Q4 2022 Zymeworks Inc Earnings Call

Yeah.

Good day, ladies and gentlemen, and thank you for standing by welcome to design works fourth quarter and full year 2022 results conference call. At this time, all participants are in a listen only mode.

After the speaker's presentation, there will be a question and answer session to ask a question. During the session you will need to press star one one on your telephone keypad at.

At this time I would like to turn the conference over to Mr. Jack Spinks.

Of Investor Relations for <unk>, Sir you may begin.

Yeah.

Good afternoon and welcome everyone.

As Jack Spinks head of Investor Relations here at Zimmer.

Today, we will discuss our fourth quarter and full year 2022 financial results as well as provide an update to our ongoing business.

Before we begin I'd like to remind you that we will be making a number of forward looking statements. During this call, including without limitation. Those forward looking statements identified in our presentation slides and the accompanying oral commentary.

Forward looking statements are based upon our current expectations and various assumptions and.

And are subject to the usual risks and uncertainties associated with companies in our industry and at our stage of development for.

For a discussion of those risks and uncertainties. We refer you to our latest SEC filings is found on our website and aside with the SEC.

Later in this call Chris <unk>, our senior Vice President and Chief Financial Officer will be discussing our financial results, including certain non-GAAP measures.

A description of our GAAP measures and a reconciliation to the most directly comparable financial measures determined in accordance with GAAP are described in detail in our press release, which is available on our website at www Dot <unk> Dot com.

Under the Investor Relations tab as a reminder, the audio and slides for this call will also be available on <unk> website. Later today now I will turn the call over to Chris Our senior Vice President and Chief Financial Officer, Chris.

Thanks, Jack and thank you everyone for joining us today for our fourth quarter and full year 2022 earnings call.

As a reminder, I'd like to note that while I'll be presenting the prepared remarks today, Kenneth Galbraith chat in <unk> and <unk>.

Other members of our executive team will be available for Q&A. Following this portion of the call.

With that I'd like to begin today's call with an overview of our financial results followed by a few recent developments are noteworthy updates across our business before we open the lines for Q&A.

This afternoon <unk> reported financial results for the fourth quarter and year ended December 31 2022.

<unk> net income for the year ended December 31, 2022 was $124 $3 million.

Or $1 90 earnings per diluted share.

Compared to a net loss of $211 8 million for year ended December 31st 2021.

Going from an annual net loss to net income was primarily related to revenue received from our collaboration agreement with jazz.

Absolutely offset by increases in expenses incurred in 2022 relative to 2021.

As reported our revenue for 2022 was $412 5 million.

Compared to $26 7 million for 2021.

Revenues for both the year and most recent three month period ended December 31, 2022, primarily related to the $375 million in upfront payments received from jazz as a result of the completion of the xenon licensing agreement combined with approximately $24 million in reimbursements from jazz.

Our expenses incurred for example, that's about between October 19th and December 31 2022.

Research and development expense for the year ended December 31, 2022, with $208 6 million.

Compared to a $199 8 million for the year.

And at December 31, 2021.

This increase of $8 8 million or 4% from the prior year related primarily to higher manufacturing and clinical trial expenses presented that's amount in 2022 and due to the restructuring exercise undertaken in the first quarter of 2022.

Were partially offset by a decrease in expenses related to reduced preclinical on that thats amounts overdosing related expenses in 2022.

As of October 19, 2022, <unk> is entitled to reinvestment from Jonathan for all <unk> related expenses.

Related to ongoing studies under the terms of the collaboration agreement finalized in Q4 2022.

General and administrative expense for the year ended December 31, 2022 was.

It was $73 4 million compared to $42 6 million for the year ended December 31 2021.

This year over year increase of $38 million or 72% was driven primarily by severance and other expenses related to our reduction in force and R&D re prioritization program that occurred in early 2022, and an increase in consulting and professional fees primarily related to the Companys re domicile to <unk>.

Come a Delaware Corporation.

The <unk> licensing agreement and other nonrecurring project based expenses.

During 2022, the company's workforce was reduced by more than one third through the reduction in force and voluntary attrition from 450 full time employees to less than 300 full time employees.

Our cash resources, consisting of cash cash equivalents and short term investments.

$192 9 million as of December 31, 2022.

Driven by the receipt of the upfront payments from jazz totaling $375 million.

In the fourth quarter.

Cash resources as of December 31, 2022 did not include $24 million and Reinvestments Association's withstand that thats related expenses from October 19th through year end 2022.

Our licensing and collaboration agreement with jazz completed the series of financially beneficial transformation initiatives and 2022, which we believe will fund our planned operations through at least 2026 and potentially beyond.

Okay.

We completed an equity offering in January 2022 comprised of a combination of common shares and pre funded warrants for gross proceeds of $115 million, which included the exercise in full of the underwriters' option to purchase additional shares.

As of March 3rd 2023, we had approximately 65 to 5 million shares of common stock and pre funded warrants outstanding and shares issuable pursuant to our Canadian exchangeable shares.

It did not issue any shares of common stock under our ATM facility. During 2022, alright as of March seven 2023 for the current year.

In January of this year, we also issued financial guidance related to our net operating cash burn for 2023.

Given the significant change in our overall net cash spend we expect to experience. This year due in large part to the reimbursement of sand that's populated expenses under our collaboration agreement with jazz.

We continue to expect our net operating cash burn for 2023 to be between 90 and $120 million, including planned capital expenditures of $15 million.

This cash burn guidance as well as our cash runway guidance includes forecasted expenses are primarily related to our early R&D programs as well as incremental expenses to support our planned phase III clinical development program, because I know thats months overdose.

For additional details on our quarterly results and for a description of our non-GAAP financial measures and a reconciliation of GAAP to non-GAAP measures I encourage you to review our earnings release and other SEC filings is available on our website at Www Dot signed months Dot com.

Now I'd like to spend a few minutes talking about early R&D portfolio, followed by a brief discussion on Sunday, that's maps overdosing Amazon Dot to map, our most advanced clinical product candidate.

We re prioritized our R&D strategy early in 2022 and had an exciting and productive year with substantial progress on executing this new R&D strategy too.

To quickly recap we recruited Dr. Paul Moore, as our new Chief Scientific Officer in June of last year.

And hosted in early research and development day in October where we previewed preclinical product candidates emerging from both our antibody drug conjugate and multi specific platform technologies designed to overcome limitations of existing therapies.

At that same event, we disclosed our two lead candidates for <unk> by 2024, GW 171, and <unk> 109, one both of which are on track to be submitted next year.

Additionally, we set some ambitious targets are progressing five novel and differentiated preclinical product candidates, including CW 171, and <unk> hundred 91 into clinical studies by 2027.

We believe that helped pursuit of this goal along with our scientific vision and path forward in the ADC or multi specific antibody space.

<unk> generated a diverse and valuable oncology product portfolio of wholly owned product candidates.

In addition to developing our own internal oncology pipeline.

Anticipate additional preclinical product candidates derived from our ADC of multi specific technologies.

<unk> with resources available from potential partners and collaborators.

We are continuing to evaluate opportunities to form additional collaborations and partnerships around both our publicly disclosed and confidential preclinical product candidates.

This partnership strategy is important as it can help us to accelerate development and advanced potential opportunities without the use of time months of shareholder capital to complement our wholly owned product pipeline.

We hope to announce the completion of additional collaborations and partnerships before the end of this year the multiple preclinical product candidates.

And helping further this objective we are excited to announce the acceptance for publication of 11 abstracts at the American Association for cancer research or ACI to be presented in mid April and Orlando, Florida.

These abstracts will be made publicly available by ACR March 14th.

I'd say ACR, we will be able to share with you additional progress on preclinical data on the announced preclinical product candidates and we spoke to early R&D day last year as well as continued progress on our technology platforms for generating additional ADC, a multi specific antibody therapeutic candidates.

Add to our preclinical product pipeline beyond 2024.

Subsequent to these presentations in Orlando, We will also plan to host a conference call to discuss the results and strategic impact. These new data will have on our path forward.

In addition to our in House development efforts, we continue to have multiple active licensing agreements with key pharmaceutical and biotechnology partners.

This portfolio of legacy platform partnerships, which consist of partnerships, where we are required to expand little if any capital to advance the programs represent a significant source of past and potential future non diluted funding.

To date, we have received approximately $118 million in upfront and milestone payments not including any amounts received for Dana that's about horizontal <unk>.

Further throughout 2023, and 2024, we expect to earn additional milestone payments under existing agreements as product candidates continue to advance through development stages by our partners.

We also retain the ability to monetize all or a portion of the future cash flows from these agreements pulling forward the value of future cash payments to provide an additional source of non dilutive capital should it be needed.

Here on slide six we can take a moment to touch on <unk> was that these artificial ward.

As you likely noticed from our earnings release issued earlier. This afternoon. We are planning to continue with a data driven development program for <unk> and advanced into selected patient cohorts in phase II clinical studies.

This will appropriately move this product candidate forward by studying <unk> in combination with other approved agents, especially checkpoint inhibitors with incremental clinical investments and previous had been benchmarks.

Previously we had anticipated a protocol expansion of our ongoing phase one clinical study. However, after careful evaluation and a better understanding of both timelines on what we believe will be the most valuable to any potential future partner.

Thus building potentially meaningful value to our shareholders.

<unk> chosen to proceed with separate phase III studies to be conducted one evaluating <unk> in combination with PD, one inhibitors and non small cell lung cancer and another in patients with breast cancer after progression on <unk> DXP and had too low patients in combination with PD one inhibitors.

With this design, we believe we can obtain the clinical data necessary to both enter into a registrational path is anticipated before the end of 2025.

And attract an appropriate partner to assist with ex U S development and commercialization.

Something we currently expect would be required before moving forward into a registration pathway.

We continue to consider other areas of interest for clinical development and evaluating <unk> with the current standard of care and had two amplified colorectal cancer patients.

Two expressing gynecological cancer patients in her two positive gastroesophageal adenocarcinoma or GE.

We anticipate that our phase II studies for <unk> will be implemented using assignments two stage study design.

