BCI Pharma signs a strategic partnership with Mithra

On November 29, 2021 Mithra (Euronext Brussels: MITRA), a company dedicated to Women’s Health, reported the holding of its Investor Day today at its R&D and production center, the Mithra CDMO in Flémalle, Belgium (Press release, BCI Pharma, NOV 29, 2021, View Source [SID1234596177]).

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As of 9:00 am CET, all presentations can be simultaneously followed by webcast on the Company’s website or by clicking here. A replay will also be available via this same link shortly after the end of the conference.

Consolidation of Donesta product candidate
Donesta is a next generation orally-administrated estetrol-based hormone therapy product candidate. Launched in late 2019, the phase III Clinical Program carried out on 2,300 postmenopausal women (40-65 years) aims to measure the treatment effects on vasomotor symptoms’ frequency and severity with different doses of E4, especially for hot flashes. Many parameters such as the impact on breast density, endometrial safety, health-related quality of life and lipids, glucose metabolism and hemostasis parameters are also among the secondary objectives of these studies2.

Convinced of the potential of E4 on other major estrogen deficiency symptoms affecting a majority of postmenopausal women, Mithra decided to broaden the scope of its Clinical Program by launching three additional studies: 1 IQVIA FY 2020 2 For more information about the E4 Comfort Phase III Program, please visit the website of Clinicaltrials.gov by clicking here. investors.mithra.com • 2 29-11-2021 PRESS RELEASE 1. A Phase 3 study on the effect of E4 on vulvovaginal atrophy (vaginal dryness, pain during intercourse, urinary tract infections); 2. A Phase 2 study on the effect of E4 on skin texture, quality and appearance; 3. A Phase 2 study on the effect of E4 on hair texture, quality and appearance. These three additional studies funded by Mithra for an amount of approximately EUR 20 million will be launched in 2022, depending on regulatory agencies’ feedback.

Graham Dixon, CSO Mithra Women’s Health, comments on this extension of the Donesta Program: "Following the publication of the WHI study in 2001, more than 65% of women decided to stop their hormonal treatment for fear of developing breast cancer or a cardiovascular disease. While this correlation was categorically denied by the scientific community as early as 2006, only 1 in 10 postmenopausal women in the world today choose to take hormonal treatment to relieve the many side effects impacting both their private and professional lives. We are convinced that thanks to its safety profile, Donesta can offer a real complete alternative to significantly improve these women’s quality of life and therefore be a gamechanger."

The primary efficacy data of the Phase 3 Donesta Program is expected by beginning of 2022. Depending on the evolution of the Covid-19 situation, study results and regulatory authorizations, Mithra believes it could achieve marketing authorization for Donesta in H1 2024 for the United States/Canada and in H2 2024 for Europe. The global menopause market is currently worth nearly USD 10 billion, and is expected to reach around USD 17 billion by 20273.

Dr. Carolyn Myers, BioEnsemble Ltd., added: "Our quantitative market research program surveying over 1000 prescribers and women confirms a large unmet medical need in the menopause market resulting from misperceptions about the use of current HT. The research also highlights the significant opportunity for a novel, safe hormone that will treat menopausal symptoms beyond VMS. Research findings confirmed that Donesta’s profile is attractive to current users of HT from which we believe Donesta can take a large share, and Donesta can make inroads amongst the 54% of women who currently do not seek medical treatment because of their safety concerns of current HT. In addition to Donesta being safe, when approved with the additional indications, it will provide women with a single product option to treat many of their symptoms long term."

Diversification of asset-based pipeline through a partnership with BCI Pharma
Considering its advanced asset-based pipeline, which has seen two major commercial launches over the past two years (the first estetrol-based product Estelle oral contraceptive and Myring vaginal ring), Mithra is strengthening its leadership position in women’s health by acquiring a new innovative development axis in a fast-growing market: inhibitors of tyrosine kinases, notably indicated in the treatment of cancer and endometriosis.

