Q1 2023 AstraZeneca PLC Earnings Call
Speaker 1: We have now seen three successive quarters of growth as we continue to launch innovative medicines and growth outpaces anticipated declines in some of our older medicines. This growth is a clear reflection of the value of our broad portfolio and our sustained focus on emerging markets over time.
Speaker 1: Our business is highly resilient with pipeline momentum accelerating as a result of both internal and external innovation. Please move to slide 7.
Speaker 1: One illustration of this momentum is our focus on initiating 30 phase III trials in 2023. I'm pleased to announce we have already dosed patients in six new phase III trials since the start of the year. This includes two trials of DATODX-D in combination with IO medicines.
Speaker 1: reflecting our confidence in the promise of this regiment to enhance outcomes for patients with lung cancer.
Speaker 1: Given that inflammatory cells play a key role in eosinophily cause azeophagitis and with T-slip being at the top of the inflammatory cascade, we've initiated the CROSSING trial for the spire, I want it to slip on the body in eoE.
Speaker 1: Supernova is a trial of our novel antibody, AZD3152, for the prophylactic treatment of COVID-19 with potential approval in the second half of this year.
Speaker 1: Here our aim is to protect people who don't mount an effective immune response to vaccination, which represents about 2% of the population.
Speaker 1: Cambria 1 is our first trial investigating commis restaurant, our next generation oral CERB, in the adjuvant breast cancer setting where there is significant opportunity to improve long-term outcomes. Finally, we initiated a trial of Vultomyris for the prevention of acute kidney injury associated with cardiac surgery.
Speaker 1: This represents an area of high unmet need with currently no approach therapies. Acute kidney injury can occur in up to 20% of patients undergoing cardiac surgery, but the risk increases to over 60% in patients with chronic kidney disease.
Speaker 1: The ARTEMIS trial focuses on those patients with ischemia where complement plays a key role. While we plan to provide an update each quarter on our new phase III trial starts, we expect a majority to those in the second half of this year.
Speaker 1: Now please turn to slide eight and Aradna can take you through our financial highlights in a quarter as well as provide some insights into how we are fully embracing artificial intelligence and machine learning across our business. And I saw that to you Aradna.
Speaker 2: Thank you, Pascal, and good afternoon, everyone. As usual, I will start with our reported P&L. Please turn to slide 9.
Speaker 2: Total revenue in the first quarter was stable compared to the prior year. Recall that Q1 of last year benefited from around $1.6 billion in COVID-19 medicine sales, which have declined as anticipated by 89% to $155 million.
Speaker 2: Excluding COVID-19 medicines, total revenue increased by 15% in the first quarter.
Speaker 2: In an effort to increase transparency, starting in Q1, we will break out recurrent revenues from partnered products into a separate line called Alliance Revenue. This line will include royalties and profit shares from partner medicines such as Inhertu and Despire in geographies where our partner books product sales.
Speaker 2: Upfront and milestone payments will continue to be reported as collaboration revenue.
Speaker 2: Hopefully, this results in improved visibility to revenue from partner medicines.
Speaker 2: Finally, we saw some relatively large core adjustments last year as a result of the unwind of the Alexion fair value inventory uplift. However, we only had 36 million of this in the quarter and it will be minimal in the future.
Speaker 2: Please turn to the next slide which depicts our core PNL.
Speaker 2: Our core growth margin in the first quarter was 83.3%, an increase of 4 percentage points compared to the prior period, which was negatively impacted by higher COVID-19 sales.
Speaker 2: Q1 2023 Core Growth Margin also benefited from product mix and lower production costs from prior quarters.
Speaker 2: On a full year basis, we still anticipate a slight improvement in gross margins compared to pre-pandemic levels.
Speaker 2: This is driven by lower COVID-19 revenue, higher oncology and Alexion sales, but impacted by increasing contribution from partner medicines and higher cost relating to inflation.
Speaker 2: In the second half of the year, we expect the usual seasonal impact from FluMist, as well as incremental cost relating to the production of our new COVID-19 antibody AZD3152.
Speaker 2: Core operating expenses increased by 9% in the quarter, however, this was partly due to lower costs in the prior year period.
Speaker 2: As Pascal mentioned, we started six new trials year to date, and we anticipated starting 30 during the full year, which will affect quarterly R&D cost phasing with R&D expenses in subsequent quarters expected to be higher than in Q1.
Speaker 2: On the SG&A side, we continue to invest behind our launches, including new indications for Infinci and Inertu, and our respiratory portfolio.
Speaker 2: On a full year basis, we still expect core operating expenses to increase by low to mid single-digit percentage, but there will be quarter on quarter variability.
Speaker 2: Other operating income of $379 million in the quarter includes a gain from the divestment of pulmonary flex tailor in the US.
Speaker 2: on top of some background level of other operating income from historical divestments.
Speaker 2: Taking these elements together, Core EPS increased by 6% at constant exchange rate to $1.92 in the quarter.
Speaker 2: Earlier this month, we announced the simplification of the agreement with SOBE and Sanofi on Nersivimab.
Speaker 2: This will simplify our P&L and result in us recognizing $718 million of other operating income in the second quarter, following the release of the liability on our balance sheet, much of which had been expensed through our core P&L.
Speaker 2: Now, please turn to slide 11. Our cash flow from operating activities of $3.1 billion was stable in the quarter despite the significant decline in COVID-19 revenue. We continue to work on improving cash conversion and have already made significant progress on that journey.
Speaker 2: Net debt increased by $2.1 billion to $25.1 billion, driven by the second interim dividend payment of around $3 billion, and approximately $2 billion in deal payments, including a second payment of around $900 million to a certain shareholders, and roughly $800 million for the recent Cincoir acquisition.
Speaker 2: For the full year, we still expect deal payments tied to prior business development transactions to be at a similar level as last year.
Speaker 2: Our current net debt to EBITDA ratio is 2.3 times or 1.9 if adjusting for the Alexion fair value uplift. As Pascal stated earlier, our guidance for the full year remains unchanged. We continue to anticipate total revenue, excluding COVID-19, to increase by low double-digit percentage.
Speaker 2: Including COVID-19 medicines, we anticipate total revenue to increase by low to mid single digit percentage. Core EPS is anticipated to increase by high single digit to low double digit percentage. Based on average March FX rates, we anticipate total revenue to increase by low double digit percentage.
Speaker 2: we anticipate a low single-digit adverse FX impact on both total revenue and core EPS.
Speaker 2: Please turn to slide 12.
Speaker 2: As a company that thrives on innovation, we are constantly evolving our ways of working and have embedded AI broadly across the organization.
Speaker 2: Over the course of this year, we plan to update you with some real-world examples each quarter on how this has helped us to improve productivity and drive innovation.
Speaker 2: This will help you to understand why we're making significant investments in this area. First, we'll focus on R&D, where we have over 400 data scientists employed and over 100 active AI projects underway. Later in his prepared remarks, many will provide examples of AI and drug discovery.
