Q4 2021 TG Therapeutics Inc Earnings Call
[music].
Operator: Greetings and welcome to the TG Therapeutics 4th quarter and year end 2021 financial results and business update call. At this time, all participants are in a listen only mode.
Greetings and welcome to the TG Therapeutics fourth quarter, and yearend 2021 financial results and business update call.
At this time, all participants Arnold listen only mode. A question and answer session will follow the formal presentation. If you would like to ask a question you May press star one on your telephone keypad, if anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad. As a reminder, this conference is being recorded it is now my pleasure to introduce your host.
Operator: A question and answer session will follow the formal presentation. If you would like to ask a question, you may press star one on your telephone keypad. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Ms. Jenna Bosco.
Ms Jenna Bosco.
Jenna Bosco: Senior Vice President of Corporate Communications. Thank you. Please go ahead.
Senior Vice President of corporate Communications. Thank you. Please go ahead.
Jenna Bosco: Thank you. Welcome, everyone, and thanks for joining us this morning. I'm Jenna Bosco, and with me today to discuss the fourth quarter and year-end 2021 financial results and provide a business update are Michael Weiss, our Chairman and Chief Executive Officer, Adam Waldman, our Chief Commercialization Officer, and Sean Power, our Chief Financial, Following our Safe Harbor Statement, Mike will provide an overview of our recent corporate developments as well as an update on our current pivotal programs.
Thank you welcome everyone and thanks for joining us this morning, I'm, Jenna Bosco and with me today to discuss the fourth quarter and year end 2021 financial results and provide a business update are Michael Weiss, our chairman and Chief Executive Officer.
Adam Waldman, our chief commercialization officer, and Sean power, our Chief Financial Officer.
Following our safe Harbor statement, Mike will provide an overview of our recent corporate developments as well as an update on our current pivotal programs.
Adam will then provide an update on our commercialization efforts and Sean will provide an overview of our financial results before turning the call over to the conference operator to begin the Q&A session.
Jenna Bosco: Adam will then provide an update on our commercialization efforts, and Sean will provide an overview of our financial results before turning the call over to the conference operator to begin the Q&A session. Before we begin, I'd like to remind everyone that we will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1992. These forward-looking statements include statements about our anticipated future operating and financial performance, including sales performance, projected regulatory milestones, clinical development plans, and expectations for our marketed and pipelined services. We caution that these forward-looking statements are subject to risks that may cause our actual results to differ materially from those intended.
Before we begin I'd like to remind everyone that we will be making forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.
These forward looking statements include statements about our anticipated future operating and financial performance, including sales performance projected regulatory milestones clinical development plans and expectations for our marketed and pipeline products.
TG cautions that these forward looking statements are subject to risks that may cause our actual results to differ materially from those indicated factors that may affect TG therapeutics operations include various risk factors that can be found in our SEC filings in.
Jenna Bosco: Factors that may affect TG Therapeutics operations include various risk factors that can be found in our SEI. In addition, any forward-looking statements made on this call represent our views only as of today, and should not be relied upon as representing our views as of any time. Subsequent, We specifically disclaim any obligation to update or revise any forward...
In addition, any forward looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent to subsequent date.
We specifically disclaim any obligation to update or revise any forward looking statements.
Michael Weiss: This conference call is being recorded for audio rebroadcast on TG's website, www.tgtherapeutics.com, where it will be available for the next 30 minutes. And now I'd like to turn the call over to Mike Weiss, our CEO. Thanks, Jenna, and thanks to everyone for joining us this morning. Well, as everyone is aware, TG has been throwing a few curveballs over the last few months. The good news, though, for those of you who are baseball fans, I actually think these are hanging curveballs that we can hit out of the park.
This conference call is being recorded for audio rebroadcast on Tg's web site Www Dot TG therapeutics Dot com, where it will be available for the next 30 days now.
Now I'd like to turn the call over to Mike Weiss our CEO .
Michael Weiss: And if we are able to do that, I genuinely believe that we'll be in a much stronger position because of it. I'll provide more color momentarily, but let's start by reviewing some of the developments, good and bad, that have occurred over the last 12 months or so. Most recently at ACTROMS, we presented additional analysis of the data from the ultimate one and two face-to-face trials of Tuxamab in the lapsing forms of MS, which we believe continues to highlight and support the potential utility of Tuxamab as a treatment option for patients with RMS. We strengthened our balance sheet by expanding our term loan facility and ended 2021 with more than $350 million in cash.
Thanks, Gena and thanks to everyone for joining us this morning.
As everyone is aware TJ has been sent a few curve balls over the last few months are the good news although for those of you who are baseball fans I actually think these are hanging curve balls that we can hit out of the park and if we are able to do that I genuinely believe that will be in a much stronger position because of it.
Michael Weiss: Toward the end of the year, we had a strong presence at the 2021 ASH Conference with three oral presentations and three poster presentations, with two of the oral presentations being chosen for highlights of ASH. Just before Ash, we announced that the FDA was planning to review, the CLL, BLA, and SNDA at an ODAC meeting to occur in the March-April timeframe. Related to the issues to be covered at ODOT just a few weeks ago, FDA placed studies investigating U2 and its components in CLL and NHL on a partial clinical hold.
I'll provide more color momentarily, but let's start by reviewing some of the developments good and bad that occurred over the last 12 months yourself.
Most recently an actress we presented additional analysis of the data from the ultimate one into phase three trials in relapsing forms of M. S, which we believe continuing to highlight and support the potential utility of Rituxan met as a treatment option for patients with RMS we.
We strengthened our balance sheet by extending our term loan facility and ended 2021 with more than $350 million in cash.
Towards the end of the year, we had a strong presence at the 2021 Ash conference with three oral presentations and three poster presentations with Tuesday, oral presentations being chosen for highlights of ash.
Just before rash, we announced that the FDA was planning to review.
The C O L. B L. A M S N D. A N O that meeting to occur in the March April time frame.
Related to the issues to be covered to do that just a few weeks ago F. D. A placed studies investigating Youtube and its components in sealing CLO and NHL on a partial clinical hold.
Michael Weiss: Also, in the fourth quarter of 2021, we announced our Biologics License Application, or BLA, for Ulbituximab to target, to treat patients with relapsing forms of multiple sclerosis was accepted by the FDA and was granted a pedophagol date of September 28, 2022.
Also in the fourth quarter of 2021 we announced our biologics biologics license application or BLA for <unk> to target.
To treat patients with relapsing forms of multiple sclerosis was accepted by the FDA and was granted a bit difficult date of September 28 2022.
We also continue to advance our early stage pipeline and presented data from <unk> 17 in one R. P. T inhibitor several times throughout the year.
Michael Weiss: We also continue to advance our early-stage pipeline and presented data from TG1701, our BTA inhibitor, several times throughout the year. We completed enrollment of approximately 165 CLL patients into the Ultra-V Phase II trial and launched the Phase III portion of that study. We published results from some of our key trials in major publications, including an integrated safety analysis of eukonic and blood advances. Unity NHL Phase 2B trial of umbilicid monotherapy in patients with relapsed or refractory non-Hodgkin's lymphoma in the Journal of Clinical Oncology and the GENUINE trial evaluating ubatuximab plus abrutinib in patients with relapsed or refractory high-risk CLL, in Lancet Hematology.
We completed an enrollment of approximately 165 CLO patients each of the ultra V phase two trial.
And launched the phase III portion of that study.
We published results from some of our key trials in major publications, including an integrated safety analysis of Uchronic in blood advances.
Unity NHL phase two b trial of umber licit monotherapy in patients with relapsed or refractory non Hodgkin's lymphoma in the journal of clinical oncology.
And the genuine trial evaluating bavituximab plus ibrutinib in patients with relapsed refractory high risk <unk>.
L L.
In lancet hematology.
