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Seattle Genetics Inc (NASDAQ:SGEN)
Q3 2019 Earnings Call
Oct 29, 2019, 4:30 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good day, and welcome to the Seattle Genetics Third quarter 2019 Financial Results Conference Call. [Operator Instructions]. At this time, I would like to turn the conference over to Peggy Pinkston, Vice President of Investor Relations. Ma'am, please go ahead.

Peggy Pinkston -- Vice President-Investor Relations

Thank you, operator, and good afternoon everyone. I'd like to welcome all of you to Seattle Genetics Third Quarter 2019 conference call. With me today, are Clay Siegall, President and Chief Executive Officer; Robin Taylor, Chief Commercial Officer; Todd Simpson, Chief Financial Officer; and Roger Dansey, Chief Medical Officer.

Accompanying today's conference call are supporting slides, which are available on our website in the Investors section, Events and Presentations page.

Following our prepared remarks today, we'll open the line for questions. We ask that you limit yourself to one to two questions to ensure we're able to get to everybody during our call today.

Today's conference call will include forward-looking statements regarding future events or the future financial and operating performance of the Company, such as those among others relating to the Company's 2019 financial outlook, including anticipated 2019 ADCETRIS sales and future revenues, cost and expenses, and the Company's anticipated timing to achieve potential future 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. Among the factors that may cause such a difference includes the difficulty in forecasting sales, revenues and expenses, and the uncertainty associated with the pharmaceutical development and regulatory approval process.

More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the Company's periodic reports filed with the Securities and Exchange Commission including the Company's quarterly report on Form 10-Q for the quarter ended June 30, 2019.

And with that, I'll turn the call over to Clay.

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Thanks, Peg and good afternoon, everyone. Seattle Genetics has reached a transformational point in it's history. We are poised to bring multiple targeted therapies to cancer patients in need. Our progress is evidenced by significant milestones across our oncology portfolio, including several in only the past few months.

First, ADCETRIS is a leading lymphoma brand that continues to grow with record revenues of $462 million year-to-date up 34% in the first 9 months of 2018. Under our collaboration with Takeda, ADCETRIS is on pace to exceed $1 billion in global sales in 2019. In addition, ADCETRIS remains the focus of a substantial clinical development program. At ASH in December 10 abstracts will feature ADCETRIS in Hodgkin and T-cell lymphomas including the 40-year follow-up from the ECHELON-1 trial in frontline Hodgkin lymphoma.

Next, in our late-stage pipeline is Enfortumab vedotin or EV which we're developing in collaboration with Astellas. During the quarter, we submitted the BLA for EV in previously treated metastatic urothelial cancer patients and it was filed by the FDA with priority review, with an action date of March 15th, 2020. If approved, EV would be our second marketed product and expand our commercial portfolio into solid tumors. Our EV US sales force is in place and we are looking forward to bringing this drug to patients in need.

In parallel, we and Astellas are advancing a robust clinical development program for EV across the spectrum of urothelial cancer, including a planned Phase III trial in first-line metastatic patients. Roger will provide more detail about the impressive data presented at the European Society for Medical Oncology Conference and our development plans for EV.

Our next late-stage clinical program is Tucatinib. Last week, we reported exciting results from our HER2CLIMB pivotal trial of Tucatinib in metastatic HER2 positive breast cancer, including patients with brain metastasis. Trial was a success and achieved its primary and two key secondary endpoints. Full results will be presented at the San Antonio Breast Cancer Symposium in December. The data further support Tucatinib as a potential best-in-class HER2 tyrosine kinase inhibitor. Our team is already preparing the NDA which we plan to submit to the FDA in the first quarter of 2020.

This would put Tucatinib in line to become our third marketed product. HER2CLIMB data also support our continued investment in the Tucatinib clinical development program in earlier lines of HER2 positive breast cancer and in other solid tumors such as colon cancer. Tisotumab Vedotin or TV is a late-stage program we are developing in collaboration with Genmab. Our initial focus is in recurrent or metastatic cervical cancer. We expect to report top line data from the TV pivotal trial called Innova 204 in the first half of 2020.

Lastly, investing in our early stage pipeline is a key part of our strategy for future growth. We are advancing multiple programs in ongoing clinical trials including ladiratuzumab vedotin or LV. We plan to report initial data at SABCS from it's ongoing clinical trial of LV, plus pembrolizumab in triple negative breast cancer patients. We will continue to advance innovative new product candidates into clinical trials including ADCs and other targeted therapies with several of these planned in 2020.

At this point, I'll turn the call over to Robin to discuss our commercial activities. Then Todd will comment on our financial results and 2019 guidance. After that, Roger will discuss our clinical development activities. Robin?

Robin G. Taylor -- Chief Commercial Officer

Thanks, Clay. ADCETRIS net sales in the US and Canada were $167.6 million in the third quarter, an increase of 32% compared to the same quarter in 2018, at an increase of 5% over the second quarter of 2019. Continuing growth in Q3 reflected an increase in the overall share of frontline PTCL patients treated with ADCETRIS and sustained share in frontline Hodgkin lymphoma.

The PTCL growth was highest among newly diagnosed ALCL patients with a significant majority receiving ADCETRIS. Our sales organization is focused on continuing to promote ADCETRIS under it's broad label that now includes six indications. They are also emphasizing the 3-year PFS data from the ECHELON-1 trial in order to continue to shift adoption for advanced stage Hodgkin lymphoma patients. The data showed that with extended follow-ups, the PFS benefit was maintained with ADCETRIS plus AVD. We're narrowing our 2019 ADCETRIS sales guidance to $625 million to $640 million.

Now I would like to transition to Enfortumab vedotin. We are encouraged by the positive reaction from investigators and key opinion leaders to the EV-201 data that was presented at ASCO. There is significant unmet need in metastatic urothelial cancer, post platinum chemotherapy and PD-1 or PD-L1 therapy and we look forward to providing a new option for patients.

