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spk17: Good afternoon, thank you for standing by, and welcome to the Aveo Oncology Second Quarter 2021 Financial Results Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one on your telephone. If you require any further assistance, please press star, then zero. I would now like to hand the conference over to your speaker, Mr. Eric Lucero, Chief Financial Officer of Aveo. Please go ahead.
spk08: Thank you, Operator. Good afternoon, and thank you all for joining us on today's call to discuss Aveo's second quarter 2021 financial results and business update. I'm joined today by Michael Bailey, Chief Executive Officer, Mike Ferraresso, Chief Commercial Officer, and Dr. Michael Neal, Chief Medical Officer. Before we begin today's call, let me remind you that during this discussion, we'll be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to important risks and uncertainties, including those that are detailed in today's press release and in the risk factors section of our most recent quarterly report on Form 10Q, which is on file with the SEC that may cause actual results to differ materially from those results expressed in Schultz's statements. Furthermore, we caution you that these forward-looking statements represent our views only as of today, and we do not assume any obligation to update these statements, whether as a result of new information, future events, or otherwise, as except as noted and may be required by law. With that, I will now turn the call over to our President and Chief Executive Officer, Michael Bailey. Michael.
spk11: Thank you, Eric, and thank you to everyone for joining us on today's call. The second quarter marked our first full quarter as a commercial stage company, and we're excited to share with you the continued progress we have made with the launch of Fatibda, or Tuvozanib, our first commercial product, as well as the progress with the rest of our pipeline and our financial results for the quarter. Today, we are pleased to report our first full quarter of Fatibda sales, which reflect a rapid commercial uptake since it was launched on March 22nd. I can say with confidence that we believe that we are off to a strong start. As many of you already know, Fatibda is an oral, once a day, VEGFR TKI approved in the U.S. for the treatment of adults with relapse or refractory advanced renal cell carcinoma, or RCC, following two or more prior systemic therapies. This approval was based on the Phase III TiVo III study. The first positive RCC Phase III study in this highly refractory setting and the first phase three study to incorporate a predefined subpopulation of patients who had received prior immunotherapy, which reflects the new standard of care in earlier lines of treatment. It is important to note that prior to FATIVDA, therapies used in these settings were often chosen based on extrapolation of clinical data from treatment and early line settings. as well as from clinical data that did not include a meaningful subpopulation of patients who received prior immunotherapy. Furthermore, due to a lack of robust prospective data in this refractory setting, coupled with tolerability concerns of other available treatment options, we know that a large percentage of patients choose to opt out of continuing on to later line therapy. Now, with the UF FDA approval for FATIVDA, the oncology community is able to offer patients an evidence-based treatment option with a favorable tolerability profile to address these significant unmet needs. While this positive Phase III data has supported the successful launch to date by differentiating FITIVDA from other available treatment options, I am pleased to say that we continue to gain valuable data from the TEVO3 trial. For example, At the 2021 ASCO annual meeting in June, we were pleased to share long-term efficacy follow-up and additional tolerability data from the TiVo3 study. Specifically, patients treated with Pitivna demonstrated a durability of response of over 20 months, more than two times that of serotonin, with the overall survival hazard ratio relative to serotonin continuing to improve with longer follow-up. In addition, an analysis of treatment emergent adverse events showed longer time to onset and a lower rate of dose reductions for these adverse events related to tibozanib as compared with serotonin. We believe these data continue to demonstrate a durability of response with FITIVDA as well as favorable tolerability profile that we know are important considerations for patients and physicians in the selection of later lines of therapy. With that setting the stage for this quarterly update, I'd like to turn the call over to Mike Barrasso to walk us through a more detailed commercial update, including second quarter metrics.
spk09: Mike? Thank you, Michael. As Michael mentioned, we are very encouraged with the launch today, and I'm excited to share with you results from our first full quarter of sales. For the second quarter of 2021, U.S. net product revenue was $6.7 million, which reflects inventory shipped to distributors in our 16% gross to net estimate. Since launching the drug in late March to the end of Q2, U.S. net product revenue was $7.8 million. Of note, Q1 sales reflected inventory build, while Q2 largely represented end-user demand. We estimate that as of the end of the second quarter, there was approximately two weeks of inventory available on the channel underscoring that our net revenue total was achieved with a lean inventory level. During the second quarter, we recorded a total of 283 commercial prescriptions, including increased prescriptions each month for a total of 453 prescriptions from launch through the end of July. This includes scripts from over 175 unique accounts across all settings, from major academic centers to the community. Finally, a total of 207 patient experience samples were requested and delivered through the end of July, and roughly 11% have already converted to a commercial prescription. We are encouraged by this, given that it takes at least a month after a patient received a sample to convert to a commercial prescription. Taken together with the data from IQVIA Brand Impact, which shows that Fotivda is the leader in share of voice in the relapse refractory RCC setting, We believe these numbers are a strong indicator of the hard work of our team, including our now fully deployed field team. Let me take a minute to discuss the commercial team that's helping drive these results. Our team is comprised of individuals who are deeply experienced in oncology, with a proven track record in reaching and impacting customers, both in person and, when required, remotely. While COVID restrictions have posed a challenge for gaining in-person access to treating oncologists, which is the case for all pharma companies, as indicated by Acuvia's in-person access statistics, our teams are executing well and we are seeing steady progress toward reaching all of our key customers. As I mentioned, we have received orders from over 175 unique accounts to date, which just scratches the surface of the 3,000 plus targeted accounts. In addition to the field sales team, we have supplemented