On March 31, 2021 Complix, a biopharmaceutical company developing a pipeline of transformative Alphabody therapeutics reported the publication in Science Advances of the results from a joint, multidisciplinary study with Belgian life sciences research Institute VIB and Ghent University (Press release, Complix, MAR 31, 2021, View Source;utm_medium=rss&utm_campaign=complix-and-vib-publish-pioneering-study-on-cell-penetrating-alphabodies-in-science-advances [SID1234577405]). The proof-of-concept study demonstrates the potential of Cell-Penetrating Alphabodies (CPABs) to efficiently penetrate the cancer cell membrane, disrupt an intracellular protein-protein interface, and cause an anti-tumor effect upon in vivo administration in relevant xenograft models.

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The article by Pannecoucke et al. can be accessed by clicking here.

CPABs are a revolutionary class of small proteins that have been designed to overcome the limitations of conventional antibodies and small molecules through combining the specific potency of biologics with the cell-penetrating capacity and stability of small molecules. Data available show that CPABs have the potential to address a wide range of disease targets, particularly intracellular targets, that are difficult for current therapies to reach.

The study, published in Science Advances, demonstrates that CPABs can be designed to efficiently penetrate the cell membrane, disrupt an intracellular protein-protein interface, and carry an albumin-binding moiety to extend their serum half-life to therapeutically relevant levels. The unique combination of these three features in a single protein scaffold is without precedent. In this publication a CPAB was engineered against MCL-1, an intracellular protein target in cancer.

The findings from this study provide strong proof of concept for the use of CPABs against intracellular disease mediators, which, to date, have remained in the realm of small-molecule therapeutics.

Dr. Ignace Lasters, CTO of Complix, commented:
"We are pleased to see the publication of this important study, which is a clear validation of our platform and highlights the potential of CPABs to directly address intracellular drug targets in oncology. Reaching the intracellular space has been a critical limiting factor in broadening the therapeutic potential of current biologicals such as monoclonal antibodies. This proof-of-concept study clearly demonstrates the potential of CPABs as a transformative, "membrane crossing" technology to address a variety of cutting-edge and challenging intracellular disease targets. This holds the promise for the creation of an entirely novel class of therapeutics with applications in oncology and beyond."

Prof. Savvas Savvides, Group leader at VIB Center for Inflammation Research, and Professor of Structural Biology at Ghent University, said:
"Our study clearly extends the currently charted protein-based drug-targeting landscape by targeting the well-known intracellular drug target MCL–1, a protein upregulated in multiple tumor types and correlated with therapy resistance. It is very exciting and rewarding to see how our longstanding collaboration with Complix has matured to provide the essential knowledge needed to tackle such a major and important challenge in the design of novel therapeutics."

Scientific publication
Erwin Pannecoucke, Maaike Van Trimpont, Johan Desmet, Tim Pieters, Lindy Reunes, Lisa Demoen, Marnik Vuylsteke, Stefan Loverix, Karen Vandenbroucke, Philippe Alard, Paula Henderikx, Sabrina Deroo, Franky Baatz, Eric Lorent, Sophie Thiolloy, Klaartje Somers, Yvonne McGrath, Pieter Van Vlierberghe, Ignace Lasters, Savvas N. Savvides. Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting. Science Advances, 26 March 2021: Vol. 7, no. 13.

On March 31, 2021 Takeda Pharmaceutical Company Limited (TOKYO:4502) (NYSE:TAK) ("Takeda") reported the completion of its previously-announced sale of Takeda Consumer Healthcare Company Limited ("TCHC") to Oscar A-Co KK, a company controlled by funds managed by The Blackstone Group Inc. and its affiliates (collectively "Blackstone") for a total value of JPY 242.0 billion1 (Press release, Takeda, MAR 31, 2021, View Source [SID1234577384]). This divestment agreement was first announced in August 2020.

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Following the transfer of shares, TCHC will be excluded from the scope of consolidation of Takeda2, and operates as Alinamin Pharmaceutical Co., Ltd ("Alinamin Pharmaceuticals").