We are actively preparing for the potential approval and commercial launch of EV. EV sales team is fully on board and in the final pace of training to ensure that we are ready to launch upon FDA approval. Our sales organization was hired from 18 different companies in addition to Seattle Genetics and has an average of 14 years oncology experience. Our team is also actively engaging with key payers to provide them with information that will help them plan and budget for future coverage and to a reimbursement decision related to EV. We are working in close collaboration with our partner Astellas to ensure the joint commercial team is launch ready.

Moving onto Tucatinib, the commercial team is excited by the results from HER2CLIMB. We have been preparing launch plans in anticipation of the data that we announced last week. Hiring of the US sales leadership team has already been initiated with a focus on deep expertise in the breast cancer space. I'm confident that we will have a highly experienced Tucatinib sales force in place in advance of approval.

In summary, ADCETRIS is the mainstay of our business and we continue to focus on expanding our newer indications of frontline Hodgkin lymphoma and PTCL. We look forward to potential approvals and launches of EV and Tucatinib and to making a difference in the lives of cancer patients.

Now, I'll turn over the call to Todd.

Todd E. Simpson -- Chief Financial Officer

Great. Thanks, Robin and thanks to everyone for joining us on the call this afternoon. Today, I'll summarize our financial results for the third quarter and year-to-date and provide a few updates to our financial outlook for the year. Total revenues were $213 million in the third quarter of 2019 and $627 million for the year-to-date. This included record ADCETRIS net sales in the US and Canada of $168 million in the third quarter and $462 million for the year-to-date.

Royalty revenues in the third quarter of this year increased to $27 million, compared to $23 million in the third quarter of 2018. For the first 9 months of 2019, royalty revenues were $66 million, compared to $59 million for the same period last year. Royalty revenues primarily reflect ADCETRIS sales by Takeda and to a lesser extent sales of Polivy under our collaboration with Roche.

Collaboration revenues were $18 million in the third quarter and $99 million for the first 9 months of 2019. This included the earned portion of $43 million in milestones achieved earlier this year, most notably triggered by Takeda's approvals of ADCETRIS in frontline Hodgkin lymphoma and the recent approval of Polivy.

R&D expenses were $196 million in the third quarter of 2019 and $518 million for the year-to-date. Growth over 2018 reflects higher investment across our pipeline, primarily on our late-stage programs Tucatinib EV and TV, as well as the upfront cost of a pre-clinical asset that we acquired in the third quarter. SG&A expenses were $96 million in the third quarter of 2019 and $259 million in the first 9 months of the year.

These are both increases over 2018 and reflect commercial efforts to support ADCETRIS in frontline Hodgkin lymphoma and PTCL, launch preparation activities for EV and costs related to supporting our other late-stage pipeline programs. We ended the third quarter with $870 million in cash and investments, which includes net proceeds of $549 million from our July common stock offering.

In addition, we hold approximately $102 million in Immunomedics common stock. These shares are mark-to-market and contributed to a small investment loss for the quarter and year-to-date this year, that created some variability in results in 2018.

Lastly, I want to highlight four updates to our financial outlook. On revenues, we are narrowing our ADCETRIS net sales guidance to a range of $625 million to $640 million. In addition, based on strong sales by Takeda, we are increasing our expectations for royalty revenues to a range of $90 million to $95 million. On expenses, we are updating our R&D expense guidance to a range of $690 million to $715 million. This reflects the technology acquisition that I referred to earlier, as well as development activities for EV and Tucatinib.

And lastly, following the positive HER2CLIMB results last week, we expect to initiate several launch preparation activities this year for Tucatinib. As a result, we are increasing our SG&A expense guidance to a range of $355 million to $370 million. We plan to provide our 2020 financial guidance on our next quarter call.

Now, I'll turn the call over to Roger.

Roger D. Dansey -- Chief Medical Officer

Thanks, Todd and good afternoon everyone. The past few months have been remarkably productive. This afternoon I will recap key outcomes and activities in our late-stage programs and highlight our development plans going forward to maximize the potential of these program for patients in need. I'll begin with Enfortumab vedotin. Positive data from the pivotal EV-201 trial in metastatic urothelial cancer patients who received prior platinum chemotherapy and PD-1 or PD-L1 treatment were presented at ASCO and published in the Journal of Clinical Oncology. The data supported our Biologics License Application that was submitted to the FDA in July and was accepted for filing by FDA in September with a PDUFA date of March 15, 2020.

We and our partners at Astellas are actively engaged with FDA in support of the application. As a reminder, in the previously received Breakthrough Therapy designation from the FDA in this patient population. Beyond our initial registration pathway, our development plan are evaluating EV in the first-line metastatic setting, as well as in earlier stages of the disease. This is supported by initial results from the Phase 1 EV-103 trial presented at ESMO in September, where we reported data from 45 metastatic urothelial cancer patients who were previously untreated and were ineligible for cisplatin-based chemotherapy. Cisplatin in eligible patients typically receive a carboplatin regimen, which is associated with a response rate of approximately 36%.

The study made outcomes for safety and in addition among those patients who received the combination of EV and pembrolizumab, the objective response rate was 71% including a 13% complete response rate. A total of 93% of patients had reduction in tumor volume. The combination of EV and pembrolizumab showed a manageable safety and tolerability profile. Importantly, we observed responses regardless of PD-L1 expression. Treatment related adverse events of clinical interest that were grade 3 or greater were rash, hypoglycemia and peripheral neuropathy. These were expected events and the rates were similar to those observed with Enfortumab vedotin monotherapy. 11% of patients had treatment related immune-mediated adverse events of clinical interest, greater than or equal to grade 3 that required the use of systemic steroids. This was consistent with the safety profile observed with pembrolizumab monotherapy, which is not appear to worsen with the addition of EV.