Mithra acquires the rights relating to two development programs led by the Belgian company BCI Pharma on innovative inhibitors of CSF1R kinase. These CSF1R inhibitors are part of a new innovative class of immune-modulatory drugs with established clinical tolerability4 and proven efficacy5. They act on the CSF1 receptor which is involved in many inflammatory processes and is over expressed in many 3 Market Research Future, 2020; IQVIA 2019 4 Cannarile et al. Journal for ImmunoTherapy of Cancer (2017) 5:53 5 Monsestime et al. Drugs in R&D (2020) 20:189–195 investors.mithra.com • 3 29-11-2021 PRESS RELEASE pathologies, in particular cancers, neurological disorders and autoimmune diseases. The innovative class of tyrosine kinases inhibitors represents the third fastest growing therapeutic class in 2020, with a 17% increase in revenues to USD 40.3 billion.

Under the terms of the contract, Mithra has an option to acquire patents covering CSF1R inhibitor series with upfront payment of EUR 2.25 million on execution of option, following the first results conducted by BCI Pharma. Mithra will fund the preclinical and clinical development with a focus on female cancers and endometriosis, while potentially targeting other orphan indications, such as metastatic breast cancer (TNBC). Currently in the preclinical stage, BCI Pharma should initiate clinical development in 2023, with marketing authorizations expected for 2031.

Dominique Surleraux, CEO at BCI Pharma said: "We are very excited to initiate this strategic partnership with Mithra. This collaboration represents the successful execution of our overarching corporate strategy to deliver new therapy from our disruptive technology which delivers novel, potent and selective kinase inhibitors. We look forward to advancing candidates to the clinic and ultimately achieving the company’s vision to bring new treatment options to patients with difficult-to-treat cancer, endometriosis and others. "

Leon Van Rompay, CEO Mithra Women’s Health, commented: "We are very pleased to collaborate with BCI Pharma on this innovative development opportunity in a fast-growing market that will allow us to diversify our pipeline in women’s health and beyond. Selective kinase inhibitors play a crucial role in many diseases and we look forward to seeing the first results of BCI’s studies on their effect on female cancers and endometriosis."

Didier Malherbe, BCI Pharma Board Chairman, added: "I’m really happy about the partnership between the two Walloon biotech companies. This demonstrates the capability of Belgium biotech to create value in a very dynamic health research environment.

Alligator announces preliminary outcome of rights issue

On November 29, 2021 Alligator Bioscience reported that rights issue of shares (the "Rights Issue") ended on 26 November 2021 (Press release, Alligator Bioscience, NOV 29, 2021, View Source [SID1234596176]). The preliminary outcome shows that the Rights Issue has been oversubscribed. Through the Rights Issue, Alligator will receive approximately SEK 257 million before transaction costs.

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Preliminary outcome

The Rights Issue comprised a maximum of 128,499,507 ordinary shares. The preliminary outcome shows that 118,336,211 shares, corresponding to approximately 92.1 per cent of the Rights issue, has been subscribed for by exercise of subscription rights. In addition, applications for subscription of 37,602,276 shares without the exercise of subscription rights, corresponding to approximately 29.3 per cent of the Rights Issue, have been received. Thus, 155,938,487 shares, corresponding to approximately 121.4 per cent of the Rights Issue, has been subscribed for with and without the exercise of subscription rights. The Rights Issue is thus oversubscribed and no guarantee commitments will be utilized.

Notification regarding allocation

Allocation of shares will be made in accordance with the allocation principles described in the prospectus that was published in connection with the Rights Issue (the "Prospectus"). A notification regarding allocation of shares subscribed for without the exercise of subscription rights will be made by post of a settlement note to each subscriber. Allocated shares subscribed for without the exercise of subscription rights shall be paid for in accordance with the instructions in the settlement note.

