Q2 2021 Aveo Pharmaceuticals Inc Earnings Call
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Ladies and gentlemen, please standby your conference will begin momentarily, ladies and gentlemen, please standby your conference will begin momentarily.
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Yeah.
Good afternoon. Thank you for standing by and welcome to the Aveo oncology second quarter 2021 financial results call at.
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I'd now like to hand, the conference over to your speaker.
Mr. Eric Who's their chief financial Officer, all of them.
Please go ahead.
Thank you operator, good afternoon, and thank you all for joining us on today's call to discuss the value of our second quarter 2021 financial results on business update I'm joined today by Michael Bailey, Chief Executive Officer, Mike Farrell Retro Chief commercial officer.
Sure.
After Mike O'neill, Chief Medical Officer.
Before we begin today's call. Let me remind you that during this discussion we will 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 such statements.
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, 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 Bayley Michael.
Thank you Eric.
And thank you to everyone for joining us on today's call.
Quarter marked our first full quarter as a commercial stage company and were excited to share with you. The continued progress we have made with the launch of forgiveness Arcimboldi, Ed our first commercial product <unk>.
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 sales, which reflect a rapid commercial uptake since it was launched on March 22nd I can say with confidence that we believe that we're off to a strong start.
As many of you already know, but timna is an oral once a day that J F. R. <unk> approved in the U S for the treatment of adults with relapsed or refractory advanced renal cell carcinoma or RCC, following 2 or more prior systemic therapy.
This approval was based on the phase III Tivo 3 studies the first positive RCC phase III study in this highly refractory setting and the first phase III study to incorporate a pre defined 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 price of <unk> therapies used in these settings, where 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 some later line therapy.
Now with the U S FDA approval for the timber 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 the day by differentiating <unk> from other available treatment options I am pleased to say that we continue to gain valuable data from the Tivo 3 trial.
For example.
At the 2021 <unk> annual meeting in June we were pleased to share long term efficacy follow up an additional tolerability data from the Tivo 3 studies.
Specifically patients treated with <unk> demonstrated the durability of response of over 20 months more than 2 times that surrounds on it.
With the overall survival hazard ratio relative to Sourav net continuing to improve with longer follow up.
In addition, an analysis of treatment emergent adverse event showed longer time to onset and a lower rate of dose reductions for these adverse events related to 2 boes as compared with Sorafenib.
We believe these data continue to demonstrate the durability of response with no debt as well as favorable tolerability profile that we know are important considerations for patients and physicians and selection of later lines of therapy.
With that setting the stage for this quarterly update I'd like to turn the call over to make better Russell to walk us through a more detailed commercial update including second quarter metrics Mike.
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 and 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 2 weeks of inventory available on the channel.
Underscoring that our net revenue total was achieved with a lean inventories 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 for major academic centers to the community.
Finally, a total of 207 patient experienced 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 <unk> brand impact, which shows that flow Timna is the leader in share of voice in the relapsed or 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-19 restrictions have posed a challenge for gaining in person access to treating oncologists, which is the case for all pharma companies as indicated by our Q V. As 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, you need to accounts to date, which just scratches the surface of the 3000 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 and areas facing access restrictions.
I would like to point out that while IV oncology drug usage declined oral oncology drug you saw an increase year over year during COVID-19.
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 switches that can be highly valuable in this context.
Through the team's efforts votive does now broadly available through a limited network of specialty pharmacies and specialty distributors by.
By limiting our distribution network. We believe we are able to improve the customer experience for those receiving <unk> at home through our best in class specialty pharmacy partners as well as for those who received <unk> or 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 centre of excellence also known as the Ace patient support hub helps to support prompt access to protiviti up for on label patients.
When a patient receives their initial prescription or hub is able to support benefits verification and assist offices and patients and navigating denials or appeals processes.
We've also implemented a quick start program to provide free treatment in 1 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 zero dollar co pay for any commercial patients and adherence programs to support patients and receiving the drug as prescribed by their health care provider.
We are pleased with the progress made by our commercial team, thus far and the positive reception <unk> has received from mycologist in patients as well as the broader medical community. We are committed to establishing furtive debt 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.
