Q2 2022 Bristol-Myers Squibb Co Earnings Call

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Good day and welcome to the Bristol Myers Squibb Second Quarter Results Conference Call.

Good day and welcome to the Bristol Myers Squibb second quarter results Conference call Today's conference is being recorded.

Today's conference is being recorded.

Thank you very much.

We've spent a lot of time working with Samit's team before approval to make sure that the, RIMS program generally was intuitive and fit into how cardiologists generally treat patients. And so far, that work up front, as well as the education we've done, is paying off.

This time I would like to turn the conference over to Mr. Tim Power Vice President Investor Relations. Please go ahead Sir.

Thanks, Sarah and good morning, everyone. Thanks for joining us this morning for our second quarter 2022 earnings call I'm.

At this time, I would like to turn the conference over to Mr. Tim Power, Vice President, Investor Relations.

A couple for Samit.

Cardiologists are generally seeing it as not a barrier. In fact, the fact that we have seen a large number of medium and small clinics get not, only RIMS certified, but get patients on to therapy, and in many cases get multiple patients on therapy, is an indicator of the fact that the RIMS program is by and large being seen as something that's very manageable for physicians and hasn't proven to be a barrier at all.

Please go ahead, sir.

First, in your Ducre Vicitinib FDA discussions to, date, has there been any mention of a box warning whatsoever, or has that not come up in any conversation?

I'm joined this morning.

Paired remarks by Giovanni for you our board Chair and Chief Executive Officer, and David Elkins, Our Chief Financial Officer, and also taking part in today's call are Chris Boerner, our chief commercialization officer.

Summit here, a lot of our Chief Medical officer, and head of global drug development.

Note that we've posted slides to BMS dot com that you can use to follow along with for Giovanni and David's remarks, before we get started I'll read our forward looking statements.

During this call, we'll make statements about the company's future plans and prospects that constitute forward looking statements actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward looking statements represent our estimates as of today and should not rely relied upon.

As representing our estimates as of any future date, we specifically disclaim any obligation to update forward looking statements. Even if our estimates change. We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items reconciliations of certain non-GAAP financial measures to the most comparable GAAP measures are available at BMS dotcom.

And I'll hand, it over now to Giovanni Thank you, Tim and good morning, everyone, let's start with our second quarter performance on slide four.

Thanks, Sarah, and good morning, everyone.

And also, given the timeframe involved, can we assume there won't be an adcom?

Moreover, I think that the RIMS program, when we designed it, was important to make sure, that patients are initiated and initiated safely and monitored over the course of their disease.

Thanks for joining us this morning for our second quarter 2022 earnings call.

I'm joined this morning with prepared remarks by Giovanni Caforio, our Board Chair and Chief Executive Officer, and by David Elkins, our Chief Financial Officer, and also taking part in today's call are Chris Berner, our Chief Commercialization Officer, and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development.

And then the second question is, based on available data, does Bristol think other cardiac myosin inhibitors will have a black box warning, or do you think they could avoid that?

And that's exactly how this process is playing out at this point.

We are midway through 2022, when we've made great progress during an important year for the company.

So very happy with respect to what we're hearing playback from physicians on RIMS.

You'll note that we posted slides to BMS.com that you can use to follow along with for Giovanni and David's remarks.

Thank you.

Thanks, Chris.

We continued to grow our inline franchises expand our new product portfolio advance our pipeline and execute important business development activities.

Before we get started, I'll read our forward looking statement. During this call, we will make statements about the company's future plans and prospects that constitute forward looking statements.

Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the company's SEC filings.

Thank you, Steve.

Sarah, can we go to our last question, please?

Our foundation is strong and positions us well for growth.

These forward looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date.

We specifically disclaim any obligation to update forward looking statements, even if our estimates change.

Before I ask Samit to answer both of your questions, let me just say, as you, know, we don't comment on ongoing discussion with regulatory authorities, but Samit will provide his perspective on both.

Yes.

With respect to our commercial performance, we delivered continued sales growth with revenue up 5% adjusting for foreign exchange and non-GAAP EPS, increasing by 18%.

We'll also focus our comments on our non-GAAP financial measures, which were adjusted to exclude certain specified items. Reconciliations of certain non-GAAP financial measures to the most comparable GAAP measures are available at BMS.com.

Samit?

We will take our last question today from Robin Karnopkis with Truist Securities.

The strong revenue growth was driven by excellent commercial execution with solid year over year growth for a while.

In line brands, particularly for <unk>, and our I O franchise and significant momentum from our new product portfolio.

And I'll hand it over now to Giovanni.

Yeah, thank you.

Thank you for taking my question.

Thank you, Tim, and good morning, everyone.

Steve, as Giovanni already mentioned, no specifics to be provided here.

All right.

Within our new product portfolio helped drive our third Io agent is off to a great start and we are pleased with the team's early execution.

What I can repeat, I think, from the past conversations we've had, is our confidence in the data itself for Ducre Vicitinib, when we think about from an efficacy perspective, differentiation and superiority that has been proven through the phase three trials versus with Tesla, from a safety perspective, showing differentiation when we think about the JAK inhibitors versus Ducre Vicitinib, first in plastic to inhibit, and this is that profile that has continued to evolve through multiple other trials that have given us other confidence to initiate the programs, as you know, in thoracic arthritis, two phase three trials ongoing, and also now looking forward to initiation of the SLE phase three trials at the end of the year, beginning of next year.

Let's start with our second quarter performance on slide four.

<unk> strengthens our position in I O and accelerates the sustainability and growth of our Io franchise.

We are also establishing a strong foundation for it comes Iris.

That's the first agent that effectively treats the underlying condition of symptomatic H.

P M.

We see a lot of potential to drive significant penetration in this large underserved and under diagnosed population.

We are midway through 2022, and we've made great progress during an important year for the company. We continued to grow our in-line franchises, expand our new product portfolio, advance our pipeline, and execute important business development activities.

We also made great progress advancing our broad set of pipeline opportunities through regulatory approvals and clinical trial readouts during the quarter.

So, quickly on Brionzi, I mean, our details didn't suggest still there's like a small, fraction, maybe 20% of people eligible that can get the drug.

In hematology, we received U S FDA approval for Brinci with a best in class label in second line large b cell lymphoma, as well as EMEA validation.

So given that you have a really broad label, you're going into second line, how do you, think you can improve this?

With this approval Rihanna. She now has the broadest patient eligibility of any car T cell therapy in relapse or refractory it'll be Seattle.

What steps are you taking to improve the vein-to-vein or brain-to-vein time?

This reinforces our opportunity for leadership in cell therapy, and further strengthens our view all brands is a key growth driver for the company with over 3 billion in or at least congested revenue potential in 2029.

And on Ducra, just a quick question there.

For the moderate patients, how are you viewing how it will be positioned versus Dermavant, or Arcutis' drug?

In cardiovascular we delivered positive phase II data for mill vaccine in secondary stroke prevention and we're looking forward to these data being presented at the European Society of Cardiology meeting next month.

The Tama came in at a lower price, pretty clean safety profile.

So, overall, we're looking forward to September 10th for Ducre Vicitinib and bringing this new medicine to patients.

How are you viewing any step edits that might be required there?

In a similar way, I would say, in the cardiac myosin inhibitors, it is difficult and not appropriate, probably, for us to comment on other people's drugs as to what the profile is going to look like and if they will have any warnings and precautions in the label or not.

What we can say, though, is, again, a belief in ChemXio, as already alluded to by Chris, as well, and David, in his remarks, our belief in the data and how physicians are acting in terms of getting trained and prescribing it to the patient.

So, overall, looking forward to initiation of our non-obstructive hypoglycemic cardiomyopathy phase three program towards the end of the year.

Thanks.

With these data in hand, we plan to initiate our phase III program by the end of the year.

Thank you.

Which provides an important opportunity to improve outcomes for patients and extend our war, leading antithrombotic business into the next decade.

In oncology, we continue to strengthen the growth outlook for Opdivo with another indication in Gi cancers, where he now has a leading position.

Our foundation is strong and positions as well for growth. With respect to our commercial performance, we delivered continued sales growth with revenue up 5%, adjusting for foreign exchange and non-GAAP EPS increasing by 18%. The strong revenue growth was driven by excellent commercial execution with solid year-over-year growth for our in-line brands, particularly for Eliquis and our I.O.

Thank you.

Thank you, Robin.

During the quarter, our financial results were strong with growth in our in line and new product businesses.

We'll go to the next question, please.

Our financial strength continues to provide us with significant flexibility to deploy capital in a balanced way including for business development.

And during the quarter, we announced an agreement to acquire turning point therapeutics, a leading precision oncology company.

On slide five let's discuss starting points lead us it or they bought Frac to name, which is a next generation potential best in class T. K I thought of getting that Ross and N. Frac driver mutations of non small cell lung cancer and advanced solid tumors.

Fortunately as you can see on this slide the key first line lung cancer data that has been announced for apples texture name is differentiated from potential competitors on duration of response and safety profile.

This acquisition will broaden our portfolio in precision oncology and in solid tumors and it is a strategic fit for the company. We expect the transaction to close in the third quarter of this year and believe it will support our medium to long term growth strategy with accretion to non-GAAP EPS and beginning in 2000.

25.

We plan to continue to leverage our financial strength to pursue transformational science through business development.

Turning to our execution scorecard on slide six we know the importance of continued delivery of key pipeline milestones and we have made tremendous progress across therapeutic areas. This year.

In addition to the key milestones I already mentioned for brands and their vaccine. We have reached mid to late stage pipeline and we are accelerating the next generation of all potential medicines.

Over time, we believe <unk> and Cc 480, or met met zinc bromide have the potential to play an important role in multiple myeloma.

In that regard we made good progress during the quarter having moved into.

Into its first Registrational trial in the second line setting of multiple myeloma.

Looking ahead I am encouraged by the breadth of opportunities for the rest of this year and beyond we look forward to the Baidu for date for new crop of CIT didn't even psoriasis in September .

We're excited for the opportunity to bring this oral of choice medicine to moderate to severe psoriasis patients soon with.

With multiple indications on the horizon beyond psoriasis, we believe that these asset has greater than 4 billion in laundry risk adjusted revenue potential in 2029.

In addition, we also expect to see data to support important expansion opportunities for other key medicines over time.

These include key data for our Beckmann Opdivo.

And rebel as will we.

We hope that these data will enable these medicines to benefit more patients and further expand the commercial potential.

I remain excited about the multiple opportunities we have across our pipeline and I look forward to continuing to update you on our progress.

franchise, and significant momentum from our new product portfolio.

As I review our performance during the first half of 2022, I'm very proud of the employees of Bristol Myers Squibb around the world together, we have built the foundation for an even stronger company with a more diversified portfolio of growth products and increased durability across each of our four key therapeutic areas.

Our performance in the quarter continues to demonstrate the resiliency of our business and our continued financial strength.

We believe this positions us well to continue to grow our business in an increasingly complex external environment. This includes microeconomic factors such as the strengthening U S dollar and accelerating inflation as well as legislative headwinds in the U S.

Within our new product portfolio, Optualag, our third I.O.

Given our growing and rapidly diversifying business and our continued financial flexibility, we remain very well positioned for the future with that I'll turn it over to David to walk you through the financials in detail David.

Yes, we'll go on to Seamus Fernandez with Guggenheim.

Oh, thanks for the question.

agent, is off to a great start, and we are pleased with the team's early execution.

So, just a couple of quick questions.

Chris?

Thank you Giovanni and thanks again for all of you joining our second quarter earnings call, let's turn to slide eight to discuss our solid topline performance.

Optualag strengthens our position in I.O. and accelerates the sustainability and growth of our I.O. franchise.

First off, you know, this is really for Giovanni.

We are also establishing a strong foundation for Kamzaius. As the first agent that effectively treats the underlying condition of symptomatic obstructive HCM, we see a lot of potential to drive significant penetration in this large, underserved, and underdiagnosed population.

You know, should Congress pass the Medicare pricing reform?

Sure.

We also made great progress advancing our broad set of pipeline opportunities through regulatory approvals and clinical trial readouts during the quarter. In hematology, we received U.S. FDA approval for Brianzi with a best-in-class label in second-line large B-cell lymphoma, as well as EMA validation. With this approval, Brianzi now has the broadest patient eligibility of any CAR T cell therapy in relapse or refractory LBCL. This reinforces our opportunity for leadership in cell therapy and further strengthens our view of Brianzi as a key growth driver for the company, with over $3 billion in non-risk adjusted revenue potential in 2029.

So, what I would say is that on Brionzi, I think in general, the focus that we have had, continues to be on, if your question is around continuing to improve on the manufacturing side, the focus there has been on making sure that we're focused really on three things.

In cardiovascular, we delivered positive phase two data for milvexian in secondary stroke prevention, and we're looking forward to this data being presented at the European Society of Cardiology meeting next month.

With this data in hand, we plan to initiate our phase three program by the end of the year, which provides an important opportunity to improve outcomes for patients and extend our world-leading antithrombotic business into the next decade.