Speaker 2: With that, please turn to slide 13 and I will hand over to Dave to take you through our oncology business performance.
Speaker 3: Thank you, Aradhana. Slide 14, please. Oncology delivered solid performance in the first quarter with total revenues of over $4 billion, up 19% versus 2022. We saw double-digit product sales growth across the US, Europe , emerging markets, and established rest of world driven by new indication launches and continued demand generation.
Speaker 3: Now turning to our individual medicines, Tigriso global revenues grew by 15% in the quarter. In the US, we saw sustained demand in both Adora and Flora, coupled with improved duration of therapy and Flora. In Europe , growth of 8% was offset by pricing clawbacks in certain markets.
Speaker 3: Tugrisa performance in China was strong, recovering as expected following fourth quarter hospital budget management dynamics resulting in first quarter growth of 17% in emerging markets.
Speaker 3: Limparza, the leading PARP inhibitor globally, delivered first quarter product sales growth of 10%. The U.S. was impacted by destocking following an inventory build in the fourth quarter in anticipation of the Propel approval. While there are opportunities for continued demand expansion in the U.S., the U.S. has been
Speaker 3: These growth areas are more challenging. Specifically, we continue to work on improving HRD testing rates in ovarian, as well as BRCA testing and prescribing rates in hormone receptor positive breast cancer. Outside the U.S., we're encouraged by lymphoma growth in Europe of 18%, including strong launch trajectory for PROPEL in Germany.
Speaker 3: Turning now to Infinzi, total revenues inclusive of In judo grew an impressive 56% fueled by new launches. This performance was driven by 66% growth in the US with strong uptake across new indications particularly topaz one in Himalaya and in Europe and Japan.
Speaker 3: Early launch momentum from TOPAZ1 has been encouraging.
Speaker 3: CalQuint's total revenues increased 31% year on year, supported by ex-US demand growth. As expected, US performance in the first quarter was impacted by destocking following Maliek Tablet approval in the third quarter of last year. Looking at new starts in TRX share in the frontline CLL setting, CalQuint's remains the clear standard of care in the face of increasing class competition.
Speaker 3: That said, we do see some impact on new share in both the relapsed refractory and frontline settings.
Speaker 3: Turning now to InHirtu, total revenue was up 203% in the first quarter to $257 million. In the US, InHirtu new patient share is now approximately 50% across both second line InHirtu positive and hormone receptor positive.
Speaker 3: HER2-low post-chemo metastatic breast cancer, reflecting the strength of our underlying clinical data. Across European markets, we're seeing rapid uptake in HER2-positive metastatic breast cancer.
Speaker 3: Finally, we achieved exciting regulatory milestones in the quarter, including first approvals in China for Calquence and mantle cell lymphoma, and in HER2 and second line, HER2 positive metastatic breast cancer. Now please turn to slide 15.
Speaker 3: In the past, we've made clear our ambition to transform patient outcomes in breast cancer, and you've seen our teams deliver towards achieving that goal. Now for the first time, we're laying out our ambition in lung cancer, and by the year 2030, we are aiming for at least half of all lung cancer patients to be eligible for an AstraZeneca medicine. While this is a high bar, we've built a clear roadmap to deliver on this ambition.
Speaker 3: Focusing first in late stage non-small cell lung cancer, we have a broad portfolio of life cycle management and novel programs, and our success depends on our ability to deliver innovative medicines in both IO sensitive and biomarker driven tumor settings.
Speaker 3: Togriso is the established standard of care in adjuvant and frontline EGFR-mutated non-small cell lung cancer, and we're looking to solidify its position as the backbone TKI therapy in EGFR-mutated space through additional combination trials.
Speaker 3: We are accelerating development of our NextWave IO assets, leveraging experience within Finzi across multiple tumor types and continuing to advance our ADC portfolio within HER2 and HER2 expressing tumors and our TROP2-targeted ADC DattoDx.
Speaker 3: Furthermore, we have recently disclosed multiple registrational trials for both novel combination regimens and by specifics. Underpinning this roadmap is also continued and important investment behind new technologies, including screening and testing tools, as well as innovative platforms such as cell therapies.
Speaker 3: We're excited about the year ahead with important lung cancer data to support achievement of our 2030 ambition. And with that, please move to the next slide and I'll transition to Susan to cover key R&D highlights.
Speaker 4: Thank you, Dave. Continuing on the theme of lung cancer, it's been an exciting quarter for early-stage disease, during which we've shared details of two key datasets that further validate the importance of moving lung cancer diagnosis and treatment to earlier stages of disease, where patients have the highest potential for cure.
Speaker 4: First, at AACR, we shared the updated data from the Aegean trial. This tested the impact of adding Infimzi to neoadjuvant chemotherapy and then continuing as adjuvant monotherapy. We had already reported encouraging pathologic complete response data for this trial in June last year. At AACR, we reported the planned interim analysis of event-free survival.
Speaker 4: which demonstrated that patients treated with the Infimzi-based regimen had a 32% reduction in the risk of which current progression events or death versus chemotherapy alone.
Speaker 4: We also shared updated pathologic complete response data showing a four-fold increase with the addition of Infimzi compared to chemotherapy alone.
Speaker 4: We look forward to discussing these data with global regulatory authorities with the goal of providing this important new treatment option to patients.
Speaker 4: Second, last month we shared positive high-level results from the ADORA phase 3 trial reporting that Zagriso showed a strong overall survival benefit compared to placebo in the adjuvant treatment of patients with eGFR mutated non-small cell lung cancer.
Speaker 4: This follows the encouraging data we presented at ESMO last year with continued benefits for Togristo in terms of disease-free survival and immediate disease-free survival of nearly five and a half years.
Speaker 4: The overall survival data which we are delighted have been selected for an ASCO plenary are the first for phase three to demonstrate survival benefit in this adjuvant setting. And they add to the extensive body of evidence generated for Tredegrisso which has now shown a statistically significant and clinically meaningful OS benefit in both the early adjuvant and late stage metastatic settings.
Speaker 4: reinforcing its standard of care position across lines. We've also had positive readouts from the DURO trial of Lempasa plus Infimzi added to chemotherapy and Bevacizumab in patients with newly diagnosed ovarian cancer without a BRCA mutation, as well as a clinically meaningful data for in HER2 across multiple HER2-expressing tumor types.
Speaker 4: from the DESTINY-PAN-TUMOR O2 trial. Both these datasets will be showcased at ASCO this year.
Speaker 4: Please turn to slide 17.
Speaker 4: In addition to Aegean, ASDR provided an opportunity for us to share data from across our diverse, career-leading oncology portfolio, including several highlights from our early-stage pipeline.
Speaker 4: We shared the first clinical data from the armored GPC3 CAR-T therapy, C-CAR31, in patients with advanced hepatocellular cancer, as well as preclinical data for our armored STEEP2 CAR-T AZD-0754 in prostate cancer models. Both C-therapies have been designed using our dominant negative transform...