This allows us to clearly designate and defined hurdle rates and stage our investment in <unk> going forward.

We expect that the conduct of these phase III studies will be expanded geographically to additional clinical sites in Asia and Europe to both improve the speed of patient recruitment and lower the overall clinical development cost of patient recruitment.

Our newly formed regional hubs will help us provide the appropriate support for this geographic expansion of our clinical development program for Zalviso.

We continue to believe that the phase one clinical data presented last year ESMO at two five milligrams per kilogram dosed every three weeks shows that <unk> has a differentiated tolerability profile relative to other head to adcs and acceptable single agent activity in a range of <unk> expressing tumors.

The keratitis seen in our phase one study is well characterized and primarily low grade being grade one or two which is both manageable and reversible.

And appropriate dose reduction management strategy was effective in managing any patients affected with keratitis and a phase one study without any significant discontinuation from the clinical study.

Importantly, we did not see that tolerability signals of consent comment to other ADC products and consequently, an attractive part of what we believes on these I can offer the potential ability to combine with other agents currently used as standard of care.

In areas, where we see the patient need and while we may be able to improve upon current efficacy seen with existing standards of care.

Incremental investment in these phase II studies, which are planned to begin enrolling patients in 2023 as warranted based on the clinical data generated to date and our recent interactions with Kols and potential partners.

Wireless spend represents a small component of our anticipated net cash operating burn guidance of $90 million to $120 million for 2023.

<unk> represents an important and investable opportunity worth pursuing as a differentiated had two ADC and post <unk> patient population.

And could provide the company with the ability to retain development and commercial rights in the U S. While working with our partners in ex U S markets.

Finally on <unk>, while we have continued to enroll and followed patients on our phase one study treated at the recommended phase II dose of two five milligrams per kilogram every three weeks as monotherapy, we will be closing the weekly cohort in order to eliminate any future additional costs associated with keeping this portion of the study open.

We expect to be able to present further data before the end of this year on that weekly data as well as additional monotherapy data generated since the data cutoff for the 2020 to ESMO presentation.

Going forward, we will be focused on opening the initial two phase III studies and generating combination data as quickly as practicable.

Finally, before we open things up for Q&A I'll briefly touch on <unk> as we still have an exciting year ahead of us and recently presented important data at <unk> Gi. This January .

I'd ask Agi, we presented updated data from our phase II trial evaluating <unk> in frontline <unk> positive metastatic GE.

These data included a first look at it on a desktop overall survival data.

Showed an impressive 84% overall survival at 18 months with the median overall survival, having not been reached.

Further the data included in overall confirmed objective response rate of 79%, including three complete responses.

Median progression free survival of $12 five months and a median duration of response of 24 months. After 26 five months of patient follow up.

The regimen was manageable tolerable and consistent with the observed safety profile as reported for other standard regimens for patients with her two positive gea.

We are working closely with Johnson Beijing to continue enrollment of patients in the phase III randomized clinical trial horizon GE, one evaluate things on it thats amount in combination with chemotherapy.

So minus two <unk> as a first line treatment for her to expressing metastatic or advance gea.

We continue to expect top line results from this pivotal study to be available in 2024.

Additionally, last quarter <unk> reported positive top line data from our phase III open label single arm clinical trial Horizon BTC, one studying <unk> as a monotherapy in patients with previously treated two amplified in expressing the Louis tract cancers.

With a confirmed objective response rate of 41, 3% and a median duration of response of $12 nine months in patients with her two amplified in expressing while I hate to see two plus three plus disease.

These data represents a potentially important steps ahead to amplified patients with DTC because that thats map has the potential to be the first had to targeted therapy in this indication.

Ah represents a chemotherapy free treatment option for patients who would otherwise receive standard of care chemotherapy in second line.

It's typically elicits overall response rates of between five and 15%.

Further we expect the full results from these data to be presented at a major medical meeting in the first half of this year and look forward to confirming that presentation as soon as practicable.

We remain very encouraged by these positive topline results is on the debt amount as well as the recently presented results of <unk>, including the first look at overall survival data for <unk> in our phase III without partners Johnson Beijing, we continue to work towards the potential regulatory path forward with development regulatory bodies in various.

Countries, where the BTC data may support an accelerated or full approval.

We will continue to work with our partners. He will provide guidance I think appropriate time for any regulatory filings.

While the initial development path and global regulatory interactions will be focused in BTC and <unk>. The two most advanced indications with ongoing pivotal trial.

We and our partners continue to evaluate the development path and other indications beyond the PTC and GE.

We have ongoing clinical development and additional indications and remain excited about the broad potential of Santa desktop and indications outside Gi cancers.

To this point <unk> is currently being used in the I spy platform trials for patients with head to expressing tumors in the neo adjuvant treatment of locally advanced breast cancer.

This and other ongoing development efforts, because I know that the map will help determine the path forward in these indications.

Last year was an important year for the company with numerous ambitious goals that were set in January of 2020 to reset the company strategy as.

As we reflect on the past year, we were able to make significant progress across multiple aspects of our business, including on the non scientific front, while we successfully completed the re domicile to Delaware, resulting in positive inflows due to index inclusion in U S based indices.

As well as a stock exchange listing change from the New York stock exchange to the NASDAQ stock market.

Are we better aligned with peers in the biotechnology sector.

As we look towards 2023, we have identified five important pillars of value are enterprise value framework.

We will look to advance in order to continue generating volume.

These five pillars are Tuesday night, Thats my collaborations with Beijing in John's.

Early research and development programs.

So maps overdosing and our legacy platform licensing portfolio.

From a business and financial standpoint, we believe we are well positioned for success with our new strategy.

We have sufficient cash to pursue our planned development activities with a significantly reduced net cash bone a focused clinical program with planned phase III study says other that's bumps over to Eitan.

A number of exciting preclinical product candidates that we are working to progress to clinical studies with a specific focus on development of a mix of antibody drug conjugates and multi specific antibodies.

We believe this focused investment and moderated future spending when combined with the scientific expertise and people working hard behind the scenes makes for a very compelling opportunity going forward.

As we remain focused on our operational goals. We will also stay true to our vision to discover develop and commercialize novel medicines that can make a meaningful difference in the lives of patients around the world impacted by difficult to treat cancers and other serious diseases.

So all of those who have been with us through what was a challenging 2022 for everyone investing in working in biotech.

<unk> now looks forward to the future from a strong financial and scientific flooding and we expect to continue delivering upon these results generating long term value for our shareholders and ultimately improving the lives of patients by generating antibody based therapeutics with the potential to dramatically improve on current standards of care and difficult to treat.

Kansas.

With that I'd like to thank everyone for listening to our prepared remarks, and I'll turn the call over to the operator to begin the question and answer session operator.

Yes.

Ladies and gentlemen, if you have a question or comment at this time. Please press star one one on your telephone keypad.

If your question has been answered or you wish to remove yourself from the queue simply press star one again.

It's more if you have a question or comment at this time. Please press star one one on your telephone keypad.

Standby, while we compile the Q&A roster.

Our first question or comment comes from the line of.

<unk> from Citi. Your line is open.

Yes, hi, thanks for taking the question.

On the <unk> 49, now called advantage, though you mentioned.

And that Youre going to start the phase one I believe except for one of the cohorts. So can you just go into a little bit more detail as to the thinking behind that so why you are moving into those two phase III non small cell one on me.

Metastatic breast cancer, great to get a better understanding.

The shift in strategy there. Thank you.

Yes, sure and I don't think.

The shift in strategy.

Thats more form over substance. So I saw the clear preference from a revenue perspective to initiate new core combination cohort.

Phase III format.

So again.

Having played out in kind of two things here one is reduced.

Perfect and clinical development costs, our prior costs are too high.

The speed of patient recruitment.

Thank you Vince.

So I think we need to improve the access and quality patients.

We can screen for these kind of home.

Got it.

<unk> been doing about that.

As a result of that position.

One thing is the product side.

Global age.

In the U S and Korea, but not beyond that and I think going internationally, Jeff talked.

Talk about.

Clearly, if we're doing filings and new countries.

Starting practice.

Study as opposed to amending our phase one study.

Variable.

I think Tony over in the early stages.

<unk> growth, which we reorganized.

Definitely bring down the internal cost or.

These clinical development costs and thank you for that group.

171 and 191.

Next year.

Clinical trial.

Come in.

And also.

Zero would be after the phase one of the side if you want to move forward.

I think we could definitely accomplished some of the cost factors.

Potentially reviewing that contracted value.

So with all that being said I think.

From a revenue perspective.

Okay.

It's not going to make.

The size of the studies or the timing.

Execution.

Also some benefits of moving forward, if we're able to generate.

Some great data in combination with <unk> 49 in multiple.

Her two indications that we have already identified.

So our target product profile, that's our value proposition, we can prove that we can move much more quickly forward for a registrational pathway in conjunction with our partner as we mentioned before an excellent market.

Bye for.

So I think there is some forward thinking.

Congrats on being able to move 49.

After these basic cohort then we'll be in a better position does that even more even more quickly.

Beyond that we're comfortable with.

The advisory Board and Im working on around non small cell lung cancer or.

I think with the breast cancer cohort that makes sense.

Our product profile at the show will be 49 in combination with that occur kind of provide some meaningful clinical benefit.

Several indications.

Focus on those patients who progressed after GSD.

So those.

Of course in those indications.

Bill.

You need to collect them.

One.

In our Ta cohort for the monotherapy, which I think would be useful.

Thank you.

Barrett endometrial cancer indication that we've mentioned before we did we did mentioned I think when we talk about it.

Last year and earlier this year.

We were mining.

Are you on the clinical data from the <unk>.

Now, let me talk to the other matter because backup care that we're looking at is going to evolve or not and obviously that.

That will be forthcoming from me great.

I think in the colorectal <unk> amplified population.

Some really interesting patient population.

I think right now we're continuing to confirm.

Around the size of that patient population data.

Pretty wide packages.

And also I think we're trying to make sure we understand the clear combination.

We would move ahead with that we can execute our clinical development plan again, some very good data.

So I think we're continuing to evaluate some of those areas, but feel comfortable moving forward with.

