Q4 2020 Karyopharm Therapeutics Inc Earnings Call

[music].

Good morning, My name is rational Ian I'll be your conference operator for today.

Vaishnavi: My name is Vaishnavi, and I'll be your conference operator for today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Fourth Quarter and Full Year 2020 Financial Results Conference Call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Mr. Ian Karp, Karyopharm's Senior Vice President, Investor and Public Relations. Please go ahead.

At this time I would like to welcome everyone to the carry of farm true Therapeutics fourth quarter and full year 'twenty 'twenty financial results Conference call.

The question and answer session to follow please be advised that this call is being recorded at the company's request I would now like to turn the call over to Mr. Ian Karp care of your farms Senior Vice President Investor and public Relations. Please go ahead.

Ian Karp: Thanks so much. And thank you all for joining us on today's conference call to discuss Karyopharm's fourth quarter and full year 2020 financial results and business update. This is Ian Karp, and I'm joined today by Dr. Michael Kaufman, our Chief Executive Officer, Mr. Mike Mason, our Chief Financial Officer, Mr. John Demery, our Chief Commercial Officer, Dr. Jaden Shah, our Chief Medical Officer, and Mr. Stephen Michener, our Chief Business Officer. On the call today, Michael will provide an overview of key recent questions.

Thanks, So much and thank you all for joining us on today's conference call to discuss carrier of pharma fourth quarter and full year 2020 financial results and business update this is Ian Karp and I'm joined today by Dr. Michael Kauffman, Our Chief Executive Officer, Mr. Mike Mason, Chief Financial Officer, John Demaree, Chief Commercial Officer, Dr. <unk> Shah Chief Medical Officer.

And Mr. Stephen mentioned of our Chief business Officer.

On the call today, Michael will provide an overview of key recent corporate developments and an update on our commercial progress and then Mike Mason will provide an overview of the fourth quarter and full year 2020 financial results, we will conclude with the Q&A portion of the call.

Ian Karp: And then Mike Mason will provide an overview of the fourth quarter and full year 2020 financial results. And we will conclude with a Q&A portion of the call. Earlier this morning, we issued a press release detailing Karyopharm's results for the fourth quarter and full year of 2020. This release, along with a slide presentation that we will reference, is available on our website at karyopharm.com. Before we begin our formal comments, I'll remind you that the various remarks we will make today constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide 3.

Earlier. This morning, we issued a press release detailing carrier part of the results for the fourth quarter and full year of 2020. This release along with the slide presentation that we will reference are available on our website the terraform back from.

Before we begin our formal comments I'll remind you the various remarks, we will make today constitute forward looking statements for purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1995 as outlined on slide three.

These include statements about our future expectations clinical developments and regulatory matters of the timeline the potential success of our products and product candidates, including our expectations related to the commercialization of mixed all the financial projections and our plans and prospects.

Ian Karp: These include statements about our future expectations, clinical developments, regulatory matters and timelines, the potential success of our products and product candidates, including our expectations related to the commercialization of Expolio, financial projections, and our plans and prospects. Actual results may materially differ from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent quarterly report on Form 10-Q, which is on file with the SEC, and in other filings that we may make with the SEC in the future.

The results may materially differ from those of indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent quarterly report on form 10-Q, which is on file with the SEC and in other filings that we may make with the FCC in the future.

Ian Karp: See you in the future.

Any forward looking statements represent our views as of today on what we may elect to update these forward looking statements at some point, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward looking statements as representing our views as of any date subsequent to today with that I'll now turn the call over to Michael Kauffman, Chief Executive Officer.

Michael P. Mason: Any forward-looking statements represent our views as of today only, but we may elect to update these forward-looking statements at some point in the future, but we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. With that, I'll now turn the call over to Michael Kaufman, Chief Executive Officer.

Thank you Ian and good morning, everyone Twenty-twenty was a pivotal year for them and I'm extremely proud of the significant progress. Our team has made towards the commercial clinical development and operational objectives with the ultimate goal of having positive impact of the lives of patients battling cancer.

Michael P. Mason: Thank you, Ian, and good morning, everyone. 2020 was a pivotal year for Karyopharm, and I'm extremely proud of the significant progress our team has made towards our commercial, clinical development, and operational objectives with the ultimate goal of having a positive impact on the lives of patients battling cancer. Most notably, our year was marked by two U.S. FDA approvals for Expovio, first in June for the treatment of patients with relapsed or refractory-diffused large B-cell lymphoma, or DLBCL, and then in late December, once-weekly Expovio received additional approval in combination with Fortezumib and dexamethasone for the treatment of adult patients with multiple myel We expect to carry the momentum of these important achievements into 2021 and have already started the year with several recent accomplishments, as outlined on slide four.

Most notably our year was marked by two U S. FDA approvals for ex bogie out first in June for the treatment of patients with relapsed or refractory diffuse large b cell lymphoma or D. L. B C. L. And then in late December once weekly ex Bogo.

We see the additional approval in combination with Bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma, who have received at least one prior therapy, we expect to carry the momentum of these important achievements in the 'twenty 'twenty, one and have already started the year with several weeks and accomplishments as outlined on slide four.

Ex bovino net product revenue from the fourth quarter and full year of 2020 were $20 2 million from $76 2 million respectively.

Michael P. Mason: Expovio net product revenue for the fourth quarter and full year of 2020 were $20.2 million and $76.2 million, respectively. Additionally, more than 170 and 700 new positions and accounts prescribed Expovio for the first time in Q4 and in 2020 overall, respectively. These achievements are particularly encouraging, keeping in mind that Expovio was only first approved for use by the FDA in July of 2019. And, of course, for most of 2020, we've all been impacted in some shape or form by the. Expansion and launch of Expovio into the second and third line treatment settings significantly increases the addressable patient population for Expovio and represents a meaningful growth opportunity for Karyopharm in both the near and long term.

And then 170 and 700, new physicians and accounts prescribing BELBUCA for the first time in Q4 and in 2020 overall, respectively. These achievements are particularly encouraging keeping in mind. The exposure. It's only first approved for use by the FDA in July of 2019 and of course for most of the 2020, we've all been impacted us.

In some shape or form by the ongoing COVID-19 pandemic.

The expansion of the launch of its probably go into the second and third line treatment settings significantly increases the addressable patient population of brakes bogie of it represents a meaningful growth opportunity for carry of farm in both the near and long term.

Separately in December. The addition of three ex probably no treatment regimens for multiple myeloma to the national comprehensive sort of networks clinical practice guidelines in oncology represented another key achievement that we believe will help further expand expose the OS utilization.

Michael P. Mason: Also in December, the addition of three Expovio treatment regimens for multiple myeloma to the National Comprehensive Cancer Network's clinical practice guidelines in oncology represented another key achievement that we believe will help further expand Expovio's utilization. As part of our pipeline progress, we recently announced that the European Medicines Agency's Committee for Medicinal Products for Human Use, or CHMP, adopted a positive opinion recommending conditional approval for Nexpovio, the brand name for Selinexer in Europe, in combination with dexamethasone for the treatment of myeloma in adult patients with heavily pretreated disease, an indication nearly identical to the approved indication that Expovio received I will talk a bit more about our expected steps for Europe in just a few minutes.

For our pipeline progress, we recently announced that the European Medicines Agency's committee for medicinal products for human use or C. H M. P adopted a positive opinion recommending the conditional approval for next Paul the brand name for Selinexor in Europe in combination with dexamethasone for the treatment of myeloma in adult patients with heavily pretreated disease.

An indication nearly identical to the approved indication that Expo the always saved in the 2019 accelerated approval issued by the FDA in the United States.

I will talk a bit more about are expecting except for Europe in just a few minutes. Additionally, we were excited to secure our first regulatory approval outside the United States and Israel for both myeloma and D. L. B C L, which when it was last week.

