 17th. This application seeks to convert PADSAVE's accelerated approval to regular approval and integrate into the label the important overall survivor data that PADSAVE has demonstrated. To address the potential for PADSAVE in metastatic patients who've received a checkpoint inhibitor and are cisplatin ineligible, we conducted cohort two of the EV201 pivotal trial. Positive data from this cohort were presented at the ASCO-GU meeting in February. Earlier this month, FDA accepted our supplemental BLA to potentially expand the U.S. label to include this population. The application is also being reviewed under our tool and has been given priority review with the same PDUFA date of August 17th. An abstract, including additional follow-up data from cohort two, will be reported at ASCO in June. Our strong PADCET data have enabled substantial regulatory progress outside of the United States. In the past two months, we and Astellas have engaged with eight regulatory authorities around the world, and marketing applications are currently under review, including in Australia and Canada, with Health Canada signing priority review. In the EU, where the application has been assigned accelerated assessment, importantly, this could shorten the time to approval. And lastly, in Japan, Brazil, Switzerland, and Singapore. We continue to advance a substantial PADSEV clinical development program, which includes two trials that could support approval in first-line metastatic urothelial cancer. We expect to complete enrollment of cohort K of the EV103 trial in cisplatin-ineligible patients receiving PADSEV plus Keytruda by the end of this year. And if data are supportive, we plan to submit a supplemental BLA after appropriate follow-up for duration of response. In addition, we continue to enroll patients into the Phase III EV302 global trial, which includes both cisplatin-eligible and ineligible patients, evaluating PADSEV plus Keytruda compared to a platinum-containing chemotherapy regimen. These trials are supported by initial data from the EV103 trial, which resulted in breakthrough therapy designation. Updated durability results and long-term outcomes from these initial data will be presented at ASCO. As we move PADD7 to earlier stages of bladder cancer, two phase three trials are enrolling patients with muscle invasive disease. Both trials utilize PADD7 in combination with Keytruda. The Keynote B15 trial, also called EV304, is enrolling cisplatin-eligible patients, and Keynote 905, also called EV303, is enrolling cisplatin-ineligible patients. Additionally, we continue to work to bring PADSEV into a clinical trial for non-muscle-invasive bladder cancer patients and have completed our initial regulatory discussion with FDA. In summary, we are making great progress with PADSEV. Turning now to Takaiza, the development team is advancing a similarly broad clinical program to support label expansions in breast cancer and investigate Takaiza in other HER2-positive cancers. In breast cancer, we are evaluating Takaiza plus Capsyla in first- and second-line metastatic patients in the HER2-clin O2 trial. Additionally, we are pleased to report that the first patient was recently enrolled in the randomized COMPASS HER2-RD trial being run by the Alliance Cooperative Group, evaluating tuchiza trascalcila in high-risk adjuvant breast cancer patients. In GI cancers, we are on track to complete enrollment in the Mountaineer trial by the end of 2021. This trial is intended to support accelerated approval in the United States for patients with advanced HER2-positive CRC. Also, we are advancing to Kaiser in several exploratory studies, including in combination with an oxalic-platin-based chemotherapy regimen in first-line GI cancers, in a basket trial for solid tumors with HER2 alterations that include mutations, and in combination with HER2 for HER2-positive breast cancer. Moving on now to et cetera, we are excited that the Echelon 1 five-year manuscript has now been accepted and we anticipate publication in the coming weeks. Results demonstrated robust and durable remission in patients with newly diagnosed advanced Hodgkin lymphoma who received et cetera in combination with ABD. five years free of disease progression is a clinically meaningful and important milestone in a cancer patient's journey. Going forward, we continue to invest in the development of etc. for several ongoing clinical trials. Notably, we have a randomized phase three trial in diffuse large B-cell lymphoma, exploratory evaluations of ectetras plus nivolumab plus AD in frontline advanced and early-stage Hodgkin lymphoma, and we are exploring ectetras in combination with Keytruda as an immunomodulatory agent in solid tumors. Now I would like to turn to our late-stage program to Sotinabidocin, which we are developing in collaboration with GenMed. Earlier this month, we announced that FDA accepted our BLA seeking approval of TB for treatment of women with recurrent or metastatic cervical cancer. The FDA has assigned a priority review, and the producer action date is October 10th. We believe TB could make a meaningful difference to these patients where there is such a high unmet need. We also recently initiated the innovative 