Based on these data, we are proposing to conduct a front-line randomized Phase III trial. We will provide additional specifics about our Phase III plans in the coming months. EV plus pembrolizumab represents a second encouraging data set that has been generated from the combination of a vedotin based ADC and a checkpoint inhibitor. We have previously shown promising data from the combination of ADCETRIS and nivolumab in several lymphoma settings. We believe in the potential of combining our vedotin based ADCs with immune checkpoint inhibitors and we are evaluating some of the cost combinations across our ADC pipeline.

The EV-103 trial is ongoing in first-line metastatic urothelial cancer patients to evaluate the combination of EV and platinum chemotherapy, as well as the triplet of EV pembrolizumab and chemotherapy. In addition, we recently expanded the trial to evaluate EV monotherapy and the combination of EV and pembrolizumab in patients with muscle invasive urothelial cancer who are cisplatin ineligible. Approximately 20% of urothelial cancer patients are diagnosed with muscle invasive disease, which is not yet spread outside the bladder. There was a significant unmet need for new therapies for these patients.

Lastly, the activity of EV in urothelial cancer suggested may have application in other Nectin-4-expressing malignancies. To that end, we have Astellas plan to start a signal finding trial in other solid tumors in the near future. I'll move on now to Tucatinib, our oral tyrosine kinase inhibitor that targets HER2. Last week, we reported positive top line results from the randomized, double-blind pivotal trial called HER2CLIMB.

The trial was conducted in 612 heavily pre-treated HER2-positive metastatic breast cancer patients, including 47% who were known to have brain metastases at study entry. Patients received either Tucatinib in combination with trastuzumab and capecitabine or trastuzumab and capecitabine unknown. We reported a statistically significant and clinically meaningful outcome on the primary end two key secondary endpoints.

The data showed that the Tucatinib regimen reduce the risk of disease progression or death by approximately half and by a greater amount in the patients with brain metastases, most importantly Tucatinib also reduce the risk of death by a third in the overall population. Tucatinib in combination with Trastuzumab and capecitabine was generally well tolerated with a manageable safety profile. Full results from HER2CLIMB are scheduled for an oral presentation at SABCS on December 11th 2019 and we expect to submit a new drug application to the FDA in the first quarter of 2020.

Next, I'll turn to ADCETRIS, which we are evaluating in several new trial for potential registration or to inform clinical practice. As previously stated, we are enrolling patients who have been retreated with ADCETRIS in Hodgkin and T-cell lymphoma to progress after prior response, including those who received ADCETRIS in the frontline setting.

We are also conducting a trial of ADCETRIS in frontline Hodgkin lymphoma and PTCL patients who are unfit for combination chemotherapy. In addition to these studies, we recently expanded an ongoing Phase II trial to evaluate ADCETRIS in a novel combination of nivolumab, bleomycin and dacarbazine in newly diagnosed and perhaps Hodgkin lymphoma patients. This regimen excludes when blasting [Phonetic], which is part of the approved ADCETRIS plus AVD regimen and adds nivolumab and blasting is known to cause neuropathy and ADCETRIS in combination with nivolumab has produced promising data in several connected trials. Combining the two most active agents in Hodgkin lymphoma, ADCETRIS and the PD-1 inhibitor in a frontline regimen has the potential to improve efficacy and reduce toxicity.

The trial reflects our long-term strategy to improve outcomes Hodgkin lymphoma patients with ADCETRIS based regimens. Another interesting opportunity we are exploring is it's use in the treatment of diffuse large B-cell lymphoma, we'll keep you posted as our plans progress. We also have a number of important presentations at ASH and look forward to continuing to expand the ADCETRIS dataset in hematologic malignancies.

Now I'll turn the call back over to Clay.

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Thanks, Roger. Before we open the line for your questions, I want to recap our key upcoming activities across our oncology portfolio. They include, first continue to establish ADCETRIS as a standard of care in frontline Hodgkin lymphoma and frontline PTCL and initiating additional clinical trials. Second working with FDA on our EV submission in collaboration with Astellas toward the March 2020 PDUFA date, initiating a Phase III trial in front line urothelial cancer and expanding EV development program with new trials.

Third reporting Tucatinib HER2-client data at SABCS, submitting an NDA to the FDA in the first quarter of 2020 and advancing a randomized trial in combination with T-DM1 and reporting top line results from the TV pivotal trial in cervical cancer in the first half of next year. We aim to continue our positive momentum through 2019 and into 2020 as we strive to bring important new drugs to cancer patients.

At this point, we'll open the line for Q&A. Operator, please open the call for questions.

Questions and Answers:

Operator

Thank you, sir. [Operator Instructions] And our first question will come from Michael Schmidt with Guggenheim.

Michael Werner Schmidt -- Guggenheim Securities -- Analyst

Thanks for taking my questions. I actually had a quite -- a pipeline question on Ladiratuzumab, as you mentioned rightfully so I think a lot of excitement around combining your ADCs with PD-1 inhibitors and you did mention the upcoming presentation of the KEYTRUDA combination study at SABCS. I was just wondering if you could help us a bit more with what investor expectation should be with respect to this update from LV plus pembrolizumab [Technical Issues].

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Michael, thank you for the question. So we are very interested in the LIV-1 ADC, it's interesting molecule, it's certainly active, we've shown that and presented that has single agent activity. And we are continuing to evaluate as a monotherapy and also in combination with pembro. We are not yet ready to go forward and announce registrational or Phase III trials. But we are continuing to develop it and trying to maximize dose schedule monotherapy combination with pembro and we're very excited about that.

