Ladies and gentlemen, thank you for standing by. Welcome to the Sanofi Second Quarter 2021 Earnings Call. I would now like to turn the call over to Eva Sheffer Jonsson, Head of Sanofi Investor Relations. Please go ahead, Eva.
Good morning, good afternoon and good evening to everyone. Thank you for joining us to review Sanofi's 2021 Q2 results followed by a Q and A session. As usual, you can find the slides to this earnings call on the Investors page of our website at sanofi.com. Moving to Slide 2, I would like to remind you that information presented in this call contain forward looking statements that involve known and unknown risks, Uncertainties and other factors that may cause actual results to differ materially. I refer you to our Form 20 F document on file with the SEC and also our Document d'Orurgistrement Universelle for a description of these risk factors.
With that, please go to Slide 3. Our speakers on the call today are Paul Hudson, Chief Executive Officer the Global Business Unit Heads, Bill Sibout Thomas Triumph, Olivier Charmey and Julie Van Angeval John Reed, Global Head of Research and Development and Jean Baptiste de Chatillon, Chief Financial Officer. For the Q and A, you have 2 options to participate. Option 1, click the raise hand icon at the bottom of your screen or option 2, With that, I'd like to turn the call over to Paul.
Well, thank you, Eva, and thanks to everyone for joining our call. I believe our results in the second quarter are compelling evidence For how Sanofi's transformation translates into accelerating performance driven by Dupixent and growth across all of our businesses, All of it exceeding expectations. I'm particularly proud of our R and D teams and their achievements in driving visible pipeline transformation. In immunology and oncology, we have impressively strengthened the early to mid stage portfolio and DUPIXENT delivered On a potential new indication in record time. We saw an acceleration of sales and EPS growth with both top line and bottom line growing by double digits 12% 16%, respectively, in constant currency.
While the strong top line growth should be viewed against the backdrop of the Q2 of 2020, When sales of Jamed, CHC and Partly vaccines were impacted by the COVID pandemic, the recovery is simply quite outstanding. The primary driver of the strong top line performance in the quarter was an acceleration of growth for Dupixent, a 57% increase in sales, Growing impressively both in the U. S. And global markets, importantly, although Dupixent sales were not as affected by the pandemic as other parts of our business, Its sales continue to accelerate with now more than 300,000 patients treated globally. In vaccines, Our other key growth driver, business momentum continued with a 16% increase in sales and growth across most franchises, With the existing franchises performing according to plan or even better, we are increasingly turning our focus on the future innovation in the Vaccines business As evidenced by the recent announcement of the creation of an mRNA center of excellence.
We also saw growth in our other businesses, Jamed and CHC, both GBUs outlined their respective mid term goals in our recent Capital Markets Day on February 5, And I feel encouraged and optimistic to see the progress that we're making both structurally and in terms of performance. Since embarking on our savings initiative at the end of 2019, we have already delivered cumulative savings of €2,100,000,000 And we continue on our path to unlock operational efficiencies across the organization. The 2nd quarter results strengthen our confidence in our growth trajectory for the year And consequently, we are raising our full year guidance to around 12% business EPS growth at constant currency. Moving to Slide 5. Today, we also announced the appointment of 3 international leaders with world class pharma expertise.
Brendan will become the new Head of Industrial Affairs. Already with Sanofi today, he has been responsible for the development and acceleration of our biologics manufacturing capacity And is leading some of our world class manufacturing sites like the Factory of the Year in Framingham, U. S. Roy, who will be joining us from Novartis, will take over the role of Sanofi's General Counsel early next year, and he brings diverse experience acquired in private practice and large pharma coupled with exceptional commercial skills. Vivien will be breaking new ground as a chair of a company that is set to become one of the world's leading API players.
She brings 30 years of Experience leading financial operations in pharmaceutical companies and also serves as an independent director on a number of boards. I'm very excited with these new appointments, a mix of internal promotion and newcomers to our company with a passion for engaging and leading teams across larger organizations. Turning to Slide 6, let us talk about what is at the core of our play to win strategy, bringing new medicines to patients in need. Before John provides more insights, I'll give a few highlights of what we've been achieving over the last 18 months to bring our priority assets To patients by beating industry benchmarks in R and D productivity. Dupixent is only at the beginning of its journey penetrating the large type 2 penetration The large type 2 patient population in atopic dermatitis and asthma.
And commercially, it is well on its trajectory to deliver on our ambition to exceed €10,000,000,000 in peak sales. Since December 2019, we have initiated trials in 6 more indications to expand the potential of this amazing once in a lifetime medicine into adjacent type 2 inflammatory diseases. As just mentioned, our latest success It's a milestone in chronic spontaneous urticaria or CSU by meeting the Phase 3 clinical trial primary endpoints, regulatory submissions for this investigative indication A plan for next year. We presented exciting data from the amsinesterin AMIRA program at ASCO in June, demonstrating its potential best in class Our first line program is well underway and we've decided to move into the adjuvant setting. We are thrilled to begin global submissions for nasevumab 1 year ahead of our initial plan.
This antibody has the potential to protect all infants during their 1st RSV season. We're looking forward to sharing the positive data from the MELODY and MEDLI studies with you in due course. Substantial progress has been made with Efra and fitusiran, our potentially life changing treatments for patients with hemophilia, I'm excited to present data from the Phase 3 studies as early as the beginning of next year. And finally, with tolebrutinib, we're enrolling across our 4 Phase 3 studies Greater than 95% of our patients retained on the Phase 2b open label extension study, Quite remarkable. We remain convinced in the transformative potential of Venlastat as a breakthrough treatment for patients living with lysosomal storage disorders With our expectation that priority assets have potentially transformative value for the company as a whole, Venglustat's Revised focus on the LSD indications has led us to reprioritize the resource deployment on those priority assets listed on the slide.
Beyond those, on the slide, we have an increasing number of other innovative molecules in our pipeline, And we will introduce further priority assets to you as the data continues to evolve. Now turning to Slide 7, Sanofi's diversity and inclusion strategy is well embedded in our play to win culture with clear priorities. Regarding gender equality, we are on an encouraging path with 40% of our leadership roles held by women today, but clearly our commitment remains for women to hold 50% of those roles by 2025. In the U. S, people of color now represent 31% of the Sanofi workforce.
And here our commitment is to align with the representation of our patient base by 2025, which is estimated to be around 37%. There is great work underway across Sanofi's organization with many best practice initiatives Of how we include diverse communities in our workforce. For example, during prior month in June, many country organizations' teams came together to drive local campaigns, providing LGBTQIA plus communities with forums to create a culture of inclusion and equality at work and beyond. While we're encouraged by our progress, we recognize that we are nowhere close to where we need to be. Our journey will only be complete when Sanofi's workforce is fully representative of our diverse society.
And now let me hand over the call to Bill to begin the Q2 business reviews. Bill?
Thank you, Paul. Starting with Dupixent on Slide 8, Dupixent delivered in an outstanding quarter with Accelerated worldwide growth of 57 percent driven by strong performance in the U. S. As well as in the ex U. S.
Markets. Annualizing at €5,000,000,000 and well on its trajectory to achieve our greater than €10,000,000,000 peak sales ambition, Dupixent added almost €200,000,000 of incremental sales in the period versus the Q1 in In office visits remaining below pre COVID levels. As we progress into the second half of twenty twenty one, We are excited about key milestones which could make Dupixent accessible to younger patient populations in both asthma and atopic dermatitis Supported by its well established long term safety profile. We are anticipating the FDA decision for 6 to 11 year olds in asthma, As well as the pivotal data in our AD trial below the age of 6, close to a year earlier than planned as enrollment completed much faster. We also continue to advance the science into additional inflammatory diseases with the key readouts in prurigo nodularis And eosinophilic esophagitis expected this year.
