Kyowa Kirin Receives European Commission Approval for Use of CRYSVITA®(burosumab) for the Treatment of Tumour-Induced Osteomalacia (TIO)

On August 19, 2022 Kyowa Kirin Co., Ltd. (TSE: 4151, Kyowa Kirin) reported that the European Commission (EC) approved CRYSVITA (burosumab) for the treatment of FGF23-related hypophosphataemia in Tumour-Induced Osteomalacia (TIO) associated with phosphaturic mesenchymal tumours (PMTs) that cannot be curatively resected or localised in children and adolescents aged 1 to 17 years and in adults (Press release, Kyowa Hakko Kirin, AUG 19, 2022, View Source [SID1234618506]).1 CRYSVITA is also already licensed in the EU for use in the rare disease X-Linked Hypophosphataemia (XLH), for children and adolescents between 1 and 17 years of age with radiographic evidence of bone disease, and in adults.2

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Also known as oncogenic osteomalacia, TIO is an acquired disorder caused by typically small, slow-growing, benign PMTs.3,4 It is a rare condition with fewer than 1000 cases reported in the medical literature,4 which mainly affects adults and with a mean onset age of 40 – 45 years.3,5 TIO is associated with progressive and debilitating musculoskeletal deficits,6,7 ultimately having a detrimental impact on ability to perform daily activities, as well as on physical and social wellbeing.8

A cure for TIO can be achieved with complete surgical resection of the causative tumour(s), however, surgical resection is not always possible due to the anatomical location and difficulty in detecting tumours.3,5 TIO may recur and persist following incomplete or unsuccessful surgical resection.9

With this approval by the European Commission, CRYSVITA is the first biologic treatment available to EU patients within its licensed indication for TIO. CRYSVITA blocks the action of fibroblast growth factor-23 (FGF23), which is produced in excess in TIO, restoring phosphate homeostasis.2,10

"The approval by the European Commission is a very welcome milestone for those living with TIO that cannot be cured by complete surgical resection," said Professor Ralf Oheim, Department of Osteology and Biomechanics, University Medical Center Hamburg. "With the challenges faced by those living with TIO and those treating it, the unmet need in TIO has been clear for a long time and today’s decision will help support those living with TIO and those healthcare professionals supporting them address such unmet need."

"This is a momentous day for the TIO community in Europe and I’m proud that Kyowa Kirin can be a part of meeting the needs of people who have such a high unmet need", said Abdul Mullick, President of Kyowa Kirin International. "Our purpose is to make people smile, and with this new indication for a rare disease with limited available treatment options, we can truly say that together with the TIO community, we are living our purpose."

With this EC approval, Kyowa Kirin International will work with local health authorities in each country under the purview of the EC to ensure that those living with TIO are able to gain access to CRYSVITA as soon as possible.

▼This medicinal product is subject to additional monitoring.

About Tumour-Induced Osteomalacia (TIO)
TIO is characterised by chronic hypophosphataemia caused by tumour(s) secreting excess fibroblast growth factor 23 (FGF23),3 which can lead to issues such as decreased intestinal absorption of phosphate and compromised vitamin D activation.3,4

The most common signs and symptoms include bone pain, difficulty walking, pathological fractures, height loss and muscle weakness.6 In TIO, muscle weakness and pain severely interfere with physical functioning, including standing up without assistance, walking and ability to work.8 The pain in TIO also severely interferes with mood and moderately interferes with enjoyment of life for those living with it.8

TIO diagnosis is often missed and/or delayed and testing serum phosphate levels is important for diagnosis.3 The only cure in TIO is complete removal of the causative tumour(s).3 Pharmacological treatment should be considered in TIO cases where tumour(s) cannot be curatively resected or localised.3 Restoring phosphate homeostasis is essential to improve the health of people living with TIO.3

About CRYSVITA (burosumab) in TIO
CRYSVITA (burosumab) was created and developed by Kyowa Kirin and is a recombinant fully human monoclonal antibody that binds to and inhibits the activity of FGF23.2 CRYSVITA blocks the action of FGF23, which is produced in excess in TIO, restoring phosphate homeostasis.2

The efficacy and safety of CRYSVITA have been demonstrated in two Phase 2 clinical trials published in the disease area of TIO.11,12 CRYSVITA was well-tolerated and demonstrated an acceptable safety profile.11,12

Following this new EC approval, CRYSVITA is now indicated in the EU for the treatment of FGF23-related hypophosphataemia in TIO associated with PMTs that cannot be curatively resected or localised in children and adolescents aged 1 to 17 years and in adults1, as well as for XLH in children and adolescents aged 1 to 17 years with radiographic evidence of bone disease, and in adults.2 CRYSVITA is given as a subcutaneous injection, every 4 weeks in adults and every 2 weeks in children and adolescents aged 1 to 17 years.2

CRYSVITA is currently approved for use in the treatment of TIO in a number of countries, including the United States13 and Japan.14

Kyowa Kirin and Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE: Ultragenyx) have been collaborating in the development and commercialisation of CRYSVITA globally, based on the collaboration and licence agreement between Kyowa Kirin and Ultragenyx.