Our non small lung cancer cohort and the breast cancer cohort.

And.

Yes.

Congrats on Rockdale.

Malaysia, and basically I think this is a better basis to do that.

Thank you.

And could provide some benefits moving much more quickly later and it does impact the timing right.

Okay got it thanks, Ken.

On Horizon <unk>.

How much of you said there in terms of the powering for the trial and also what is the primary comparison as the doublet versus chemo or the triplet versus chemo.

You could just.

Comment there thanks.

Yes, so we did publish.

The physical design and other features of the study in August of last year and is available on our website.

So there isn't a more upscale.

The publication.

Sites available for our more details mature available there.

But each of the two arms are in about <unk> compared to <unk> plus chemo.

That's the network.

To describe that in a publication so I encourage you to read that.

We did also disclose there.

The point, where we're going to get a PFS.

That will do an interim readout at the same time, and then decide what to do with that data and we still believe we're on track with top line data for that study will be available.

2024.

We can sharpen that guidance also.

Is that in conjunction with with both Jonathan.

As we move.

Going forward.

Okay. Thank you.

Okay I'm sorry.

We continue.

Continuing to.

All of the patients in the study.

Beijing.

Presented some initial data on last year on the truckload versus the base.

The first line patients so that data.

And.

PD one so we did have some data last year. We've obviously recruited more patients on study and is a much more mature much longer follow up which means that there is much more mature.

So obviously at some point, we hope we'll get.

Based on that data set which will hopefully give some further guidance as to how that might be useful in patient populations.

The weighted guidance from Beijing.

That might be available and Theyre also continuing to enroll.

Turning to follow.

Our study.

Thanks to study in first line breast cancer without having to have enough impactful, which we also talked about presented last year and also we have more patients and all that probably longer follow up. So we will be looking for basically the guide on when those might be.

Go ahead David.

In phase III with more mature data longer follow up with a better understanding of our guidance of where where that might be useful.

Some populations always at guidance.

Okay, great. Thank you Ken.

Yes.

Thank you. Our next question or comment comes from the line of James <unk> from Wells Fargo. Mr. Shen. Your line is now open hey, guys.

Alright, Hey, guys.

Quick question on the.

Horizon Gea study Im.

Im looking at a comparator keynote 811, where do they it looks like they are really enrich for PD Lone high and her Q3 plus patients can.

Can you say anything on whether horizon will have a more even mix of PD, one and her two positive patients and then I got a follow up.

Yes again.

Not enriching for PD lone status so.

It will hopefully be a more recruitment more.

Best of luck.

Real World, how these patients show up arguing from gastric acid function in these patients.

In our study.

And we will obviously break that out as a pre specified sub population to understand what the impact is.

On patient populations.

Whether people want us involved.

We haven't seen that.

And then data.

Thank you.

Okay, well start can understand the impact of all of them.

That patient population.

Yes. It does look like it is skewed a little bit.

But come away with ICP.

Not sure how that how that happened or whether that will be the case.

Patient population.

The cohort of patients that was published.

Thanks.

Got it and then for the VW 40 lines breast indications.

What are the potential combo partners that you would explore with 49 or is that still sort of under wraps.

Yes, it's still under wraps I think.

That's probably all we can.

Non small cell lung cancer and breast cancer indications.

<unk>.

Morning, guys.

And get more details on <unk> dot Gov as soon as we have I think one thing.

Once it's out there that won't be able to answer.

Ask your additional question.

We're obviously looking to use it it would be 49.

Combination wherever we can.

It will be.

Enbrel, where we can.

Wasteful.

We think thats the value proposition.

Ken do you have now.

The ADC.

Choice to use a combination potentially after progression obviously DSD.

And multiple indication.

Okay.

Meaningful way and in a number of those indications.

As we're talking about the value proposition thats, our target product profile. So we have to find ways to test that hypothesis.

Exactly.

Certainly from a cost perspective, we've had and.

And if we see something that's going to be beautiful there that would be able to partner quickly and move forward with registration strategy.

Yes.

Got it can I ask just one question on the ice by addition of <unk>.

It's a really interesting study design, where treatments get added and removed based on their efficacy so and it's in your adjuvant.

Is this something that's being handled by jazz and partners or is that something that you guys were working on prior to handing the ended added metal over.

No.

The group testing geography multiple different agents.

It's a really it's a really it's because we were having some discussions last year about doing that.

Obviously waited until we completed the jazz collaboration.

So a lot of jobs to opine on that decision.

The first thing.

Yes.

After that collaboration probably soft a little bit about maybe some interest, but I think it's a really I think we've always.

Hi, Matt.

Application was in the earlier.

Through the cycle that we can define.

Okay populations that I think you've seen that in our presentation last year and is that even without the tax on first line breast cancer with <unk>.

Over 90%.

So pretty interesting and I think we're entering to see what comes out of it.

Adjuvant study.

Platform that they have in <unk>.

As you know.

There was a pretty interesting way to test multiple agents in a way that you can provide some instant data back to the sponsor.

What to do with that data from a registrational path.

Got it thank you so much.

Youre welcome.

Thank you. Our next question or comment comes from the line of Stephen Willey from Stifel. Mr. Willey. Your line is now open yes, thanks for taking the questions.

Maybe just another quick one on the projected horizon Gea disclosure in 'twenty four or are you still planning on completing enrollment.

Before the end of 'twenty three.

And I think in the European trial registered Theres, a suggestion that the primary PFS analysis is expected to occur within a month over the last patient being randomized I guess is.

Is that description something that you would characterize as still being accurate.

Yes, I think you've seen a change in our guidance.

Then Jonathan conferences finish which is not unusual.

And Jeff does like to guide on availability of top line data versus patients.

Roland.

So our guidance will be the top line it will be about 124, as we expect that we can sharpen that guidance.

Jasmine, making them do.

Do that to be more specific than that.

The guidance right now we won't give anything beyond that I think you will.

Fee income trial European registry, a number of different other data points around.

Yes, thats or completion of study.

Comment on that further than just sticking to the we're on track right now to get top line data in 2024.

Really great and we're working to do that.

Okay.

Okay, and then maybe just a question for Chris with respect to just clarity on Sandy related R&D spend in 2003 I know the.

Quarterly numbers here, then fairly lumpy.

I guess, if you look at the last three quarters. Specifically is is that lumpiness something that we should expect to continue into 2023 or have you guys done some of the necessary manufacturing work such that that should kind of smooth out a little bit as we get into 'twenty three with respect to just thinking about the.

R&D reimbursement and close to the top line.

Yes, thanks for the question.

So yes, we did have some lumpiness through 2022, as we were undertaking some of the manufacturing run.

A lot of this kind of expense is behind us now.

As we go into 2023, there will still be some ebbs and flows.

We won't be guiding on specific numbers for each individual quarter.

Worth, noting that as we incur expenses within a quarter reimbursements from gas will actually come back in the following quarter. So there'll be a mismatch between the P&L and the cash flow from quarter to quarter as we advance through 2023.

So we will still be some quarter to quarter shifting.

That we can anticipate as we go forward.

Okay, So that jazz reimbursement comes a quarter in arrears.

That's correct yes.

Okay, and then maybe just lastly, I guess.

Yeah.

Does the disclosure of her too.

Her to climb O two data, which is looking at the cat and the cat silo in I guess, mostly.

Second line patients, but I think a lot of the conversations we've had with suggest that thats, maybe a regimen that gets institutionalized post her too if that data looks good.

Does.

Does that data set at all kind of change your thoughts around.

TWD 49 in breast cancer.

I'm not sure.

Does that I mean, we obviously look at all John .

All data and evolving data and what impact it might have.

On commercial opportunities or our development pathway regulatory pathway for the program.

With that Ian.

So that would be 49, and I think you need to pay attention to that and try to react.

I think from our perspective, our value proposition and our target product profile, maybe putting that I don't think there is any different.

We need to show the ability to combine.

Sure.

And show up meaningfully.

Clinical meaningful benefit.

More than one indication of multiple indications several.

And this pace.

And I think and in breast cancer, we still need to see what that looks like for you to do it looks like in one or two more population.

We need to look at what it looks like specifically in patients who progressed.

To the XP.

And hopefully on our quality of patient.

Doesn't have 11 or 12 or 13 prior therapies as we did in some of our phase one data. So it's something that's a pretty interesting indication for us.

Right.

Evolving data I think we've done gone up advisory board work with Kols that we understand where we are there.

It could be for maybe 49 in patients.

I think we've done enough potential partnering discussions.

And know what value will be paid for.

Okay that is generated.

For both non small cell lung cancer and breast cancer.

Two core cohort of patients that we think we can improve our target product profile.

We have the opportunity to do.

That with additional indications inside the envelope of how much we want to make in the timeframe, we have to make that honor.

That will do that.

Alright, thanks for taking questions.

Thank you. Our next question or comment comes from the line of Brian Cheng from J P. Morgan Mr. Chin. Your line is now open.

Hey, guys. Thanks for taking my question.

I think you have a couple of presentations coming up at SCR.

Next month, so what should our focused beat there from your presentation in your call. If you can give us some.

Maybe one just expectation that would be great.

I think everything.

Policy as well.

I think the market effectively.

<unk>.

I think we're trying to showcase both the next product that come in the clinic next.

Next year. So you are really important for us.

As well as continuing to show what the platform is capable of doing for products, John that because we're going to pick our target and our products are going to file in 'twenty five this year and we want people to understand the next product coming in the block of itself. We've got additional new data we've generated since our R&D day.

As of October .

We will try and highlight new and additional data, which has been developed which I think as.

Okay understanding of what we're doing is differentiated and why are we doing and why or why we think we'll be successful at the product formats and the targets that we.

Collected as well as the platform's ability to continue to generate.

Five new <unk> in the next five years, including one upon that one next year that will all be novel diversified on both sides of the.

Our portfolio.

<unk>.

Multicenter.

Antibody therapeutics.

Yes.

As well as I'll be I'll be differentiated and meaningful assets that we can keep unencumbered first of all as long as.

As long as possible. So I think there will be all.

A lot of things there between products.

The new platform that we're working right now there is also one.