And in oncology, we continue to strengthen the growth outlook for Opdivo with another indication in GI cancers, where it now has a leading position.

Otherwise stated all I will discuss our sales performance growth rates on an underlying basis, which excludes the impact of foreign exchange.

During the quarter, our financial results were strong, with growth in our in-line and new product businesses.

Can you just help us understand what impacts you think this is likely to have, whether it be on innovation, but also on your own long-term guidance from that perspective?

Second quarter revenues were approximately $11 $9 billion growing 5% year over year. This performance was driven by robust growth of our in line and new product portfolio of 16% more than offsetting a recent eloise, let's now double click on our new product portfolio performance on slide nine.

Our financial strength continues to provide us with significant flexibility to deploy capital in a balanced way, including for business development.

And, you know, are you hopeful that there might be, should this go through, potential changes that could temper the impact, perhaps, a push out of this small molecule argument of, you know, nine years of protection and perhaps maybe push that out to 12 or 13 years?

And during the quarter, we announced an agreement to acquire Turning Point Therapeutics, a leading precision oncology company.

On slide five, let's discuss Turning Point's lead asset, ripotrectinib, which is a next-generation potential best-in-class TKI, targeting the ROS and NFREC driver mutations of non-small-cell lung cancer and advanced solid tumors.

Just wondering if there are any opportunities to think a little bit more constructively about this.

Global revenues were nearly $500 million more than doubling revenue versus prior year growth over prior quarter was also very strong up 38%, primarily due to strong launches of a basketball and after a lag which I will touch on in a moment.

I'm very pleased with the performance of our new product portfolio and its future potential with two additional launches year to date and decrepit sitting as anticipated approval in six weeks, our new product portfolio, a significant expansion opportunities and the potential to generate greater than $25 billion in revenue on a non risk adjusted basis in 2029.

I look forward to updating you on these products as they continue to realize their full potential.

The performance of our solid tumor portfolio as shown on slide 10 was strong opdivo sales in the quarter continued to grow globally, driven by demand for our newly launched and core indications.

In the U S. We delivered 12% growth for Opdivo versus prior year, driven by demand in first line lung renal and gastric cancer as well as adjuvant esophageal and bladder cancers, partially offset by some fly up to like in first line melanoma.

Internationally revenues were also strong growing 13%, primarily due to growth from new indications, particularly first line lung and renal cancers.

We continue to secure reimbursement in many countries.

Looking forward, we expect continued growth throughout two vote from our new and expanding indications in both early and late stage cancers.

Your voice sales grew 7% globally and in the U S revenues were consistent with prior year as we experienced some variability in RCC of melanoma as well as higher inventory burn and gross to net adjustments this year.

Importantly, as you can see on the slide, the key first-line lung cancer data that has been announced for ripotrectinib, is differentiated from potential competitors on duration of response and safety profile.

Importantly, sequential revenues grew 5% primarily driven by demand in first line lung cancer and we continue to expect growth for the brand.

This acquisition will broaden our portfolio in precision oncology and in solid tumors, and it is a strategic fit for the company.

We expect the transaction to close in the third quarter of this year and believe it will support our medium- to long-term growth strategy, with accretion to non-gap EPS beginning in 2025.

Now to our strong launch of up do you like the first fixed dose combination of lag three and PD one inhibitor, while still early in the launch we have already generated $58 million of sales in the quarter, driven primarily by robust demand and $10 million of stocking.

The robust demand for up to like has mainly been in line with our strategy taking share from PD, one monotherapy and as expected some use in place of up do you have a year of boy combination.

Internationally, we were pleased with the recent C. H M. P positive opinion in Europe , and look forward to realizing optimize potential to be the new standard of care in patients with metastatic melanoma around the world.

Turning to our growing cardiovascular portfolio on slide 11, starting with Ela cliffs are leading <unk> globally with strong revenue growth of 20% year over year.

In the U S sales increased 27% versus prior year, driven primarily by demand growth and favorable gross to net adjustments.

As a reminder, looking to the third and fourth quarters, we expect the usual dynamics for Medicare coverage gap with second half revenues being lower than first half as we've seen in previous years.

Internationally sales grew 9% versus a year ago. This growth was primarily driven by increased share across key markets as the brand continues to be the number one or multiple countries.

This was partially offset by pricing actions in many markets as demand grows and to a smaller extent at risk generic launch in the U K and the Netherlands for the second half of the year, we expect the impact of at risk generic launch to be about $250 million.

Now turning to our most recent launch comes Iris as you know the vast majority of patients initiating treatment on campus hires are starting on a free trial offer for at least 30 days.

And then the $3 million recorded in revenue in the quarter was mainly due to stocking.

During the second quarter, we successfully laid the foundation leveraging our strong CV leadership in Rems certified over 1000 health care professionals. We are now focused on broadening our user base and supporting initiation of patient sometimes obvious we were pleased with the physician feedback thus far and look forward to helping more patients living with symptomatic.

H C M.

Moving onto a few of our hematology products on slide 12, starting with Revlimid sales in the quarter were approximately $2 $5 billion sales were primarily impacted by generic entry, particularly in international markets.

In the U S. While we did experienced demand softness from the volume limited generic entry in the quarter, we understand the specialty pharmacies are mainly utilizing the current generic for new patients to ensure continuity of treatment.

As mentioned in past, we know there will be variability quarter to quarter based on how generics will deploy their volume.

As additional entrants will be coming to the market in the U S. In the third quarter, we expect Q3 revenues to be approximately $2 $1 billion, we maintain our full year global sales guidance of $90 billion to $95 billion.

<unk> global revenues grew 9% versus prior year, primarily driven by demand for triple place regimens in earlier lines and extending duration of treatment.

Now moving to read those out which generated $172 million in the quarter up a strong 36% versus prior year in the U S. We're seeing encouraging trends in patient adherence and extent extended treatment duration.

So out of the U S. Rub also continues to grow driven by demand in both Mds and beta thalassemia associated anemia, and as we obtain reimbursement in additional countries.

First, on Brionzi, you have to, on cell therapy generally, you have to stay focused on operational, issues.

Finally, turning to our cell therapy assets at Beckman Brianti Beckman generated strong revenues in the quarter equaling $89 million. This represents a 36% sequential increase over last quarter, driven by expanded capacity and vector supply that.

Obviously, we spoke about the issue that hit the success rates with this program in the, quarter, but clearly, that's going to be one area of focus for us.

And as part of that, you obviously are continuing to stay focused on improving turnaround time, and that's a clear focus for the manufacturing team.

Above and beyond that, though, what I would say is most critical for us at this stage, in the launch for both Abecna and Brionzi is to continue to be focused on vector supply and drug product supply, continue to increase that.

So we encourage to treat more multiple myeloma patients demand continues to outpace supply and we are focused on further expanding capacity, including additional manufacturing sites in the future.

As it relates to the sales in the quarter were $39 million demand remains strong for the brand or the sales were impacted by lower than expected manufacturing Successories, which now have been addressed importantly, as Giovanni mentioned, we are very pleased to have received a differentiated broad second line label and large b cell lymphoma patients.

We're working hard with health authorities to increase capacity on drug supply for Brionzi, at our existing facilities.

We're working hard and investing to expand capacity early next year to enable uptake for this indication as we work through building additional capacity to treat more patients in earlier lines. We expect revenues in the third and fourth quarters to be largely similar to the first quarter of this year.

We're also bringing on two state-of-the-art facilities in Devens, Massachusetts, and at, Leiden's in the Netherlands that I think are going to be an important component of how we continue to expand the capacity for that product coming into the first part of next year.

Moving on to immunology product summary on slide 13, our rents your global sales grew 11% versus prior year due to expanded U S sales driven by increased market share as well as demand in international markets.

Turning to suppose your global sales for the quarter was $66 million more than doubling sales versus last year, primarily due to the expansion of suppose you into ulcerative colitis.

Sequentially in the U S sales were primarily driven by a combination of favorable gross to nets.

And wholesaler buying patterns of approximately $20 million.

Importantly, we are encouraged by the 24% demand growth over the previous quarter and we remain focused on working to further expand by them. So we can continue to improve access in 2023 inter.

Internationally as Appose your continues to secure reimbursement in other markets for M. S. N U C.

And then, separately, you know, hoping to just get a little bit of, you know, color on the launch dynamics around Ducrevicitinib.

And then with respect to Ducravacitinib, I think the focus as we look at Ducravacitinib, is first and foremost recognizing that the most important thing with this asset, as you think about access generally, is going to be the value story that you have to tell.

And we have a very strong story to tell with Ducravacitinib.

Closing out on immunology, we very much look forward to broadening our portfolio with another first in class asset our selective <unk> inhibitor to Travis sitting at our commercial and medical teams are in place and we're ready for launch.

You know, you guys are commenting on your enthusiasm to kind of get this product to, market and to patients.

As I mentioned earlier, we anticipate demand is going to be strong for this.

Just wanted to get a better sense of, you know, should the label actually have a jack-boxed warning, you know, which we don't necessarily anticipate, but should that occur?

Also recognize that you have two phase three studies that show head-to-head data against, the current standard of care for the patients who are being treated with moderate to severe psoriasis.

You know, what are you hearing from physicians with regard to the opportunity to kind of work around that?

Maybe just as a clarifying question, we've gotten a lot of questions from investors on the possibility that if there were a jack warning, could it actually be post-biologic?

So we have a very strong story to tell with payers.

And then in terms of those dynamics, I'm actually less concerned about competition with topicals, in particular, because, remember, a lot of topicals are going to stay on board as you move into oral therapies and psoriasis.

Now, let's turn to slide 14 to discuss the second quarter P&L I've already discussed our revenue. So I'll now focus on the other key line item non-GAAP nine Oh line items.

Doesn't make a lot of sense to us.

Gross margins decreased primarily due to product mix, partially offset by foreign exchange and related hedging settlements.

Our operating expenses, excluding acquired in process R&D were broadly in line with prior year, driven by higher investments around our new product portfolio and pipeline offset primarily by foreign exchange.

Acquired in process R&D charges in the quarter were $400 million, primarily driven by the buyout of our royalty obligation for Ken XI is a $295 million as well as the $90 million upfront for bridge bio.

This accounted for 17% impact to diluted EPS.

In process R&D charges in the prior year were approximately $793 million, which accounted for a 30 cent impact to diluted EPS.

The second quarter.

Tax rate was impacted by earnings mix and lastly, we delivered strong non-GAAP EPS growth in the quarter up 18% year over year. This includes the 14th that impact of acquired in process R&D, excluding acquired in process R&D non-GAAP EPS would have grown 7%.

Just wondering where you guys stand on that, you know, proposal.

So I think the dynamics that we're most looking at are, first, making sure that we provide, very quick access for patients who have plans with open access. And as we talked about last quarter, in this market, as opposed to other markets that we've, talked about, many patients are covered by plans that will have open access at launch.

Now moving to the balance sheet and capital allocation on slide 15, the company's balance sheet remained strong with $13 $2 billion in cash and marketable securities on hand as of June 30th.

And then, obviously, we're going to have to continue to build volume in order to expand, coverage for those plans that don't have open access at launch.

And there it's going to be all about driving volume and then leveraging that volume to, get into a better access position overall.

Thanks so much.

Thank you Chris and you know from my perspective let me just say again that what we are hearing, from physicians all the time is that they consider Brianzi as the best-in-class CD19 CAR-T and I look forward to the opportunity to have a significant increase in capacity, at the beginning of next year which will be important for us.

Cash flow from operations in the first half of the year was $6 $1 billion in the quarter. It was approximately $2 $3 billion, which was impacted by a cash tax payment and we expect cash flow from operations to rebound in Q3 and Q4.

Our capital allocation priorities remain unchanged business development continues to be a top priority and we continue to execute on this priority with the announcement of the planned acquisition of turning point therapeutics.

We plan to continue to leverage our financial strength to pursue transformational science through business development.

We remain committed to continued debt reduction in the quarter, we repaid $2 $9 billion of debt.

We remain committed to returning capital to shareholders.

Executed a $5 billion ASR earlier this year on being opportunistic about repurchases in the future.

Turning to our execution scorecard on slide six, we know the importance of continued delivery of key pipeline milestones, and we have made tremendous progress across therapeutic areas this year.

Thank you, Seamus.

In addition to the key milestones I already mentioned for Brianzian-Milvexian, we have a rich mid- to late-stage pipeline, and we are accelerating the next generation of potential medicines. Over time, we believe ibridomide and CC480 or mezigdomide have the potential to play an important role in multiple myeloma. In that regard, we made good progress during the quarter, having moved ibridomide into its first registrational trial in the second-line setting of multiple myeloma.

Now turning to our 2022 non-GAAP guidance on slide 16.

I am encouraged by the breadth of opportunities for the rest of this year and beyond.

Let me start on pricing reform and then Chris will comment on Ducrovost-Suttonib.

We look forward to the PDUFA date for the cravacidinib in psoriasis in September.