The divested portfolio included a variety of over-the-counter ("OTC") medicines and health products that generated total revenues of over JPY 60.0 billion in fiscal year 2019. TCHC’s strong regional brands included Alinamin, its top selling product and Japan’s first vitamin B1 preparation, and Benza, a cold remedy. Takeda is confident that under Blackstone, Alinamin Pharmaceuticals will be well-positioned to continue growing and developing its product offerings in the years to come to address the evolving needs of consumers.

Takeda intends to use the proceeds from the sale to reduce its debt and accelerate deleveraging towards its target of 2x net debt/adjusted EBITDA within FY2021 – FY2023.

Takeda has sustained momentum in its divestiture strategy and has exceeded its $10 billion non-core asset divestiture target. Takeda has announced 12 deals since January 2019, for a total aggregate value of up to approximately $12.9 billion.

The sales price is currently anticipated to be approximately JPY 230.0 billion, subject to certain adjustments, including net debt and working capital of TCHC and Takeda Healthcare Products Company Limited as of March 31, 2021. With the completion of the transfer of shares, a pre-tax gain of approximately JPY 140.0 billion on the sale of shares of a subsidiary will be recognized, and Takeda anticipates Reported Net Profit attributable to owners of the Company to increase by approximately the same amount in the fiscal year ending March 31, 2021 (FY2020). Since the gain on the sale of shares of the subsidiary relates to the divestiture of a non-core business, there will be no impact on Core Operating Profit or Core Net Profit.

1 Enterprise value. Actual sales price will be determined after adjustment for items including net debt and working capital of TCHC and Takeda Healthcare Products Company Limited ("THP").
2 As a result of the share transfer, a wholly owned subsidiary of TCHC, THP, will also be excluded from the scope of consolidation of Takeda.

On March 31, 2021 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Commission (EC) has approved Cabometyx (cabozantinib) in combination with Bristol Myers Squibb’s Opdivo (nivolumab) for the first-line treatment of advanced renal cell carcinoma (aRCC) (Press release, Ipsen, MAR 31, 2021, View Source [SID1234577383]). This decision marks the first approval for Cabometyx in combination with another therapy in Europe and the third indication of Cabometyx in renal cell carcinoma (RCC).

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"Today’s EC approval for the use of Cabometyx in combination with Opdivo provides an important new first-line treatment option for patients living with advanced renal cell carcinoma," said Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen. "At Ipsen, we’re proud that this, now approved, treatment option not only addresses key efficacy benefits, but also the need to maintain quality of life for patients. We look forward to collaborating with a broad range of European stakeholders to bring this unique combination to eligible patients living with advanced renal cell carcinoma."

The EC approval is based on results from the pivotal Phase III CheckMate -9ER trial, presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 and published in the New England Journal of Medicine (NEJM) on 3 March 2021. In the trial, Cabometyx in combination with Opdivo demonstrated significant improvements across all efficacy endpoints. In patients receiving the combination, median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months respectively (HR: 0.51; 95% CI: 0.41–0.64; p<0.0001).1 Overall survival (OS) also demonstrated statistically significant improvements, reducing the risk of death by 40% versus sunitinib (HR: 0.60 [98.89% CI: 0.40-0.89]; p=0.001; median OS not reached in either arm).1 In addition, Cabometyx in combination with Opdivo demonstrated a superior objective response rate (ORR), with twice as many patients responding compared to sunitinib (55.7% vs. 27.1%; p<0.0001) and 8.0% vs. 4.6% achieved a complete response respectively.1 Key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.1 The combination was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor components in first-line aRCC.1

Additional data from the CheckMate -9ER trial were also presented in February at the recent American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Genitourinary Cancers Symposium (ASCO GU). These data highlighted sustained superior efficacy of Cabometyx in combination with Opdivo versus sunitinib for the first-line treatment of aRCC with a median follow-up of 23.5 months, as well as data suggesting significantly improved health-related quality of life (HRQoL) outcomes for the combination versus sunitinib.2,3 These HRQoL data, also included as part of the recently published NEJM publication, demonstrated that the combination was associated with a lower treatment burden, a decline in the risk of confirmed deterioration in HRQoL and a reduction of disease-related symptoms compared to sunitinib.1,3