Thank you Mike.
Beyond the launch of a tiptoe youre pleased with the progress we have made this past quarter in the clinic, let's start with Doctor Hoffman immunotherapy combination programs.
When considering first line advanced RCC, the introduction of immunotherapy Veg F receptor T. K I combinations represented a significant shift in the treatment landscape.
I wanted my previous reported data from our phase 1.2 to Nemo study of <unk> in combination with the volume out more on Tivo, 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 the data from the Geneva study showed what appeared to be synergistic anti tumor effects on overall response rate or RR and progression free survival PFS as well as favorable tolerability in both treatment naive and previously treated patients with advanced RCC.
Look forward to enhancing our understanding of the potential of this combination following prior immunotherapy and the Geneva 2 trial.
It is being conducted under our March 2021 on 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 <unk> immunotherapy program in patients with a Pat on cellular carcinoma or ACC another area in which we believe to Boston and has the potential to serve as an attractive.
That's your ex receptor T K O I to be used in combination with immunotherapy.
Enrollment in the phase II portion on the phase 1 b 2 deductive trial of coupons on me.
In combination with <unk>, mab or infancy, Astrazeneca PD L..1 therapy continues.
At the ESMO Gi cancers symposium in January we shared data from the phase 1 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 debt decision there and it turns on <unk> combination, which is an emerging standard in the care of the frontline setting.
Of note we are excited to share with you today that we will be amending enrollment to include patients previously treated with Bevacizumab and then Tessa lose your map the adoption of that decision they have a tesla lose Ya man.
The frontline standard of care has created a need to define a new standard of care following frontline immunotherapy combination.
This is very similar to the RCC situation that inspired the to me about 2 trial.
And we're excited to enroll this new population of patients and 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 at the line from our previously expectation on previous expectation at the end of 'twenty 'twenty 1.
Moving on to <unk>, our H T F C met ITG antibody.
At the Ash annual meeting in June we were pleased to report positive results from the phase 2 study of cyclic to summit as a single agent or in combination with rituximab or urban box on Egfr targeted antibody.
The study was conducted in patients with metastatic head and neck squamous cell carcinoma H.
H N S. C C who have failed prior immunotherapy chemotherapy and cetuximab known as Pan refractory disease.
<unk> Cetuximab combination on met the study's primary endpoint of median PFS.
Of note for future studies patient with human papilloma virus negative or HPV negative disease, who.
Who received cycle of Tusa man and Cetuximab combination demonstrated both a superior O R. R.
And median PFS versus historical controls.
Specifically patients with HPV negative disease, who received cyclic tusa men in total.
A man produced prolonged PFS.
Sponsored of 38%, which included 2 complete responses.
P G negative H M. C. C is normally associated with poor outcomes compared to HPV positive disease, particularly in the per refractory setting with no effective treatments currently exists.
In addition, HTS expression is generally higher in HPV negative patients and HPV positive patients, indicating more of a role in tumor growth and progression for HTS in HPV negative tumors.
While we and our clinical collaborators on 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 <unk> that will be pushed back from the first half of <unk>.
'twenty 2.
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.
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 80 percentile.
Research and development expense for the second quarter of 2021 was $6.9 million.
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 <unk> 2 trial costs and expenses for manufacturing of study drug material for a potential Registrational study looks like what she was on that.
We now expect R&D expense to be in the $30 million range for the year the $10 million decrease in expected R&D expenses, primarily attributable to the aforementioned delay in a clinical study manufacturing for flight, which is on that.
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 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 on investments and available credit under the Hercules facility will be sufficient to fund our launch and all current pipeline plans, we have share today, including the phase III Tivo trial, the phase II deductive study the phase 1 <unk> hundred 80, <unk> study and clinical drug.
Supply and manufacturing.
Full overview of results for the second quarter of 2021 are available in our quarterly report on form 10-Q.
I will now turn the call back over to Michael Bayley Michael.
Thank you Eric.
Close we believe we are well positioned for continued success with the commercial launch of a tidbit here on the U S.