Michael P. Mason: Additionally, we were excited to secure our first regulatory approval outside the United States, in Israel, for both myeloma and DLBCL, which we announced last week. Turning now to other program updates from our ongoing hematological and solid tumor clinical studies. Our Phase 3 CNDOS study evaluating Expovio in patients with DLBCL passed its planned interim futility and upsizing analysis, and we look forward to the top-line results expected in the second half of this year. In addition, the first patient in the Phase 2-3 Export DLBCL-030 study, evaluating Expovio in patients with DLBCL, has now been treated, and this study will serve as a confirmatory study for Expovio Finally, on the financial front, we ended the quarter with a strong cash position of approximately $276.7 million that, along with expected future revenues, we anticipate will be sufficient to fund our planned operations into late 2022.

Turning now to other program updates from our ongoing hematological and solid tumor of clinical studies.

Our phase III, the Endo study evaluating exposure endometrial cancer passed its planned interim futility and upsizing analysis, and we look forward to the top line results expected in the second half of this year.

In addition, the first patient in the phase two or three export the L. B C. L. O three O study evaluating exposure on patients with the L. B C. L has now been treated treated in this study will serve as the confirmatory study for ex bogie of has accelerated approval of D. L. P. C. L granted last year.

Finally on the financial front, we ended the quarter with the strong cash position of approximately $276 $7 million that along with expected future revenues, we anticipate will be sufficient to fund our planned operations into late 'twenty 'twenty two.

Let me now turn to slide five to provide additional details on Expo via the sales performance through 2020 in the first three quarters of 2020, we generated steady increased sales for <unk> due to both the unique attributes of exposure as well as the hard work of our dedicated commercial team.

Michael P. Mason: Let me now turn to slide 5 to provide additional details on Expovio's sales performance through 2020. In the first three quarters of 2020, we generated steady increased sales for Expovio due to both the unique attributes of Expovio as well as the hard work of our dedicated commercial team. Net sales for both the full year of 2020, as well as for the fourth quarter specifically, were largely driven by prescription demand from both academic and community-based oncologists for patients with penta-refractory multiple myeloma.

Net sales for the both the full year of 'twenty 'twenty one of those for the fourth quarter, specifically were largely driven by prescription demand from both academic and community based oncologists for patients with penta refractory multiple myeloma. The five per cent decrease the product sales in the fourth quarter as compared to the third quarter was the result of the impact from both the recent surge in.

U S. COVID-19 cases as well as some increased competition for patients more specifically as we turn to slide six we believe the surge in COVID-19 cases impacted both patient visits to their health care provider as well as in person access for carry of farms commercial team to its physician customers.

Michael P. Mason: The 5% decrease in product sales in the fourth quarter as compared to the third quarter was a result of the impact of both a recent surge in U.S. COVID-19 cases and some increased competition for pay hits.

Additionally, increased competition from recently launched drugs in penta refractory myeloma and in refractory D. L. B C. All of that he has also contributed to some additional sales pressure in the quarter.

Michael P. Mason: More specifically, as we turn to slide six, we believe the surge in COVID-19 cases impacted both patient visits to their health care provider, as well as in-person access for Karyopharm's commercial team to its physician customers. Additionally, increased competition from recently launched drugs in pentarefractomyeloma and in refractory DLBCL settings also contributed to some additional sales pressure in the quarter. However, we are seeing a meaningful rebound in demand, and new patients have started since the expanded approval, further reinforcing our confidence in the future growth potential for Expovio.

However, we are seeing a meaningful rebound in demand and new patient starts since the expanded approval further reinforcing our confidence in the future growth potential for ex <unk>.

As mentioned previously. The addition of multiple exposure of combination regimens to the M. C. C N guidelines and the expanded FDA approval of expose the I'll provide a strong tailwind for sales growth in December following declines in October and November.

We're still on the very early stages of the launch of exposure the only for the second and third line settings, but we expect to see significant increase in annual sales largely driven by both earlier use and longer duration of treatment in patients with myeloma.

Michael P. Mason: As mentioned previously, the addition of multiple Expovio combination regimens to the MCCN guidelines and the expanded FDA approval of Expovio provided strong tailwinds for sales growth in December, following declines in October and November. We're still in the very early stages of the launch of Exposio into the second and third line settings, but we expect to see a significant increase in annual sales, largely driven by both earlier use and longer duration of treatment in patients with myeloma.

Moving now to slide seven the graph here shows the prescription refill rate for ex bogie over 2020 from both the first and second refills to those patients eligible for the refills. These numbers have remained encouraging throughout 2020 and are significantly higher as compared to our initial launch period in 2019. These refill rates coupled with an average daily.

Three treatment cycles per patient as of the end of 2020 further reinforced the positive feedback we have received from physicians.

Michael P. Mason: Moving now to slide seven, the graph here shows the prescription refill rate for Expovio over 2020 for both the first and second refills for those patients eligible for these refills. These numbers have remained encouraging throughout 2020 and are significantly higher as compared to our initial launch period in 2019. These refill rates, coupled with an average of nearly three treatment cycles per patient as of the end of 2020, further reinforce the positive feedback we have received from physicians and patients regarding their experience and use of Expovio.

And patients regarding their experience and uses of exposure.

Importantly, the patient discontinuation rate due to the side effects remain relatively low at 13%, which we believe is a testament to more and more positioned gaining comfort and helping the operations prevent and manage the side effects of fixed bogie of with proper prophylactic and supportive therapies as well as dose modification.

In addition to the expanded label for <unk> via on the US we believe the future international expansion of the exposure in Europe will be another key strategic area of growth of carry of farm, which I'll now highlight on slide eight.

Michael P. Mason: Importantly, the patient discontinuation rate due to side effects remained relatively low at 13%, which we believe is a testament to more and more physicians gaining comfort in helping their patients prevent and manage the side effects of exfobia with proper prophylactic and supportive therapies, as well as dose modification.

The see HMP positive opinion for next phobia, which was issued at the end of January could lead to our first regulatory on Europe and recognizes the positive clinical benefit risk profile of the world exposure.

We look forward to the European Commission's final decision on an ex bogie of submission, which is expected in April of 'twenty 'twenty. One we intend to submit a second regulatory filing based on the data from the phase III Boston study with the goal of further expanding the global reach of next 12 additional patients in need of new treatment options and encouragingly, even before of possible.

Michael P. Mason: In addition to the expanded label for Expovio in the U.S., we believe the future international expansion of Expovio in Europe will be another key strategic area of growth for Karyopharm, which I'll now highlight on slide 8. The CHMP positive opinion for Nexfovio, which was issued at the end of January, could lead to our first regulatory approval in Europe and recognizes the positive clinical benefit-risk profile of oral Nexfovio. We look forward to the European Commission's final decision on the Expovio submission, which is expected in April 2021.

European regulatory approval, the European Hematology Association and European Society for medical oncology recently updated their treatment guidelines for myeloma in November of 2020, and added Selinexor Velcade Dex amounts from regiment to their second line.

Recommendations and Selinexor with dexamethasone to the third line plus treatment guidelines.

In parallel to the regulatory experts, we're also continuing to evaluate potential collaborations with partners in Europe and Japan.

Michael P. Mason: We intend to submit a second regulatory filing based on the data from the phase three Boston study, with the goal of further expanding the global reach of Expovio to additional patients in need of new treatment options. And encouragingly, even before possible European regulatory approval, the European Hematology Association and European Society for Medical Oncology recently updated their treatment guidelines for myeloma in November of 2020 and added Selenexer, Velcade, and a dexamethasone regimen to their second line. Recommendations, and Selenexa with dexamethasone to the Third Line Plus Treatment Guidelines.