We are updating our revenue guidance to be approximately $46 billion. This year, reflecting the significant appreciation of the U S dollar to other global currencies.

We're excited for the opportunity to bring this oral of choice medicine to moderate to, severe psoriasis patients soon.

With multiple indications on the horizon beyond psoriasis, we believe that this asset has, greater than $4 billion in non-risk-adjusted revenue potential in 2029.

In addition, we also expect to see data to support important expansion opportunities, for other key medicines over time. These include key data for abecma, obdivo, obdulag, and reblozone. We hope that this data will enable these medicines to benefit more patients and further expand, their commercial potential.

Excluding the effects of currency the underlying sales growth for the business expected to be 2% versus 'twenty 'twenty. One we estimate the FX impact full year sales at today's spot rate to be about $1 $5 billion.

We continue to expect our in line and new product portfolio to grow in the low double digit range and reaffirm our L O guidance, including Revlimid guidance of $90 billion to $95 billion for the year.

Gross margin is expected to be approximately 79% up 100 basis points from previous guidance due to favorable impact of currency and related hedging settlements our operating expense guidance. Excluding acquired in process R&D remained unchanged declining in the low single digits versus prior year. This is primarily driven by favorability in EF.

<unk> as well as cost discipline in terms of phasing for the second half of the year, we expect a more even phasing of expenses than in prior years.

All said, we are reaffirming our non-GAAP adjusted EPS guidance based on the underlying strength of our portfolio mitigating currency translation from our natural hedges and hedging program.

I remain excited about the multiple opportunities we have across our pipeline, and I look forward, to continuing to update you on our progress.

So first of all, as you know, discussions are ongoing in Congress and it's difficult, to speculate exactly on the bill and some of the details that will be included in the bill.

Now more broadly I want to thank all of you for participating in the call.

Before we move to Q&A I, just want to express my gratitude to all our colleagues around the world for continuing to deliver strong commercial clinical and financial results.

As I review our performance during the first half of 2022, I'm very proud of the employees, of Bristol Myers Squibb around the world. Together, we have built the foundation for an even stronger company with a more diversified, portfolio of growth products and increased durability across each of our four key therapeutic areas.

This was a strong quarter for the company.

Zillionths Hoover company and exciting catalysts ahead like me energized by the growth opportunity ahead of US I'll now turn the call back over to Tim and Giovanni for Q&A. Thanks.

Our performance in the quarter continues to demonstrate the resiliency of our business, and our continued financial strength.

We have good momentum with our in-line business that are very positive dynamics with our new, product portfolio and that positions as well for the second half of the year which again will be very important for the company.

We believe these positions as well to continue to grow our business in an increasingly complex, external environment.

There will also be, obviously, a long period during which implementation of some of the measures will be clarified and some of the dynamics will be really important to understand.

I look forward to continuing to answer your questions and our IR team will be available, for any follow-up you have.

This includes macroeconomic factors such as the strengthening U.S. dollar and accelerating, inflation as well as legislative headwinds in the U.S.

Thanks, David sorry, because we go to our first question. Please.

Given our growing and rapidly diversifying business and our continued financial flexibility, we remain very well positioned for the future.

With that, I'll turn it over to David to walk you through the financials in detail.

So with respect to your question on would there be an impact to innovation.

So thanks again and have a good day.

So first of all, we've consistently said that the elements of reform that improve affordability, for patients we are supportive of.

Thank you I'd like to ask a question. Please take note by pressing star one on your telephone keypad.

And so as an example, the redesign of the Part D benefit and establishing an out-of-pocket cap for patients, that's very beneficial and we are definitely very supportive of that.

There are elements in the bill, however, which are obviously very detrimental to innovation and particularly price setting by the government at 9 and 13 years, obviously have the potential to have a negative impact on innovation overall.

I would say that with respect to the impact for our company, there's two things I can, say at this point.

First of all, it's really not helpful to look at our exposure to the channel today.

I think it's important to really understand the dynamics that will develop over the next few years before these policies are implemented.

David?

And a couple of things I'd like to say, first of all, obviously, as you know, rev limit revenues in the U.S. are declining rapidly.

Eloquence, we share that 50% with Pfizer.

Thank you and that does conclude today's teleconference.

And then importantly, as you think about Obdivo, that loses exclusivity at the end of the decade.

If you're using a speaker phone. Please make sure. Your mute function is turned off Hawaii was taken up to reach our commitment again that is star one to ask a question, we'll pause for just a moment to allow everyone in our opinion signup for cluster.

So what I can say is that our rapidly diversifying portfolio and a significant number of new medicines that we're launching today and would be launching before some key elements of this policy are implemented, position us well to navigate the challenges associated with reform for the entire industry.

Thank you, Giovanni, and thanks again for all of you joining our second quarter earnings, call.

But obviously, there is much more than we need to learn, first of all, through a potential finalization of the bill.

We do appreciate your participation.

Let's turn to slide 8 to discuss our solid top-line performance.

And second, really understanding better some of the elements of its implementation.

And we'll take our first caller from Chris.

<unk> with Goldman Sachs.

Okay.

Unless otherwise stated, I will discuss our sales performance growth rates on an underlying, basis, which excludes the impact of foreign exchange. Second quarter revenues were approximately $11.9 billion, growing 5% year over year. This performance was driven by robust growth of our inline and new product portfolio of, 16%, more than offsetting our recent LOEs.

So maybe I'll pick up, Seamus, on the question regarding Ducrapacid Nib and the launch.

Hi, This is Dan on for Chris. Thanks for taking our question two from US first on the mill vaccine read out if you could maybe frame some areas of focus into the ESC data and provide any additional color into how you're thinking about the phase III program that the data is in house and then second on Kenzie, Yes, if theres any.

Additional feedback you can provide on some of the early launch dynamics and your expectations into the second half of the year and early next year. Thank you.

Let's now double-click on our new product portfolio performance on slide 9.

So, we're, as you know, very excited about the opportunity to launch this product.

Global revenues were nearly $500 million, more than doubling revenue versus prior year. Growth over prior quarter was also very strong, up 38%, primarily due to strong launches of, APECMA and OptiLag, which I will touch on in a moment.

Thank you Dan.

Some it will answer your question on mill vaccine and Chris provide some some incremental Carl comes Iris. Thanks.

As was referenced previously, the commercial and medical teams are in place. They're ready to go.

Thank you Giovanni and thank you Dan for the question Alexia uncertainty looking forward to having the data presented at ESC in discussing our results and of course I as you know.

The detailed with all the specifics of the data itself, but I think the two questions that probably are important to answer them.

When we look at the data and that would be ones related to the efficacy specifically when it comes to impact on.

Clinically Oh ischemic strokes in the second of course is to look at our bleeding rates and more specifically over there one that physicians and patients would be interested to know about would be probably the later to in trucking it bleeds rare patients with strokes.

Tends to be to have a b as well as you.

Okay.

And so those are the kinds of questions that we set out to answer and I think those are the questions that people, who got interest you know before Tim dialect any pocket on to Chris.

They're very experienced.

Yes, I could take it to.

Thanks, Amit and thanks, Dan for the question. We are very pleased with the early launch of <unk>, while it's still very early days, we're off to a very good start and what I would say is that by and large the performance that we're seeing is aligned to our expectations and I would highlight maybe two or three things first awareness is very good we've seen it.

I'm very pleased with the performance of our new product portfolio and its future potential, with two additional launches year-to-date and Ducravacit and its anticipated approval in six weeks. Our new product portfolio has significant expansion opportunities and the potential, to generate greater than $25 billion in revenue on a non-risk-adjusted basis in 2029.

I look forward to updating you on these products as they continue to realize their full potential.

The performance of our solid tumor portfolio, as shown on slide 10, was strong.

Optiva sales in the quarter continue to grow globally, driven by demand for our newly launched, and core indications.

In the U.S., we delivered 12% growth for Optiva versus prior year, driven by demand in first-line lung, renal, and gastric cancer, as well as adjuvant esophageal and bladder cancers, partially offset by some OptiLAG and first-line melanoma.

You know, what I've said previously, I think, is where we'll start this conversation, which is that we explore every meaningful scenario as we think about the launch of any new product.

Internationally, revenues were also strong, growing 13% primarily due to growth from new indications, particularly first-line lung and renal cancers.

As we continue to secure reimbursement in many countries.

But we continue to index heavily on the scenario where we think that the preclinical and clinical data support. And that is that this is a unique mechanism of action that is clearly differentiated from other products in the class.

Looking forward, we expect continued growth from Optiva from our new and expanding indications in both early and late-stage cancers.

Year-over-year sales grew 7% globally.

And actually, when we talk to customers, we get an almost uniform alignment that that's the right way to think about Ducrapacid Nib, that the mechanism, based on all of the data that we've seen, is unique and it is differentiated.

And in the U.S., revenues were consistent with prior year, as we experienced some variability in RCC and melanoma, as well as higher inventory burn and grossed to net adjustments this year.

It's differentiated not only from Jax, but it's differentiated, most importantly, from the current standard of care for oral agents treating moderate to severe patients.

Incredibly strong enthusiasm for the product from both physicians and patients importantly, the feedback that we're getting on the clinical program has been overwhelmingly positive and consistent I'm going to give you something yet on that patients are seeing significant benefit both in terms of feel and function and that benefit is being seen.

Importantly, sequential revenues grew 5%, primarily driven by demand in first-line lung cancer.

And we continue to expect growth for the brand.

Now to our strong launch of OptiLAG, the first fixed-dose combination of a LAG-3 and PD-1 inhibitor.

While still early in the launch, we have already generated $58 million in sales in the quarter, driven primarily by robust demand and $10 million of stocking.

The robust demand for OptiLAG has mainly been in line with our strategy, taking share from PD-1 monotherapy and, as expected, some use in place of Optiva-Urobory combination. Internationally, we are pleased with the recent CHMP positive opinion in Europe and look forward to realizing OptiLAG's potential to be a new standard of care in patients with metastatic melanoma around the world.

Moving to our growing cardiovascular portfolio on slide 11, starting with Eliquis, our leading OAC globally, with strong revenue growth of 20% year-over-year. In the U.S., sales increased 27% versus prior year, driven primarily by demand growth and favorable gross to net adjustments.

As a reminder, looking to the third and fourth quarters, we expect the usual dynamics from Medicare coverage gap, with second-half revenues being lower than first half, as we've seen in previous years.

Internationally, sales grew 9% versus a year ago. This growth was primarily driven by increased share across key markets, as the brand continues to be the number one OAC in multiple countries. This was partially offset by pricing actions in many markets as demand grows and, to a smaller extent, at-risk generic launch in the U.K. and the Netherlands.

For the second half of the year, we expect the impact of at-risk generic launch to be about similarly $250 million.

Now, turning to our most recent launch, ChemZios.

As you know, the vast majority of patients initiating treatment on ChemZios are starting on a free trial offer for at least 30 days.

And then the $3 million recorded in revenue in the quarter was mainly due to stocking.

Very early in fact as early as four weeks post initiating treatment.

And that's really important because it's driven a lot of enthusiasm both from patients and its giving physicians a reason to believe that the product is living up to the promise that we have in terms of physician experience. The feedback has been very positive the rems education that we've.

During the second quarter, we have successfully laid the foundation, leveraging our strong CV leadership in REMS to certify over 1,000 healthcare professionals.

Initiated as intuitive getting on and certified for Rems has been straightforward and as David mentioned, that's translated to over 1400, H C piece being Rems certified and one thing I would highlight is that this is probably the most important leading indicator for for this product launch given the fact that you don't have that.

We are now focused on broadening our user base and supporting the initiation of patients on ChemZios.

We are pleased with the physician feedback thus far and look forward to helping more patients living with symptomatic OHCM.

Moving on to a few of our hematology products on slide 12, starting with Revlimid, sales in the quarter were approximately $2.5 billion. Sales were primarily impacted by generic entry, particularly in international markets. In the U.S., while we did experience demand softness from the volume-limited generic entry in the quarter, we understand that specialty pharmacies are mainly utilizing the current generic for new patients to ensure continuity of treatment.

As mentioned in past, we know there will be variability quarter-to-quarter based on how generics will deploy their volume.

As additional entrants will be coming to the market in the U.S. in the third quarter, we expect Q3 revenues to be approximately $2.1 billion.

We maintain our full-year global sales guidance of $9 to $9.5 billion.

Pomelo's global revenues grew 9% versus prior year, primarily driven by demand for triple-base regimens in earlier lines and extending duration of treatment.

Now moving to Revlozel, which generated $172 million in the quarter, up a strong 36% versus prior year.

History of Rems in the cardiovascular space physicians are going to be Rems certified if they haven't tend to use the last thing I would highlight is we're seeing a healthy increase in the number of centers prescribing week over week, we don't see any access issues on the horizon that would prevent these patients who are getting onto therapy converting to drug and so like.

And so as we step back and think about this product, we anticipate very strong demand for Ducrapacid Nib based on the clinical profile from two phase three studies that show clear superiority relative to the existing standard of care.