John .

49.

Juan.

Unrelated to that.

That's correct.

A little over a week or so I think by double NPR. So.

We'll be able to answer more of that question.

Abstracts are released.

And then next week or so and then beyond that obviously.

And information are available on the posters for all.

No.

And maybe just one follow up on.

Sandy sales side.

You talked about how <unk>.

Partnership is to this program.

Seems that you are already in discussion with a couple of potential partners.

When do you think that it will be a good time to bring in a partner for <unk> and <unk>.

Is there a bar that you need to hit.

For the phase two that Youre doing an analyst CNR cell metastatic breast.

They need to head for before these are partners jumping in.

Yes, good question.

Obviously, we don't we do not have clinical data E Commerce, maybe 49 with other standard of care.

A big part of the value proposition for our development partner that we'd like to generate that.

That data obviously, having early part of your vessels is crazy because it helps.

Yes.

Designing clinical programs, so we like doing that.

R R.

Current investment thesis around <unk> 49.

<unk> is not core to the five and five.

Could you be valuable assets that we'd like to invest incrementally in.

Phase II clinical development stage.

The goal after that is to get an ex U S partner.

To work with us if we get clinical data, which showed that patients should go forward.

We'd like the terms of that you'd also be viable it up.

To fund the potential for us to retain the U S commercial rights and develop that further to the market. After the partnering job not off our balance sheet. So you have to have data to support partner being able to have a transaction was good.

It will allow us to be able to undertake that as well as <unk>.

Convinces ourself.

Reasonable undertaking.

To retain U S rights for further development.

Commercialization of Enzo ourselves and so we also have to reinvent ourselves.

There is the potential that we could do a global licensing deal with one party that was attractive to us.

Because again it doesn't affect the 505 strategy, we have or the non her two assets that were generating behind that.

And then so I mean to get.

I believe we need some indication.

As I mentioned, that's going to be 49 can be effectively combined.

Was that Medicare and indications that matter.

And shows.

Interesting signals of efficacy to show that the registrational pathway for that agent to.

A second line agent or B, the second choice Hercules AEP behind <unk> was a very commercially attractive.

Especially in non small cell lung cancer in the breast cancer indications.

Some of the other ones are still installed.

Install evaluating.

Some of that combination data is going to be necessary to convince.

Our partner on the value that we'd be looking for but also commit ourselves to work off of.

To retain.

The U S right.

Great. Thanks for taking my question.

Thank you.

Our next question or comment comes from the line of Charles Zhou from Guggenheim Partners.

Mr. <unk>. Your line is now open.

Hey, guys. Thanks for taking the questions.

My first one perhaps on Zen as any dent a med fronts.

Frontline gastric cancer.

I'm kind of wondering given that you've had that recent any plus chemo data earlier this year as well as what we saw from <unk> 22 last year from B B gene I guess.

With the potential.

Data from the single arm phase two later this year any color around like how much more confidence we could obtain around the potential additive clinical benefit of layering on PD one on top of your regimen. Thanks.

Yes.

The easiest way to answer that question would be to complete the phase III study is going on now which fully randomized two one to one to one contrast, chemo does that mean.

Doublet and triplet, including including.

Thank you.

And the best place for Us to.

Ask that question.

I heard all of the patients study readout, the PFS and then from all of Us.

Look at the subpopulation analysis.

I think just an insight.

Suffice to be able to answer that question Thats what were working toward.

As.

As expeditiously as we can obviously to deal with that on January <unk>.

Encouraging.

The kols and ourselves and transformation.

On the doublet.

Hopefully, we'll get a chance for an update on additional data.

The triplet.

Thank you put out last year and get some more.

Understanding of what that looks like.

To be more patient numbers in that in the long term follow up that might be something more read into that but.

But obviously the reason we're doing a large multinational randomized.

Andy.

To try and provide clarity on the answer to that question that you have.

Got it great and maybe one more question on <unk>, so perhaps a bit of a follow up to something that's already been kind of asked a bit but during your prepared remarks, I think you had.

You mentioned something about a pre determined benchmarks that could justify further development beyond the phase twos and long as well as posting her to breast cancer.

Any additional color around.

What those could possibly be or.

What was your thinking was.

Generating some of those benchmarks. Thank you.

Yes, I mean, we've obviously.

I'd like to start with on the Redetermination.

What does clinically meaningful data looks like and in combination.

The indications Orion studies so.

Yes.

Some.

David.

The impairment that we think would be meaningful that would be encouraging.

Excellent partner and again urging us to think about.

Retaining U S rights, so if any of those further.

Further develop it with the proceeds from an excellent partnership and use that as our first commercial entree into the U S.

We frequently had.

At this time, which is really good.

Process to work through about the totality of data matters and quality.

<unk> and volume data matters.

But those are all pre determined that exist that way.

Others will do and I think.

Once we generate that data will have some idea.

What we think about moving forward or which indications make the most of them.

Got it great. Thanks for taking the questions.

Yes.

We've done a lot of work since I got here a year ago on looking at the indication the commercial market reserve add more as you saw we just did one recently in.

In Japan in January which weren't able to do earlier.

We have a pretty good sense from.

Partnering discussions and our Kols and our actions.

We're going to be 49, with app to generate data to be.

Pet for moving forward.

Thank you again, ladies and gentlemen, if you have a question or comment at this time. Please press star one one on your telephone keypad.

Our next question or comment comes from the line of Andrew Berens from SBB Leerink. Mr. Bearings. Your line is open.

Hi, guys.

Couple of questions for me.

GW back combination of strategy of checkpoint.

Can you share any preclinical data that you have that support our combination strategy.

Do you have any concerns that keratitis could be exacerbated by immunotherapy is ocular tox.

Known side effect with checkpoint inhibitors, and then what do you think the regulatory strategy will eventually be demonstrate GW board that will be added to the background efficacy you would see with.

Checkpoint inhibitor alone.

Yeah. Good question I don't think we've disclosed any of the preclinical data that we would have.

On the combination.

We don't believe there won't be any.

Any further impact on the current guidance.

But as long as you run combination studies.

In cohort one.

Thanks Ole.

We will do that to be able to confirm that obviously one of the benefits of <unk> 49 in the.

Or to ADP is the tolerability issues that we have to deal with or are limited to grade one grade two keratitis, which caused a significant discontinuation.

<unk>.

Patients on it.

Adam.

Provide a substantial amount of dose reduction.

Beyond that we don't have neutropenia neuropathy pneumonitis.

And any signals of that.

So obviously, we think the volatility profile means that you can.

Provide an effective combination without overlapping toxicities and we think there may be.

Synergies between.

PD one.

Because as you pointed out inventory statin payload and that might be from a mechanism standpoint.

We will have one abstract at ACR around some initial thoughts around the mechanism of TWD 49 that might provide some additional information to that.

Obviously going forward in non small cell lung cancer I mean can you wanted to use there.

In a variety of different into.

Indications, including in no known ultimate mutation. So there is some.

Good data already on existing around <unk>.

Just that indication, we obviously have to show that adding 49 to that.

The PD one.

Her two population.

Provides.

A benefit.

Fourth partner.

Part of what we're doing in the design of the cohort that we have.

And both are over expressing that hurts and amplify that hurts the mutant population.

Also lung cancer.

In addition on the breast cancer side.

<unk> not been very effective.

Yes.

Indication study in breast cancer, but.

Yes.

There isn't one PD, one to be more useful and indication.

Because of this synergistic effect that might occur with your fab Pelican PD ones, we'd like to explore that before that clinically.

And look at that.

That's accurate or not.

Okay. Thank you.

Thank you our next question or comment comes from the line of.

David Martin from Bloom Burton.

Mr. Martin Your line is now open.

Thanks for taking my questions.

First question regarding the phase two indications for CW <unk> 49.

You presented phase one data at ESMO last year.

I think there was one lung cancer patients there were relatively few in her two failures some few.

Or too low patients.

Post that presentation did you then kind of focus your recruitment on patients sub 50.

Phase two characteristics I mean, we see larger cohort or larger groups of those patients and the updated data later this year.

Yes, that's accurate so obviously after the cutoff for as we continue to recruit.

The phase one study in monotherapy.

Most of the week.

Dosing, which we were doing which we were out on.

But also to continue to recruit additional patients on monotherapy.

At the recommended phase two dose of $2 five megs per every three weeks.

And we focused on enrolling patients that were closer to our.

Our strategy going forward in combination so.

Hopefully all of that data set which.

Which put out we haven't given guidance for this year, but we'll do that as we as soon as.

We were able to be specific you should see additional monotherapy.

Activity was going to be 49.

And some of those patient populations, where would've been nice to see more before the ESMO.

And obviously.

That leaves a little bit of our thinking.

Going forward into looking at the combination strategy.

A reasonable contribution taking much activity in the highest quality patients being on track.

Okay great.

Well the phase twos be randomized like I assume you'll do a dose escalation single arm initially, but then will be each turn into randomized trials.

Yes, we havent given any specifics yet.

This cohort is item and we won't do that install and up on.

<unk> Dot Gov, obviously, we're trying to.

Go quickly.

Recruiting the right patients in the <unk>.

Cohort after.

After the question as to whether we have a value proposition here.

Or not.

And if we do then be able to move really quickly into a registration pathway and so there's a lot of factors are considering how we're designing and executing these.

These studies so I think once you Stefan control stock out we're happy to answer.

Those questions about why we designed the way we did.

Okay. Thanks, that's it for me.

Thank you.

Thank you I'm showing no additional questions in the queue at this time I would like to turn the conference back over to management for any closing remarks.

That's great well. Thank you. Thank you Peter.

Today and for your questions.

There's a lot of progress last year enzyme works and I think for 2023, we've got really good momentum across the business. We're really looking forward to having a great couple of NCR coming up in April and those abstracts will be available publicly soon.

We're very encouraged to have 11 different abstracts accepted.

This meeting last year, we had zero.

So we're really looking forward to having a fulsome disclosure of the products and platforms and the early R&D group.

505 strategy that we have and talking more about that and we look forward to.

They are doing that very quickly.

So thank you for your time and attention look forward to reporting more progress as we move forward through the year.