We're committed to making ex bovey all about available on Europe, if approved in April with the greatest opportunity come potentially before the end of 'twenty 'twenty one when we would hope to receive an expanded approval in Europe based on the data from our phase III Boston study.

I'd be remiss, if I did not mention from updates on a number of additional exciting pipeline of opportunities that we're pursuing per exposure, which can be seen on slides nine and 10.

We have a robust clinical development plan for exposure of in both Hematological malignancies and solid tumors. This includes our phase III. The Endo study in patients with endometrial cancer, where we expect to have of topline data readout before the end of this year on.

Michael P. Mason: In parallel to the regulatory experts, we're also continuing to evaluate potential collaborations with partners in Europe and Japan. We're committed to making Expovio available in Europe if approved in April, with the greatest opportunity to come potentially before the end of 2021, when we would hope to receive expanded approval in Europe based on the data from our Phase 3 Boston study. I'd be remiss if I did not mention updates on a number of additional exciting pipeline opportunities that we are pursuing for Expovio, which can be seen on slides 9 and 10.

I'll note that there are two additional new important clinical trials, we plan to initiate in 2021, which we will believe will help further define the odd clinical utility of exposure out of a potential partner of choice with other active anticancer agents.

First we expect to initiate a new randomized phase III study evaluating <unk> in combination with palm of list of dexamethasone in patients with previously treated myeloma if the <unk>.

Results of this trial of positive this regimen would represent a potent oral drug option to patients with refractory disease.

Michael P. Mason: We have a robust clinical development plan for Expovio in both hematological malignancies and solid tumors. This includes our phase 3 CNDO study in patients with endometrial cancer, where we expect to have a top-line data readout before the end of this year. I'll note that there are two additional important new clinical trials we plan to initiate in 2021, which we believe will help further define the broad clinical utility of Expovio as a potential partner of choice with other active anti-cancer agents.

We plan to initiate a new phase II study evaluating <unk> in combination with keytruda in patients with newly diagnosed or recurrent metastatic melanoma.

Particularly excited about this study based on some encouraging data from the M. D. Anderson of investigator sponsored trial evaluating the combination regimen, which was presented at the annual ESMO conference in 2020.

With that I'll now turn the call over to Mike Mason to review the quarterly financials Mike.

Michael P. Mason: First, we expect to initiate a new randomized phase 3 study evaluating Expovio in combination with Pomalyst and dexamethasone in patients with previously treated myeloma. If the results of this trial are positive, this regimen would represent a potent oral drug option for patients with refractory disease. Next, we plan to initiate a new Phase 2 study evaluating Expovio in combination with Keytruda in patients with newly diagnosed or recurrent metastatic melanoma. We're particularly excited about this study based on some encouraging data from the MD Anderson Investigator Sponsored Trial evaluating this combination regimen, which will be presented at the annual ESMO conference in 2020.

Thank you Michael since we issued a press release earlier today with the Paul.

The results I will just focus on the highlights which begin on slide 12 net product revenue for the fourth quarter of 2021 22.

The $2 million compared to 17 7 million of.

Fourth quarter of 2019 net product revenue from the year ended December 31.

One of US $6 2 million compared to 35 out of the.

Year on the 20th.

The estimated growth net of discount.

From 2020 fell within our estimated range of 15 to 20 years.

License and other revenue from the fourth quarter of 2020 was $14 9 million compared to zero point of $4 million for the fourth quarter of 2019.

Increase was driven by a $9 8 million on payment from messaging from milestone payments associated with regulatory filings in Asia.

As all of the $5 million upfront payment from forest therapeutics on the execution of a commercial distribution agreement for cash.

Michael P. Mason: With that, I'll now turn the call over to Mike Mason to review the quarterly financials. Mike. Thank you, Michael.

Licensing and other revenue on 25, or $31 9 million compared to $10 4 million in spite of vaccine.

Michael P. Mason: Thank you, Michael. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which began on slide 12. Net product revenue for the fourth quarter of 2020 was $20.2 million, compared to $17.7 million for the fourth quarter of 2019. Net product revenue for the year ended December 30, 2020, was $76.2 million, compared to $30.5 million for the year ended 2019. The estimated gross net discount for Expovio in 2020 fell within our estimated range of 15 to 20 percent.

R&D expenses for the fourth quarter of 2020, or $37 2 million compared to $31 6 million from the fourth quarter of 2019 R&D expense for the year end of 'twenty, 'twenty 458 million compared to $122 3 million of the year end 2019 the.

The increase in R&D expenses from 2020 of our 2019.

Primarily attributable cost incurred related to our COVID-19 trial activity, which will not recur in 2021.

On continued activity on our other ongoing clinical trials of regulatory items.

Selling general and administrative expense on the fourth quarter of 2020 was $33 9 million compared to $28 4 million for the fourth quarter of two dose Inc.

Michael P. Mason: License and other revenue for the fourth quarter of 2020 was $14.9 million, compared to $0.4 million for the fourth quarter of 2019. This increase was driven by a $9.8 million payment from Antigen for milestone payments associated with regulatory filings in Asia, as well as a $5 million upfront payment from Forest Therapeutics upon the execution of a commercial distribution agreement in Canada. License and other revenue in 2020 will be $31.9 million compared to $10.4 million in 2019.

The increase in SG&A expenses compared to the prior year of steel primarily as your activities to support the U S commercialization of Ohio.

On slide 13, you can see the cash cash equivalents of restricted cash and investments as of December 32020.

Totaled 207.

$7 million compared to the chart on 8 million or some of their first shop on that team.

Finally based on our current operating plans kind of farm expects non-GAAP, R&D and SG&A expenses, which excludes stock based compensation expense on the full.

Michael P. Mason: R&D expenses for the fourth quarter of 2020 were $37.2 million, compared to $31.6 million for the fourth quarter of 2019. R&D expenses for the year ended 2020 were $150.8 million, compared to $122.3 million for the year ended 2019. The increase in R&D expenses in 2020 compared to 2019 was primarily triggered by costs associated with and incurred related to our COVID-19 trial activity, which will not reoccur in 2021, and continued activity in our other ongoing clinical trials and regulatory activities. Selling general and administrative expense for the fourth quarter of 2020 was $33.9 million, compared to $28.4 million for the fourth quarter of 2019.

Full year of 2020 of arms would be in the range of 280, instead of $300. The company expects the system.

Cash cash equivalents of investments and the revenue is expected to generate from ex Bobbio product sales and other license revenue will be sufficient to fund planned operations into the late <unk>.

We are not providing revenue guidance for 2021 today.

Just began the initial launch of exposure.

It's expanded indications.

Do you expect the meaningful growth from 2021 relative to 2020, but the ramp of sales increasing in the second half of the year and we expect to see the benefits on the longer duration of treatment for multiple myeloma patients being prescribed the exposure earlier on their treatment of horse and or in combination with all of them all.

I'll now turn the call back over to Michael for some concluding remarks Michael.

Thank you Mike before moving to the Q&A, Let me highlight some of the key commercial clinical and regulatory milestones that we expect for 'twenty 'twenty one on slide 14.

First we are actively in the process of launching expose the O into the second and third line settings in myeloma in the US and we expect a significant increase in annual sales of 'twenty and 'twenty, one as compared with 2020 net.

Michael P. Mason: The increase in SG&A expenses compared to the prior year was due primarily to activities to support the US commercialization of SOIA. On slide 13, you can see that cash and cash equivalents for restricted cash investments as of December 30, 2020, totaled $276.7 million compared to $265.8 million as of December 1, 2019. Finally, based on our current operating plans, Karyopharm expects non-GAP, R&D, and SG&E expenses, which excludes stock-based compensation, for the full year 2021 to be in the range of 280 to 300 million.

Next we anticipate a decision on the conditional approval of <unk> in Europe based on the storm data in April and plan to submit the Boston data the type two variation shortly thereafter, which could result in an expanded approval in Europe later this year.