their efforts with extensive marketing outreach, spanning a wide variety of formats in order to increase awareness in areas facing access restrictions. I would like to point out that while IV oncology drug use has declined, oral oncology drug use saw an increase year over year during COVID, as both physicians and patients are seeking treatments that can be administered in the at-home setting. We're hopeful that orally administered drugs with low rates of dose modifications, such as Fotivda, can be highly valuable in this context. Through the team's efforts, Fotivda is now broadly available through a limited network of specialty pharmacies and specialty distributors. By limiting our distribution network, we believe we are able to improve the customer experience for those receiving Fotivda at home, through our best-in-class specialty pharmacy partners, as well as for those who receive FOTIVDA directly from the treatment facility. We have designed our network to allow oncology practices who dispense directly to their patients to do so not only for the first month of treatment, but for the duration of treatment. We believe our model is unique within the RCC space. Our comprehensive support services provided through the Aveo Access Center of Excellence, also known as the ACE Patient Support Hub, helps to support prompt access to Fortivita for on-label patients. When a patient receives their initial prescription, our hub is able to support benefits verification and assist offices and patients in navigating denials or appeals processes. We've also implemented a Quick Start program to provide free treatment in one-week increments to get patients on therapy should there be any delays in securing verification of coverage. We are pleased to share that to date we have been very successful in securing coverage with minimal payer issues. We also have a $0 copay for any commercial patients and adherence programs to support patients in receiving the drug as prescribed by their healthcare provider. We are pleased with the progress made by our commercial team thus far and the positive reception FOTIVDA has received from oncologists and patients as well as the broader medical community. We are committed to establishing Fortivda as the market leader in its indicated population, and we look forward to updating you on our efforts over the coming quarters. With that, I would now like to turn the call over to Dr. Mike Needle to review the clinical opportunities within our pipeline.
spk06: Thank you, Mike. Beyond the launch of Fortivda, we are pleased with the progress we have made this past quarter in the clinic. Let's start with our devosinib immunotherapy combination programs. When considering first-line advanced RCC, the introduction of immunotherapy VEGF receptor TKI combinations represented a significant shift in the treatment landscape. Supported by previous reported data from our Phase I-II Tenevo study of tavazimib in combination with nivolumab or Optivo, Bristol-Myers Squibb's anti-PD-1 therapy, It is our belief that this combination could benefit patients in the relapsed or refractory setting. Recall that data from the Tenevo study showed what appeared to be synergistic anti-tumor effects on overall response rate, ORR, and progression-free survival, PFS, as well as favorable tolerability in both treatment-naive and previously treated patients with advanced RCC. We look forward to enhancing our understanding of the potential of this combination following prior immunotherapy in the Tenevo 2 trial, which is being conducted under our March 2021 clinical trials collaboration and supply agreement with Bristol Myers Squibb. We are pleased to share today that we expect to commence enrollment in the trial in the third quarter of this year. In parallel, we are continuing with our Tavazanib immunotherapy program in patients hepatocellular carcinoma, or HCC, another area in which we believe tavazanib has the potential to serve as an attractive VEGF receptor TKI to be used in combination with immunotherapy. Enrollment in the phase two portion of the phase 1b2 deductive trial of tavazanib in combination with durvamumab or infimsi, AstraZeneca's PD-L1 therapy continues. At the ASCO GI Cancer Symposium in January, we shared data from the phase 1B portion of the trial, which showed no dose-limiting toxicities and demonstrated a 29% partial response rate and 71% disease control rate. These findings were comparable with the bevacizumab and atezolizumab combination, which is an emerging standard in the care of the frontline settings. Of note, we are excited to share with you today that we will be amending enrollment to include patients previously treated with Bevacizumab and Atezolizumab. The adoption of Bevacizumab and Atezolizumab as the frontline standard of care has created a need to define the new standard of care following frontline immunotherapy combination. This is very similar to the RCC situation that inspired the Tenevo 2 trial. And we're excited to enroll this new population of patients in the deductive study. And with the amendment to the study, we anticipate full enrollment to be completed in the first half of 2022, which is a delay from our previous expectation at the end of 2021. Moving on to ficlotuzumab, our HGF-CMET IgG antibodies. At the ASCO annual meeting in June, we were pleased to report positive results from the Phase II study of ficletuzumab as a single agent or in combination with cetuximab, or Erbitux, an EGFR-targeted antibody. The study was conducted in patients with metastatic head and neck squamous cell carcinoma, HNSCC, who have failed prior immunotherapy, chemotherapy, and cetuximab, known as panrefractory disease. The ficletuzumab-situximab combination arm met the study's primary endpoint of median PFS. Of note for future studies, patients with human papillomavirus negative or HPV negative disease who received ficletuzumab and situximab combination demonstrated both a superior ORR and median PFS versus historical controls. Specifically, patients with HPV-negative disease who received ficletuzumab and cetuximab produced prolonged PFS and a response rate of 38%, which included two complete responses. HPV-negative HNSEC is normally associated with poorer outcomes compared to HPV-positive disease, particularly in the panrefractory setting, when no effective treatment currently exists. In addition, HGF expression is generally higher in HPV negative patients than HPV positive patients, indicating more of a role in tumor growth and progression for HGF in HPV negative tumors. While we and our clinical collaborators are very encouraged with these data, primarily due to a shortage of required key raw materials and manufacturing supplies, also used in COVID-19 vaccines, the potential start date for any registration study with fliclituzumab will be pushed back from the first half of 2022 into 2023. In the meantime, we will continue our dialogue with regulators to identify the optimal registration study design for the program and look forward to providing updates on this and any potential partnering discussions in the coming quarters. I will now turn the call over to Eric to discuss second quarter 2021 financial results. Eric?