"The combination of nivolumab and cabozantinib pairs two proven agents for advanced renal cell carcinoma that together have shown superior efficacy across key endpoints and subgroups of patients compared to sunitinib in the CheckMate -9ER trial. Additionally, the combination’s safety profile was manageable with known protocols, leading to a low rate of treatment-related discontinuations," said Marc- Oliver Grimm, M.D., Professor of Medicine and Urology Department Head, Jena University Hospital. "With today’s approval, clinicians in the EU will be able to offer patients with advanced renal cell carcinoma an additional combination therapy that may help them achieve early control of their disease and improve survival outcomes."

This approval allows for the marketing of Cabometyx in combination with Opdivo in this indication in all 27 member states of the European Union, Norway, Liechtenstein and Iceland. The U.S. Food and Drug administration approved Cabometyx for patients with aRCC as a first-line treatment in combination with Opdivo in January 2021.

Ipsen thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

About renal cell carcinoma
There are over 400,000 new cases of kidney cancer diagnosed worldwide each year.4 Of these, renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 90% of cases.5,6 It is twice as common in men, and male patients account for over two thirds of deaths.4 If detected in the early stages, the five-year survival rate is high, but for patients with advanced or late- stage metastatic RCC the survival rate is much lower, around 12%, with no identified cure for this disease.7,8

About the CheckMate -9ER trial
CheckMate -9ER is an open-label, randomized, multi-national Phase III trial evaluating patients with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus Opdivo (n= 323) versus sunitinib (n= 328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Cabometyx (cabozantinib)
Cabometyx is currently approved in 57 countries, including in the European Union, the U.K., Norway, Iceland, Liechtenstein, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong- Kong, Singapore, Macau, Jordan, Lebanon, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador and Thailand for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, the U.K., Liechtenstein, Norway, Iceland, Canada, Australia, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador and Thailand for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, the U.K., Liechtenstein, Norway, Iceland, Canada, Australia, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, Russian Federation, Ukraine, Turkey, Lebanon, United Arab Emirates, Peru, Panama, Guatemala, Chile, Dominican Republic, Ecuador and Thailand for HCC in adults who have previously been treated with sorafenib.

The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (SmPC) and in the U.S. Prescribing Information (PI).

Cabometyx is marketed by Exelixis, Inc. in the United States and by Takeda Pharmaceutical Company Limited in Japan. Ipsen has exclusive rights for the commercialization of Cabometyx outside of the U.S. and Japan. Cabometyx is a registered trademark of Exelixis, Inc.

On March 30, 2021 Junshi Biosciences, a leading innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies, reported financial results for the full year 2020 and provided corporate updates (Press release, Shanghai Junshi Bioscience, MAR 30, 2021, View Source [SID1234633504]).

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Full Year 2020 Financial Highlights

Total revenues increased 106% to RMB1,595 million for the full year ended December 31, 2020. Sales of toripalimab reached RMB1,003 million with gross profit margin of 89%. Additional revenues included out-licensing revenue of RMB405 million and research collaboration service revenue of RMB 88 mil.
The research and development ("R&D") expenses were RMB1,778 million for the full year ended December 31, 2020, representing an increase of 88% from the same period in 2019. The increase was primarily due to continued increasing investment in in-house projects and more R&D collaboration and license-in activities. The R&D fields of the Company have expanded from monoclonal antibodies to more drug types, including small molecule drugs, antibody drug conjugates (ADCs), bifunctional fusion proteins and cell therapies, as well as the exploration of next-generation innovative therapies for cancer and autoimmune diseases.
Net cash from financing activities was RMB4,414 million for the full year ended December 31, 2020, which was mainly attributable to the successful new issuance of A shares on the STAR Market of the Shanghai Stock Exchange (the "STAR Market") with RMB4,497 million through the initial public offering on 15 July 2020.
Total comprehensive expense was RMB1,688 million for the full year ended December 31, 220, representing an increase of 128% compared to the year 2019, which was mainly attributable to the revenue from sales of toripalimab, revenue from out-licensing and service income but offset by the increasing R&D expenses, administrative expenses and selling and distribution expenses.
Cash and cash equivalents as of December 31, 2020 were RMB3,385 million compared to RMB1,214 million as of December 31, 2019. The increase mainly came from funds raised from the listing of the Company’s A shares on the STAR Market on 15 July 2020.
Business Highlights