Finally in the second half of this year, we expect top line data from the phase III at the end of study in endometrial cancer as well as multiple clinical trial initiations in the presentation of additional combination data with exposure on other cancer therapies at various medical meetings.

Michael P. Mason: The company expects that its cash, cash equivalents, and investments and the revenue it expects to generate from Expovio product sales and other licensed revenues will be sufficient to fund its planned operations into late 2020. We are not providing preventive guidance for 2021 today, as we have just begun the initial launch of Expovio and its expanded indication, but we do expect to see meaningful growth in 2021 relative to 2020, with the ramp of sales increasing in the second half of the year, as we expect to see the benefit of a longer duration of treatment for multiple myeloma patients being prescribed Expovio earlier in their treatment course and or in combination with Velcade. I'll now turn the call back over to Michael for some concluding remarks. Michael.

Before we open the call to questions I do recognize our full carry of farm team for a truly remarkable of 'twenty 'twenty. We've already started the new year off strongly and I'm confident that we are well positioned to execute on the commercial clinical development and operational goals and growth opportunities outlined today. We appreciate your ongoing support and look forward to keeping you updated on our future progress.

I'll now turn the call over to the operator for questions operator.

We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone, if you're using a speakerphone. Please pick up your handset before pressing the keys to withdraw your question. Please press Star then two please limit yourself to one question and one follow up if you have from.

The questions you may reenter the question queue at this time, the real pause momentarily to assemble our roster.

Michael P. Mason: Thank you, Mike. Before moving to the Q&A, let me highlight some of the key commercial, clinical, and regulatory milestones that we expect for 2021 on slide 14. First, we are actively in the process of launching Expovio into the second and third line settings for myeloma in the U.S., and we expect a significant increase in annual sales in 2021 as compared with 2020. Next, we anticipate a decision on the conditional approval of an exp

The first question comes from Maury Raycroft of Jefferies. Please go ahead.

Hi, good morning, everyone and congrats on congrats on the progress thanks for taking my question.

So for sales, we likely won't see of major rise in the number of refills and at least the next quarter and so if the numbers are presented in aggregate and that's.

If the numbers are presented in aggregate. So would you consider breaking out that number or other sales numbers by line of treatment in 2021, I guess do you plan on providing more granularity going forward.

Operator: Finally, in the second half of this year, we expect top-line data from the Phase 3 CNDO study in endometrial cancer, as well as multiple clinical trial initiations and the presentation of additional combination data with Expovio and other cancer therapies at various medical meetings. Before we open the call to questions, I do want to recognize our full Karyopharm team for a truly remarkable 2020. We've already started the new year off strongly, and I'm confident that we are well positioned to execute on the commercial, clinical development, and operational goals and growth opportunities outlined today. We appreciate your ongoing support and look forward to keeping you updated on our future progress. I'll now turn the call over to the operator for questions. Operator?

Let me turn it to Ian to start.

Yes. Thanks.

Hi.

I think for now the reality is in terms of the the clarity of data we get.

We don't see from our.

From our distributors and specialty pharmacies, we don't get a level of data that tells US what line of therapy. The ex Libya of prescription was given that so we right now we don't have that clarity.

We do get some of that information from market research, which will do later on the year, but that will be available later in the year. So I think we will see kind of.

The launch play out.

And as we get more information I think it will be.

More specific in terms of where the growth is coming.

Got it Okay, and then one follow up just on potential BD opportunities in Europe. Just wondering if you could say anything additional on that and if that could take place.

The prior to the the Boston acceptance and approval there.

Let me turn that over to Steven mentioned on our Chief business Officer Steven.

Hi, good morning, more of it's a great question and certainly since we've gotten the positive opinion in Europe, there's been a lot of great momentum. So we're currently under a number of discussions.

Operator: We will now begin the question and answer session. To ask a question, you may press star, then one on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the key.

So for both Europe, and Japan, and we're looking to make some decisions on hopefully in the in the next few months will be can bring debt effectively to our European patients I think the other thing I would add to us but on a positive note. We've had a lot of interest beyond just the multiple myeloma indications.

Maurice Thomas Raycroft: To withdraw your question, please press star, then two. Please limit yourself to one question and one follow-up. If you have further questions, you may re-enter the question. At this time, we will pause momentarily to assemble our roster. The first question comes from Maurice Raycroft with Jefferies.

I've never looking to expose us.

And help out beyond just the the first part of our hematology portfolio.

Maurice Thomas Raycroft: Please go ahead. Hi, good morning, everyone, and congratulations. Congratulations on the progress. Thanks for taking my question. So for sales, we likely won't see a major rise in the number of refills for at least the next quarter.

Great. Okay. Thank you for taking my questions.

The next question comes from Brian Abrahams with RBC capital markets. Please go ahead.

Hey, good morning.

Thanks for taking my questions Congrats on all of the progress.

Maurice Thomas Raycroft: So if the numbers are presented in aggregate, and that's if they are.

So I'm curious what some of the key metrics that you guys are going to be looking for in order to assess our earlier line of uptake I guess beyond new patient starts is this primarily duration is there anything that you might be able to tell from dose levels, just given the spread on that already and I I understand you're not looking for us or not expecting of major.

Maurice Thomas Raycroft: Represented in aggregate. So would you consider breaking out that number or other sales numbers by line of treatment in 2021? I guess you plan on providing more granularity going forward?

Ian Karp: Let me turn it to Ian to start.

Ian Karp: Yeah, thanks, Maury. I think for now, the reality is, in terms of the clarity of data we get, we don't see from our, from our distributors, and especially pharmacies, we don't get a level of data that tells us what line of therapy the ex povio prescription was given in. So we, right now, we don't have that clarity. We do get some of that information from market research, which we'll do later in the year, but that won't be available to us until later in the year. So I think we'll see kind of, you know, let's, let the launch play out, and as we get more information, I think we'll be more specific in terms of where the growth is coming from.

The inflection until closer to the back half of the year, but how.

How quickly might you expect some of these potentially are the potential leading indicating signals to manifest themselves and you're starting to see any initial trends here since December on now that we're a close to mid February.

Yeah, Let me, let me start with Ian and then move it over to John <unk>, Our Chief Commercial Officer Ian.

Yes, great question.

I mean, clearly one of the one of the the.

Most of the obvious indicators will be new patient starts and for some of the data that we receive and we did mentioned on the call on the call that we have seen an uptick in <unk>.

Our growth certainly growth in new patient starts so that's certainly encouraging and.

And we'll continue to follow that.

We've also seen a reduction in the percentage of exposure of prescriptions at the 80 milligram twice a week dose.

Maurice Thomas Raycroft: Got it. Okay. And then one follow-up just on

Maurice Thomas Raycroft: [inaudible]

And an increase in the doses.

Maurice Thomas Raycroft: Just wondering if you could say anything additional on that and if that could take place prior to Boston's acceptance and approval.

That would indicate that the exposure.

Used in combination of doses lower than the 80 milligrams twice a week. So we think that's also another positive indicator of the where physicians are likely choosing to use exposure.

Stephen Michener: Let me turn that over to Stephen Michener, our Chief Business Officer. Stephen? Hi, good morning, Maury.

Stephen Michener: It's a great question, and certainly, since we've gotten the positive opinion in Europe, there's been a lot of great momentum. So we're currently in a number of discussions with both Europe and Japan, and we're looking to make some decisions that, hopefully, in the next few months, we can bring that effectively to our European patients. I think the other thing I would add is that, on a positive note, we've had a lot of interest beyond just the multiple myeloma indications, and something that we're looking to promote and help out beyond just the first part of our hematology portfolio.

As a combination regimen.

Now, we don't have visibility as to what percentage of that is with Velcade what presented that.