spk08: Thanks, Mike. Total revenue for the second quarter of 2021 was $7.6 million, with U.S. net product revenue for the second quarter of 2021 was $6.7 million. Our sales force was sized in conjunction with external consultants to achieve near-census coverage. Given our status as a leader in the share of voice in the relapsed or refractory RCC setting, we believe that our level of spend is appropriate and effective. We continue to expect that our total commercial spend for the year will be approximately $40 million. Furthermore, we continue to expect gross margins to be in the mid to high 80th percentile. Research and development expense for the second quarter of 2021 was $6.9 million and compared with $4.4 million for the second quarter of 2020. Our original 2021 R&D guidance of $40 million for our existing pipeline plans included the initiation of the Tenevo 2 trial costs and expenses for manufacturing of study drug material for a potential registrational study for flaclituzumab. We now expect R&D expense to be in the $30 million range for the year. The $10 million decrease and expected R&D expenses primarily attributable to the aforementioned delay in our clinical study manufacturing for plaquituzumab. Given the size of our existing commercial organization and our R&D plans as described, we believe that our corporate staff is appropriately sized for this level of activity. Selling general and administrative expenses for the second quarter of 2021 were $14.9 million, compared with $3.7 million for the second quarter of 2020. We continue to expect that our total G&A spend for the year will be approximately $20 million. We ended the second quarter 2021 with cash, cash equivalents, and marketable securities of $102.9 million, compared with $121.4 million at the end of the first quarter. The lower net cash burn for the second quarter compared to prior quarters reflects the addition of our first full quarter of U.S. product revenues, as we expect our spending levels to remain relatively constant, we anticipate that net cash burn to continue to decline as we expect our revenues to continue to increase. We believe our cash from planned revenues, existing cash, cash equivalents and investments, and available credit under the Hercules facility will be sufficient to fund our launch and all current pipeline plans we have shared today, including the Phase III Tenevo trial, the Phase II deductive study, the Phase I AB380 study, and clinical drug supply manufacturing. A full overview of results for the second quarter of 2021 are available in our quarterly report on Form 10Q. I will now turn the call back over to Michael Bailey. Michael?
spk11: Michael Bailey Thank you, Eric. To close, we believe we are well positioned for continued success with the commercial launch of Fatibda here in the U.S., as well as the continued advancement of the balance of our pipeline programs. We look forward to providing updates on our progress in the coming quarters as we continue on our mission of improving the lives of patients with cancer. We'll now open the line to Q&A. Operator?
spk17: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question will come from Steven Wiley with Stiefel. Please go ahead.
spk15: Hi, this is Bonnie Quach on for Steve Willey. Thanks for taking our questions. So my first question is about the Fativda sampling program. Can you share anything about how long you intend to keep running that program? And my second question is, how do the 175 ordering accounts look in comparison to the greater than 3,000 number of accounts you've been actively targeting after launching Fativda? Any color that you could provide would be helpful.
spk10: Thanks. Sure, Bonnie. This is Michael Bailey. I'll turn it over to Mike Ferra to add some color.
spk09: Great. Thanks for the question, Bonnie. So, starting with the samples, we definitely see this as a launch support program, and it's been a really valuable tool for the team, and I think it shows our conviction in the product to get that pre-sample to help generate initial trials. As we mentioned, access is still difficult. So for a while in our launch, there are still accounts we'll be seeing for the first time. And so it is still useful to have that sample program. But we do see it phasing down and ultimately phasing out. It is a launch patient experience program. And we're really pleased, again, with the impact to date. And as far as the 175 unique accounts so far, again, I think this speaks to the opportunity in front of us and the challenges of launching during COVID. it's difficult to access a lot of your customers in person and to get the frequency you need out of the gate. So often to convert an account, it takes a few visits. It's going to take us a little bit longer to get to that point with all of our key accounts. But we see it as really there's a tremendous opportunity still in front of us and that there are a lot of accounts who we think are great potential prescribers of Fortivda. We continue to make penetration. As we said, our scripts are growing every month so far, month on month. And we think we'll continue to penetrate that and get broader adoption over time.
spk15: Great. Thank you so much, and congrats on the progress.
spk03: Thank you.
spk17: Thank you. Our next question will come from Andrew Behrens with SBB Learing. Please go ahead.
spk20: Hi. Thanks.
spk21: Congrats on the quarter, guys. I was wondering if you have any idea of the type of duration you're seeing. I know it's early, but just trying to get a sense Or was there a warehouse of end stage patients that came onto the drug? Or should we expect similar duration to what you saw in the pivotal program? And then also, I guess, how many unique prescribers are you seeing prescribed TiVo? And are these prescribers, how many scripts are the average prescriber writing so far?
spk23: Thanks for the question, Andrew. I'm going to turn that over to Mike.