Speaker 4: and the persistence of CAR T copies out to at least 149 days, which is substantially more than has been observed were there any other GPC3 CAR T products?
Speaker 4: We also presented preclinical data from our in-house ADC platform. Our ADCs have been designed to maximize therapeutic index with a proprietary linker payload.
Speaker 4: The platform has a novel potent Toprisomerase 1 inhibitor which provides bystander tumor kill activity and a linker designed to provide a high degree of stability in the peripheral circulation with minimal free payload exposure.
Speaker 4: AZD9592, a bispecific ADC targeting eGFR unmet, and AZD8205 targeting B7H4 are already in phase one. And AZD5325 targeting folate receptor alpha will enter the clinic later this year.
Speaker 4: Finally, we provided our first disclosure for the novel lead epigenetics molecule AZPRMT5 inhibitor which is a potent MTAP selective PRMT5 inhibitor with anti-tumor activity in MTAP deleted tumours.
Speaker 4: Loss of the mTAP gene occurs across approximately 15% of all tumors and this provides an opportunity to selectively target these tumors and spare healthy tissue. This program will enter phase one shortly. And with this, please advance to the next slide and I'll hand over to Ruud to cover biopharmaceuticals performance. Thank you Susan. Turn to slide 19.
Speaker 5: Total revenue from biopharmaceuticals was $4.5 billion in the quarter, with CVRM growing 22% and RNI growing 8%.
Speaker 5: Revenues from our COVID-19 medicines declined to 155 million dollars due to the completion of our vaccine contracts last year and lower average health sales in the United States and Europe .
Speaker 5: Farsiiga continued to be the main driver in global CBRM, growing 39% to $1.3 billion, driven by multiple geographies including the US, Europe , Japan and the emerging markets. Although it is worth noting that Farsiiga enjoyed some gross-dended benefits in Q1 that may not recur in future quarters.
Speaker 5: We also saw over 60% growth for Ruxedustat in China and for Lokalma globally. Lokalma is now available in 27 markets having achieved potassium binder market share leadership in 8 of these markets.
Speaker 5: RNI's growth to $1.6 billion was helped by a recovery of demand for in-hill products in China as lockdown restrictions eased and also strong growth in Europe and other emerging markets. Please turn to slide 20.
Speaker 5: Over the last two years, the downward trends in Symbicort, Pumicort and other older brands have been more than offset by growth from Fesenrat, Despius, Safnello and Breastree.
Speaker 5: These combined brands grew at 46% in quarter one, and they now make up over one third of RNAI revenue. Biologics are a fast growing class of medicines, and only a fifth of patients who are eligible for a biologic medicine are currently receiving one.
Speaker 5: FASENRA continues to sustain leadership in total market share in severe ease in the philic asthma and the SPIES launch momentum continues at a rapid pace.
Speaker 5: In quarter one we saw continuous growth in the US and rapid uptake elsewhere in Japan. In Japan, the SPY has already captured new to brand absolute leadership just a few months after launch. The SPY is now available in six markets.
Speaker 5: and the auto-injector was approved in the US and the EU at the start of the year. Our in-hill portfolio also contains innovative medicines that have a long life cycle ahead. Next year, El Supra will add a fifth medicine to our newly launched brands and in quarter one, Bresterie grew 73%.
Speaker 5: BreastRe is benefiting from increased awareness of triple therapies, which was boosted by the 2023 report for the Global Initiative for Chronic Obstructive Lung Disease.
Speaker 5: The report advocated a short-handed path to triple fixed dose therapies in order to reduce mortality. In recent quarters, Breastery has accelerated new patient share gains in the U.S. and Europe and retained its leadership position in China with a 70% share of new to brand prescriptions.
Speaker 5: This quarter we also announced a new production site in Tsingtao, which will support breast-free continuous growth in China, which is home to 100 million patients with COPD. With that, I will now hand over to Manet, who will discuss the development programs that will drive future innovation of our biopharmaceuticals portfolio.
Speaker 6: Thank you, Rude, and please turn to slide 21. This slide outlines our assets across asthma and COPD. And as Rude highlighted, we have a strong legacy in respiratory medicine. With our broad portfolio, we're committed to continued respiratory leadership.
Speaker 6: Here we highlight the breadth of our commercial portfolio and illustrate our focus on emerging science involving immune mechanisms, lung damage and cell repair processes.
Our on-market inhaled medicines are already considered frontline standard therapies and we're also developing a number of novel add-on oral, inhaled and biologic therapies for patients whose diseases are not adequately controlled by existing medicines.
Our IL-33 targeted antibody, to the rakimab, offers a differentiated mechanism of action. The reduced form of IL-33 regulates the ST2 pathway responsible for inflammatory drive, whilst the oxidized form of IL-33 regulates the RAGE pathway responsible for the response of the melody response.
for epithelial dysfunction and mucus production. And toziracumab inhibits both signaling pathways with the potential to reverse key pathogenic features of COPD.
Tespar Aranti T-Slip remains the first and only biologic enosma approved without biomarker or phenotype.
T-slip is an epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of multiple drivers of airway inflammation.
We also have several other early stage assets in our pipeline including inhaled T-slip and inhaled JAK which should enter phase 2 in the second half of this year based on solid proof of mechanism data. We are confident this rich pipeline will provide the right building blocks to continue to drive leadership in respiratory diseases over the long term.
Please turn to the next slide.
At AAN we presented 66 weeks data for M. clonticin in ATR polyneuropathy building on the 35 week data presented last year at ISA.
We saw a statistically significant and clinically meaningful change from baseline versus an external placebo on the co-primary endpoints of reduction of transthiuratin and on the modified neuropathy impairment score plus 7, as well as the Norfolk quality of life questionnaire.
It was really encouraging to see the continued improvement on the quality of life questionnaire, which is designed to capture and quantify the impact of neuropathy on the lives of patients. HTRPN patients have identified sensory deficits and autoimmune GI symptoms as the most difficult symptoms to manage, and thus continued and sustained improvement in the quality of life questionnaire.
is an important indication of clinical benefit for these patients. We look forward to sharing this data with regulators globally as we seek approval from Plontasone.
At ECMIID, we also provided new data on AZD3152, our COVID-19 log-acting antibody. In vitro studies demonstrated that AZD3152 neutralizes all COVID-19 variants, including Arcturus, the latest variant of concern.
and we hope to make AZ-3152 available as a new prophylactic treatment in the second half of this year.
Z3152 available as a new prophylactic treatment in the second half of this year. Please turn to slide 23.
As Aradhana discussed earlier, artificial intelligence is embedded across our organization and within R&D we're using AI across all our therapy areas to discover new medicines more efficiently.
Understanding the biology of disease is critical to identifying the right drug targets and pathways. It is one of the most important decisions we make in drug discovery. We are applying AI and machine learning to build biomedical knowledge graphs across all our disease areas. And these visual representations depict...
relationships between vast datasets derived both within and external to AstraZeneca. Now scientists use these knowledge graphs to glean novel insights into disease biology as well as new pathways and targets to prosecute.