301 Global Phase 3 trial in a similar population of recurrent or metastatic cervical cancer patients that is intended to support global regulatory applications and serve as the confirmatory trial in the United States. Turning now to Liduratuzumab-Lidotin, we continue to work with our partner to co-develop LV as monotherapy and in combination with Keytruda in live one expressing solid tumors. Our clinical development program is focused on optimizing dose and schedule as monotherapy and in combination with Keytruda in breast cancer. A basket trial is also currently enrolling patients with lung, head and neck, prostate, esophageal, gastric cancer, and melanoma. Across the rest of our pipeline, I'd like to summarize a few recent highlights. At the AACR meeting in early April, we presented several compelling preclinical data sets of our Phase I clinical programs. This included SEA-TIGIT, where we showed the enhanced anti-tumor activity when combining SEA-TIGIT with a checkpoint inhibitor or a vedotin-based ADC. In addition, we described encouraging preclinical data with SGN-B6A and SGN-STMV, both of which are novel vedotin-based ADCs that have recently entered the clinic. We also entered into a clinical trial collaboration with Pfizer under which we will evaluate SEA-TIGIT in combination with Sarsenimab, their subcutaneous PD-1 inhibitor. The combination will be evaluated as part of our ongoing Phase 1 SEA TIDGE trial in advanced solid tumors and lymphomas. And lastly, we completed enrollment in our clinical trial evaluating SEA CD40 as part of a combination regimen for the treatment of pancreatic cancer. We expect to report clinical data from the trial sometime later this year, which will inform next steps with this novel effect-to-function enhanced non-fucosylated antibody that binds CD40. In closing, we have achieved many important milestones and have made significant progress across our pipeline in the first quarter of 2021. We look forward to providing you with further updates as the year progresses, and now I will turn the call over to Clay.
spk11: thank you roger the past year has been pivotal for cgen and the company is well positioned for the future today we have a deep and diverse pipeline a multi-product commercial portfolio and additional potential approvals on the horizon additionally we have powerful partnerships a broad geographic footprint and substantial financial strength to maximize our assets from our early stage pipeline to our expanding portfolio of approved medicines. The solid foundation we have built sets the stage for CGEN's next phase of innovation and execution. I am confident in our ability to continue delivering cutting-edge innovation and medicines that make a meaningful difference to the lives of cancer patients. I would like to thank everyone listening to this call for your continued interest in CGEN. Operator, please open the line for Q&A.
spk07: We will now begin the question and answer session. To ask a question, you may press star then 1 on your touch tone phone. If you're using a speaker phone, please pick up your handset before pressing the keys. To withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster. Our first question comes from Jeff Meacham from Bank of America. Please go ahead.
spk08: Hey, guys. This is Greg Harrison for Jeff. Thanks for taking our question. The question is, what sort of physician reception have you seen with respect to pets after the cases of Steven Johnson syndrome that came out? On our end, we've heard KOL saying it won't affect prescribing much and they can screen out the higher risk patients, but just wanted to see what you guys are hearing on your end.
spk11: So, Greg, thank you for the question. You know, PADSEV has really delivered a very strong launch with rapid penetration into our labeled indications following its approval right at the end of 2019, so really full year of 2020. You know, concerning the label, safety is always a top priority for us, and label updates inform physicians on what to do and how to work with patients to prevent anything from happening. Our sales reps have been educated. Healthcare professionals have been updated and educated, and physician sentiment remains very positive on the risk-benefit profile, the very positive risk-benefit profile with PADSF. It has not been an impediment to adoption. It is a very rare occurrence, and it has not changed practice on use of PADSF. Roger, did you want to add anything to that?
spk02: Thanks, Clay. So the label, you know, skin reactions have been part of the PADSF safety profile for some time. And so this was an important sort of post-marketing observation that was just extended into the label. So, you know, from the beginning, we messaged very carefully around safety. It's important. Most of the side effects are transient and reversible. And, you know, we think it's valuable for physicians to understand this. So, again, from a medical perspective, this does not change the risk-benefit for PADSET, and we believe it will continue to be used. And we certainly haven't changed any of our clinical trial plans.
spk08: Great, thank you.
spk07: Next question comes from Matthew Harrison from Morgan Stanley. Please go ahead.