spk09: Sure. Great questions, Andrew. So for duration of therapy, the reality is it's just too early. We're in our first full quarter of sales. If you think back to the TiVo 3 study, we had 18% of patients still progression-free at two years. So it's going to take us a while to really see, you know, what percent of patients stay on this drug for a long duration, and that ultimately is We'll create our average, but we're really pleased with what we've seen so far. We'll continue to track, but it will take quite a while before that's really a robust duration number. As far as number of prescribing accounts, as we mentioned, there's been 175 unique accounts to date, and we've had 453 scripts to date. So you could do the division there to get the average. As you can imagine with sales building every single month, A lot of the accounts have just kind of started, and we'll see additional volume build over time and refills build over time.
spk21: Okay. So the unique prescriber is the same thing as the unique account that you're citing?
spk09: Correct. So basically patients can get our drug through the mail order, in which case it's delivered through a specialty pharmacy, and that would be a prescriber, or they get it directly from their prescribing facility or their treating facility, which they would buy through a specialty distributor so that we get a mix of prescriptions to a physician and sales to an account. So we, we add those together to come up with this kind of account prescriber number for you of unique individuals or institutions using the drug.
spk20: Okay. Thanks a lot. And congrats again. Thanks Andrew.
spk17: Thank you. Our next question will come from Colleen Casey with Baird. Please go ahead.
spk14: Hi, good afternoon. Thanks so much for your questions and congrats on all the progress. For the early launch, I guess, do you have any anecdotal data on what type of patients physicians are putting on in the early stages? Potentially what line of treatment or anything special about these patients?
spk11: Yeah, Mike can certainly share some anecdotes. We don't have a quantity of data to really give a breakdown at this point. But Mike,
spk09: Yeah, thanks for the question, Colleen. And it is just as Michael said, it's anecdotes at this point. We're seeing a range of patient types, as we had mentioned in our last call from just the initial patients. We have some who are two prior systemic therapies, that kind of typical third-line patient. We're certainly seeing some later-line patients who maybe have failed a few more lines of treatment and had run out of options. But It's early days, and you don't get that data on all of your patients, so it's going to take a while for us to build up a robust data set of the patient types, but we're pleased with what we're seeing, and we're seeing a range of patients that can benefit from treatment.
spk14: Great. That's helpful. Thank you. And on the sample program, I think you mentioned you're converting about 11% of those to commercial drug. I guess what happens to the other percent of those, and kind of how do you see that changing in the future?
spk09: Mike? Sure. So ultimately, we expect all of those samples to get used. That's the expectation. And, you know, as you can imagine, the sample gets delivered to a practice. It means the practice has interest in the drug, and they want to have it available for the next patient that comes in. So if the patient were to come in the very next day after they got it, it would be about a month until we saw a conversion. So, you know, it's going to take a while off, and it doesn't line up just like that. But ultimately, these bottles are out giving us a great presence in these practices where it's difficult to access during COVID. And when they have the appropriate patient, I mean, many may have requested for a patient who's currently in the second line, and they think, there may be an option needed in a month or two. So, you know, it could take a little bit of time, but ultimately we believe these samples are being requested because they're strong interest. And when they have the right patient, they're going to utilize those in a month later, it turns into a commercial script.
spk11: Yeah. Just to add color that this is not a sample drop, um, like in, in some of the, uh, non-specialty markets, this is requested specifically by the physicians.
spk14: Got it. That's helpful. Thank you. And then I know you got a question earlier about duration, and it's still early for that, but do you have any early insight into discontinuations so far?
spk04: Mike, do you want to talk about that?
spk09: Yeah, we really don't. It's too early to say. We don't always get the information. A lot of our sales go through accounts where you just see volume going into the account. You don't have any information about the patient. So You know, it's something that with more time on the market and we'll have more tools and resources to get a meaningful data set. But again, we are seeing growth month on month. We're seeing script growth month on month, and we're really pleased with the trajectory.
spk13: Okay, great. Thanks so much for taking our questions.
spk03: Operator, are there any other questions?
spk17: Thank you. Our next question will come from Arthur He with HC Wainwright.
spk02: Hey, good afternoon, guys. This is Arthur He for RK. Thanks for taking my question. I had two questions. One is on the TIBDA. Regarding the gross net rate as the estimated 16 cents, Could we assume that could be a wrong rate in the near term, or could we see that could go down?
spk05: Eric, do you want to tackle that one?
spk08: Yeah, thanks for the question. Yeah, I think we've been stating for a while that we believe that our gross-to-net would be similar over time to what you've seen in other sort of oral oncology RCC cases. type products. So we would expect that the gross to net, which is currently, as you said, around 16%, that that'll just probably creep up a little bit over time. You'll see Exalexis, for example, is a little bit higher than that.
spk02: Okay, thank you. And my second question is regarding the FICO program. So could you give us more color regarding the shortage of the manufacturing? Do you have any plan to looking for an alternative manufacturing partner to produce the drug. Thank you.
spk11: Yeah, thanks, Arthur, for the question. So our agreement with our contract manufacturer called for beginning manufacturing in Q3 of this year. They recently informed us that they're having difficulty getting key raw materials manufacturing supplies because they're being used for COVID vaccines. So we clearly understand that challenge. The process to switch manufacturers, and I don't think that would fix our problem, to be honest with you, because this is about raw materials, and so the raw materials are generally sourced from many of the same places. So we've certainly turned over all the stones that we could, and we're anxiously waiting for a confirmation of a new date, and we'll provide you with updates as appropriate.
spk02: Thank you for that. Thanks for taking my question.
spk17: Thank you. I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Mr. Michael Bailey for any closing remarks.
spk11: Thank you, and thank you all for joining us today. We appreciate your continued support, and we look forward to updating you all on further progress in the coming quarters.