As well as the continued advancement of the balance of our pipeline programs.
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.
Now open the line for Q&A operator.
Mhm.
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 standby, while we compile the Q&A roster.
Our first question will come from Stephen Wiley with Stifel. Please go ahead.
Hi, This is Bonnie quach on for Steve Willey. Thanks for taking my questions. So my first question is about the statistical sampling program can you share anything about.
How long you intend to keep running that program and my second question is how does this 175 ordering accounts and luck in comparison to the greater than 3000 number of accounts. We've been actively targeting after lunch is there any color that you could provide would be helpful. Thanks.
Sure Bonnie this is Michael Bailey on.
I'll turn it on that over to Mike first on some color.
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 free sample to help generate initial trials so as we.
<unk> access is still difficult so for a while on our launch are still accounts will be seen 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 that the challenges of launching during COVID-19, it's difficult to access a lot of your customers in person and to get them.
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 theres, a tremendous opportunity still in front of us and that there are a lot of accounts, who we think are great potential prescribers up for tender 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.
Great. Thank you so much on congrats on the progress.
Thank you.
Yes.
Thank you. Our next question will come from Andrew Barron with SVP Leerink. Please go ahead.
Hi, Thanks, Congrats on the quarter guys.
Was wondering if you have any idea of the type of duration, you're seeing I know it's early but.
But just trying to get a sense for where it.
Was there a warehouse event stage patients that came onto the drug or should we expect similar duration towards you saw then.
And the pivotal program and then also.
I guess, how many unique prescribers are you seeing prescribed.
Prescribed tivo.
Are these prescribers how many scripts are the average prescriber, writing so far.
Thanks for the question Andrew.
Moving to turn that over to Mike.
Sure Great questions, Andrew so for duration of therapy.
Reality is it's just too early where we're on our first full quarter of sales.
You think back to the Tivo 3 study, we had 18% of patients still progression free at 2 years, So it's going to take us a while to really see.
What percentage of patients stay on this drug for a long duration and that ultimately.
We'll create our average, but we're really pleased with what we've seen so far and we will 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 we spent 175 unique accounts to date and we've had 453 scripts.
Day, 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 I'm, just kind of started and we'll see additional volume build overtime and refill it spilled over time.
Okay.
Unique prescribers.
Prescriber is the same thing is really unique accounts that you're citing.
Correct.
Basically patients can get our drugs 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 the treating facility, which they would buy through specialty distributors. So that we get a mix of prescriptions to a physician and sales to an accounts. So we.
We add those together to come up with this kind of account prescriber number for Ya, a unique individuals or institutions using the drug.
Okay. Thanks, a lot and congrats again.
Thanks, Andrew.
Thank you. Our next question will come from Colin <unk> with Baird. Please go ahead.
Hi, good afternoon. Thanks, so much for taking my questions and congrats on on our progress.
For the early launch I guess do you have any anecdotal data on what type of patients physicians are putting on in the Earth day here potentially what line of treatment or anything special about these patients.
Yeah, Mike can certainly share some anecdotes we don't have.
Quantity of data to really give a breakdown at this point, but Mike.
Yeah. Thanks for the question Colleen and it is just as Michael said, it's anecdotal 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.
2 prior systemic therapies that they're kind of typical third line patients. 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.
It's early days and are 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.
Great. That's helpful. Thank you and on the simple program I think you mentioned, you're converting about 11% of those 2 commercial drugs I'm I guess, what happened to the other percentage of those and kind of how do you see that changing in the future.
Right.
Sure. So ultimately we expect all of those samples to get us there.
The expectation and 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.
It's going to take a while off and it doesn't line up just like that but ultimately. These these models are out giving us a great presence in these practices, where it's difficult to access during COVID-19 and when they have the appropriate patient and many may have requested for a patient who is currently in the second line and they think there may be an option needed in a month.
So it could take a little bit of time, but ultimately we believe these samples are being requested because theres strong interest and when they have the right patient that they're going to utilize those in a month later it turns into a commercial script.
Yes, just to add color that this is not a sample drop.
And some of the.
Non specialty markets. This is requested specifically by the physician.