Michael Weiss: And of course, in quarter one of 2021, a little over a year ago today, we received FDA approval of Yukonic to treat patients with relapsed refractory, marginal zone lymphoma, and follicular lymphoma, marking our very first FDA approval. With that, let me review our late stage development programs, following which I will turn the call over to our Chief Commercialization Officer, Adam Waldman, to discuss some of the commercialization highlights. All right, so let's begin with the discussion of the ultimate one and two phase three trials, which evaluated ubatuximab monotherapy compared to teriflunomide in relapsing forms of MS. As noted in the past, both studies met their primary end point with Oobatuximab treatment demonstrating a statistically significant reduction in annualized relapse rate, referred to as ARR, with Oobatuximab treatment resulting in historically low levels of annualized relapse rate.
And of course in quarter, one of 2021 a little over a year ago. Today, we received FDA approval of your kind of <unk> to treat patients with relapsed or refractory marginal zone lymphoma, and Follicular lymphoma.
Our very first FDA approval.
With that let me review our late stage development programs, following which I will turn the call over to our Chief commercialization Officer, Adam Waldman to discuss some of the commercialization highlights.
Alright, so let's begin with a discussion of the ultimate one and two phase three trials, which evaluated talks about monotherapy compared to tariff solidified in relapsing forms of M. S.
As noted in the past both studies met their primary endpoint with no treatment demonstrating a statistically significant reduction in annualized relapse rate referred to as a R. R.
You've been talking to have treatment, resulting in historically low levels of annualized relapse rate and.
Michael Weiss: In addition to the primary endpoint, we've had the opportunity over the past year to present several different sub-analyses of this data, all of which have strengthened our confidence in the utility of Lubetuximab to provide a meaningful treatment option to patients with RMS, if approved. On the regulatory front, we were extremely pleased to announce the FDA accepted our BLA for Obotuximab. Treat Patients with RMS and granted a PDUFA goal date, as I mentioned earlier, of September 28, 2022.
In addition to the primary endpoint with <unk>.
Had the opportunity over the past year to present several different sub analysis of this data all of which have strengthened our confidence in the utility of rituxan up riding meaningful treatment option to patients with RMS if approved.
On the regulatory front, we were extremely pleased to announce the FDA accepted our BLA for Botox a mab.
To treat patients with RMS and granted a paducah go date as I mentioned earlier of September 28, 2022.
Michael Weiss: Adam will discuss our launch prep activities, but let me highlight again that we have built an all-star team of MS talent from around the industry. These folks have fantastic relationships in the Microsoft community, which have enabled us to gain invaluable insight.
Adam will discuss our launch prep activities, but let me highlight again that we have built an all star team of M. S talent from around the industry. These folks have fantastic relationships in the M. S community, which have enabled us to gain invaluable insights.
Michael Weiss: After spending several days last week at ACTRIMS in back-to-back-to-back meetings, I am more confident than ever in the potential of the Lupituximab in RMS. With the CD20 class already accounting for the largest portion of new starts and switches, which is sometimes referred to as the dynamic market, we see Obituximab as having the potential to play an important role in the treatment of relapsing forms of MS. All right, now let's talk about our CLL VLA-SNDA and the upcoming ODAC.
After spending several days last week at actress and back to back to back meetings I'm more confident than ever in the potential of little bit touching that in Rms.
The C D 20 class already accounting for the largest portion of new starts and switches, which is sometimes referred to as the dynamic market. We.
We see it we'll be talking about as having the potential to play an important role in the treatment of relapsing forms of M. S.
Alright, now, let's talk about R. R. C. L. L. B L. A S N D E and the upcoming or DAC.
Michael Weiss: So I just want to remind everyone, first and foremost, that the UnityCILA study, which is the primary study supporting the BLA SNDA with conducted under-special protocol assessment, and met its primary endpoint of progression-free survival and all key secondary endpoints. We submitted a BLA-SNDA for the YouTube combination in the treatment of CLL and received a PDUFA goal date of March 25, 2022. In September of 2021, we received a request from the FDA to conduct analysis of overall survival. While OS was stated as a secondary endpoint, there was no plan to analyze it prior to the end of the trial, which has not yet occurred.
I just wanted to remind everyone.
First and foremost that the unity <unk> study.
Which was which is the primary study supporting the BLA S. N da was conducted under special Protocol assessment.
And met its primary endpoint of progression free survival and all key secondary endpoints.
We submitted a BLA S N da for the use of combination in the treatment of CLO and received a <unk> date of March 25th 2022.
Michael Weiss: Importantly, the Unity CLL study was not powered for overall survival, which would have required dramatically more overall survival events. And in addition, a significant number of patients on the control arm crossed over to the U2 arm, collectively making the OS results hard to interpret. Furthermore, since we were not planning an OS analysis until the end of the trial, not all the data was collected at the time FDA requested the overall survival analysis, leaving about 15% of the patients, with outdated or missing survival stats. Despite these material shortcomings, we conducted the analysis and sent it to the FDA as requested.
In September for 2020 , one we received a request from the FDA to conduct analysis of overall survival.
Oh, that's a stated as a secondary end point there was no plan to analyze it prior to the end of the trial, which has not yet occurred importantly, the union unity <unk> study was not powered for overall survival, which would have required dramatically more overall survival events.
And in addition, a significant number of patients on the control arm crossed over to the U two warm collectively making the OS results hard to interpret.
Furthermore, since we were not planning an O S analysis until the end of the trial not all the data was collected at the time after.
FDA requested the overall survival analysis, leaving about 15% of the patients.
Without dated or missing survival status.
Despite these material shortcomings, we conducted the analysis incentive to the F D as requested.
Michael Weiss: As has been reported previously, that analysis showed an imbalance in favor of the control arm. The hazard ratio was 1.23, but when excluding COVID, it was 1.04. A hazard ratio above 1 implies potential harm of a therapy and below 1 a potential benefit. Given the shortcomings of the OS analysis, and similar results from other pivotal phase 3 studies in CLL, we didn't see this OS imbalance as concerning. Some of those examples included the original overall survival analysis from CLL-14, which was the approval study for the Nataclax Plus Obinatusa Mass.
As has been reported previously that analysis showed an imbalance in favor of the control arm.
The ratio was one point to three but when excluding COVID-19 . It was 1.04.
A hazard ratio of above one implies potential harm of a therapy and below one a potential benefit.
Given the shortcomings of the OS analysis.
Similar results from other pivotal phase III studies in C. O L. We didn't see this O S imbalance as concerning.
Some of those examples included the original overall survival analysis from C. O L 14, which was the approval study for Vanadic lax plus I've been to choose a map.
Michael Weiss: Similar to our trial, the control arm was Obinutuzumab Clorambucil, and at the time of approval, the hazard ratio was 1.24. No adjustment there because, of course, that study was conducted before COVID, so that would not have been a confounding factor. We also took a look at the overall survival results from the Illuminate study, which was used for approval of Ibrutinib plus abinituzumab. Again, similarly, the control arm was Obinutuzumab Calambracel, same as ours.
Similar to our trial the control arm was a bit of choosing a chlorambucil and at the time of approval. The hazard ratio was 1.24.
No adjustment there because of course in that study was conducted before COVID-19 . So that would not have been a confounding factor.
We also took a look at the overall survival results from the illuminate study, which was used for approval of Ibrutinib plus I've been to choose a map.
Again similarly, the control arm was open to choose not to clamber, so same as ours.
Michael Weiss: The overall survival outcome in this study was even more peculiar. Here, the hazard ratio was 0.921, so below one at the time of approval, but in long-term follow-up, turn negative against a brutitive for the hazard ratio of 1.083. Both of these instances highlight the challenges of using underpowered overall survival analysis. So I think everyone could imagine our surprise when in November of 2021, the FDA notified us that they plan to host a meeting of the, Oncologic Drugs Advisory Committee, referred to as ODAC, and ODAC being much easier to say, of course, in connection with its review of the BLA for ibuprofen and the SNDA for melissa, stemming from the OS imbalance.
Overall survival outcome in this study was even more peculiar here the hazard ratio was <unk> nine to one so below one at the time of approval, but in long term follow up turn negative against Ibrutinib with a hazard ratio of 1.083.