spk17: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. music music Good afternoon, thank you for standing by, and welcome to the Aveo Oncology Second Quarter 2021 Financial Results Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one on your telephone. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your speaker, Mr. Eric Lucero, Chief Financial Officer of Aveo. Please go ahead.
spk08: Thank you, Operator. Good afternoon, and thank you all for joining us on today's call to discuss Aveo's second quarter 2021 financial results and business update. I'm joined today by Michael Bailey, Chief Executive Officer, Mike Ferraresso, Chief Commercial Officer, and Dr. Michael Neal, Chief Medical Officer. Before we begin today's call, let me remind you, that during this discussion we'll be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to important risks and uncertainties, including those that are detailed in today's press release and in the risk factors section of our most recent quarterly report on Form 10-Q, which is on file with the SEC that may cause actual results to differ materially from those results expressed in Shutt's statements. Furthermore, we caution you that these forward-looking statements represent our views only as of today, and we do not assume any obligation to update these statements, whether as a result of new information, future events, or otherwise, as except as noted and may be required by law. With that, I will now turn the call over to our President and Chief Executive Officer, Michael Bailey. Michael.
spk11: Thank you, Eric, and thank you to everyone for joining us on today's call. The second quarter marked our first full quarter as a commercial stage company. and we're excited to share with you the continued progress we have made with the launch of Fatibda, or Tuvozanib, our first commercial product, as well as the progress with the rest of our pipeline and our financial results for the quarter. Today, we are pleased to report our first full quarter of Fatibda sales, which reflect a rapid commercial uptake since it was launched on March 22nd. I can say with confidence that we believe that we are off to a strong start. As many of you already know, Fatibda is an oral, once a day, VEGFR TKI approved in the U.S. for the treatment of adults with relapse or refractory advanced renal cell carcinoma, or RCC, following two or more prior systemic therapies. This approval was based on the Phase III TiVo III study. The first positive RCC Phase III study in this highly refractory setting and the first Phase III study to incorporate a predefined subpopulation of patients who had received prior immunotherapy, which reflects the new standard of care in earlier lines of treatment. It is important to note that prior to FATIVDA, therapies used in these settings were often chosen based on extrapolation of clinical data from treatment and early line settings. as well as from clinical data that did not include a meaningful subpopulation of patients who received prior immunotherapy. Furthermore, due to a lack of robust prospective data in this refractory setting, coupled with tolerability concerns of other available treatment options, we know that a large percentage of patients choose to opt out of continuing on to later line therapy. Now, would the UF FDA approval for FATIVDA the oncology community is able to offer patients an evidence-based treatment option with a favorable tolerability profile to address these significant unmet needs. While this positive Phase III data has supported the successful launch to date by differentiating FITIVDA from other available treatment options, I am pleased to say that we continue to gain valuable data from the TEVO3 trial. For example, At the 2021 ASCO annual meeting in June, we were pleased to share long-term efficacy follow-up and additional tolerability data from the TIBO3 study. Specifically, patients treated with Pitivna demonstrated a durability of response of over 20 months, more than two times that of serotonin, with the overall survival hazard ratio relative to serotonin continuing to improve with longer follow-up. In addition, an analysis of treatment emergent adverse events showed longer time to onset and a lower rate of dose reductions for these adverse events related to tibozanib as compared with serotonin. We believe these data continue to demonstrate a durability of response with FITIVDA as well as favorable tolerability profile that we know are important considerations for patients and physicians in the selection of later lines of therapy. With that setting the stage for this quarterly update, I'd like to turn the call over to Mike Barrasso to walk us through a more detailed commercial update, including second quarter metrics. Mike?
spk09: Thank you, Michael. As Michael mentioned, we are very encouraged with the launch to date, and I'm excited to share with you results from our first full quarter of sales. For the second quarter of 2021, U.S. net product revenue was $6.7 million, which reflects inventory shipped to distributors in our 16% gross to net estimate. Since launching the drug in late March to the end of Q2, U.S. net product revenue was $7.8 million. Of note, Q1 sales reflected inventory build, while Q2 largely represented end-user demand. We estimate that as of the end of the second quarter, there was approximately two weeks of inventory available on the channel underscoring that our net revenue total was achieved with a lean inventory level. During the second quarter, we recorded a total of 283 commercial prescriptions, including increased prescriptions each month for a total of 453 prescriptions from launch through the end of July. This includes scripts from over 175 unique accounts across all settings, from major academic centers to the community. Finally, a total of 207 patient experience samples were requested and delivered through the end of July, and roughly 11% have already converted to a commercial prescription. We are encouraged by this, given that it takes at least a month after a patient received a sample to convert to a commercial prescription. Taken together with the data from IQVIA Brand Impact, which shows that Fotivda is the leader in share of voice in the relapsed refractory RCC setting. We believe these numbers are a strong indicator of the hard work of our team, including our now fully deployed field team. Let me take a minute to discuss the commercial team that's helping drive these results. Our team is comprised of individuals who are deeply experienced in oncology, with a proven track record in reaching and impacting customers, both in-person and when required, remotely. While COVID restrictions have posed a challenge for gaining in-person access to treating oncologists, which is the case for all pharma companies, as indicated by Acuvia's in-person access statistics, our teams are executing well, and we are seeing steady progress toward reaching all of our key customers. As I mentioned, we have received orders from over 175 unique accounts to date, which just scratches the surface of the 3,000 plus targeted accounts. In addition to the field sales team, we have supplemented their efforts with extensive