We have a unique mechanism of action that's clearly differentiated and we think positions us well to become the oral branded of choice for these moderate to severe psoriasis patients.

Sum it up our performance is in line with expectations, we're happy with what we're seeing and we very much look forward to the continued uptake of this product over the course of the year.

In the U.S., we're seeing encouraging trends in patient adherence and extended treatment duration.

Outside of the U.S., Revlozel continues to grow, driven by demand in both MDS and beta thalassemia-associated anemia, and as we attain reimbursement in additional countries.

And as was implied in the premise of your question, we're very excited to launch this product, Thank you Chris.

Great. Thanks, Chris can we go to the next question. Please.

Sarah, could we go to the next question please?

Absolutely.

Thank you and next we'll take Andrew Baum with Citi.

Finally, turning to our cell therapy assets, Abecma Embryonzy.

Next we'll take Luisa Hector with Berenberg.

Abecma generated strong revenues in the quarter, equaling $89 million. This represents a 36% sequential increase over last quarter, driven by expanded capacity and vector supply.

Hello.

Thank you.

Though we encourage to treat more multiple myeloma patients, demand continues to outpace supply, and we are focused on further expanding capacity, including additional manufacturing sites in the future.

Thank you for taking my question.

As it relates to Embryonzy, sales in the quarter were $39 million. Demand remained strong for the brand, although sales were impacted by lower-than-expected manufacturing success rates, which now have been addressed.

First question on the old axiom.

Importantly, as Giovanni mentioned, we are very pleased to have received a differentiated, broad second-line label in large B-cell lymphoma patients.

We are working hard and investing to extend capacity early next year to enable uptake for this indication.

Is there any possibility you could expedite what's going to be a very large and long duration clinical trial program through the adoption of <unk>.

As we work through building additional capacity to treat more patients in earlier lines, we expect revenues in the third and fourth quarters to be largely similar to the first quarter of this year.

Moving on to our immunology product summary on slide 13, Orenthia global sales grew 11% versus prior year due to expanded U.S. sales, driven by increased market share, as well as demand in international markets.

Turning to Zyposia, global sales for the quarter were $66 million, more than doubling sales versus last year, primarily due to expansion of Zyposia into ulcerative colitis.

Sequentially in the U.S., sales were primarily driven by a combination of favorable growth to NETs and wholesale buying patterns of approximately $20 million.

Importantly, we are encouraged by the 24% demand growth over the previous quarter and remain focused on working to further expand volume so we can continue to improve access in 2023.

Internationally, Zyposia continues to secure reimbursement in other markets for MS and UC.

Closing out on immunology, we very much look forward to broadening our portfolio with another first-in-class asset, our selective TIK2 inhibitor to crevacitinib.

Our commercial and medical teams are in place, and we're ready for launch.

Now let's turn to slide 14 to discuss the second quarter P&L.

MRI defined sided stroke within the composite endpoint either to expedite and travel to decrease the adding the quad for the trials.

I've already discussed our revenues, so I'll now focus on the other key non-GAAP line items. Gross margins decreased primarily due to product mix, partially offset by foreign exchange and related hedging settlements.

Our operating expenses, excluding required in-process R&D, were broadly in line with prior year, driven by higher investments around a new product portfolio and pipeline, offset primarily by foreign exchange.

Acquired in-process R&D charges in the quarter were $400 million, primarily driven by the buyout of a royalty obligation for Ken Zayas of $295 million, as well as a $90 million upfront for BridgeBio.

This accounted for a 17% impact to delayed EPS. Acquired in-process R&D charges in the prior year were approximately $793 million, which accounted for a $0.30 impact to diluted EPS.

The second quarter tax rate was impacted by earnings mix.

Second could you comment on whether you are exploring your 18.

And lastly, we delivered strong non-GAAP EPS growth in the quarter, up 18% year over year. This includes the $0.14 impact of acquired in-process R&D. Excluding acquired in-process R&D, non-GAAP EPS would have grown 7%.

Now moving to the balance sheet and capital allocation on slide 15.

The company's balance sheet remains strong, with $13.2 billion in cash and marketable securities on hand as of June 30th. Cash flow from operations in the first half of the year was $6.1 billion. In the quarter, it was approximately $2.3 billion, which is impacted by a cash tax payment, and we expect cash flow from operations to rebound in Q3 and Q4.

Our capital allocation priorities remain unchanged. Business development continues to be a top priority, and we continue to execute on this priority with the announcement of the planned acquisition of Turning Point Therapeutics.

We remain committed to continued debt reduction.

In the quarter, we repaid $2.9 billion of debt, and we remain committed to returning capital to shareholders. We executed a $5 billion ASR earlier this year and remain opportunistic about repurchases in the future.

19 Dmitry.

Now turning to our 2022 non-GAAP guidance on slide 16. We're updating our revenue guidance to be approximately $46 billion this year, reflecting the significant appreciation of the U.S. dollar to other global currencies.

Excluding the effects of currency, the underlying sales growth for the business is expected to be 2% versus 2021. We estimate the FX impact to full-year sales at today's spot rate to be about $1.5 billion.

Coffee excuse me be empty auto immune indications given some of the recent data.

We continue to expect our in-line and new product portfolio to grow in the low double-digit range, and reaffirm our LOE guidance, including revelments guidance, of $9 to $9.5 billion for the year. Gross margin is expected to be approximately 79%, up 100 basis points from previous guidance, due to favorable impact of currency and related hedging settlements.

Our operating expense guidance, excluding required in process R&D, remain unchanged, declining in the low single digits versus prior year. This is primarily driven by favorability in FX, as well as cost discipline.

In terms of phasing for the second half of the year, we expect a more even phasing of expenses than in prior years.

All said, we are reaffirming our non-gap adjusted EPS guidance based on the underlying strength of our portfolio, mitigating currency translation from our natural hedges and hedging program.

Yeah.

And then finally one of your competitors.

Hum.

Drinking daycare vehicle might be calculated lake pool.

That's got a lot more hands up.

Bristol has won it.

If you could provide us any update on that.

Before we move to Q&A, I just wanted to express my gratitude to all our colleagues around the world for continuing to deliver strong commercial, clinical, and financial results.

No.

The resiliency of our company and exciting catalysts ahead make me energized by the growth opportunity ahead of us.

I'll now turn the call back over to Tim and Giovanni for Q&A.

Thank you Andrew I'll ask Samit to answer your three questions.

Thanks, David.

You showed your slide on business development, highlighting the importance there.

Sarah, could we go to our first question, please?

I just wanted to check, has there been any shift in the activity, the trends in companies coming to you versus you approaching other companies?

Thank you.

Just any more recent trends given the longer duration now of suppressed valuations, just whether you're seeing any shift in those dialogues that you're having with targets.

Yes, Thank you Johnny and thank you Andrew a very thoughtful questions as always.

If you would like to ask a question, please signal by pressing star 1 on your telephone keypad.

If you're using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment.

Thank you.

Thanks Luisa.

I would say nothing has changed there.

It continues to be an area of great focus for us.

They're not obviously, you're going to get into the phase III indications right now.

But from a phase II perspective.

Can you get to see the data and what is important is from a physician's perspective, what matters really is the clinical strokes and those certainly will be the questions to discuss all.

When the data presented on the CD 19 side, certainly very intriguing data and the other immune disease, especially in the UK.

Patients who are severely impacted by the disease. Those are the things that we are continuing to discuss from a scientific perspective, how to explore ways to explore and certainly not hidden from us and as we evolve in our thinking there.

We're looking at bringing new science into the company.

Sure.

Everyone wherever you are going to that the judge the German data already thinking I have to say and as we presented earlier this year.

You are right, the valuations are resetting now for a longer period of time and we plan on continuing to be very active in this field.

It's always been a priority for us.

Thanks Giovanni.

<unk> seen the data on CRC from Oh from a competitor from our perspective, we have see a delay for antibodies and developing demand peoples related pro body as well as the obstacles. They put bodies. So there are three that are in development. The way. We think about it is number one we have an ongoing study in M. S. N E R sleep on that.

Can we go to the next question please?

You know like we just initiated the abdulla lag compared them to the standard of care and for our future developments Forsythia Newport antibodies do you have to think about combination strategies, because we know that many of times even in the past and single agents have been used in response rates ultimately in registration trials have really been single digit low single.

In fact, so we will obviously be able to share the data. Once we have these combination studies completed are there currently ongoing too early to talk about the data at this time, but certainly of that up with you guys.

Thank you.

Thank you Simon.

We'll move on to Tim Anderson with Wolf Research.

Can we go to the next one please.

Again, that is star 1 to ask a question.

Hi.

Well take our next question from Geoff Meacham with Bank of America.

Yeah.

Hey, guys. Thanks, so much for the questions had a commercial one and in the pipeline one Chris on ROE blows, though can you talk about the the U S trends you know what the duration of therapy look like today.

Let's say a year ago and it does demand support upside.

So your peak forecast.

And then some.

Or Giovanni I know, turning turning point hasn't closed yet, but you know how much of the focus is.

And we'll pause for just a moment to allow everyone an opportunity to signal for questions.

I have a question on Milvexian, which is historically when companies have added together anti-platelet therapies or anti-coagulant therapies to try to achieve better results, it pretty much always results in higher bleeding and that calculation is whether that higher bleeding is more than offset by higher efficacy.

So in an SSP setting, just theoretically ignoring any data you already have at hand, shouldn't we expect that same sort of thing where we would likely see at least some additional bleeding, and then we'd have to weigh it against efficacy or is it in the realm of possibilities that you really don't see any additional bleeding in that triple therapy arm?

As I O plus targeted therapy four for Bristol looking forward I know you Ross, one combos or probably more likely than not to come to play out in the pipeline, but beyond that do you guys see this as sort of a new a new type of modality.

And then on tick two, you guys expressed high confidence in the molecule, wondering why you haven't advanced yet to mild to moderate patients.

Just sort of a bolt on to an Io Io strategy. Thank you.

Thank you, Jeff Chris why don't you start on <unk>.

And then summit will comment on our oncology.

I'll call. It just strategy yeah. Thanks for the question Jeff.

If you're fairly confident in the label, why not push ahead in phase three and start to expand the market like what Tesla has already done?

We are pleased with the continued uptick that we're seeing with rebels, though we had good growth in the quarter versus prior year as well as sequentially I would highlight a few things first we're continuing to see good acquisition of new paid patients for this product one of the things that we look very carefully at is what are physicians perceptions of the product and importantly, how quickly.

Thank you, Tim.

Let me just ask Sameh to answer your question both on Milvexian and also plans for Ducrovacetinib.

Thank you and certainly looking forward to, again, the presentation of the Milvexian data.

I obviously cannot get into specifics of the data itself, but let me just reiterate that the two questions that would be important from everybody's perspective is on the efficacy, looking at the clinical strokes.

And secondly, from a bleed perspective, it becomes very important what kind of bleed, and especially when we think about the fatal bleed, intracranial bleed, meaningful bleed that become important.

If you look at the past, what you will see is those kinds of things that made people a little bit worried.

So again, we can discuss more when we have the data presented at EHC around Milvexian.

On tick two, certainly we are very pleased with the profile for the oral tick two inhibitor that has obviously evolved and continues to evolve in multiple other indications as well.

As we look to the mild to moderate psoriasis, as you said before, we are looking to bring in the topical formulation.

The phase two trials are about to begin from the phase two or from the tick two perspective, and that's our foray into the mild to moderate psoriasis.

They're moving patients off of Esa is to get onto <unk> therapy that time on Esa is when patients are not getting an adequate response continues to shorten which is a leading indicator of the number of patients that will be within the indication that we have and importantly were seeing nice trends in both dosing and administration the.

As you know, the pleuritic trial was conducted in the moderate to severe plaque psoriasis patients, and then, of course, multiple phase three trials in various indications.

First of all, in pleuritic arthritis that are ongoing, and then SLE starting later this year, and phase two trials that are ongoing in UC as well as in chronic disease.

Thank you.

Thank you.

Average M D S dose by cycle has grown steadily during the course of this launch and has increased this year. That's resulted in improved efficacy and longer duration of therapy, which to your question is been up 6%. This year relative to where we were in 2021 and while your question was mainly focused I think on the U S. I would highlight that ex U.

The launch is early but we're seeing very good uptake in the early launch markets, notably markets.

Like Germany, and then we will have additional access and reimbursement decisions ex U S. So overall, we feel very good about where we are and we look forward to continued uptake of this product as we go through the remainder of the year.

And thanks, Chris and Jeff Bob maybe I can take on the turning point question. So first of all excited about the acquisition marked a turning point therapeutics.

Looking forward to bringing that protecting it to patients in the second half of next year.

Around the combination those are all going to be always data dependent and so exploration will continue although at this time certainly there is a lot of mileage and lots of emergence of data geeky I combinations of tyrosine kinase inhibitors, which are not necessarily mutation specific titles and kind of just which have.

Generally a lot of interest and a lot of data and had been approved in multiple indications when combined with Io therapies, but it does provide additional opportunity in the future to look at.

