On November 22, 2024 Zenyaku Kogyo Co., Ltd. (Japanese-only website) and Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that Zenyaku obtained regulatory approval from the Ministry of Health, Labour and Welfare (MHLW), for an additional dosage and administration of an anti-CD20 monoclonal antibody Rituxan intravenous injection 100 mg and 500 mg [generic name: rituximab (genetical recombination)] (hereafter, "Rituxan"), which is co-marketed by both companies, for "chronic idiopathic thrombocytopenic purpura*1 in children" (Press release, Hoffmann-La Roche, NOV 22, 2024, View Source;category= [SID1234648562]).

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Chronic ITP had previously only been approved for use in adults with specified dosage and administration, and its use in children had not been approved. The Japanese Society of Pediatric Hematology/Oncology requested the addition of dosage and administration for Rituxan for "chronic ITP in children." It was evaluated that this request qualified for a public knowledge-based application at the "58th evaluation committee on unapproved or off-labeled drugs with high medical needs" held on March 22, 2024. It was officially decided that a public knowledge-based application could be submitted at the "Pharmaceutical Affairs Council’s First Committee on Drugs" held on April 26, 2024. In response to this, Zenyaku submitted a public knowledge-based application for the addition of dosage and administration on May 24, 2024, and obtained approval.

ITP is an autoimmune disease in which autoantibodies against platelet membrane proteins are expressed1) 2) 3), leading to thrombocytopenia due to platelet destruction and impaired production. It is recognized as a designated intractable disease (designated intractable disease 63) by the national government. The etiology of ITP is unknown, and the mechanism of autoantibody production has not been clearly elucidated.
Many newly diagnosed pediatric ITP patients often exhibit severe thrombocytopenia. However, serious bleeding such as intracranial hemorrhage is rare4) 5) 6), and often resolve spontaneously. It is estimated that 30-56%7) 8) 9) of cases require treatment. On the other hand, some cases may show resistance to primary treatments such as corticosteroids or intravenous immunoglobulin therapy10). Both domestic and international clinical guidelines10) 11) 12) recommend Rituxan as one of the treatment options for such pediatric ITP patients.

Rituxan is an anti-CD20 monoclonal antibody that specifically binds to CD20, a protein expressed on B cells, excluding hematopoietic stem cells and plasma cells. It attacks target B cells using the immune system equipped with the human body, and damages cells. The influence of B cells has been suggested as a pathogenic factor in ITP13) 14) 15), and by eliminating B cells with Rituxan, therapeutic effects are expected for chronic ITP that shows resistance to primary treatments.

Zenyaku and Chugai will continue working closely together so that Rituxan can further contribute to the treatment of chronic ITP not only in adults but also in children.

Trademarks used or mentioned in this release are protected by law.

*1 Idiopathic thrombocytopenic purpura is considered an autoimmune disease targeting platelets, and it has also been referred to as "immune thrombocytopenia" in recent years.
*2 Approved dosage and administration
Chronic idiopathic thrombocytopenic purpura
The usual dose is 375 mg/m2 of rituximab (genetical recombination) administered as an intravenous infusion once weekly for four weeks.
*3 Rituxan’s indication for chronic ITP was initially approved for adults in June 2017, and now additional approval has been obtained for use in children.
Sources