spk01: Hi, Clay and team. This is Connor on for Matthew. So on TESO, could you comment on the outlook for the Keytruda combination and I guess how quickly you could move that into a registrational program? And then quickly, are you seeing any competition from Trideldy? And what are your expectations for the impact on that drug to pass up? Thank you.
spk11: Okay, thank you. So two completely different questions. One is on TV plus Keytruda. So let's start with that. So we're very pleased with how TV is moving along. You know, as we said, we took to Sotomayor TV, and we have submitted it, and we now have a due date. We have, you know, with, you know, the accelerated approval timelines. So we're pleased with that. And the current therapies for metastatic cervical cancer are really poor. They're generally with response rates of less than 15%, median OSs between six and nine and a half months. So it is a significant unmet need, certainly in the US and around the world, incredibly significant. And so our program includes a big part of it, which is combining with Keytruda, and chemotherapy. So we have multiple arms there. And that's in earlier lines of cervical cancer. And so we're very pleased with the success there of getting patients to the trials and, you know, putting together a real opportunity there. We have not presented any data yet, but the trials have been going very well. and we will be at an appropriate time presenting the data and information on these and making decisions to whether or not you go to a pivotal trial. It's my hope that we see great data and we go into a pivotal trial to try to get to try to get the kind of data that you could submit for earlier stage cervical cancer, which could be really beneficial to patients and also a substantial market. Roger, do you want to add anything to what we're doing with TB and Keytruda? Right.
spk02: So, Clay, exactly as you say, we have a monotherapy path for approval, which is currently under review, and that same monotherapy in late-line cervical cancer with a global trial that's running, But, of course, our interest is in combinations as well in order to move into earlier lines of therapy. And I think we're well positioned with regard to the way, you know, we're evaluating combinations of chemotherapy and Keytruda such that if we do get positive readouts, we can take those combinations forward into, you know, further clinical development.
spk11: So your second question is about competitive impact of Tridelvi. First of all, I want to say that we are very pleased that there are more options for patients. We are a very patient-friendly company and think about how best, you know, providers and doctors can treat patients with life-threatening diseases. So the more, the better for patients. So second of all, PADSET has become the standard of care and it's approved in the case. It's really entrenched in the metastatic post-platinum, post-PD1.
spk10: And PADSEV has shown, oh, you know, it is – we're very pleased with where PADSEV is in the lineup.
spk11: Now, Roger, you may be able to discuss any updates or thoughts connected with that.
spk02: Sure. So, you know, as Clay indicated, you know, the more treatments that are available for patients, the better. However, the PADSEV program, which is substantial, has already, you know, created – You know, the use of PADSEV in a specific line of therapy, and it is, as you say, essentially a standard of care, which is difficult to display. So we're glad that Tredelvi is there. However, we do see PADSEV having a very strong value proposition. The next question, Ms.
spk07: Sachs. Please go ahead.
spk12: Thank you. Maybe just a question on Tucaiza here. You noted that it's the most utilized product in second-line positive HER2 positive patients with brain mets. Can you just comment on what you're seeing in the same setting in patients without brain mets?
spk11: Sure. So thanks for the question on Tucaiza. As you know, Tucaiza is approved for patients with visceral disease as well as patients with brain mets. And we are certainly using it in both patients and getting a lot of uptake there. Chip, could you comment a little bit on either the dynamics in the market of using Teqiza in brain mets and in patients with visceral disease?
spk13: Yeah, thanks, Glenn, very much. So we're pleased with the progress that the Kaiser is making. We're seeing both increased utilization in patients with and without brain mites. We're now the most used product in second line and beyond for people with brain mites. So, again, uptake has been robust on visceral mets as well, and it continues to grow.
spk12: Thank you.
spk07: The next. Question comes from Corey Kazimoff from J.P. Borgen. Please go ahead.
spk20: Hey, good afternoon. This is Turner on for Corey. Thanks for taking my question. So just one on the Phase I SEA CD40 study. And, you know, as you mentioned in prepared remarks, enrollment completed with around 159 patients across a bunch of different tumor types. Can you just give us a sense of how many tumor types moved into expansion cohorts, or was it just pancreatic cancer? And also just assuming you see signals with indications like pancreatic later this year, what do you see as potential next steps? Thanks.