On Slide 9, let me highlight the positive results Of Dupixent in patients with chronic spontaneous urticaria announced today. CSU bears the hallmarks of Type 2 inflammation And is characterized by hives and or skin swelling and is associated with intense itch. This chronic disease has Potentially severe impact on quality of life and is typically treated with antihistamines. However, for up to 50% of people living with CSU, Their disease remains uncontrolled. An estimated 300,000 moderate to severe patients are eligible for biologics in the U.
S. Putting this into context, the eligible population is as large as the number of patients on Dupixent globally today. The top line results at 24 weeks from Study A of the LIBERTY Cupid trial program demonstrated that DUPIXENT nearly doubled the reduction in And its approved indications. Regulatory submissions are planned to begin next year as Study B of the trial program, A study of patients who remain symptomatic despite antihistamines and omalizumab is ongoing with expected readout in H1, 2022. Moving on to Slide 10 and taking a closer look at our approved indications in the U.
S, Dupixent has the potential to address the lives of over 3,000,000 patients. Clearly, we are only at the beginning of penetrating the large US market with only 6% of the biologics eligible AD patients treated today. Similarly, in asthma and nasal polyps, we're only starting to unlock the opportunity and have a tremendous growth potential ahead of us. Driven by our ambition to expand into the pediatric populations, we have the opportunity to add an incremental 150,000 young patients in total In our core indications, separately, we are executing on a robust clinical development program in multiple adjacent Type 2 indications, Which could unlock additional growth opportunities. These indications combined have the potential to address an additional population of 600,000 patients in the future.
Notably, let me remind you that we consider the type 2 COPD indication and upside to our Peak sales ambition and therefore have not included this significant population in the patient number for the adjacent indications on this slide. Advancing to Slide 11 and turning to the other specialty care franchises. The rare disease franchise continued to deliver growth In the Q2, with higher sales in all reported regions and strong performance from our Pompe and Fabry franchises. Growth rates have to be seen also against the backdrop of the Q2 of 2020 due to COVID when receiving treatment was very challenging for patients. In Pompe specifically, we are looking forward to the FDA PDUFA date for avaglucosidase alfa in August.
Our neurology and immunology franchise was down slightly as Abagio continued to be resilient in the increasingly crowded MS market. The franchise showed strong growth of 14% outside the U. S. Offset by the expected lower U. S.
Sales with recent competitive launches. Rare blood disorder grew 17% excluding sales to Sobe. Franchise growth was mainly driven by increased sales of Alprolix And Keblevi in the U. S. As planned, sales to Sobei were lower in the second quarter and we anticipate this dynamic to continue into the second half of twenty twenty one.
As our presence in oncology is reemerging, sales of the oncology franchise were up 25%, Supported by the encouraging uptake of Sarklica and Libtayo, which collectively achieved more than 300% growth. With that, I turn over to Thomas to update you on the vaccines business.
Thank you, Bill. Vaccines delivered another strong quarter with 16% growth demonstrating that our business is progressively getting back towards the pre pandemic trajectory. The U. S. Business performed particularly well, growing 84%, recovering from a low Q2 2020, in particular the Menagerie's franchise That was already off to a good start in Q1.
We launched 2 important new product in the U. S. This quarter. MenQuadPhi, The only FDA approved quadrivalent menagococcal vaccine indicated for individuals above 2 years of age and Vaxelis, The first and only exavenant pediatric vaccines in the U. S.
Outside the U. S, sales were negatively impacted by lower birth rates And by ongoing COVID-nineteen immunizations that have been prioritized over routine immunizations. Flu had a solid performance, up 9% versus Q2 last year. And we continue to plan for a record Northern Hemisphere flu season in terms of sales. From a phasing perspective For this North Hemisphere season, we still expect around 50% of those sales to occur in the Q3 of the year.
Also, We initiated our global Phase 3 study for a recombinant COVID-nineteen vaccines candidate. We assume to collect sufficient events by Q4 this year to read out the data. Meanwhile, a rolling submission process has already started in the EU. For the mRNA COVID-nineteen vaccine candidate, We continue to expect Phase III data in Q3 of this year. On Slide 13, let me explain how Vaxelis We'll simplify routine infant vaccination in the U.
S. Prior to the vaccine list launch, infants receive a pentavalent vaccine plus a separate vaccine To protect against 6 diseases. Altogether, this represents 5 of 6 injections in the 1st 6 months of age. This is shown on the left part of the chart. With Vaxelis, we can now reduce the number of injections required from 5 or 6 down to 3 injections.
As you know, exavallant pediatric vaccines have been launched in our Western markets and have taken majority share within 3 years of launch. We do expect Vaxelis to capture significant market share in the U. S. From both available pentavalent vaccines. For your reference, Pentacel, the Sanofi pentavalent U.
S. Brand represented around 2 third of our 2020 PPH U. S. Sales. Importantly, Pentacel sales will not completely disappear because of the booster regimen shown on the lower part of the slide.
Infants who receive Vaxelis for their primary vaccination will likely receive a pentacel booster dose To continue immunization with consistent antigens, meaning that while Vaxelis cells will replace Pentacel in the primary series, Pantacel is likely to become the booster of choice at 18 months of age. Vaxelis is commercialized through our joint partnership with Merck, Leveraging both companies' existing commercial teams instead of setting up a separate infrastructure. Sales are recorded by the joint partnership With Sanofi booking 50% of the profit, I'm glad to share today that this setup is profit making from the very start. Let's now talk about Sanofi's MR and A center of excellence on the next slide. We did recognize the potential of this technology before the COVID-nineteen pandemic, Signing the initial transit buyer agreement in 2018.
From that time we saw mRNA as an additional tool in our vaccine toolbox. Sanofi's Ameri Center of Excellence will accelerate the development and delivery of the next generation vaccines by bringing together 400 dedicated employees in both in the U. S. And France with end to end expertise from R and D to CMC And from manufacturing to regulatory filing. We will be science driven and explore both unmodified and modified mRNAs To get the best possible construct.
In parallel, we recently invested in Evolutive Vaccines Factory, a very innovative industrial concept, Versatile enough to accommodate mRNA manufacturing in addition to other technologies. With this investment in mRNA, We are looking forward to delivering an innovative next generation of vaccines beyond pandemic with the ambition of a minimum of 6 clinical candidates by 2025. With this, I now hand over to Olivier for General Medicines.
Thank you, Thomas. In General Medicines, we are Extremely pleased with the performance of the Q2, which reflects on the execution of our strategy. Our core assets delivered 12% growth during the period. The 6 key brands in our core asset portfolio reported solid growth in the quarter. LOVENOX was up 25% and continued to benefit from inclusion in the WHO guidelines for the treatment of hospitalized severe COVID-nineteen patients In addition to a low base last year due to deferred elective surgery.
Toujeo grew 8% due to the launch execution in China and Continued strong adoption in European markets. Toujeo remains on track to reach blockbuster status. Plavix returned to growth in the Q2 and grew in both volume and sales in China, up 8% in sales more than 1 year for its inclusion in the VBP. On the other key brands, let me point to differentiating data for SOLIQA Presented at ADA in June, the SOLIMIC study demonstrated improved blood sugar control without weight gain For patient on therapy with Soliqua versus premixed insulin, we believe this provides us with the opportunity to further drive growth of Soliqua In large markets, we have premixed insulin are still widely used. So broadly stable sales performance of our non core portfolio Benefited from the pricing environment this quarter offsetting the loss of revenues from our strategic portfolio streamlining initiative.