Trading in BTA

The final outcome of the Rights Issue is expected to be announced on 1 December 2021. Trading in BTA (Sw. betald tecknad aktie) is currently taking place at Nasdaq Stockholm and will cease when the Rights Issue has been registered by the Swedish Companies Registration Office, which is expected to take place around week 50, 2021. BTA:s will then be converted to ordinary shares.

Number of shares and share capital

The Rights Issue provides Alligator with proceeds amounting to approximately SEK 257 million before transaction costs. As a result of the Rights Issue, Alligator’s share capital will increase by SEK 51,399,802.80 to a total of SEK 85,666,338 and the total number of shares will increase by 128,499,507 shares to a total of 214,165,845 shares, all ordinary shares.

Guarantee Commitments

In connection with the Rights Issue, the Company has entered into agreements on guarantee commitments. For the guarantee commitments, a commission is paid, either in cash or in the form of newly issued shares in the Company. The subscription price for any shares issued to guarantors has been set to SEK 2.10, corresponding to 90 per cent of the volume-weighted average share price (VWAP) for the Company’s share on Nasdaq Stockholm during the subscription period in the Rights Issue (i.e. during the period 12 – 26 November 2021. In case all guarantors would choose to receive guarantee commission in shares, a total of a maximum of 10,660,763 new shares would be issued as guarantee commission.

Advisers

DNB Markets, a part of DNB Bank ASA, Sweden Branch and Redeye AB act as Joint Global Coordinators in connection with the Rights Issue. Setterwalls Advokatbyrå AB acts as legal adviser to Alligator and Baker & McKenzie Advokatbyrå KB acts as legal adviser to the Joint Global Coordinators in connection with the Rights Issue. Aktieinvest FK AB acts as the issuing agent in the Rights Issue.

This information is information that Alligator Bioscience AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08:30 a.m. CET on 29 November 2021.

European Commission Approves LENVIMA® (lenvatinib) Plus KEYTRUDA® (pembrolizumab) for Patients With Certain Types of Endometrial Carcinoma

On November 29, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada) reported that the European Commission has approved the combination of LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A., for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum‑containing therapy in any setting and who are not candidates for curative surgery or radiation (Press release, Eisai, NOV 29, 2021, View Source [SID1234596163]). This marks the first combination of tyrosine kinase inhibitor with immunotherapy approved in Europe for these patients with advanced or recurrent endometrial carcinoma.

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The approval is based on results from the pivotal Phase 3 Study 309/KEYNOTE-775 trial, in which LENVIMA plus KEYTRUDA demonstrated statistically significant improvements in overall survival (OS), reducing the risk of death by 38% (HR=0.62 [95% CI, 0.51-0.75]; p<0.0001), and progression-free survival (PFS), reducing the risk of disease progression or death by 44% (HR=0.56 [95% CI, 0.47-0.66]; p<0.0001), versus chemotherapy (investigator’s choice of doxorubicin or paclitaxel). The median OS was 18.3 months for LENVIMA plus KEYTRUDA versus 11.4 months for chemotherapy. The median PFS was 7.2 months for LENVIMA plus KEYTRUDA versus 3.8 months for chemotherapy. The objective response rate (ORR) was 32% (95% CI, 27-37) for patients treated with LENVIMA plus KEYTRUDA versus 15% (95% CI, 11-18) for patients treated with chemotherapy (p<0.0001). Patients treated with LENVIMA plus KEYTRUDA achieved a complete response (CR) rate of 7% and partial response (PR) rate of 25% versus a CR rate of 3% and a PR rate of 12% for patients treated with chemotherapy.

"This approval is welcome news for patients in Europe, and is based on the first Phase 3 study evaluating an immunotherapy and tyrosine kinase inhibitor combination that showed superior overall survival for patients with advanced or recurrent endometrial cancer compared to chemotherapy," said Dr. Gregory Lubiniecki, Vice President, Clinical Research, Merck & Co., Inc., Kenilworth, N.J., U.S.A. Research Laboratories. "Regardless of mismatch repair status, patients whose endometrial cancer progresses or returns after prior platinum-containing systemic therapies now have a combination treatment option in KEYTRUDA plus LENVIMA that demonstrated a 38% reduction in risk of death compared to chemotherapy alone."