spk11: Sure. So I have in previous calls talked about my interest in it. It's just such a huge unmet medical need and how that's something that I felt, you know, as a cancer biologist and someone making cancer drugs. but I was really hopeful that we could make an impact on pancreatic cancer patients. So certainly that's been an important part of this study. Roger, can you talk a little bit about, you know, where we are with SCA-SB40 in our plan? And, you know, later on this year, we are, you know, planning. I think we committed to presenting data for SEA CD40 sometime this year. Now, that does not mean that we're going to wait to making that. We can make programmatic decisions at any time and meet with regulators at any time and try to go forward on this, you know, really emerging, exciting program. But, Roger, can you talk a little bit about what we're looking at in our arms before making any decisions on pivotal trials?
spk02: Sure. Yeah. So the CD40 program began as essentially a monotherapy program. We have an active agent. We have responses based on monotherapy. We then pivoted the program from monotherapy into a combination approach. and that initial focus is in pancreatic cancer. So we are interested in testing CD40 plus chemotherapy plus a PD-1 inhibitor in frontline pancreatic cancer, and that's the data that we will be focusing on. However, from a biologic and sort of scientific perspective, we are interested in the construct of combining a CD40 ag together with some form of cell killing through chemotherapy, together with a PD-1 inhibitor. So we are working on plans potentially to look at other possibilities for further CD4D development, but the initial focus in the combination space is pancreatic cancer.
spk07: The next question comes from Michael Schmidt from Guggenheim. Please go ahead.
spk03: Hey, guys. Thanks for taking my question. I had another one on the early stage pipeline, specifically on the titchet antibody. It looks like other titchet antibodies have had rather similar single-edge negativity in phase one studies with a few antigo responses seen there. I guess, to what degree would you expect an antibody like yours with enhanced effect or function to potentially improve upon these competitor molecules?
spk11: So thank you for the question on our SCA digits. So we're just studying it now, so we've not reported any data at this point. But pre-clinically, we saw that we had a very high effector function because it uses our SCA technology, which we've talked about before, how that augments effector function while decreasing the inhibitory effector function. So I'm not going to go through all that again since I've talked about it a lot. But we are very excited to take our drug into clinical trials. The hope of any drug is to see single-agent activity, and then the hope of any drug is that not only does it work in single-agent activity, but we have a lot of plans on what to do in combination with a PD-1 inhibitor and with a single agent. And so we're working on advanced solid tumors and lymphomas, and we're cranking forward. And so I look forward to a time where we're presenting data.
spk07: Okay, thank you. The next question comes from Andrew Behrens from SVB LearLink. Please go ahead.
spk18: Thanks. I wanted to see if you guys would give us some color about the presentation. I guess it's Cohort K that's going to be at ASCO. Will it be a larger sample size than what you presented previously, or will it be the same 45 patients with a longer follow-up?
spk11: You know, I'll turn it over to Roger for that. Roger, how about you addressing that?
spk02: Yeah. So, Andy, thanks for the question. It's actually cohort A. So it's the original data set, some 45 subjects that we saw that initial remarkable signal. And the data we presented has been mature. It's even more mature now, and we're excited to bring that forward so you can see what the what the long-term outcomes look like with this combination of PADC plus Keytruda in cisplatin ineligible patients with cancer. So it's not COVID-K, it's COVID-A.
spk18: Okay. I appreciate it.
spk07: The next question comes from Kenan McKay from RBC Capital Markets. Please go ahead.
spk19: Hey guys, congrats on the quarter. An elaboration on a prior question and then a separate question. Roger and Claude, you've mentioned completing that SEA CD40 study in pancreatic cancer data later this year and but it has seemed like you're excited about this one, but just hoping you can contextualize a little bit more, you know, what is the win here? Is being stable disease enough to get excited in pancreatic cancer, given the huge, huge, huge unmet medical need that was mentioned, or do you really need to see responses to really have conviction there? And then just on TAGSA, wondering if you could help us with the breakdown of the bladder cancer market and the incremental size of that metastatic and locally advanced bladder cancer market that was previously treated with a PD-1 or PD-L1 but is ineligible for cisplatin. Just trying to think about the incremental add from that SDLA that we're expecting to come online later this year.
spk11: Thank you. Sure. Can you talk a little bit about the question Kenan asked about what we can expect with the potential additional market?
spk13: Yeah, absolutely, Clay. So this is a smaller segment of the population, but nevertheless I think a meaningful number of patients. There is an important unmet need given these are typically older patients. They suffer from multiple comorbidities like poor kidney function. We are already seeing some unpromoted utilization, but we think there's a remaining opportunity once we get labeled to promote to.