Got it that's helpful. Thank you.
And then I know you got the question earlier on about duration and it's still early for that but do you have any early insight into discontinuation.
2 question why it's on the tip the regarding the gross nads right as the estimate of 16 per cent crue, assuming that could be around on rating neogen could we see that could go down.
Eric you unpack a wetland.
Yeah. Thanks for the question I think we've been stating for awhile that we believe that our gross to net would be similar over time to what you've seen at other sort of oral oncology R. C. C type products. So so we would expect that the gross to net which is currently as you sat around 16% that that'll just probably creep up a little bit over.
Time, you'll see ex Lexis for example is a little bit higher than that so.
Okay. Thank you and my second question is regarding the the FICO program.
So could you give us more cutter regarding the the shortage of the manufacturing do you have any plan to looking for a automated manufacturing partner to produce the drive.
<unk>.
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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 list Nolan after the speaker presentation. There will be a question and answer session to ask a question. During the session you will be surprised star 1 on your telephone.
If you require any further assistance. Please press star 1 zero I would now like to hand, the conference over to your speaker missed.
Mr. Eric was zero Chief financial officer of avail.
Please go ahead.
Good afternoon, and thank you all for joining us on today's call to discuss the better the second quarter of 2021 financial results on business update on.
On joined today by Michael Bailey, Chief Executive Officer, My share of retro cheese commercial officer and.
And after Michael Neil Chief Medical Officer total.
We begin today's call. Let me remind you that during this discussion will 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 then the risk factors section of our most recent quarterly report on form 10-Q, which is on file with the SEC. It may cause actual results to differ materially from those results expressed an shut statements. Furthermore, we caution you that these forward looking statements.
<unk> represent our views only as of today and we do not assume any obligation to update these statements.
As a result of new information future events or otherwise except as noted.
May be required by law with that I will now turn the call over to our President and Chief Executive Officer, Michael Bailey Michael.
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. We're excited to share with you. The continued progress we have made with the launch of forget the arch of those in in our first commercial product as well as the progress with the rest of our pipeline and our financial results for the Coke.
Water.
Today, we are pleased to report our first full quarter. If it says the sales which reflect a rapid commercial uptake since it was launched on March 22nd I can say with confidence that we believe that we were off to a strong start.
As many of you already know for tip day as an aural once a day that's F. R. T. K I approved in the U S for the treatment of adults with relapse or refractory advanced renal cell carcinoma R. R. C C. Following 2 or more prior systemic therapy.
Disapproval was based on the phase 3 T. Bo 3 study the first positive RCC phase 3 study in this highly refractory setting and the first day 3 study to incorporate a predefined subpopulation on patients who had received prior immunotherapy, which reflects the new standard Karen.
Early the line is a trip.
It is important to note that price of <unk> therapies used in these settings, where 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 site 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 U F F D. A approval from the tip. The 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 days 3 day that has supported the successful launch the day by differentiating forgive that from other available treatment options I am pleased to say that we continue to gain valuable data from the tebow 3 trial.
For example.
At the 2021 <unk> annual meeting in June we were pleased to share longterm actually follow up an additional tolerability data from the T. Bo 3 study.
Specifically patients treated with contempt that demonstrated the durability of response of over 20 months more than 2 times that of Saddam isn't it.
With the overall survival hazard ratio relative to her on the continuing to improve with longer follow up.
In addition, an analysis of treatment emergent adverse event showed longer time to onset and a lower rate of dose reduction to these adverse events related to those in it as compared with the rock in it.
We believe these day to continue to demonstrate a durability of response with that as well as favorable tolerability profile that we know are important considerations for patients and physicians and selection of later lines of therapy.
With that setting the stage for this quarterly update I'd like to turn the call over to make fair Russell to walk us through a more detailed commercial update including second quarter metrics Mike.
Thank you Michael.
Michael mentioned, we are very encouraged with the lunch today and I'm excited to share with your results from our first full quarter of sales.
Cause the second quarter of 2021 U S. Net product revenue was 6.7 million, which reflects inventories ship to distributors and are 16 per cent 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.