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program you may now disconnect everyone have a wonderful day.

[music].

[music].

Good day, ladies and gentlemen, and thank you for standing by welcome to design works fourth quarter and full year 2022 results conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one one.

All your telephone keypad.

At this time I would like to turn the conference over to Mr. Jack Spinks.

Oh Investor Relations first time works, Sir you may begin.

Good afternoon and welcome everyone.

My name is Jack Spinks head of Investor Relations here at <unk> today.

Today, we will discuss our fourth quarter and full year 2022 financial results.

Well provide an update of our ongoing business.

Before we begin I'd like to remind you that we will be making a number of forward looking statements. During this call, including without limitation. Those forward looking statements identified in our presentation slides and the accompanying oral commentary.

Forward looking statements are based upon our current expectations and various assumptions and.

And are subject to the usual risks and uncertainties associated with companies in our industry and at our stage of development for.

For a discussion of those risks and uncertainties.

For you to our latest SEC filings is found on our website and as filed with the SEC.

Later in this call Chris <unk>, our senior Vice President and Chief Financial Officer will be discussing our financial results, including certain non-GAAP measures.

<unk> of our GAAP measures and a reconciliation to the most directly comparable financial measures as determined in accordance with GAAP are described in detail in our press release, which is available on our website at www Dot <unk> Dot com.

Under the Investor Relations tab as a reminder, the audio and slides from this call will also be available on <unk> website. Later today now I will turn the call over to Chris Our senior Vice President and Chief Financial Officer, Chris.

Thanks, Jack and thank you everyone for joining us today for our fourth quarter and full year 2022 earnings call.

As a reminder, I'd like to note that while I'll be presenting the prepared remarks today, Kenneth Galbraith chat in <unk> and <unk>.

Other members of our executive team will be available for Q&A. Following this portion of the call.

With that I'd like to begin today's call with an overview of our financial results followed by a few recent developments are noteworthy updates across our business before we open the lines for Q&A.

This afternoon <unk> reported financial results for the fourth quarter and year ended December 31 2022.

<unk> net income for the year ended December 31, 2022 was $124 3 million.

Or $1 90.

Earnings per diluted share.

Compared to a net loss of $211 8 million.

The year ended December 31st 2021.

Swinging from an annual net loss to net income was primarily related to revenue received from our collaboration agreement with jazz, partially offset by increases in expenses incurred in 2022 relative to 2021.

As reported our revenue for 2022 was $412 5 million.

Compared to $26 $7 million for 2021.

Revenues for both the year and most recent three month period ended December 31, 2022, primarily related to the $375 million in upfront payments received from jazz as a result of the completion of the zone at depth.

Licensing agreement combined with approximately $24 million in reimbursements from jazz for expenses incurred for zone. That's about between October 19th and December 31 2022.

Research and development expense for the year ended December 31, 2022 with $208 $6 million.

Compared to $199 $8 million for the year ended December 31 2021.

This increase of $8 8 million or 4% from the prior year related primarily to higher manufacturing and clinical trial expenses does that not that amount in 2022 and due to the restructuring exercise undertaken in the first quarter of 2022.

These were partially offset by a decrease in expenses related to reduced preclinical on that thats, a month's overdosing related expenses in 2022.

As of October 19, 2022, <unk> is entitled to reimbursement from Johnson for all <unk> related expenses related to ongoing studies under the terms of the collaboration agreement finalized in Q4 2022.

General and administrative expense for the year ended December 31 2022.

It was $73 4 million compared to $42 $6 million for the year ended December 31 2021.

This year over year increase of $30 8 million or 72% was driven primarily by severance and other expenses related to a reduction enforce and R&D re prioritization program that they've had in early 2022, and an increase in consulting and professional fees primarily related to the Companys re domicile to.

Become a Delaware Corporation.

The <unk> licensing agreement and other nonrecurring project based expenses.

During 2022, the company's workforce was reduced by more than one third through the reduction in force and voluntary attrition.

450, full time employees to less than 300 full time employees.

Our cash resources, consisting of cash cash equivalents and short term investments.

$492 9 million as of December 31, 2022.

Obviously, driven by the receipt of the upfront payments from jazz totaling $375 million in the fourth quarter.

Our cash resources as of December 31, 2022 did not include $24 million and reimbursements associated with funded debt related expenses from October 19th through year end 2022.

Licensing and collaboration agreement with jazz completed the series of financially beneficial transformation initiatives and 2022, which we believe will fund our planned operations through at least 2026 and potentially beyond.

Okay.

We completed an equity offering in January 2022 comprised of a combination of common shares and pre funded warrants for gross proceeds of $115 million, which included the exercise in full of the underwriters' option to purchase additional shares.

As of March 3rd 2023, we had approximately 65 to 5 million shares of common stock and pre funded warrants outstanding and shares issuable pursuant to our Canadian exchangeable shares.

We did not issue any shares of common stock under our ATM facility. During 2022, alright as of March seven 2023 for the current year.

In January of this year, we also issued financial guidance related to our net operating cash burn for 2023.

Given the significant change in our overall net cash burn we expect to experience. This year due in large part to the reimbursement of sand that's populated expenses under our collaboration agreement with jazz.

We continue to expect our net operating cash burn for 2023 to be between 90 and $120 million, including planned capital expenditures of $15 million.

This cash burn guidance as well as our cash flow. My guidance includes forecasted expenses are primarily related to our early R&D programs as well as incremental expenses to support our planned phase III clinical development program, because I know thats months overdose.

For additional details on our quarterly results and for a description of our non-GAAP financial measures and a reconciliation of GAAP to non-GAAP measures I encourage you to review our earnings release and other SEC filings available on our website at Www Dot <unk> Dot com.

Now I'd like to spend a few minutes talking about early R&D portfolio, followed by a brief discussion on Sunday, that's some upside without an Amazon a better map, our most advanced clinical product candidate.

We re prioritized our R&D strategy early in 2022 and had an exciting and productive year with substantial progress on executing this new R&D strategy to.

To quickly recap we recruited Dr. Paul Moore, as our new Chief Scientific Officer in June of last year.

And hosted in early research and development day in October where we previewed preclinical product candidates emerging from both our antibody drug conjugate and multi specific platform technologies designed to overcome limitations of existing therapies.

At that same event, we disclosed our two lead candidates for IND by 2024, GW 171, and <unk> 191, both of which are on track to be submitted next year.

Additionally, we set some ambitious targets are progressing five novel and differentiated preclinical product candidates, including GW 171, and <unk> 191 into clinical studies by 2027.

We believe that helped pursuit of this goal along with our scientific vision and path forward in the ADC and multi specific antibody space.

Helped generate a diverse and valuable oncology product portfolio of wholly owned product candidates.

In addition to developing our own internal oncology pipeline, we anticipate additional preclinical product candidates derived from our ADC of multi specific technologies.

<unk> with resources available from potential partners and collaborators.

We are continuing to evaluate opportunities to form additional collaborations and partnerships around both our publicly disclosed and confidential preclinical product candidates.

This partnership strategy is important as it can help us to accelerate development and advanced potential opportunities without the use of XIAFLEX as shareholder capital to complement our wholly owned product pipeline.

We hope to announce the completion of additional collaborations and partnerships before the end of this year for multiple preclinical product candidates.

And helping further this objective we are excited to announce the acceptance for publication of 11 abstracts at the American Association of cancer research or ACR to be presented in mid April and Orlando, Florida.

These abstracts will be made publicly available by ACR on March 14.

I'd say ACR, we will be able to share with you additional progress on preclinical data on the announced preclinical product candidates that we spoke to at our R&D day last year as well as continued progress on our technology platforms for generating additional ADC, a multi specific antibody therapeutic candidates.

So our preclinical product pipeline beyond 2024.

Subsequent to these presentations in Orlando, We will also plan to host a conference call to discuss the results and strategic impact. These new data will have on our path forward in.

In addition to our in House development efforts, we continue to have multiple active licensing agreements with key pharmaceutical and biotechnology partners.

This portfolio of legacy platform partnerships, which consist of partnerships, where we are required to expand little if any capital to advance the programs represent a significant source of past and potential future non diluted funding.

To date, we have received approximately $119 million in upfront and milestone payments not including any amounts received because I know thats math horizontal <unk>.

Further throughout 2023, and 2024, we expect to earn additional milestone payments under existing agreements as product candidates continue to be advanced through development stages by our partners.

We also retain the ability to monetize all or a portion of the future cash flows from these agreements pulling forward the value of future cash payments to provide an additional source of non dilutive capital should it be needed.

Here on slide six we can take a moment to touch on <unk> or <unk> for short.

As you likely noticed from our earnings release issued earlier. This afternoon. We are planning to continue with a data driven development program <unk>.

And advanced into selected patient cohorts in phase II clinical studies.

This will appropriately move this product candidate forward by studying <unk> in combination with other approved agents, especially checkpoint inhibitors.

With incremental clinical investments and predetermine benchmarks.

Previously we had anticipated a protocol expansion of our ongoing phase one clinical study. However, after careful evaluation and a better understanding of both timelines on what we believe will be the most valuable to any potential future partner.

Thus building potentially meaningful value to our shareholders. We have chosen to proceed with separate phase III studies to be conducted.

One evaluating <unk> in combination with PD, one inhibitors and non small cell lung cancer and another in patients with breast cancer after progression on <unk> DXP and had too low patients in combination with PD one inhibitors.

With this design, we believe we can obtain the clinical data necessary to both enter into a registrational path for <unk> before the end of 2025.

And attract an appropriate partner to assist with ex U S development and commercialization.

Something we currently expect would be required before moving forward into a registration pathway.

We continue to consider other areas of interest for clinical development and evaluating <unk> with the current standard of cabin had two amplified colorectal cancer patients.

Two expressing gynecological cancer patients in her two positive gastroesophageal adenocarcinoma or GE.

We anticipate that our phase III studies for <unk> will be implemented using assignments two stage study design.

This allows us to clearly designate and defined hurdle rates and stage our investment in <unk> going forward.