Both of these instances highlight the challenges of using underpowered overall survival analysis.
So.
And I think everyone could imagine our surprise when in November of 2021 the FDA notified us that they plan to host a meeting of the.
Oncologic drugs Advisory Committee, refrigerants, Oded, and Oh vaccine much easier to say of course in connection with its review of the BLA for other types of NAD and the S N D or thrombolysis.
Stemming from the O S imbalance.
Michael Weiss: It is also evident with the regulatory action seen for other PI3K inhibitors that there is a concern with the overall class, that is influencing the way the FDA is viewing this data. We spent the next two months trying to close the information gap.
It is also evident with the regulatory action see for other peer three K inhibitors that there is a concern with the overall class.
That is influencing the way the FDA is viewing this data.
We spent the next two months trying to close the information gap. We were pleased to report about a month ago that we were able to reduce the missing survival information from 15% down to 5%.
Michael Weiss: We were pleased to report about a month ago that we were able to reduce the missing survival information from 15% down to 5%, and we were further pleased to report at a high level. That the capture of the additional survival data, the overall survival analysis, both in the ITT and the COVID censored populations, the overall survival hazard ratios. Improved, from what we have seen, the original submission to the FDA. We've provided that update to the FDA late last month.
When we were further pleased to report at a high level.
That the capture of the additional survival data the overall survival analysis, both in the I T T and the Covid censored populations the overall survival hazard ratios.
Improved.
From what we had seen in the original submission to the FDA, we provided that update to the FDA late last month.
Michael Weiss: We also spent a considerable amount of time doing a deep dive into the survival data, literally reviewing patient by patient to try to understand causality. For now, I will be brief and in summary will say, from TG's standpoint, and that of our independent external medical and statistical advisors that the totality of the Unity CLL data suggests that the overall safety profile is generally in line with currently available tumors for CLL, especially when focusing on treatment-related death.
We also spent considerable amount of time doing a deep dive into the survival data literally reviewing patient by patient to try to understand causality.
For now I will be brief in summary, we'll say from TG standpoint.
And that of our independent external medical and statistical advisers that the totality of the unity sale data suggests that the overall safety profile is generally in line with currently available treatments for C O L, especially when focusing on treatment related deaths.
Michael Weiss: Since we received notification of the ODAC, the team has been hard at work preparing for the upcoming meeting, and we are looking forward to the opportunity to showcase, under critical review, that Eukonic is a unique PI3K inhibitor with a differentiated toxicity and tolerability profile and with the potential to fill an unmet need in the treatment of CLL. With that, I'll turn the call over to Adam Waldman, our Chief Commercialization Officer, to share a bit about our current commercialization efforts and preparations for potential launches later this year.
Since we received notification of the O that the team has been hard at work preparing for the upcoming meeting and we were looking forward to the opportunity to showcase under critical review that you're kind of <unk> is a unique guthrie, Ken inhibitor with a differentiated toxicity and tolerability profile.
And with the potential to fill an unmet need in the treatment of CLO.
With that I'll turn the call over to animal women, our chief commercialization officer.
Share a bit about our current commercialization efforts and preparations for potential launches later this year.
Adam.
Adam Waldman: Yep, thanks, Mike. And good morning, everyone. I'm excited to provide an update on our commercial performance and execution in Q4, as well as our plans for expansion and potential commercialization of U2 and CLL and Oobletuximab in relapsing forms of MS in 2022. First, for Eukonic, we just passed the one-year anniversary of the approval and we continue to see broad usage and positive feedback amongst prescribers in the U.S. market. Our teams did an excellent job working through the challenges in the quarter to increase awareness and educate health care providers on Econics unique profiles.
Yeah, Thanks, Mike and good morning, everyone I'm excited to provide an update on our commercial performance and execution in Q4.
As well as our plans for expansion and potential commercialization of Youtube and C O L and O Botox, a mab in relapsing forms of biomass in 2020 two.
First for your Connick, we just passed the one year anniversary of the approval and we continue to see broaden usage and positive feedback amongst prescribers in the U S market.
Our teams did an excellent job working through the challenges in the quarter to increase awareness and educate healthcare providers on <unk> unique profile.
Adam Waldman: It is clear that you kind of give healthcare providers a novel treatment option for patients who have seen multiple previous therapies, the marginal zone lymphoma and follicular lymphoma, And with the recent withdrawals of Idelalysib and Dubalistib from the lymphoma market, Eukonik is now the only oral PI3K approved for these patients. Despite the continued COVID headwinds in the quarter, we continue to see progress. Net sales grew 14%.
It is clear that you kind of gives health care providers, a novel treatment option for patients who have seen multiple previous therapies for marginal zone lymphoma, and Follicular lymphoma and.
And with the recent withdrawals of I don't I dealt with Elisa and Duvelisib.
On the market.
Connick is now the only oral PR three K approved for these patients.
Despite the continued COVID-19 headwinds in the quarter, we continued to see progress in that.
Sales grew 14%.
Adam Waldman: 2.3 million in net revenue in Q4, bringing the full year 2021 net revenue, to 6.5 million. Interestingly, overall demand for Eukonic increased 25% quarter over quarter. However, we also continue to see Eukonic demand and revenue impacted by patient affordability issues. As a result, we provided free drug to about 37% of Econiq treated patients, through our TG patient support program in Q4 and throughout 2021. What remains encouraging is that eukonic awareness and familiarity among targeted treaters remains high, and prescribers continue to cite strong eukonic performance across key product attributes.
With $2 3 million in net revenue in Q4, bringing the full year 2021 net revenue.
$6 5 million.
Interestingly overall demand for Ya Connick increased 25% quarter over quarter. However, we also continued to see your connick demand in revenue impacted by patient affordability issues. As a result, we provided free drug to about 37% of your comic treated patients through our T. G. A patient support program in Q4.
And throughout 2021.
What remains encouraging is that your colic awareness and familiarity among targeted treaters remains high prescribers.
Prescribers continue to state sites strong iconic performance across key product attributes.
Adam Waldman: Additionally, the eukonic prescriber base continues to increase, and we are observing new patient starts in both new and existing accounts. We have also seen greater uptake in the community setting, which accounted for an estimated 65% of new patient starts in Q4. We are very encouraged by the feedback from health care providers and third-party research regarding buconic use continues to remain very positive.
Additionally, you Connick prescriber base continues to increase and we are observing new patient starts in both new and existing accounts.
I've also seen greater uptake in the community setting, which accounted for an estimated 65% of new patient starts in Q4.
We are very encouraged by the feedback from health care providers and third party research regarding your kind of Hughes, which continues to remain very positive.
Adam Waldman: Physicians that have used Econiq report an appreciation for its differentiation and they see the benefit that it brings to patients. We also know the continued positive experience across a broadened prescriber base in the community will help lay the foundation for a successful CLL launch in the future. Our hematology teams are continuing our planning efforts to focus on the U2 CLL launch objectives. The U2 CLL launch will be an important milestone for our hematology franchise, and we remain confident that we can leverage the experience from the Eukonica launch, along with the enhancement of internal commercial capabilities to deliver a successful CLL launch.
Missions that abuse iconic reported an appreciation for its differentiation and they see the benefits that it brings to patients.
We also know the continued positive experience across a broader prescriber base in the community will help lay the foundation for a successful CLO launch in the future. Our hematology teams are continuing our planning efforts to focus on the Youtube CLO launch objectives.
Youtube CLO launch will be an important milestone for our hematology French franchise.
Main confident that we can leverage the experience from your Konica launch along with the enhancement of internal commercial capabilities to deliver a successful CLO launch.
Adam Waldman: Our commercial execution efforts continue to improve, which has led us to optimize account segmentation, prioritization, and solidified relationships in the hematology community. Now, turning to MS, we just, as Mike mentioned, we just returned from the ACTRUM meetings last week. And the feedback from thought leaders and the overall energy around Uber Tuxenab data was incredibly exciting.