IN8bio Announces Closing of Exercise Option to Purchase Additional Shares in Public Offering

On August 19, 2022 — IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative gamma-delta T cell therapies utilizing its DeltEx platform, reported that the underwriter of its previously announced underwritten public offering of common stock which closed on August 16, 2022 has partially exercised its option to purchase an additional 268,949 shares at the public offering price of $1.90 per share, resulting in additional gross proceeds of approximately $0.5 million (Press release, In8bio, AUG 19, 2022, View Source [SID1234618505]). After giving effect to the partial exercise of the option to purchase additional shares, the total number of shares sold by IN8bio in the public offering increased to 5,663,686 shares and gross proceeds increased to approximately $10.75 million.

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H.C. Wainwright & Co. acted as the sole book-running manager for the offering.

The shares were offered by IN8bio pursuant to a registration statement on Form S-1 (File No. 333-266620) that was previously filed with, and subsequently declared effective on August 11, 2022, by the U.S. Securities and Exchange Commission (SEC). The offering was made only by means of a prospectus that formed a part of the effective registration statement. The final prospectus relating to and describing the terms of the offering was filed with the SEC on August 12, 2022. Electronic copies of the final prospectus may be obtained by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at (212) 856-5711 or email at [email protected]. The final prospectus is also available on the SEC’s website at View Source

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities of IN8bio, nor shall there be any sale of these shares of common stock in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Michael Sen to succeed Stephan Sturm as CEO of Fresenius

On August 19, 2022 Fresenius reported Michael Sen (53) will become Chief Executive Officer on October 1, 2022 (Press release, Fresenius, AUG 19, 2022, View Source [SID1234618504]). He was appointed unanimously by the Supervisory Board of Fresenius Management SE today to succeed Stephan Sturm (59), who will leave the company on good terms on September 30. Michael Sen will, in addition, continue to serve as CEO of Fresenius Kabi until a successor is decided for this position.

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Michael Sen has been responsible for the Fresenius Kabi business segment on the Fresenius Management Board since April 2021. Previously, he was a member of the Management Board of Siemens AG, where he was responsible for the healthcare business Siemens Healthineers and for Siemens’ energy business. From 2015 to 2017 he was Chief Financial Officer of E.ON SE.

Stephan Sturm has been a member of the Fresenius Management Board since 2005, beginning as CFO. He became CEO of Fresenius on July 1, 2016.

Stephan Sturm said: "Fresenius has always been more than just a job to me. This company was and is still close to my heart. I look back with gratitude and pride on my more than 17 years here, during which we accomplished a lot together and developed Fresenius into a leading global healthcare company – one that provides ever more people with ever better medicine. I’m especially thankful for the many colleagues with whom I was privileged to work, and with whom I will remain connected even after my time at Fresenius. This is a great company, with outstanding growth prospects."

Wolfgang Kirsch, Chairman of the Supervisory Board of Fresenius, said: "On behalf of the entire Supervisory Board, I want to thank Stephan Sturm for his many years of outstanding commitment and service to Fresenius. Starting from his time as CFO he has played a major role in our successful development and in our continued, profitable growth. As CEO he has steered our company through increasingly rough waters over the past few years, and kept it on course. The pandemic, in particular, did not make this easy. Stephan Sturm has identified totally with our company and devoted all his energy and capabilities to its success. For this we owe him respect and great thanks. Following the orderly transition to his successor, I sincerely wish him all the very best for the future.

"At the same time, I’m very pleased that in our own ranks we have, in the person of Michael Sen, an outstanding manager who is supremely well qualified to take on this important position," Kirsch added. "He has extensive and relevant experience in industry. He is accomplished in designing and implementing transformation and change processes. And he has strategic skills, as he has shown during his first year-and-a-half as CEO of Fresenius Kabi with the development of ‘Vision 2026’ and the successful start to its implementation. My colleagues on the Supervisory Board and I are firmly convinced that the Management Board, under Michael Sen’s leadership, will give new impetus to our growth strategy. In this he has our full support. I wish him good luck and great success."

