Dosing of first patients with RXC004 and Anti-PD1

On April 28, 2021 Redx Pharma (AIM: REDX), the drug discovery and development company focused on cancer and fibrosis, reported that it has successfully initiated dosing of the first patient cohort with a combination of RXC004, the Company’s lead drug candidate, and nivolumab (OPDIVO-Bristol Myers Squibb, an anti-PD-1 antibody) (Press release, Redx Pharma, APR 28, 2021, View Source [SID1234578603]). RXC004 is also currently being evaluated as monotherapy in a Phase 1 clinical study, from which top line results are expected by mid 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The primary objective of the Phase 1 combination study is to evaluate the safety and tolerability of RXC004 in combination with nivolumab in patients with advanced malignancies (ClinicalTrials.gov Identifier:NCT03447470). The announcement today confirms that the first three patients have initiated treatment with 1mg RXC004 along with nivolumab. The results from the combination study are expected to read out in H2 2021 and will be used to define a dose of RXC004 to be used in combination with standard dose nivolumab in a Phase 2 study in patients with genetically selected microsatellite stable (MSS) metastatic colorectal cancer (MSS mCRC), which is planned to start to recruit patients in H2 2021.

Lisa Anson, Chief Executive Officer of Redx Pharma said: "We are delighted to have initiated dosing of our first patient cohort in our Phase 1 RXC004 and anti-PD1 combination study. We believe that RXC004 has the potential to offer clinical benefit both as a monotherapy and in combination with immunotherapies for patients with Wnt-driven advanced solid tumours.

This important milestone opens our combination study programme, which is an exciting addition to our ongoing Phase 1 monotherapy study which is on track to report headline results by mid 2021"

What is RXC004?
RXC004 is a potent, selective, oral small molecule inhibitor of the enzyme, porcupine, a key activator of Wnt ligands in the Wnt signalling pathway. Aberrant Wnt signalling contributes directly to tumour growth and plays an important role in immune evasion, which leads to resistance to immune checkpoint inhibitors such as nivolumab. By selecting patients with tumours that have high Wnt ligand dependency, such as tumours with mutations in the RNF43 gene and fusions in the RSPO gene family, RXC004 has an opportunity to both directly inhibit the tumour growth and have an immune-enhancing effect to attack the tumour.

Why are we testing anti-PD1 and RXC004 in combination?
Immune checkpoint inhibitors (ICIs) such as anti-PD-1 antibodies have revolutionised the treatment of cancer, but do not work in all patients. Wnt pathway activation can enhance the ability of the tumour to evade destruction by the immune system and could contribute to lack of response to ICIs in these tumours. Our scientists have demonstrated preclinically that RXC004 can block activation of the Wnt pathway and restore the ability of the immune system to fight the tumour. Thus, RXC004 offers potential as a monotherapy or combination therapy, which we are now testing in clinical trials.

RXC004 Clinical trials
RXC004 is currently being investigated in a Phase 1 study, with top line safety and tolerability data as a monotherapy expected by mid 2021, with more detailed data expected to be presented at a conference in H2 2021. Following completion of the monotherapy Phase 1, clinical proof-of concept monotherapy studies in genetically-selected patients with metastatic colorectal cancer, genetically selected pancreatic cancer and all comers biliary cancer are expected to initiate. These studies are in addition to the combination study programme

Innate Pharma Files its 2020 Universal Registration Document (Document d’Enregistrement Universel) and 2020 Annual Report on Form 20-F

On April 28, 2021 Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) ("Innate" or the "Company") reported the filing of its 2020 Universal Registration Document (Document d’enregistrement universel) for the year ending December 31, 2020 with the French market authority "Autorité des Marchés Financiers" ("AMF") on April 27, 2021 (Press release, Innate Pharma, APR 28, 2021, View Source [SID1234578602]). It can be downloaded (in French) on the Company’s website and on the AMF’s website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company also announced today the filing of its annual report on Form 20-F for the year ending December 31, 2020 with the United States Securities and Exchange Commission ("SEC"). It can be also be accessed on the Company’s website and on the SEC’s website.

Oncternal Therapeutics Announces Presentation of Two Abstracts at ASCO 2021 Virtual Meeting

On April 28, 2021 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of two abstracts at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting being held virtually from June 4-8, 2021 (Press release, Oncternal Therapeutics, APR 28, 2021, View Source [SID1234578601]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Oral Presentation:

Abstract Number for Publication: 11500

Abstract Title: TK216 for relapsed/refractory Ewing sarcoma: Interim phase 1/2 results

Session Title: Sarcoma

Session Date and Time: June 4, 2021 from 1:30 pm – 4:30 pm Eastern Time
Poster Presentation:

Abstract Number for Publication: 7556

Abstract Title: Phase 1/2 study of cirmtuzumab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL)

Poster Session: Hematologic Malignancies — Lymphoma and Chronic Lymphocytic Leukemia

Session Date and Time: June 7, 2021 at 11:30 am Eastern Time
About TK216
TK216 is an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as prostate cancer and acute myeloid leukemia (AML). TK216 was developed based on discoveries in the laboratory of Jeffrey Toretsky, M.D., at Georgetown Lombardi Comprehensive Cancer Center, who discovered inhibitors of EWS-FLI1 using a novel chemical screening assay. In preclinical models, TK216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to TK216 for the treatment of Ewing sarcoma. TK216 is an investigational medication that has not been approved by the FDA for any indication.