Cooper N, Bussel J. The pathogenesis of immune thrombocytopenic purpura. Br J Haematol 2006; 133(4): 364-374.
Berchtold P, McMillan R, Tani P, Sommerville-Nielsen P, Blanchette VS. Autoantibodies against platelet membrane glycoproteins in children with acute and chronic immune thrombocytopenic purpura. Blood 1989; 74(5): 1600-1602.
Taub JW, Warrier I, Holtkamp C, Beardsley DS, Lusher JM. Characterization of autoantibodies against the platelet glycoprotein antigens IIb/IIIa in childhood idiopathic thrombocytopenia purpura. Am J Hematol 1995; 48(2): 104-107.
Neunert CE, Buchanan GR, Imbach P, et al. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood 2008; 112(10): 4003-4008.
Neunert CE, Buchanan GR, Imbach P, et al. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS). Blood 2013; 121(22): 4457-4462.
Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019; 3(22): 3780-3817.
Grimaldi-Bensouda L, Nordon C, Leblanc T, et al. Childhood immune thrombocytopenia: A nationwide cohort study on condition management and outcomes. Pediatr Blood Cancer 2017; 64(7). doi: 10.1002/pbc.26389.
Grainger JD, Rees JL, Reeves M, Bolton-Maggs PHB. Changing trends in the UK management of childhood ITP. Arch Dis Child 2012; 97(1): 8-11.
Bennett CM, Neunert C, Grace RF, et al. Predictors of remission in children with newly diagnosed immune thrombocytopenia: Data from the Intercontinental Cooperative ITP Study Group Registry II participants. Pediatr Blood Cancer 2018; 65(1). doi: 10.1002/pbc.26736.
The Japanese Society of Pediatric Hematology/Oncology. Clinical Practice Guidelines for Childhood Immune Thrombocytopenia 2022 from the Japanese Society of Pediatric Hematology/Oncology. The Japanese Journal of Pediatric Hematology/Oncology 2022; 59(1): 50-57.
Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv 2019; 3(22): 3780-3817.
Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 guidelines for immune thrombocytopenia. Blood Adv 2019; 3(23): 3829-3866.
Kuwana M, Kaburaki J, Ikeda Y. Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura: role in production of antiplatelet autoantibody. J Clin Invest 1998; 102(7): 1393-1402.
Chang M, Nakagawa PA, Shirley A, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood 2003; 102(3): 887-895.
Li X, Zhong H, Bao W, et al. Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood 2012; 120(16): 3318-3325.

On November 22, 2024 Nanjing Leads Biolabs Co., Ltd. (hereinafter referred to as "Leads Biolabs") reported that LBL-024, an anti-PD-L1/4-1BB bispecific antibody independently developed by the company with global intellectual property rights for the treatment of neuroendocrine cancer, has obtained Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) (Press release, Nanjing Leads Biolabs, NOV 22, 2024, View Source [SID1234648556]). This marks another significant milestone following the Breakthrough Therapy Designation granted to LBL-024 by the Center for Drug Evaluation (CDE) of National Medical Products Administration (NMPA) in China.

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Dr. Charles Cai, Chief Medical Officer of Leads Biolabs, said "LBL-024 obtained Breakthrough Therapy Designation from CDE in October this year for the treatment of advanced extrapulmonary neuroendocrine cancer. Our clinical data to date has been very encouraging, suggesting that LBL-024 could meaningfully improve outcomes of patients living with this devastating disease. The grant of ODD from FDA further underscores the exceptional potential of LBL-024 to address a critical gap in this therapeutic area. These policy supports for obtaining Orphan Drug qualification will greatly expedite the commercialization of LBL-024, potentially changing the treatment landscape for patients with advanced neuroendocrine cancer who currently have few therapeutic options."

Dr. Xiaoqiang Kang, founder, chairman and CEO of Leads Biolabs, said "The receipt of ODD for LBL-024 from FDA represents a pivotal milestone in our global strategy. This designation not only enables LBL-024 to receive additional policy support and resource allocation during its development, accelerating its path to market and positioning it as a potential first-in-class therapeutic antibody targeting 4-1BB worldwide, but also provides us with greater market opportunities and avenues for growth on a global scale."

About LBL-024

LBL-024 is a tetravalent bispecific antibody that simultaneously targets PD-L1 and 4-1BB, serving dual functions: blocking the immunosuppressive PD-1/PD-L1 pathway, and selectively co-stimulating 4-1BB in the tumor microenvironment to enhance immune responses. The dual functions of LBL-024—lifting PD-1/PD-L1 immune inhibition and intensifying 4-1BB modulated T cell activation—synergistically enhance the anti-tumor immune response.