"Until recently, women in Europe with advanced or recurrent endometrial cancer have faced a difficult prognosis and had few treatment options," said Corina Dutcus, M.D., Vice President, Clinical Research, Oncology Business Group at Eisai Inc. "The approval of LENVIMA plus KEYTRUDA in this setting reflects the progress that we have made in our collaboration with Merck & Co., Inc., Kenilworth, N.J., U.S.A. in developing solutions for those diagnosed with difficult-to-treat cancers. We thank the patients, families and healthcare providers who made this milestone possible."

In the Study 309 trial, the most common adverse reactions of these patients (≥20%) for LENVIMA plus KEYTRUDA* were hypertension (63%), diarrhoea (57%), hypothyroidism (56%), nausea (51%), decreased appetite (47%), vomiting (39%), fatigue (38%), decreased weight (35%), arthralgia (33%), proteinuria (29%), constipation (27%), headache (27%), urinary tract infection (27%), dysphonia (25%), abdominal pain (23%), asthenia (23%), palmar-plantar erythrodysaesthesia syndrome (23%), stomatitis (23%), anaemia (22%), and hypomagnesaemia (20%).

This approval allows marketing of LENVIMA plus KEYTRUDA in all 27 EU member states plus Iceland, Liechtenstein, Norway and Northern Ireland. LENVIMA plus KEYTRUDA is now approved by the European Commission for two different types of cancer: for advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation and for the first-line treatment of adult patients with advanced renal cell carcinoma.

*According to the information listed in the SmPC (Summary of Product Characteristics)

About Study 309/KEYNOTE-775 Trial

The approval was based on data from Study 309/KEYNOTE-775 (ClinicalTrials.gov, NCT03517449(New Window)), a Phase 3 multicenter, open-label, randomized, active-controlled study conducted in 827 patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. Participants may have received up to two platinum-containing therapies in total, as long as one was given in the neoadjuvant or adjuvant treatment setting. The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade ≥3 fistula, uncontrolled BP (>150/90 mmHg), significant cardiovascular impairment or event within previous 12 months or patients who had active autoimmune disease or a medical condition that required immunosuppression. The primary efficacy outcome measures were OS, and PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1. Secondary efficacy outcome measures included ORR as assessed by BICR.

Patients were randomized 1:1 to receive LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg intravenously every three weeks) or investigator’s choice, consisting of either doxorubicin (60 mg/m2 every three weeks) or paclitaxel (80 mg/m2 given weekly, three weeks on/one week off). Treatment with LENVIMA plus KEYTRUDA continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for KEYTRUDA, a maximum of 24 months. Administration of LENVIMA plus KEYTRUDA was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated. A total of 121/411 (29%) of patients treated with LENVIMA plus KEYTRUDA received continued study therapy beyond RECIST-defined disease progression. The median duration of the post-progression therapy was 2.8 months. Assessment of tumor status was performed every eight weeks.

About Endometrial Cancer1,2,3,4,5

Endometrial cancer begins in the inner lining of the uterus, which is known as the endometrium and is the most common type of cancer in the uterus. Worldwide, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers in 2020 (these estimates include both endometrial cancers and uterine sarcomas; more than 90% of uterine body cancers occur in the endometrium, so the actual numbers for endometrial cancer cases and deaths are slightly lower than these estimates). In Japan, there were more than 17,000 new cases of uterine body cancer and more than 3,000 deaths from the disease in 2020. In Europe., it is estimated there were more than 130,000 new cases of uterine body cancer and more than 29,000 deaths in 2020. The five-year relative survival rate for metastatic endometrial cancer (stage IV) is estimated to be approximately 17%.

