Mabwell Announces CDE Approval to Initiate Phase III Clinical Trial of 9MW2821 for Urothelial Carcinoma in Combination with PD-1 Inhibitor

On August 26, 2024 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported that its submission to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for "a randomized, controlled, open-label, multicenter Phase III clinical study of 9MW2821 in combination with Toripalimab versus standard chemotherapy in first-line locally advanced or metastatic urothelial cancer" has been approved (Press release, Mabwell Biotech, AUG 26, 2024, View Source [SID1234646105]). The corresponding Phase III clinical study has been initiated and is currently in the enrollment stage. As of the announcement, 9MW2821 has been approved for three pivotal clinical trials.

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9MW2821 is a novel Nectin-4-targeting ADC independently developed by Mabwell, and it is the first of its kind in China to initiate clinical trials on the same target, with more than 400 subjects enrolled in the clinical studies for multiple indications. The results of existing clinical studies have demonstrated outstanding therapeutic efficacy and safety profile. The pivotal Phase III clinical study, "an open-label, randomized Phase 3 study to evaluate 9MW2821 vs investigator’s choice of chemotherapy in subjects with locally advanced or metastatic urothelial cancer who have previously received PD-(L)1 inhibitor and platinum-containing chemotherapy", is currently in the enrollment stage.

About Urothelial Carcinoma
Bladder cancer, a form of urothelial carcinoma, stands out among its various subtypes for its significant impact on public health. The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) reports that bladder cancer is the ninth most common malignant tumor in incidence and ranks thirteenth in mortality among all malignant tumors. According to The Global Cancer Statistics published by the International Agency for Research on Cancer (IARC) in 2022, there were approximately 614,000 new cases and 220,000 deaths from bladder cancer worldwide. The Disease Burden of Malignant Tumors in China 2022, released by the National Cancer Center in February 2024, reported 92,900 new cases and 41,400 deaths from bladder cancer in China, placing it eleventh and thirteenth globally in terms of new incidences and mortality, respectively. As a prevalent cancer in China, urothelial carcinoma is characterized by a propensity for metastasis, a high recurrence rate, and a short survival time in its advanced stages. It represents a significant disease burden and poses a serious threat to the survival and quality of life of those affected.

About 9MW2821
9MW2821 is a site-specific conjugated novel Nectin-4 targeting ADC developed by Mabwell using ADC platform, and the first drug candidate to enter clinical study among the Nectin-4-targeting ADCs developed by Chinese companies. As the first therapeutic drug candidate targeting Nectin-4 in the world to reveal clinical efficacy data in cervical cancer (CC), esophageal cancer (EC) and breast cancer, 9MW2821 has been granted Fast Track Designation by FDA in 2024 for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC), recurrent or metastatic CC progressed on or following prior treatment with a platinum-based chemotherapy regimen, and locally advanced or metastatic Nectin-4 positive triple-negative breast cancer (TNBC); 9MW2821 has also been granted Orphan Drug Designation by FDA for the treatment of EC, and Breakthrough Therapy Designation by CDE of NMPA, for the treatment of locally advanced or metastatic urothelial carcinoma that has failed previous platinum-based chemotherapy and PD-(L)1 inhibitor therapy.

9MW2821 achieves site-specific modification of antibody through proprietary conjugation technology linkers and optimized ADC conjugation process. After injection, 9MW2821 can specifically bind to Nectin-4 on the cell membrane surface, be internalized and release cytotoxic drug, and induce the apoptosis of tumor cells.

Veracyte to Participate in the Morgan Stanley 22nd Annual Global Healthcare Conference

On August 26, 2024 Veracyte, Inc. (Nasdaq: VCYT) reported that Marc Stapley, chief executive officer, and Rebecca Chambers, chief financial officer, will participate in a fireside chat at the Morgan Stanley 22nd Annual Global Healthcare Conference on Thursday, September 5, at 2:35 p.m. Eastern Time (Press release, Veracyte, AUG 26, 2024, View Source [SID1234646102]).

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A live audio webcast of the company’s presentation will be available by visiting Veracyte’s website at View Source A replay of the webcast will be available for 90 days after the live presentation broadcast.