About Cirmtuzumab
Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of MCL or CLL, in a collaboration with the University of California San Diego (UC San Diego) School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, Oncternal is supporting two investigator-sponsored studies being conducted at the UC San Diego School of Medicine: (i) a Phase 1b clinical trial of cirmtuzumab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer, and (ii) a Phase 2 clinical trial of cirmtuzumab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory CLL.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. The FDA has granted Orphan Drug Designations to cirmtuzumab for the treatment of MCL and CLL/small lymphocytic lymphoma. Cirmtuzumab is in clinical development and has not been approved by the FDA for any indication.

Sanofi continued its growth trajectory. Strong increase in Q1 2021 business EPS(1) at CER

On April 28, 2021 Sanofi reported Q1 2021 sales increase of 2.4% at CER driven by growth drivers Dupixent and Vaccines (Press release, Sanofi, APR 28, 2021, View Source [SID1234578570])

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Specialty Care sales grew 15.3%, due to strong Dupixent performance (+45.6% to €1,047 million) and oncology launches
Vaccines up 5.3%, driven by PPH franchise and demand for influenza vaccines in southern hemisphere
General Medicines core assets grew 4.4%, while GBU sales were down 3.8%
CHC decreased 7.3% due to COVID related stocking in Q1 2020 and low demand for cough and cold brands in Europe
Q1 2021 business EPS(1) growth at CER driven by efficiency and sales performance, supported by a one-time payment

Business EPS(1) was €1.61 up 5.2% on a reported basis and up 15.0% at CER
Business EPS(1) includes an incremental 8 cents due to a payment related to the termination of a collaboration in Japan
IFRS EPS was €1.25
Progress on implementation of the Corporate Social Responsibility strategy

Sanofi has become a member of the top five companies of the 2021 Access to Medicine index
Sanofi announced Sanofi Global Health, a newly formed non-profit unit within the company, a new cornerstone of its CSR strategy
Full-year 2021 business EPS guidance affirmed

Sanofi expects 2021 business EPS(1) to grow high single digit(2) at CER, barring unforeseen major adverse events. Applying average April 2021 exchange rates, the currency impact on 2021 business EPS is estimated to be between -4% to -5%.
Sanofi Chief Executive Officer, Paul Hudson, commented:

"Our strong first-quarter performance is the result of the continued execution of our Play to Win strategy to drive growth and bring innovative medicines to patients. Dupixent continues its outstanding performance with impressive growth in the U.S. and strong uptake in global markets, including China. Vaccines delivered growth in its core segments. We initiated and completed enrollment of our Phase 2 study for our recombinant COVID-19 vaccine candidate in the first quarter and results are expected next month. Following the communication of our ESG strategy at the end of 2020 and embedding it into our business priorities, we have recently created the Sanofi Global Health Unit, dedicated to increasing access to 30 medicines considered essential by the WHO. Sanofi is uniquely positioned to make this difference to society, which can be scaled and sustained over time, given our portfolio of essential medicines and broad geographic presence."

Changes in net sales are expressed at constant exchange rates (CER) unless otherwise indicated (definition in Appendix 7)
(1) In order to facilitate an understanding of operational performance, Sanofi comments on the business net income statement. Business net income is a non-GAAP financial measure (definition in Appendix 7). The consolidated income statement for Q1 2021 is provided in Appendix 3 and a reconciliation of reported IFRS net income to business net income is set forth in Appendix 4; (2) 2020 restated business EPS was €5.86; (3) Free cash flow is a non-GAAP financial measure (definition in Appendix 7).

2021 first-quarter Sanofi sales

Unless otherwise indicated, all percentage changes in sales in this press release are stated at CER1

In the first quarter of 2021, Sanofi sales were €8,591 million, down 4.3% on a reported basis. Exchange rate movements had a negative effect of 6.7 percentage points, mainly driven by the decrease of the U.S. dollar, Brazilian real, Russian ruble, Turkish lira, and Argentine peso and Japanese yen. At CER, Sanofi sales increased 2.4%.

First-quarter 2021 operating income

First-quarter business operating income (BOI) increased 4.0% to €2,638 million. At CER, BOI increased 13.3%. The ratio of BOI to net sales increased 2.4 percentage points to 30.7% versus the prior year.