Our commute our commercial execution efforts continued to improve which has led us to optimize account segmentation prioritization and solidified relationships in the hematology community.
Now turning to MFS, we just as Mike mentioned, we just returned from the Acura meetings last week.
And the feedback from thought leaders in the overall energy around who both tux map data was incredibly exciting.
Adam Waldman: Over the fourth quarter and early part of this year, we continue to make great strides in launch preparation for MS. We're actively building and expanding our MS-focused field-based roles with remarkable talent, with extensive MS experience and deep relationships with the MS community. These team members are focused on continued engagement with the MS stakeholders, including prescribing health care providers, their staff, payers, and advocacy groups to gather insights through advisory boards, one-on-one personalized meetings, and at conferences, including the recently held conference last week. During these engagements, we consistently hear positive feedback in Ubitoximab's clinical profile. Regarding the efficacy, the annualized relapse rate of less than 0.1 differentiates Ubitoximab amongst others in the class.
Over the fourth quarter and early part of this year, we continue to make great strides in launch preparation for all of us.
Adam Waldman: On the safety front, the incidence of infections and serious infusion-related reactions seen in the clinical trials appears to be a differentiating based on physician feedback. Finally, in terms of convenience, the shorter infusion is seen as a competitive advantage among existing anti-CD20s. Healthcare providers, specifically advanced practice providers, reference the shorter infusion time as a benefit to their patient infusion experience. Highlighting that almost 80% of people living with MS struggle with spasticity or tightness or stiffness of the muscles and bladder dysfunction, urinary urgency, meaning sitting in a chair for an extended period of time is obviously not ideal.
Were actively building and expanding our M. S focused field based roles with remarkable talent with extensive experience and deep relationships with the Ms community. These.
Sean Power: Our research also indicates that the majority of top MS centers of excellence experience capacity constraints with infusions, making a shorter infusion potentially attractive. Over the coming months, we will continue our pre-launch activities and preparations to launch Viproximab, which will leverage a customer-focused commercialization strategy that we believe will enable ubotuximab to become a meaningful treatment option for relapsing MS patients.
These team members are focused on continued engagement with the M S stakeholders, including prescribing health care providers their staff payers and advocacy groups together insights two advisory boards, one on one personalized meetings and conferences, including the recent we held conference last week.
During these engagements we consistently hear positive feedback loop Rituxan labs clinical profile regarding the advocacy of the annualized relapse rate of less than 0.1, differentiates who will talk cement amongst others in the class.
On the safety front, the incidence of infections and serious infusion related reactions seen in the clinical trials appears to be a differentiating based on physician feedback.
Finally in terms of convenience the shorter infusion is seen as a competitive advantage among our existing anti CD 20 <unk>.
Health care providers, specifically advanced practice providers referenced the shorter infusion time as the benefits of their patient infusion experience highlighting that.
Almost 80% of people living with them has struggled with specificity.
Tightness or stiffness of the muscles and bladder dysfunction urinary urgency.
He is sitting in the chair for extended period of time is obviously not ideal.
Our research also indicates that the majority of top M. S centers of excellence experienced capacity constraints.
With infusions, making a shorter infusion potentially attractive.
Over the coming months, we will continue our prelaunch activities and preparations to launch the pucks Mab.
Which will lever our customer focused customer focused commercialization strategy that we believe will enable who bill talks about become a meaningful treatment option for relapsing Ms patients.
With that I'll hand, it over to Sean power our CFO .
Thank you Adam and thanks again, everyone for joining us.
Sean Power: Earlier this morning, we reported our detailed financial results, which can be viewed on the investors and media section of our website. I'll begin with our cash position. As Mike highlighted, we were happy to strengthen our balance sheet in the fourth quarter of 21 with the upsizing of our term loan facility, allowing us to end the year with approximately $350 million in cash, cash equivalents, and investment securities. And as Adam just discussed a few moments ago, we reported $2.3 million of Euconic Net Product Revenue in the fourth quarter, resulting in cumulative net product revenue of $6.5 million for 2021, the first 10 months of our product launch.
Earlier. This morning, we reported our detailed financial results, which can be viewed on the investors and media section of our website.
I'll begin with our cash position as Mike highlighted we were where we're happy to have strengthened our balance sheet in the fourth quarter of 'twenty, one with the upsizing of our term loan facility, allowing us to end the year with approximately $350 million in cash cash equivalents and investment securities.
And as Adam just discussed a few moments ago, we reported $2 3 million of your chronic net product revenue in the fourth quarter, resulting in cumulative net product revenue of $6 5 million for 2020 . One the first 10 months of a product launch.
Sean Power: Our net loss for the fourth quarter of 2021, excluding non-cash items, was approximately $79 million, in line with our expectations, which was an increase of $7 million quarter over quarter from Q3 of 21, where we saw a net loss, excluding non-cash items, of approximately $72 million. As compared to the third quarter of 2021, the increase was primarily driven by an uptick in research and development costs, which pertain primarily to CMC expenses incurred in the fourth quarter of 2021.
Our net loss for the fourth quarter of 2021 excluding noncash items was approximately $79 million in line with our expectations, which was an increase of 7 million quarter over quarter from Q3 of 'twenty, one where we saw a net loss excluding noncash items of approximately 72 million.
As compared to the third quarter of 2021, the increase was primarily driven by an uptick in research and development costs, which pertain primarily to CMC expenses incurred in the fourth quarter of 2021 .
Sean Power: Our gap net loss for the fourth quarter of 2021, inclusive of non-cash items, was $93.3 million, or $0.70 per share, compared to a net loss of $88.2 million, or $0.71 per share, during the comparable quarter in 2020.
Our GAAP net loss for the fourth quarter of 2021 inclusive of noncash items with 90 to $93 3 million or <unk> 70 per share compared to a net loss of $88 2 million or <unk> 71 per share during the comparable quarter in 2020.
Sean Power: Our net loss for the full year ended December 31, 2021, excluding non-cash items, was approximately $287 million, compared to $199 million for the 2020 year-end. The year-over-year increase in net loss is primarily driven by an increase in SG&A expenses associated with the launch of Econic and planning for the potential future launches of U2 and CLL and Oobletuximab in RMS. Additionally, we saw an increase in our R&D expenses year over year, which is primarily attributable, again, to CMC expenses in preparation for commercialization and for our Phase III clinical trials.
Our net loss for the full year ended December 31st 2021, excluding noncash items was approximately $287 million compared to $199 million for the 2020 year end.
The year over year increase in net loss is primarily driven by an increase in SG&A expenses associated with the launch of a contact and planning for the potential future launches of Youtube M. C. L O and Uber talks a mab and Rms.
Additionally, we saw an increase in our R&D expenses year over year, which was primarily attributable again to CMC expenses in preparation for commercialization and for our phase III clinical trials.
Sean Power: The gap net loss for the year ended December 31st, 2021, inclusive of non-cash items, was $348.1 million, or $2.63 per share, compared to a net loss of $279.4 million, or $2.42 per share, for the year ended December 31st, 2020.
The GAAP net loss for the year ended December 31, 2021 inclusive of noncash items was 348 1 million or $2 63 per share compared to a net loss of $279 4 million or $2 42 per share for the year ended December 31st 2000.
'twenty.
Operator: In terms of what we expect moving forward, as we've previously disclosed following our company streamlining efforts, we project our burn in the first two quarters of 2022 to be between 55 and 65 million, down rather sharply from where it's been trending. With that, we believe our current cast will take us well out into 2023. With that, I will now turn the call back over to the conference operator to begin the Q&A.
In terms of what we expect moving forward as we've previously disclosed following our company streamlining efforts we project our burn in the first two quarters of 2022 to be between 55 and $65 million down rather sharply from where its been trending.
With that we believe our current cash will take us well out into 2023.
With that I'll now turn the call back over to the conference operator to begin the Q&A.
Operator: Thank you. The floor is now open for questions. If you would like to ask a question, please press star 1 on your telephone keypad at this time. A confirmation tone will indicate your line is in the question queue.