marketing outreach, spanning a wide variety of formats in order to increase awareness in areas facing access restrictions. I would like to point out that while IV oncology drug use has declined, oral oncology drug use saw an increase year over year during COVID. as both physicians and patients are seeking treatments that can be administered in the at-home setting. We're hopeful that orally administered drugs with low rates of dose modifications, such as Fotivda, can be highly valuable in this context. Through the team's efforts, Fotivda is now broadly available through a limited network of specialty pharmacies and specialty distributors. By limiting our distribution network, we believe we are able to improve the customer experience for those receiving FOTIVDA at home, through our best-in-class specialty pharmacy partners, as well as for those who receive FOTIVDA directly from the treatment facility. We have designed our network to allow oncology practices who dispense directly to their patients to do so not only for the first month of treatment, but for the duration of treatment. We believe our model is unique within the RCC space. Our comprehensive support services provided through the Aveo Access Center of Excellence, also known as the ACE Patient Support Hub, helps to support prompt access to Fortivita for on-label patients. When a patient receives their initial prescription, our hub is able to support benefits verification and assist offices and patients in navigating denials or appeals processes. We have also implemented a Quick Start program to provide free treatment in one-week increments to get patients on therapy should there be any delays in securing verification of coverage. We are pleased to share that to date we have been very successful in securing coverage with minimal payer issues. We also have a $0 copay for any commercial patients and adherence programs to support patients in receiving the drug as prescribed by their healthcare provider. We are pleased with the progress made by our commercial team thus far and the positive reception FOTIVDA has received from oncologists and patients. as well as the broader medical community. We are committed to establishing Fortivda as the market leader in its indicated population, and we look forward to updating you on our efforts over the coming quarters. With that, I would now like to turn the call over to Dr. Mike Needle to review the clinical opportunities within our pipeline.
spk06: Thank you, Mike. Beyond the launch of Fortivda, we are pleased with the progress we have made this past quarter in the clinic. Let's start with our Tavazanib immunotherapy combination programs. When considering first-line advanced RCC, the introduction of immunotherapy VEGF receptor TKI combinations represented a significant shift in the treatment landscape, supported by previous reported data from our Phase I-II Tenevo study of Tavazanib in combination with Nivolumab or Optivo, Bristol-Myers Squibb's anti-PD-1 therapy, It is our belief that this combination could benefit patients in the relapsed or refractory setting. Recall that data from the Tenevo study showed what appeared to be synergistic anti-tumor effects on overall response rate, ORR, and progression-free survival, PFS, as well as favorable tolerability in both treatment-naive and previously treated patients with advanced RCC. We look forward to enhancing our understanding of the potential of this combination following prior immunotherapy in the Tenevo 2 trial, which is being conducted under our March 2021 clinical trials collaboration and supply agreement with Bristol Myers Squibb. We are pleased to share today that we expect to commence enrollment in the trial in the third quarter of this year. In parallel, we are continuing with our Tavazanib immunotherapy program in patients hepatocellular carcinoma, or HCC, another area in which we believe tavazanib has the potential to serve as an attractive VEGF receptor TKI to be used in combination with immunotherapy. Enrollment in the phase two portion of the phase 1b2 deductive trial of tavazanib in combination with durvamumab or infimsi, AstraZeneca's PD-L1 therapy continues. At the OSCO GI Cancer Symposium in January, we shared data from the phase 1B portion of the trial, which showed no dose-limiting toxicities and demonstrated a 29% partial response rate and 71% disease control rate. These findings were comparable with the bevacizumab and atezolizumab combination, which is an emerging standard in the care of the frontline settings. Of note, we are excited to share with you today that we will be amending enrollment to include patients previously treated with Bevacizumab and Atezolizumab. The adoption of Bevacizumab and Atezolizumab as the frontline standard of care has created a need to define the new standard of care following frontline immunotherapy combination. This is very similar to the RCC situation that inspired the Tenevo 2 trials. And we're excited to enroll this new population of patients in the deductive study. And with the amendment to the study, we anticipate full enrollment to be completed in the first half of 2022, which is a delay from our previous expectation at the end of 2021. Moving on to ficlotuzumab, our HGF-CMET IgG antibodies. At the ASCO annual meeting in June, we were pleased to report positive results from the Phase II study of ficletuzumab as a single agent or in combination with cetuximab, or Erbitux, an EGFR-targeted antibody. The study was conducted in patients with metastatic head and neck squamous cell carcinoma, HNSCC, who have failed prior immunotherapy, chemotherapy, and cetuximab, known as panrefractory disease. The ficletuzumab-situximab combination arm met the study's primary endpoint of median PFS. Of note for future studies, patients with human papillomavirus-negative or HPV-negative disease who received ficletuzumab and situximab combination demonstrated both a superior ORR and median PFS versus historical controls. Specifically, patients with HPV-negative disease who received ficletuzumab and cetuximab produced prolonged PFS and a response rate of 38%, which included two complete responses. HPV-negative HNSCC is normally associated with poorer outcomes compared to HPV-positive disease, particularly in the panrefractory setting, where no effective treatment currently exists. In addition, HGF expression is generally higher in HPV negative patients than HPV positive patients, indicating more of a role in tumor growth and progression for HGF in HPV negative tumors. While we and our clinical collaborators are very encouraged with these data, primarily due to a shortage of required key raw materials and manufacturing supplies, also used in COVID-19 vaccines, the potential start date for any registration study with fliclituzumab will be pushed back from the first half of 2022 into 2023. In the meantime, we will continue our dialogue with regulators to identify the optimal registration study design for the program and look forward to providing updates on this and any potential partnering discussions in the coming quarters. I will now turn the call over to Eric to discuss second quarter 2021 financial results. Eric?