Pharmaceuticals

First-quarter 2021 Pharmaceutical sales increased 3.8% to €6,563 million, with double-digit growth of the Specialty Care portfolio mainly driven by the strong performance of Dupixent which largely offset lower sales in General Medicines in Europe and the U.S.

Specialty Care

In the first quarter, Dupixent (collaboration with Regeneron) sales were strong despite the COVID-19 environment and increased 45.6% to €1,047 million. In the U.S., Dupixent sales of €793 million (up 41.6%) were driven by continued strong demand in atopic dermatitis (AD) in adult, adolescent patients, and children aged 6 to 11 years, continued uptake in asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Dupixent total prescriptions (TRx) increased 51% (year-over-year) and new-to-brand prescriptions (NBRx) grew 16% despite fewer in-person physician visits which remain below the pre-COVID level. In Europe, first-quarter Dupixent sales grew 52.2% to €137 million reflecting continued growth in AD in key countries and additional launches in asthma in European markets. In Japan, sales were €59 million (up 53.7%), where strong demand was moderated by the government price decrease implemented in April 2020. Dupixent was approved in China for the treatment of adults with moderate-to-severe AD in June 2020 and is listed on the NRDL (National Reimbursement Drug List) as of March 2021. At the end of the first quarter, Dupixent was launched in 49 countries with approximately 260 000 patients on therapy.

In the first-quarter, Neurology and Immunology sales were down 3.4% to €581 million, impacted primarily by the decline of Lemtrada sales.

Aubagio sales decreased 1.1% in the first quarter to €500 million, due to lower sales in the U.S. reflecting increased competition partially offset by demand growth partly related to clinical trial supply and price upside in Europe.

First-quarter Lemtrada sales decreased 44.9% to €24 million, primarily due to the COVID-19 pandemic, which has led to a decrease in infused immune reconstitution therapies such as Lemtrada.

First-quarter Kevzara (collaboration with Regeneron) sales were up 10.9% to €57 million driven by Europe and Rest of the World which largely offset lower U.S. sales reflecting the recent strategic decision to reduce promotional efforts.

In the first quarter, Rare Disease sales increased 4.4% to €770 million, primarily driven by higher demand particularly in Rest of the World (up 10.2%). Sales in Europe increased 0.4% and compared to a high base in the first quarter of 2020 due to an inventory build related to the COVID-19 environment.

First-quarter Cerezyme sales increased 4.2% to €178 million, driven by strong growth in Rest of the World (up 18.4%). First-quarter Cerdelga sales increased 13.8% to €62 million driven by new patient accruals in the three regions. Sales of the Gaucher franchise (Cerezyme + Cerdelga) increased 6.5% (to €240 million) in the first quarter.

First-quarter Myozyme/Lumizyme sales increased 0.8% to €235 million supported by new patient accruals in the U.S. (up 11.5%) which offset lower sales in Europe and negative phasing effect in Rest of the World.

First-quarter Fabrazyme sales increased 4.7% to €208 million driven by higher sales in Rest of the World and Europe. In the U.S. sales decreased 2.9% reflecting lower treatment compliance during the COVID-19 pandemic.

First-quarter Oncology sales increased 25.8% to €221 million, driven by the Sarclisa and Libtayo launches.

First-quarter Jevtana sales decreased 2.9% to €126 million following the entry of generic competition in Europe (down 11.8%) at the end of March. In the U.S., sales were up 5.0%. In the U.S., the Jevtana composition of matter patent will expire in September 2021. From May to July 2020, Sanofi filed patent infringement suits against all generic filers on Jevtana under Hatch-Waxman in the U.S. District Court for the District of Delaware asserting two method of use patents (US 10,583,110 and US 10, 716,777), both of which expire in October 2030. Sanofi has reached settlement agreements with some of the defendants and the suit against the remaining defendants currently stayed. In Europe, generic competition has started in certain countries after the expiration of Jevtana’s market exclusivity in March 2021.

Libtayo (collaboration with Regeneron) sales were €26 million (up 125.0%) in the first quarter driven by increased demand in metastatic cutaneous squamous cell carcinoma (CSCC) as well as additional country launches. In February, Libtayo was approved in two new indications in the U.S. as a monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of ≥50% and for patients with advanced basal cell carcinoma. Libtayo sales in the U.S. are reported by Regeneron.

Sarclisa was approved in March 2020 in the U.S. for the treatment of adults with relapsed refractory multiple myeloma (RRMM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and in June by the European Commission in certain adults with RRMM. First-quarter Sarclisa sales were €34 million driven by additional country launches. First-quarter sales in the U.S. and in Europe were €12 million and €13 million, respectively. In Rest of the World sales (€9 million) were driven by a strong performance in Japan. At the end of March, the FDA approved Sarclisa in combination with carfilzomib and dexamethasone for patients with relapsed multiple myeloma.