Turning to China. Sanofi participated successfully in the BBB Wave 5 bidding for eloxetine in June with implementation expected in the Q4. We do not expect significant sales impact on the full year from the VBP wave 5, But we remain vigilant to learn about any potential mechanism for the inclusion of the insulin class. Part of the transformation of the General Medicine business continues to be the streamlining of our sales products and reduction of our geographic footprint, And we delivered on this commitment with recently announced product divestment and a more simplified infrastructure in European countries. Overall, we are confident in our strategy execution and on track to deliver on our commitment to stabilize sales by 2025 as compared to the 2020 pace.
With that, I hand over the call to Julie.
Thank you, Olivier. I'm very pleased with our return to growth in the Q2, not only versus last year, but also on a pre COVID comparison. And I'm happy to say this strong performance is, to a large extent, the result of the new focus on our key brands and markets that we shared with you in February. The double digit growth in the quarter also reflects the strong recovery of the CHC market against the low basis for comparison of the prior year When in person pharmacy traffic was significantly impacted by the pandemic, coupled with the unwinding of the high inventory at the consumer level. Our priorities put behind our wellness categories are driving growth with Digestive Wellness performing particularly well in the Q2 led by our brands Endergiamina, Buscopan, Dulcolax as well as essentiale in lever care.
I'm also encouraged by the acceleration of our sales through the e commerce channel with significant growth from some brands and in key markets. Importantly, we execute on our strategy to reduce the complexity of our portfolio. We recently signed a couple of meaningful divestiture agreements, which enable us to increase focus on our strategic brands. Another very important step to note is that to date, 10 legal entities have successfully become stand alone, which is in line with our road map to create a fast moving consumer health care entity with agile and adapted ways of working. In summary, both the return to growth of our CHC business in the Q2 as well as the advancements on our strategic roadmap Increase our confidence in the value of our business.
With that, I'm happy to hand it over to John for an update on transforming R and D.
Thank you, Julie. Turning to Slide 16 now. When I joined the Sanofi team in mid-twenty 18, We set out to fundamentally transform our pipeline and bolster productivity of the R and D organization. Moreover, We aim to accomplish this transformation with a flat or even declining budget by making the necessary trade offs and mandating far more focus. Key to this ambition has been the rigorous prioritization of projects.
I'm proud to say the productivity of Sanofi R and D has doubled. And this is reflected in the pipeline. Comparing the 2017 Sanofi portfolio with the 2021 Shows the results both in quantity and most importantly, quality of molecules in development. With respect to quantity, we've achieved an 80% increase in the number of NMEs in development without increasing our budget. And with respect to quality, 89% of our molecules in development now have a clear 1st in class or best in class target profile.
A few examples of molecules that began their development journey since 2018 are listed here, Ranging from our oral selective estrogen receptor grade or amsinestrin for breast cancer to our brain penetrant oral BTK inhibitor for multiple sclerosis to Our exquisitely engineered extended pharmacology factor VIII replacement for hemophilia A, EFA. 2, our non alpha interleukin 2 molecule For immuno oncology, created using a recently acquired synthetic biology platform that I had been monitoring for a couple of years waiting for de risking data that Provided the confidence to pounce on the opportunity. In addition, our IRAK4 to greater in collaboration with Chimera recently achieved clinical proof of mechanism. The reinvigoration of the Snowflake pipeline has been greatly accelerated through M and A with 6 innovative companies bolted on. These are supplementing our pipeline and importantly, adding drug discovery platforms contributing to improved research productivity going forward.
Today, our drug discovery toolbox is much more diverse, going beyond small molecules, insulins and recombinant enzymes to add platforms and antibodies Fully human monoclonal antibodies from QIAIMAN, synthetic biology inspired recombinant proteins from Syntorix, mRNA delivered in vivo into selective types of cells using highly engineered nanoparticles from Tidal, Universal NK cell therapies for immuno oncology from QIATIS and even new twists on small molecules from Principia. Moving to Slide 17. Among our late stage oncology assets is amsinestrin, Our oral selective vestrin receptor grader or SERD. This molecule has the potential to become a best in class endocrine backbone therapy for hormone What makes amsinestrin best in class? Well, it's all about the structure of the molecule, Setting Emsenestrin apart from competitors.
You can think of SIRG as having 2 components, a core scaffold that binds the estrogen receptor shown in the box, And an arm shown in green that engages cellular protein degradation machinery to eliminate the estrogen receptor from cells. Now Sanofi's, the greater arm is a bit different from competing surge, but our scaffold is entirely different. As a result, Amsynestrant possesses competitive efficacy, but without the side effect baggage of competing surge. This best in class tolerability profile really matters when treating early stage breast cancer, particularly in the adjuvant setting Where women can be on therapy for 10 years. We've launched a broad program to assess the efficacy and tolerability of amsinastrin across All lines of therapy from early to late.
Our fast to market opportunity is found in the study we call EMIRA 3 In late line metastatic breast cancer, this is a high bar challenge for Amsynestra, particularly in a world where most women will have already failed an aromatase inhibitor combined with the CDK4six inhibitor. But if successful, IMIRA3 could bring amsinestrin to market within 7 years well ahead of standard Industry cycle times. We anticipate the event driven readout for EMEA-three in the second half of this year. Our Phase 1 data showed a respectable 36% clinical benefit rate, which rose to 64% for patients who had not already received fulvestrant or kinase inhibitor. Treatment related adverse events were mostly grade 1, some grade 2, but Unlike competing surgeons, no grade 3.
EMIR5 in frontline metastatic breast cancer Compares CDK4six inhibitor, palbociclib, in combination with either rmsinesterin or an aromatase inhibitor. We expect this trial to be fully enrolled faster than planned if the enthusiastic response from the investigator community continues at the current pace. At ASCO last month, we presented our pilot data for amsinestrin combined with pavlcyclib, reporting an overall response rate of 34% And an impressive clinical benefit rate of 74% for this combination. Again, our safety profile was consistent with best in class Tolerability. Today, we are the only company having demonstrated encouraging Phase 1 combination efficacy data At the Phase III dose.
For early breast cancer, our first foray into the adjuvant setting is set to begin towards the end of this year. As announced at ASCO, we're pleased and honored to join forces with some of the world's leading oncology cooperative groups working on breast cancer To conduct a seminal trial in aromatase inhibitor intolerant patients whose tumors have high risk features. Our study will put amsinestrin head to head against tamoxifen. While representing a subset of the adjuvant population, This study design affords the opportunity to reach the market relatively quickly by adjuvant standards. Recognize That an estimated 30% of women with early stage breast cancer failed to complete the prescribed 5 years of adjuvant therapy Due to tolerability challenges with the aromatase inhibitors.
Now on Slide 18, please. I can point to several other examples of our progress in oncology that also occurred in Q2. 1st, SAR-two forty five, a potential best in class non alpha interleukin-two molecule from the Synthorix platform now being tested in Several oncology indications and contexts as monotherapy and as combination therapy. In our broad phase 2 program, We are leveraging 245's impressive ability to selectively expand effector T cells without undue expansion of immunosuppressive regulatory T cells by combining 245 either with our cemiplimab or with Merck's pembrolizumab. In addition, 245 will be tested in combination with ADCC competent antibodies such as cetuximab to leverage the impressive NK cell expansion That our molecule stimulates in patients at very well tolerated doses.