We expect that the conduct of these phase III studies will be expanded geographically to additional clinical sites in Asia and Europe to both improve the speed of patient recruitment and lower the overall clinical development cost of patient recruitment.

Our newly formed regional hubs will help us provide the appropriate support for this geographic expansion of our clinical development program for Zalviso.

We continue to believe that the phase one clinical data presented last year at ESMO at two five milligrams per kilogram dosed every three weeks shows that <unk> has a differentiated tolerability profile relative to other adcs and acceptable single agent activity in a range of <unk> expressing tumors.

The keratitis seen in our phase one study is well characterized and primarily low grade being grade one or two which is both manageable and reversible.

And appropriate dose reduction management strategy was effective in managing any patients affected with keratitis and a phase one study without any significant discontinuation from the clinical study.

Importantly, we did not see other tolerability signals of consent comment of other head to ADC products and consequently, an attractive part of what we believes on these that can offer the potential ability to combine with other agents currently used as standard of care.

In areas, where we see the patient need and where are we.

We may be able to improve upon current efficacy seen with existing standards of care.

Incremental investment in these phase III studies, which are planned to begin enrolling patients in 2023 is warranted based on the clinical data generated to date and our recent interactions with Kols and potential partners.

Wireless spend represents a small component of our anticipated net cash operating burn guidance of $90 million to $120 million for 2023.

<unk> represents an important and investable opportunity worth pursuing as a differentiated had two ADC and post <unk> patient population.

And could provide the company with the ability to retain development and commercial rights in the U S. While working with our partners in ex U S markets.

Finally on <unk>, while we have continued to enroll and followed patients on our phase one study treated at the recommended phase II dose of two five milligrams per kilogram every three weeks as monotherapy, we will be closing the weekly cohort in order to eliminate any future additional costs associated with keeping this portion of the study open.

We expect to be able to present further data before the end of this year on that weekly data as well as additional monotherapy data generated since the data cutoff for the 2020 to ESMO presentation.

Going forward, we will be focused on opening the initial two phase III studies and generating combination data as quickly as practicable.

Finally, before we open things up for Q&A I'll briefly touch on <unk> as we still have an exciting year ahead of us and recently presented important data ask Agi. This January .

At <unk>, we presented updated data from our phase III trial evaluating zander debt amount in frontline her two positive metastatic GE.

These data included a first look at Santa <unk> overall survival data.

Showed an impressive 84% overall survival at 18 months with a median overall survival having not been reached.

Further the data included in overall confirmed objective response rate of 79%, including three complete responses.

Median progression free survival of $12 five months and the median duration of response of 24 months. After 26 five months of patient follow up.

The regimen was manageable tolerable and consistent with the observed safety profile as reported for other standard regimens for patients with her two positive gea.

We are working closely with Johnson Beijing to continue enrolment of patients in the phase III randomized clinical trial horizon GE, one evaluating <unk> in combination with chemotherapy.

So minus two elysium app as a first line treatment for <unk> expressing metastatic or advanced.

We continue to expect top line results from this pivotal study to be available in 2024.

Additionally, last quarters <unk> reported positive top line data from our phase II open label single arm clinical trial Horizon BTC. One studying is on a desktop app as a monotherapy in patients with previously treated two amplified in expressing the Louis tract cancers.

With a confirmed objective response rate of 41, 3% and a median duration of response of $12 nine months in patients with her two amplified in expressing while I hate to see two plus three plus disease.

These data represents a potentially important steps ahead to amplified patients with DTC because that thats map has the potential to be the first had to targeted therapy in this indication.

Ah represents a chemotherapy free treatment option for patients who would otherwise receive standard of care chemotherapy in second line.

But typically elicit overall response rates of between five and 15%.

Further we expect the full results from these data to be presented at a major medical meeting in the first half of this year and look forward to confirming that presentation as soon as practicable.

We remain very encouraged by these positive top line results is on the debt amount as well as the recently presented results of <unk>, including the first look at overall survival data for <unk> in our phase III without partners Johnson Beijing, we continue to work towards the potential regulatory path forward with the relevant regulatory bodies in various.

Countries, where the BTC data may support an accelerated or full approval.

We will continue to work with our partners. He will provide guidance I think appropriate time for any regulatory filings.

While the initial development path and global regulatory interactions will be focused in BTC and gea. The two most advanced indications with ongoing pivotal trial we.

We and our partners continue to evaluate the development path and other indications beyond the BTC and DEA.

We have ongoing clinical development and additional indications and remain excited about the broad potential of Santa desktop and indications outside Gi cancers.

To this point <unk> is currently being used in the I spy platform trials for patients with head to expressing tumors in the neo adjuvant treatment of locally advanced breast cancer.

This and other ongoing development efforts present, a desktop app will help determine the path forward in these indications.

Last year was an important year for the company with numerous ambitious goals that were set in January of 2020 to reset the company strategy as.

As we reflect on the past year, we were able to make significant progress across multiple aspects of our business, including on the non scientific front, while we successfully completed the re domicile to Delaware, resulting in positive inflows due to index inclusion in U S based indices.

As well as a stock exchange listing change from the New York stock exchange to the NASDAQ stock market.

Or are we better aligned with peers in the biotechnology sector.

As we look towards 2023, we have identified five important pillars of value are enterprise value framework.

We will look to advance in order to continue generating volume.

These five pillars are Tuesday night, Thats, my collaborations with Beijing, and James our early research and development programs.

That's what I observe it open and our legacy platform licensing portfolio.

From a business and financial standpoint, we believe we are well positioned for success with our new strategy.

We have sufficient cash to pursue our planned development activities with a significantly reduced net cash burn.

Our focus clinical program with planned phase III study says other thats mumps overdose.

And a number of exciting preclinical product candidates.

Working to progress the clinical studies with a specific focus on development of a mix of antibody drug conjugates and multi specific antibodies.

We believe this focused investment in moderated future spending when combined with the scientific expertise and people working hard behind the scenes makes for a very compelling opportunity going forward.

As we remain focused on our operational goals. We will also stay true to our vision to discover develop and commercialize novel medicines that can make a meaningful difference in the lives of patients around the world impacted by difficult to treat cancer and other serious diseases.

So all of those who have been with us through what was a challenging 2022 for everyone investing in working in biotech.

I must now looks forward to the future from a strong financial and scientific flooding.

To continue delivering upon these results generating long term value for our shareholders and ultimately improving the lives of patients by generating antibody based therapeutics with the potential to dramatically improve on current standards of care and difficult to treat cancers.

With that I'd like to thank everyone for listening to our prepared remarks, and I'll turn the call over to the operator to begin the question and answer session operator.

Ladies and gentlemen, if you have a question or comment at this time. Please press star one one on your telephone keypad.

If your question has been answered or you wish to remove yourself from the queue simply press star one one again, what's more if you have a question or comment at this time. Please press star one one on your telephone keypad. Please.

Please standby, while we compile the Q&A roster.

Our first question or comment comes from the line of <unk> <unk> from Citi. Your line is open.

Yes, hi, thanks for taking the question.

So on the <unk> 49, now called <unk>.

You mentioned that Youre going to start the phase one I believe except for one of the cohorts can you just go into a little bit more detail as to the thinking behind that so why you are moving into those two phase III one in the non small cell one of the most.

Metastatic breast cancer, great to get a better understanding of the <unk>.

The shift in strategy there. Thank you.

Yes, sure and I don't think.

The shift in strategy.

As more form over substance. So I think it is a clear preference from a revenue perfect.

To initiate new core combination cohort.

In our phase III format.

So again.

Now we pointed out in our kind of two things here one is reduced.

Reduced.

Perfect and clinical development costs, our prior costs are too high.

Crude is speed of patient recruitment.

Because I think we've been slow I think we need to improve the asset quality patients.

That we can screen for these kind of I just want to book value.

A number of things <unk> been doing about all of that position.

One thing is the project site.

Globally, the phase one for dialing in.

Got it in Korea, but not beyond that and I think going internationally.

Contact talked about.

We're doing filings and new countries.

Starting perhaps in a phase II study as opposed to amending our phase one study is comparable I think Tony over.

Over in the early stages of development group, which we reorganized.

Definitely bring down the internal cost or.

These clinical development cost and thank you for that group.

Caring for 170 1191.

Next year.

Clinical trial.

Come on.

And also what we're doing.

As always we have for the phase one to decide if we want to move forward in phase two and I think we could definitely account for some of the cost of being affected by it.

Potentially reviewing that contracted value mix.

So with all that being said I think I think there is a clear preference from a revenue perspective that we do this in phase II talking to make a difference in the size of the studies or the timing.

Our execution.

Also some benefits of moving forward, if we're able to generate.

Some great data in combination with <unk> 49 in multiple.

Her two indications that we've already identified.

Our target product profile, that's our value proposition, we can prove that we can move much more quickly forward to a registration pathway in conjunction with our partner as we mentioned before in excellent markets.

By starting pace now so I think there is some forward thinking that if we are successful in being able to move 49.

After these basic cohort then we'll be in a better position does that even more even more quickly.

Beyond that.

We're comfortable with the advisory board on working down around non small cell lung cancer moving forward.

I think with the breast cancer cohort that makes sense.

Higher product profiles to show 49 in combination with better care.

Some meaningful clinical benefit.

Several indications.

We focus on those patients who have progressed after GSD.

Those cohort in those indications.

Bill.

You too.

In phase one.

RGA cohort for the monotherapy, which I think would be useful.

Thank you.

Bearing in repo cancer indication as I mentioned before we did we.

We did mention I think when we talked about it.

Last year and earlier this year.

We're waiting.

You on the clinical data from the <unk>, especially in ovarian and endometrial cancers as backup care that we're looking at is going to evolve or not and obviously that data.

That will be forthcoming from E rate.

And the colorectal the hertz or amplified population doesn't really interesting patient population product.

I think right now we're continuing to confirm the data around the size of that patient population. Because obviously there is a pretty wide activation and also I think we're trying to make sure we understand the clear combination.

Let's move ahead with that we can execute our clinical development plan again, some very good data.

So I think we are continuing to evaluate some of those areas feel comfortable moving forward with a non small lung cancer cohort.