LBL-024 received IND approvals from both FDA and NMPA on July 30, 2021 and September 9, 2021 respectively to conduct phase Ⅰ/Ⅱ clinical research, and has achieved outstanding results. Sponsored by Leads Biolabs, led by Professor Shen Lin from Beijing Cancer Hospital with participation of multiple clinical trial centers, the current clinical data demonstrate that LBL-024 monotherapy has more than doubled both the Objective Response Rate (ORR) and Overall Survival (OS) compared to existing treatments for this disease. Based on the current treatment status and the available safety and efficacy data, LBL-024 has entered into a single-arm pivotal trial for extrapulmonary neuroendocrine carcinomas in July 2024 and stands as the globally first 4-1BB-targetd drug candidates to have reached pivotal stage, according to Frost & Sullivan.

About Neuroendocrine Cancer

Neuroendocrine carcinoma (NEC) is a class of poorly differentiated, high-grade neuroendocrine neoplasms (NEN), which originate in the diffuse neuroendocrine cell system and may occur in many different sites. Its molecular characteristics are significantly different from those of neuroendocrine tumors (NET). NEC can be divided into pulmonary NEC and extrapulmonary NEC, among which pulmonary NEC includes small cell lung cancer (SCLC) and pulmonary large cell neuroendocrine carcinoma (p-LCNEC). According to previous data collected, the number of new cases of SCLC is about 98,193, p-LCNEC is about 19,639, and extrapulmonary NECs is about 9,820 in the United States every year. As a result, there are an estimated 127,652 new cases of NECs in the United States each year, meeting the FDA’s definition of a rare disease.

Symptoms of NEC can vary depending on the type of tumor, its location in the body and the hormone released. The survival rate of NEC varies according to the type of cancer and whether it spreads. Specifically, the 5-year survival rate of pulmonary NECs is 5.6%, digestive tract NECs is 13.1%, and other primary NECs are 26.0%. Due to the limited effective treatment options available for patients, the overall survival rate of NEC is low, and more effective new treatment options are urgently needed.

About Orphan Drug Designation

Orphan drugs are medications used for the prevention, treatment, and diagnosis of rare diseases. According to the Orphan Drug Act of the United States, Orphan Drug Designation is established to encourage the development of drugs for treating rare diseases. It provides a series of incentives for new drug development, including but not limited to: (1) tax credits for clinical trial expenses; (2) specific guidance from FDA on all stages of clinical research; (3) exemption of the application fee for new drug registration; and (4) 7 years of market exclusivity after listing.

On November 21, 2024 Allink Biotherapeutics, a clinical-stage biotechnology company pioneering next-generation bispecific antibody and ADC therapeutics, reported two significant milestones in the development of its lead program ALK201 (Press release, Shanghai Allink Biotherapeutics, NOV 21, 2024, View Source [SID1234648782]). The U.S. Food and Drug Administration (FDA) just cleared the company’s Investigational New Drug (IND) application, and first patient has been successfully dosed in Australia.

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Aberrations in FGF/FGFR2 signaling pathways are extensively documented in multiple malignancies, including gastroesophageal adenocarcinoma and breast cancer, correlating with poor clinical outcomes. ALK201 is an innovative ADC candidate targeting FGFR2b a critical oncogenic driver that has demonstrated clinical validation in various solid tumors . Leveraging the company’s proprietary hydrophilic linker and rationally selected payload, extensive preclinical studies of ALK201 have demonstrated robust anti-tumor activity and a promising therapeutic window, supporting its development as a potentially transformative ADC for FGFR2b-associated malignancies.

"The FDA’s IND clearance and first patient dosing in Australia represent significant milestones of ALK201, our first ADC program, advances into clinical development," said Hui Feng, Ph.D., Chief Executive Officer of AllinkBio. "The rapid advancement from first preclinical candidate to clinical stage exemplifies our R&D team’s operational efficiency. Encouraged by robust preclinical data demonstrating the anti-tumor efficacy in FGFR2b-expressing solid tumors. We are strategically advancing our clinical development to swiftly bring this potential therapeutic option to address unmet medical needs worldwide."