spk11: So going to your question on pancreatic cancer, Kenan, You know, there are a lot of things you can look at. Now, the study we have enrolled and will be presenting data on will provide us a lot of information on ORR, objective response rate. And just for reference, the gemabraxane ORR is about 23%. So, you know, if we come in with 24%, it's not going to be meaningful. So it has to be substantively above the 23%. Second of all, we want to look at the duration of response. We do that with every drug we do, whatever disease it is. We look at duration of response. And you don't want a duration that's super short because that doesn't really help patients. It's not that meaningful. And, you know, the regulators also want to see duration. So we want to see it for ourselves in this lead-in trial. And then You know, the other thing is we want to, you know, try to take an initial look at saying, you know, can we learn anything about OS? Now, it's not a randomized study. That would be the next study we did. well cataloged information on pancreatic cancer and what OS is. So we think we'll get a handle on that and be able to say, okay, we have ORR, we have duration, and we have some trends in OS because it's not going to be statistically meaningful to our data. That would happen next. But we have trends there. And we saw these kind of things in other drugs we developed, and it's important to look at them and say, how are you doing in all these really critical data sets? And that's what we've been doing, and I have gone on record saying I am really interested in this and excited about what we're seeing initially. To that extent, we publicly said we're going to expand what we're doing. Pancreatic cancer, a lot of people in history have seen data on a little bit, a few patients, and once you go to a lot of patients, it hasn't really panned out. So we're trying to be appropriately – studying this to know, you know, in an expanded population from our initial, you know, evaluation, will the data hold? Will it be exciting? And should we go into a pivotal trial with it? And this is something, is the way this is not to S40. This is something we've done with other drugs and expanded what we've done and get a really good handle. And I think that by doing these expansions, studies of single-arm studies, your hit rate of phase threes in randomized studies is much higher. And I think that our hit rate historically has been high once we get some additional conviction based on a little bit bigger study and not just a tiny study. So that's what we did with this. We had a very small amount of data. We were, you know, I was, you know, speaking for myself, I was excited with it. The clinical team here wanted to really be sure of what we're seeing. So that's what the data that will come out is. Roger, do you want to have any comments on this?
spk02: I think so. It is a single-arm experiment, and obviously the key points are exactly as you say. What's the rate of response? What does progression-free survival look like? And what does overall survival look like? And there is a very clear record of what to expect with standard care. If we see positive data, we'll be able to make some decisions about what a potential next step could be.
spk19: Awesome. Thank you guys so much. That's very, very helpful.
spk07: And that's something I'd come to be excited about. The next question comes from Gina Wang from Barclays. Please go ahead.
spk04: This is Sheldon for Gina. Thanks for taking our question. Maybe just one quick question about Europe. We're glad to hear that you have launched in Germany, France, and Austria. So what do you see the potential ramp-up there over the course of the next year? How many additional markets will you expect to enter? And also a related question on price of your potential European launch. So do you expect the launch pace to be roughly the same?
spk11: So first of all, thank you about the Kaiser question about Europe. We are very pleased with our progress. Kaiser is now approved in 36 countries worldwide, and that includes the EU and the UK. We have general managers in the major countries. They're building teams. They have deep industry experience. We have done commercial launches now, as we've said, in Germany and France within one month of the EMA approval, so that's brand new. We are working to make Tatais available as quickly as possible and feasible in all the European countries. But we have to navigate the local HTA processes. So that takes time. They don't all come on at once. I mean, this is, you know, a little bit of a different process than in the U.S. where, you know, you could say that once U.S. approvals, all states are approved. But in Europe, you have to go one at a time at a time. And we don't just do them sequentially. We're working on it at the same time. But it still is not all at once. And then with regard to the U.K., we are actively engaging with the organization called NICE, with a decision expected in the fourth quarter. Very big efforts to get it into all these countries, with just a few of the countries recently having commercial launches. And, you know, so right now we expect the majority of Takai's revenues to come from the U.S., and that's what we are for now. But, you know, in the future we expect more and more to come from Europe.
spk07: The next question comes from Steven Wiley from Stiefel. Please go ahead.
spk15: Hi, this is Ellen on for Steve. So I understand decatinib is being evaluated in combination with N4. So I'm just curious what the bar for success is there and maybe how you're thinking about the safety profile of this combination.