In the first quarter, Rare Blood Disorder franchise sales were down 0.7% (€272 million). Excluding industrial sales to Sobi, first-quarter sales were up 5.1% driven by Alprolix and Cablivi performance which more than offset Eloctate sales decrease in the U.S. As already communicated, Alprolix and Eloctate industrial sales to Sobi are expected to be significantly lower in 2021 than in 2020.

Eloctate sales were €134 million in the first quarter, down 9.9%. Excluding industrial sales to Sobi, Eloctate sales were down 3.4% mainly due to lower U.S. sales (-5.0%) as a result of ongoing competitive pressure. Sales in the Rest of the World were down 23.8% reflecting lower industrial sales to Sobi.

First-quarter Alprolix sales were down 1.8% to €100 million. Excluding industrial sales to Sobi, Alprolix sales were up 3.0%, mainly driven by patient switches from standard half-life factors and prophylaxis conversion. Sales in the Rest of the World were down 19.2% reflecting lower industrial sales to Sobi.

Cablivi for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP), a rare and acute blood disorder, generated sales of €38 million (up 66.7%) in the first quarter of which €22 million from the U.S. (up 60%) driven by increase disease and product awareness as well as adoption of new ISTH (International Society on Thrombosis and Haemostasis) TTP guidelines. In Europe, sales were €15 million (up 66.7%) driven by new country launches. Globally, diagnosis of the disease and product awareness remain impacted by the COVID-19 environment.

General Medicines

General Medicines sales were down 3.8% to €3,672 million in the first quarter. Sales of the core assets2 were 1,474 million up 4.4% (and up 6.3% excluding Praluent U.S. sales3), driven by strong performance of Lovenox. Non-core assets sales were €2,010 million, down 9.9% reflecting notably portfolio streamlining, lower Lantus and Aprovel/Avapro sales and some negative COVID-19 impact. First-quarter industrial sales were €188 million up 8.8%.

In the first quarter, global Diabetes sales decreased 1.7% to €1,175 million. The growth in the Rest of the World (up 5.3%) was driven by Lantus, Toujeo launch in China and Soliqua performance. In the U.S., the Diabetes sales decrease 5.3%. In Europe, sales decreased 10.2% largely affected by patient stockpiling related to the COVID-19 environment in the first quarter of 2020.

First-quarter Toujeo sales increased 5.1% to €253 million driven by the launch in China. Lower sales in Europe reflected the high base in the first quarter 2020 due to patient stockpiling. In the U.S., Toujeo sales were stable with volume growth offsetting average price decrease.

Lantus sales were €652 million, down 3.7% in the first quarter, mainly due to a continued decline in average U.S. net price, increasing usage of Toujeo, biosimilar glargine competition and lower sales in Europe (patient stockpilling in the first quarter of 2020). In Rest of the World, sales increased 4.9%.

First-quarter Soliqua sales increased 29.7% to €44 million driven by growth in the three regions and notably by launches in Rest of the World (up 44.4%) and performance in the U.S. (up 27.3%)

In the first quarter, Cardiovascular and Established Rx Products sales decreased 5.6% to €2,309 million reflecting strong Lovenox growth more than offset in particular by lower sales of Aprovel/Avapro, divestments and some COVID impact.

First-quarter Lovenox sales increased 30.4% to €401 million, driven by Rest of the World (up 50.7%), and Europe (up 10.5%) reflecting demand increase driven by recent guidelines recommending the use of low molecular weight heparins in hospitalized COVID-19 patients which more than offset biosimilar competition and postponed procedures.

Plavix sales were down 4.0% in the first quarter to €251 million mainly reflecting lower sales in Europe (down 23.7%) and Japan. In China, first-quarter Plavix sales were €117 million, up 0.8%.

First-quarter Aprovel/Avapro sales were down 39.7%% to €101 million, primarily reflecting a short-term supply constraint.

First-quarter Praluent sales decreased 20.5% to €56 million, due to lower sales in the U.S. reflecting the restructuring of the collaboration with Regeneron which was effective on April 1, 2020. Sanofi has sole responsibility for Praluent outside the U.S. while Regeneron has sole responsibility for Praluent in the U.S. Excluding U.S. sales3 , Praluent sales grew 26.8% driven by a strong performance in Europe (up 20.0%) and Rest of the World (up 45.5%) driven by the launch in China. Praluent was relaunched in Germany at the beginning of April 2021.

Multaq sales were €72 million, down 3.7% in the first quarter due to lower sales in the U.S. impacted by the COVID-19 environment.

Pharmaceuticals business operating income

In the first quarter, business operating income (BOI) of Pharmaceuticals decreased 4.6% to €2,515 million (up 2.9% at CER). The ratio of BOI to net sales decreased by 0.7 percentage points to 38.3%. At CER, the ratio decreased 0.4 percentage points reflecting higher SG&A spends as well as increased "Other operating expenses" mainly reflected Regeneron MAbs alliance despite an improvement of the gross margin.