Clearly SABCS will be from a Seattle Genetics standpoint a big show on Tucatinib because we have a lot to discuss there, but LIV-1 is also important to us. And additionally, I may point out that the basket trials a trial in a variety of different tumor types that have LIV-1 expression has recently opened. So that's something we're working on as well.

Michael Werner Schmidt -- Guggenheim Securities -- Analyst

Great, thanks. And then maybe a follow-up, so you mentioned the upcoming trial results for the TV study and cervical cancer from the TV 204 trial. Can you just remind us of sort of expectations for what are the clinical barriers here in terms of efficacy to -- for approvability?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

There is a lot there and maybe I'll give you a few comments, but Roger can also follow up. And if you look at relapsed cervical cancer, it's in fact grim prognosis, no one survives this, this is bad and despite Carticel and vaccines, not everyone gets vaccine across the globe and in the US. And so there is still unfortunately a need for therapies for relapsed cervical cancer. And if you look at perhaps the most recent approval in cervical cancer, it was pembro in PD-1 high-expressers with a 14 that's 14% response rate, but they were durable responses.

And if you look at chemotherapy that has been used in a lot of publications, there are I would say the range is probably somewhere between 8% and maybe 16%, 17% response rate, sometimes with durations that are tiny measured in two months, a duration where with a checkpoint you can get a year or so of duration, which is likely why it got approval, even with needs to minimis response rate because it had duration. So I think those maybe can help you give you some landmarks of what's out there. And clearly we want to do well by patients and have a best response. We can have with single agent, look at this in future in combination. Roger, do you have any color you want to add beyond that?

Roger D. Dansey -- Chief Medical Officer

No, Clay, I agree with your comment that the bar is set by historical precedent and we need to wait for the TV results, see, they match up.

Michael Werner Schmidt -- Guggenheim Securities -- Analyst

Great, thanks. There is lot to talk about obviously, but congrats on all the pipeline progress in the quarter. I'll hop back in the queue.

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Thanks.

Operator

Thank you. Our next question comes from Kennen Mackay with RBC Capital Markets.

Kennen B. MacKay -- RBC Capital Markets -- Analyst

Hi, thanks so much for taking the question. Congrats on the quarter and the narrowed in slightly raised guidance, maybe a quick commercial question. First, I'd hope for a little bit more color on the growth of ADCETRIS in frontline PTCL and higher growth in CTCL is where its like two factors are at play, all of those patients are CD30 positive and I think the NCCN guidelines there may be a little bit more generous versus other PTCL. So I was wondering, of those two drivers, which had been the bigger impediment to use outside of CTCL sort of lack of broad CD30 testing there or just lack of supportive data and really what can be done about that to increase utility outside of CTCL. And then I have one quick follow-up.

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

So, you know, there has been -- a lot of worked on looking at CD30 expression in both CTCL and in PTCL. And if you asked scientifically, are there patients with PTCL and CTCL that are absolutely negative for CD30, I could not with a clear conscience say that there are patients that are truly negative. What I can tell you is there are some patients that have low scores on histology when looking at a single module. But if you look at other nodules they could be high. Keep in mind. CD30 is an activation antigen. And if you take some tissues that are low or in background with histology and you do other types of techniques to look at expression, you can see CD30 expression there. So to me it's not totally is our CTCL and PTCL CD30 positive or negative. It's more of a what the rate, what the expression level is and are some really in the background of histology, which is kind of a blunt tool although readily used across different cancer centers. So it's an easy tool to use.

But having said that, you're asking about what can we do about that, how can we grow and there has been trials done and evaluated for instance in CTCL that were presented not that long ago, showing that you have CD30 positive and then CD30 I will call histology [Technical Issues] product is in the field longer and study this. And Roger, you know a lot about expression of this. And is that something that you want to comment on in to?

Roger D. Dansey -- Chief Medical Officer

Yeah, no, I think and Clay has made the point that there is a dynamic nature to this expression and there is a sampling variability and we have data not just in CTCL, but in other diseases as well with CD30 expression. One would expect it to mark for responses where we have parent CD30 negative is negativity where we see response. From a testing perspective obviously pathologists are an important part of this and getting the pathologist to understand the importance now of CD30 testing in PTCL because it is a therapeutic that can make a difference, it's something that we are obviously focused on and interested in trying to improve adoption of scoring and the appropriate reporting of pathology.

Kennen B. MacKay -- RBC Capital Markets -- Analyst

Great, thank you very much. And then I had one quick pipeline follow-up. I'm up here in Boston at the AACR-NCI-EORTC Triple Conference and some of your data on the next generation peg good Codorad linkers and tubulysin paying loads was presented up here maybe enabling higher paying load delivery per ADC. Can you maybe help us understand the utility of these technologies. And I think this is getting used on one of your next generation ADCs SGN-228A which is in Phase 1, if I am right on that, could you maybe help us understand when we might see some of that initial data and what to look for in that data? Thank you very much and congrats again.

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Thanks, Kennen. So thank you for the introduction to talk about stuff that's part of our growing technology and our leadership in ADCs. So we are really excited about our newest ADC in clinical trials that we call 228A targets CD228 or what's referred to as p97. And this is expressed on a variety of solid tumors and we have also not only just use this target, but we have used that new confirmation in ADC that utilizes pet groups, utilizes an implode. You may be aware that with ADCETRIS and with LV, we utilize approximately four drugs per antibody molecule. And with our newest technology with 228, we're using eight drugs per antibody molecule, but it has a completely different linker and a completely different stabilization agent and we've been working on this and it's in clinic now and it's an exciting prospect for us.

One of the commitments that we've made is after we became the industry leader in ADC is to stay there and that's to continue investing in our technology and continue to make drugs that are more potent, but also safer and try to work on our liquid systems to make them more specific for the tumor. And so this is one example where we are very hopeful with our technology and we are investing in new ADCs. But as you will see going forward, we have a couple of new technologies to build on what we already have is in leadership positions. And I think that the future will be a good one for ADCs not only at Seattle Genetics, but in other companies as other companies are making advances in really helping patients.