spk11: Sure, absolutely. you know, we think that Tecaiza is a great drug to combine with and use, you know, in a lot of different regimens. Roger, can you talk a little bit about what you're thinking with Tecaiza and R2?
spk02: Yeah, so both drugs are highly active, and obviously combining active drugs in oncology is a potentially fruitful path in terms of trying to find effective combinations. And just bear in mind, because in HER2 is trastuzumab plus chemotherapy, it's essentially the same sort of conceptual construct as was in HER2 prime, where we combined ticatinib with trastuzumab and chemotherapy, which is capecitabine. So it's following the path, frankly, that we are taking with ticatinib in multiple other places. I don't think we've set any bars. We need to explore. And we'll see, you know, once we have some data to hand, we can determine whether you know, what potential value that regimen, you know, may have as a combination. From a safety perspective, again, I don't think we have any expectations one way or the other. I don't think we're expecting amplification of safety from either side. But we need to generate the data, and then we can evaluate.
spk15: Okay, great. Thanks for taking the question.
spk07: Next question is from Andy Shea from William Blair. Please go ahead.
spk06: So, Grace, thanks for taking my question. So I'm just wondering if you could elaborate on your strategic positioning for SG and CD30C. Would that be kind of an improved product to the medical community, or, you know, you would be exploring areas where you actually are not as amenable to be targeted by et cetera?
spk11: So I appreciate very much the question. We definitely have second generation molecules that we're working for et cetera. There's actually a few of them that we're working on. And one of them we call C, as you refer to. But there are some different molecules. Quite frankly, they're all exciting. it would not be impossible for us to take more than one to phase one study and compare them there and then decide which one to go with. So I don't want to rule that out either. There are some, you know, technologies that I'm not at liberty right now to explain exactly, but, you know, I think are exciting. You know, I have a unique perspective and having been one of the pioneers in this field and building it up and the fields now really taken on a life of its own. And it's a lot of companies now work on ABCs. So I look in the past and some of the ABCs and how they were made were with bad linkers and natural product drugs, and I call that 1.0. And then there was, you know, better drugs, synthetic drugs, and much better linkers that are in drugs like et cetera, and Pasev, and Polovi from Roche, and others. And so I call that, you know, ADC's 2.0, if you will. And then how will we get, as a field, to ADC's 3.0? And what can we do? And what are the technologies that are needed to continue improving the efficacy in patients and decreasing any of the side effects that you have? That's always the goal. Or what the docs say, getting a better risk-benefit ratio. And how can we do that? And what can we do? So we've spent many years that we have, and I am really jazzed up about these new technologies based on all of their preclinical data in efficacy and in safety, including non-human primates. So I think what you'll see from us is another generation of new ADCs that may have different payloads, different linkers, different ways of thinking about how to do these different toxicities or lack thereof, and those are coming. So we are working hard on ADC 3.0, so stay tuned. We'll be talking about it as soon as it's appropriate to.
spk07: The next question comes from Jay Olson from Oppenheimer.
spk09: Please go ahead. Oh, hey, thanks for taking the questions, and congratulations on all the progress. Since you have an October PDUFA for TV, can you talk about some of the work that you've done to prepare for the launch, including anything on? And then separately, as you look across your broad product portfolio and pipeline, do you see any gaps that you want to prioritize for business development purposes? Thank you.
spk11: Okay. So the first questions on TV and launch and reimbursement and all the rest, You know, we certainly have submitted and we're certainly working with regulators on this. We have a PDUFA date. We're working on, you know, combinations with Keytruda and with chemotherapy. We've talked about that already in the call. So there's a lot going on that, you know, we'll work on, you know, and we'll continue to work on in front of our PDUFA date of October 10th. But, you know, we're really excited that this could be our fourth drug. And we think it's something we understand. We know how it helps patients. The confirmatory study is continuing, and we've planned enrollment in the U.S. and abroad. And, you know, certainly when you look at the commercial planning, we will go ahead and make sure that this gets launched. We're working with our partner, GenMap, on this. Chip, do you want to have a brief comment? I don't want to say too much about this. It's a little early, and it's, you know, it's also bad. I don't think, you know, we want to outline too much yet. We're, you know, just got only a few weeks ago, we got accelerated status for approval. So, I don't want to get, you know, ahead of where we are. But, Chip, can you give some general comments?