These sorts of combinations and more specific a prespecified populations and selected patient populations, but those are the data that we generated at the current time too early to tell.

Thank you Simon.

Eric can we go to the next question. Please.

And we'll take our first caller from Chris Schupatini with Goldman Sachs.

We'll move on to Evan Seigerman with BMO.

Thank you we'll take our next question from Chris <unk> with J P. Morgan.

Hi, this is Dan on for Chris.

Hi, guys.

Thanks for taking our question.

Thank you so much for taking my question.

Oh, great. Thanks, so much for the questions I guess the first one for me was on Briana Z in terms of what's the latest on maybe the timing and maybe as importantly, the magnitude of your capacity expansion. It sounds like this might have been getting pushed out into 2020 three versus I think previously you were talking about maybe a <unk> target I just wanted to elaborate a bit more on what's happening there.

Two from us.

I want to talk on the kind of dynamics, between OpDivo and OpDuoLAG.

First, on the Milvexian readout, if you could maybe frame some areas of focus into the ESC data and provide any additional color into how you're thinking about the Phase 3 program now that the data is in-house.

And then second, on Camsios, if there's any additional feedback you can provide on some of the early launch dynamics and your expectations into the second half of the year and early next year.

Can you provide more color for the split between patients who are switched from OpDivo to OpDuoLAG?

Thank you.

Thank you, Dan.

Samit will answer your question on Milvexian, and Chris provides some incremental color on Camsios.

Thanks.

And then one, on turning point, I know kind of when you announced the deal, it was still kind of TBD on the pre-NDA discussions with FDA.

And then my second question was on Kim Diose I know, there's a bit of a lag between when docs get certified for the Rems and when Bristol actually starts to generate sales for the drug, but but as we just kind of think about the sales ramp from here should we be thinking about this as a fairly gradual process or is this a product that could see us.

Sure.

Any update on that, that maybe will give us more confidence that you're able to launch, in the second half of next year?

Thank you, Giovanni, and thank you, Dan, for the question on Milvexian.

Thank you.

Thanks, Evan.

Let me just answer quickly your question on turning point before Chris addresses your OpDuoLAG question.

Steeper ramp starting sometime later this year given the 30th some identified kind of patients out there I'm trying to say in terms of expectation setting of how to how to think about the ramp up given some of the I guess the promising initial data in terms of the number of physicians getting certified et cetera. Thank you.

Thank you Chris.

Chris Thanks for the question Chris on beyond the what I would say just at the outset around cell therapy in general is that the demand in the quarter for both of these products are backed by an <unk> was strong we continue to be very pleased with the feedback on the profiles of these products and importantly, how those profiles position us competitively with respect to <unk>.

Certainly looking forward to having the data presented at ESC and discussing the results.

And of course, as you know, we'll go into the details of the specifics of the data itself.

But I think there are two questions that probably are important to answer when we look at the data. And that would be one related to the efficacy, specifically when it comes to impact on clinically proven ischemic strokes.

And the second, of course, is to look at bleeding rates. And more specifically over there, one that physicians and patients would be interested to know about would be probably related to intracranial bleeds, where patients with strokes have a propensity to have bleeds, as well as if there are any fatal bleeds.

And so those are the kinds of questions that we set out to answer, and I think those are the questions that people will be very interested to know.

So, as you know, we continue to operate as two separate companies.

At the same time, as we've mentioned before, first of all, we remain confident in the ability to close in the third quarter of this year.

As David mentioned earlier, we had underlying demand that was very strong. We're obviously very pleased with the second line approval and the fact that it's given us the broadest label of any car T. In D. L. B C L.

And we're still looking at the launch of REPO in the second half of next year.

But as David also mentioned sales were impacted in the quarter by manufacturing success rates those success rates. The issue underlying that was resolved and we expect success rates to improve as we head into this quarter.

More generally around manufacturing with <unk> given the broader label. We had obviously hoped to have increased capacity in the second half of this year. We're now anticipating that in Q1 of 2023 delivering that capacity is a top priority. The focus here is on increasing increasing both vector and drug product supply I will note that.

We've seen a nice increase in the capacity for our beckmann driven by successful drug product expansion and increasing in vector supply and we anticipate that that same focus will be now applied to.

<unk> Z and have every expectation that we'll be able to deliver on that that capacity is going to be important because given the broad label with this product and the compelling profile slot availability is going to be critical so.

The good news is we have a very strong manufacturing team focused on increasing the supply and we look forward to delivering that supply in the first part of the year as four campus iOS and the pace of launch I would view this as a steady increase in the number of patients. They were gonna be for things that are really going to determine the pace of this launch physician and patient demand the volume of rim.

Five physicians how quickly those patients come to get on Kansas Io therapy, and then obviously the conversion of those patients to commercial drug and I would say really across all of those dimensions. We're happy with what we're seeing as I referenced earlier, it's in line with where we expect it to be this early in the launch.

As I mentioned earlier the demand for the product is very strong we're getting great feedback from both patients and physicians I spoke to the volume of users and the fact that we're seeing a nice increase in the number of Rems certified physicians every week.

We had told you previously I think in fact last quarter that we expected patients to initiate therapy during their routine visits and that's largely playing out though I would say we've seen a number of accounts, including some of our smaller and medium sized accounts quickly getting multiple patients onto drug. We're also seeing some of our larger accounts.

Organizing Kansas iOS clinic days, so that they can efficiently bring larger volumes of patients initiate them and monitor them.

So again, that's where we thought it would be and then finally as I referenced earlier.

Access is going to be an important consideration here virtually all oral specialty products like <unk> go through this period of two to six months.

Getting onto formulary during that period. The majority of patients are going to go onto free product. That's what we're seeing here, but again the good news is we're not seeing any access issues. So we don't foresee any challenges converting those patients to commercial drug. So when you add it up we expect the volume is going to increase over the course of the year.

And then you'll see those patients convert to commercial sales S formulary status as a cheap but bottom line. We're on we're very happy with what we're seeing thus far very much inline with expectations.

So, Kamzaios, let me pass it on to Chris to take it through.

So, all good, there.

Thanks, Chris.

Can we go to the next question please.

Thanks, Ahmed, and thanks, Dan, for the question.

Chris?

We are very pleased with the early launch of Kamzaios.

Thank you, we'll take our next caller from Steve Scala with Cowen.

Well. Thank you very much couple for summit first in your due curve of CIT to Nib F. D. A discussions to date has there been any mention of a box warning whatsoever or has that not come up in any conversation and also given the timeframe involved can we assume there won't be.

While it's still very early days, we're off to a very good start.

Sure.

And what I would say is that, by and large, the performance that we're seeing is aligned to our expectations.

And I would highlight maybe two or three things.

First, awareness is very good.

We've seen incredibly strong enthusiasm for the product from both physicians and patients. Importantly, the feedback that we're getting on the clinical program has been overwhelmingly positive and consistent. And to give you some vignette on that, patients are seeing significant benefit, both in terms of feel and function. And that benefit is being seen very early, in fact, as early as four weeks post-initiating treatment. And that's really important because it's driven a lot of enthusiasm both from patients, and it's given physicians a reason to believe that the product is living up to the promise that we have.

In terms of physician experience, the feedback has been very positive.

The REMS education that we've initiated is intuitive. Getting on and certified for REMS has been straightforward.

An AD com and then the second question is based on available data does Bristol think other cardiac myosin inhibitors.

We'll have a black box warning or do you think they could avoid that thank you.

So, we're very pleased with where we are with the OpDuoLAG approval and the early uptake.

Thank you Steve.

The execution of the team has been very strong, and physician reaction has been quite positive.

In terms of the dynamics within the market, shares in first-line metastatic melanoma are in the low double digits for OpDuoLAG.

Before I ask Samit to answer both of your questions. Let me just say as you know we.

We have seen some early use in second-line plus patients.

That's mainly driven by the, fact that, remember, the flow of newly diagnosed metastatic melanoma patients can be somewhat staggered just given the volume of patients you have in this market.

And so, what we're seeing is not only are physicians using the product in first-line, but they're also looking to use it in second-line as patients either progress or they're willing to switch patients.

We're mostly, displacing PD-1 monotherapy. That's to be expected just given the strength of the clinical data with a more than 2x improvement in PFS and a strong trend towards overall survival relative to PD-1 monotherapy.

In terms of who those patients are, that dynamic's playing out largely as expected.

We are seeing some modest conversion of OpDivo UroVoy to OpDuoLAG, but at this point, that's very much within what we had expected.

We don't comment on ongoing discussion with the regulatory authorities, but summit will provide his perspective on both the summit.

Yes. Thank you.

As already mentioned more specifics will be provided here.

I can.

Pete I came from the past conversations we've had is our confidence in the data itself what do you.

Do you think about it from an efficacy perspective differentiation and superiority that has been proven through the phase III trial versus a Tesla.

Safety perspective, showing differentiation when do you think about the JAK inhibitor switches.

First in class.

And it has that profile that have continued to work through multiple other trials.

Has given us the confidence to initiate the programs as you know in Psoriatic arthritis Jupiter 2000.

And also now looking forward to initiation of the ethylene safety trials at the end of the year beginning of next year. So overall, we're looking forward to September dental group a date in bringing this new medicine to patients and similarly, I would say in the cardiac myosin inhibitors, it is difficult and not appropriate for us to comment on other people's drugs.

So, overall, I would say OpDuoLAG, first, the performance continues to be very good.

It's early days, but certainly, we have strong momentum.

And the interplay between dual IO, single-agent IO, and OpDuoLAG is largely as expected.

What the profile is going to look like and if they will have any warning Victor cautions in the label or not what we can say, though is again I believe in Ken's iOS as already alluded too bye bye, Chris as well and David in his remarks our.

And, as David mentioned, that's translated to over 1,400 HCPs being REMS certified.

Thank you, Chris.

Belief in the data and how physicians are reacting in terms of getting trained and prescribing it to the patients. So overall looking forward to the initiation of our mom obstructive hypertrophic cardiomyopathy phase III program towards the end of the year.

And one thing I would highlight is that this is probably the most important leading indicator for this product launch.

Let's go to our next question, please, Sarah.

Given the fact that you don't have a history of REMS in the cardiovascular space, physicians are going to be REMS certified if they have intent to use.

Thank you.

Thank you.

We go to the next question please.

We'll take our next question from Terrence Flynn with Morgan Stanley.

Well go on to Siemens Fernandez with Guggenheim.

The last thing I would highlight is we're seeing a healthy increase in the number of centers prescribing week over week.

Hi.

Oh, Thanks for the question. So just a couple of quick questions per stop.

Right.

No.

Thanks for taking the question.

This is really for Giovanni.

Maybe as we think ahead to Milvexian and the various Phase III opportunities, I would just welcome your perspective on why the Xarelto Compass data didn't really change the treatment paradigm in patients with CAD-PAD.

Congress passed the Medicare pricing reform.

Again, I know you're not going to comment in terms of where you're going right now in terms of Phase III opportunities, but just trying to think about risk-benefit in some of these other populations where Eliquis hasn't really found much usage.

Just help us understand what impact you think this is likely to have whether it be on innovation, but also on your own long term guidance from that perspective, and you know are you hopeful that there might be should this go through a potential changes that could temper the impact perhaps.

Thank you.

Thank you, Terence.

A push out of this small molecule argument of of you know nine.

Nine months nine years of protection, and perhaps maybe pushed that out to 12 or 13 years.

Just wondering if there is there any opportunities to think a little bit more constructively about this and then separately I'm, hoping to just get a little bit of a color on the launch.

Dynamics around do Kravitz that nib you guys are are commenting on your enthusiasm to kind of get this product to market and to patients.

Just wanted to get a better sense of you know should the label.

I actually have a Jack a boxed warning you know, which we don't necessarily anticipate but should that occur.

What are you hearing from physicians with regard to the opportunity to kind of work around that and maybe just as a clarifying question. We've gotten a lot of questions from investors on the possibility that if there were a jack warning could it actually be post biologic doesn't make a lot of sense to us just wondering where you guys stand on that proposal.

Thanks, so much.

We don't see any access issues on the horizon that would prevent these patients who are getting onto therapy converting to drug.

Samit?

And so, if I sum it up, performance is in line with expectations.

Yeah, look, again, Nelvik GM is a Factor 11 inhibitor, and the first of its kind.

Thank you Seamus, let me start on pricing reform and then Chris will comment on two cross certain names. So first of all as you know discussions are ongoing in Congress and it's difficult to speculate exactly on the bill it and some of the details there will be included in the <unk>.

We're happy with what we're seeing, and we very much look forward to the continued uptake of this product over the course of time, of the year.

Great.

Thanks, Chris.

That will also be obviously, a long period during which an implementation of some of the measures will be classified in some of the dynamics would be a really important to understand so with respect to your question on would there be any.

Any impact to two innovation. So first of all we've consistently said that the elements of reform that improve affordability for patients. We are supposed to go up.

And so as an example, the redesign of the part D benefit in establishing an out of pocket cost for patients that's very beneficial.