About LENVIMA (lenvatinib) Capsules

LENVIMA, discovered and developed by Eisai, is an orally available kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 75 countries including Japan, in Europe, China and in Asia, and in the United States for locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer. In addition, LENVIMA has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 70 countries including Japan, in Europe, China and in Asia, and in the United States for first-line unresectable hepatocellular carcinoma. LENVIMA has been approved for monotherapy as a treatment for unresectable thymic carcinoma in Japan. It is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including in Europe and Asia, and in the United States the treatment of adult patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. LENVIMA has been approved in combination with KEYTRUDA (generic name: pembrolizumab), for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) in United States and in Europe. LENVIMA has been approved in combination with KEYTRUDA as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in the United States, and has been approved for the similar indication (including conditional approval) in over 10 countries such as Canada and Australia. In some regions, continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials. In Europe, it is approved in combination with KEYTRUDA (generic name: pembrolizumab) as the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation.

About KEYTRUDA (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck & Co., Inc., Kenilworth, N.J., U.S.A. has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

About the Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. Strategic Collaboration

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

In addition to ongoing clinical studies evaluating the LENVIMA plus KEYTRUDA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumor types across more than 20 clinical trials.

Eisai’s Focus on Cancer

Eisai focuses on the development of anticancer drugs, targeting the tumor microenvironment (with experience and knowledge from existing in-house discovered compounds) and the driver gene mutation and aberrant splicing (leveraging RNA Splicing Platform) as areas (Ricchi) where real patient needs are still unmet, and where Eisai can aim to become a frontrunner in oncology. Eisai aspires to discover innovative new drugs with new targets and mechanisms of action from these Ricchi, with the aim of contributing to the cure of cancers.

European Commission Approves LENVIMA® (lenvatinib) Plus KEYTRUDA® (pembrolizumab) as First-Line Treatment for Adult Patients With Advanced Renal Cell Carcinoma

On November 29, 2021 Eisai (Headquarters: Tokyo, CEO: Haruo Naito) and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada) reported that the European Commission has approved the combination of LENVIMA (KISPLYX in the European Union [EU] for the treatment of advanced renal cell carcinoma [RCC]), the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus, KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A., for the first-line treatment of adult patients with advanced RCC (Press release, Eisai, NOV 29, 2021, View Source [SID1234596162]).

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The approval for advanced RCC is based on results from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, in which LENVIMA plus KEYTRUDA demonstrated statistically significant improvements versus sunitinib in the efficacy outcome measures of progression-free survival (PFS), reducing the risk of disease progression or death by 61% (HR=0.39 [95% CI, 0.32-0.49]; p<0.0001) with a median PFS of 23.9 months versus 9.2 months for sunitinib, and overall survival (OS), reducing the risk of death by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=0.0049) versus sunitinib. Median OS was not reached at the time of analysis in either study arm. The objective response rate (ORR) was 71% (95% CI: 66-76) for patients treated with LENVIMA plus KEYTRUDA (n=355) versus 36% (95% CI: 31-41) for patients treated with sunitinib (n=357; p<0.0001). Patients treated with LENVIMA plus KEYTRUDA achieved a complete response (CR) rate of 16% and partial response (PR) rate of 55% versus a CR rate of 4% and a PR rate of 32% for patients treated with sunitinib.

"A key focus of our collaboration with Eisai is to advance our clinical development program to evaluate the potential of KEYTRUDA plus LENVIMA to improve responses across different types of cancer, including renal cell carcinoma," said Dr. Gregory Lubiniecki, Vice President, Clinical Research, Merck & Co., Inc., Kenilworth, N.J., U.S.A. Research Laboratories. "Today’s approval of KEYTRUDA plus LENVIMA brings a new treatment option to patients with advanced renal cell carcinoma in Europe, and further validates our efforts to research this promising combination of an immunotherapy and tyrosine kinase inhibitor for some of the most difficult-to-treat cancers."