Ordspono™ (odronextamab) Approved in the European Union for the Treatment of Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-cell Lymphoma

On August 26, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Commission (EC) has approved Ordspono (odronextamab) to treat adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy. This marks the first regulatory approval of Ordspono in the world for these patients (Press release, Regeneron, AUG 26, 2024, View Source [SID1234646101]). Ordspono is a bispecific antibody that acts by linking the lymphoma cell to a killer T cell.

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"The EC approval of Ordspono is a meaningful advancement for EU patients and their physicians as a new option to treat both indolent and aggressive lymphomas," said Stefano Luminari, M.D., Professor of Oncology at the University of Modena and Reggio Emilia, hematologist at the Hematology Unit of Arcispedale Santa Maria Nuova in Reggio Emilia, and a trial investigator. "In clinical trials, Ordspono demonstrated remarkable complete response rates in follicular lymphoma, as well as compelling efficacy results in diffuse large B-cell lymphoma, including in the post-CAR-T setting. Physicians, especially in the community setting, will have an off-the-shelf option that can be administered out-patient – offering the chance for complete remission."

The approval is based on results from the Phase 1 ELM-1 and pivotal Phase 2 ELM-2 trials, which demonstrated robust, durable response rates in adults with R/R FL or R/R DLBCL:

In R/R FL, results from ELM-2 (N=128) as assessed by an independent review committee (IRC) showed an objective response rate (ORR) of 80%, with 73% achieving a complete response (CR). Among complete responders, the median duration of response (DoR) was 25 months (95% confidence interval [CI]: 20 months to not estimable [NE]).
In R/R DLBCL,
results from ELM-2 (N=127) in patients who were CAR-T therapy naive, as assessed by an IRC showed 52% ORR, with 31% achieving a CR. Among complete responders the median DoR was 18 months (95% CI: 10 months to NE).
results from ELM-1 (N=60) in patients who had progressed after CAR-T therapy, as assessed by an IRC showed 48% ORR, with 32% achieving a CR. Among responders (n=29), the median DoR was 15 months (95% CI: 3 months to NE).
The most common adverse reactions were cytokine release syndrome (CRS; 54%), neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), diarrhea (24%) and COVID-19 (22%). The most common serious adverse reactions were CRS (14%), pneumonia (9%), COVID-19 (9%) and pyrexia (6%). Ordspono can cause serious or fatal infections, and CRS, which may be serious or life-threatening.

"Ordspono marks the first approval from our bispecific antibody platform, which we hope will increasingly contribute to our growing portfolio of practice-changing medicines for oncology and other diseases," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. "Building upon this approval, we are excited about our OLYMPIA program, which includes multiple Phase 3 trials investigating Ordspono as a monotherapy and in various combinations, in earlier lines of therapy. We’re also excited to be advancing our broader pipeline of CD3 and other bispecific therapies, both to additional hematologic cancers such as myeloma, as well as to solid tumors."

About FL and DLBCL
FL and DLBCL are the two most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL). While FL is a slow-growing subtype, it is an incurable disease, and most patients will relapse after initial treatment. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment. It is estimated that approximately 120,000 FL cases and 163,000 DLBCL cases are diagnosed annually worldwide. In Europe, it is estimated that approximately 15,000 FL cases and 31,000 DLBCL cases are diagnosed each year.

About the Ordspono (odronextamab) Clinical Trial Program
Ordspono is a CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing. Ordspono as monotherapy is indicated for the treatment of adult patients with R/R FL or R/R DLBCL, after two or more lines of systemic therapy. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu in due course.

ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including a cohort of patients who had progressed after CAR-T therapy.

ELM-2 is an ongoing, open-label, multicenter Phase 2 trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint is ORR according to the Lugano Classification as assessed by IRC, and secondary endpoints include CR, progression-free survival, overall survival and DoR.

Regeneron is conducting a broad Phase 3 development program, known as OLYMPIA, investigating odronextamab in earlier lines of therapy and other B-NHLs. In addition, Regeneron is investigating odronextamab in combination with a costimulatory bispecific antibody, REGN5837 (CD22xCD28), and Regeneron’s PD-1 inhibitor cemiplimab for R/R aggressive B-NHL through the ATHENA-1 and CLIO-1 studies, respectively. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority. For more information, visit the Regeneron clinical trials website, or contact via [email protected] or +1 844-734-6643.