AI-enabled processes are also transforming the discovery of small and large molecule leads. Within small molecule drug discovery, we use proprietary AI-enabled platforms to generate small molecules twice as fast as our traditional discovery processes.
These algorithms use both generative models and novel scoring functions. In antibody discovery, we use AI-enabled deep screening programs to identify potential lead antibodies in as little as three days compared to traditional methods which take several months.
The scale and pace with which these new AI and machine learning innovations can accelerate drug discovery is really exciting and we look forward to providing additional examples of AI driven innovation over the balance of the year.
Please move to the next slide and I will now hand over to Mark to cover rare diseases. Thank you, Miné. Please move to slide 25.
In the first quarter, Rediz's total revenues grew 14%, contributing $1.9 billion. A strong performance in the quarter was primarily driven by patient demand, as well as some benefits from certain tender market orders.
Ulter Miris grew 61% in the quarter, reflecting successful and accelerated conversion from Soliris across shared indications.
61% in the quarter, reflecting successful and accelerated conversion from Soliris across shared indications.
We saw an increased number of complement naive patient treated with ultimiris, advancing our ambition to expand ultimiris use into a broader population, which we estimate to be two to three times larger than the addressable soliris patient population.
Consequently, Solirez declined 13% in the quarter as conversion accelerated. However, this decline was partially offset and the increase in conversion accelerated.
by growth in NMO and tender market order timing in certain emerging markets.
Though we are excited by this phone performance in the quarter, I want to mention a couple of key dynamics. First, I want to mention a couple of key dynamics.
As we continue to execute a conversion strategy from Soliris to Ultomeris, Ultomeris annual treatment cost is approximately one third lower than Soliris.
Furthermore, additional indications from Ultramyris require negotiation in some legislation as the eligible patient population expands. Therefore, as we move from ultra-ware such as PNH to where population such as
We anticipate increased pricing pressure. We fully expect the patient volume growth to offset the impact of this negotiation, although they present pricing headwinds in the near term. We remain confident in our C5 franchise, conversion and expansion strategies, and for the full year, we will continue to develop new strategies.
we expect ultimiris revenue to be broadly in line with that of SOLIRIS. Beyond the complement
Strancic grew 28% and Cossé Lugo grew over two times in the first quarter.
driven by strengths of patient demand and geographic expansion. Please move to the next slide. At the American Academy of Neurology Congress earlier this week, we presented data across Mestana Gravis, NMO, and dermatomyositis.
Notably, we presented real-world data highlighting the clinical benefit of C5 inhibition.
evaluating the change in concomitant therapies for patients receiving SEDIRIS. In practice, HEPs initially treat patients with eye doors or a corticosteroid to manage symptoms and then when symptoms are under control, they evaluate the use of additional therapies to sustain symptom control.
and ultimately look to minimize storage usage.
At one year treatment with Soliris, 76% of patients reduce their high dose steroid use, further demonstrating the clinical benefit of C5 inhibition on patient outcomes. We hope to show a similar reduction in ultramaries registry where analysis is ongoing.
We have highlighted new phase 1 data in our third generation C5 inhibitor, Gefurimab, a novel by specific evolution antibody.
Its low molecular weight enables subconious self-administration, binding to albumin to expand half-life, which allows for convenient weekly dosing.
The results demonstrated Gefurimab's favorable safety and tolerability profile, as well as its ability to achieve near-complete
demonstrated Gefurimab's favorable safety and tolerability profile, as well as its ability to achieve near-complete terminal complement inhibition.
This data further supports ongoing direct to phase three, pre-veiled trial in adult mercedena gravis. Separately following discussion of regulatory authorities, I'm disappointed to announce the termination of our Alexion 1840 Wilson disease program, despite
positive results from the phase III focus trial announced in 2021. Data from the program will be presented at an upcoming Medical Congress.
Please turn to the next slide.
In addition to our strength in C5, I also wanted to highlight or compliment
Factor D inhibitor. Factor D is a regulator of the alternative pathway upstream of C5.
The selective inhibition of the alternative pathway allows the other pathways to remain intact to fight infection, and this may provide a safety advantage.
We believe that factor D is the most tractable target given its stable circulating concentration in the plasma.
With three differentiated assets, our Fact2D portfolio has the potential to unlock value in several indications, including PNH, Myasthen Agravis, geographic atrophy, and renal indications.
Our most clinically advanced is Danny Copan, which most recently was submitted for regulatory approval in PNH patients with clinically significant extravascular hemolysis.
We have also seen positive phase II from the meerkopon as a monotherapy in PNH.
and election 2080, the third of Factor D, has recently doors in phase 1.
We look forward to providing further updates on our Factor D portfolio and our broader pipeline in future quarters. Please turn to slide 29 and I will hand the call back to Pascal for closing remarks.
Thank you, Max. If we move to the next slide, please. So for the reminder of 2023, we have a number of important trial readouts that have the potential to redefine care for patients. This includes the first phase three trial of DATU-DXD in lung cancer, and I'm pleased to tell you that we now expect the results from a second trial of DATU-DXD.
Tropion Brice 2001 in the second half of this year. Finally, we are making excellent progress towards our medium and long-term strategy ambitions and I'm thrilled to announce we are the top-ranked pharmaceutical company on the Financial Times' 2023 Europe Climate Leaders list.
Looking ahead, this is shaping up to be another exciting year for our company and I look forward to updating you on our progress. With that, I'll hand the call back to Andy.
Two questions please. First topic is Datto TXD two-part. TLO2 and O4 are duasco. So I wondered Susan if you could just give us some colour what we should be looking for. Are we expecting PFS data? And is it fair to be comparing that to keynote 189 as we think about confidence into 07 and 08? And then just on the breast data you mentioned Pascal TB01 and you've also got TB02.
Thank you.
Thanks. Thanks very much Sachin. So Susan do you want to take the first one or should we see and then David you take the other one? Yeah sure. So obviously with the TLO2 we're going to have updated data with the combination of data DXD with immuno oncology agents and again with TLO4.
We have data in combination with chemotherapy plus other agents. So I think you can look at durable response rate. It's always difficult to look at endpoints like progression-free survival in single-arm studies because there are differences in patient populations that are accrued versus other things that are out there. But that's what I suggest you look for.
Great. So on, Sachin, your first question around the opportunity with Datto in breast cancer, maybe the first thing that I would just point out here, and we talked about this in the context of Destiny-Breasto 4 and Destiny-Breasto 6, a large number of breast cancer patients in the metastatic setting, hormone response...