In the second panel, SAR-eight eighty one is a Trailblazing entrant into the frontier of checkpoint inhibitors partnered with Beyond Biosciences. 881 targets ILT-two, a checkpoint receptor found principally on myeloid cells and NK cells, as well as a subpopulation of PD-one negative exhausted T cells. That molecule just entered Phase 1, and we are anxious to combine 881 with other molecules in our portfolio. In the 3rd panel, Snelpi's first entry into cell based therapeutics is represented by the universal NK cell platform With the objective to bolster our emerging focus on NK cell based immunotherapies. We expect these universally compatible NK cells to combine well with Other molecules in our portfolio.
And finally, in the 4th panel, I would highlight our antibody drug conjugate molecule, tusamitamabraftansim, Our potential 1st in class, CCAM5 targeting ADC, now in phase 3 for advanced lung cancer. TUSA aims to not only become the standard of care for patients with CKAM5 high expressing tumors in second line post immunotherapy, But also to become the cornerstone of therapy in first line non small cell lung cancer in combination with a PD-one. Looking beyond lung cancer, this quarter we started a basket trial in additional CCAM5 expressing tumor types, namely Rest in pancreatic. My final slide, Slide 19, lists the pipeline milestones expected for the second half of the year. It includes potentially registration enabling pivotal trial readouts for DUPIXENT in 3 new indications.
You heard about one of those from Bill. We have pivotal trial readouts also for our internally invented anti CD38 antibody, Sarclisa, in treatment naive frontline myeloma And for our internally invented oral SERD, amsinestrin, in late line breast cancer and for rilzabrutinib, the oral BTK inhibitor acquired from acquired from Principia, which we'll read out later this year for a dermatology indication. We also expect to put an additional 5 molecules into the into the clinic in the second half of twenty twenty one, including some really interesting multi specific nanobodies. Finally, I would mention with pride that the FDA approved fexonidazole for the treatment of African sleeping sickness. Bexonidazole was discovered in our laboratories in Frankfurt and developed in collaboration with the non profit organization Drugs for Neglected Disease Initiative.
It represents the 1st convenient oral therapy for African trepannosomiasis, a milestone in Sanofi's long stand commitment To eradicate this neglected tropical disease, the FDA will issue a priority review voucher for this accomplishment. And with that, I hand over to our CFO, Jean Baptiste.
Thank you. Thank you, John. On Slide 21, turning to our financial performance. Company sales increased 12.4% in the 2nd quarter, which helped to drive a 16.4% EPS growth in the period. We are improving on our gross margin, improving 40 bps in the quarter, 70 bps at constant exchange rate, resulting from our favorable portfolio shift to Specialty Care products and efficiencies within Industrial Affairs.
This improvement is more than compensated for lower gross margin in the vaccines unit that was affected this quarter by product disruptions With limited remaining shelf life due to the pandemic, R and D spending increased during the quarter, driven by advancements of our priority asset. We also continue to add R and D spend from recent acquisitions with the 3 deals closing during the quarter, partially offset by operational efficiencies. Higher SG and A spending was driven mainly by investment in advertising and promotion behind our specialty care products, but also needs to be seen against a low level of 1 year ago. Other operating income benefited from capital gains on portfolio divestments of around EUR 50,000,000. In the same period last year, we booked a €157,000,000 gain on the revaluation of the retained Regeneron shares.
And lastly, our EPS growth continues to be supported by the anticipated lower effective tax rate of 21%, which we guided to in February as part of the full year financial guidance. On Slide 22, we believe that our strong performance in the first half Puts us on the right path towards meeting our communicated midterm finance target financial target with BOI margin of at least 30% in 2022. Driven by a 7% top line growth, we increased the BOI margin in the first half of twenty twenty one by 100 bps 28.3 percent or 160 bps at constant exchange rate. If you would exclude the product portfolio divestment related capital gains From the other operating income and expense line, both in the first half of twenty twenty and twenty twenty one, The underlying BOI improvement at constant exchange rate reaches 170 basis points. This is achieved solely Through sales growth, shift in product mix and efficiencies.
The underlying improvement in BOI is expected to continue With Dupixent as a primary driver, we now expect Dupixent to be accretive to BY margin for the full year of 2022 instead of by the end of 2020 As previously communicated. Importantly, we also have plans in place to deliver significant COGS improvement on Dupixent from 2023 onwards. On Slide 23, I will now provide an update on our savings initiatives. As of H1 2021, we have achieved around €2,100,000,000 of cumulative savings, adding another €450,000,000 savings in the past 6 months. We continue to make strong progress, especially in the area of smart spending.
We expect that COVID related savings of €230,000,000 are not permanent. So those need to be seen in addition to the overall €1,000,000,000 target. Savings added to operational excellence were Generated mainly in manufacturing and this will also be the main area for future savings to reach our goal of €1,000,000,000 next year. We remain on track to achieve our target of €2,500,000,000 savings by 2022 with most of this year's or next year's savings to be reinvested behind our growth drivers on key programs in R and D. Moving to Slide 24.
Free cash flow continues its positive trend. Compared to the 2018 base, it has increased by more than 100%. This is again driven by Sanofi's solid business performance and smart spending initiatives. The comparable period in 2020 benefited from larger asset disposals Not repeated in 2021. And in addition, we had significant cash outflows in the first half of twenty twenty one to finance M and A on business development deals.
As a matter of principle, we stand by our midterm target concerning free cash flow, which we intend to continue To maximize while investing in science. On Slide 25, we summarize expected dynamics for the second half of twenty twenty one. For pharma, we expect continued growth from Dupixent and Gen Med core assets. For Lovenox, in particular, we expect growth rates to slow. The latest round of China VBP will be implemented late Q3 to Q4 this year and uncertainties remain around the mechanism for insulin class inclusion.
For vaccines, we expect another record flu season and continued recovery of meningitis on the accounting of Vaxelis On lower birth rate may affect DPH sales. In Consumer Health, we expect to make further progress on business simplification Similar to what we saw in the first half. In terms of non sales items, we expect to continue improvement in gross margin. With the expansion of our pipeline, R and D spend is likely Trend in line with the increase in the first half. On a separate topic, we plan to host a vaccine investor event in Q4 of this year, where we expect to discuss our industry leadership and our emerging pipeline.
On Slide 26, based on the strong results Of the 1st 6 months of the year, we are raising our full year guidance for 2021 business EPS. We now expect business EPS to grow around 12% at CER. The outlook regarding foreign exchange impact continues to be negative by minus 4% to minus 5% based on July average exchange rate. So let's open the call now to Q and A. I hand it back to Eva.
Thank you. So we will now open the call to your questions. As a reminder, we would like So for the Q and A, you have 2 options to participate. Option 1, by us. Now we will take the first question.
Thank you, Eva. So we will start the Q and A with Peter Verdult at Citi. Pete?
Yes, thank you. Good afternoon. Pete Bedalt, Citi. Two questions. Just for Paul or JB, realize it's not going to be today, but when is the earliest You might think to update the market on your midterm financial targets.
I only ask this question in light of the business trends you're posting, The fact that you've absorbed the hit from the Regeneron stake disposal and increased R and D from M and A and you're now guiding to Dupixent being accretive Sooner than previously expected. So just an update there and then very quickly just a quick strategic one for Paul. KOLs love DUPIXENT but a consistent message we hear is that The need for an oral efficacious oral with a safe to safe clean side effect profile is the biggest Area of unmet need. Now JAKKS hit on efficacy, but we could we'd debate and probably agree that safety is not as clean as hoped. So just strategically outside of JAKKS, what would your interest level be to add an oral mechanism To your atopic dermatitis, if that sort of profile does emerge over the coming years?