Operator

Okay, thank you. Our next question comes from Salveen Richter with Goldman Sachs.

Salveen Richter -- Goldman Sachs -- Analyst

Thanks. Could you just comment on the next steps for tucatinib may be in colorectal cancer and perhaps plans look at other indications such as gastric or the frequency of HER2 expression is much higher?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Thank you very much for the question. Roger, can you talk a little bit about maybe on data and what we're doing next. And then also touch on other diseases.

Roger D. Dansey -- Chief Medical Officer

Right. So, thanks for the question and obviously the HER2 climb results, which are really and be remarkable, it does point to the potential business nature of Tucatinib. And so we are interested in -- since you're creating a program around Tucatinib which will include expanding into other areas of breast cancer, Clay has already mentioned the TDM-1 trial which is in earlier stage of metastatic disease, they have a neoadjuvant effort through by two and we are looking at other areas as well.

With regard to HER2 expressing tumors that are outside of breast cancer, we did have very exciting data, a small data set but very exciting at SMO, with a combination of Trastuzumab Tucatinib for the response rate that's north of 50% and look pretty durable. So we're excited about taking that on so much so that that was an investigator-initiated trial, which we've taken over essentially only IND and the trial is now Seattle Genetics open-sponsored trial. And we plan to continue to evaluate third line colorectal cancer HER2 positive in a broader patient population utilizing amounts in their trial and that obviously if that data is we produce or what you think it will be that's an area of potential seeking potential registration outcomes.

And in earlier lines of colorectal cancer, even though the frequency is in sort of 2% to 5% range, nevertheless it's an important unmet need and it's a large addressable population. So we're working on thinking about what we could do earlier. With regard to gastric exactly as you say, this is another opportunity and we already have thought through internally what a development plan could look like. We're not ready to share that information at this point, but we are definitely interested in gastric and potentially other HER2 expressing tumors as well.

Salveen Richter -- Goldman Sachs -- Analyst

And a follow-up if I may, at this point, how much is HLA driver with ADCETRIS revenue growth versus PTCL?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

You know, I'll turn it over to Robin in a moment, but the general answer is we really don't split them up and both of them are very important to us. Robin you want to give a little color?

Robin G. Taylor -- Chief Commercial Officer

Sure. HLA is certainly one of the key revenue growth areas for ADCETRIS. And I think there is certainly room to grow with Hodgkin lymphoma. We've seen good uptake both in PTCL and Hodgkin lymphoma, but if you look at Hodgkin lymphoma is really facing a much more entrenched usage chemotherapy. The three-year PFS data that we presented has really helped us get traction in terms of physicians understanding the benefit of ADCETRIS and we will have for your follow-up data at ASH. I think as the data matures with Echelon-1 when one can see is there is -- we've seen that continued benefit from the 3-year PFS data. The more we can show that there is an interim benefit, I think the more that we are going to be able to convert physicians understanding the benefit of ADCETRIS. In terms of the relative contribution as Clay said, we don't split those up, but I believe that Hodgkin lymphoma is continuing to be an important driver for us. We've seen obviously rapid uptake with PTCL as well and I think that's -- has been very encouraging.

Operator

Thank you. Our next question will come from Gena Huidong Wang with Barclays.

Gena Huidong Wang -- Barclays -- Analyst

Thank you for taking my questions and the first one also regarding the commercial question. So, I'm wondering how's the first line PTCL and the Hodgkin lymphoma, the growth trajectory or growth rate in this quarter compared to the last quarter?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

So we don't report the specific growth of the disease types, no. As a whole, we've had a lot of growth year-over-year and quarter-over-quarter we grew a little about 5%. And so that is -- it's a strong growth rate within what we have it for guidance. And we're excited about that and we expect that ADCETRIS over time year-to-year will continue to grow as a brand as we make more progress there.

But the specifics of PTCL for instance as you ask is not something we present. What I will say is that with PTCL we had OS from our first data set. So it is a less challenging discussion with doctors, when you go out with OS data, where with Hodgkin lymphoma, it was contemplated to be -- to take a number of years to get there because you need a certain amount of events to see statistical volumes.

So we are not there and it is important for us to follow the protocol as it said and as it's written and try to get to those events. But in the meantime, the gold standard is 5 years and docs look at that with Hodgkin lymphoma. Our additional data which we published showed 2 year worth of data and some doctors and it was great data, some doctors converted and some didn't. And then last year we put out our 3 years data and we had a nice bump in our revenues and more docs took it on and the data got actually better, it wasn't just continuation of two to three years that look better. And now this year, we're going to show our at ASH coming up in a couple of months, we're going to show 4 year data. And then next year, presumably we have ASH but it's way too early to speculate, we'll show the 5 year gold standard data. And I think that that will go a long way to addressing any questions without even having OS data. So, we're really excited to continue to age the data and go forward.

Gena Huidong Wang -- Barclays -- Analyst

Great. And then just quick follow up, quick question regarding the EV-103 hopefully. So you did mention that you plan to start randomize the Phase III trial in first-line, just wondering any additional color you can provide and giving those individual 130 data reported at ASCO and we will be thinking about triple it versus double or it will be EV-103 plus pembro versus [Indecipherable]?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

No, we have not yet spelled out the exact trial and that's something as soon as we start the trial we will spell it out, that's been our history that it's not appropriate to state the exact trial till it starts. So stay tuned, we will be doing that. But Roger, perhaps you can give some color on your thoughts on in bigger and the kind of approaches we could take to go toward approval and the importance of it.