Thank you the floor is now open for questions. If he would like to ask a question. Please press star one on your telephone keypad at this time a confirmation tone will indicate your line is in the question queue. You May Press Star two if you would like to remove your question from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star key.
Operator: You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Once again, that's star 1 to register a question at this time. Our first question, coming from Chris Howardton of Jeffries, please go ahead. That's great.
Once again Thats Star one to register a question at this time.
Our first question is.
Coming from Chris Howerton of Jefferies. Please go ahead.
Chris Howardton: Thank you so much for taking the questions, and obviously look forward to all the more positive curveballs and for you to hit those hanging curveballs, Mike. So, appreciate it. I guess for me, two questions would be, one is, I know, Adam, you started to describe some of the efforts with respect to MS commercialization. I guess I'm curious if you can provide a little more thoughts in terms of how you're thinking about the size of that sales force.
That's great. Thank you so much for taking the questions and and obviously look forward to all the the more positive curve balls and for you to hit those hanging curve balls mics I appreciate it.
The I guess for me two questions would be one it is I know Adam you started to describe some of the efforts with respect to.
M S commercialization I guess I'm curious if you can provide a little more thoughts in terms of how you're thinking.
About the size of that sales force and maybe if you could give us some initial thoughts around our spending towards either direct to patient.
Chris Howardton: And maybe if you could give us some initial thoughts around spending towards either direct to patient or DTC type of spending in this setting. The second question would be if you could give us some indication as to what you think the confirmatory trials might look like for follicular and marginal zone, and if I have any follow-ups, I'd appreciate it. Great. Adam, you want to go ahead first and I'll jump in on the confirmation trial.
Or D T C type of spending and in this setting.
The second question would be if you could give us some indication as to what you think the confirmatory trials might look like for Follicular.
And marginal zone and family farms I'd appreciate it thanks.
Right. Adam you want to go ahead first and I'll show you something on the confirmation trial.
Adam Waldman: Sure, so Chris, thanks for the question. On the first part of the question, which was the Salesforce size, you know, we benchmarked other companies. We know generally what the size of their forces are.
Sure. So Chris Thanks for the question on the first part of the question, which was the sales force size you know, we we benchmark other companies we know.
Generally what the Oh.
Size of theirs, they're their forces are we have not finalized our our commercial engagement model quite yet.
Adam Waldman: We have not finalized our commercial engagement model quite yet. But, you know, I think the range that I've been saying before is anywhere between 80 and 100 people. This market is incredibly concentrated. A vast majority of the patients are being seen at 550 centers across the U.S. and centers of excellence. You do not need a huge team to be able to do this.
But you know I think the range that I've been saying before is anywhere between 80 and 100 people.
This market is incredibly concentrated a vast majority of the patients are being seen it at 550 centers across the U S and centers of excellence.
Do not need.
Huge team to be able to do this and also being the third CD 20.
Adam Waldman: And also being the third CD20 to market, you know, we think we can come in in an existing and growing market and do quite well. On the patient, the second question was around patient or direct-to-consumer. We do not anticipate, we think Novartis and Roche are doing a great job on commercials, expanding the CD20 market. And we believe we will not have to do commercials, but certainly some direct-to-patient through digital channels and social channels will be part of our plan going forward. Excellent. Thanks, Adam.
It's a market you know we think we can you'll come in an existing and growing market and do quite well.
On the patient the second question was around patient or direct to consumer we do not anticipate a we think novartis and Roche are doing a great job on commercials are expanding the CD 20 market.
And we believe we will not have to do commercials, but but certainly are some directed to patients through digital channels and social channels will be part of our plans going forward.
Excellent Thanks, Adam.
Michael Weiss: And then Chris, as far as the confirmation trial from Arizona Follicular, we've been in discussions with the FDA for, So in this presentation, I'm going to just basically focus on ME talk. We're definitely going to be covering drugs, epidemic drugs and other in the criteria engagements and a small number of variants. So, a crankier in the EHR curve. Again, I think it's only fitting that we take this with a grain of salt when you're looking at metrics. I mean, that's pretty much been the model to date.
And then Chris there's as far as the confirmation trial from Arizona Follicular, a we've been in discussions with the FDA for <unk> for.
The decent amount of time, we've been back and forth with them.
A number of times I think we're getting close to two trial design, but not very different I mean, there's been studies that are that are out there that have been they're being conducted or were being conducted.
You know looking at.
Compared to either.
Kingdom chemo immunotherapy.
Or.
I mean, that's pretty much been the model to date, so not really much of an update there. Unfortunately, but we're getting to my knowledge I'm talking to the team recently, we're getting closer I think where we're.
Michael Weiss: So not really much of an update there, unfortunately, but we're getting, to my knowledge, talked to the team recently, we're getting closer. I think we're hopefully gonna get down to the nitty gritties and get that up and running as soon as we can. Okay. All right. Well, that's very good.
Hopefully you're going to get down to the Nitty, gritties and get that up and running as soon as we can.
Okay, Oh, well, that's very good I will hop back in the queue to let my colleagues ask questions and I really appreciate it. Thank you.
Thanks, Chris.
Chris Howardton: I will hop back in the queue to let my colleagues ask questions, and I really appreciate it. Thank you. Thank you. Our next question is coming from Eric Joseph of J.P. Morgan. Please go ahead. Oh, hi. This is Sean. I am for Eric.
Thank you. Our next question is coming from Eric Joseph of Jpmorgan. Please go ahead.
Eric Joseph: So, thanks for taking our question. And we first want to dig a little bit into the ACTRIS data that you shared recently. So, more specifically, on the neutralizing antibodies and anti-drug antibodies from the Alkermene trial. Basically, can you help us to put these data into the context of other existing anti-CD20s in the market? And then as a follow-up, how or if the differences we see here could have any meaningful longer-term efficacy implications? And just want to pick up your thoughts on that.
Oh, Hi, this is Sean.
Eric Thanks for taking my question and we first of all our visibility into the actress.
Can you talk about your shareholders employees, so I'm more specifically on the on your card.
What are you, saying I'm sorry, the drug I have already saw from the oxide trial.
Basically can you help us to put these data in until the contacts of other existing tie on you know what I'm, saying, you're trying to you're selling in the market and then as a follow up and how or if there's a difference as we see here or it could have on your medium for a longer term efficacy implications and.
Just want to.
Pick up your thoughts on that thanks.
Sure Yeah, I mean that data is quite similar to what you'd expect to see with the rituxan.
Michael Weiss: Thanks. Sure. Yeah, I mean, that data is quite similar to what you'd expect to see with Rituxan, which obviously has... Years and years of experience in the marketplace, the data is pretty clear that none of it had any impact on safety or efficacy and we wouldn't anticipate it to have any impact going forward. All right, thank you. Thank you. Our next question is coming from Althea Young of Cantor. Please go ahead. Hey, guys. I like the name change.
Which obviously has years and years of experience in the marketplace are the data is pretty clear that none of it had any impact on on safety or efficacy and we wouldn't anticipate it to have any impact going.
Going forward.
Alright. Thanks.
Thanks.
Thank you.
Thank you. Our next question is coming from Alethia Young of Cantor. Please go ahead.
Althea Young: A couple questions for me. Could you talk a little bit about, I guess, it's a little trickier, but with the panel and the upcoming discussions around, you know, whatever the FDA is kind of looking for with PI3 kinase, like, you know, what kind of evidence do you think can provide? Like, can you give us any kind of more color on kind of numerical trends that you're seeing as it stands right now?
Hey, guys I like to know what I'm, saying a couple of questions for me.
[laughter].
Can you talk a little bit about I guess, it's a little trickier, but with the panel and upcoming discussions around you know whatever the FDA kind of looking forward.
You know what kind of evidence do you think can provide like can you give us any kind of more color on kind of numerical trends that you're seeing as it stands right now and then I guess just a question that I kind of got it and just wanted to you know have you opine on it for the record as you know.