spk13: Yeah, sure, Clay, absolutely. So we have key personnel in the commercial organization in place. They've been in place for some time now, and have been working to make sure that we're launch ready by the time of the PDUFA date. Like Clay mentioned, we're looking forward to also pulling some of the best practices that we've had in the PADSA event to Kaisa launches.
spk07: The next question comes from Ben Benjamin from J&P Securities. Please go ahead.
spk05: Hey, good afternoon, guys. Thanks for taking the questions. I guess mine is regarding the non-muscle invasive opportunity. Can you maybe provide some color regarding the discussions with the... The trial is planned for BCG on responsive patients, but do you have any thoughts on moving that either in combination or potentially supplanting BCG?
spk11: Sure. Thanks, Ren, for the question. Roger, do you want to... Can you address what we can talk about now?
spk02: Sure. So non-muscle invasive bladder cancer is a large unmet need. As you point out, BCG Unresponsive is the place to begin. But depending upon what the product's profile looks like in terms of its efficacy and safety, There's always a possibility to, you know, consider combinations, and a lot of folks are going with combinations with BCG or potentially, you know, looking for, you know, a new gold standard. What's attractive about PADSEV in terms of its possibility, and it is just at this point a possibility, is that in the preclinic experiments that we've done, We have almost no systemic exposure, and that's an important part of the equation for patients who are not going to die necessarily of the bladder cancer, but need it to be managed and try. That's the one point. The other is that the target, which is next in four, is highly expressed not only in the advanced and metastatic populations and in muscle-invasive, but in non-muscle-invasive as well. So we have an opportunity to instill PADSA tests, you know, giving intravesical PADSA to see if we can, you know, gain control first of BCG unresponsive. And then if we have a strong, you know, positive benefit risk that we would like to take forward, yes, we would clearly want to develop it further. Okay.
spk07: Thank you. The next question comes from Chechong Zhu from .
spk21: Hi, thanks for taking my question. I have a quick one on your CD40 antibody. Can you talk about the biology on that target, that why you think your sugar engineered FCE enhance antibody can work better than other antibodies? I think field seems like the side effects could be the issue, I guess. Why do you think FCE enhance could maybe avoid that problem. Thank you.
spk11: It's positive how to address this, but what we're looking at is trying to enhance the activity that you get through effector function and also decrease the inhibition that you get. When you look at PD-1s, they release the brake on T cells, so it's a very fine balance between getting more activity but releasing inhibition, and we think that our SCA technology does have some properties that no one else has, and we've observed them in preclinical models, and we've talked about them a lot, and so we're really excited about it. Now, the proof is in the pudding. We have to go and we have to test this in humans that have cancer, and see what we, you know, obtain, both on safety, because we're very, very, you know, cautious about making sure we're safe in patients and really transparent about that, but also in efficacy and seeing what happens. And in addition to working with this as a single link, there's a lot of efforts going on to bring it in combinations. And, you know, that's something with the PD-1 inhibitor, and that's something that's important as part of the trial. So we're bullish on the molecule, we're bullish on our technology, and we're hopeful, but we're not ready to discuss or present the data.
spk07: Thank you. The next question comes from Brad Canino from Credit Suisse. Please go ahead.
spk16: Thank you. I want to ask, is some of the moderation in the PADSEV cells growth over the past three quarters due to patients being too sick to continue to a third-line therapy and not getting the opportunity to try PADSEV? And then more broadly, Clay, how do you think about the low systemic treatment penetration in metastatic bladder cancer overall, and then maybe how PADSEV can change that when it gets approved in earlier lines?
spk11: Okay, so these are questions that I certainly want Chip to answer. to comment on. Chip, do you want to see how you can answer this?
spk13: Yeah, absolutely. So it's not uncommon at this stage of a launch to see product growth begin to decelerate. PATSEP is a standard of care. We are very optimistic about the change. changing market dynamics in this marketplace. PD-1s and PD-L1s have moved up utilization into the front line. We think that's going to continue in 2021, which will provide PADS-EV an opportunity to increase its treatable patient population.
spk07: There are no more questions in the queue. This concludes our question and answer session. I'd like to turn the conference back over to Peggy Pinkston for any closing remarks.
spk00: Okay, thank you, Operator, and thanks, everybody, for joining us this afternoon. Have a great evening.
spk07: The conference is now concluded. Thank you for attending today's presentation.
Disclaimer