About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.

RedHill’s Opaganib Granted Orphan Drug Designation by the FDA for Childhood Cancer, Neuroblastoma

On August 26, 2024 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to opaganib for treatment of neuroblastoma, a type of childhood cancer that develops from immature nerve cells and accounts for 15% of all pediatric cancer-related deaths (Press release, RedHill Biopharma, AUG 26, 2024, View Source [SID1234646100]).

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Orphan Drug designation provides for a seven-year marketing exclusivity period should opaganib be approved in neuroblastoma and may confer additional benefits such as accelerated development and review times, potential grant funding and possible tax credits.

"RedHill is proud to have received a second orphan-drug designation for opaganib in oncology, following its previous designation for cholangiocarcinoma (CCA, also known as bile duct cancer). This designation for neuroblastoma – the most common infancy malignancy and for which new options are urgently needed – adds to opaganib’s potential as a novel oncological agent," said Dr. Mark Levitt, Chief Scientific Officer at RedHill. "Opaganib has broad oncology potential with promising preliminary clinical data in solid tumor cancers such as prostate cancer and CCA, and data from a range of U.S. government supported and Apogee conducted preclinical studies in various indications, including radioprotection, and also in combination with RedHill’s RHB-107. We also see such utility extending to the potential for opaganib to have a sensitizing effect in hormone receptor pathway inhibition therapy, which the Company expects to test in a planned externally funded Phase 2 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to opaganib for treatment of neuroblastoma, a type of childhood cancer that develops from immature nerve cells and accounts for 15% of all pediatric cancer-related deaths.

Orphan Drug designation provides for a seven-year marketing exclusivity period should opaganib be approved in neuroblastoma and may confer additional benefits such as accelerated development and review times, potential grant funding and possible tax credits.

"RedHill is proud to have received a second orphan-drug designation for opaganib in oncology, following its previous designation for cholangiocarcinoma (CCA, also known as bile duct cancer). This designation for neuroblastoma – the most common infancy malignancy and for which new options are urgently needed – adds to opaganib’s potential as a novel oncological agent," said Dr. Mark Levitt, Chief Scientific Officer at RedHill. "Opaganib has broad oncology potential with promising preliminary clinical data in solid tumor cancers such as prostate cancer and CCA, and data from a range of U.S. government supported and Apogee conducted preclinical studies in various indications, including radioprotection, and also in combination with RedHill’s RHB-107. We also see such utility extending to the potential for opaganib to have a sensitizing effect in hormone receptor pathway inhibition therapy, which the Company expects to test in a planned externally funded Phase 2 study."

Neuroblastoma usually affects children aged five or younger but does also occur in older children. In the United States, approximately 650 new cases are diagnosed each year, accounting for around 10% of all childhood cancer cases. Treatment typically involves a combination of surgery, chemotherapy, radiation therapy, and sometimes targeted therapy or immunotherapy. New options are urgently needed.

The neuroblastoma market is expected to reach almost $1.5 billion before the middle of the next decade.

Opaganib is in development for multiple oncology, viral, inflammatory and diabetes and obesity-related indications, including COVID-19, Ebola, acute respiratory distress syndrome (ARDS) and radio/chemical protection.

About Neuroblastoma
Neuroblastoma is a type of cancer most commonly affecting babies and young children. It is rare but is the most common infancy malignancy with a median age of diagnosis of 17 months. In the U.S. it accounts for up to around 10% of all childhood cancer cases. It affects around 11 to 13 kids per million children aged younger than 15 years old – with incidence rising to 65 per million in babies under one year old, equating to approximately 650 new cases each year.

Neuroblastoma originates from nerve cells called neuroblasts, which are found in the adrenal glands (located above the kidneys) and in nerve tissue along the spine, chest, abdomen, or pelvis. The exact cause of neuroblastoma is not well understood, but genetic mutations and abnormalities are known to play a role. Some cases may be linked to genetic syndromes or family history, although most occur sporadically without a clear inherited pattern.

