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European Commission Approves Cabometyx® in Combination With Opdivo® as a First-Line Treatment for Patients Living With Advanced Renal Cell Carcinoma

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.

Junshi Biosciences Announces Full Year 2020 Financial Results And Provides Corporate Updates

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]).

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.

Transcript of conference call held on March 30, 2021

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

InDex Pharmaceuticals enters agreement with Parexel Biotech for phase III clinical study of cobitolimod for ulcerative colitis

On March 30, 2021 InDex Pharmaceuticals Holding AB (publ) reported that the company has entered an agreement for services with global clinical research organization (CRO) Parexel Biotech for the phase III study CONCLUDE(Press release, InDex Pharmaceuticals, MAR 30, 2021, View Source [SID1234584071]). The study will evaluate the efficacy and safety of the drug candidate cobitolimod for the treatment of moderate to severe left-sided ulcerative colitis.

"We are excited to advance cobitolimod into phase III, which is the final stage of development before application for market approval. After the successful collaboration in our recent phase IIb study CONDUCT, we are very pleased to collaborate once again with Parexel Biotech as our clinical development partner", says Peter Zerhouni, CEO of InDex Pharmaceuticals. "Parexel Biotech is a leading global CRO with considerable experience managing phase III studies in inflammatory bowel disease, which will ensure an efficient execution of the study."

CONCLUDE is a randomised, double-blind, placebo-controlled, global phase III study to evaluate cobitolimod as a novel treatment for patients with moderate to severe left-sided ulcerative colitis. The induction study will include approximately 400 patients, and the primary endpoint will be clinical remission at week 6. Patients responding to cobitolimod in the induction study will be eligible to continue in a one-year maintenance study, where they will be treated with either cobitolimod or placebo.

Apart from the dosing 250 mg x 2, which was the highest dose and the one that showed the best efficacy in the phase IIb study CONDUCT, the phase III study will also evaluate a higher dose, 500 mg x 2, in an adaptive study design. This higher dose has the potential to provide an even better efficacy than what was observed in the phase IIb study.

"We are pleased to partner with InDex Pharmaceuticals on the phase III clinical trial CONCLUDE to evaluate a potential new therapy for patients with moderate to severe ulcerative colitis," said Jim Anthony, Senior Vice President and Global Head, Parexel Biotech. "Our collaboration with InDex Pharmaceuticals demonstrates our commitment to designing innovative solutions that draw from our global clinical experience and therapeutic expertise to fulfill unmet medical needs on behalf of patients worldwide."

For more information:
Peter Zerhouni, CEO
Phone: +46 8 122 038 50
E-mail: [email protected]

Publication
The information was submitted for publication through the agency of the contact person set out above at 8:00 CET on March 30, 2021.

Cobitolimod in brief
Cobitolimod is a first-in-class Toll-like receptor 9 (TLR9) agonist that can provide an anti‐inflammatory effect locally in the large intestine, which may induce mucosal healing and relief of the clinical symptoms in ulcerative colitis. Cobitolimod met the primary endpoint in the phase IIb study CONDUCT and demonstrated an outstanding combination of efficacy and safety. The results were recently published in the reputable medical journal, The Lancet Gastroenterology & Hepatology. Data from four previous completed placebo-controlled clinical trials support the efficacy and safety demonstrated in the CONDUCT study.

Medigene AG: Publication of research on co-receptor independent MAGE-A4-specific T cell receptor

On March 30, 2021 Medigene AG (Medigene, FSE: MDG1, Prime Standard), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported the publication of a peer-reviewed paper entitled, "Development of a CD8 co-receptor independent T cell receptor specific for tumor-associated antigen MAGE-A4 for next generation T-cell-based immunotherapy" covering preclinical research on a T cell receptor (TCR) specific for a peptide derived from the MAGE-A4 protein in the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, MediGene, MAR 30, 2021, View Source [SID1234577444]). The research was conducted by Medigene’s scientists in collaboration with scientists from bluebird bio, Inc. (bluebird bio, NASDAQ: BLUE). The paper was published online: View Source

The paper describes the discovery and characterization of a MAGE-A4-specific TCR and provides detailed scientific information highlighting the robust potency and exquisite specificity of this TCR against a MAGE-A4-derived peptide.

This MAGE-A4-specific TCR is the most advanced program in Medigene’s collaboration with bluebird bio. This TCR differs from other MAGE-A4 TCRs currently in development elsewhere as it works independently of the T cell co-receptor CD8, which is found on killer T cells. As shown in the paper, this enables T cells equipped with this MAGE-A4 TCR to detect and kill tumor cells expressing MAGE-A4 in a preclinical setting, including helper T cells which express CD4 and not CD8.

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer of Medigene: "We are delighted to see the high quality of our collaborative research with bluebird bio recognized by this scientific publication. This MAGE-A4-specific TCR, being CD8 co-receptor independent, can activate MAGE-A4-specific responses in either CD4 helper or CD8 killer T cells. In this way, the TCR enables the broadest functional T cell response against MAGE-A4-positive tumor cells and, as demonstrated in preclinical in vivo models, strong control of tumor growth.
Our allogeneic T cell priming, and selection technology was used very successfully to isolate this TCR. This technology is well suited to finding such non-mutated, high avidity TCRs specific for different antigens which we believe will be key to developing next generation TCR-T cells for solid cancer."

Scientific Information
The MAGE-A4-specific HLA-A2-restricted TCR was isolated using Medigene’s allogeneic priming technology to stimulate and screen T cells from an HLA-A2-negative donor for cells with the desired specificity. In preclinical research, the TCR has a favorable activity profile and superior in vivo potency compared to other specific MAGE-A4 TCRs tested (including those isolated from HLA-A2-positive donors who have tolerized T cell repertoires to self-antigens presented by HLA-A2). This non-mutated, high avidity MAGE-A4-specific TCR is CD8 co-receptor-independent, allowing effector functions to be elicited in CD4 helper T cells transduced to express the TCR. These CD4 TCR-T cells not only supported an anti-tumor response by direct killing of MAGE-A4-positive tumor cells, but also upregulated certain properties associated with helper function, such as surface marker expression and release of key cytokines.