And the breast cancer cohort.

As.

And the SP.

<unk> population in phase II I think this is a better basis to do that in international expansion and could provide some benefits moving much more quickly later and it does impact the timing right.

Okay got it thanks, Ken.

On horizon.

How much of you said there in terms of the powering for the trial and also what is the primary comparison is it the doublet versus chemo or the triplet versus herceptin chemo.

Okay.

Comment there thanks.

Yes so.

We did publish.

The physical design and other features of the study in August of last year and is available on our website and take a look at that.

A more publications on this one.

Web sites available for our more details mature available there.

But each of the Tomorrow's, our independent lead compared to <unk> plus chemo.

That's the way it works.

Just describe that in a publication so I encourage you to read that.

We did also disclose there.

The point, where we're going to get a PFS.

That will do an interim read out at the same time, and then decide what to do with that data and we still believe we're on track with top line data for that study will be available.

2024.

We can sharpen that guidance.

That in conjunction with with both Jonathan.

As we move.

Okay.

Okay. Thank you.

Okay, I'm, sorry, just to add that.

We are continuing to.

Follow the patients in the study that Beijing had.

Or is that just some initial data on last year on the truckload side.

This patient was running in first line patients of that data.

Chemo and.

Other PD one so we did have some data last year. We've obviously recruited more patients in that study and is a much more mature much longer follow up which means that there is much more mature.

So obviously at some point, we all get update on that.

That which will hopefully give some further guidance as to how that might be useful in patient population as a whole.

The weighted guidance from basing on what that means.

That might be available and there are also continuing to enroll.

Turning to follow.

Our study.

Thank you study in first line breast cancer without having to have enough impactful as we also talked about presented last year and also we have more patients and all that probably longer. So we'll be looking for patients to guide on when those might be available.

Perfect.

In phase two with more mature data longer follow up in better understanding our guidance of where where that might be useful.

Some populations as always our guidance.

Okay, great. Thank you Ken.

Okay.

Thank you. Our next question or comment comes from the line of James <unk> from Wells Fargo. Mr. Shen. Your line is now open hey, guys.

Alright, Hey, guys.

Quick question on the.

Horizon Gea study Im.

Im looking at a comparator keynote 811, where do they it looks like they are really enrich for PD Lone high and her Q3 plus patients can.

Can you say anything on whether horizon will have a more even mix of PD, one and her two positive patients and then I got a follow up.

Yes, well again.

Sometimes we're not enriching for PD lone status so.

It will also give you a more recruitment more.

Thanks.

Real World, how these patients show up arguing from gastric acid functionality.

In our study.

And we will obviously break that out as a pre specified sub population to understand what the impact is.

On patient populations.

Whether people want us involved.

We haven't seen that.

And then data.

Thank you Jessica.

Okay, well stocked and understand the impact of.

I'll bet in that patient population.

Yes, It does look like it is.

A little bit.

But come away with one status in ICP.

Sure how that how that happened or whether that will be the case when you see the whole patient population.

A cohort of patients.

To support the accelerated approval.

Got it and then for the VW 40 nines breast indications.

What are the potential combo partners that you would explore with 49 or is that still sort of under wraps.

Yes, it's still under wraps I think.

That's probably all we can about those non small cell lung cancer and breast cancer indications.

Good morning, guys up and running and get more details up on control Dot Gov. As soon as we have I think once it once it's up there that won't be able to answer.

Additional questions.

Robinson looking to use it it would be 49.

Combination wherever we can.

That would be.

<unk>, where we can.

To wasteful.

We think thats the value proposition.

<unk> nine the ADC.

Choice to use a combination potentially after progression obviously DSD.

And in multiple indication.

In a meaningful way and in a number of those indications.

As we're talking about the value partners and Thats, our target product profile. So we have to find ways to test that hypothesis.

Perfect.

Efficiently from a cost perspective, we had and if we see something that's going to be meaningful there that would be able to partner quickly and move forward with registration strategy.

Okay.

Got it can I ask just one question on the ice by addition of <unk>.

It's a really interesting study design.

<unk> get added and removed based on their efficacy so and it's in your adjuvant.

Is this something that's being handled by jazz and partners or is that something that you guys were working on prior to handing the ended Adam that Oliver.

The current study group testing, obviously multiple different agents.

So really it's a really it's because we were having some discussions last year about doing that.

Obviously waited until we completed the jazz collaboration.

So a lot of jobs to opine on that decision and the first thing.

Perfect.

After that collaboration probably soft a little bit about maybe some interest, but I think it's a really I think we've always hypothesized that math.

Application was in the earlier.

Treatment cycle and volume.

Okay populations and I think you've seen that in our Canadian pellet Beijing last year and does that impact after tax on first line breast cancer with <unk>.

Over 90%.

So pretty interesting and I think we're going to see what comes out of it.

Human study I think the platform that they have in <unk>.

Good to know.

It was a pretty interesting way to test multiple agents in a way that you can provide some instant data back to the sponsor.

And then decide what to do with that data from a registrational path.

Got it thank you so much.

Youre welcome.

Thank you. Our next question or comment comes from the line of Stephen Willey from Stifel. Mr. Willey. Your line is now open yes, thanks for taking the questions.

Maybe just another quick one on the projected horizon Gea disclosure in 'twenty four or are you still planning on completing enrollment.

Before the end of 'twenty three.

And I think in the European trial Register Theres, a suggestion that the primary PFS analysis is expected to occur within a month over the last patient being randomized I guess is.

Is that description something that you would characterize as still being accurate.

Yes, I think you've seen a change in our guidance.

And Jonathan just finished which is not unusual.

And Jeff does like to guide on availability of top line data versus patients enrolled.

Enrollment.

So our guidance will be in the top line it will be about 102024, and the extent that we can sharpen that guidance.

Jasmine, making them more will do that to be more specific than the calendar year, but that guidance right now we won't give anything beyond that I think you will see.

Fee income trials European registry, a number of different other data points around.

PFS or completion of study.

Comment on that further than just sticking to the Ron property now to get top line data in 2024 from that and that's really great and we're working to do that.

Okay.

Okay, and then maybe just a question for Chris with respect to just clarity on Sandy related R&D spend in 2003 I know the.

Quarterly numbers here, then fairly lumpy.

If you look at the last three quarters, specifically is is that lumpiness something that we should expect to continue into 2023 or have you guys done some of the necessary manufacturing work such that that should kind of smooth out a little bit as we get into 'twenty three with respect to just thinking about the.

R&D reimbursement and close to the top line.

Yes, thanks for the question.

So yes, we did have some lumpiness through 2022, as we were undertaking some of the manufacturing run.

All of this kind of expense is behind us now.

We go into 2023, there will still be some ebbs and flows.

The guiding on specific numbers for each individual quarter.

It's worth noting that as we incur expenses within a quarter reimbursements from gas will actually come back in the following quarter. So there'll be a mismatch between the P&L and the cash flow from quarter to quarter as we advance through 2020, but it will still be some quarter to quarter shifting.

That we can anticipate as we go forward.

Okay, So that jazz reimbursement comes a quarter in arrears.

That's correct yes.

Okay, and then maybe just lastly, I guess.

Sure.

Does the.

As you have heard too.

Her to climb O two data, which is looking at the Cadillac <unk> silo.

I guess, mostly.

Second line patients, but I think a lot of the Kols conversations we've had with suggest that thats, maybe a regimen that gets institutionalized post her too if that data looks good.

Does.

Does that data set at all kind of change your thoughts around.

<unk> 49 in breast cancer.

I'm not sure.

Got it and then we obviously look at all.

All data and evolving data.

It might have.

Commercial opportunities or our development pathway regulatory pathway for the program towards that end.

And I think you need to pay attention to that and try to react.

I think from our perspective, our value proposition and our partner product profile, maybe putting that I don't think it isn't any different.

We need to show the ability to combine.

With that is there.

And show a meaningfully clinical meaningful benefit.

More than one education, a multiple indications at all.

And this pace.

And I think in breast cancer, we still need to see what that looks like it looks like in the <unk> population and we need to look at what it looks like specifically in patients who progressed post two.

DXP.

And hopefully on our quality of patient.

It doesn't have 11 or 12 or 13 prior therapies as we did in some of our phase one data. So I still think that's a pretty interesting indication for us.

Evolving data I think we've done.

Advisory Board work with Kols that we understand where we're at.

There could be maybe 49 in patients I think we've done enough potential partnering discussions.

No.

It will be paid for.

<unk> generated so I think for both non small lung cancer and breast cancer.

<unk> core cohort of patients that we think we can improve our target product profile.

We have the opportunity to do.

That with additional indications inside the envelope much because that's what we want to make in the timeframe, we have to make that up there.

That will do that.

Alright, thanks for taking questions.

Thank you. Our next question or comment comes from the line of Brian Chin from J P. Morgan Mr. Chin. Your line is now open.

Hey, guys. Thanks for taking my question.

I think you have a couple of presentations coming up at SCR.

Next month, so what should our focus beat there from your presentation in your call. If you can give us some.

Maybe one just expectation that would be great.

I think everything.

Policy as well.

I think mark and secondly, there is some.

<unk>.

I think we're trying to showcase both the next product that's coming to the clinic next year I think are really important for us.

As well as continuing to show what the platform is capable of doing from products, John that because we're going to pick our targets and our products are going to file in 2045 this year.

Wanted people to understand the next product coming in the block of itself.

Additional new data we've generated.

Our R&D day presentation in October .

Try and highlight new and additional data, which has been developed which I think as always.

The understanding of what we're doing is differentiated and why are we doing and why or why we think we'll be successful with the product formats and the targets that we have.

Collected as well as the platform the ability to continue to generate.

Five new <unk> in the next five years, including 171 upon that one next year.

We'll all be novel diversified on both sides of the.

Our portfolio.

<unk>.

A multicenter.

Antibody therapeutics.

Yes.

As well as all be it will be differentiated and meaningful assets that we can keep unencumbered inventory solve as long as.

As long as possible. So I think there'll be a whole host of things there between products.

The two platforms that we're working right now there is also one.

John .

49.

Juan.

Unrelated to us.