First-quarter Vaccines sales increased 5.3% to €915 million reflecting higher PPH vaccines sales and strong flu vaccines demand partly offset by lower sales of travel vaccines and adult booster due to the COVID-19 pandemic.

Influenza vaccines sales increased by 23.8% in the first quarter to €77 million, reflecting strong demand in the southern hemisphere which were partly offset by the U.S. due to the earlier supply to the market as compared to the 2019/2020 flu season.

In the first quarter, Polio/Pertussis/Hib (PPH) vaccines sales increased 14.9% to €533 million benefiting from the favorable phasing of shipments. In the U.S., PPH sales were up 40.4% driven by the timing of the CDC order for Pentacel and in the rest of the World, strong polio vaccines sales reflected the favorable phasing of public tenders. Supply for Vaxelis in the US will be available in June 2021. Developed as part of a joint-partnership between Sanofi and Merck, Vaxelis is the first and only hexavalent combination vaccine approved in the U.S. to help protect infants and children against six infectious diseases, including diphtheria, tetanus, pertussis (whooping cough), poliomyelitis, hepatitis B and invasive disease due to Haemophilus influenzae type b. Vaxelis in market sales will not be consolidated.

First-quarter Menactra sales were up 3.8% to €127 million. MenQuadfi, which is the only U.S. FDA-approved quadrivalent meningococcal vaccine indicated for all patients above 2 years of age, was launched in the U.S. in March 2021.

Adult Booster vaccines sales decreased 8.7% in the first quarter to €100 million, primarily reflecting the COVID-19 impact on Adacel in the U.S. and Repevax in Europe.

First-quarter Travel and other endemic vaccines sales decreased 37.4%, due to extensive travel restrictions globally.

Vaccines business operating income

In the first quarter, business operating income (BOI) of Vaccines increased 43.2% to €371 million reflecting the payment from Daiichi Sankyo. At CER, BOI increased 48.6%. The ratio of BOI to net sales was 40.5% (and 27.5% excluding the payment from Daiichi Sankyo).

In the first quarter, Consumer Healthcare (CHC) sales decreased 7.3% to €1,113 million primarily reflecting a weak cough and cold season due to social distancing measures and wearing of masks as well as a high base for comparison in the first quarter of 2020 which benefited from pantry loading related to COVID environment. First-quarter sales were also impacted by divestments of non-core products.

In the U.S., first-quarter CHC sales increased 2.3% to €283 million, reflecting growth of Digestive and Mental Wellness categories as well as Allergy partially offset by the decline of the Pain category.

In Europe, first-quarter CHC sales decreased 19.3% (to €334 million) mainly reflecting lower incidence of colds due to social distancing measures and wearing of masks, as well as a high base for comparison in the first quarter of 2020 which benefited from pantry loading related to COVID environment. First quarter CHC sales were also impacted by divestments of non-core products.

In the Rest of the World, first-quarter CHC sales decreased 3.6% to €496 million, reflecting lower sales in Allergy, Cough and Cold and pain categories impacted by the COVID environment partially offset by the growth of the Digestive and Mental Wellness categories.

CHC business operating income

In the first quarter, business operating income (BOI) of CHC decreased 18.4% to €394 million. At CER, BOI decreased 8.9% reflecting lower sales. The ratio of BOI to net sales decreased 1.8 percentage point to 35.4% versus the prior year.

First-quarter sales in the U.S. increased 6.4% to €2,893 million driven by the strong sales performance of Dupixent, which more than offset lower General Medicines sales.

In Europe sales decreased 5.6% in the first quarter to €2,228 million reflecting lower sales of General Medicines, CHC and Vaccines partly offset by Dupixent, Aubagio and oncology sales growth.

In the Rest of the World, sales increased 4.3% to €3,470 million in the first quarter driven mainly by the strong performance of Lovenox, Dupixent, Vaccines, Diabetes, and Rare Disease which more than offset lower CHC and Rare Blood Disorders franchise sales. Sales in China increased 8.4% to €726 million, driven by Toujeo and Dupixent launches, as well as established Rx Products and CHC performance. In Japan, first-quarter sales decreased 8.7% to €434 million due to lower sales of Established Rx Products and CHC.