That's the question to you. Thanks.
Okay, Pete. Thanks so much. Maybe JB, mid term guidance and how we're balancing investment in R
and D and how performing and how we're going to navigate that.
Yes. Thanks. It's important to reiterate our prediction on our midterm target. We said we will be Turning toward 32% BOI margin by 202530% in 2022. And this is for always the same reason.
You see how we move forward. We reinvest our savings to stimulate the growth And to enrich a pipeline, you will see more of that. And it's that's why we are not looking at beating those expectations in terms of BOI margin, because the priority is how to reach another level of growth in the midterm. So priority to the science, priority to the pipeline, priority to growth.
Thanks, Jebi. Peter, in answer to the question, Dupixent sets a very high bar on safety and efficacy. You've seen we've added CSU, at least the data Today, we're very excited about the long term with Dupixent. You also know from what we presented, I think, on February 5 that We're excited about some of our adjacent mechanisms. 2 of them all or wilzabrutinib will go into atopic dermatitis and Our Iraq 4degrader will also be in atopic dermatitis.
So we recognize there may be a place for it. But let's be clear, I think, Dupixent sets a very high bar. Of course, adjacent, again, we have the OX40 ligand injection with the CAMAP Acquisition. But no, we know patients will are very interested in orals, but we also know safety and efficacy are the number one Reasons to choose, we feel over time and we laid out on February 5, we've got the full picture for whatever patient need will be, but importantly, safety and efficacy of the next decade plus.
The next decade plus.
The next question is from Wimal Kapadia at Bernstein. Wimal?
Well, great. Thanks very much for taking my questions. Wilma Capadia from Bernstein. So firstly, just on CSU. Now that you've seen at least the first Part of the data, has your thinking evolved into the potential eligible patient populations where DUPI could be used?
Previously, we've talked about Zolair refractory patients And potentially populations with low IgE. So whilst I appreciate you have not seen Part B of the data, which will be key, has your thinking changed for the potential of Guppy In CSU. And then my second question is just on about glucosides alfa in Europe. What sort of delay are we potentially looking at for approval? I'm just curious What EMA's rationale here is, does it relate to the fact that they don't really see similar proteins with different glycosylation patterns As a new substance.
And then just tied to that, does your decision to ask for further consideration reflect a different pricing strategy for the product, I. E, You're looking for a premium price versus Myozymes.
Thank you.
Okay, Vimal, thank you. Bill, going to head towards you for CSU and the potential patient populations in Part A, Part B and maybe before you hand back, you'd like to make a comment on avowed glucosidase.
Yes. So first of all, thanks for the question. You asked from a timing perspective, we would expect that the CHMP reexamination would take place sometime in Q4 2021. We're not going to comment too much on any of the specific details. We believe that it's a new act And from a pricing perspective, too early to comment on pricing.
Look, we think this is going to be the Leading product in Pompe. So we would expect that it'd be recognized for that innovation. So then maybe switching to CSU. I mean, look, first of all, we're really just excited about these results in this first Phase 3 study of CSU. And maybe just to provide a little bit of context here of where we think this Sitsum what the opportunity is.
Now starting with this is a indication that has really still a really significant High level of unmet need and there's really been limited innovation in the place when you think about it. The last Positive Phase 3 readout was in 2013. So there's a lot of unmet need there. And we have we know that a significant number of the patients are uncontrolled. So to give you just an idea of the size here, we think the biologic population Should be about 300,000 patients and those they have moderate to severe disease and they don't respond adequately to standard of care, which is antihistamines Alone.
Now the opportunity with the biologic, it's under penetrated at the moment. Omelizumab, we think it's about 15% of eligible patients that are currently treated with that. And we expect that The penetration in this indication could double over time to near 30%. Now we also know that with omalizumab That about half the patients are uncontrolled. So we look at this as a couple of a few sources.
First of all, There's the expansion of the market. There's a profile that we think that is going to be better. Ours is has a strong safety profile, Dupixent, no black box and it has at home administration. So we've got the right profile and large market, low penetration, Better profile, we're really excited about this. Hope that gives you an idea of what the opportunity is.
Great, very helpful.
Thanks. Yes. Thanks, Bill. Also, it's interesting to watch what the off treatment durability was, not that we'd ever recommend that, but Interesting to see how we may be targeting some of the underlying mechanisms in CSU. And I think it's going to be fascinating.
Look forward to the Part B And what that tells us, because then maybe we have the complete picture and that's going to be very exciting for patients. Who's next?
The next question is from Jo Walton at Credit Suisse. Jo?
Apologies. I've got 2 questions please. 1 on the COVID vaccines And the use of adjuvant. So when your vaccine your original vaccine is an adjuvanted one. Is it is it a 2 injection regime.
Just trying to think how convenient it would be and whether you feel that you will have something that is sufficiently differentiated that it could be widely used In Western markets whether you feel that the existing vaccines of Pfizer for example that just now so entrenched that Then the regulators are not going to be that interested in going for an incremental approach. And my second question is just on the Dupi CSU data. Excellent news that you've got such strong each data there. Do you think there's anything that you can use to sort of See how that would help against lebrikizumab because I understand it lebrikizumab one of their key elements Is that they can show better itch than is normally seen. So I wonder how you feel at that how you compare there?
Thank you.
Okay. Thanks, Joe. Maybe, Thomas, you want to comment on what our place could be? I think we have some pretty firm ideas you want to share.
Yes. Thank you, Joe. So indeed I confirm the COVID-nineteen regimen in primary is a 2 dose regimen. But you know that in parallel we're also testing Testing, sorry, booster possibility, which will be then a one dose regimen. And what's interesting and we've communicated about it before is that We're looking at the ability for the protein adjuvanted platform to be a booster of every any single platform that has been used in the primary sales.
So whether you received an adenovirus platform or whether you received an mRNA platform or a protein platform, we believe there's a chance for our product to be a 1 dose booster For all of these thermostable at room temperature therefore. But of course, as we mentioned before, it's going to be Q4 data. So we'll remain completely data driven. And in Q4, we will read out the booster data and the primary data. And that will determine where we're going from, forward from this product.
Yes. Thanks, Tom. I think we're all expecting there's enough volume of vaccines for primers that will be certainly as go through the remainder of the year worldwide, in fact, that we see our role mainly as a boost of our data strong. I think we're going to play a really interesting part. And we're optimistic that, that will be the case.
And that's I'm not sure, but as a booster, it would be a watch. On your other point on Dupi, I mean, I can toss it to Bill. I think our data is really strong in CSU, Right. And I think we've still get to get to Part B. I mean, we're really pleased with the data.
I can't stress that enough. And the size of the unmet need, It's significant, really significant. We've said it before, but lebri and the other IL-13s, they're only half the answer. We're in IL-thirteen, IL-four. You've seen lebri, I think, discontinued or failed from recollection in asthma.
And so you start to understand the importance of treating type To inflammation, I think we have best in class, frankly. Bill, do you want to add something?
No, I agree. Just the read over, It just supports our efficacy in a disease with itch. And as Paul said, IL-thirteen, it's an incomplete profile, right? I mean, it all comes back As we think about this asset to the fundamental biology of the IL-four, IL-thirteen and we think that's just so key and you're seeing These continue readouts in disease after disease that rely on that mechanism of action. So positive, Great opportunity for us, just continues to fill in the picture for what the potential of Dupixent is.
Great. Thank you.
The next question is from Geoff Porges at Leerink. Geoff?