Michael Sen, CEO of Fresenius Kabi and designated CEO of Fresenius, said: "I’m very pleased about the trust being placed in me and in my capabilities. I am taking on leading this company, which brings both great responsibility and excitement, with respect but above all with great joy and confidence. This is because, despite the temporary challenges and headwinds we encounter, our prospects for achieving future success are very promising: The markets we are active in are fundamentally attractive, and our businesses in many areas are strongly positioned. Being agile and taking prudent strategic decisions will enable us to tap into our full potential and accelerate our growth dynamics again. Together with my Management Board colleagues and all our employees, I will devote my full energy to this. Fresenius is a fantastic company that creates value in so many ways, and I have a strong personal commitment to advancing innovation in medicine for the health and well-being of all people. I want to contribute so that, going forward, all our stakeholders will benefit even more from an even stronger Fresenius."

Menarini Group’s Elacestrant Marketing Authorization Application Accepted for Review by the European Medicines Agency (EMA) for the Treatment of ER+/HER2- Advanced or Metastatic Breast Cancer

On August 19, 2022 The Menarini Group ("Menarini"), a privately held Italian pharmaceutical and diagnostics company, and Stemline Therapeutics ("Stemline"), a wholly-owned subsidiary of the Menarini Group, reported that EMA has validated the Marketing Authorization Application (MAA) for elacestrant, a selective estrogen receptor degrader (SERD), for patients with ER+/HER2- advanced or metastatic breast cancer (Press release, Menarini, AUG 19, 2022, View Source;Advanced-or-Metastatic-Breast-Cancer/?feedref=JjAwJuNHiystnCoBq_hl-RLXHJgazfQJNuOVHefdHP-D8R-QU5o2AvY8bhI9uvWSD8DYIYv4TIC1g1u0AKcacnnViVjtb72bOP4-4nHK5ieT3WxPE8m_kWI77F87CseT [SID1234618503]). Validation of the application confirms the submission is complete and begins EMA’s centralized review procedure.

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"There is a major unmet need in the treatment of advanced or metastatic ER+/HER2- breast cancer after resistance builds in the earlier lines of treatment," commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. "The acceptance of our application for review by the EMA represents a significant step for our company and we look forward to working with the agency to potentially bring elacestrant to patients suffering from second- and third-line ER+/HER2- advanced or metastatic breast cancer in Europe."

The Phase 3 EMERALD study (NCT03778931) evaluated elacestrant compared to SOC endocrine monotherapy (investigators’ choice of either fulvestrant or an aromatase inhibitor) in ER+/HER2- advanced or metastatic breast cancer patients. The study results were recently published online in the Journal of Clinical Oncology (JCO) on May 18, 2022. Further post-hoc analysis from the study will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 taking place September 9-13, 2022, in Paris, France.

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc, who conducted and successfully completed the EMERALD study. Based on the positive phase 3 data, Stemline submitted a MAA to EMA on July 27, 2022. The regulatory review for elacestrant is also underway in the U.S. as the Food and Drug Administration (FDA) has recently accepted a New Drug Application for elacestrant designating a Priority Review. The Menarini Group is now fully responsible for global registration, commercialization and further development activities for elacestrant.

About Elacestrant (RAD1901) and the EMERALD Phase 3 Study
Elacestrant is an investigational selective estrogen receptor degrader (SERD). In 2018, elacestrant received Fast Track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+/HER2- advanced/metastatic breast cancer patients. The study enrolled 477 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoint of the study was progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR) and safety.

Accutar Biotechnology Receives NMPA Clearance of IND Application for AC0176 in Prostate Cancer

On August 19, 2022 Accutar Biotechnology, Inc., a clinical stage biotechnology company focusing on artificial intelligence (AI)-empowered drug discovery, reported that the China National Medical Products Administration (NMPA) has cleared the company’s investigational new drug application (IND) for AC0176 for the treatment of patients with metastatic Castration Resistant Prostate Cancer (mCRPC) (Press release, Accutar Biotechnology, AUG 19, 2022, View Source [SID1234618502]). AC0176 is an orally bioavailable chimeric degrader molecule designed to target Androgen Receptor (AR) protein with high potency and selectivity.

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"Prostate cancer is one of the most common cancers among men in China, and the speed of increase in its incidence and death rates ranks highest in China. We are excited about the IND clearance of AC0176 in China, after its IND clearance and initiation of the first-in-human Phase 1 study in the US early this year," said Jie Fan, Ph.D., Chief Executive Officer, Accutar Biotechnology, Inc. "We look forward to accelerating the development of AC0176 and furthering our commitment to bringing innovative medicines to patients worldwide."

The Phase 1 study in China will assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of AC0176 treatment in Chinese patients with mCRPC. Accutar expects to begin enrollment of this study in the second half of this year.

About AC0176

AC0176 is an investigational orally bioavailable, chimeric degrader of androgen receptor (AR) for the potential treatment of prostate cancers. AR is a hormonal transcription factor, and plays important roles during prostate cancer onset and progression. In preclinical studies, AC0176 has demonstrated potent and selective AR protein degradation with broad coverage of AR mutants, favorable pharmacological properties, as well as promising anti-tumor activities in animal models.