And so there's certainly a multi-blockbuster opportunity in breast cancer to replace that systemic chemotherapy. Now exactly how the puzzle pieces in the overlap between Akinoriksa and Sharman Octavia venture
Tropion Breast 01, I think we need to see some of the data and how that plays out. But I'd encourage you to think about, and that's the reason we talk about kind of the breast cancer as a portfolio, I talked about lung cancer as a portfolio today, because I think that we've got an opportunity across those assets to be able to really create very good commercial opportunity.
by replacing systemic chemo. Maybe the last just kind of point here of note on TB01. So that study is in a post endocrine therapy and post first systemic therapy. That's an earlier line than what we've seen out of Tropix O2. So I think that that gives you a sense competitively too.
that it's well positioned competitively depending on the data. On CalQuintz and what we've been seeing there, we continue to win the overwhelming majority of new starts in the frontline CLL setting. This is really our key area of promotional focus. In terms of market share, we are seeing impact from XANU as a new entrant.
We've seen the majority of their impact come in the relapse for factory setting. We have seen some impact come in the frontline setting. Some of their impact in the frontline setting has come at the expense of CalQuinz, though the majority of it has come at the expense of Abrutinib, the first generation BTKI. I would also say that within this context, we certainly expect the BTK to be a very positive impact on the production of the new technology.
to work hard to keep Calpens as the clear standard of care within the frontline setting. Thanks Dave. James Gordon at JPM. Go ahead James. Hello, James Gordon from JPM Morgan. Thanks for taking the questions. Two please. One about the C5 franchise and also competition. So Novartis presented their detailed Iptakapan Factor B data and it did suggest potentially competitive efficacy.
versus Saliris and Ultimiris and it's oral but do you think it does look competitive? How should we read that data? Can we compare it to what you've shown for Saliris and Ultimiris in PNH? And you mentioned you've got a few things of your own so you've got factor Ds but is the focus more the factor Ds now or is the excitement more actually on 17-20?
When do you think you could have either 1720 or a monotherapy factor D on the market to compete with the Bartas?
And the second question was just an infinium, really strong performance in Q1. Can you break down the performance a bit as in as much of that the acceleration coming from hemilary liver or Poseidon? And is the performance very front-end weighted because in judo you charge more upfront and then it sort of tapers off over the patient's treatment or is this like a clean Q1 number we can extrapolate from for the rest of the year?
So James actually thank you the first question was actually two questions so it's three questions in total. Mark do you want to take the first two and see if I have franchise and IPTAKOPAN and also then the factor the portfolio versus 1720? Yes so first of all the first question on IPTAKOPAN
First of all, I would like to caution everybody on doing indirect comparison of very different clinical trials, especially when the population that are included in the trials are very different. Just to provide an illustration of that, the C5 inhibitors of Alexion, Solireis and Ultramyris usually include...
bone marrow failure patient, we do represent about 30 to 40% of the actual PNH population. The second difference, the second visible difference is that the trials of Iptacopone are enriched with EVH, extravascular hemolysis and...
and anemia patients suffering from anemia and therefore when you measure improvement of hemoglobin it's probably easier to demonstrate the benefit. But just to go back to the comparison, we as you have said James, we also believe in the potential for proximal inhibitors factor B or factor D to play a role.
in the treatment of PNH, whether this will be in co-therapy as we have already demonstrated with Danny Copan, or first factor D, or whether it will be in monotherapy as we are trying to demonstrate in Vermi Copan, this remains to be seen. The key objective for PNH are obviously the control of intravascular hemolysis.
and to prevent thrombosis, otherwise you are increasing significantly the mortality risk. So we need to be seeing these results over time. Again you know co-therapy versus monotherapy. To turn to your second question or third question, all you know is 1720.
For us, 1720 is an improved generation over the first 2C5. It's a sub-cut formulation provided on a weekly regimen. We are still continuing the development. We have a trial on myasthenia gravis that is progressing very well.
So we are not abandoning the third generation of C5, we are also exploring the factor D. And as I described in my script, we have three of these factor D and each of them will be positioned slightly differently across the development momentum.
generation of C5, we are also exploring the factor D and as I described in my script, we have three of these factor D and each of them will be positioned slightly differently across the development momentum. Thanks Mark.
So James, there are two parts to your question, as I understand it. The first is around the sources of growth that sit within the Infinze number and then the second is really the durability of that growth. On the first piece, I'm really pleased to say that the growth...
is coming from multiple areas for Infinzium Judo. We see across geographies and also across indications that the performance was really driven for the quarter. Maybe to start first, and importantly, we do see, albeit a minority, still an important part of the growth coming from the existing indications. So,
also growing and continuing to grow nicely. And in fact, Poseidon is an area where approved, so in the US in particular, but also now getting underway in Japan, we're beginning to make inroads there as well. On your question specifically about in judo, just to share and to be helpful, from judo sales for the quarter were 37 million.
And for last quarter, they were 15 million. So it's actually a minority of the 900 million in the quarter. So it's not a front loaded, in judo effect that you're seeing here. This really is Infinzi TRXs that's driving this. And I expect us to continue to grow going forward. I do think we've probably got a little bit of bolus on Topaz one, but I think all the other dimensions that I've described.
that we've had in biologic success there. In terms of, does that invite your thinking at all in development in this space and equally more broadly biologics in COPD and actually just outline the population in particular you're looking at in the Tuzza Rocky Mab COPD phase three study and how that differs. And then secondly on farxetia combos, I know this comes up every quarter, but can you just give us an update as the respectfully audenting Genocide Nation.
to see a molecule, a biologic molecule work in COPD because I think it sort of gives us confidence that actually the programs we have with the Ficenra, with Tozo, hopefully with our T-slip molecules as well, will ultimately be positive. I think in terms of, obviously we need to see the phase two data from our phase...
former smokers and current smokers, people with more than two exacerbations, and ultimately will be helped, defined by the phase two study that's reading out. For the Facetinra program in COPD, which is the most advanced program we have, we're using it off our two failed phase three programs.
and that's in patients that have had exacerbations again three or more exacerbations and also have higher
So overall, I think I'm more optimistic now that I've seen a program work in the biologic space, but ultimately it will be determined by readouts from our data.
I think the phase 2 data is moving. I can't talk about it too much because we haven't announced the data, but I would say we're very much still on track, both in terms of the Zibo-DAPA program, the MR program and Baxterstat as a monotherapy but also in combination.
and hopefully during the course of the year we'll be able to talk about the phase 3 investment decisions but it's a little bit too soon yet to talk about data specifically but I would say they're still on track in terms of our expectations for phase 3 IDs and launches. Thank you, Armani. And then ultimately Peter, the objective is really to develop a portfolio of combinations of
Sorry, I had to unmute. Two questions from me. One just, you mentioned on Togressa, one of the drivers this quarter was improved duration of therapy for flora. I was just wondering if you could provide more color around that as we're getting asked a lot, particularly ahead of whatever we may see, Mariposa. And then just chamizostrin and adjuvant.
I know that design of Cambria 1 does allow for prior CDK46 for two years, but, you know, does a potential change in adjuvant standard of care, you know, we'll see it ASCO change your thinking about that study, or just any thoughts on adjuvant there. Thank you. Thanks. Deb, do you want to take the first one and then the second one? Yeah. So, in terms of, Emily, the duration of therapy that we're seeing in the real-world context –
of that is to be determined. But I think to the point that you're making, it's obviously quite relevant as we think about how clinicians see the efficacy that they get from monotherapy to GRISO. And it's something that I've commented on in past quarters that certainly the efficacy that's coming through the monotherapy together with the tolerability is what...