Althea Young: And then, I guess, you know, just a question that I kind of get and just wanted to, you know, have you opine on it for the record is, you know, is there any concern of flow back read through to ongoing MS, even though obviously different regimen things? Yeah, thanks, Malithia. So, I mean, I'll start with the second half.
Is there any concern of blood flow black read through to ongoing M. S. Even though obviously different different regimen. Thank here.
Yeah. Thanks Alethia.
So I mean, I'll start with the second half, but no I mean, we don't anticipate any any blow back for M. S.
Michael Weiss: No, I mean, we don't anticipate any blowback for MS. I mean, most of the concerns that have been addressed, not all, have been focused on the PI3K. That seems to be an area that the FDA has expressed significant concerns across, you know, the entire class. As you know, we've maintained that we believe that our PI3K is different, and the safety and tolerability profile is different, in our opinion, and we think the data supports that.
Some of the concerns that have been addressed not all I've been focused on on the tier three K Ah that seems to be an area that the FDA has expressed significant concerns across you know.
The entire class.
You know we've we've maintained our that we believe that our RPI three K is different and the safety and Tolerability profile is different than.
In our opinion and we think the data supports that so yeah, I think where we're going to we're pulling out you know every every piece of data that we will be sharing a with O DAC like I said in the prepared remarks we've.
Michael Weiss: So, yeah, I think we're going to, we're pulling out, you know, every piece of data that we'll be sharing with ODAC. Like I said in the prepared remarks, we've, You know, we've gone patient by patient to understand what happened to just to double, triple check that, you know, that the drug wasn't causing harm to patients. But, you know, when you're dealing with an underpowered OS analysis, there's going to be a lot of noise in the data. And obviously, we had to deal with COVID, which, you know, CLL patients are generally immunocompromised. They're at high risk to begin with.
You know, we've gone patient by patient to understand what happened to just to to double and triple check that you know that the drug wasn't causing harm to patients, but you know when you're dealing with an underpowered O S analysis, there's going to be a lot of noise in the data and obviously, we had to deal with Covid.
Which you know CLO patients are generally immuno compromise there they are at high risk to begin with anytime you're treating them.
Michael Weiss: Anytime you're treating them, they're going to be at higher risk. So, you know, we think that, you know, obviously, in a world where COVID didn't exist, the data would be pretty non-meaningful. And particularly now that we have the missing data, that we didn't have when we did the first. Look at the at the at the OS, You know, you do a COVID adjustment and, you know, I can assure you that there is no survival issue there. Again, you know, unfortunately for us, you know, we were the classes come under attack. We've been lumped into that class.
We're gonna be at higher risk.
So yeah, we think that you know.
In a world where COVID-19 didn't exist.
The data would be pretty non non meaningful and particularly now.
Now that we have the missing data.
That we that we didn't have when we did the first.
Look at the at the AR at the O S.
You know you do a COVID-19 adjustment and yeah I can assure you that there is no survival issue there.
Again, you know unfortunately for us we.
We're the classes come under attack.
Michael Weiss: But I do think that, you know, given the opportunity to spend time with the ODAC panel and make them aware of the fundamental differences of this molecule versus the others, and then share with them the safety data in as much detail as we have time to provide, plus the You know, comparisons. I mean, when you look at the comparisons to the approved agents, I could assure you that the U2 regimen, in terms of, you know, SAEs, grade 3s, and treatment related deaths does not stand out, might be slightly higher on the grade 3s and SAEs, but, you know, middle of the pack in, in treatment-related deaths.
We've been lumped into that class, but I do think that you know.
Given the opportunity to spend time with the <unk> panel and make them aware of the fundamental differences of this molecule versus the others and then share with them.
The safety data in as much details, we have time to provide plus the.
No comparison I mean, when you look at the comparisons to the approved agents Ah I can assure you that the Youtube regimen.
In terms of U S. A he's grade threes.
And treatment related deaths does not stand out might be slightly higher on the great. The reason I say, he's but you know middle of the pack in.
And no treatment related deaths. So again, it's it's it's not like there's some some obvious issue and like I said, we've been patient by patient. The good news is like we've shared all that data now with the F. D. A M.
Michael Weiss: So, again, it's not like there's some obvious issue, and like I said, we've been patient by patient. The good news is, look, we've shared all that data now with the FDA, and my assessment of the situation is they are taking it very seriously. What I can tell is they're working very hard to find the truth, and that's all we could ask for.
You know my assessing the situation as they are taking it very seriously.
There you know they are working to what I can tell us they're working very hard to find the truth and that's all we can ask for so our fingers are crossed.
Michael Weiss: So, our fingers are crossed. We've sent them a lot of information, a lot of new data over the last, you know, Thank you, everyone. Again, my assessment is that they're looking for the truth.
We've sent them a lot of information a lot of new data.
Over the last.
Two three or four weeks.
They've been back to us with that.
Multiple rounds of follow up questions. So they're working hard on it there they're there.
I've got my assessment is that they're looking for the truth, we feel comfortable.
Michael Weiss: We feel comfortable that there's there's no, Major concern here and, you know, hopefully the FDA will see it that way, and hopefully we'll have that opportunity to share that with ODEC as well. Awesome. Thank you very much.
That there's there's no.
A major concern here and.
Hopefully the FDA will see it that way.
And hopefully we'll have that opportunity to share that would go down as well.
Yeah.
Awesome. Thank you very much.
Thank you.
Michael Weiss: Thank you. Thank you. Our next question is coming from Mayank Mamtani of B Riley. Please go ahead. Hi. Good morning, team. This is Sahil Han for Mayank.
Thank you. Our next question is coming from my uncle Pantani of B Riley. Please go ahead.
Mayank Mamtani: Congratulations on all the progress. Maybe just a brief follow-up from the previous question. Could you clarify how much, if any, of the data package for MS is going to be considered at the U2 ODAC meeting, with that obviously being a component of the therapy? And then also, is there an ADCOM anticipated for the MS opportunity prior to the September PDUFA date? So, the answer to the first question is zero.
Hi, Good morning thing Mr. Sahil on for Mike.
Actions on all the progress maybe just a brief follow up from the from the previous question, but could you clarify how much if any of the you know data package for our M. S is going to be considered at the U two O DAC meeting with that obviously being a component of the therapy. And then also is there an AD com anticipated for the M S opportunity prior to the September .
Paducah date.
So the answer the first question is zero.
Michael Weiss: And, you know, as of now, the FDA has said on the MS side that they are not planning to host an ODAC. Again, as we've learned from the CLL side, that as they review the data, they may come to a different conclusion. At the outset, they noted that they were not planning to host not an ODAC, but an advisory panel for the neurology division.
And you.
As of now the FDA has said on the M. S side that they are not planning to host to know that.
Then as we've learned from the CLO side that.
As they review the data that they may come to a different collision at the outset. They did they they noted that they were not planning to us now.
Michael Weiss: Okay, great. Thank you. And then maybe one more from us.
Oh.
Not exactly an advisory panel for the Neurology Division.
Michael Weiss: Could you talk about your latest thoughts on the, you know, 2025 revenue guide of $1 billion and how that mix might now be viewed between oncology and MS? Yeah, I mean, I think until we know where we are with, with the UnitySeal application. I don't think we can update that guidance. So for the moment, We will just leave that as an open question until we see the results of the ODAC and, More importantly, beyond that, the decision of the FTA. Yeah, absolutely. That makes sense.
Okay, great. Thank you and then maybe one more from us.
Talk about your latest thoughts on that.
Twenty-five revenue guide of 1 billion and how that mix might now be viewed between oncology and M. S.
Yeah, I mean, I think until we know where we are with.
We only sell application I don't think we can update that guidance so for the moment.
We will just leave that as an open question until we see the results of the O DAC and and.
More importantly beyond that the decision of the F D a.
Mayank Mamtani: All right. Thanks for taking our questions. I appreciate it. You got it.
Yeah, absolutely that makes sense alright, thanks for taking our questions I appreciate it.
You got it.
Ed White: Thank you. Our next question is coming from Ed White of HC Wainwright. Please go ahead. Hi, this is Steve on for Ed.