Another anti myeloma agent, but certainly we're encouraged that the percentage of prescriptions written for the 80 milligram dose is.

Is coming down quite significantly so those are the kinds of things that we're looking at and I think you mentioned.

As we get into the probably the second half of the year, we'll really be looking at duration of treatment.

And that is a metric that we can follow with us.

Half of our business that goes through the specialty pharmacy as you can see what the numbers of prescriptions that each individual patient of getting but again, that's the number that we wouldn't expect to materially increase until we get to the back half year.

Brian Corey Abrahams: Great. Okay, thank you for taking my question. The next question comes from Brian Abrahams with RBC Capital Markets. Please go ahead. Hey, good morning.

As the duration.

Brian Corey Abrahams: Thanks for taking my questions. Congratulations on all the progress. So, I'm curious what some of the key metrics that you guys are going to be looking for in order to assess earlier line uptake, I guess beyond new patient starts. Is this primarily duration? Is there anything that you might be able to tell from dose levels, just given the spread on that already? I understand you're not expecting a major inflection until closer to the back half of the year, but how quickly might you expect some of these potential leading indicators to manifest themselves? Are you starting to see any initial trends here since December now that we're close to mid-February?

We get a benefit from the duration of true I don't know John if there's anything you'd add to the yeah. Thanks. Ian in addition to the duration of therapy in the US Ku next to look at what combinations of getting we also are doing monthly HEU readouts to look at in terms of prescribed by line of therapy on by combination so that'll be a leading indicator of.

Jake.

We also have pulse research going on on a regular basis, the measure of physician opinions and prescribing intent as well as the number of AD boards to track perception of perception changes over time all of those of us you'll be leading indicators to the launch success on our uptake in the Boston the space.

Great and what are you seeing on some of those are I guess just initially.

Ian Karp: Yeah, let me start with Ian and then move it over to John, our Chief Commercial Officer, Ian.

You know with the label expansion and N C C N guideline inclusion.

John.

Yeah, well of course, we're still less than two months into launch we're very encouraged by what we're seeing there the feedback we're receiving from physicians and the one on one meetings and the market research and the AD boards has been quite positive and we're already seeing an increase in prescription demand relative to what we saw as mentioned for October and November.

Ian Karp: Yeah, great question. I mean, clearly, one of the most obvious indicators will be new patient starts. And for some of the data that we received, and we did mention on the call, we have seen an uptick in, or certainly growth in, new patient starts. So that's certainly encouraging. And we'll continue to follow that.

We were able to launch of immediately add approval of across all functions of the company, which was imperative and we're seeing the impact of that in the context of the rapid promotional efforts, we're already seeing the chefs Ian mentioned in terms of dosage and more patients now starting on ex V D and starting on ex D. So early signs from the market research.

Ian Karp: We've also seen a reduction in the percent of Expovio prescriptions at the 80 milligrams twice a week dose and an increase in the doses that would indicate that Expovio is being used in combination, so doses lower than 80 milligrams twice a week. So we think that's also another positive indicator that more physicians are likely choosing to use Expovio as part of a combination.

And from the AD boards of positive again, it's early but what are the leading indicators are ahead of the right direction.

John Demery: Now, we don't have visibility as to, you know, what percent of that is with Velcade and what percent of that is with another anti-myeloma agent, but certainly, we're encouraged that the percentage of prescriptions written for the 80 milligram dose is coming down quite significantly. So, those are the kinds of things that we're looking at, and I think you mentioned that, as we get into probably the second half of the year, we'll really be looking at duration of treatment. And that is a metric that we can follow with at least half of our business that goes through the specialty pharmacies. We can see what the numbers of prescriptions that each individual patient is getting, but again, that's a number that we wouldn' I don't know, John, if there's anything that you'd like.

That's really helpful. And then maybe just a quick follow up if I could with respect to the competitive landscape I'm curious what your market research and on the ground physician discussions or are telling you or some of the key considerations for us for docs in their choice of the new myeloma treatment to add onto the add on in the later and later stage refractory patients and I'll hop back in the queue. Thanks.

Yeah, Let me, let me start here and then I'll turn it over some of the others on the call I think the main point here is is that while there are a number of different therapies people can take in the second and third line settings of the actually the regimen is is really unique and in many ways first of all of it is the therapy that appears to have the fewest number of OS.

We're all doses and the least amount of clinic time that of patients required to spend.

John Demery: In addition to duration of therapy and the FKU mix to look at what combinations we're getting, we also are doing monthly ATU readouts to look at intent to prescribe by line of therapy and by combination. So that'll be a leading indicator of uptake. We also have PULSE research going on on a regular basis to measure physician opinions and prescribing intent, as well as the number of ad boards to track perception and perception changes over time, all of which will be leading indicators for the launch success and our uptake in the Boston space.

That's a super important point of anytime, especially when you consider the three quarters of the patients are over 70 years old.

And really don't don't have ease of transportation and so on and and most of the in fact, no patients were the ones who spent a lot of time at the hospital on that's even more important during COVID-19. The second point is that the data we get from the study are potentially very relevant to the real world use of it.

The fact that we used once weekly velcade in the experimental arm and this is the only study that's resulted in a velcade based approval that's used to actually what people what doctors are treating with so it's a it's a very unique regimen and the last point to make us and.

John Demery: Right. And what are you seeing on some of those, I guess, just initially, as you know, with the label expansion and NCCN guideline inclusion?

John Demery: Do you want it? No.

John Demery: Yeah, well, of course, we're still less than two months into launch, but we're very encouraged by what we're seeing there. The feedback we're receiving from physicians in the one-on-one meetings, in the market research, and in the ad boards has been quite positive. And we're already seeing an increase in prescription demand relative to what we saw, as mentioned, for October and November. We were able to launch immediately upon approval across all functions in the company, which was imperative.

And I think John's researches really on this carefully for US is that we represent the fourth independent mechanism for use in the early early levels of disease.

Obviously, the the Proteasome inhibitors image and see the 38 monoclonal antibodies are very important in these areas, but when a patient goes through them and sometimes now in front lots of patients are getting all three of these regiments plus steroids.

John Demery: And we're seeing the impact of that in the context of the rapid promotional efforts. We're already seeing the shift that Ian mentioned in terms of dosage and more patients now starting on XVD than starting on XD. So early signs from the market research and from the ad boards are positive. Again, it's early, but the early leading indicators are headed in the right direction.

It begs the question of what to do in the second and third lines and we represent the fourth independent mechanism. That's now approved in combination of use there and not only approved for Velcade, but has on CCM guidance beyond that for Pom and ER and Dara with data of course with Kyprolis.

Michael P. Mason: That's really helpful. Let me do just a quick follow-up if you could. With respect to the competitive landscape, I'm curious what your market research and on-the-ground physician discussions are telling you are some of the key considerations for doctors in their choice of a new myeloma treatment to add on in later stage refractory patients. I'll hop back in the queue, thanks.

Do you want to add anything in the job.

No I think you're exactly right Michael.

The key consideration of Israeli novel non transaction. They have their P is the image that the giving and including the <unk> 30 eights from the first line.

Michael P. Mason: Yeah, let me start here and then we'll turn it over to some of the others on the call. I think the main point here is that while there are a number of different therapies people can take in the second and third line settings, the XPD regimen is really unique in many ways. First of all, it appears to have the fewest number of overall doses and the least amount of clinic time that a patient is required to spend.

New mechanisms of key consideration and then convenience at the end of the day because of lot of these patients will lift from many years and so having something that's well tolerated.

Without residual of long term side effects of Keith leaves us from when they're thinking about sequencing and what theyre looking at the earlier lines of therapy. So those are the two key considerations when I think of it.