So the Cambrian1 study is designed to capture that patient population that have had two to five years of adjuvant endocrine therapy with or without a CDK46 inhibitor. So the reinforcement of the benefit that you see of a CDK46 inhibitor in the adjuvant setting I think actually makes this trial even more relevant because there are patients that can benefit from extended aducan therapy in adjuvant setting and these are patients with intermediate or high risk of...
an allosteric oral PCSK9 inhibitor that doesn't have a food interaction which differentiates itself from Merck's agent. You have got an open label phase two trial so you're seeing data but it's very difficult to find any published clinical data including your patterns of indications of efficacy of LDL lowering just to give some sense of contrast versus both
repatha, praluant, but also murk's data. So perhaps you could share with us given you have highlighted it I know you're excited about the product given the data that you have seen animal as well as human are you comfortable that it's going to deliver efficacy in a similar ballpark to the praluant, repatha and murk at least in terms of LDL
in combining with toparice summarize inhibitors, whether you think that the efficacy doesn't have a strong enough rationale or there's something else I might be missing here. Thank you.
So, shall I go first to the PCSK, it's a great question and we're being somewhat cagey I think on purpose because obviously it is a very competitive space, Andrew. So am I confident that we're going to have a target product profile that's competitive? What I'll say is that we've given ourselves, like we did actually for the injectable PCSK9, I think a tough threshold for what we would take forwards and to...
but I think it looks encouraging, but I wouldn't, it's not a home run yet.
So thanks for the question about PARP inhibitors in non-small cell lung cancer. So you know there are a subset of lung cancer patients that have mutations in HRR genes that may have increased sensitivity to PARP inhibition. We're awaiting the readout of studies that looking at the combination of PARP inhibition plus IO.
move into phase three or close to phase three, then of course we anticipate that the standards of care can continue to
Thank you. Thank you, Suzanne. Tim Anderson at Wolf. Over to you, Tim. Okay, thank you. On Tregriso, Aspera usually maintains that Tregriso monotherapy will likely remain the backbone for most patients in frontline lung.
Yet you started this small combination study with amavantumab in front line. So can you talk about the rationale behind that and why start that when we recently why why wouldn't you have started that many months ago, even all the way back in 2022. What was the trigger and you know why such a small size trial that so you can quickly advance it into a larger page three.
EGFR mutated space, we see Togriso clearly as the backbone of therapy for all patients being treated for EGFR mutated within obviously our labeled indication. And we think the majority are mono, but we've also made really clear that we do know that there is a desire. But we also know there is a desire.
to treat some patients with combination therapy, and really here we see FLORA2 as being, hopefully, if the results in the phase three look like those from OPAL, appropriate for a certain subset of patients. We also have acknowledged and seen that as the chrysalis data and the meriposa data were unfolding.
that there may indeed be a role for some subset of patients to be treated with the amavant-nab combo. It's within that context that we've initiated the study that you described. It's called Ostarra. It's a non-registrational medical affairs led study. It's a relatively small...
practice informing study as opposed to something with registrational intent. Really trying to answer questions for those who might have it down the road around the safety and the combinability of Togrisso and Amavantab in the future if there was a physician who was interested in that. So I would say that this isn't in any way a departure.
from the view that we've got on Togrisso, it is an additive component to a belief that Togrisso is the backbone of therapy moving forward.
Okay, in terms of DASA-DXD at the risk of being boring, I want to be entirely consistent with what I said before which is that the profile that we have for DASA-DXD we're confident about based on the design of the ADC with the linker warhead combination and the data in lung cancer in particular from the data from the phase one study which is not just showing a response rate in
later lung cancer patients, but the durability of response is what gives us confidence in the ability to beat the standard of care in the second line study. But we run phase three trials in order to get the results and we're eagerly awaiting the results of the Tropion Lung O1 as is everybody on the call. Thank you. Thanks Suzanne. Simon Baker, Redburn, over to you Simon.
Thank you, Pascal. Two questions, if I may. Firstly on Datto, and apologies if I missed a comment on this, but the timing on Tropium-Bresto 1 appears to have accelerated quite significantly. I just wonder if there's anything you could comment on that. And also with Datto, there was a very interesting poster at AACR looking at resensitisation in resistant cell lines, the specific example being...
today's proposals for pharma legislation reform proposed by the European Commission. Thanks so much.
So for TROPIA-Bresto 1, I think we're delighted that the call for this trial was six months ahead of schedule which I think just reflects the level of unmet need and the level of interest in the data program at this particular setting. So that's really the explanation for the acceleration.
I mean, there are two parts to it. I think one part is really the sort of a long-term impact of something like this on Europe and I think really that as it relates to Europe , I mean, this is the wrong response to an important issue, to an important issue and the issue is...
access to medicines in Europe . And we know that Europe has been behind the US in terms of access, but quite frankly it's also falling behind Japan and it's rapidly falling behind China as well. And that has been associated with...
Europe also falling behind the US but now also China in terms of clinical trials and emergence of biotechs. I was in China the last couple of weeks and you can see the innovation is really impressive in that country. So that's really this potential legislation is really.
for various stakeholders and participants to comment and discussions will take place. Nothing will be coming into legislation for another two years. So in terms of commenting on the impact, I think it is a little bit early in details and we should wait for the end result of this discussion and see what comes out of the legislation.
But I guess really again the sort of general underlying message that this kind of approach sends is that Europe is not really the most attractive place for the industry to invest in and the reality is that there is an enormous amount of innovation in the US to tap into. We have all known that but there is a rapidly increasing, very, very large amount of innovation in China actually. While Bread and
The next question is Mathias Ekblom at Andes Banken. Mathias, over to you. I have two please. So staying on China.
which you touched upon in the previous question. I was just curious to hear a bit more on why you decided to bring it up in the CEO statement in this report emphasizing the growth and pace of innovation. If it was something in particular that made it sensible to bring up in this quarter and not earlier. And then secondly, I'm curious to understand if there is more.
what is these assets that would interest AstraZeneca going forward. Thanks so much. Thanks, I'll take the first one and I'll ask also Leon to jump in and Mark maybe you want to take the Wilson termination question. The reason I've brought it up is that I really think that we wanted to signal that China is back. I mean the economy is bouncing.
And they really are implementing a very impressive program in terms of stimulating economy and driving innovation. And that plays into a whole series of new innovative technologies and products that are coming out of the biotech sector.
So we wanted to signal this because first of all, China is an important market, of course, and then it's also not only an important market in terms of helping patients and driving growth, but it's also an important market in terms of tapping into innovation. Leon can talk about this and maybe also Sivann could comment on some of the...