The Phase 1 multicenter clinical trial was designed to investigate ALK201, evaluating its safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity in patients with advanced solid tumors. The study consists of two sequential segments: a dose-escalation phase to determine the maximum tolerated dose (MTD), followed by a clinical expansion phase in which biomarker-guided patient populations will be further investigated.

AllinkBio team’s strategic vision and outstanding R&D execution capability have enabled the company growing from a preclinical to clinical stage biotech in about one year. The company’s deep expertise in molecule discovery and drug design, combined with a sophisticated biomarker-driven approach, has empowered swift development of a number of promising therapeutic candidates. AllinkBio is highly committed to bringing innovative precision therapeutics to patients in need.

About ALK201
ALK201 is a novel FGFR2b targeted ADC, in development as a potential treatment for multiple solid tumors. FGFR2b is a promising target with its mutations and overexpression comprehensively implicated in oncogenesis across diverse solid tumor landscapes. ALK201 is currently being evaluated in a Phase 1 study.

On November 21, 2024 Intensity Therapeutics, Inc. (Nasdaq: INTS), ("Intensity" or the "Company") a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that it has entered into a securities purchase agreement with a single healthcare focused institutional investor for the issuance and sale of 1,237,113 shares of its common stock in a registered direct offering at a purchase price of $2.425 per share (Press release, Intensity Therapeutics, NOV 21, 2024, View Source [SID1234648578]).

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In a concurrent private placement (the "Private Placement" and together with the Registered Offering, the "Offerings"), the Company also agreed to issue to the same investor warrants to purchase up to 1,237,113 shares of its common stock (the "Common Warrants"). The Common Warrants have an exercise price of $2.95 per share, will be exercisable commencing six months from the date of issuance, and will expire five and one-half years following the date of issuance.

The gross proceeds from the Offerings, before deducting the placement agent’s fees and other offering expenses payable by the Company, are expected to be approximately $3 million. The Company expects to use the net proceeds from the Offerings for general working capital.

A.G.P./Alliance Global Partners is acting as lead placement agent for the Offerings and Brookline Capital Markets, a division of Arcadia Securities, LLC, is acting as a co-placement agent for the Offerings.
The Offerings are expected to close on or about November 22, 2024, subject to the satisfaction of customary closing conditions.

The shares (or common stock equivalents in lieu thereof) offered to the institutional investor described above are being offered pursuant to a registration statement on Form S-3 (File No. 333-280681), which was declared effective by the Securities and Exchange Commission (the "SEC") on July 11, 2024. The Offering is being made only by means of a prospectus which is a part of the effective registration statement. The Common Warrants will be issued in a concurrent private placement. A final prospectus supplement and the accompanying prospectus relating to the registered direct offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Additionally, when available, electronic copies of the final prospectus supplement and the accompanying prospectus may be obtained from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected], or Brookline Capital Markets, a division of Arcadia Securities, LLC, 600 Lexington Avenue, 20th Floor, New York, NY 10022, or by telephone at (646) 256-5258, or by email at [email protected].
The private placement of the Common Warrants and the shares underlying the Common Warrants offered to the institutional investor will be made in reliance on an exemption from registration under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act") and Regulation D promulgated thereunder. Accordingly, the securities issued in the concurrent private placements may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

On November 21, 2024 BPGbio, Inc., a leading biology-first, AI-powered clinical-stage biopharma company focused on mitochondrial biology and protein homeostasis, reported that it will co-present two pivotal studies with Stanford Medicine’s Department of Neurology at the Society for Neuro-Oncology (SNO) 2024 Annual Meeting, taking place November 21-24, 2024, in Houston, Texas (Press release, BPGbio, NOV 21, 2024, View Source [SID1234648568]). The presentations will highlight BPM31510 and BRG399—potential glioblastoma multiforme (GBM) therapies that were identified by the company’s proprietary NAi Interrogative Biology Platform, a causal AI-powered system designed to reveal hidden cause-and-effect relationships within patient biology.

