On June 25, 2022 Dragon Boat reported that its IND application of the innovative anti-CLDN 18.2/CD47 bi-specific antibody (bsAb) injection (R&D code: BC007) was officially accepted by National Medical Products Administration (NMPA) under the acceptance number CXSL2200267 (Press release, Dragonboat Biopharmaceutical, JUN 25, 2022, View Source [SID1234616258]). This drug is the first domestic clinical filing of the CLDN 18.2/ CD47 bsAb, which is intended for the treatment of late stage solid tumors.

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BC007 is a innovative bsAb targeting CLDN 18.2 and CD47 and the early-stage development was completed collaboratively by Sanyou and Dragon Boat. Validation results of the in vivo efficacy showed that BC007 exhibited dose-dependent anti-tumor effects against CLDN18.2 overexpressing CDX mouse models of human gastric cancer, human pancreatic cancer and human colon cancer, and was significantly better than the selected comparator antibody. In the safety studies, hematological toxicity is one of the common challenges of CD47 targeting antibodies. But in the cynomolgus monkey toxicity study, multiple doses of BC007 was administered for 5 weeks without animal death, and the hematological toxicity was mild and well tolerated by the animals.

In March this year, the IND application of anti-CLDN 18.2 antibody injection (BC008) developed by Dragon Boat has been approved by National Medical Products Administration. In the future, Dragon Boat will bring greater clinical benefits to the patients by exploring more treatment options.

Dr. Guojun Lang, CEO of Sanyou, said "We sincerely congratulate Dragon Boat on the NMPA acceptance of IND application with the CLDN 18.2/CD47 bsAb, which is another milestone after the clinical approval of the anti-CLDN 18.2 nanoantibody co-developed by Sanyou and Dragon Boat in March. This project further proves the outstanding competency of Dragon Boat in the field of innovative biopharmaceutical research and development. This project is also another successful case of Sanyou’s Cooperative Project Organization (CPO) business model. We wish the clinical studies will proceed successfully and benefit the patients as soon as possible".

About CLDN 18.2

Tight junction protein claudin-18 isoform 2 (CLDN18.2) is a member of the claudin family, which includes tight junction proteins that establish paracellular barriers to control the molecular passage and motions among cells. Normally, CLDN 18.2 is expressed only on the surface of differentiated epithelial cells of the gastric mucosa. However, after the development of malignant tumors, tight junction proteins are disrupted, exposing the CLDN 18.2 epitope on the surface of tumor cells. Studies have shown high CLDN 18.2 expression in the tumor cells of 50%-80% of gastric cancer patients and 60% of pancreatic cancer patients.

About CD47

CD47 is a glycosylated transmembrane protein, a key member of the immunosuppressive signaling pathway, which inhibits macrophage phagocytosis and mediates the immune escape mechanism of various malignant tumors, mainly by interacting with the inhibitory receptor signal-regulatory protein alpha (SIRPα), which is widely recognized as a "don’t eat me" signal. Numerous studies have shown that CD47 is overexpressed in different types of tumors, including myeloma, smooth muscle sarcoma, acute lymphoblastic leukemia, and non-Hodgkin’s lymphoma.

On June 24, 2022 Genor Biopharma (Stock code: 6998.HK) reported that the company has entered into a cooperative development agreement (the "Cooperative Development Agreement") with Suzhou Abogen Biosciences Co., Ltd ("Abogen") to jointly develop globally innovative mRNA products and related pharmaceuticals (Press release, Genor Biopharma, JUN 24, 2022, View Source [SID1234616255]).

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According to the Cooperative Development Agreement, the Group’s biological antibody development platform will be integrated with Abogen’s mRNA technology platform to enable the Group and Abogen to jointly research and develop mRNA drugs for tumor treatment.