Deals we did and Suzanne was also in China for a couple of weeks. So, you know, we both came back definitely impressed with the progress that has been made in this country and the last reason I wanted to signal it is that You know it plays to our strengths as a company. We are the largest pharma company in China. We have a tremendous team and Really it Positions us very well to benefit from everything that's happening in that country Leon. Do you want to?
sort of comment and maybe you could also comment on some of the things we are doing across China and the various headquarters etc. Yeah, I think before I comment on China, I think emerging market is overall quite exciting and China is about 14-15% and the outside China emerging market is growing much faster, also 14-15%. So it's really worth looking at.
Within China, I think we are number one company with quite solid position. We actually speed up our global import product portfolio rapidly to benefit the Chinese patients. So this year we have Incirl2 and...
also Calcorns and also we launched our rare disease portfolio. So all these things are very exciting for import portfolio and also we have a 1 billion US dollar fund, venture fund investing into companies we are familiar and also interested in and attractive I think Susan.
and many global research team helping us to identify interesting targets to invest. So, plus we are also closely working with many China rising startup companies and we work with the hatch man.
on developing their CMAT drug, sevallatinib. And also as a starting point and in the future, I mean, Susan's team also signed several deals in cell therapy and also in claudin 18.2. And also we hope also to tap into the neuro-oncology rising innovation in China. So.
should benefit from rising innovation in China to make these innovation also accessible to the people outside China. So, thanks Leon. Just a couple of comments on the deals that we've done. So as you said, building on the relationship we've had with Hutchison Metafarma for Savaletinib, we've done three deals in the last 12 months with Cellular Biomedicine Group for the cell therapy asset, where they're helping by running the...
an antibody drug conjugate with an MMAE warhead again targeting claudin 18.2. So I do think you know as Pascal has said we've come back from China excited and energized by the interactions that we've got there the level of innovation and the science the quality.
the number of companies that are starting up in that space, it's very exciting and the quality of the investigators that you can work with is also really good. So I think it is an opportunity for us to leverage our position there and help us to actually...
not just think about China delivering for China, but China innovation delivering for globally relevant indications and accelerating that. So I think that's the opportunity that's there to be had. Thanks, Susan. Mark? First of all, let me remind you of the reason why Alexa invested in 1840. Wilson disease is a disease with an extremely high medical need where no innovation has taken place for decades beyond the copper chelators. So this is why Alexa invested in it.
Regarding the recent decision that we made, it's basically a case of looking at the totality of data and also close interaction with regulators.
The phase 3 that we produced in 2021 produced positive results, but then we conducted, as you mentioned, two mechanistic studies whose results were less clear. So when you look at the overall totality of the data, it was not possible for us to demonstrate that clearly.
a benefit risk for the Wilson population and then we decided to discontinue.
Thank you Mark. James Quigley at Morgan Stanley . Go ahead James. Hey it's Mark Purcell from Morgan Stanley . Apologies with the mix-up. Two questions. Firstly Pascal could you help us understand and put into context the pan-tumor opportunity for NhR2. So firstly the sort of probability and breadth of...
of the pantouma approval you may get from the PantryMOT2 trial, plans to move into earlier lines and then the importance of the PantryMOT1 trial in HER2 mutant cancer in terms of wrapping up a sort of broader opportunity there. And then sort of secondly the lung cancer slide 15 is super helpful.
I just wondered, given the sort of progress and the investment that's being made in gastric and GI tumours, could you sort of provide us some perspective of where you're heading here? I sort of know, as Susan just mentioned, the cholera 18.2 ADC opportunities, obviously validated with the Astellas monclamansibori and response rates of over 75% and potential combination there. So the gastric opportunity firstly and then secondly the...
calorific cancer opportunity where the EJFR tumor by specific ADC looks super exciting. So your thoughts there would be great. Thank you Thanks very much for that. Do you want to cover those? Okay, so thanks for the interest in the pan tumor in HER2 data which as I said are going to be shared at ASCO. So I think we probably have
more detailed conversation there about that. Obviously this is something we need to discuss with regulatory authorities and there'll be a question about the appropriate biomarker cut off across different indications. So I think we are also of course looking at the HER2 mutant setting. There is an overlap between the HER2 mutation and HER2 over expressions. So the HER2 mutant tumors are quite often highly over concerned and there will be data that
that's why we're excited about the coordinating point to ADC asset there. You know obviously we're also looking at combinations of ADC plus IO agents across the portfolio. With regards to the EG4 met by specific in colorectal cancer, yes there is over expression of both of these targets within colorectal
real potential is for these molecules but you're right that this is an area of interest for us.
Thank you Susanne. She must go over to you. Thanks for the question. So really my only question is on Iplontroson. We saw some impressive data presented at the recent neuro meeting. Hoping you could comment on that and also follow up.
potential? So I think we were particularly pleased with the functional data in terms of quality of life because we continue to see an improvement which I think is you know looks I think quite compelling and obviously I think the data that we've seen now and the consistency our data gives us more confidence given the mechanisms this is going to work well in cardiomyopathy as well.
So it's a relatively small population but there's a very large overlap with the main indication in cardiomyopathy. As we have announced, the FDA has accepted our filing and we are expecting hopefully a positive outcome in the second half of this year and the team in the United States is working of course on the pre-launch activities. Uniquely we are preparing ourselves for the CM indication, the much larger indication.
roughly there are between 300 and 500,000 patients worldwide with the CM, but there's also tremendous under-diagnosis in the CM. Most of those patients are detected very late in their disease state. Clearly with our activities in the HEF-PEP indication with Vassiga, we are expecting that the diagnosis rate will at least double moving forward. So all in all, it's a very substantial population.
in order to promote our product in the CM category. Of course, that will be a little bit later, that will be after 2024, but all in all, all the lights at the moment are clearly green. Thanks. Emmanuel Pavadakis, Deutsche Bank. Thanks for taking the question. APPS, first one on Propel, Head of the Advisory Review tomorrow.
Any perspectives you could give us on the FDA's stance that it is keen to potentially restrict approval to not just the HRR but actually the BRCA subgroup patients. So be interested to hear your thoughts on...
those documents and expectations into tomorrow. And then perhaps a question on floor two ahead of the imminent redo headline data. Perhaps you could help frame our expectations on PFS in light of the OPAL data that was presented at ASCO last year where you saw a 70% PFS rate at 24 months. Should we be thinking of a high 20s medium PFS that is achievable?
of the androgen receptor downstream signaling in Alaparib. So AR is involved in DNA repair in AR-driven cells and actually depends on part one. So with the combination, you get increased DNA damage selectively in AR-driven cells regardless of the brachistasis. And we have data to demonstrate that. So this is different from the monotherapy settings such as varying cancer, late line settings.
hence the difference I think with magnitude. The second point I make is the effect size in the BRCA wild type cannot be explained by false negative ctDNA testing. There's high agreement for the ctDNA and tissue testing in 94%. So if you look at the patients that are ctDNA negative and tissue undetermined, that's 226 patients in the
could be effectively misclassified. This cannot explain the effect size. And third point is that the evidence does not support that there's an OS detriment. I think identifying the double negatives both ctDNA and tissue-based negative study is looking at a subgroup of a subgroup. And in fact in the BRCA undetermined group the OS hazard ratio is 0.71. So if you look at the totality of the data and the totality of the secondary endpoints, I think it supports a good benefit risk profile for ELAPRIB in this.
patient population in combination with abiraterone. So you know that's our position. We'll represent that strongly at the ODAC tomorrow and we look forward to seeing what the results of that are. In terms of FLORA2, you know the OPAL data that was published is in a reasonable size patient population about 60 patients. So I think it gives you a reasonable confidence about the number of patients that are in that study was 31 months.
