On November 22, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the National Medical Products Administration (NMPA) in China has approved WELIREG (belzutifan), for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery (Press release, Merck & Co, NOV 22, 2024, View Source [SID1234648579]). WELIREG is a first-in-class oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor and is the first and only approved HIF-2α inhibitor in China. This approval is based on objective response rate (ORR) and median duration of response (DOR) results from the Phase 2 LITESPARK-004 trial and is the 17th approval of WELIREG for these patients globally.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This approval of WELIREG brings the first and only systemic therapy to adult patients in China with certain VHL disease-associated tumors who, to date, have not had access to a non-surgical treatment option to help manage manifestations of VHL disease," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "We are committed to bringing innovative treatment options to patients in need around the world and are proud to offer eligible adult patients in China a first-in-class HIF-2α inhibitor as a possible treatment option."

In August 2021, WELIREG was approved in the U.S. for the treatment of adult patients with VHL disease who require therapy for associated RCC, CNS hemangioblastomas or pNET, not requiring immediate surgery. The efficacy of WELIREG was evaluated in LITESPARK-004, an open-label clinical trial in 61 patients with VHL-associated RCC. In the LITESPARK-004 trial, WELIREG showed an ORR of 49% (95% CI, 36-62) in patients with VHL-associated RCC (n=30/61); all responses were partial responses (PR). Median DOR for these patients was not reached, with ongoing responses ranging from 2.8+ to 22.3+ months; among responders, 56% (n=17/30) maintained a response for at least 12 months.

Patients enrolled in LITESPARK-004 had other VHL-associated tumors, including CNS hemangioblastomas and pNET. In patients with VHL-associated CNS hemangioblastomas (n=24) in this trial, WELIREG showed an ORR of 63% (95% CI, 41-81) (n=15/24), with a complete response (CR) rate of 4% (n=1/24) and a PR rate of 58% (n=14/24). Median DOR for these patients was not reached, with ongoing responses ranging from 3.7+ to 22.3+ months; among responders, 73% (n=11/15) maintained a response for at least 12 months. In patients with VHL-associated pNET (n=12) in this trial, WELIREG showed an ORR of 83% (95% CI, 52-98) (n=10/12), with a CR rate of 17% (n=2/12) and a PR rate of 67% (n=8/12). Median DOR for these patients was not reached, with ongoing responses ranging from 10.8+ to 19.4+ months; among responders, 50% (n=5/10) maintained a response for at least 12 months.

WELIREG is also approved in the U.S. for the treatment of adult patients with advanced RCC following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI), based on results from the Phase 3 LITESPARK-005 trial. Merck is evaluating WELIREG in advanced RCC and other tumor types through a broad clinical development program, including in Phase 2 and 3 trials evaluating WELIREG as monotherapy and in combination with other medicines.

About LITESPARK-004

LITESPARK-004 is an open-label Phase 2 trial (ClinicalTrials.gov, NCT03401788) evaluating WELIREG for the treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received WELIREG (120 mg orally once daily) until disease progression or unacceptable toxicity. The primary endpoint is ORR in VHL disease-associated RCC. Secondary endpoints in RCC tumors include disease control rate, DoR, time to response, progression-free survival, time to surgery and safety. Additionally, this study evaluated response rates in other common VHL disease-associated tumors including pNET and CNS hemangioblastomas.

About von Hippel-Lindau disease

Von Hippel-Lindau disease is a rare genetic disease that impacts an estimated 200,000 people worldwide. Patients with VHL disease are at risk for recurrent, benign blood vessel tumors as well as some cancerous ones. The most commonly occurring tumor is renal cell carcinoma, a form of kidney cancer, which occurs in about 70% of patients with VHL disease.

About WELIREG (belzutifan) 40 mg tablets, for oral use

Indications in the U.S.

Certain von Hippel-Lindau (VHL) disease-associated tumors

WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Advanced Renal Cell Carcinoma (RCC)

WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI).

Selected Safety Information for WELIREG

Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

Anemia

WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG.

In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months).

The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established.

In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88% of patients with advanced RCC and 29% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% received ESAs only, and 12% received both transfusion and ESAs.

Hypoxia

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.

Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

In LITESPARK-004, hypoxia occurred in 1.6% of patients.

In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events. Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 months).

Embryo-Fetal Toxicity

Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Adverse Reactions

In LITESPARK-004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

In LITESPARK-005, serious adverse reactions occurred in 38% of patients. The most frequently reported serious adverse reactions were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Fatal adverse reactions occurred in 3.2% of patients who received WELIREG, including sepsis (0.5%) and hemorrhage (0.5%).

WELIREG was permanently discontinued due to adverse reactions in 6% of patients. Adverse reactions which resulted in permanent discontinuation (≥0.5%) were hypoxia (1.1%) and hemorrhage (0.5%).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Of the patients who received WELIREG, 28% were 65 to 74 years, and 10% were 75 years and over. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Adverse reactions which required dosage interruption in ≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%), fatigue (3.2%), and hemorrhage (2.2%).

Dose reductions due to an adverse reaction occurred in 13% of patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients. The most frequently reported adverse reactions which required dose reduction (≥1.0%) were hypoxia (5%) and anemia (3.2%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (88%), fatigue (43%), musculoskeletal pain (33%), increased creatinine (34%), decreased lymphocytes (34%), increased alanine aminotransferase (32%), decreased sodium (31%), increased potassium (29%), and increased aspartate aminotransferase (27%).

Drug Interactions

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

Pediatric Use

Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

On November 22, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported the pricing of its "reasonable best efforts" public offering with participation from the CEO and existing and new healthcare focused investors for the purchase and sale of up to 40,000,000 shares of common stock and warrants to purchase up to 20,000,000 shares of common stock at a combined offering price of $0.20 per share and accompanying warrant (the "Offering") (Press release, Aptose Biosciences, NOV 22, 2024, View Source [SID1234648572]). The Company expects to receive aggregate gross proceeds of approximately $8 million, before deducting placement agent fees and other offering expenses, and assuming no exercise of the warrants. The warrants will have an exercise price of $0.25 per share, will be exercisable immediately and will expire five years from the issuance date.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The closing of the Offering is expected to occur on or about November 25, 2024, subject to the satisfaction of customary closing conditions. The Company intends to use the net proceeds from this Offering for working capital and general corporate purposes.

A.G.P./Alliance Global Partners is acting as the sole placement agent for the Offering.

The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-281201) previously filed with the Securities and Exchange Commission ("SEC") on August 2, 2024, as amended, which was declared effective on November 21, 2024. This Offering is being made only by means of a prospectus forming part of the effective registration statement. A preliminary prospectus relating to the Offering has been filed with the SEC. An electronic copy of the final prospectus relating to the Offering may be obtained, when available, on the SEC’s website located at View Source and may also 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].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities 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.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.