We estimate that as of the end of the second quarter. There was approximately 2 weeks of inventory available on the channel underscoring that are net revenue total was achieved with a lean inventory level.
During the second quarter, we've 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 for major academic centers to the community.
Finally, a total of 207 patient experienced 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 for my Qiviut brand impact, which shows that <unk> is the leader and share a voice in the relapsed refractory RCC setting. We believe these numbers are a strong indicator of the hard work of our team including are 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 and reaching in impacting customers both in person and when required remotely well.
While COVID-19 restrictions have posed a challenge for gaining in person access to treating oncologist, which is the case for all pharma companies as indicated by a Q V. As in person access statistics are 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, you need to accounts to date, which just scratches the surface of the 3000 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 and areas facing access restrictions.
I would like to point out that while Ivy oncology drug use has declined oral oncology drug use on increase year over year during COVID-19.
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 for Tuesday can be highly valuable in this context.
Alright, this past quarter and the clinic, let's start with Doctor Mazda immunotherapy combination programs.
When considering first line advanced RCC, the introduction of immunotherapy VEGF receptor PKI combinations represented a significant shift and the treatment landscape supported by previous reported data from our phase 1 to 2 Nivo study of devices on me in combination.
With the volume ma'am or on Tivo, Bristol Myers Squibb anti P. D..1 therapy. It is our belief that this combination could benefit patients and to relax on refractory center.
Recall the data from the Tivo study showed what appeared to be synergistic anti tumor effects on overall response rate O R. R and progression free survival P. F S as well as favorable tolerability and both treatment naive I previously treated patients with advanced RCC.
We look forward to enhancing our understanding of the potential of this combination.
Prior immunotherapy and the Geneva to trial, which is being conducted under our March 20th 21 clinical trials collaboration on 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 Doctor <unk> immunotherapy program in patients with Apatow cellular carcinoma or HCC another area in which we believe to Verizon has the potential to serve as attractive.
Digest receptor TK are to be used in combination with immunotherapy.
Enrollment in the phase II portion of the phase 1 day to deductive trial of deposits in combination with Donovan Mcnab Orange <unk> Astrazeneca P. D. L..1 therapy continues.
At the Osco Gi cancer Symposium in January shared data from the phase 1 b portion of the trial, which showed no dose limiting toxicity and demonstrated a 29 per cent partial response rate and 71% disease control rate.
These findings were comparable with the Bevacizumab and it turns elisia maps combination, which is an emerging standard and the care of the frontline setting.
Of note we are excited to share with you today that we will be amending enrollment to include patients previously treated with Bevacizumab and it has elysium at the adoption of debt decision may I have on that Tesla lose you ma'am.
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 rspca situation that inspired the to me about 2 trial.
We're excited to enroll this new population of patients and the deductive study and with the amendment to the study we anticipate fully enrollment to be completed in the first half of 2022, which is at a line from a previously expectation our previous expectation at the end of 2021.
Moving on to <unk> or H T F C. Matt I G G antibody.
At the <unk> annual meeting in June we were pleased to report positive results from the phase 2 study of cycling to somebody out as a single agent Orange combination with to talk Samantha or herb attacks on Egfr targeted antibody.
The study was conducted in patients with metastatic headed next squamous cell carcinoma H N. S. C. C who has failed prior immunotherapy chemotherapy and to talk to the man known as Pan refractory disease. The <unk>. So talk to me of combination on met this study's primary endpoint of me.
D M P F S.
Of note for future studies patient with human papillomavirus negative or HPV negative disease, who.
Who received <unk> and Cetuximab combination demonstrated both a superior O R. R.
And medium PFS versus historical controls.
Specifically patients with HPV negative disease, who received <unk> and Patuxent ma'am produce prolonged PFS on a response rate of 38%, which included 2 complete responses.
HPV negative H a S. E. C is normally associated with poor outcomes compared to HPV positive disease.
Particularly in the pay of a factory setting, but no effective treatment. Currently exist. In addition, HCF expression is generally higher in HPV negative patients and HPV positive patients, indicating more of a role in tumor growth on progression or H G F and HPV negative tomb.