spk08: Thanks, Mike. Total revenue for the second quarter of 2021 was $7.6 million, with U.S. net product revenue for the second quarter of 2021 was $6.7 million. Our sales force was sized in conjunction with external consultants to achieve near-census coverage. Given our status as a leader in the share of voice in the relapsed or refractory RCC setting, we believe that our level of spend is appropriate and effective. We continue to expect that our total commercial spend for the year will be approximately $40 million. Furthermore, we continue to expect gross margins to be in the mid to high 80th percentile. Research and development expense for the second quarter of 2021 was $6.9 million and compared with $4.4 million for the second quarter of 2020. Our original 2021 R&D guidance of $40 million for our existing pipeline plans included the initiation of the Tenevo 2 trial costs and expenses for manufacturing of study drug material for a potential registrational study for flaclituzumab. We now expect R&D expense to be in the $30 million range for the year. The $10 million decrease and expected R&D expenses primarily attributable to the aforementioned delay in our clinical study manufacturing for plaquituzumab. Given the size of our existing commercial organization and our R&D plans as described, we believe that our corporate staff is appropriately sized for this level of activity. Selling general and administrative expenses for the second quarter of 2021 were $14.9 million, compared with $3.7 million for the second quarter of 2020. We continue to expect that our total G&A spend for the year will be approximately $20 million. We ended the second quarter 2021 with cash, cash equivalents, and marketable securities of $102.9 million, compared with $121.4 million at the end of the first quarter. The lower net cash burn for the second quarter compared to prior quarters reflects the addition of our first full quarter of U.S. product revenues, as we expect our spending levels to remain relatively constant, we anticipate that net cash burn to continue to decline as we expect our revenues to continue to increase. We believe our cash from planned revenues, existing cash, cash equivalents and investments, and available credit under the Hercules facility will be sufficient to fund our launch and all current pipeline plans we have shared today, including the Phase III Tenevo trial, the Phase II deductive study, the Phase I AB380 study, and clinical drug supply manufacturing. A full overview of results for the second quarter of 2021 are available in our quarterly report on Form 10Q. I will now turn the call back over to Michael Bailey. Michael.
spk11: Thank you, Eric. To close, we believe we are well positioned for continued success with the commercial launch of Fatibda here in the U.S., as well as the continued advancement of the balance of our pipeline programs. We look forward to providing updates on our progress in the coming quarters as we continue on our mission of improving the lives of patients with cancer. We'll now open the line to Q&A. Operator?
spk17: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question will come from Steven Wiley with Stiefel. Please go ahead.
spk15: Hi, this is Bonnie Quach on for Steve Willey. Thanks for taking our questions. So my first question is about the Fativda sampling program. Can you share anything about how long you intend to keep running that program? And my second question is, how do the 175 ordering accounts look in comparison to the greater than 3,000 number of accounts you've been actively targeting after launching Fativda? Any color that you could provide would be helpful.
spk10: Thanks. Sure, Bonnie. This is Michael Bailey. I'll turn it over to Mike Ferra to add some color.
spk09: Great. Thanks for the question, Bonnie. So, starting with the samples, we definitely see this as a launch support program, and it's been a really valuable tool for the team, and I think it shows our conviction in the product to get that pre-sample to help generate initial trials. As we mentioned, access is still difficult. So for a while in our launch, there are still accounts we'll be seeing for the first time. And so it is still useful to have that sample program. But we do see it phasing down and ultimately phasing out. It is a launch patient experience program. And we're really pleased, again, with the impact to date. And as far as the 175 unique accounts so far, again, I think this speaks to the opportunity in front of us and the challenges of launching during COVID. it's difficult to access a lot of your customers in person and to get the frequency you need out of the gate. So often to convert an account, it takes a few visits. It's going to take us a little bit longer to get to that point with all of our key accounts. But we see it as really there's a tremendous opportunity still in front of us and that there are a lot of accounts who we think are great potential prescribers of Flotibda. We continue to make penetration. As we said, our scripts are growing every month so far, month on month. And we think we'll continue to penetrate that and get broader adoption over time.
spk15: Great. Thank you so much, and congrats on the progress.
spk03: Thank you.
spk17: Thank you. Our next question will come from Andrew Behrens with SBB Wearing. Please go ahead.
spk20: Hi. Thanks.
spk21: Congrats on the quarter, guys. I was wondering if you have any idea of the type of duration you're seeing. I know it's early, but just trying to get a sense Or was there a warehouse of end-stage patients that came onto the drug? Or should we expect similar duration to what you saw in the pivotal program? And then also, I guess, how many unique prescribers are you seeing prescribed TiVo? And are these prescribers, how many scripts are the average prescriber writing so far?
spk23: Thanks for the question, Andrew. I'm going to turn that over to Mike.