During the full year ended December 31, 2020, we have achieved significant progress with respect to our product commercialization, clinical trials, pipeline expansion and construction of production bases, including:

Toripalimab was successfully included in the new catalogue of the National Reimbursement Drug List upon negotiations, which will further enhance the domestic affordability and accessibility of the drug.
The supplemental new drug application ("NDA") for toripalimab received a second conditional approval for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma after failure of at least two lines of prior systemic therapy.
Toripalimab has been granted 1 breakthrough therapy designation, 1 fast track designation and 3 orphan-drug designations by the U.S. Food and Drug Administration (the "FDA") for the treatment of mucosal melanoma, nasopharyngeal carcinoma and soft tissue sarcoma, and has been included in the Drug List of the Procedure for Breakthrough Therapy Designation by the National Medical Products Administration (the "NMPA"). The supplemental NDA of toripalimab for the second-line treatment of metastatic urothelial carcinoma received priority review from the NMPA in July 2020. With accelerated clinical trials domestically and abroad, more than 30 clinical studies covering more than 15 indications in respect of toripalimab have been conducted globally, including in China and the United States.
In September 2020, the Independent Data Monitoring Committee (the "IDMC) determined that toripalimab in combination with standard chemotherapy as the treatment for patients with recurrent or metastatic nasopharyngeal carcinoma met its pre-specified primary endpoint at the interim analysis of a randomized, double-blind, placebo-controlled, international multi-center, Phase III clinical study. In February 2021, the supplemental NDA of toripalimab in combination with chemotherapy for the first-line treatment of patients with advanced, recurrent or metastatic nasopharyngeal carcinoma was accepted by the NMPA.
In December 2020, the IDMC determined that toripalimab in combination with standard chemotherapy as the first-line treatment of patients with advanced non-small cell lung cancer met its pre-specified primary endpoint at the interim analysis of a randomized, double-blind, multi-center, phase III clinical study.
As of the date of this announcement, we have 30 drug candidates, including 28 innovative drugs and 2 biosimilars, covering 5 major therapeutic areas including malignant tumors, autoimmune diseases, chronic metabolic diseases, neurological diseases and infectious diseases.
TAB004/JS004 (recombinant humanized anti-BTLA monoclonal antibody injection) was approved for clinical trials in China by the NMPA in January 2020, and the dosing of the first patient was completed in the Phase I clinical trial in April 2020. In addition, it has completed the dose-escalation stage in Phase I in the U.S. and entered the dose-expansion stage.
JS005 (recombinant humanized anti-IL-17A monoclonal antibody for injection) completed the dosing of the first subject in the Phase I clinical trial which was conducted in China in May 2020. At present, the Phase I clinical study has been completed and the Phase II clinical trial is underway.
JS108 (recombinant humanized anti-Trop2 monoclonal antibody -Tub196 conjugate) was approved for clinical trials in China by the NMPA in July 2020 and completed the dosing of the first patient in November 2020.
TAB006/JS006 (specific anti-TIGIT monoclonal antibody injection) obtained the clinical trial approval from the NMPA and the FDA in November 2020 and February 2021, respectively.
Entered the field of anti-infection treatment and worked together to fight the pandemic. At the beginning of the outbreak, we quickly launched a neutralizing antibody R&D project (generic name: etesevimab; project code: JS016) with the Institute of Microbiology, Chinese Academy of Sciences ("IMCAS") for the treatment and prevention of the novel coronavirus disease ("COVID-19") in order to combat the pandemic.
In May 2020, the Company and Eli Lilly and Company entered into an agreement to collaborate on the research, development and commercialization of potential preventive and therapeutic antibody therapies for COVID-19, and Lilly was granted an exclusive license to conduct research, develop and commercialize JS016 outside Greater China.