"Renal cell carcinoma is the most common type of kidney cancer in both men and women, marking the significance of the European approval for the LENVIMA plus KEYTRUDA combination," said Corina Dutcus, M.D., Vice President, Clinical Research, Oncology Business Group at Eisai Inc. "We remain committed to continuing to explore this combination therapy with the goal of improving care for people living with cancer. The participation of many patients, families and healthcare providers made this approval possible, for which we are very grateful."

In the CLEAR/KEYNOTE-581 trial, the most common adverse reactions (≥30%) for LENVIMA plus KEYTRUDA* were diarrhoea (61.8%), hypertension (51.5%) fatigue (47.1%), hypothyroidism (45.1%), decreased appetite (42.1%), nausea (39.6%), stomatitis (36.6%), proteinuria (33.0%), dysphonia (32.8%), and arthralgia (32.4%).

This approval allows marketing of LENVIMA plus KEYTRUDA in all 27 EU member states plus Iceland, Liechtenstein, Norway and Northern Ireland. LENVIMA plus KEYTRUDA is now approved by the European Commission for two different types of cancer: for the first-line treatment of adult patients with advanced renal cell carcinoma and for advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation.

*According to the information listed in the SmPC (Summary of Product Characteristics)

About CLEAR/KEYNOTE-581 Trial

The approval was based on data from the CLEAR(Study 307)/KEYNOTE-581 trial (ClinicalTrials.gov, NCT02811861(New Window)), a Phase 3, multicenter, open-label, randomized trial conducted in 1,069 patients with advanced RCC with clear cell component including other histological features such as sarcomatoid and papillary in the first-line setting.

Patients were enrolled regardless of PD-L1 tumor expression status. The study excluded patients with active autoimmune disease or a medical condition that required immunosuppression. Randomization was stratified by geographic region (North America and Western Europe vs. "Rest of the World") and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic groups (favorable vs. intermediate vs. poor). The primary efficacy outcome measure was PFS based on Blinded Independent Central Review (BICR) using RECIST 1.1, and PFS results were consistent across pre-specified subgroups, MSKCC prognostic groups and PD-L1 tumor expression status. Key secondary efficacy outcome measures were OS and ORR.

Patients were randomized 1:1:1 to receive LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg intravenously every three weeks for up to 24 months), or LENVIMA (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily for four weeks on treatment, followed by two weeks off treatment). Treatment continued until unacceptable toxicity or disease progression as determined by investigator and confirmed by BICR using RECIST 1.1. Administration of LENVIMA plus KEYTRUDA was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. KEYTRUDA was continued for a maximum of 24 months; however, treatment with LENVIMA could be continued beyond 24 months. Assessment of tumor status was performed at baseline and then every eight weeks.

About Renal Cell Carcinoma (RCC)1,2,3,4,5,6

Worldwide, it is estimated there were more than 431,000 new cases of kidney cancer diagnosed and more than 179,000 deaths from the disease in 2020. In Japan, there were more than 25,000 new cases and 8,000 deaths in 2020. In Europe, it is estimated there were more than 138,000 new cases of kidney cancer diagnosed and more than 54,000 deaths from the disease in 2020. Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCC. Renal cell carcinoma is about twice as common in men as in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Approximately 30% of patients with RCC will have metastatic disease at diagnosis. Survival is highly dependent on the stage at diagnosis, and the five-year survival rate is 13% for patients diagnosed with metastatic disease.