The outlook for children with neuroblastoma can vary widely. Factors affecting prognosis include the stage of the disease at diagnosis, the age of the child, and specific biological characteristics of the tumor. Neuroblastoma is known for its ability to sometimes regress spontaneously in very young children, but it can also be aggressive and challenging to treat, accounting for 15% of pediatric cancer-related deaths.

About Opaganib (ABC294640)
Opaganib, a proprietary investigational host-directed and potentially broad-acting drug, is a first-in-class, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with anticancer, anti-inflammatory and antiviral activity, targeting multiple potential diseases, including obesity-related syndromes, prostate cancer and cholangiocarcinoma (bile duct cancer), gastrointestinal acute radiation syndrome (GI-ARS), Sulfur Mustard exposure, COVID-19, Ebola and other viruses as part of pandemic preparedness.

Opaganib’s host-directed action is thought to work through the inhibition of multiple pathways, the induction of autophagy and apoptosis, and disruption of viral replication, through simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).

Opaganib has been selected for evaluation by two U.S. government countermeasures programs for Acute Radiation Syndrome (ARS) and Sulfur Mustard exposure, both funded by the NIH: The Radiation and Nuclear Countermeasures Program (RNCP), led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the HHS National Institutes of Health, for the nuclear medical countermeasures (MCM) product development pipeline selected opaganib for development as a potential treatment for Acute Radiation Syndrome (ARS); and the Chemical Medical Countermeasures (Chem MCM) Program and the Chemical Countermeasures Research Program (CCRP), managed respectively by the Administration for Strategic Preparedness and Response (ASPR) / Biomedical Advanced Research and Development Authority (BARDA) and NIH/NIAID selected opaganib for evaluation as a potential medical countermeasure (MCM) against Sulfur Mustard exposure.

Opaganib has demonstrated antiviral activity against SARS-CoV-2, multiple variants, and several other viruses, such as Influenza A and Ebola. Opaganib delivered a statistically significant increase in survival time when given at 150 mg/kg twice a day (BID) in a United States Army Medical Research Institute of Infectious Diseases (USAMRIID) in vivo Ebola virus study, making it the first host-directed molecule to show activity in Ebola virus disease. Opaganib also recently demonstrated a distinct synergistic effect when combined individually with remdesivir (Veklury, Gilead Sciences Inc.), significantly improving potency while maintaining cell viability, in a U.S. Army-funded and conducted in vitro Ebola virus study.

Being host-targeted, and based on data accumulated to date, opaganib is expected to maintain effect against emerging viral variants. In prespecified analyses of Phase 2/3 clinical data in hospitalized patients with moderate to severe COVID-19, oral opaganib demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations versus placebo on top of standard of care. Opaganib has demonstrated its safety and tolerability profile in more than 470 people in multiple clinical studies and expanded access use. Data from the opaganib global Phase 2/3 study was published in medRxiv.

Opaganib has received Orphan Drug designation from the FDA for the treatment of neuroblastoma and cholangiocarcinoma and has undergone studies in advanced cholangiocarcinoma (Phase 2a) and prostate cancer. Opaganib also has a Phase 1 chemoradiotherapy study protocol ready for FDA-IND submission.

Opaganib has also shown positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, radioprotection, viral, inflammatory, and gastrointestinal indications.

ORIC Pharmaceuticals to Participate in Upcoming Investor Conferences

On August 26, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that management will participate in the following investor conferences in September (Press release, ORIC Pharmaceuticals, AUG 26, 2024, View Source [SID1234646099]):

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2024 Wells Fargo Healthcare Conference – Participating in a fireside chat on Thursday, September 5, 2024, at 8:00 a.m. ET
Baird 2024 Global Healthcare Conference (Available to conference attendees only) – Participating in a fireside chat on Tuesday, September 10, 2024, at 10:50 a.m. ET.
2024 Cantor Global Healthcare Conference – Participating in a fireside chat on Thursday, September 19, 2024, at 8:35 a.m. ET
Live webcasts of the Wells Fargo and Cantor discussions will be available through the investor section of the company’s website at www.oricpharma.com. Replays of the webcasts will be available for 90 days following the events.