So I think that's the basis for assumption for FLORA2. You can obviously get some regression to the mean as you move from phase two to phase three, but I think we're confident in that effect size and the tolerability profile that we actually see for the combination. So I think this is going to be an important potential new opportunity for Sigrisso.
represents a choice that then patients can have. Not every patient will want a combination therapy but I think it represents a potential opportunity for those patients with bulkier disease or the endo-endo dispection. Thanks Suzanne. Matthew Westman, questions? Thank you very much. Two questions if I can. The first is a follow-up on Tropion Breast 01. Susan, you mentioned that recruitment was six months ahead of expectations but the readouts been brought forward I think nearly 18 months so can you explain the difference? Is it that you've shifted the focus to the PFS endpoint or co-primary endpoint rather than OS?
one. We have a dual primary endpoint of PFS and OS in this study. The endpoints haven't changed but the rapid accrual just gives us the opportunity for that to be read out at an earlier point.
you know, beyond the end of the year versus now coming into the year. So, you know, I don't think it really is as big a shift in the time lines as you're indicating. I think Suzanne, maybe this is a good time to give yourself a bad on the back and your team, because our recruitment has been incredibly fast and the team has done a beautiful job. Yeah. Well, let me give all the credit to the team, because other ones that have done the work. So, Christian Massachese's team and Michelle Sample, who's led the operations team, have done a great job here. You know, in terms of Chopin Lungo 1, what we said before, in terms of clinical meaningfulness, you know, you're expecting, you know, if you look at the contact 01 data set.
something in the range of four to five months, medium PSS for the control. I think it's a reasonable assumption and it's well sized for a clinically meaningful benefit, which would probably be in the range of two to three months on that background. I don't think that's changed either. That answers your question. Thank you. Louis Sector, learn back. Louis Sartre, go ahead.
Hi there, thanks Pascal. So maybe just a quick one again for Susan on when we might see the first response rate data for the internal ADCs that you highlighted. And then perhaps just if you can quantify in Q1 anything on price impact, there seem to be various movements particularly European clawback for mentioned in the press release.
So maybe split between US and Europe any impact on price and then stocking or gross to net impacts, which were also scattered throughout the press release. Thank you. Thank you, Louise. Susan, do you want to take the first one and Orwood you would take the second one? And you know, Dave, if you want to step in also, please do so. Maybe start with Orwood.
Yes, I would anticipate that we would share data probably next year for the early phase ADCs. Okay, and regarding Louisa, the clawbacks in itself in Europe specifically are not unusual. We are facing that year after year. It's our normal business practice and we are just flagging it.
in order to provide a little bit more color to our business performance. That's also true in the United States, very well of course in the United States, we are negotiating our crisis on an annual basis, and there are rebates and of course gross to net adjustments and we at least in the foreseeable future.
We expect to continue that. And of course, there's new legislation that potentially are coming in our own our way in the United States with the IRA, but all in all currently it's clearly business as usual. I mean, I think the only piece, Louisa, that I'd add to that is that I commented in my remarks on CalQuence and Limpar's stocking in the quarter. I don't have much more to add, but that certainly was relevant for both of those.
Michael Lucien, UBS? Thank you, two questions, please. Just going back to the speed of recruitment for both Flora 2 and Murray Posa. How do you square that with your view that monotherapy, if R is going to be the standard of care, if it has to be square at all? Just interested in your thought that both of these trials have recruited.
in Mariposa are recruited first and what does that mean in terms of physicians' interest in this combination? Well I mean there are patients who will want even more benefit than can be achieved with monotherapy to GRIS-SUR. But I'm just pointing out that if you look at the totality of patients that you're treating with HFR mutant lung cancer, a lot of them elderly.
you know, oral monotherapy that they can take at home is an attractive option. But if you're looking at patients that want to recruit at clinical trial sites and academic centers, that's a different patient population who are often looking for more options. So I think there's a large number of patients that have got first-line metastatic non-small cell lung cancer.
it's a big indication there's lots of opportunity to improve on the current standard of the camera. Maybe you could comment on the parts of it also from a commercial viewpoint, how do you see this FLORA2 and Mariposa combination and physicians reactions to those? Absolutely, so on Limparza, Michael on a sequential first versus fourth quarter
On the global sales, we see growth across Europe in demand. We see growth in rest of world also within international. In terms of within the US right now, I would say the demand is relatively stable net of the stocking that we described. I again made comments on this. There is opportunity for us to continue to grow Limparsa. Some of these opportunities are more challenging. It's about driving testing rates and ovarian and the HRD.
certain patients with a presentation of more aggressive disease. We also know that certainly if we're able to replicate the PFS results on the response rates of nearly 90% that we see in Opal along with the PFS of 31 months that we are seeing within Opal that there will be a subset of patients for whom that combination is something that physicians may very well want to be utilizing.
And so, as Susan said, while we believe that the majority of patients will be seen as most appropriate for monotherapy because it's oral, because we're getting good, you know, approaching two years PFS, and because the side effect profile is well understood for certain patients where the disease appears more aggressive, getting that response rate using FLORA 2 will be seen as attractive, and I think that that could translate into further
growth in terms of duration of therapy as well in terms of the period of time that they stay on Togressone. Thank you Dave. We will take the last question. Amara Singh at Interon. Go ahead Amara. Hi there. Thanks. It's Nars Sharon from Interon. Just a question on, a couple of questions on the power bench please.
So, I'm work with done to just then collect the eating into that CLL space and just could you all understand how far the BTK class is growing. And then secondly, how do you see pricing evolving for the BTK, particularly for Catwents? It seems also a really good price to be pulling quite materially over the last year or so.
Thank you. Thanks. So thanks for the question. On the first of the questions, and really I guess I'll focus my answer in the US. What we're seeing is that Venetoclax has been relatively stable in terms of its frontline
second line and frankly third line CLL share. I think that within that context, we have actually seen growth in the BTKI class. I think one of the benefits that's come from a new entrant in this next generation BTKIs is that it's created class growth, which I think has been certainly beneficial to CalQuiNS.
In terms of your second question, it's a good one and an important one. Historically, I've commented that contracting pricing gross to net has been relatively, I would say, sort of rational and lower pressure. We do see mounting gross to net pressures in the US, within the BTKI class, and I do think that as we look forward towards our...
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