Roger D. Dansey -- Chief Medical Officer

Sure, thanks, So as you can see the EV-103 trial offers you a road map as to how we're thinking about what possible combinations we can use and as Clay said, we haven't disclosed those, but you can get a sense of the data generation that we will need to support the Phase III frontline trial. With regard to Envigo it's a positive trial, the OS didn't quite make it obviously from a -- from an efficacy perspective, although it's hard to cross compare. But we are encouraged by our EV pembro data, which has been a response rate of 70%, which is an unusual outcome in this disease. And again, cross trial comparisons of -- have limits for sure, but the response rates that were shown with the tisotumab together with chemotherapy would suggest that at this point anyway, what are our plans to proceed into a frontline trial would suggest that we have a good shot to potentially improving the outcomes further.

Operator

All right, thank you. Our next question comes from Andrew Berens with SVB Leerink.

Andrew Scott Berens -- SVB Leerink LLC -- Analyst

Good afternoon. Thanks for taking the questions. I guess is what is primarily for Roger, one of the buzzes that came out of the EV presentation in Barcelona was potential synergies between vedotin and checkpoint and I think it's one of the things a lot of investors are also thinking about in regards to have the value of the platform. Do you guys have any additional color for us regarding what could be driving potential synergies? And is there anything about the payload for the linker that differentiate in regard to other ADC approaches?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

So, Roger?

Roger D. Dansey -- Chief Medical Officer

Sure, thanks for the question and so it's the Holy Grail of drug development is to be able to put two drugs together and have a better outcome than in individual drugs alone and certainly that response rate is high. Proof of synergy is a very different thing, which requires a high level of scientific rigor. And what I can say is that from a mechanistic perspective, you think about what an ADC is, it's essentially a targeted therapy. So, delivering a payload to a group of tumor cells, inducing in those tumor cells things like immunogenic cell death, replicate of stress, such that the the tumor microenvironment may become favorable for an inflammatory response and may in fact be amenable into an immune response that would be assisted by taking the breaks off an immune response by giving a PD-1 or PD-L1 inhibitor. And in the sense of, chemotherapy may be much more, much more permissive in terms of what other cells could potentially damage, one could speculate that that limited delivery of a cytotoxic payload just the tumor cells may keep the microenvironment more intact, that's one possibility. With regard to the actual data in terms of what does -- could 71% represent a represent synergy?

What is interesting is if you look at the data, you can see that there is a response regardless of PD-L1 expression, which is encouraging. We don't have EV monotherapy data at this point to sort of make the comparison. So it's very hard from a pure numbers perspective to say this is what would you expect with pembro and this is what you could expect from EV. But regardless of whether it's synergy or not, the clinical data are pretty compelling and it's certainly compelling us to move forward on the development program.

Andrew Scott Berens -- SVB Leerink LLC -- Analyst

Okay. Is there anything about Vedotin specifically or your linker technology that could make it hard for another ADC to have similar effects?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

You know Andy, you're asking a really good question. And there is a lot of work going on in our research effort that I do not -- our research group I should say that do not are not ready for full discussion. And we're, what we're doing is in general is we're evaluating all the different type of payloads. And their impact on immunogenic cell death. And I could tell you that they're not all the same and Vedotin work really well there. And I don't want to say more than that at this point and at some point in future we'll put our research data in appropriate conference like an AACR type conference, but we're really excited with our choice of Vedotin and how they work well with immuno-oncology agents like PD-1's.

Operator

Thank you. Our next question will come from Andy Hsieh with William Blair.

Andy Hsieh -- William Blair -- Analyst

Great, thanks for taking my questions and congratulations on the quarter. So it's encouraging to see that Seattle is really hoping to expand the frontline treatment paradigm for Hodgkin lymphoma and also MTCL. So just curious these Phase III trials usually take anywhere from three to five years to run, anything you guys learn from the ECHELON programs in terms of potential surrogate endpoint to kind of shorten these trials?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

So it's a good question. I think especially in the Hodgkin lymphoma space there is the Stage 1 and 2 that we do not yet have approval in for example. And despite that there is a lot of good data that's been presented, but albeit they're relatively small trials and they're not approval trials, but the data is strong. And I think that when you look at work that's going on, whether it's in Europe with consortiums or cooperative groups in the US or corporate studies, I think that there is a building momentum for using ADCETRIS in a lot of lines of Hodgkin lymphoma. But we have to continue really powering through trials and try to look at some novel endpoints and they don't take very long. And I think that is something that is up for discussion with regulators. I can't give you any details on that. Roger, is there anything else you want to say based on what we can?

Roger D. Dansey -- Chief Medical Officer

Yeah I think Clay is right thereof, it's not just corporate trials, the trial is what can be fairly long-term trial. There are cooperative groups and so on which are important entities in those trial execution. We are interested -- what we talked about today was a signal-finding study to see if we could in a single-arm trial show what ADCETRIS, nivo, Adriamycin dacarbazine combination could look like in frontline advanced Hodgkin lymphoma. And we think if that data is compelling enough that could then be the genesis for yet more work either by ourselves or by others to see because the ultimate goal is to cure as many people as we can. And that's I think what our focus is on in terms of developing new treatments for Hodgkin lymphoma new combinations.

Andy Hsieh -- William Blair -- Analyst

And a follow-up is I can, so in terms of DLBCL, Clay, I think in 2015 ASCO when the company decided to forgo the frontline opportunity, I'm just wondering what changed there. I think you mentioned about just the markets were pretty crowded and given kind of failures in the frontline setting one with REVLIMID, one with IMBRUVICA, were those kind of the genesis behind the rationale to look at potentially frontline DLBCL again?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

So first of all, we are in NCCN with DLBCL. And so we hear back from doctors who utilize it. And that's an important thing to try to understand what's going on in the world and we figured that out over the last couple of years. And have been able to talk to docs and been able to understand the benefit that ADCETRIS has in DLBCL. The landscape has changed and not necessarily we had big victories as you say. And there are other specifics that we have in mind, but we have not announced a specific trial yet and -- but it's coming and we're excited with it and it's something that we need to obviously work through regulators and with the team here at Seattle Genetics and we're trying to go forward and see if we can get another label in DLBCL, so stay tuned on that.