Thank you
very much for the question. Just to follow-up on an earlier question First, Tom Guppy, the injection frequency in addition to the injectable administration is an issue and many of your competitors with large biologics Adapted their product profile to reduce the frequency of dosing. I'm wondering if you have projects internally To potentially pursue that, that would actually also act as life cycle extensions. And then
Wondering if you could just talk a little bit
more, John, about Rilza. It's something you didn't really highlight, but you're going to have the Pampers readout by the end of the year. And to what extent or as a different way, what are you looking for in the Pemphigus readout that would potentially Tell you about the likelihood of the drug succeeding in some of those much larger indications that you've talked about, say asthma and atopic
Thanks, Geoff. Bill, dosing interval, DP?
Yes. Look, I think, Geoff, thanks for the question, first of all. Look, you got to look at the whole profile, right, because people are taking the product for efficacy first and foremost, Safety and then you look at convenience and that's why we've gone back to the JAKs a bunch of time. That may be a convenient way to dose but it's going to be a If it makes it to market ever, a highly black box broad immunosuppressant. So you can have you could have something which is incredibly Convenient to take, but if it is has bad side effects, It isn't going to make the difference.
So we think that the profile that we have with Dupixent and it continues to play itself out Time and time again in every indication in every geography that dosing is not a challenge for us. It's the whole profile of the drug that people are looking at. So we feel Extremely confident in being able to compete with anyone who enters this market in the foreseeable future with the profile that we have, including
frequency. Well, so Bill, we I think what surprises most of you, it surprised me when I joined the company, it's very rare that the 1st to launch in a major disease is 1st and best. And you have to get your heads around that a little bit Because we've touched on the IL-thirteen's half the answer. We look at IGE, Black Box, we look across and we say Everybody has got something that they have to be working on or to communicate. We have great safety.
We have Excellent efficacy right across all these indications. And normally that comes later in a disease. We've gone out front. It is the best medicine. If you look at the development of the sales performance, as we really crushed Q2 and go on, it's basically stood on the top of safety and efficacy.
It's an incredible profile. You have to accept that first was best, and that's an unusual situation, I know. John, Rilza read across from Fenfigus to potential other indications?
Yes, thanks for the question. Rilza has brought potential in several contexts, but Pemphigus is a classic auto antibody driven disease and our Phase 2 data showed Tested the mechanism of RILs are there and we're quite impressive and that's what caused us to move into the Phase 3. We have Similarly impressive data in another auto antibody driven disease, namely ITP, immune thrombocytopenic purpura. So A couple examples there where the molecule has achieved proof of concept and we're in Phase 3 for both of those indications and we're doing more in auto antibody driven diseases Based on the confidence building data we've seen in those, in terms of the Extension then into some of the other indications, I think there are some similarities in some cases, and then there are differences in others. And that's why we're doing the we're intending to test Rilza across a number of indications.
The interest Thing about Rilza is that it has ways it has several mechanisms by which it can interfere with allergic and autoimmune activity, Blocking B cell receptor signaling, blocking FCR receptor signaling is the 2 main mechanisms, but others as well. So I think there's a strong rationale To pursue RILSA across these indications, it's nice to have an oral as well in our portfolio As we try to probe some of this Type 2 inflammatory landscape.
Thank you, John.
The next question will be from Graham Parry at Bank of America. Graham?
Thanks for taking my questions. So firstly on mRNA flu vaccines. Sanofi's started Phase 1 dose rating trials with monovalent mRNA candidate, but Werner and Pfizer BioNTech are talking or going into the clinic with Straight with quadrivalent. So does that put you behind because you're trying to be sort of careful about getting the right dosing levels? Just thoughts on differences in some of the competitors' trial.
So AstraZeneca has announced the SERENA-six trial looking at ctDNA This is Ed. Yes, so one mutation.
Graham, I think we've lost you a little bit.
Yeah.
Maybe you want to dial back in. We'll take the first question, which I think was an MR and A. Was the next question heading towards Ameren Sainte? I can't It was hard for me to tell. But maybe, Tom, you'd like to talk about where we're at monovalent, quadrivalent mRNA.
Yes. Thank you, Graham. Indeed, as you noticed, we started our 1st flu mRNA trial, a monovalent Trial as you mentioned a few weeks ago. We're going to get the data pretty soon. And the goal is you need to learn, as you remember, that's our second mRNA trial after the COVID-nineteen 1.
So it's a starting flu mRNA. We want to compete aggressively, which is why we have set up the center of excellence, Extremely important for us, but indeed moving forward and we'll build up on this in Q4 during the investors event, we are going to move forward a broader platform switching to corevalent Flu moving forward.
Thank you.
Thank you. So the next question will be from Mark Purcell at Morgan Stanley. Mark?
Thank you very much for taking the questions. First one on Amasa restaurant, IMira 3. If you do not see superiority in terms of efficacy, are the data fallible? And then some of your competitors are going a little bit broader in So I just wonder what your options are there relative to the AI Insulin Patient Group? That's the first question, if I may.
And then the second question, just going back to Rilza and starting Phase II trials in asthma, CSU and AD. Could you sort of help us understand the approach here in terms of a combination approach versus a sequential approach? That will be useful as we sort of think about the broader franchise longer term.
Okay. John thanks, Mark. John, comments on amicinesterone and potential for superiority or not and filing strategy. And then maybe on the combination approaches in RILs, I'm not sure there's much we can share on that at the moment, but Maybe tackling emsinesterone first.
Yes. So on the emsinesterone, as you can imagine, if the EMEA-three study should Not show superiority, but should show a very strong profile, perhaps numerically better than fulvestrant, which is one of the Standard of care agents that we believe the investigators are turning to a lot in this population. It will really be a discussion with the regulators. So that's going to be, I think, how we would See that playing out, so I can't really give you a definitive answer to really be dependent on the regulatory discussion. In terms of the adjuvant, I mean there are a number of ways to tackle the adjuvant space and that we see different companies try to do it different ways.
We're compelled to focus initially on the higher risk patients that are more likely to have relapses That obviously can give you answers quicker, and should be a more robust test. The study that we designed in the aromatase inhibitor intolerant, that concept really emerged from the collaborative work we've done with these cooperative Groups which are the leaders in the field around how to do adjuvant studies and One of the patient populations with the greatest unmet need. And so it's through combining our best thinking with theirs that we came up with this Study is our initial entry, but that won't be the only adjuvant study we'll do. We're planning others as well. We're currently working those plans up, But we feel that the study we've outlined, EMEA 6, is a great place to start.
And I would say, so far the Back from regulators as we've presented our plans there, it's been very positive, requesting essentially no changes in the design, etcetera. And what was it?
RILSA combinations in asthma and other illnesses, I said it maybe it's a bit too early, but you may have a view.
Yeah, I think probably too early to really pontificate about what might be a future combination therapy. Let's see what Rilza monotherapy does, the strong rationale to believe that as a monotherapy it could Make a tangible difference in diseases like asthma based on the centrality of BTK and in the immunobiology and The cellular signaling mechanisms that are believed to be prominent. So let's get that done first and then we can think about where we go from there.
Thank you, both.
Thanks, John. I mean, there is depending on how the profile evolves, there is an add on opportunity clearly in some of those Illnesses and that's not uncommon in treating asthma, for example, but we'll see what we get to. Next question?
So the next question is from at Sutcliffe at UBS. Laura?
Hello. Thank you. First question is on insulin, please. Is the approval Glincine and Glargine in the U. S.