As an innovative, platform and integrated company with the ability to carry out innovative medical research and development, preclinical research, clinical development, registration, Chemistry, Manufacturing and Controls (CMC) development and commercialised manufacturing, the Company strives to develop globally innovative advantageous products with patents around the world. At present, the Company has successfully established the global first-in-class ("FIC")/ best-in-class ("BIC") differential research and development platform for early identifying bi-specific/multi-specific antibodies in immune-oncology. Innovation and exploration of FIC/BIC potential have been conducted in multi-dimension based on the in-depth understanding of our research and development team regarding targeted antibody molecular biology, cell biology and immunological mechanisms. To date, a number of projects for discovering bi-specific/multi-specific antibodies with FIC/BIC potential have been initiated. The Company is optimistic about the prospects of the application of mRNA technology in the pharmaceutical field. Through this cooperation, the Company expects to fully leverage the Company’s early exploration of highly differential FIC/BIC potential and the advantages of the respective platforms of both parties to accelerate the exploration and research and development of potential mRNA drugs for tumor treatment.

On June 24, 2022 Bold Therapeutics, a clinical-stage biopharmaceutical company, reported that they will be attending the Metals in Medicine Gordon Research Conference focusing on Advancing the Use of Metal-Based Compounds and Nanotheranostics for Personalized Medicine (Press release, Bold Therapeutics, JUN 24, 2022, View Source [SID1234616254]). The conference will be held in Andover, New Hampshire from June 26 to July 1, 2022, bringing together over 150 academic, industry, and government experts.

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Adam Carie, Director of CMC & Nonclinical Development, will be presenting on behalf of Bold Therapeutics in the "Clinical Advances for Metals in Medicine" session. He is joined by Shane Harrypersad, Senior Scientist, CMC.

This presentation will include previously embargoed data (shown below) recently presented at the 2022 American Society of Cancer Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in a session entitled "BOLD-100-001 (TRIO039): A Phase 1b dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patients with advanced gastrointestinal solid cancers: Interim safety, tolerability, and efficacy." In addition to demonstrating that BOLD-100 was safe and generally well-tolerated, this data showed remarkable outcomes in the treatment of 3rd line or later treatment-resistant metastatic colorectal cancer (mCRC) in combination with FOLFOX – including in patients that had previously failed on FOLFOX alone. In the initial six patients, Progression-Free Survival (PFS) significantly exceed expected PFS for this patient population, handily exceeding the current best-in-class approved therapies for 3rd line mCRC, Bayer’s Stivarga (regorafenib) and Taiho’s Lonsurf (trifluridine and tipiracil).

While only the earliest efficacy data from the Phase 1b portion of the study was available for presentation at ASCO (Free ASCO Whitepaper), the colorectal arm of the BOLD-100-001 Phase 2 trial has since fully enrolled (N=22) and Bold Therapeutics expects to announce additional efficacy data in mCRC by year-end.

Bold Therapeutics’ BOLD-100 is a first-in-class ruthenium-based small molecule therapeutic that (1) alters the unfolded protein response (UPR) through selective GRP78 inhibition; and (2) induces reactive oxygen species (ROS) which causes DNA damage and cell cycle arrest. Collectively, these effects result in cell death in both sensitive and resistant cancers, giving BOLD-100 the potential to significantly improve outcomes in a wide range of both solid and liquid tumors in combination with other anticancer therapies ranging from traditional chemotherapies to targeted therapies to immuno-oncology agents. BOLD-100 is currently being studied in a multinational Phase 2 trial in the treatment of advanced gastrointestinal cancers actively enrolling at 13 clinical sites: six in Canada; two in the U.S.; and five in South Korea.

"Bold Therapeutics is excited to present these remarkable results at the Gordon Research Metals in Medicine Conference showcasing the cutting-edge, multi-disciplinary work being performed at Vancouver-based Bold Therapeutics" noted Dr. Carie. "With our Phase 2 clinical trial well underway at sites in Canada, the United States, and South Korea, we are excited to connect with other leaders in the development of metal-based oncology therapeutics with a goal of improving outcomes for patients. With unique expertise in metallochemistry and manufacturing, translational research and rapid and efficient early-stage clinical development, Bold Therapeutics is actively seeking additional preclinical-stage metal-based therapeutics to in-license, develop and commercialize."

In parallel, Bold Therapeutics is actively seeking global development partners to support two additional parallel Phase 2 studies: (1) BOLD-100 in combination with a proteasome inhibitor (e.g. Takeda’s Velcade (bortezomib) or Amgen’s Kyprolis (carfilzomib)) in the treatment of multiple myeloma; and (2) BOLD-100 in combination with a standard-of-care agent in the treatment of bladder cancer. Compelling preclinical data supporting these development initiatives is available under confidentiality.