Andy Hsieh -- William Blair -- Analyst

Great. Thanks for taking all my questions.

Operator

Thank you. Our next question will come from Shanshan Xu with Berenberg Capital Markets.

Shanshan Xu -- Berenberg Capital Markets -- Analyst

Hi, thank you for taking my questions, a few quick ones from me. So this year at ASH, I believe you will have the full-year update for ECHELON 1 on the PFS front. Can you please update with us, when should we expect the OS update for ECHELON 1?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Yeah, like I said earlier in the call, OS has a preset target number for events and at that point is when we open up the trial and we have not hit that, it is -- has always been contemplated to be quite a number of years. So we're just not there and it would be inappropriate for me to try to tell you when I think it's going to be since it's a hard prediction. In the meantime, we are getting PFS data and our PFS data is ageing from two years to three years to four years presentation in a couple of months at ASH, we're excited to do that. And then next year hitting that gold standard of five years PFS and as we get closer to the five year PFS data time point, doctors ask about the OS less because if you're at five year PFS and your lines are pretty flat in the Kaplan-Meier plots that signifies really what the doctors need to know. So while we are going and planning on getting OS, I think that 5 year PFS is going to be very significant as well.

Shanshan Xu -- Berenberg Capital Markets -- Analyst

No problem. And next one is that given the strength of the data from HER2CLIMB and the fact that you're already in niche aided HER2CLIMB, two for Tucatinib plus TDM-1, we actually look forward to including this market opportunity in our model. So how should we think about the size of the indicated patient population for Tucatinib and TDM-1 combination, considering the dynamic in the treatment arena for HER2 positive breast cancer patients.

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Right. Well, we haven't really come out yet at this point and talk about the size of the population. I mean it's a little premature for us, we just came out with our data to start talking about what we think size of population is and which leads right into a marketplace discussion which leads into a pricing discussion. We have done a lot of work on this. We have been doing a lot of work. We're intending for HER2CLIMB to be not just a US product, but a global product. I mean we have a randomized study and a great dataset. We're really looking forward to presenting that dataset at San Antonio. And so I think that the market opportunity is substantive and you'll be hearing more from us on that in the future.

Operator

Thank you. Our next question will come from Silvan Tuerkcan with Oppenheimer.

Silvan Can Tuerkcan -- Oppenheimer -- Analyst

Thank you for taking my question and congrats on all the progress this quarter. It's very promising that you think about moving into muscle invasive bladder cancer with EV. What types of data have you seen before to inform the utility of EV in the setting?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Thanks for the question, I will turn it over to Roger to give you his thoughts on muscle invasive bladder cancer, which is a really big opportunity and an unmet medical need opportunity, but we have not -- we have recently opened a cohort of patients. So we're just now treating our first patients in muscle invasive. So if you're asking what is our clinical data? We're assembling our first clinical data, if you're asking about pre-clinical about why we are looking at this, we have looked at expression of Nectin-4 and the pre-metastatics and certainly it's expressed strongly there as well. And there's been a bunch of pre-clinical work that have been done to show that we think that this could be very effective and not only muscle invasive, but even earlier stage in a non-muscle invasive.

So in all stages of bladder cancer, which is a very substantial size market with about 80,000 incidents in just US each year, for those three types of cancers, the metastatic, the muscle invasive and the non-muscle invasive. So a lot of preclinical work, substantial amount of clinical work in metastatic both the single agent in combination. And now we're treating patients in muscle invasive. Roger, is there any further details?

Roger D. Dansey -- Chief Medical Officer

Yeah, I think so EV is obviously active in metastatic disease and so one could, it's not a difficult step to take to expect that it may have meaningful activity in Nectin-4 expressing non-metastatic disease and so I think that's where we are. We obviously as Clay said we need to generate the data, so we can see exactly what the effect of EV monotherapy is and also look at the combination. And as you know, the landscape from muscle invasive bladder cancer because there is a meaningful unmet need is busy right now. And there were lots of trials that are running. And so understanding what a regulatory path forward could look like, we already have evidence, we have worked examples ahead of us.

And so if we are able to take EV into a randomized trial essentially the population splits into cis-ineligible and cis-eligible and the reason why its cis-eligible versus ineligible because cisplatin is the only drug that's shown versus cisplatin combination is the only combination that is shown to actually have benefit in the muscle invasive space. And so you can see clinical trial designs, compartmentalize those two populations. And we would be interested obviously in both. We have generated data with EV pembro in the cisplatin ineligible metastatic population, so we do have that first piece of information and just stay tuned, we're working on moving EV-4 into these earlier lines of bladder cancer.

Silvan Can Tuerkcan -- Oppenheimer -- Analyst

Great, thank you so much. And a quick follow-up if I may, I'm also encouraged that you already expanded Tucatinib. What made you initiate Tucatinib plus Kadcyla and was anything promising that you've already seen in the HER2CLIMB data set or is it just a commercial mission?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Please keep in mind that there was a study that had been done, an early study that was single arm not randomized, but it combined Tucatinib and Kadcyla. And the data had been presented at a conference and they were very strong. So we do have the early data. And to us together with the early data and the outstanding HER2CLIMB data that you'll see in San Antonio, it makes sense to go earlier in line and invest in it. And this time, it's a randomized study and so we don't need to do another single arm study that's been done and the safety and efficacy or the risk benefit that some docs call it, looked pretty darn and good, but it was a single arm study. So we are investing in a randomized study that is up and running.