That.

I know there'll be as abstracts.

A little over a week or so I think by double NPR. So.

I will answer more of that question is those abstracts are released.

And then next week or so and then beyond that obviously.

More information available on the focus for all.

All of those.

And maybe just one follow up on that.

Sandy sales side.

You talked about how pinpoints.

Partnership is too.

Program.

It seems that you are already in discussion with a couple of potential partners.

When do you think that it will be a good time to bring in a partner for <unk>.

Is there a bar that you need to hit.

For the phase two that you're doing and ask as CNR cell metastatic breast.

Do you need to head for before these are partners jumping in.

Yes, good question.

Obviously, we don't we do not have clinical data and comments, maybe 49 with other standard of care.

A big part of the value proposition for our development partners that we'd like to generate that.

That data obviously, having early partners vessels is crazy.

It helps.

Designing clinical programs, so we like doing that.

I think R. R.

We're an investment thesis around <unk> 49.

<unk> is not core to the five and five <unk>.

Could you be valuable assets that we'd like to invest incrementally in <unk>.

Phase II clinical development stage.

The goal after that is to get an ex U S partner.

To work with us if we get clinical data, which showed that the patient should go forward.

We'd like the terms of that you'd also be viable it up.

To fund the potential for us to retain the U S commercial rights and develop that further to market offer the partnering deal not off our balance sheet. So yes.

David the support partner being able to have a transaction with you.

It will allow us to be able to undertake that as well as <unk>.

Convinced ourselves that.

Even while undertaking.

To retain U S rights for further development.

Commercialization of any though ourselves and so we also have to reinvent ourselves.

There is the potential that we could do a global licensing deal with one party of that was attractive to us.

Because again it does not.

505 strategy, we have or non her two assets that were generating behind that.

And that is so.

I mean to get that I believe we need some indication.

As I mentioned thats going to be 49 can be effectively combined.

The standard of care and indications that matter.

And it shows.

Interesting signals of efficacy to show, there's a registration pathway for that agent to.

B, a second line agent or B, the second choice Hercules AEP behind <unk>, which is very commercially attractive.

Especially in non small cell lung cancer in the breast cancer indications.

Some of the other ones are still installed.

We're still evaluating I think some of that combination get is going to be necessary to convince.

Our partner on the value that we'd be looking for but also going into our developments of our philosophy.

To retain.

The U S.

Great. Thanks for taking my question.

Thank you.

Our next question or comment comes from the line of Charles Zhou from Guggenheim Partners.

Mr. <unk>. Your line is now open.

Hey, guys. Thanks for taking the questions.

My first one perhaps on Zen as any debtor mab in frontline gastric cancer I'm kind of wondering given that you've had that recent <unk> plus chemo data earlier this year as well as what we saw from <unk> 22 last year from Beijing I guess.

With the potential update from the single arm phase. Two later this year any color around like how much more confidence we could obtain around the potential additive clinical benefit of layering on a PD one on top of your regimen. Thanks.

Yes.

The easiest way to answer that question would be to complete the phase III study that's going on now which is fully randomized two one to one to one to try to chemo chemo doublet and triplet, including putting.

Thank you.

So the best place for US to answer that question is the hurdle of the patients studying redone the PFS and then from all of us.

Look at the sub population analysis.

I think this insight.

And be able to answer that question Thats what were working towards.

As expeditiously as we can obviously to deal with that on January pretty encouraging.

The kols and ourselves and drive in Beijing on on the doublet.

We will get a chance for an update on.

All data from the triplet.

You put out last year and get some more understand.

Understanding of what that looks like.

To be more patient numbers in that in the long term follow up so it might be something more to read into that but obviously the reason we're doing a large multinational randomized study.

As to try and provide clarity on the answer to that question that you have.

Got it great and maybe one more question on ASEAN is genies, though perhaps a bit of a follow up to something that's already been kind of asked a bit but during your prepared remarks, I think you had mentioned.

<unk> mentioned something about a pre determined benchmarks that could justify further development beyond the phase twos and long as well as posting her to breast cancer.

Any additional color around.

What those could possibly be or.

What was your thinking was.

Generating some of those benchmarks. Thank you.

Yes, I mean, we've obviously.

I'd like to start with on the Redetermination.

What does it mean.

Paul.

Looked like any combination in the indications arena studies so yes.

Some data.

David that we predetermine that we think.

Would be meaningful that would be encouraging.

Excellent partner and we gained purging process think about.

Retaining the oil price does any of those further.

Further develop it with the proceeds from an excellent partnership and use that as our first commercial entree into the U S.

We bring some of that ahead.

Head assignments that are really good.

Process to work through with the totality of data matters and quality.

<unk> and volume data matters.

But those are all pre determined that the same way that others will do and I think.

What's the general data, while some idea.

What we think about moving forward or which indications make the most of them.

Got it great. Thanks for taking the questions.

Yes.

We've done a lot of work since I got here a year ago on looking at the indication the commercial market reserves AD boards you saw we just did one recently in.

In Japan in January which weren't able to do earlier.

I have a pretty good sense from.

Potential partnering discussions and our Kols and our actions.

We're going to be 49 with <unk> to generate data.

Pet for moving forward.

Thank you again, ladies and gentlemen, if you have a question or comment at this time. Please press star one one on your telephone keypad.

Our next question or comment comes from the line of Andrew Berens from SBB Leerink. Mr. Bearings. Your line is open.

Alright, guys.

Couple of questions for me.

GW back combination of strategy of checkpoint can.

Can you share any preclinical data that you have that support our combination strategy.

Do you have any concerns that keratitis could be exacerbated by immunotherapy is ocular tox is.

Known side effect with checkpoint inhibitors, and then what do you think the regulatory strategy will eventually be demonstrate GW board that will be added in the background efficacy you would see with.

Checkpoint inhibitor alone.

Yeah. Good question I don't think we've disclosed any of the preclinical data we would have.

On the combination.

We don't believe there will be any.

Any further impact on the tariffs.

But it's one of the reasons you run combination studies.

And cohort five airplanes that we will we will do that to be able to confirm that obviously one of the benefits is going to be 49%.

Our two ADC is the tolerability issues that we have to deal with or are limited to grade one grade two keratitis, which don't cause.

Discontinuation.

Patients on it.

And.

Provide a substantial amount of dose reduction.

We don't have neuropathy.

Neuropathy pneumonitis trials, we haven't seen any signals of that.

So obviously, we think the tolerability profile means that you can.

Provide an effective combination without overlapping toxicities and we think there may be.

Synergies between.

PD, one and 40.

Pointed out inventory payload that might be from a mechanism standpoint.

We will have one abstract at ACR around some initial thoughts around the mechanism of TWD 49 that might provide some additional information to that.

Obviously going forward in non small cell lung cancer I mean, if you wanted to use there.

And a variety of different.

Indications, including and wasn't no known automobile patients. So there is some.

Good data already on existing around those.

Jose just that indication without a cap to show that adding 49 to that.

The PD one.

<unk> population.

<unk>.

Benefit.

Fourth Department.

Part of what we're doing in the design of the cohort that we have.

And both of them are expressing that hurts and amplify that hurts the mutant population.

Im also lung cancer.

In addition on the breast cancer side.

<unk> been very effective in its use.

Use.

Indication study in breast cancer, but.

There isn't.

PD, one PD one to be oriented on indication.

Because of this synergistic effect that might occur with your fab panels, and PD ones, we'd like to explore that before that clinically.

And look at that.

Thats accurate or not.

Okay. Thank you.

Thank you our next question or comment comes from the line of.

David Martin from Bloom Burton Mr. Martin Your line is now open.

Thanks for taking my questions.

First question regarding the phase III indications for CW <unk> 49.

You presented phase one data at ESMO last year.

I think there was one lung cancer patients there were relatively few in her two failures some few.

Or too low patients.

Post that presentation did you then kind of focus your recruitment on patients that fit the bill.

Two characteristics, we see larger cohort or larger groups of those patients and the updated data later this year.

Yes.

So obviously after the cut out for as we continue to recruit.

The phase one study in monotherapy.

Posted.

Weekly dosing, which we were doing with were add on.

But also to continue to recruit additional patients on monotherapy at.

The recommended phase two dose of $2 five megs per every three weeks.

And we focused on enrolling patients that were closer to.

Our strategy going forward in combination so.

Hopefully all of that data set which.

Which will put out we haven't given guidance yet.

For this year, but we'll do that as we as.

As soon as we're able to be specific.

Should see additional monotherapy data and activity.

Activity was going to be 49.

Some of those patient populations were would have been nice to see more before the ESMO.

And obviously.

That leaves a little bit of our thinking.

Forward into looking at the combination strategy.

A reasonable contribution taking much activity in the highest quality patients being on track.

In the study.

Okay great.

Will the fees to be randomized like I assume you'll do a dose escalation single arm initially, but then will be each turn into randomized trials.

Yes, we havent given any specifics.

The core design and we won't do that install upon.

<unk> Dot Gov, obviously, we're trying to.

Go quickly.

Regarding the resignation and the right cohort.

To answer the question as to whether we have a value proposition.

Or not.

And if we do then be able to move really quickly into registration pathway and so there's a lot of factors are considering how we are designing and executing these.

These studies, so I think once Suffolk control stock out we're happy to answer those.

Questions about why we designed the way we did.

Okay. Thanks, that's it for me.

Thank you.

Thank you I'm showing no additional questions in the queue at this time I would like to turn the conference back over to management for any closing remarks.

Okay well. Thank you. Thank you for your attention today and for your questions.

There's a lot of progress last year in <unk> and I think for 2023, we've got really good momentum across the business. We're really looking forward to having a great couple of ACR coming up in April .

Abstracts will be available publicly soon.

We're very encouraged to have 11 different abstracts accepted for.

For this meeting last year, we had zero.

So we're really looking forward to having a fulsome disclosure of the products and platforms and the early R&D group.

And the 505 strategy that we have and talking more about that and we look forward to.

They are doing that very quickly.

So thank you for your time and attention look forward to reporting more progress as we move forward through the year.

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program you may now disconnect everyone have a wonderful day.