Built into your internal expectations for the year or should we be thinking about downside there? And then second question is on amsinesterant. I was just wondering if you could talk about the Drug interactions you see between Antonesterin and CDK4six. I remember at ASCO, your AMER1 poster revealed the dose dependent decrease in So just wondering if you've learned anything more there and how that's impacted your decision making across the program at this point? Thanks.
Thanks, Laura. So maybe a good chance to bring in Olivier to talk about Glargine U. S.
Yes. So Laura, thank you for your questions. There is no surprise for us as this is something that we had built in our plan. And when I shared the profile of the Sales for General Medicine at the beginning of the year at the CMD on February 5, this is something that we are incorporated. For 2020, we see relatively minimal impact.
For 2022, I remind you that assembly will have a 1 year Exclusivity, so we view that as another competitor on top of Baselgr in a space where, of course, there are very significant rebates. Of course, Toujeo is not impacted. So everything is built in our plan.
Thank you. John, I'm Sinester and Drug Interactions.
Yes, we don't believe it's an issue. We know that So our SERD has a mild to moderate SIP induction, but, Palbo is The label improves its use with moderate SIP enducers. Palbo also, because of its toxicity profile, often has to be down dosed About a third of patients at least they have to skip doses or reduce doses because of kind of titrate the, The side effect profile of the drug, so we feel that we're well within a comfort zone there At the 200 milligram dose, we also know that we're well above the level needed to fully saturate estrogen receptors. We get that And that dose is less than 150 milligrams. So we feel that we're in good shape there and I think that would be validated by the Phase 1 data that we presented at ASCO just a couple of months ago with showing a strong overall response rate and a clinical benefit rate That leads us to be even more confident that this combo can go forward.
The frontline setting in which testing the combo. I would say incidentally, those studies are enrolling very well. The investigator community is quite enthusiastic. So we hope to get that fully rolled ahead Scheduled.
Thanks, John. Next question?
The next question is from Peter Welford at Jefferies. Peter?
Hi. Yes. Thanks for taking my questions. So 2. Firstly, just sticking with Anastasia for a minute.
Just thinking about the question about superiority, I'm curious if you had a chance to see, I think it was the Veronica study that was presented from Roche, which was a failed study. But Curious on your view on the PFS rates we're seeing in that study around sort of 2 to 3 months. And is that representative of what you believe The control arm, I guess, patients who don't get amsenestrad could achieve? Or is it something we should be thinking about that makes your control patients Perhaps different to what was reported in that study. Secondly then, just on Dupixent, obviously, It could result in CSU and other trials coming.
I guess, could you help us think about what are the triggers in terms of your original framework that you set out for that £10,000,000,000 What are the triggers to potentially revise that? CSC, obviously, big indication, now looks positive. What else do we have to see for the balance to tip to that potentially to look conservative? Thank you.
Thank you, Peter. John, I'll come to you really on amsenescent or rather specifically a ROCE trial failure, which I'm not I don't have at my fingertips, you may have a view. On DUPE, I think we laid it all out pretty clearly in December 2019. First thing we said, dollars 10,000,000,000 plus, and I think the plus gets forgotten sometimes and it shouldn't. Secondly, the major patient population that was not included was COPD.
And We're delighted with CSU. The scale of the population that comes into play on CSU is equivalent To those that we're currently treating with DUPIXENT. And so you have to understand that's an event ultimately for this medicine. And then beyond that COPD, I mean, Bill can give you some more stats, but it is there are over 700,000 patients think roughly that are biologic eligible. So Bill, do you want to touch on that also as an additional trigger that goes beyond the 10 plus that's already been communicated?
Yes, absolutely, Paul. And as I said in my remarks, COPD isn't included. And look, that's a really exciting opportunity for us. And We have 2 assets that are actually there and sometimes I think we forget that we've got Dupixent which will be addressing The Type 2 COPD population and then we have itopecumab which is our anti IL-thirty three again in partnership with Regeneron Which will have more of a non Type 2 COPD focus, but also some a little bit of Type 2. And to give you the idea of the Scale, if you look at the Type 2 disease, we think it's over 300,000 patients And that's really firmly where DUPI can play.
If you add in that non type 2 former smokers, It's over 350,000 patients. So between the two products, we get a really, really meaningful piece, Almost 700,000 additional patient potential in an area where there are no other therapies that are available, biologics that is. We know some of the IL-5s are taking a look at it. They've had mixed results. They'd be focused solely in the type 2 space.
But you know, this looks like a great opportunity for us. Just to remind you, we'll have dupi pivotal data expected in 2023 and itopecumab In 2024. So we've got a lot to look forward to there. Just a comment if you allow me to talk about the greater than 10,000,000,000 as well. There is so much potential in the indications that we have and what we've just talked about.
What we've really done, we have an obsessive focus on execution and we have created a real global playbook for How we roll out each of these indications in each market around the world and what you're seeing in each of the markets that we're launching is Similar uptake like we saw in the U. S, which is just really, really strong. And I think it all goes back again to the profile of the product. It's the best product in each of the indications that we're in and that's going to help us get to the greater than $10,000,000,000 and with the addition of something like a COPD. So I'll leave it there.
Yes. Well said, Bill. And this the I've seen a lot of global executions My career and this is really top class what the team have done and it bodes very well for the launches that follow because it's not easy to do it, but you're Starting to see the world come online now to Dupixent. John, I don't know whether you had a comment on Roche's failed study.
I guess just to remind that the standard of care has been evolving in hormone receptor positive breast cancer and The context in which we'll be testing amsinestrin, which we are testing is in a Largely a post CDK4six inhibitor world, there just aren't any data yet on Anti hormonal agents as monotherapies in this post CDK4six inhibitor Class of patients or there just aren't very many data. Ours will be probably the first randomized assessment, randomized clinical trial assessment Of endocrine therapies in that context. So it'll be, I think setting a strong foundation for how to think about Using molecules like emsenestrin, the world's 3rd class in that setting. We don't obviously can't predict what the PFS will be, but I would just say that we are in an event driven study and This study has not reached enough events yet, so we cautiously interpret that as a good sign. But we'll see how things settle out when the data emerge.
But it looks like we're trending To PFS is more in the 4 to 6 months kind of window right now based on how the events are coming in.
Okay. Thank you, John. Next question?
For the next question, we have Seamus Fernandez at Guggenheim. Seamus?
Thanks very much. Can you hear me?
Yes, we got you.
Great. So just a couple of quick questions. Wanted to just ask quickly, as it relates to IMEIRA3, Just trying to get a better understanding of if you feel this trial is You know, warrants the amount of attention that is being afforded it by The Street. It seems like this is a small potential indication. Just wanted to get a better sense of if this should be viewed as altering the opportunity for Sure.
And if the trial should show an equivalent result, and then separately, As we think about the MS opportunity, obviously this is an area of great enthusiasm when you presented the initial data, Hoping that we might see some follow-up data at a medical meeting in that same population Where we see longer term data, is that something that we could see either later this year or perhaps Early next year to validate that strong early signal that we saw. Thanks so much.
Thanks Seamus. I'll give you my view, I guess, on the Emera 3, which is I think there's a convergence of things that make this interesting. Of course, for us, It's a stepping stone in restoring our credibility in science. So I think it gets a disproportionate amount of attention for that Because we have a lot of readouts coming over the next sort of 12, 24 months. And I think we obviously, everybody would like to see a positive, not least for patients.
Secondly, whilst I don't think the if you like the business opportunity is significant, it is the first step on a journey. We will learn a ton And we will understand, we put everything on the table. We're doing all the studies. We've not hesitated because we approach things differently. And then, of course, I think the conversation is juiced somewhat by the fact that the competition, we believe have inferior molecules, but Really creating the debate and creating the level of interest.