R&D update at the end of the first quarter 2021

Regulatory update

The U.S. Food and Drug Administration (FDA) approved Sarclisa in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy, and the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion. Sarclisa is already approved in the U.S and Europe for use combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
The FDA approved Libtayo monotherapy for patients with first-line advanced non-small cell lung cancer with PD-L1 expression of >50%. These data were published in The Lancet demonstrating superiority in extending overall survival (OS) compared to chemotherapy even with a high crossover rate. The FDA also approved Libtayo as the first immunotherapy indicated for patients with advanced basal cell carcinoma.
The European Commission approved Plavix for use in combination with aspirin in adult patients with moderate to high-risk Transient Ischemic Attack (TIA) (ABCD2 score ≥4) or minor Ischemic Stroke (IS) (NIHSS1 ≤3) within 24 hours of either the TIA or IS event. Usage under this new indication can continue for 21 days, followed by long-term single anti-platelet therapy.
The FDA accepted Dupixent for review in children with moderate-to-severe asthma. The submission is supported by data demonstrating Dupixent significantly reduced severe asthma attacks and is the only biologic to improve lung function in children aged 6 to 11 years in randomized Phase 3 trial, and further adds to the well-established safety profile of Dupixent. The target action date for the FDA decision is October 21, 2021. Also, the European Medicines Agency (EMA) has confirmed receipt of the submission for Dupixent in children with moderate-to-severe asthma.
Efanesoctocog alfa, formerly known as BIVV001, in collaboration with Sobi and in development for hemophilia A was granted Fast Track designation by the FDA.
SAR445136, formerly known as BIVV003, an ex-vivo cell therapy developed in collaboration with Sangamo for the treatment of sickle cell disease, was granted Fast Track designation by the FDA. Also, the EMA’s Committee for Orphan Medicinal Products (COMP) granted Orphan Drug Designation based on early data from three patients that had 52 weeks, 13 weeks, and 29 days of follow-up, respectively.
Portfolio update

Phase 3:

The XTEND-Kids trial for efanesoctocog alfa (formerly known as BIVV001) in pediatric patients with hemophilia A enrolled its first patient.
The second pivotal trial to study itepekimab in chronic obstructive pulmonary disease (COPD) (AERIFY-2) enrolled its first patient.
An Independent Data Monitoring Committee (IDMC) recommended to stop a Libtayo Phase 3 trial in advanced cervical cancer for positive results on OS. Patients with either squamous cell carcinoma or adenocarcinoma recurrent or metastatic cervical cancer were randomized to receive either Libtayo monotherapy or an investigator’s choice of commonly used chemotherapy.
Final results of Part A of the sutimlimab pivotal Phase 3 CARDINAL open label, single-arm study evaluating the safety and efficacy of sutimlimab for 26 weeks in people with cold agglutinin disease were published in the New England Journal of Medicine. Sutimlimab, a first-in-class investigational C1s inhibitor, met the primary and secondary endpoints in the study and demonstrated sustained inhibition of classical complement pathway mediated hemolysis with improvements in anemia within one week of treatment.
The amended protocol for all ongoing adult and adolescent fitusiran clinical studies, aimed at further enhancing the benefit-risk profile, was presented at the 14th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD). The dose for adults and adolescents will be reduced to 50 mg every other month (six times a year), with the potential to adjust the dose and/or dose frequency based on an individual patient’s anti-thrombin levels. A re-start of dosing and recruitment in the pediatric trial is expected later this year.

Phase 2

CARMEN-LC05, a trial investigating tusamitamab ravtansine, an anti-CEACAM5 antibody-drug conjugate (ADC), in combination with pembrolizumab versus pembrolizumab alone in patients with first-line non-squamous NSCLC started. Inclusion criteria include expression of CEACAM5 as demonstrated prospectively by a centrally assessed Immunohistochemistry (IHC) assay of ≥2+ in intensity involving at least 50% of the tumor cell population and PD-L1 positive tumor (TPS ≥1%). Patients with EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations are excluded.
Development for Dupixent for grass allergy has been discontinued.
SAR445088, a complement inhibitor formerly known as BIVV020, has entered a study in adults with persistent/chronic immune thrombocytopenia (ITP).
SAR441344, a CD40L antibody, has entered a study for Sjogren’s Syndrome, an autoimmune condition that is most common in older women and affects the tear and saliva glands.
A new study to select the most appropriate antigen dosage for Phase 3 evaluation of an adjuvanted recombinant protein COVID-19 vaccine candidate (SP0253) was initiated and already completed enrollment. In parallel, development work has commenced against emerging variants, which will be used to inform next stages of the program. Trials results and the start of a global Phase 3 study are expected in Q2 2021. The trial program is supported by the United States’ Biomedical Advanced Research and Development Authority (BARDA).
MRT5500 (SP0254), an mRNA vaccine candidate against SARS-CoV-2, entered Phase 1/2 to assess safety, immune response and reactogenicity. Three different dose levels will be investigated. Interim results are expected in Q3 2021. In parallel, preclinical studies are underway to evaluate additional mRNA candidates against emerging SARS-CoV-2 variants
SP0230, a novel multicomponent meningococcal Group B Vaccine, in development for adults, adolescents, toddlers, and infants started Phase 1/2.