Silvan Can Tuerkcan -- Oppenheimer -- Analyst

Great, thank you so much for taking my questions.

Operator

Thank you. Our last question in the queue comes from Tazeen Ahmad with Bank of America.

Tazeen Ahmad -- Bank of America -- Analyst

Hi guys. Thanks so much for taking my questions. Maybe Todd a couple on the financials, so as you guys diversify out away from ADCETRIS and a lot of the key studies for ADCETRIS have read out, you are putting more money now into the rest of the pipeline, whether it be EV or Tucatinib or TV. Can you give us a sense about the waiting of expenses for modeling purposes for EV versus the rest of the program on a go forward basis? Should we assume that EV is the bulk of expenses just based on what you said or do you think that it will be more equal spread across all of your pipeline products? Thanks.

Todd E. Simpson -- Chief Financial Officer

Yeah, so great question. I don't know that I can give you specifics on exactly how it spreads, but historically ADCETRIS has been the prominent driver of our expenses. We've now got six labels, we've run a number of very large clinical trials. And while we're continuing to do additional work some of which you heard on the call today, it's becoming a probably a lower overall percentage of our investment in R&D, what is now really starting to come forward are investments in programs like EV, where as you heard today, we've got a very expansive development program for that compound, as well as Tucatinib.

I think the HER2CLIMB data to us turns this into a program, not a clinical trial. You've heard a little bit about our work that's already starting in combination with Kadcyla in lines of therapy before the HER2CLIMB setting. And then certainly we're looking at things like colorectal cancer where the data that we presented as well were quite encouraging. So, you know, I think maybe to get back to your question, I think you'll see a growing share of expense hitting programs like Enfortumab and Tucatinib. ADCETRIS will continue to be substantial, but probably becoming a smaller contributor to the overall pie. And then, we'll obviously look to see what else comes out of the pipeline. We've got TV in a pivotal study in a very broad portfolio of earlier stage assets that we just talked a little bit about today.

Operator

Okay. Thank you. The next question comes from Chad Messer with Needham & Company.

Chad Messer -- Needham & Company -- Analyst

Great, thanks for taking my question and congrats on all the recent progress. First real quick, is there any word you can say about the preclinical assets that Todd referred to in prepared remarks, maybe you can just a rough idea what the spend on that was?

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Well, I can tell you not from a financial standpoint that we do a lot of different deals and we bring in technology, we bring in preclinical assets. This has happened like almost every year we do, small different deals. And some of them work out really well and some of them they are just in our research front. And Todd, you could talk a little about why it was in -- why you mentioned it.

Todd E. Simpson -- Chief Financial Officer

Yeah, sure. So, not that it was a huge deal, but it was the principle driver of why we increased our R&D guidance just a bit. So, I won't -- I can't give the numbers out, but that was the main contributor. And as Clay mentioned, it's a really interesting preclinical asset that we think could become a clinical asset relatively soon, so that's what got us excited about it.

Chad Messer -- Needham & Company -- Analyst

Great. Yeah, that's very helpful. And then just for a follow-up, let me -- couple of questions here, but they're all very related, if you can indulge me, I wanted to go back to TV. Clay, you mentioned how terrible relapsed cervical cancer is and that not everybody gets vaccinated, so it's still a problem. What is your view of the kind of opportunity in relapsed cervical cancer, but also for TV, I know you're looking at a whole bunch of other cancers that express tissue factor. So your thoughts on the opportunity for a tissue factor targeting therapy more broadly. And then tissue factor itself -- can you just remind me is that sort of sparingly expressed across tumor types say like a CD30 is or is it a little bit more uniform? Thanks for taking my questions.

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Sure. So, first of all on TV, we are -- we expand the past just cervical for sure. We have a trial that's listed on clintrial.gov that's in ovarian cancer. And we have a Basket study, we're working on in other types of cancers. So, stay tuned for us to report in the future when we have enough substantive data at appropriate peer-reviewed conferences like we always do on the data outside of cervical that we're working on. So there is a lot of interest in it.

And you asked about the expression of TF or tissue factor and that's something that's expressed broadly on solid tumors at very high density. It's not really a heme target, so I wouldn't expect us to go and do a lot of lymphoma, leukemia myeloma type work with it, rather it's more on the solid tumors that you would expect, the big solid tumors. And the expression on cervical and things like ovarian are very high. So, really good targets and important diseases that need additional therapies that have unmet need for a lot of patients. So we're really excited about our partnership with Genmab working on TV and we continue to look forward to presenting more and more data.

Operator

Thank you, sir. We now have no further questions in the queue.

Peggy Pinkston -- Vice President-Investor Relations

Okay. Thank you, operator and thanks everybody for joining us today. Have a good night.

Operator

[Operator Closing Remarks]

Duration: 65 minutes

Call participants:

Peggy Pinkston -- Vice President-Investor Relations

Clay B. Siegall -- President, Chief Executive Officer and Chairman of the Board

Robin G. Taylor -- Chief Commercial Officer

Todd E. Simpson -- Chief Financial Officer

Roger D. Dansey -- Chief Medical Officer

Michael Werner Schmidt -- Guggenheim Securities -- Analyst

Kennen B. MacKay -- RBC Capital Markets -- Analyst

Salveen Richter -- Goldman Sachs -- Analyst

Gena Huidong Wang -- Barclays -- Analyst

Andrew Scott Berens -- SVB Leerink LLC -- Analyst

Andy Hsieh -- William Blair -- Analyst

Shanshan Xu -- Berenberg Capital Markets -- Analyst

Silvan Can Tuerkcan -- Oppenheimer -- Analyst

Tazeen Ahmad -- Bank of America -- Analyst

Chad Messer -- Needham & Company -- Analyst

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