On June 24, 2022 Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY, along with its subsidiaries together referred to as "Dr. Reddy’s") reported that it has acquired a portfolio of branded and generic injectable products from Deer Park, Illinois based-Eton Pharmaceuticals, Inc. (NASDAQ: ETON) (Press release, Dr Reddy’s, JUN 24, 2022, View Source [SID1234616253]).

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The portfolio includes the Biorphen (phenylephrine hydrocholoride) Injection and Rezipres (ephedrine hydrochloride) Injection NDAs with nine separate combinations of strengths and presentations and one first-to-file approved ANDA for Cysteine Hydrochloride for the U.S. One strength each of Biorphen and Rezipres are currently commercially available in the U.S. The acquisition will complement Dr. Reddy’s U.S. institutional business with limited competition injectable products.

Under the terms of the agreement, Dr. Reddy’s acquired the Eton portfolio for an upfront payment of approximately $5 million in cash, plus contingent payments of up to $45 million. The acquisition supports Dr. Reddy’s efforts to accelerate and expand affordable medications for patients.

"Long before the COVID-19 pandemic, there have been concerns about access to some critical care products for hospitals and health systems. This acquisition provides our North America organization with a foundational footprint to help address products that are not always readily available for patients," says Marc Kikuchi, Chief Executive Officer, North America Generics, Dr. Reddy’s. "For these and many other reasons, I believe we are well-positioned to integrate the portfolio and grow the business."

The value of total addressable market for these products in the U.S. is approximately $174 million for the calendar year ending in April 2022 according to IQVIA.

*IQVIA Retail and Non-Retail MAT April 2022

RDY-0622-419

On June 24, 2022 Kyowa Kirin Co., Ltd. (TSE: 4151, Kyowa Kirin) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended that CRYSVITA (burosumab) be approved 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, JUN 24, 2022, View Source [SID1234616252]).1 CRYSVITA is also already licensed 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 less 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 location and difficulty in detecting tumours.3,5 TIO may recur and persist following incomplete or unsuccessful surgical resection.9

If approved by the European Commission (EC), CRYSVITA will be the first biologic treatment available to European patients with TIO, which blocks the action of FGF23, restoring phosphate homeostasis.2,10

"Being diagnosed with a rare condition, like TIO, does present many challenges for patients and treating physicians, including the diagnostic process and the current lack of specific therapies. The unmet need for people living with TIO is clear, so this positive CHMP opinion is a very important step forward for those who cannot be cured by tumour removal and for the healthcare professionals supporting them," said Professor Ralf Oheim, Department of Osteology and Biomechanics, University Medical Center Hamburg.

"For people diagnosed with TIO in Europe, we are a step closer to being able to deliver the first biologic treatment for those who cannot undergo surgical removal of tumours," said Abdul Mullick, President of Kyowa Kirin International. "This positive CHMP opinion is a much welcomed milestone for CRYSVITA, which is currently approved for use in Europe in adults and children with X-Linked Hypophosphataemia. I’m proud that Kyowa Kirin International is helping those living with TIO, as part of our extensive work in supporting those with rare diseases gain access to life changing therapies for their diseases."

Administered by a subcutaneous injection, CRYSVITA is a recombinant fully human monoclonal antibody that binds to and inhibits the activity of FGF23, restoring phosphate homeostasis.2 The efficacy and safety of CRYSVITA have been demonstrated in two Phase II clinical trials published in the disease area of TIO.11,12 CRYSVITA has been approved for clinical use in X-Linked Hypophosphataemia (XLH) across the European Union (EU) and Great Britain (GB) since 2018, and in this indication is presently approved for use in children and adolescents aged 1 and 17 years of age with radiographic evidence of bone disease, and in adults.2

The EC will review the CHMP recommendation and a final decision on the expansion of the recommended use for CRYSVITA for the treatment of FGF23-related hypophosphataemia in 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 is expected in the coming months. This means that use of CRYSVITA in this TIO indication is not currently approved in the EU or GB.

▼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 phosphate absorption 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, 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

CRYSVITA is presently indicated for the treatment of XLH in children and adolescents aged 1 to 17 years with radiographic evidence of bone disease, and in adults.2 If approved by the European Commission, CRYSVITA would be indicated 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 adults.1 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.