And of course, our data comes early and I think everybody will be trying to find an angle on that. Just to remind you, we're going all in and pushing right across. We're very confident in the science behind our molecule. We think it will be the winner. This will be an important stepping stone, but not the defining moment.
But we are and remain optimistic. The Second question was on the Ship 2, I think. Did I hear that right? Sorry, did I miss it?
Can you hear me still?
Yes. Sorry. Could you repeat the question on tolebrutinib?
Yes. It was If we might see some additional data. Right. With that same patient population perhaps either at a meeting Later this year or perhaps at like an AAN next year or something like that?
Yes. I don't Bill, why don't you comment On our plans for sharing data, if you have them at your fingertips.
Yes, I've got a little bit here. I mean, there isn't so much that's going to read out Additionally from the trial, we have Ectorum's, which is going to be in October in 2021, and we'll be presenting some additional information. We at EAN in June, we presented the effect of BTK on Modulating microglia driven neuroinflammation and MS progression, that's a recent presentation we had for it. So You know, we the focus has been in getting all of our studies up and running. We've moved extremely fast, And I think we've really set the pace for all of the BTK.
Some, as you know, when we Started this thing, there wasn't so much talk about BTK and now everyone is adding their BTK to try to catch up. We believe that this is the best in disease potential profile across the full spectrum of MS. Brain penetrant Brain penetrance is really, really important. And brain penetrance is important, but achieving A pharmacologically relevant brain penetrant level is the most important thing. Otherwise, you're You're just not going to see that effect.
And that's why we think it works across the broad spectrum of MS. So stay tuned for data. Everything is progressing very well and the community is really excited and we are as excited as we were the day We first mentioned it.
Yes. Thanks, Bill. And we mentioned I think I mentioned upfront that 95% of the patients in the open label extension are What, over a year, I guess. And those that stepped out were because of non drug related events. So it's quite interesting for us because that's a good leading indicator, we believe.
I think Bill just touched on the Pharmacologically relevant crossing of the brain barrier. As always, when you're trying to be pioneering and you're going to Great day. Everybody is dusting off their BTKs and trying to find a way to come around the edges. But the proof of the pudding will be in the data And we're way out in front and you know we recruited the studies pretty fast and in a pandemic. So I think that's pretty exciting what is around the corner.
The next question is from Luisa Hector at Berenberg. Luisa?
Hello. Thank you. So maybe just one question on your announcement of the investment into the mRNA Center of Excellence. I just wondered if you could split that €400,000,000 in terms of CapEx, R and D spend. And as I understand it, it is budget neutral.
So I just wonder whether other can you specify particular plans that have been scaled down to allow for this investment. Thank you.
Ruiza, thanks so much. Thomas?
Hello, Ruiza. So indeed, as you mentioned, it's about €400,000,000 investment annually to accelerate the end to end R and D of the next generation of vaccines. As you mentioned, it's going to be fully financed through resource 1st reallocation. How do we do that? We made a number of changes in our preclinical and early clinical programs.
We don't disclose those targets really. And we are clearly focusing most of our investments on MR and M going forward. As mentioned in the presentation, it's really a potential that we see for the future and that's why we're pushing for 6 clinical targets by 2025.
Yes, thank you. And we have, towards the end of the year, an Investor Day where we'll try and share a bit more detail around that. JB, I don't think we split The CapEx, OpEx. It's mainly OpEx. I think it says a lot about this organization.
We know how to do vaccines and we've done extraordinarily well, but we're not naive. And if we see an opportunity, we'll go after it. Now actually, When you start looking at the landscape, it's really about pivoting in a select number of areas. It's not right across the board. It's about going and getting stuck in pretty fast because The distance to catch up is actually manageable.
So it was a question of whether we had The courage to pick our areas and double down. And I think we're seeing that right across the company, frankly, but we're seeing it mRNA 2, and I think it says a lot about the leadership in vaccines that were not with the head buried in the sand. Okay, next question.
We'll take the final questions from Keyur Parekh at Goldman Sachs. Keyur?
Hi, thank you. And my apologies if these questions have been asked already, but 2 please, if I may. First one on China and insulin BBP. Our And in fact, yesterday there was a meeting held by the National Healthcare Security Administration, a roundtable with all the key insulin players To discuss the plans and the feedback for potential in Chilean VBP, I was wondering if there are any insights that you're able to share From this perspective, what your base case expectation today is and how we should think about the timing and the impact of this? That's question number 1.
And then secondly, relative to euro API, just wondering JB, if you can provide us with some incremental details from a Timeline perspective of kind of when we should expect this company to be standalone and what the plan is from your Perspective on separating this from Sanofi and potentially raising some capital out of it. Thank you.
Thanks, Keyur. Olivier, VBP,
China. So, Keyur, thank you for your question. You understand that I'm not going to comment on working meeting with the authorities. But we when we share our assumption at the Capital Market Day at the beginning of the year, we incorporated, of course, the impact of VPP Your VPP like scenario. So for us, there is no surprise.
The exact mechanism, the scope, The timing is not known. And we feel very confident given our track record in managing VBP In our ability to grow volume, we have been able on Plavix to grow the volume the 1st year by more 9.0. And we continue to grow volume as the 2nd year and you saw that in the quarter. So for us, nothing unexpected, Really in line with what I shared with you at the beginning of the year.
Thanks Olivier. JB, your API? Yes. Thank you, Caio, for this question. It reminds us that we are effectively driving the transformation of Sanofi on multiple fronts.
We are setting up consumer health as a standalone unit. We are transforming our commercial footprint with distributors versus subsidiaries in many regions, so it's many fronts. Our euro API is one of them, and it's fully on track. We said In December 2019, that we would be aiming to deliver in H1 2022. We are there.
Carve out is happening as planned. The financials are also as planned. The activity is improving strongly since We manage it as a standalone unit, and it's getting ready for this IPO in H1 2022. We are expecting to have a very small accretive impact on Sanofi. I remind you, we don't do it Many as a financial player, but we do it really to drive this deep simplification we do across the board.
As we also execute on our commitments on divestment of the long tail of products, both in Gen Med and in consumer health, So we are really executing transformation on multiple fronts. Thank you very much.
Yes. Thanks, Chibi, and thanks for the question, Just on that last point about the simplification of the company, it's like when we I think you touched on it, JB, some of the divestments. You should expect to see us do things like that because there's a lot of things that we have levers to pull to simplify our business, To make us more agile and more productive and that are real opportunities for us. So you should expect more of that. Delighted with the progress made in your OPI.
Says a little bit about the transformation that's ongoing and how creative we can be to create value. Maybe just before we just close the call down, delighted with the financials through Q2, very pleased With how we're doing, whilst I recognize everybody else had a low Q2 last year and the comps are relevant, I think our underlying growth is something that's more resilient than perhaps gets picked up, and you'll see that evolve over the rest of the year. I think we've raised guidance, so you know we're confident in the financials. Dupi, well ahead of where any of you, I think, would have And we're delighted with the progress and we've added CSU, which I think was a major step frankly in terms of addressable patient populations In terms of the data at least. And our science moves on.
And of course, you've asked about Emera, you're asking about Rilza, you're asking these are the right things. Between the fall and into the 1st part of next year, there's readouts, publications and data. And that's what we're about. And that's sort of The piece that we're all excited about getting to on top of merely financials, although they take a lot of hard work too. So thank you to everybody for your attention today.
The transformation continues at Sanofi and we look forward to connecting with you over the coming weeks months.
Thank you all, and thank you everyone for joining us today.