Phase 1

SAR441566, a first, next generation, oral small molecule TNF inhibitor that in contrast to anti-TNF biologics blocks specifically the TNFR1 pathway, started Phase I in inflammatory conditions.
SAR444656, an IRAK4 degrader being developed for atopic dematitis in collaboration with Kymera also known as KT474, started a Phase I trial in healthy volunteers. SAR444656 is the first IRAK4 degrader to be studied outside of oncology.
Sanofi decided to not opt in on REGN4018, REGN5459, or REGN5458. Sanofi no longer has any non-compete obligations on refused candidates under the amended and restated IO Discovery and Development agreement, which terminated on March 16 2021.
Development of SAR441169, ROR gamma T antagonist in collaboration with Lead Pharma, was terminated in psoriasis.
SAR440234, T cell engaging multi specific antibody, has been discontinued in leukemia.
An update of the R&D pipeline at as of March 31, 2021, is available on our website:

View Source

Collaborations

On January 12, 2021 Sanofi entered into a global licensing agreement with Biond Biologics for BND-22, a novel immune checkpoint inhibitor targeting the ILT2 receptor.
On February 23, 2021 Sanofi entered into a collaboration with Sirion to innovate gene therapy treatment with improved adeno-associated virus capsids.
Agreements related to COVID-19 vaccines

Sanofi will support manufacturing and supply of BioNTech’s mRNA COVID-19 vaccine, co-developed with Pfizer, providing fill and finish for over 125 million doses. Initial supplies will originate from Sanofi’s production facilities in Frankfurt from summer of 2021.
Sanofi will support manufacturing of Janssen´s COVID-19 vaccine and through its vaccine manufacturing plant in Marcy l’Etoile, France, formulate and fill vials at a rate of approximately 12 million doses per month.
Expanding affordable access to those most in need

Sanofi has become a member of the top five companies of the 2021 Access to Medicine index, recognizing its work to make medicines accessible and available in low- and middle-income countries. Sanofi has moved up two places in the overall company ranking compared to its position in 2018, performing particularly well in Research & Development (4th place) and Product Delivery (3rd place). This recognition resonates strongly with Sanofi’s Corporate Social Responsibility strategy. Embedded in Sanofi’s long-term strategy, the company’s CSR commitment is based on four pillars in which Sanofi is uniquely positioned to make a difference: access to medicines, support for vulnerable communities, preservation of the environment, and inclusion and diversity of its employees.

On April 7, 2021, Sanofi announced a new cornerstone of its CSR strategy, Sanofi Global Health, a newly formed nonprofit unit within the company, dedicated to increasing access to medicines considered essential by the World Health Organization (WHO) for patients in the world’s 40 poorest countries. Thirty of Sanofi’s medicines will be provided across a wide range of therapeutic areas, including cardiovascular disease, diabetes, tuberculosis, malaria, and cancer. Sanofi Global Health will also fund the training of healthcare professionals or the set up and development of sustainable care systems for those who suffer from chronic diseases and require complex care.
Sanofi Global Health is the first global initiative to provide access to such a broad portfolio of medicines, in so many countries and across several therapeutic areas, while funding local support programs.

Sanofi released its 2020 Integrated Report: click here to start the experience.

2021 first-quarter financial results

Business Net Income4

In the first quarter of 2021, Sanofi generated net sales of €8,591 million, a decrease of 4.3% and an increase of 2.4% at CER.

First-quarter other revenues decreased 14.0% (down 6.4% at CER) to €295 million, reflecting lower VaxServe sales of non-Sanofi products (€228 million, down 12.9% at CER).

First-quarter Gross Profit decreased 4.1% to €6,202 million (up 2.6% at CER). The gross margin ratio increased 0.1 percentage points to 72.2% (72.3% at CER) versus the first quarter of 2020. This increase mainly reflected the improvement of the Pharmaceuticals gross margin ratio (from 74.9% to 75.2%) driven by growing weight of Specialty Care as well as some efficiency gains in Industrial Affairs. Vaccines gross margin ratio decreased 2.9 percentage point to 62.0% due to product mix. CHC gross margin ratio improved from 67.7% to 68.0%.

Research and Development (R&D) expenses decreased 5.5% to €1,266 million in the first quarter. At CER, R&D expenses decreased 1.7% reflecting significant increase in key assets development offset by operational efficiencies and lower costs on mature projects. In the first quarter, the ratio of R&D to sales decreased 0.2 percentage point to 14.7% compared to the prior year.

First-quarter selling general and administrative expenses (SG&A) decreased 6.3% to €2,194 million. At CER, SG&A expenses were down 0.7%, reflecting increased investments in Specialty Care and Vaccines which were more than offset by smart spending and operational excellence initiatives. In the first quarter, the ratio of SG&A to sales decreased 0.6 percentage point to 25.5% compared to the prior year.

First-quarter operating expenses were €3,460 million, a decrease of 6.0% and 1.1% at CER.