Michael P. Mason: And that's a super important point at any time, especially when you consider that three-quarters of the patients are over 70 years old and really don't have easy access to transportation and so on. And, in fact, no patient really wants to spend a lot of time at the hospital, and that's even more important during COVID.

The positions this combination of wells.

Thanks, So much that's really helpful color I appreciate it.

The next question comes from Peter Larson with Barclays. Please go ahead.

Hi, Thanks for taking my questions.

Michael P. Mason: The second point is that the data we get from this study is potentially very relevant to the real world, the fact that we used Velcade once weekly in the experimental arm. This is the only study that's resulted in a Velcade-based approval that's used actually what people, and doctors are treating with. So it's a very unique regimen. And the last point to make, and I think John's research has really honed this carefully for us, is that we represent the fourth independent mechanism for use in the early stages of disease.

I guess the first one is just the brand well the current duration of treatment is if you can get us give us any kind of sense around that and.

Where that could potentially increase to overtime.

Sure Ian.

Yeah, I mean, well.

Well, we've said then.

Certainly we said it on the call. It's about three the three months right now where through through 2020.

And that's been consistent for probably the last couple of quarters.

And also consistent with the data that we saw coming out of the original storm study that showed about a three months average duration of treatment and remember they're on.

Michael P. Mason: Obviously, the proteasome inhibitors, IMIDs, and CD38 monoclonal antibodies are very important in these areas. But when a patient goes through them, and sometimes now in the front line, patients are getting all three of these regimens plus steroids, it begs the question of what to do in the second and third lines. And we represent the fourth independent mechanism that's now approved in combination for the use there, and not only approved for Velcade but has MCCN guidance beyond that for POM and DARA, with data, of course, for Kyprolis. Jay, do you want to add anything, and then John? No.

The patients that are on for a month and the patients that are on for over a year, but the the average is about three.

What we did see in the Boston study was that the average was about 10 months on therapy. So I think that gives you sort of the range from the clinical studies.

And our hope is that obviously, we were able to grow the average duration of therapy from the point of three today to something closer to 10.

But obviously time will tell how effective we are at moving as many patients in the Canada earlier lines of treatment. So that's where the number of stand today and I think that gives you some sense of how high they could possibly go.

Michael P. Mason: No, I think you're exactly right, Michael. The key consideration is really novel mechanisms of action. They have their PIs and images that they're giving, including CD38s in the first line. New mechanisms are a key consideration, and then convenience at the end of the day, because a lot of these patients will live for many years. And so having some...

Is there any kind of sense that they are ticking up or do you think that's more of a kind of.

Back half out of me.

Event.

Yes, it's weighted it's way too early to know that yes. The 10 months I was talking about was from the Boston study just go on here.

Yes. There is again there is it's way too soon to dollar if theres been any changes to the average duration of treatment.

Okay. Thank you and then is there any way of kind of quantifying the COVID-19 impact on weather.

Michael P. Mason: Thanks so much. That's really helpful, Collar. I appreciate it.

Whether it's the number of scripts on the number of the new docs and.

Peter Richard Lawson: The next question comes from Peter Larson with Barclays; please go ahead. Hi, thanks for taking my questions. I guess the first one is just around what the current duration of treatment is, if you can give us any kind of sense around that and where that could potentially increase over time. Sure.

On kind of what gives you the confidence that the this is a kind of of temporary event versus the kind of hidden penetration.

John do you want us talking about that.

Yeah, we do think the Covid impact us having multiple impacts we know in person visits by our sales force nurse liaisons per teams to the key stakeholders continues to be impacted in most parts of the country research estimates that we've seen are that 15 to 20 per cent of Hp's HCP as can be seen.

Ian Karp: [inaudible] Yeah, I mean, well, what we've said, and certainly we said it on the call, it's about three months right now, and we're through 2020. And that's been consistent for probably the last couple of quarters.

Ian Karp: And also consistent with the data that we saw coming out of the original STORM study that showed about a three month average duration of treatment. And remember, you know, there will be patients that are on for a month, and there will be patients that are on for, you know, over a year, but the average is about three months. What we did see in the Boston study was that the average was about 10 months on therapy.

In person when.

The continued to believe that it's challenging to educate physicians in this environment and are putting in place multiple tactics, both digitally and with the additional training on virtual engagements to try and enhance that.

Outside of the impact of Covid includes reduced patient visits that we saw from bit of different data sources, particularly with the spike as mentioned in the fourth quarter of a dual impact we saw from Covid in the context of the fourth quarter.

Ian Karp: So I think that gives you sort of the range from the clinical studies. And our hope is that, you know, obviously, we were able to grow the average duration of therapy from a point of three today to something closer to 10. But obviously, you know, time will tell how effective we are at moving as many patients as we can to early levels of treatment. So that's where the numbers stand today. And I think that gives you some sense of how high they could possibly go.

But it sounds like this is definitely a kind of of the temporary issue as opposed to kind of kind of pronounce on.

From a loan row.

Yeah, absolutely, we're seeing a lot more doctors get interested in essence and remember this is a fundamentally different asset now in the <unk>.

Second and third line setting with patients now getting a new option of very convenient option of very real life set of data to kick in which the based on clinical decision to administer ex V. D. And then as we set of additional support with the other so so we absolutely believe this is the this is the fundamental the is at the beginning of a fundamentally new.

Ian Karp: Is there any kind of sense that they are ticking up, or do you think that's more of a kind of back half-year event?

Ian Karp: It's yeah, it's way, it's way too early to know that. Yeah, the 10 months I was

Ian Karp: Boston Study, just to be clear.

Ian Karp: Yeah, there's, again, there's, it's way too soon to know if there's been any changes to the average.

New asset and ramp for <unk> in myeloma.

Peter Richard Lawson: Okay, thank you. And then is there any way of kind of quantifying the COVID impact on whether it's the number of scripts on the number of new doctors and kind of what gives you the confidence that, you know, this is a kind of a temporary event versus an Unknown Speaker of the Board of Trustees. Transcripts provided by Transcription Outsourcing, LLC. John, do you want to?

Great. Thanks for taking my questions.

The next question comes from Jonathan Chang with SVP Leerink. Please go ahead.

Good morning, and thanks for taking my questions.

First question why wouldn't we see an inflection in sales until the second half of Boston, If I understand the first half numbers might not fully reflecting longer duration of treatment of shouldn't reflect the significantly increased number of patients available on the earlier line setting.

John Demery: Yeah, we do think the COVID impact is having multiple impacts. We know in-person visits by our sales force. Unknown Attendee, Detlef Winckelmann, Reshma Rangwala, Elhan Webb, Sohanya Cheng, Johoon Kim, Karyopharm Therapeutics Inc. Unknown Attendee, Detlef Winckelmann, Reshma Rangwala, Elhan Webb, Sohanya Cheng, Johoon Kim, Karyopharm Therapeutics Inc.

Yes, I'll turn that to Ian to start.

Yeah, we certainly we do expect that I'm not sure. So I'm sorry, if that wasn't clear we absolutely do expect growth beginning in this first quarter of this year. So absolutely we expect to see growth.

Peter Richard Lawson: But it sounds like this is definitely a kind of temporary issue as opposed to you kind of capping out on multiple myelomas.

Because to your point, we should have additional patients are we do have additional patients that were now eligible to treat and that's the much larger patient pool. So we absolutely expect to see growth relative to the to the fourth quarter of last year I think the point that we're making us that that growth should accelerate.

Michael P. Mason: Yeah, absolutely. We're seeing a lot more doctors get interested in this. And remember, this is a fundamentally different asset now in the second and third line setting, with patients now getting a new option, a very convenient option, a very real-life set of data on which to base a clinical decision to administer XVD. And then, as we said, additional support with the other. So we absolutely believe this is the beginning of a fundamentally new asset and pathway for Expovio and Myeloma.