Thank you. Our next question is coming from Ed White of H C. Wainwright. Please go ahead.
Steve: Thanks for taking our question. Can you provide your thoughts on your year 15 strategy and timing for MS? Yeah, so we are we are currently fully evaluating that opportunity. We were in the process We've got a small team that's already set up a sort of a SWAT team in Europe That's modeling out and how we plan to approach, The European Theater, as one might say.
Hi, This is Steve on for Ed. Thanks for taking our question can you provide your thoughts on your European strategy and timing for M. S.
Michael Weiss: So we don't have any details beyond that, but we are mapping it out and I think the timing would be probably six months or so beyond the approval for MS in the U.S. All right, thank you. Thank you. Our next question is coming from Matt Kaplan of Vladenburg Zalman. Please go ahead. Hi, good morning. Good morning.
Yeah. So we are a we're currently fully evaluating that opportunity. We are in the process. We've got a small team that's already set up a sort of a swat team in Europe , that's modeling out and how we plan to approach the year.
P in theater and it's one of my saying so we don't have any any details beyond that but we are mapping it out and I think the timing would be you know probably six months or so beyond.
The approval for for M S and the U S.
Alright, thank you.
Thank you. Our next question is coming from Matt Kaplan of Ladenburg Thalmann. Please go ahead.
Hi, good morning.
Matt Kaplan: I just wanted to back up to the OS analysis a little bit. You know, thanks for all of the detail you provided there. Given your interaction with the FDA since you submitted, I guess, the data in late January, what do you think, how is the FDA going to handle this? Will this be viewed as a major amendment, push out the PDUFA date, or will it just be, they'll be able to complete their analysis in a faster timeline? So we don't know.
Good morning.
Just wanted to go back up to the OS analysis, a little bit you know thanks for all of the detail you provided there.
Given your interaction with the FDA since you submitted I guess the the data in late January what do you. What do you think Oh, how is the FDA going to handle this will this be viewed as a as a major amendment push out that particular day or will it just be they'll be able to complete their analysis.
A N N a.
Faster timeline.
So we don't know you know given the state of the timeframe for the old DAC of March April time frame, we have always assumed again with no.
Michael Weiss: So, you know, given the stated timeframe for the ODAC of March-April timeframe, we have always assumed, again, with no further information from the FDA, this is just us sitting around spitballing that, you know, that the PDUFA date would not likely be met, right, and we've said that publicly. Having said that, the FDA does have the right at any time to call any of the data submissions that we've provided as major amendments, which would give them the opportunity to push the PDUFA date back, I think, three months.
No no further information from yesterday. This is just a sitting sitting around spit balling that.
You know that the the Paducah date would.
Would not likely be met right and we've said that publicly.
Having said that the FDA does have the right at any time to call any of the data submissions that we've provided as major amendments.
It would give them the opportunity to pushed the Paducah date back I think three months so.
Michael Weiss: So So, So, So, So, So, So, So, So, So, So, So, So, So, So, So, So, So, So, So, You know, we don't know exactly what the FDA's thinking on that one. They haven't spoken to us about it at all, but certainly that is a possibility that they can take the updated data that we've provided to them, declare it as a major amendment, and push the PDUFA date back. That would give them plenty of time to host the ODAC and not have to miss their PDUFA date.
Michael Weiss: So, again, we don't know. We have no further information than what we've shared and what I've said here today. But, again, those are all logical possibilities that could happen.
You know, we don't know exactly what the Fda's.
Thinking on that one they haven't spoken to us about at all but.
Certainly that is a.
The possibility that they can take the the updated data that we've provided to them declared as a major amendment and push them to do FID date back that would give them plenty of time to host the O DAC and not have to Miss the Paducah date. So yeah. We don't we don't know we have no further information than what.
We've shared in and when I've sat here today, but again those are all logical.
Possibilities that could occur.
Matt Kaplan: Okay, helpful. And, and I guess, now that we're in, we're in March, when do you expect the FDA to give you an indication on the timing for the potential ODAC meeting? The last I heard is that the FDA will post it publicly for all to see, and at that point, everyone will know the date of the ODAQ. And then, just lastly, on the new OS data that you submitted, you mentioned that there was kind of a positive improvement once you were able to decrease the number of patients that had missing data to 5% or less. Can you give us a little bit more detail in terms of the improvement in OS that you observed when you did that?
Okay.
And I guess now that we're in we're in March.
When do you expect the F D. A to give you an indication on the timing for the potential Kodak meeting.
The last I heard is that the FDA will were posted publicly for all to see and at that point.
Everyone will know the date of the old deck.
Okay, and then and then just lastly on the new OS data that you submit it.
Mentioned that there was a kind of a positive improvement once you were able to decrease the number of patients that were had missing data to 5% or less can you give us a little bit more detail in terms of the improvement in and I'll ask that you observed when you did that.
Michael Weiss: So you'd like the actual numbers, Matt? Yes. I would love to share the numbers, but we made a decision that we did not want to do that until the FDA had a full opportunity to review all of the information that we provided them. But what I can say, which I've said qualitatively, is that both the 1.23, which was the ITT, went down, and the 1.04 for the COVID went down. So both those numbers are lower than they were. And again, we're seeking the truth, right?
So he was like the actual numbers Matt yes.
[laughter] I would love to share the numbers, but we made a decision that we did not want to do that until.
Until the FDA had a full opportunity to review all the information that we provided them, but what I can say, which I've said qualitatively is that both the one point to three which was the I T. T went down and the one point O four for the Covid went down so so both of those numbers are lower than <unk>.
We're and again you know again, we're seeking the truth right. So at the time, we presented the first analysis to them, we were missing 15% of the information. So what we provided them was.
Michael Weiss: So at the time we presented the first analysis to them, we were missing 15% of the information. So what we provided them was... what we knew at the time, but not everything. So we were able to close that information gap and get it down to 5%. So we're still missing 5%.
What we knew at the time, but not not everything so we were able to close that information gap down to 5%. So we're still missing 5%. So we got closer to the truth of what the OS analysis was at the time now again.
Michael Weiss: So we got closer to the truth of what the OS analysis was at the time. Now again, which is great, so in actuality, had we had all the information at the time we submitted it, the numbers we had presented to the FDA would have been lower. That's that's still not, you know, because of the fact that the the OS is underpowered. Understanding the truth of whether U2 provides a benefit in oversurvival or does not, is a far way off no matter what, right? Because when you're looking at underpowered analysis, You don't have, essentially the answer is you don't have enough information to get above the noise.
Which is great. So it so in actuality had we had all the information at the time, we submitted it.
We have presented to the FDA would have been lower.
Yeah.
That's that's still not you know.
Because of the the fact that the the OS is underpowered.
Understanding the truth of weather.
You too provided a benefit in overall survival or it does not.
It's a far way off no matter, what right because when you're looking at underpowered analysis.
You don't have essentially with the answers you don't have enough information to get above the noise and as I mentioned in my prepared remarks, you see these things will swing back and forth. Because every time you pick another new cutoff date, you, there's gonna be a lot of randomness.
Michael Weiss: And as I mentioned in my prepared remarks, you see these things will swing back and forth because every time you pick another new cutoff date, there's going to be a lot of randomness. In particular, if you're not powered for it. I think we mentioned this in one of the previous conference calls, but we really would need minimum, minimum of 600 events. And that would be a pretty nice improvement in overall survival, and it could be as high as, I think, 2,000 events, for what is most likely the improvement in survival, given all the current new standard of cares that are out there.
Particularly if you're again, you're not you're not powered for it so you know.
We've mentioned this in maybe one of the previous conference calls, but we really would need you know minimum minimum of 600 events.
And that would be a pretty nice improvement in overall survival and it could be as high as I think 2000 events.
For for what is most likely the improvement in survival given all of the current new standard of cares that are out there and you're not expecting the same level of improvement in survival that you would see in PFS.