<unk>.
While we in our clinical collaborators on very encouraged with these data primarily due to a shortage of required keyboard materials on manufacturing supplies also used in COVID-19 vaccines.
Potential start date for any registration studied with <unk> will be pushed back from the first half of 2022 into 2023 and.
In the meantime, we will continue on dialog with regulators to identify the optimal registration study design for the program and look forward to providing updates on this and any potential partner indiscretions in the coming quarters I will now turn the call over to Eric to discuss second quarter of 2021 finance.
Results Eric.
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 refractory RCC setting we believe that on a 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 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 Tivo to trial costs and expenses for manufacturing of study drive material for a potential registration I'll study recycle choose on that we.
We now expect R&D expense to be in the $30 million range for the year. The 10 million dollar decrease and expected R&D expenses, primarily attributable to the aforementioned delay on a clinical study manufacturing for like witches amount.
Given the size of our existing commercial organization and R&D plans as described we believe that our corporate staff is appropriately sized for this level of activity.
Selling general on 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 corner 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 quarter's 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 nurse net cash burn to continue to decline as we expect our revenues to continue to increase.
We believe our cash from plan revenues existing cash cash equivalents some investments in available credit under the Hercules facility will.
Will be sufficient to fund our launch and all current pipeline plans, we have share today, including the phase 3 to Nivo trial. The phase 2 deductive study the phase 180, 380 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 10-Q.
I will now turn the call back over to Michael <unk> Michael.
Thank you Eric to close we believe we are well positioned for continued success with the commercial launch a petition day 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 well.
Now open the line to Q&A operator.
<unk>.
[noise]. Thank you as a reminder to ask a question you would need to pass style..1 on your telephone so let's try your question past the pound cake.
Stand by a volley compounded Q&A last day.
My first question what comes on Stephen Wiley listing all please go ahead.
Hi, This is Bonnie <unk> on for Steve Lily Thanks for taking my questions.
So my first question is about the statistical sampling program can you share anything about how long you intend to keep running that program and my second question is how does with 175 ordering accounts unlucky in comparison to the greater than 3000 number of accounts has been actively targeting.
After lunch and forget that any color that you could provide would be helpful. Thanks.
Sure on AIDS is Michael Bailey I'll turn it over to my parents on to colors.
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 free sample to help generate initial trial. So as we mentioned access is still difficult. So for awhile and our launch are still accounts will be seeing you 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 experienced program and where.
We're really pleased again with the impact the date.
And as far as the 175 unique accounts. So far again I think this speaks to the opportunity in front of us and that the challenges of launching during COVID-19, 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 to convert an account. It takes a few visits it's gonna take us a little bit longer to get to that point with all of our key accounts, but we see it is really there's 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 on <unk> we continue.
To make penetration as we said our scripts are growing every month, so far month on month, and we think will will continue to penetrate that it and get broader adoption overtime.
Okay, great. Thank you so much on congrats on my progress.
Thank you.
Thank you. Our next question will come from Andrew Barron S. T D.
<unk>. Please go ahead.
Hi, Thanks, Congrats on a quarter goes.
I was wondering if you have any idea of the type of duration, you're saying I know, it's early but trying to get a sense.
Or work was there a warehouse with on stage patients that came out of the drug or should we expect similar duration towards you saw in in the pivotal program.
Also I guess, how many unique prescribers are you soon prescribed tivo.
Are these prescribers how many scripts are the average prescriber, writing so far.
Thanks for your question, Andrew I'm Gonna turn that over to Mike.
Sure Great questions, Andrew So for duration of therapy that reality is it's just too early where we're on our first full quarter of sales. If you think back to the Tivo..3 study we had 18 per cent of patients still progression for you 2 years. So it's gonna take us a while to really see.
What what percentage of patients stay on this drug for a long duration and that ultimately.
Will create our average, but we're really pleased with what we've seen so far will 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 that the division there to get the average you know as you can imagine with sales building every single month.
A lot of the accounts have just kind of started and we'll we'll see additional volume build overtime and refill spelled overtime.