And we are definitely very supportive of that there are elements into beal, However, which are obviously very detrimental.

Two innovation and particularly.

Rice setting by the government are at nine and 13 years.

Obviously, having the potential to have a negative impact on our all innovation overall I would say that with respect to the impact for our company. There's two things I can say at this 0.1st of all it is.

Really not.

Helpful to look at our exposure to the channel today I think it's important to really understand the dynamics that will develop over the next few years before these policies are implemented and a couple of things I like to say first of all obviously as you know.

Limit our revenues in the U S are declining rapidly Alec which we shared at that 50% with a Pfizer and then importantly, as you think about opdivo that loses exclusivity at the end of the decade. So what I can say is that our rapidly diversifying.

Portfolio and a significant number of new medicines that we're launching today and we'll be launching before some key elements of this policy our are implemented.

Position us well to navigate the challenges associated with the reforms for the entire industry, but obviously there is much more than we need to learn first of all to what potential finalization of the beall and Sac on really understanding better some of the elements of its implementation.

Certainly there are others that are in development as well.

So maybe I'll pick up shipments on the question regarding do crab is sitting there then the launch so whereas you know very excited about the opportunity to launch this product as was referenced previously the commercial and medical teams are in place they're ready to go Theyre very experienced.

So looking forward to the presentation of that data and then discussing the Phase III plans, which will be towards the end of this year, the initiation, as Giovanni mentioned in his comments early on.

What I've said previously I think is where we'll start this conversation which is that we explore every meaningful scenario as we think about the launch of any new product, but we continue to index heavily on the scenario, where we think that.

The preclinical and clinical data support and that is that this is a unique mechanism of action that is clearly to differentiate it differentiated from other products in the class.

And actually when we talk to customers, we get a almost uniform.

Alignment that that's the right way to think about do crab are sitting at that the mechanism based on all of the data that we've seen is unique and it is differentiated to differentiate it not only from JAKKS, but it's differentiate it most importantly from the current standard of care for oral agents treating moderate to severe patients and so as.

We step back and think about this product we anticipate very strong demand for <unk> based on the clinical profile from two phase III studies that close show clear superiority relative to the existing standard of care. We have a unique mechanism of action that is clearly differentiated and we think positions us well to become the oral branded of choice.

For these moderate to severe psoriasis patients.

And as was implied in the premise of your question. We're very excited to launch this product and we look forward to the <unk> date in September .

Sarah, can we go to the next question, please?

Thank you Chris there because we go to the next question. Please.

Thank you.

Absolutely next we'll take Luisa Hector whether they're in bird.

Next, we'll take Andrew Baum with Citi.

Hello. Thank you for taking my question you shall I just missed it.

Highlighting the importance that I just wanted to check has there been any shift in.

Thank you.

The activity trends and companies coming to you that.

Other companies just any more recent trends given that there.

Graduation, now depressed valuations.

Okay.

And those dialogues that you're having with target. Thank you.

Yeah.

I would say nothing has changed there continues to be an area of great focus for us we're looking at bringing new science into the company you.

You are right that valuations are resetting now for a longer period of time and we plan on continuing to be very active in this field its always been a priority for us.

Thanks, Giovanni can we go to the next question. Please.

First question on Norvexian.

Well move on to Tim Anderson with Wolfe Research.

Is there any possibility you could expedite what's going to be a very large and long-duration, clinical trial program through the adoption of MRI-defined silent strokes within a composite endpoint, either to expedite the trial or to decrease the N required for the trial?

Second, could you comment on whether you are exploring your CD19 CAR-T, excuse me, BRAMG, for autoimmune indications, given some of the recent data in lupus?

And then, finally, one of your competitors announced some intriguing data with an AP, in MSS colorectal cancer.

I know that Bristol has one in, I think, Phase 2.

Hi, I have a question on Val Tex N, which are historically when companies have added together anti platelet therapy or anti coagulant therapy.

To try to achieve better results it pretty much always results in higher bleeding in that calculation is whether that higher bleeding is more than offset.

By higher efficacy.

S S P setting.

Theoretically ignoring any data you already have in hand shouldn't we expect that same sort of thing, where we would likely see at least some additional bleeding.

And then we'd have to weigh it against the ethic a fee or is it in the realm of possibilities that you really don't see any additional bleeding and that triple therapy arm.

And then on pick too.

You guys expressed a high confidence in the molecule wondering why you havent advanced yet to mild to moderate patients.

If you're fairly confident in the label.

Why not push ahead in phase three and start to expand in the market like what Tesla is already done.

If you could provide us any update on that, that would be useful.

Thank you Tim Let me just ask a summit to answer your question both of them they'll vaccine.

And also our plans for a new cross selling them.

Many thanks.

Yes. Thank you.

And certainly looking forward to again the presentation of the non we've seen data on that.

I obviously cannot comment on why Xeralto, but certainly Aliquist, with its indication, you heard Chris and David mention early on as to what has been accomplished with Aliquist and continues to accomplish very effective treatment.

I, obviously cannot get into specifics of the data itself.

I reiterate that the two questions are that.

It'd be important from everybody's perspective is on the efficacy looking at a clinical strokes and secondly from a lead perspective, it becomes very important what kind of lead and especially when we think about the fatal bleeds in Japan leads meaningful bleed that become important Ah if he.

You look at the past.

What you will see those kinds of things that made people a little bit worse.

So.

Again, we can discuss more when we have the data presented at ESC Baz axiom.

<unk> certainly.

We are very pleased with the profile for the oral dual inhibitor that has obviously evolved and continues to evolve and multiple other indications as well as we look to the mild to moderate slices as we've said before we're looking to bring in the topical formulation will save some trials are about to begin and they'll face to walk from the two perspective and.

So our foray into the mark to market. So I said as you know before the trial was conducted in a moderate to severe patients.

Patients and then of course multiple phase III trials in various indications first of all and so I think alternatives that are ongoing and then I said he's starting later this year and phase II trials that are ongoing UC as well as in our call. Thank.

Thank you, Andrew.

I'll ask Samit to answer your three questions.

Thank you.

So can we go to the next one piece there.

Thank you, we'll move on to and then secret men with BMO.

Yes.

Hi, guys. Thank you so much for taking my question I wanted to talk on the kind of dynamics between up to Opdivo and up to a lag can you provide more color on the split between patients who were switched from Opdivo swap Youll lag and then one on turning point I know kind of when you announced the deal it was still kind of TBD on the pre NDA.

<unk> with FDA any update on that on that maybe will give us more confidence that you are able to launch in the second half of next year. Thank you.

Thank you, Johnny, and thank you, Andrew.

Thanks, Kevin Let me just answer quickly your question on turning point before Chris addresses your I'll do a live question. So as you know we continue to operate as two separate companies.

Very thoughtful questions, as always.

Companies at the same time as we've mentioned before first first of all we remain confident in that behavior to close in the third in the third quarter of this year and we're still.

Looking at the launch of rebel in the second half of next year. So all good there.

For Norvexian, look, we're not obviously going to get into the Phase 3 indications right, now, but from a Phase 2 perspective, you will certainly get to see the data.

Chris sure. So we're very pleased with where we are with the op do lag a approval in the early uptake the execution of the team has been very strong and physician reaction has been a it has been quite positive.

And what is important is, from a physician's perspective, what matters really is the clinical, strokes, and those certainly will be the questions to discuss when the data are presented.

On the CD19 side, certainly very intriguing data in the autoimmune disease, especially, in the SLE phase, SLE patients who are severely impacted by the disease.

Those are the things that we continue to discuss from a scientific perspective, how, to explore, where to explore, and certainly not hidden from us.

And as we evolve in our thinking, we'll share with everyone where we are going with that.

The German data were very intriguing, I have to say, and as were presented earlier this, year.

For CTLA-4, we've seen the data on CRC from a competitor.

In terms of the dynamics within the market shares in first line metastatic melanoma are in the low double digits for op do lag we have seen some early use in second line plus patients that's mainly driven by the fact that remember the flow of newly diagnosed.

From our perspective, we have three CTLA-4 antibodies in development.

The non-tricosylated pro-body, as well as the non-tricosylated pro-body.

Static melanoma patients can be.

Somewhat staggered just given the volume of patients you have in this market and so what we're seeing is not only our physicians using the product in first line, but they're also looking to use it in second line as patients either progress or they are willing to switch patients in terms of who those patients are that dynamics playing out largely as expected we're mostly done.

Placing PD one monotherapy that's to be expected just given the strength of the clinical data with a more than two X improvement in PFS and a strong trend towards overall survival relative to PD. One monotherapy. We are seeing some modest conversion of Opdivo Euro boy to opt to lag, but at this point that's very much with.

And what we had expected so overall I would say up to lag first the performance continues to be very good or it's early days, but certainly we have strong momentum.

The interplay between a dual I O a single agent I O and off do lag is largely as expected.

Thank you.

Our next question please Sarah.

Thank you we'll take our next question from.

Parents, playing with Morgan Stanley .

Hi, Thanks for taking the question.

Maybe summit as we think ahead to no vaccine and the various phase three opportunities would just welcome your perspective on why those are relative compass data. It didn't really change the treatment paradigm in patients with C. E D. P E D.

Again, I know you're not going to comment in terms of you know where you're going right now in terms of phase III opportunities, but just trying to think about risk benefit in some of these other populations, where Alex with hasn't really found much much usage. Thank you.

Thank you Terence summit.

So, there are three that are in development.

Hello again.

Is that is that a factor 11 inhibitor and the first of its guy and certainly there are others that are in development as well. So looking forward to the presentation of that data and then discussing plans, which will be towards the end.

The way we think about it is, number one, we have an ongoing study in MFS-CRC that we, just initiated with OptioLag, comparing to the standard of care.

This year the initiation of that Giovanni mentioned in his comments early on.

I, obviously cannot comment on why is it alto, but certainly Alex with for this indication you've heard.

Chris and David mentioned early on as to what has been accomplished with adequate and continues to accomplish very effective treatment. We are trying to solve with factor Xa inhibitors. Some of the shortcomings that have been left behind core inhibitors.

We are trying to solve with Factor XI inhibitors some of the shortcomings that have been left behind for the Factor X inhibitors, and especially from the Phase II trials, we're looking at also the combination of it with dual anti-platelet therapies.

Inhibitors, and especially from the phase II trials. We're looking at also the combined combination of good dual anti platelet therapy. So that's the that's the overall intent for the future development can look at multiple other opportunities in the IDM as well as on.

So that's the overall intent for the future development, to look at multiple other opportunities in the arterium, as well as on the venous side from Naloxone as a single agent, as well as in the combination with the background therapy.

The venous side from a vaccine as a single agent as well as in the combination.

With the with a background therapy, so more to follow uncertainty after the data presentation that we can have a wider dialogue on the indications and again. Thank you.

So more to follow, and certainly after the data presentation, we can have a wider dialogue on the indications and the plans.

Thank you.

Thanks, so much and neither can we go to the next question. Please.

Well take our next call.

Thanks so much.

Matthew Phipps with William Blair.

Sarah, can we go to the next question, please?

Hi, Thanks for taking my questions. Another melanoma landscape question. The results of Dream seek were presented at the recent ESCO, sorry, Opdivo, you or maybe it should be used even ahead of a brass inhibitor combinations do you think that's enough to drive more uptake of Opdivo in your board and that's sitting in the front line or is this.

And for future development for CTLA-4 antibodies, we have to think about combination strategies, because we know that many a time, even in the past, when single agents have been used, the response rates ultimately in registration trials have really been single digits or low single digits, in fact.

You're going to explore additional trials, maybe newer she julie for antibodies.

Yeah.

Thank you Chris.

We'll take our next caller from Matthew Phipps with William Blader.

Sure well thanks for the question Matthew we have long believed that Io has promised and improving the outcome of BRAF mutant positive patients today as you may know the use of I O, particularly as a first line treatment in that population is still somewhat limited it's around 30% to 35% of that part.

So, we will obviously be able to share the data once we have these combination studies, completed. They are currently ongoing.

Hi.

Too early to talk about the data at this time.

But certainly aware of the CRC data.

<unk> the dream seek data that were presented actually last year at osco are potentially practice informing in that they provide I think important insights into how to best sequence dual I O therapy relative to targeted therapy and in particular.

They show that the use of dual Io before targeted Caf Mec AR therapy led to a significant improvement in our two year overall survival.

In that regard the data are compelling and it can inform practice the one big caveat to keep in mind here is that targeted therapy combination use for first right first line BRAF mutant patients has been very sticky.

And so while we may see some use of dual I O in the frontline setting based on dream seek I would anticipate that would be mainly in an academic setting primarily because that's where the data are going to be most known remember we can't promote to this data. So I think it's unlikely you're going to see broader adoption that said its encouraging data and it could have an <unk>.

In fact on selected customers.

Thank you, Samit.

Thanks, Dave.

Thanks, Chris can we go to the next question. Please.

Thank you we'll move on next to it.

Carter Gould with Barclays.