First-quarter other current operating income net of expenses was -€101 million versus -€247 million in the prior year and included a €119 million payment from Daiichi Sankyo related to the termination of a vaccines collaboration in Japan. This line included an expense of €279 million (versus an expense of €243 million in the first quarter of 2020) corresponding to the share of profit to Regeneron of the monoclonal antibodies Alliance, reimbursement of development costs by Regeneron and the reimbursement of commercialization-related expenses incurred by Regeneron.

The share of profit from associates was stable at €9 million. Following the sale of its Regeneron stake at the end of May 2020, Sanofi restated its previously reported non-GAAP indicator (Business Net Income) and excluded the effect of equity method of accounting for Regeneron investment in 2019, Q1 2020 and Q2 2020.

First-quarter business operating income4 (BOI) increased 4.0% to €2,638 million. At CER, BOI increased 13.3% and 8.4% excluding the payment from Daiichi Sankyo. The ratio of BOI to net sales increased 2.4 percentage points to 30.7% (and to 29.3% excluding the payment from Daiichi sankyo) versus the prior year.

Net financial expenses were €85 million in the first quarter versus €75 million in the same period of 2020.

First-quarter 2021 effective tax rate was 21.0% versus 22% in the first quarter of 2020. Sanofi expects its effective tax rate to be around 21% in 2021, everything being equal in the U.S.

First-quarter business net income4 increased 5.1% to €2,017 million and increased 14.7% at CER. The ratio of business net income to net sales increased 2.1 percentage points to 23.5% (and 1 percentage point excluding the payment from Daiichi Sankyo) versus the first quarter of 2020.

In the first quarter of 2021, business earnings per share4 (EPS) was €1.61, up 5.2% on a reported basis and up 15.0% at CER (up 9.8% at CER excluding the payment from Daiichi Sankyo). The average number of shares outstanding was 1,249.3 million versus 1,251.3 million in first quarter 2020.

Reconciliation of IFRS net income reported to business net income (see Appendix 4)

In the first quarter of 2021, the IFRS net income was €1,566 million. The main items excluded from the business net income were:

An amortization charge of €389 million related to fair value remeasurement on intangible assets of acquired companies (primarily Genzyme: €126 million, Bioverativ: €79 million, Boehringer Ingelheim CHC business: €50 million and Ablynx: €42 million) and to acquired intangible assets (licenses/products: €23 million). These items have no cash impact on the Company.
Restructuring costs and similar items of €156 million related to streamlining initiatives.
A €132 million tax effect arising from the items listed above, mainly comprising €89 million of deferred taxes generated by amortization and impairments of intangible assets and €42 million associated with restructuring costs and similar items (see Appendix 4).

Capital Allocation

In the first quarter of 2021, free cash flow5 increased by 23.6% to €1,925 million, after net changes in working capital (+€422 million), capital expenditures (-€378 million) and other asset acquisitions6 (-€277 million), proceeds from disposals4 (€82 million), and payments related to restructuring and similar items (-€244 million). As a consequence, net debt decreased from €8,789 million at December 31, 2020 to €6,823 million at March 31, 2021 (amount net of €13,948 million cash and cash equivalents).

iCo Therapeutics Inc. Announces Closing of Upsized Subscription Receipt Private Placement

On April 28, 2021 iCo Therapeutics Inc. ("iCo" or the "Company") (TSXV: iCo) (OTCQB: iCoTF) reported that it has closed its previously announced private placement (the "Financing") in connection with its proposed business combination with Satellos Bioscience Inc. ("Satellos") by way of a plan of arrangement (the "Arrangement") in accordance with Section 192 of the Canada Business Corporations Act (Press release, iCo Therapeutics, APR 28, 2021, View Source [SID1234578569]). The completion of the Arrangement will result in the reverse takeover of the Company as defined in the policies of the TSX Venture Exchange ("TSXV") and the resulting entity will continue to operate in the life sciences industry under the name "Satellos Bioscience Inc." (the "Resulting Issuer").

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pursuant to the Financing, the Company issued 85,294,117 subscription receipts (the "Subscription Receipts") at a price of $0.085 per Subscription Receipt for aggregate gross proceeds of approximately C$7.25 million. Each Subscription Receipt will entitle the holder thereof to receive, upon satisfaction of certain escrow release conditions, including without limitation, the completion of the Arrangement, and without payment of additional consideration, one common share of the Resulting Issuer (a "Resulting Issuer Share"). The proceeds from the Financing have been placed in escrow and, upon satisfaction of the escrow release conditions, will be used for research, development, and general corporate expenses of the Resulting Issuer.

The Resulting Issuer Shares issued in connection with the Financing will be subject to a hold period expiring 4 months and one day from the date of issuance in accordance with applicable Canadian securities laws. Additionally, in connection with the Financing, certain Resulting Issuer Shares issued to former shareholders of Satellos pursuant to the Arrangement will be subject to a lock-up agreement.

The Financing was led by Bloom Burton Securities Inc. and includes Richardson Wealth Ltd.