Okay. So so you Miss the unique Uhm prescriber is the same thing is very unique accounts that you're citing.
Correct. So the.
Basically patients can get our drugs 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 the training facility, which they would visor specialty distributor. So that we get a mix of prescriptions to a physician and sales too and accounts. So we we add though.
Together to come up with this kind of account prescriber number for Ya, a unique individuals or institutions using the drug.
Okay. Thanks, a lot and congrats again.
Thanks and you.
Thank you. Our next question will come from Colleen Crazy with that go ahead.
Hi, good afternoon. Thanks, so much for answering the questions on King ethanol progress.
For the early lunch I guess do you have any anecdotal data on what type of patients physicians are putting on on the Earth day again, especially on what line of treatment or anything special about these patients.
Yeah, I can certainly share some anecdotes, we don't have quantity of data to really give a breakdown at this point, but Mike.
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 our last call from just the initial patience. We we have some who are 2 prior systemic therapies that they're kind of typical third line patient. We're certainly seeing some later lie on patients who maybe have failed.
A few more lines of treatment and and had run out of options, but it's early days and are are you don't get that data on all of your patients. So it's gonna 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 we're seeing a range of patients that can.
Benefit from treatment.
Great. That's helpful. Thank you and I'm a simple program I think you mentioned, you're converting about 11% of those <unk> commercial drug I guess, what what happened to the other per cent of those and kind of how do you see that changing in the future.
Alright.
Sure. So ultimately we expect all of those samples to get used that that's the expectation and 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.
It's gonna take awhile off and it it doesn't line up just like that but ultimately these these bottles are out giving us a great presence in these practices, where it's difficult to access during COVID-19 and when they have the appropriate patient I mean, many may have requested for a patient who is currently in the second line and they think there may be an option needed in a month.
Or 2 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 the months later it turns into a commercial script.
Yeah, just to add color that this is not a sample drop like in some of the non.
Non specialty markets. This is requested specifically by the condition.
Got it that's helpful. Thank you and then I know you got a question earlier about duration. It so early for that but do you have any early insight into discontinuation.
So far.
Like any check <unk> check on that.
Yeah, we really don't it's too early to say, but we don't always get the information on 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 it's something that with more time on the market and a lot more tools and resources to get a meaningful dataset.
But again, we are seeing growth month on month, we're seeing script gross month on month on where we're really pleased with the trajectory.
Okay, great. Thanks, so much for taking my questions.
Operating rooms or any other questions.
Thank you. Our next question will come from Arthur Heber H C line right.
Hey, good afternoon guys.
Author fucking for Archie Thanks for taking my question I had.
2 question why it's on the tip the regarding the gross net right as the estimated 16 per cent.
We assuming that could be around on rating neogen.
Could we see that could go down.
Air Gewen Tango right on.
Yeah. Thanks for the question I think we've been stating for awhile that we believe that our gross to net would be similar over time to what you've seen at other sort of oral oncology RCC type.
Type products. So so we would expect that the gross to net which is currently as you sat around 16% that that'll just probably creep up a little bit over time, you'll see ex Lexis for example is a little bit higher than that so.
Okay. Thank you and my second question is regarding the the FICO program.
So could you give us more color regarding the shortage of the manufacturing do you have any plan to looking for a automated manufacturing partner to produce the drive through.
<unk>.
Yeah, Thanks, either to the question K as their name without a contract manufacturer called for forgiving manufactured in Q3 of this year. They recently informed us that they are having difficulty getting key <unk> key raw materials manufacturers supplies, because there'd be used for COVID-19 vaccine. So we clearly understand that channel.
The process to switch manufacturers and I don't think that would fix our problem to be honest with you. Because this is this is about raw materials and so the the raw materials on January Sears for many of the same places. So we certainly turned over all the stones that we could and we're.
You know actually waiting for confirmation of a new day.
Hi, David updates as appropriate.
Oh, Thank you for that day, thanks for taking my question.
Yeah, I I'm showing no further questions and it came at this time I would now like to turn the call back within the next day, Michael Danny friend clothing on my.
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.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may know.