About LENVIMA (lenvatinib); available as 10mg and 4mg capsules

LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 75 countries including Japan, in Europe, China and in Asia, and in the United States for locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer. In addition, LENVIMA has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 70 countries including Japan, in Europe, China and in Asia, and in the United States for first-line unresectable hepatocellular carcinoma. LENVIMA has been approved for monotherapy as a treatment for unresectable thymic carcinoma in Japan. It is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including in Europe and Asia, and in the United States the treatment of adult patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. LENVIMA has been approved in combination with KEYTRUDA (generic name: pembrolizumab), for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) in United States and in Europe. LENVIMA has been approved in combination with KEYTRUDA (generic name: pembrolizumab) as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in the United States, and has been approved for the similar indication (including conditional approval) in over 10 countries such as Canada and Australia. In some regions, continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials. In Europe, it is approved in combination with KEYTRUDA (generic name: pembrolizumab) as the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation.

About KEYTRUDA (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck & Co., Inc., Kenilworth, N.J., U.S.A. has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

About the Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. Strategic Collaboration

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

In addition to ongoing clinical studies evaluating the LENVIMA plus KEYTRUDA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumor types across more than 20 clinical trials.

Eisai’s Focus on Cancer

Eisai focuses on the development of anticancer drugs, targeting the tumor microenvironment (with experience and knowledge from existing in-house discovered compounds) and the driver gene mutation and aberrant splicing (leveraging RNA Splicing Platform) as areas (Ricchi) where real patient needs are still unmet, and where Eisai can aim to become a frontrunner in oncology. Eisai aspires to discover innovative new drugs with new targets and mechanisms of action from these Ricchi, with the aim of contributing to the cure of cancers.

Subtle Medical and Bayer Collaborate to Advance Deep Learning Research to Harness the Power of AI in Medical Imaging

On November 28, 2021 Subtle Medical, a leading healthcare technology company, and Bayer, a leading life science company with extensive expertise from diagnosis to care, reported a collaboration to explore opportunities to utilize AI (artificial intelligence) to aid in image acquisition in radiology (Press release, Bayer, NOV 28, 2021, View Source [SID1234596168]). The companies will investigate the potential of Subtle Medical’s state-of-the-art AI algorithm, SubtleGAD, for use in contrast-enhanced MRI exams to enhance image quality and will explore potential new areas for contrast media use.

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"At Bayer, we are constantly striving to advance medical knowledge and provide the best possible therapeutic and diagnostic options for physicians and patients," said Prof. Dr. Olaf Weber, Head of Radiology Research and Development at Bayer. "We are pleased to collaborate with Subtle Medical to harness the power of AI, with the ultimate goal of providing physicians with the means for optimal diagnosis for their patients."

Subtle Medical’s AI technologies acquire and improve high quality images from both accelerated and low dose scans.

MRI exams enable physicians to obtain detailed images of the body and help them answer critical medical questions in the diagnosis and monitoring of disease. In light of an aging population, the need for medical imaging to facilitate diagnosis, treatment decisions and therapy planning has grown. Artificial intelligence is a promising tool to support radiologists in their task to provide accurate and timely diagnosis to their patients, in addition to offering opportunities to speed up imaging exam times and reduce dose. In particular, Subtle Medical’s suite of deep learning technologies aid in higher quality image acquisition from both accelerated and low dose scans. Both companies are looking forward to joining forces to drive innovation in medical imaging.

"We are proud to collaborate with Bayer to combine our expertise and drive innovative solutions in light of the ever increasing demands of medical imaging," said Dr Ajit Shankaranarayanan, Chief Product Officer at Subtle Medical. "At Subtle Medical, we are committed to continued innovation and the development of AI tools that create a meaningful impact for both radiologists and patients."

Subtle Medical’s clinically validated AI-powered software solutions increase the efficiency of image capture by improving the quality of accelerated and low dose imaging. Subtle’s solutions are compatible with all scanner brands, models and field strengths so institutions can see the benefit across their entire scanner fleet. Meet with Subtle Medical at RSNA 2021.

"Bayer is a key partner due to their clinical expertise and proven track record in medical imaging. Such collaborations across the industry will be crucial to unlock the power of AI, ultimately benefiting patients, improving imaging capabilities and patient diagnosis worldwide," said Josh Gurewitz, Chief Commercial Officer at Subtle Medical.