spk09: Sure. Great questions, Andrew. So for duration of therapy, the reality is it's just too early. We're in our first full quarter of sales. If you think back to the TiVo 3 study, we had 18% of patients still progression-free at two years. So it's going to take us a while to really see, you know, what percent of patients stay on this drug for a long duration, and that ultimately is We'll create our average, but we're really pleased with what we've seen so far. We'll continue to track, but it will take quite a while before that's really a robust duration number. As far as number of prescribing accounts, as we mentioned, there's been 175 unique accounts to date, and we've had 453 scripts to date. So you could do the division there to get the average. As you can imagine with sales building every single month, A lot of the accounts have just kind of started, and we'll see additional volume build over time and refills build over time.
spk21: Okay. So the unique prescriber is the same thing as the unique account that you're citing?
spk09: Correct. So basically patients can get our drug through the mail order, in which case it's delivered through a specialty pharmacy, and that would be a prescriber, or they get it directly from their prescribing facility or their treating facility. which they would buy through a specialty distributor so that we get a mix of prescriptions to a physician and sales to an account. So we add those together to come up with this kind of account prescriber number for you of unique individuals or institutions using the drug.
spk20: Okay. Thanks a lot and congrats again. Thanks, Andrew.
spk17: Thank you. Our next question will come from Colleen Cusey with Baird. Please go ahead.
spk14: Hi, good afternoon. Thanks so much for your questions and congrats on all the progress. For the early launch, I guess, do you have any anecdotal data on what type of patients physicians are putting on in the early stages, potentially what line of treatment or anything special about these patients?
spk11: Yeah, Mike can certainly share some anecdotes. We don't have a quantity of data to really give a breakdown at this point, but Mike,
spk09: Yeah, thanks for the question, Colleen. And it is just as Michael said, it's anecdotes at this point. We're seeing a range of patient types, as we had mentioned in our last call from just the initial patients. We have some who are two prior systemic therapies, that kind of typical third-line patient. We're certainly seeing some later-line patients who maybe have failed a few more lines of treatment and had run out of options. But It's early days, and you don't get that data on all of your patients, so it's going to take a while for us to build up a robust data set of the patient types, but we're pleased with what we're seeing, and we're seeing a range of patients that can benefit from treatment.
spk14: Great. That's helpful. Thank you. And on the sample program, I think you mentioned you're converting about 11% of those to commercial drug. I guess what happens to the
spk09: other percent of those and kind of how do you see that changing in the future mike sure so ultimately we we expect all of those samples to get used that that's the expectation and you know as you can imagine the sample gets delivered to a practice it means the practice has interest in the drug and they want to have it available for the next patient that comes in So if the patient were to come in the very next day after they got it, it would be about a month until we saw a conversion. So, you know, it's going to take a while off and it doesn't line up just like that. But ultimately these bottles are out giving us a great presence in these practices where it's difficult to access during COVID. And when they have the appropriate patient, I mean, many may have requested for a patient who's currently in the second line and they think, there may be an option needed in a month or two. So, you know, it could take a little bit of time, but ultimately we believe these samples are being requested because they're strong interest. And when they have the right patient, they're going to utilize those in a month later, it turns into a commercial script.
spk11: Yeah. Just to add color that this is not a sample drop, um, like in, in some of the, uh, non-specialty markets, this is requested specifically by the physician.
spk14: Got it. That's helpful. Thank you. And then I know you got a question earlier about duration and it's still early for that, but do you have any early insight into discontinuations so far?
spk04: Mike, do you want to talk about that?
spk09: Yeah, we really don't. It's too early to say. We don't always get the information. You know, a lot of our sales go through accounts where you just see volume going into the account. You don't have any information about the patient. So, You know, it's something that with more time on the market and a lot more tools and resources to get a meaningful data set. But again, we are seeing growth month on month. We're seeing script growth month on month, and we're really pleased with the trajectory.
spk13: Okay, great. Thanks so much for taking our questions.
spk03: Operator, are there any other questions?
spk17: Thank you. Our next question will come from Arthur He with HC Wainwright.
spk02: Hey, good afternoon, guys. This is Arthur for RK. Thanks for taking my question. I had two questions. One is on the TIVDA. Regarding the gross net rate as the estimated 16 cents, Could we assume that could be a wrong rate in the near term, or could we see that could go down?
spk05: Eric, do you want to tackle that one?
spk08: Yeah, thanks for the question. Yeah, I think we've been stating for a while that we believe that our gross-to-net would be similar over time to what you've seen in other sort of oral oncology RCC cases. type products. So we would expect that the gross to net, which is currently, as you said, around 16%, that that'll just probably creep up a little bit over time. You'll see Exalexis, for example, is a little bit higher than that.
spk02: Okay, thank you. And my second question is regarding the FICO program. So could you give us more color regarding the shortage of the manufacturing? Do you have any plan to looking for an alternative manufacturing partner to produce the drug. Thank you.
spk11: Yeah, thanks, Arthur, for the question. So our agreement with our contract manufacturer called for beginning manufacturing in Q3 of this year. They recently informed us that they're having difficulty getting key raw materials manufacturing supplies because they're being used for COVID vaccines. So we clearly understand that challenge. The process to switch manufacturers, and I don't think that would fix our problem, to be honest with you, because this is about raw materials. And so the raw materials are generally sourced from many of the same places. So we've certainly turned over all the stones that we could, and we're anxiously waiting for a confirmation of a new date. We'll provide you with updates as appropriately.
spk02: Thank you for that. Thanks for taking my question.
spk17: Thank you. I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Mr. Michael Bailey for any closing remarks.
spk11: Thank you, and thank you all for joining us today. We appreciate your continued support, and we look forward to updating you all on further progress in the coming quarters.
spk17: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.
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