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The first study, titled "Optimizing brain cancer therapy: balancing tumor eradication and normal tissue preservation with BPM31510," explores BPM31510’s superior ability to preserve healthy cells compared to standard cancer treatments in mouse, rat, and human glioblastoma cell lines. The study demonstrates BPM31510’s ability to effectively target and diminish cancer cells while selectively allowing the growth of healthy brain cells, an effect that standard treatments fail to achieve. Researchers also showed that the BPM31510 significantly improved survival in glioma implanted mice and rats compared to the control group, mirroring the results from the ongoing phase 2b trial on BPM31510 for GBM and highlighting BPM31510’s potential in brain cancer therapy.

The second study, titled "Improved anti-glioblastoma efficacy by BRG399, a novel oral microtubule binding agent," presents findings on BRG399’s anti-cancer activity. BRG399, a novel pan-cancer therapy, works by disrupting the cell division process in both solid and liquid tumors. BRG399 was also found to induce an immune memory response, protecting against tumor recurrence. The study confirmed that BRG399 can cross into the brain, target tumor cells, and improve survival in rat glioma models.

"Standard cancer treatments that focus solely on destroying tumors often harm healthy tissue in the process," said Seema Nagpal, M.D., principal investigator of the BPM31510 GBM phase 2b trial and Clinical Professor of Neurology and Neurological Sciences at Stanford Medicine. "These new treatments are taking novel targeted approaches on glioma cancer cells and we are excited to share the encouraging results from our studies with our peers and industry researchers."

"Our ongoing clinical and preclinical trials for BPM31510 and BRG399 are continuously deepening our understanding of these promising therapies," said Niven R. Narain, Ph.D., President and CEO of BPGbio. "By putting biology first, our NAi Platform has enabled us to optimize every aspect of these therapies, from dosing and timing to patient selection and potential indication expansion opportunities."

Poster Presentation Details:

Optimizing brain cancer therapy: balancing tumor eradication and normal tissue preservation with BPM31510
Date and Time: November 22, 2024, 7:30 p.m. – 9:30 p.m. CST
Location: Hall B3, George R. Brown Convention Center, Houston, Texas
Presenter: Abbas Khojasteh, Ph.D.
Abstract Number: DDDR-13

Improved anti-glioblastoma efficacy by BRG399, a novel oral microtubule binding agent
Date and Time: November 22, 2024, 7:30 p.m. – 9:30 p.m. CST
Location: Hall B3, George R. Brown Convention Center, Houston, Texas
Presenter: Stephane Gesta, Ph.D.
Abstract Number: DDDR-14
About BPM31510

BPM31510IV is BPGbio’s lead candidate in late-stage development for aggressive solid tumors such as glioblastoma multiforme (GBM) and pancreatic cancer. Other topical and oral formulations of the investigational agent are also being developed as a potential treatment for several rare diseases. The compound has demonstrated a tolerable safety profile and shown potential clinical benefits across multiple disease indications. Validated by BPGbio’s NAi Interrogative Biology platform, BPM31510 induces a hallmark shift in the tumor microenvironment (TME) by modulating mitochondrial oxidative phosphorylation in aggressive tumors, leading to cancer cell death. In many mitochondrial diseases, restoring CoQ10 levels can overcome the effect of mutations in genes that lead to mitochondrial dysfunction. BPM31510 has been granted Orphan Drug Designation by the FDA for GBM, pancreatic cancer, and epidermolysis bullosa (EB), as well as Rare Pediatric Disease Designation for primary CoQ10 deficiency and EB.

About BRG399

BRG399 is a BPGbio-developed candidate being studied for its therapeutic potential as a treatment for solid and liquid tumor cancers as well as diseases associated with inflammation. This experimental drug, a first-in-class, anti-mitotic agent with broad-spectrum anti-cancer activity and favorable pharmacological properties for clinical testing, is being designed for oral delivery. BRG399 is leading the new oncology drug pipeline for BPGbio which includes drug candidates uniquely targeting E2 enzymes.