Throughout the year and certainly as we get into the second half of the year because not only do you have the benefit of more patients, but you have the benefit of the longer duration of treatment for.

For patients that are getting treated today. So that was the that's the dynamic that we expect to see.

Understood just one follow up to that.

Kind of Boston and the early online sales kind of Hawaii, the storm opportunity and are you seeing any evidence of that.

Jonathan Chang: Great. Thanks for taking my question. The next question comes from Jonathan Chang with SVB Learing. Please go ahead. Good morning, and thanks for taking my questions. First question: why wouldn't we see an inflection in sales until the second half for Boston? So I understand the first half numbers might not fully reflect a longer duration of treatment, but shouldn't they reflect the significantly increased number of patients available in the earlier line setting?

Yeah.

Yeah, well I mean, most nearly all drugs are used multiple times in the given patient during their journey on the therapy.

And so.

The the real use of exposure you will not be really the storm.

Ministration, but it'll be in earlier lines, we expect it'll be mostly expose the OBL backs with some expose the O pom Dex if someone wants to use on N C C and guided all oral therapy and then later on it could be exposure Dara dex or exposure of Kyprolis Dex.

Ian Karp: Yeah, I'll turn that to Ian to start.

Ian Karp: Yeah, yeah, we certainly, we do expect, I'm not sure, so I'm sorry if that wasn't clear, we actually do expect growth beginning in this first quarter of this year. So absolutely, we expect to see growth because, to your point, we should have additional patients, or we do have additional patients that we're now eligible to treat, and that's a much larger patient pool. So we absolutely expect to see growth relative to the fourth quarter of last year.

In the later lines. So we do expect net we will see multiple uses of exposure, we don't have any data on it yet.

Anecdotally, we've heard of a couple of patients who are getting their second course of exposure out in their treatment journey, but right now it's too small numbers.

Got it thank you.

The next question comes from Eric Joseph The J P. Morgan. Please go ahead.

Good morning, this us Hannah on for Eric Thanks for taking our questions just a couple of from us.

Ian Karp: I think the point that we're making is that growth should accelerate throughout the year and certainly as we get into the second half of the year because not only do you have the benefit of more patients, but you have the benefit of the longer duration of treatment for patients that are getting treated today. So that was the, that's the dynamic that we expect to see.

The first what is the status of commercial preparations for an ex Nokia on the U R. You're scaling from the penta refractory population or scaling more in anticipation of accessing the third and second line patient populations of the Dolphins of mission and then I have another one here.

Jonathan Chang: Okay. Just one follow-up to that. Could Boston and the earlier line sales cannibalize the storm opportunity?

Yes, Steve do you want to take that.

Sure. So you know as we mentioned before we are very excited that we got the positive opinion on the storm indications, we aren't having the number of discussions right now both internally and with the external partners on the best way to leverage that opportunity with the pending Boston.

Michael P. Mason: Yeah.

Michael P. Mason: during their journey on therapy. And so the real use of expo will not be really the storm.

Jonathan Chang: Unknown Speaker, Unknown Interpreter, Unknown Interpreter, Unknown Interpreter, Unknown [inaudible]

Hannah: Got it. Thank you. The next question comes from Eric Joseph with J.P. Morgan. Please go ahead. Good morning, this is Hannah on behalf of Eric. Thanks for taking our questions. Just a couple from us. So first, what is the status of commercial preparations for nixpovio and you? Are you scaling for the pentorefractory population or scaling more in anticipation of accessing the third and second line patient populations of the Boston submission? And then there is another one after that.

Indication that should come hopefully by the end of the sheer so it's something that we're just really working through in terms of how the best bring that asset to that market appropriately with all the different pricing implications on sequencing that we can we can work through so hopefully that answered your question.

I'd just add we absolutely have the will make the drug available once it's got a European commission approval of assuming that that goes well.

Exactly the real the real market opportunity here is clearly in the Boston type population.

Stephen Michener: Yeah, Stephen. Do you want to take that?

Stephen Michener: Sure.

Stephen Michener: So, you know, as we mentioned before, we are very excited that we got a positive opinion on the storm indication. We are having a number of discussions right now, both internally and with external partners, on the best way to leverage that opportunity with the pending Boston indication that should come hopefully by the end of this year. So it's something that we're just really working through in terms of how to best bring that asset to that market appropriately with all the different pricing implications and sequencing that we can work through.

And so the the big Big push that we're gonna have is going to be for the Boston hoped the Boston approval by the end of the year, but we will have the drug available for patients.

On time.

Okay, great. Thank you that's helpful. And then also in that vein do you expect that because there's some ex prescribing patterns will differ between the E. On the us just preliminary thoughts on that.

Jason do you want on that.

In terms of prescribing pattern.

Stephen Michener: So hopefully that answered your question. Just to add, we absolutely will make the drug available once it's got European Commission approval, assuming that goes well. The real market opportunity here is clearly in the Boston population, and so the big push that we're going to have is going to be for Boston approval by the end of the year, but we will have the drug available for patients on time.

I can just jump in and just real quick.

One of the problems in Europe is the one of that one of the challenges is us if theres a lot less reimbursement for off label use and so physicians tend to be restricted to what the on label at least in certain in most of the countries. There are some countries that are more liberal.

And provided that the line of therapy as appropriate physicians would be using the drug as they see fit but I think the the main difference will be just on the restricted access all of a reimbursement John do you want to pick up on that.

Michael P. Mason: Okay, great. Thank you. That's helpful. And then, also in that vein, do you expect that physician prescribing patterns will differ between the EU and the US? Just my preliminary thoughts on that.

Jaden Shah: Jayden, do you want to take this?

Now, let's say well prescribing patterns may differ somewhat across the us and Europe early research that we've done does get the positive reaction from the ex the Edr Boston profiles. So we do expect to have good penetration in the European market as well once they launch in that indication.

Jaden Shah: In terms of prescribing patterns,

Jaden Shah: Unknown Speaker.

John Demery: I can just jump in and do it real quick. One of the problems in Europe is that one of the challenges is that there's a lot less reimbursement for off-label activities. And so physicians tend to be restricted to what's on the label, at least in certain areas, in most of the countries. There are some countries that are more liberal, and provided that the line of therapy is appropriate, physicians would be using the drug as they see fit. But I think the main difference will be just restricted access or reimbursement. John, do you want to pick up on that?

Okay, great very helpful. Thanks for taking the question.

Uh huh.

The next question comes from Mike All of US with Baird. Please go ahead.

Yeah.

Hi, guys. Thanks for taking the questions and congratulations on all of the progress as well.

John Demery: Prescribing patterns may differ somewhat across the U.S. and Europe, but early research that we've done does get a positive reaction for the XED or Boston profile. So we do expect to have good penetration in the European market as well once we launch that education.

Maybe I could just ask the follow up on some of the prior questions related to <unk> trends.

Do you guys sort of mentioned on.

The increase in demand starting in December and also in January So just curious of the month over month trend, where you're seeing an acceleration there and then of a follow up.

Hannah: Okay, great. Very helpful. Thanks for taking the question. The next question comes from Mike Allswood-Baird. Please go ahead. Hi guys, thanks for taking the questions and congratulations on all the progress as well.

Hello, everybody I think well, yes, I think we'll leave it at again, we don't want to get.

And of the weeds in terms of weekly or monthly.

Unknown Attendee: Maybe I could just ask to follow up on some of the prior questions related to OVO trends. You guys sort of mentioned an increase in demand starting in December and also in January. So just curious, the month-over-month trend, were you seeing an acceleration there? I'll have a follow-up.

Prescription trends, so we'll leave that to our our quarterly summation. When we have these kind of the call I think suffice it to say we are pleased with.

On the early indicators in the growth that we're seeing since approval.

And again I think when we get to our full Q1 numbers it'll be much clearer in terms of average on overall for the for the full first quarter.