The international authoritative journal, Nature, published the results of etesevimab pre-clinical research, which reported for the first time that the neutralizing antibody of SARS-CoV-2 can significantly inhibit COVID-19 infection in the test on non-human primate rhesus monkeys, showing the dual effect of treatment and prevention with a value for conversion into clinical practices.
As of the date of this announcement, we have completed a Phase I study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of etesevimab among healthy Chinese subjects, and initiated international multi-center Phase Ib/II trials among COVID-19 patients.
The FDA granted Lilly, our partner, the Emergency Use Authorization for investigational etesevimab 1,400 mg and bamlanivimab 700 mg together, for the treatment of mild to moderate COVID-19 in patients who were at high risk for progressing to severe COVID-19 and/or hospitalization.
The National Institutes of Health (NIH) in the United States recommended the use of etesevimab and bamlanivimab together for the treatment of mild to moderate COVID-19 outpatients with a higher risk of clinical progression in its recently updated "COVID-19 Treatment Guidelines".
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive scientific opinion, for etesevimab administered together with bamlanivimab.
Broadened the layout of product pipeline through co-development/license-in and other means. Apart from developing drug candidates on our own technology platforms, we also actively collaborated with outstanding domestic and overseas biotechnology companies to further expand our product pipeline and broaden the layout of drug combination therapies.
We entered into a research collaboration and license agreement with Revitope Oncology, Inc. and its wholly-owned subsidiary Revitope Limited. The parties will collaborate in the R&D of the next-generation of T-cell engaging cancer immunotherapies that utilize Revitope’s Precision GATETM Technology Platform together with the Company’s antibody technology platforms.
By forming a company jointly with IMPACT Therapeutics, Inc., we collaborated in the development of senaparib, a PARP inhibitor, and own 50% of its interests within mainland China, the Hong Kong Special Administrative Regions ("Hong Kong") and the Macau Special Administrative Regions ("Macau"). Both parties will collaborate in conducting clinical trials, manufacturing, and commercializing preparations for various indications of senaparib within the above-mentioned collaboration territory.
We entered into a shareholders collaboration agreement with Beijing Eirene Biotech Co., Ltd. for the formation of a joint venture company mainly engaged in the R&D, clinical application and market development of the CD39 drug. The CD39 product has a unique and innovative design concept to achieve high efficacy and reduce potential systemic adverse effects by selectively targeting the immune suppressive cells with high CD39 expression in the tumor microenvironment. The joint venture company will be owned 50% by the Company and 50% by Beijing Eirene upon its formation.
We entered into a collaboration agreement with Wigen Biomedicine Technology (Shanghai) Co., Ltd. ("Wigen Biomedicine") for the world-wide joint development, production and commercialization of four of Wigen Biomedicine’s anti-tumor small molecule drug candidates (XPO1 inhibitor, Aurora-A inhibitor, EGFR-exon20 inhibitor and fourth-generation EGFR inhibitor).

All these collaborations will broaden and strengthen our product layout in the oncology field to cover more tumor types, in the hopes of providing more treatment options for tumor patients in China and abroad in the future.
In order to optimize the capital structure, focus more on the development of the principal business, improve operating efficiency, increase our investment in research and development, and better serve technological innovation, we made every effort to prepare for the listing of the Company’s A shares on the STAR Market which were successfully listed on the STAR Market on 15 July 2020.

On March 30, 2021 Spectrum Pharmaceuticals presented Transcript of conference call (Presentation, Spectrum Pharmaceuticals, MAR 30, 2021, View Source [SID1234598650]).

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