Great. Good morning, Thanks for taking the questions I wanted to go to the Ela question exactly kind of what which countries are baked into sort of the second half headwind and you mentioned the $2 50 of headwind on the on the quarter, you've made some intra quarter comments and we've seen some additional.

Countries have generics like Canada, and I guess, just bigger picture is it more appropriate to still think about <unk> as a tailwind to overall company growth in 'twenty three I given some of these headwinds it seems like every month, there's a new country are sort of watching generics and I guess, then secondly, just onto kravis sitting nib.

How are you guys thinking about those IBD indications right now and specifically sort of the the viability of those higher doses and if anything has shifted based on your conversations with FDA around psoriasis.

Sir, can we go to the next one, please?

My question is another melanoma landscape question.

Thank you let me just let me just.

The results of DreamSeq were presented at the recent ASCO showing Updevo and Urovoid maybe should be used, even ahead of BRAF inhibitor combinations.

Start on the illiquid and then David will provide some some some more insight and Chris I'll answer. Your second question. So what's what's referred to by by David in terms of the impact of EU generics for the rest of the year at this point is the U K and the Netherlands, and let me just.

Do you think that's enough to drive more uptake of Updevo and Urovoid in that setting in the front line, or is this something you're going to explore with additional trials, maybe newer CTLA-4 antibodies?

Bakken.

And Ah remind you were where we are in the U K.

Thank you.

As you know the high court that found a composition of matter of balance to be invalid, and obviously, we strongly disagree with that ruling because that's the same patent that was actually upheld and reaffirmed in both the U S and Canada last year.

And we're.

We're seeking permission to appeal the Netherlands is very different because in the Netherlands, a generic company decided to launch before the trial.

That actually took place on the merits.

And ER, obviously that trial.

Still ongoing there are generics of.

Oh, Alec was that we expect to enter the market in Canada that was planned later.

Later this year.

And as we've communicated before that are that are similar lawsuits are ongoing in other.

In other EU countries in every county actually is completely independent.

Each jurisdiction, we'll make a.

A decision independent from our perspective, we will continue to be very much convinced about the strength of our IP and we'll defend our every case and they can have any commentary David Yeah. Encoder also just recall the vast majority of our growth comes from the U S and we have patent protection until April 1st of 2028.

We'll take our next question from Jeff Meacham with Bank of America.

Chris?

Hey, guys.

Sure.

So feel really strong about the growth potential continued growth potential of ela with by that but just to contextualize our business in the U K, it's about $500 million and what we said is it'll be about <unk> between the U K and the Netherlands, it'll be about $250 million this year and as Giovanni talked about in the other European markets will continue to to figures.

We defend our intellectual property in there.

Some context on how we're thinking about the growth potential of El question. Despite this.

And then maybe I'll, just say something very briefly on IBD and turn it over to Simon to talk about the development IBD is obviously, a large and underserved market.

Some elements are more competitive than others, but in general there's still a need for multiple oral options here and given the profile that we've seen with drew crowds are certainly through the psoriasis program I.

I think from a commercial standpoint, there would certainly be an intriguing opportunity for us, but summit can speak more directly to the clinical plans.

Thanks so much for the questions.

Well, thanks for the question, Matthew.

We have long believed that IO has promise in improving the outcome of BRAF mutant-positive patients. Today, as you may know, the use of IO, particularly as a first-line treatment in that population, is still somewhat limited.

Yes, so just to keep it very brief.

Both trials are ongoing in phase two right now one in Crohn's disease, ulcerative colitis and based on data, we will be making decisions on.

And that's one of the doses.

I would say it has no bearing no bearing at all on that.

In terms of who will be with your glucose admit in September one of the slides since program. So Mr. Sean Thank you.

So let's start can we go to the next question. Please.

Had a commercial one and a pipeline one.

It's around 30 to 35 percent of that population.

Thank you we'll move on next to Dane Leone with Raymond James.

Chris, on reblozal, can you talk about the U.S. trends?

The DreamSeq data that were presented actually last year at ASCO are potentially practice-informing in that they provide, I think, important insights into how to best sequence dual-IO therapy relative to targeted therapy. And in particular, they show that the use of dual-IO before targeted TAF-MEC therapy led to a significant improvement in two-year overall survival. So, in that regard, the data are compelling, and it can inform practice.

Hi, Thank you for taking the question.

You know, what does duration of therapy look like today versus, say, a year ago?

The one big caveat to keep in mind here is that targeted therapy combination used for first-line BRAF mutant patients has been very sticky.

And does demand support upside to your peak forecast?

And so, while we may see some use of dual-IO in the front-line setting based on DreamSeq, I would anticipate that would be mainly in an academic setting, primarily because that's where the data are going to be most known.

And then, Samit or Giovanni, I know Turning Point hasn't closed yet, but, you know, how, much of a focus do you have?

Two strategy ones for me.

And this is something that comes up in almost every investor conversation.

Remember, we can't promote to this data.

So you got to win with mill vaccine. The views that you really have to have that head to head comparative trial.

Versus ride that are in Afib and aphids going to represent the majority of the addressable market.

For a mill vaccine and so the question is from.

A lot of People's perspective from a timeline. It seems like you guys might be behind Bayer on that front could.

Could you just.

Maybe address what your strategy is to get into he said what you view as the timelines for success and then generally.

How you view head to head trials as potentially mitigating.

The L. O E are associated with eloquent as we go through this decade, and then kind of the same point, there's a lot of questions of how you preserve our adopt Eva revenues going forward and how much you can actually swap out.

With further studies of Abdulla lag and you have a number of ongoing but what do you really see as the potential of abdulla lag a peak sales.

From what you know now between.

What's going to cannibalize, opdivo and potentially Uruguay versus where we're going to be de novo markets for pure growth. Thank you.

Thank you let me just ask answer your your Abdulla lag question first and then summit is best position to comment on <unk> and so on on Abdulla lag as we've.

So, I think it's unlikely you're going to see broader adoption.

That said, it's encouraging data, and it could have an impact on selected clients.

As we've stated before we see great potential for <unk>.

Thank you.

And as you look at and in fact, we've articulated our perspective is that peak sales for the asset can be from a non risk adjusted.

Basis are above $4 billion in revenue and that of course comes from a number of indications.

We'll move on next to Carter Gould with Barclays.

Great.

And when you look at our the indications that we're currently studying of course melanoma is the entry for a laggard, but there are trials ongoing in colorectal cancer liver cancer and lung cancer and in some cases those are indications, where we currently have a presence with opdivo and <unk>.

Some cases, they're new indications.

You are right that we look at all be a lag as an opportunity.

To provide durability to our Io Io franchise and assuming continued successful development that is clearly a potential for audio lag to be playing in a meaningful part of the current revenue space for them for Opdivo with respect to mill vaccine again, some into I'll call. It.

Let me just remind you that you know as he is he's said before.

We'll be able to provide much more insights into the development program. Once you've seen that we presented the data and obviously, we're looking at a broad set of indications well beyond it.

But summit.

So just very briefly thank you Giovanni what I would say that are.

There will be a data presentation, both from a competitor molecule and ourselves at the same time.

Let's see neither of the two companies that started the C program that our partners Janssen and Uh Huh.

BNS we're of course looking forward to initiation of that program. Later this year as I said earlier bolt on the venous and arterial side of things single agent combinations, and then you'll be able to talk about the competitors as well so thank you.

Thanks, So much Sir please go to the next one please.

Thank you we'll move on to common.

With UBS.

Good morning.

Hey, good morning, and congrats on the quarter.

Hum.

When should we expect to see the the fourth line update on this asset and could you just walk us through the broader development plan and timing around this please and then maybe just a follow up on business development. Just how should we think about this going forward in terms of your therapeutic areas of mechanisms of interest in what are you now thinking is still sort of.

Thanks for taking the questions.

I wanted to go to Eloquist and exactly kind of which countries are baked into sort of the second half headwind.

Well the deal size. Thanks.

And I guess then secondly, just on to Kravacitib, how are you guys thinking about those IBD indications right now and specifically sort of the viability of those higher doses, and if anything has shifted based on your conversations with FDA around psoriasis?

Thank you summit.

Sure I will start with the big demand uncertainty.

The data that we presented already as a single agent or in combination of thing.

Quite interesting.

Interesting and certainly very helpful. In terms of thinking of longer term development bank for music to my the data update will be Oh, I think of the ash or are the next steps on things that we won't be able to find for the ongoing single arm open label study more importantly, as you have seen in the scorecard that Oh.

It was presented by Giovanni earlier.

Victimised has two phase III trials planned to start in.

And then they come in.

I think 2023.

Look at the combination with Petrobras as well as to look at the combination.

Oh, there it can be.

I do a comparison versus pharma littermate. So those two are the second line plus indication right now Mike is going to be tested and we're looking forward to those indications in 2022.

I'll give it back to Giovanni for the BD question.

Thank you.

Thank you.

And from a BD perspective, what I can say is we remain size agnostic, we have tremendous financial flexibility. What we look at is compelling science in areas that.

That we know well and the opportunity to continue to further strengthen the outlook of the company in the second half of the decade and beyond.

And obviously do that through deals that generate value for patients and for shareholders.

Let me just start on Eloquist, and then David will provide some more insight, and Chris, answer your second question.

We're running short on time, but maybe it's time to squeeze two last ones and maybe the next one please Sarah.

So what's referred to by David in terms of the impact of EU generics for the rest of the year at this point is the UK and the Netherlands.

Absolutely we'll take our next question from Mohit Bansal with Wells Fargo.

And let me just step back and remind you where we are.

In the UK, as you know, the High Court had found our compositional matter patent to be invalid.

Great. Thanks for taking my question, maybe a question on another question and it comes idle.

And obviously, we strongly disagree with that ruling because that's the same patent that was actually upheld and reaffirmed in both the US and Canada last year, and we're seeking permission to appeal.

The Netherlands is very different because in the Netherlands, a generic company decided to launch before the trial actually took place on the merits, and obviously that trial is still ongoing.

There are generics of Eloquist that we expect to enter the market in Canada that was planned later this year.

And as we've communicated before, there are similar lawsuits ongoing in other EU countries, and every country actually is completely independent, and each jurisdiction will make a decision independent.

So from our perspective, we continue to be very much convinced about the strength of our IP and will defend every case in every country.

When we spoke to cardiologists there was some concerns raised by general cardiologists talking about ramps and how.

Maybe on the fascist cardiomyopathy clinic.

Our patients are better equipped to handle this so one is it too and number two like to watch and distal Ken Ken had a make it easy for doctors and the last one is do you know how what percentage of the patient population is do generic specialty cardiomyopathy clinic. Thank you.

David?

Yeah, and Carter, also just recall the vast majority of our growth comes from the US, and we have patent protection until April 1st of 2028.

So feel really strong about the continued growth potential of Eloquist by that.

Thank you Chris sure so with respect to the Rems and sort of how that's been received as I mentioned earlier the feedback on the Rems process has been very favorable from physicians is straightforward to get certified we've spent a lot of time working with summit's team before approval to make sure that the Rems program Gen.

Chris, why don't you start on reblozal?

And then Samit will comment on oncology strategy.

But just to contextualize, our business in the UK is about $500 million, and what we said is it'll be about – between the UK and the Netherlands, it'll be about $250 million this year.

Yeah, thanks for the question, Geoff.

And as Giovanni talked about, and the other European markets, we'll continue to vigorously defend our intellectual property in there.

We're very pleased with the continued uptick that we're seeing with reblozal.

So hopefully that provides some context on how we're thinking about the growth potential of Eloquist despite this.

And then maybe I'll just say something very briefly on IBD and turn it over to Samit to talk about the development.

IBD is obviously a large and underserved market.

Some elements are more competitive than others, but in general, there's still a need for multiple oral options here.

But Samit can speak more directly to the clinical.

And given the profile that we've seen with Ducrava, certainly through the psoriasis program, I think from a commercial standpoint, there would certainly be an intriguing opportunity for us.

Thanks so much sir, can we go to the next question please?

Thank you, we'll move on next to Dane Leone with Raymond James.

Hi, thank you for taking the questions.

<unk> was intuitive and fit into how a cardiologist generally treat patients and so far that work upfront as well as the education, we've done is paying off.

Cardiologists are generally seeing it as not a barrier in fact, the fact that we have seen a large number of medium and small clinics get not only rems certified but get patients onto therapy and in many cases get multiple patients on therapy is an indicator of the fact that the Rems program is buying.

Large being seen as something that's very manageable for our physicians and hasn't proven to be a barrier at all Moreover, I think that the Rems program. When we designed it was important to make sure that patients are initiated an ambitious initiated safely and monitored over the course of their disease and that's exactly how this this process.

This is playing out at this point, so very happy with respect to what we're hearing play back from physicians on Rems.

Two strategy ones for me, and this is something that comes up in almost every investor conversation.

Thanks, Chris can we go to our last question. Please.

Yes, we will take our last question today from Robin Karnofsky with tourists security.

For you guys to win with Milvexian, the view is that you really have to have that head-to-head comparative trial versus Riva in AFib, and AFib is going to represent the majority of the addressable market for Milvexian.