Ian Karp: Yeah, I think we'll, yeah, I think we'll leave it at, again, we don't want to get too into the weeds in terms of weekly or monthly prescription trends. So we'll leave that to our quarterly summation when we have these kinds of calls. I think suffice it to say we are pleased with the early indicators and the growth that we're seeing since approval. And again, I think when we get to our full Q1 numbers, it'll be much clearer in terms of how we did overall for the full first quarter.

Got it that's fair and then maybe just the follow up on N E C N guidelines of it.

So you've got recommendation in combination with Velcade, which is on label, but you've also got a recommendations off label with Palm of list in doors of the Lex and I know, it's early but just since those guideline updates have you noticed the notebook sort of an off label use in those combinations right.

Unknown Attendee: Got it, that's fair. And then maybe just a follow-up on NCCN guidelines.

Unknown Speaker: , and Michael M.. .. .. .. .. ....

John Demery: John, you want to take that? Yeah, man.

John do you want to take that demand.

Yes.

Unknown Attendee: Unknown Attendee

Sure glad to address that so our sales team and marketing team of course, the only promote expose the O on US approved FDA label, which is that the ex the combination we do know that many physicians and payors rely on the NCC guidelines to help make treatment decisions and as you mentioned on D. C. On recently added three different exposure.

John Demery: Sure, glad to address that. So our sales team and marketing team will, of course, only promote Expovio on its approved FDA label, which is the XBD combination.

John Demery: We do know that many physicians and payers rely on the NCCN guidelines to help make treatment decisions.

John Demery: And as you mentioned, NTCN recently added three different Excovio regimens, the Bortezomib regimen, or XVD, in combination with their Tumamab, or XDD, and with Pomalidomide, or XPD. Unknown Speaker Unfortunately, the once weekly XPD regimen was approved with category one recommendation, which represents the highest level assigned by the NCCN. As we track in secondary market research, as you mentioned, and we're doing going forward, we will look at a breakout and see how much use it is in XPD versus XPD versus XKD, etc. It's too early to have those data to date, but those are data we'll gather for market research as we go through.

Regimens.

And the more it hasn't been the regimen or ex C. D of combination, but they're tuned the Mavericks EDI and on the way the mine are ex T D.

Importantly, the once weekly ex vivo regimen was approved what category, one recommendation, which represents the highest level of assigned by the end of CCN.

Whereas we track and secondary market research as Ian mentioned and were doing going forward, we will book at a breakout and see how much use us in ex D D versus ex P D versus ex KD et cetera, it's too early to have those data to date, but those are data won't gathered from market research as we go throughout the year.

Unknown Attendee: Got it. Thank you very much.

Got it thank you very much.

Edward Patrick White: The next question comes from Ed White with HC Wainwright. Please go ahead. Morning, everyone.

The next question comes from Ed White with H C. Wainwright. Please go ahead.

Yeah.

Good morning, everyone maybe.

Maybe.

Michael P. Mason: Maybe, If I could ask a question on the pipeline. You can list your priorities and solid tumors. You mentioned the endometrial and metastatic melanoma studies, but I just wanted to get an update on lung colorectal cancer and GBM.

If I can ask a question on the pipeline.

If you can lift your priorities in solid tumors, you had mentioned the endometrial and metastatic melanoma studies I just wanted to get an update for lung.

Colorectal cancer and GBM.

Michael P. Mason: Yeah, well, those are all, you know, these are all sort of equal priorities. We're enrolling patients into our own studies in all the ones that you mentioned, lung, colorectal, and GBM. You have single-agent activity in GBM, which we've talked about 10%, and we've seen activity as well in colorectal, and we've seen an investigator-sponsored trial, as I've mentioned, that's been ongoing now with some activity in the lung. So, you know, this drug seems to be a very important add-on therapy or addition to some of the active drugs that are used across multiple different indications, and that's because this is a fundamental mechanism of, we attack a fundamental mechanism of cancer, which is the inactivation of tumor suppressor proteins, and we reactivate those tumor suppressor proteins.

Yeah.

Yeah, well those are all of you know the these are all sort of equal priorities, where we're enrolling patients into our own studies and all of the ones that you mentioned lung colorectal and G. B M. You have single agent activity in GBM, which we've talked about 10%.

We've we've seen activity as well in colorectal.

And we've seen an investigator sponsored trials I've mentioned, that's been ongoing now with some activity in lung. So we you know this drug seems to be a a very important add on therapy or addition to some of the active drugs that are used across multiple different indications and that's that's because there's been a fundamental mechanism of.

We attack upon us on mechanism of cancer, which is inactivation of tumor suppressor proteins and we reactivate those tumor suppressor proteins and then of course don't forget we have our C. Endo phase III study read out by the end of this year, where we're using our expo the O versus placebo in the maintenance setting after frontline therapy, so broadly active.

Michael P. Mason: And then, of course, don't forget, we have our CNDO Phase III study ready by the end of this year where we're using Expovio versus placebo in the maintenance setting after frontline therapy. So, broadly active drug, and we're being very careful about how we use our precious resources, but we see it across a number of different therapies, and we'll pick the best winners and move them forward as expeditiously as possible.

Drug and you know were being very careful about how we use our precious resources, but we see it across the number of different therapies, and we'll pick the best winters and move them forward as expeditiously as possible.

Michael P. Mason: And maybe just talking about resources. Question for Mike or Ian. Did you use the ATM in the fourth quarter or thus far in 2021? And are you including any proceeds from the ATM in the cash runway guidance? Thanks.

Great. Thanks, Michael and maybe just talking about resources.

The question for Mike or E on.

Did you use the ATM.

In the fourth quarter or thus far in.

2021 and or.

Are you, including any proceeds from the ATM in the cash runway guidance. Thanks.

Michael P. Mason: Yeah, so we certainly don't comment on ongoing fundraising. The ATM, we definitely did not use it during the fourth quarter. And we don't don't include that in our guidance. It's more about current, you know, improved indications plus current collaborations that we already have in place offset by spend, which we guide to would be somewhere between 280 and 300 million in 2021.

Mike.

Yes.

So we certainly don't comment on ongoing fund raising.

But on the ATM, we definitely did not use of during the fourth quarter.

And we just don't include that in our in our guidance, it's more on current improve into indications plus current.

Collaborations that we already have in place offset by the spend which we guidance it would be somewhere between $2 80, and 300 million net.

Okay. Thanks, Mike and also just.

Michael P. Mason: Okay, thanks, Mike. And also, just as far as that guidance goes on the runway, does that include any milestone payment or potential milestone payment from a European partnership?

As far as that guidance goes on the runway does that include any.

Milestone payment of potential milestone payment from a European partnership.

We don't include any new.

Michael P. Mason: So we don't include any new, when that got into any new collaborations, obviously it's something that's a big part of Stephen's focus for 2021, as well as the entire, you know, company to make sure we're ready to commercialize in Europe, but no, it does not include any new. New Alliance.

When does that guidance of any new collaborations obviously, its something thats the big part of Stephens focus for 'twenty one of the entire.

The company and to make sure we're right in the commercialized in Europe, but no. It does not include any significant payments or from new alliances.

Michael P. Mason: Okay, great. Thanks for taking my question. This concludes our Q&A session. I would like to turn the conference back over to Michael Kauffman, CEO, for any closing remarks.

Okay, great. Thanks for taking my questions.

Okay.

This concludes our Q&A session I would like to turn the conference back over to Michael Kauffman CEO for any closing remarks.

Yes.

Michael P. Mason: Thank you everybody for joining today's call, and we do look forward to updating you on our progress as soon as we can. Talk to you soon. Bye-bye.

Thank you everybody for joining today's call and we do look forward to updating you on our progress as soon as we can talk to you soon bye bye.

The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

Operator: The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

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