Michael Weiss: Again, you're not expecting the same level of improvement in survival that you would see in PFF. So we're looking at about 100 of them. Give or take, maybe 110, 120, and to get even reasonable information would be 600 to 2,000.
So we're looking at about 100 events give or take maybe 100 and turn them into 'twenty and to get even reasonable information would be 600 to 2000.
Michael Weiss: Knowing the truth, and particularly again in light of the crossover, knowing what the truth is of whether there's a true benefit or not, is extremely challenging to glean from this kind of information. So again, that's why I think it is important that we've gone patient by patient. And again, to the FDA's credit, we do appreciate that they're taking great time and care to look at the information on a patient by patient basis to get a better sense of what's going on with you two and these patients. So... Very long answer Matt, but I can't give you the number that you've asked for, but I can assure you that the numbers are lower than they were.
Knowing the truth on particularly again in light of the crossover knowing what the truth is of whether those are true benefit or not.
Yeah.
Is extremely challenging to.
To glean from this kind of information.
So again, that's why I think it's it is important that we've got on patient by patient.
And again to the Fda's credit and we do appreciate that they're taking great time and care to look at the information on a patient by patient basis to get a better sense of of what's going on with with you too in these patients so.
Very long answer, Matt, but I can't give you the number that you've asked for it but I can assure you that the numbers are are lower than they were.
Michael Weiss: Okay, now that's the added detail is very helpful. Just shifting gears to MS, previously, you've spoken about going to market with a competitive price strategy. Given your interaction and ongoing interaction with potential payers and the profile of the drug, what are your current thoughts on that? Yeah, so again, we we continue to evaluate. I mean, this will come down to the wire.
Okay now that's the added detail is very helpful.
Just shifting gears to en masse.
M T V C U E.
Spoken about going to market with a competitive price strategy.
Even your interaction and ongoing interaction with potential payers.
And the.
Profiling the trial, what what are your current thoughts on on that right now.
Michael Weiss: I mean, we are constantly engaging with players, uh... to try to refine that pricing model that will optimize the access for for oobly uh... in ms and that is you know more and more as we do more adwords with the physicians all they they care about is will their patients have access to the drug, So they just, as long as they can write the script and have a high level of confidence that they're going to get the drug, they're going to be on board with Ubli as, in many cases, as their primary CD20. So our job continues to be to find the right pricing strategy that makes the most sense. And I think, you know, there's probably some component that includes lower price, some component that includes some discount, and there's a balance out there.
Yeah. So again, we continue to evaluate them this will come down to the wire I mean, we are constantly engaging with payers.
To try to refine that pricing model that will optimize the access for for uplink.
In M S and that is you know.
More and more as we do more AD boards with the position all they they care about is will their patients have access to the drug.
Right. So they just as long as they can write the script didn't have a high level of confidence that they're going to get the drug.
They're gonna be onboard with newly as in many cases as their primary C. D. 20. So our job is continues to be to find the right pricing strategy that makes the most sense and I think you know.
There's probably some component that in includes lower price. Some component that includes some discount and there's a balance out there, but again, it's too early to tell even now because we continue to go back and forth and and and discuss it with the payers.
Michael Weiss: But again, it's too early to tell even now, because we continue to go back and forth and discuss with the payers. But yeah, it's important. We continue to believe it. We continue to feel confident that we can work with Price to make a difference and can make sure that Ubli is accessible to as many patients as possible across the country. Okay. And last question, I guess, given that the ultimate studies were wrapped up some time ago, can you talk about any potential exposure you have given the current war in Ukraine and the review ongoing at FDA? Does that pose any problem? Oh, the war in Ukraine, is that what you're asking about, Matt? Yeah, yeah, any issues with MS? Yeah. Yeah, I wouldn't think so.
But yeah. There's it's important we continue to believe it will continue to feel confident that we can work with with price.
To make a difference and can make sure that.
Let me be as accessible to choose many patients as possible across the country.
Okay and our last question.
So given that they are the ultimate studies were wrapped up some time ago can you talk about any potential exposure you have given the current war and your crane and the review.
Ongoing at FDA.
Is that does that pose any problems.
Oh, the warm cranes, all you're asking about my yeah, yeah any.
Issues with them yeah.
Michael Weiss: The studies obviously completed a while ago, so I don't, I mean we have all that data has been extracted, cleaned, and brought to the U.S., so I'm not concerned about that. You know, in terms of potential FDA inspections, they've, you know, to my knowledge, they've chosen sites that are not in the Ukraine to inspect at this moment, so unless something changes and they decide they need to get to the Ukraine, which obviously would be a challenge under the current circumstances, I don't see that as any barrier to the FDA's review process from that standpoint.
Yeah, I wouldn't think so the the studies, obviously completed a while ago.
So I don't mean, we have all that data that's been extracted cleaned and brought to the U S. So I'm not concerned about that.
Michael Weiss: So, no, I'm not seeing anything that's concerning from our standpoint, with what's going on over there. Obviously, there's lots of things to be concerned about for the patients and everyone else there. Okay, great, great. Thank you. Thank you. This brings us to the end of our question and answer session. I would like to turn the floor back over to Mr. Weiss for closing comments. Great.
You know in terms of potential FDA inspections are they've you know to my knowledge they've chosen sites that are not in the Ukraine to inspect at this moment.
So unless something changes and they decided they need to get to the Ukraine, which obviously would be a challenge under the current circumstances I don't see that as any barrier to to the Fda's review process.
From that standpoint, so no I am not I'm not seeing.
Anything that's concerning from our standpoint with what's going on over there obviously, there's lots of things to be concerned about.
So the patients and everyone else there.
Okay, great great. Thank you.
Thank you this brings us to the end of our question and answer session I would like to turn the floor back over to Mr. Weiss for closing comments.
Yeah.
Michael Weiss: I just want to thank everyone again for joining us. To wrap up, I'll just quickly review some of the upcoming goals and objectives for 2022. Obviously, preparing for the upcoming ODAC has been a, Dr. Joseph, Sean Power, Michael Weiss, Edward White, Matthew Kaplan, Michael DiFiore, Noah across a number of different conferences for the remainder of this year, and hopefully obtaining FDA approval by the target BDUFA date of September 28th, 2022. We'll continue preparing for the potential launches of U2 and CLL and Uber, Tux, and Avon RMS.
Great.
I just wanted to thank everyone again for joining us.
To wrap up I'll, just quickly review some of the upcoming goals and objectives.
For 2022.
Preparing for the upcoming O DAC is been a oh.
A big effort for the company as I mentioned in the prepared remarks, and we're looking forward to hopefully obtaining a favorable outcome and ultimately obtaining approval for you to treat patients with C. O L. A we're looking forward to presenting additional analysis from the ultimate one and two trials.
Uh huh.
Across a number of different conferences for the remainder of this year.
And hopefully obtaining FDA approval by the target, but do for date of September 28 2022.
Ah well continue preparing for the potential launches of Youtube C. O L and we will talk to you now have in RMS will continue to work on our early pipeline candidates.
Michael Weiss: We'll continue to work on our early pipeline candidates, and of course, during the course of the year, we'll have opportunities to write updated oncology data at major medical meetings. So, looking forward to a very pivotal year for us, obviously, these two approvals being of utmost importance for us, and we'll continue to work toward those. So, I just want to thank everyone again for joining us. Have a great day. Ladies and gentlemen, thank you for your participation. This concludes today's event. You may disconnect your line to log off the webcast at this time and enjoy the rest of your day. [music] Ok, let's try it... [music]
And of course during the course of the year, we'll have opportunities to write updated oncology data at major medical meetings. So looking forward to a very pivotal year for US. Obviously these two approvals are being about most important for us and will continue to work toward those so I just wanted to thank everyone again for joining us have a great day.
Ladies and gentlemen, thank you for your participation. This concludes today's event you may disconnect. Your lines have log off the webcast at this time and enjoy the rest of your day.
Uh huh.
Okay.
Yeah.
Yeah.
Yeah.
Yeah.
Yeah.
[music].
[music].
Yeah.