And then kind of to the same point, there's a lot of questions of how you preserve the Opdiva revenues going forward and how much you can actually swap out with further studies of Opdua Lag.

Thank you for taking my question Alright so.

And you have a number ongoing, but what do you really see as the potential of Opdua Lag peak sales from what you know now between what's going to cannibalize Opdiva and potentially Yervoy versus where it's going to be DeNovo markets for pure growth.

Thank you.

I mean, our details it suggests still there's like a small fraction maybe 20% of people eligible if they can get the drug. So given that you have a really broad label you're going into second line. How do you think you can improvement proved that's what steps are you taking them to improve the vein to vein or brain debate in time, and then you Craigslist.

Let me just answer your Opdua Lag question first, and then Samit is best positioned to comment on Milvexian.

So, on Opdua Lag, as we've stated before, we see great potential for Opdua Lag.

Quick question there for the moderate he says how are you viewing how long it'll be positioned versus.

Jeremy that or Archie just described the Tam at came in at a lower price pretty clean safety profile. How are you viewing them any step edits that might be required there.

Thank you Robyn Chris sure what I would say is that on Briana Z I think in general the the focus that we've had continues to be on if your question is around <unk>.

Continuing to improve on the manufacturing side. The focus there has been on making sure that we're focused really on three things first on Brian do you have on cell therapy generally you have to stay focused on operational issues obviously.

We spoke about the issue that hit the success rates with this program in the quarter, but clearly that's going to be one area of focus for us and as part of that you. Obviously are continuing to stay focused on improving turnaround time, and that's a clear focus for the manufacturing team above and beyond that though what I would say it is most critical.

For us at this stage in the launch for both are back now and beyond is to continue to be focused on vector supply and drug product supply continue to increase that we're working hard with health authorities to increase capacity on drug supply for Briana Z at our existing facilities. We're also bringing on two state of the art facilities in Devins, Massachusetts, and the light and it.

License in the Netherlands.

I think we're going to be an important component of how we continue to expand the capacity for that product.

Coming into the first part of next year, and then with respect to do crab assist nib.

And as you look at, and in fact, we've articulated our perspective that peak sales for the asset can be from a non-risk-adjusted basis above $4 billion in revenue.

I think the focus as we look at do crab is sitting at his first and foremost recognizing that the most important thing with this asset as you think about access generally is going to be the value story that you have to tell and we have a very strong story to tell with do crab are sitting nib as I'd mentioned earlier, we anticipate demand is going to be strong.

And that, of course, comes from a number of indications.

And when you look at the indications that we are currently studying, of course, melanoma is the entry for Opdua Lag, but there are trials ongoing in colorectal cancer, liver cancer, and lung cancer.

And in some cases, those are indications where we currently have a presence with Opdiva.

This also recognize that you have two phase III studies that show head to head data against the current standard of care for the patients who are being treated with moderate to severe psoriasis. So we have a very strong story to tell with Payors and then in terms of those dynamics I'm actually less concerned about.

'bout competition with a topical.

In particular, because remember a lot of topical theyre going to stay on board as you move into oral therapies in psoriasis. So I think the dynamics that we're most looking out our first making sure that we provide very quick access for patients who have plans with open access and as we talked about last quarter in there.

This market as opposed to other markets that we've talked about many patients are covered by plans that will have open access at launch and then obviously, we're gonna have to continue to build volume in order to expand coverage for those plans that don't have that open access at launch and there it's going to be all about <unk>.

<unk> volume and then leveraging that volume to get into a better access position over time.

Thank you Chris.

And you know from my perspective, let me just say again that what we are hearing from physicians.

All the time is that they consider brands. He is the best in class C 19, casualty and I look forward to.

The opportunity to have.

A significant increase in capacity at the beginning of next year, which will be important for us now more broadly I want to thank all of you for <unk>.

In some cases, there are new indications.

You are right that we look at Opdua Lag as an opportunity to provide durability to our IEO franchise.

If anything in the call this was.

We had good growth in the quarter versus prior year as well as sequentially.

And assuming continued successful development, there is clearly a potential for Opdua Lag to be playing in a meaningful part of the current revenue space for Opdiva.

With respect to Milvexian, again, Samit will comment.

One quarter for the company, we have a good momentum with our in line business that are very positive dynamics with our new product portfolio.

Let me just remind you that, as he's said before, we'll be able to provide much more insights into the development program once you've seen and we've presented the data.

And obviously, we're looking at a broad set of indications well beyond AFIB.

I would highlight a few things.

Thanks a lot.

But Samit?

First, we're continuing to see good acquisition of new patients for this product.

Sir, can we go to the next one please?

Just very briefly, thank you Giovanni.

One of the things that we look very carefully at is what are physicians' perceptions of, the product, and importantly, how quickly they're moving patients off of ESAs to get on to reblozal therapy.

What I would say is that there will be data presentation both from the competitor molecule and ourselves at the same time at ESC.

That time on ESAs when patients are not getting an adequate response continues to shorten, which is a leading indicator of the number of patients that will be within the indication that we have, and importantly, we're seeing nice trends in both dosing and administration.

Neither of the two companies have started the Create3 program and our partners Jensen and I and BMS, we are of course looking forward to initiation of that program later this year.

The average MDS dose by cycle has grown steadily during the course of this launch and has increased, this year.

As I said earlier, both on the venous and arterial side of things, single agent combinations, and then we'll be able to talk about the competitors as well.

That's resulted in improved efficacy and longer duration of therapy, which to your question, has been up 6% this year relative to where we were in 2021.

So, thank you.

And while your question was mainly focused, I think, on the U.S., I would highlight that, ex-U.S., the launch is early, but we're seeing very good uptake in the early launch markets, notably markets like Germany, and then we'll have additional access and reimbursement decisions ex-U.S.

So, overall, we feel very good about where we are, and we look forward to continued uptake, of this product as we go through the remainder of the year.

And thanks, Chris.

And that positions us well for the second half of the year, which again would be very important for the company and look forward to continuing to answer your questions and our IR team will be available for any follow up you have so thanks again and have a good day.

And Jeff, maybe I can take on the turning point question.

Thank you.

So, first of all, excited about the acquisition of Turning Point Therapeutics and looking, forward to bringing Ripotrexanib to patients in the second half of next year.

We'll move on to Colin Briscoe with UBS.

Your question around the combinations, those are all going to be always data-dependent, and so explorations will continue, although at this time, certainly, there is a lot of knowledge and lots of emergence of data, TKI combinations or tyrosine kinase inhibitors, which are not necessarily mutation-specific tyrosine kinases, which have generated a lot of interest and a lot of data and have been approved in multiple indications when combined with IO therapies.

Hey, good morning and congrats on the quarter.

But it does provide additional opportunities in the future to look at these sorts of combinations, in more specific, pre-specified populations and selected patient populations, but those will be data that will need to be generated at the current time too early to tell.

On the victim side, when should we expect to see the fourth line update on this asset and could you just walk us through the broader development plan and timing around this please?

And then maybe just to follow up on business development, just how should we think about this going forward in terms of your therapeutic areas or mechanisms of interest and what are you now thinking is your sort of sweet spot for deal size?

Thanks.

Thank you, Samit.

Thank you.

Great.

Samit?

Thank you.

Thank you.

Sarah, can we go to the next question, please?

Sure.

We'll take our next question from Chris Scott with J.P. Morgan.

And from a BD perspective, what I can say is we remain size agnostic.

I will start with mesigtamide and certainly the data that we presented already as a single agent combination has been quite interesting and certainly very helpful in terms of thinking a longer term development plan for mesigtamide.

Great.

We have tremendous financial flexibility.

Thank you, Chris.

Thank you.

More importantly, as you have seen in the scorecard that was presented by Giovanni earlier, mesigtamide has two phase three trials planned to start in the coming, I think, 2023 to look at the combination with caprolis as well as to look at the combination in the head to head comparison versus pomalidomide.

Thanks so much for the questions.

What we look at is compelling science in areas that we know well and the opportunity to continue to further strengthen the outlook of the company in the second half of the decade and beyond and obviously do that through deals that generate value for patients and for shareholders.

Thanks for the question, Chris.

So those two are the second line plus indication where mesigtamide is going to be tested and we're looking forward to those initiations in 2023.

I guess the first one for me was on Brionzi in terms of what's the latest on maybe the, timing and maybe, as importantly, the magnitude of your capacity expansion.

And I know we're running short on time, but I think we maybe have time to squeeze two last ones in.

That does conclude today's teleconference. We do appreciate your participation at this time you may now disconnect.

On Brionzi, what I would say just at the outset around cell therapy in general is that the, demand in the quarter for both of these products, Becme and Brionzi, was strong.

I'll give it back to Giovanni for the BD question.

It sounds like this might have been getting pushed out into 2023 versus I think previously, we were talking about maybe a 4Q target, and I just wanted to elaborate a bit more on what's happening there.

Maybe go to the next one, please, Sarah.

We continue to be very pleased with the feedback on the profiles of these products and, importantly, how those profiles position us competitively.

And then my second question was on Kim Dias.

Absolutely.

Thank you.

Thank you.

With respect to Brionzi, as David mentioned earlier, we had underlying demand that was, very strong.

I know there's a bit of a lag between when docs get certified for the REMS and when Bristol, actually starts to generate sales for the drug.

We'll take our next question from Mohit Bansal with Wells Fargo.

We'll take our next caller from Steve Scala with Cohen.

Chris?

We're obviously very pleased with the second-line approval and the fact that it's given us the, broadest label of any CAR-T in DLBCL, but as David also mentioned, sales were impacted in the quarter by manufacturing success rates. Those success rates, the issue underlying that was resolved, and we expect success rates, to improve as we head into this quarter.

But as we just kind of think about the sales ramp from here, should we be thinking about, this as a fairly gradual process, or is this a product that could see a steeper ramp starting sometime later this year, given that there are already some identified kind of patients out there?

Great.

Sure.

More generally around manufacturing with Brionzi, given the broader label, we had obviously, hope to have increased capacity in the second half of this year.

I'm just trying to see in terms of expectation setting of how to think about the ramp, given, some of the, I guess, the promising initial data in terms of the number of physicians getting certified, et cetera.

Thanks for taking my question.

So with respect to the RIMS and sort of how that's been received, as I mentioned earlier, the feedback on the RIMS process has been very favorable from physicians. It's straightforward to get certified.

We're now anticipating that in Q1 of 2023.

Maybe a question on another question.

Delivering that capacity is a top priority.

So when we spoke to cardiologists, there were some concerns raised by general cardiologists talking about ramps and how maybe only cardiomyopathy clinics with more patients are better equipped to handle this.

The focus here is on increasing both vector and drug product supply.

Yeah.

So one, is it true?

I will note that we've seen a nice increase in the capacity for Becme driven by successful, drug product expansion and increasing in vector supply, and we anticipate that that same focus will be now applied to Brionzi and have every expectation that we'll be able to deliver on that.

And number two, to what end Bristol can help make it easy for doctors?

That capacity is going to be important because given the broad label with this product and, the compelling profile, slot availability is going to be critical.

And the last one is, do you know what percentage of patient population is treated at specialty cardiomyopathy clinics?

Yeah.

So the good news is we have a very strong manufacturing team focused on increasing the, supply, and we look forward to delivering that supply in the first part of the year.

As for ChemZyos and the pace of launch, I would view this as a steady increase in the, number of patients.

There are going to be four things that are really going to determine the pace of this, launch. Physician and patient demand, the volume of RIM-certified physicians, how quickly those, patients come to get on ChemZyos therapy, and then obviously the conversion of those patients to commercial drug.

And I would say really across all of those dimensions, we're happy with what we're seeing. As I referenced earlier, it's in line with where we expect it to be this early in the, launch.

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As I mentioned earlier, the demand for the product is very strong.

We're getting great feedback from both patients and physicians.

I spoke to the volume of users and the fact that we're seeing a nice increase in the number, of RIM-certified physicians every week.

We had told you previously, I think in fact last quarter, that we expected patients to, initiate therapy during their routine visits, and that's largely playing out.

Though I would say we've seen a number of accounts, including some of our smaller and, medium-sized accounts, quickly getting multiple patients on the drug, we're also seeing some of our larger accounts organizing ChemZyos clinic days so that they can efficiently bring larger volumes of patients, initiate them, and monitor them.

So again, that's where we thought it would be.

And then finally, as I referenced earlier, access is going to be an important consideration, here.

Virtually all oral specialty products, like ChemZyos, go through this period of two to, six months of getting onto formulary. During that period, the majority of patients are going to go onto free product.

That's what we're seeing here.

But again, the good news is we're not seeing any access issues, so we don't foresee any, challenges converting those patients to commercial drugs.

So when you add it up, we expect the volume is going to increase over the course of the, year, and then you'll see those patients convert to commercial sales as formulary status is achieved.

So bottom line, we're very happy with what we're seeing thus far, very much in line, with expectations.

Thanks, Chris.

Sarah, can we go to the next question, please?

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