On June 26, 2024 Korean scientists reported to have investigated HVH-2930, an innovative HSP90 inhibitor in reshaping HER2-positive breast cancer treatment (Press release, Korea University, JUN 26, 2024, View Source [SID1234644559]). Unlike previous HSP90 inhibitors, this compound circumvents limitations by bypassing heat shock response induction. It demonstrates promising efficacy in inducing cancer cell apoptosis and effectively overcomes treatment resistance. In preclinical studies, HVH-2930 showed substantial promise, offering hope for better treatment outcomes. Its potential for diverse HER2-overexpressing malignancies indicates a paradigm shift in cancer therapy, anticipating enhanced effectiveness and increased availability.

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HER2-positive breast cancer, known for its aggressive nature due to the overexpression of the HER2 protein, poses significant challenges in treatment. Current standard treatments for HER2-positive breast cancer typically involve a combination of HER2-targeted therapies like trastuzumab, chemotherapy, and hormone therapy. However, the emergence of resistance highlights the need for novel approaches for improved outcomes.

In this relentless pursuit of treatment solutions, a team of researchers at Korea University led by Professor Jae Hong Seo have achieved a significant milestone with the development of HVH-2930, a promising inhibitor targeting heat shock protein 90 (HSP90), the findings of which were published in Theranostics on 31 March 2024. Prof. Seo shares, "We have highlighted the pivotal role of HSP90, an oncogenic protein, in fueling tumor growth by activating key receptor tyrosine kinases, including HER2. While previous N-terminal HSP90 inhibitors faced challenges like inducing the heat shock response (HSR) and toxicity, HVH-2930, a C-terminal HSP90 inhibitor, shows promise."

The study utilized both in vivo and in vitro methods to investigate HER2-positive breast cancer and potential treatments. In laboratory settings, breast cancer cells were cultured alongside normal mammary cells, using advanced cytometry techniques to assess cell viability, apoptosis, and functionality. Additionally, protein interactions were studied to uncover underlying molecular processes. In mouse models, tumor cell implantation was used to study tumor growth dynamics and treatment responses.

The findings revealed that HVH-2930 effectively induced apoptosis in breast cancer cells without triggering the heat shock response (HSR), a notable feature that distinguishes it from other treatments. By selectively targeting HSP90, HVH-2930 downregulated HER2 signaling, crucial in breast cancer progression. Impressively, in xenograft mouse models, HVH-2930 inhibited tumor growth, angiogenesis, and cancer stem cell-like properties without causing toxicity. Moreover, when combined with paclitaxel, HVH-2930 exhibited a synergistic antitumor effect, suggesting its potential as a promising therapeutic strategy for HER2-positive breast cancer. These results signify a significant advancement in targeting the HSP90 chaperone machinery for breast cancer treatment.

Prof. Seo shares "HVH-2930 stands as a groundbreaking advancement in meeting the critical needs of HER2-positive breast cancer patients, notably those resistant to trastuzumab. With its potential application in other HER2-overexpressing cancers like gastric and esophageal cancers, it holds promise for treating a wider range of patients. Moreover, its anticipated affordability compared to current therapies could significantly enhance accessibility, particularly in resource-limited settings such as underdeveloped countries."

On June 26, 2024 Simcere Zaiming, an innovative oncology company and a subsidiary of Simcere Pharmaceutical Group (2096.HK), reported that Enlituo (generic name: cetuximab beta injection), a new generation anti-epidermal growth factor receptor (EGFR) antibody drug developed in collaboration with Mabpharm Limited (2181.HK), has recently received approval from the China National Medical Administration (NMPA) for marketing (Press release, Jiangsu Simcere Pharmaceutical Company, JUN 26, 2024, View Source [SID1234644558]). Enlituo is indicated for use in combination with the FOLFIRI regimen as a first-line treatment for RAS/BRAF wild-type metastatic colorectal cancer (mCRC).

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According to the ‘Cancer Incidence and Mortality in China, 2022’ by the National Cancer Center, colorectal cancer ranks as the second most common cancer in China. Annually, there are 1.571 million new cases and 240,000 deaths, imposing a substantial disease burden on the society. When colorectal cancer patients develop metastasis, the primary treatment options often include chemotherapy and targeted drugs. Previous clinical studies have demonstrated the effectiveness of EGFR-targeting antibody drugs in treating malignant tumors, particularly mCRC, in patients without RAS/BRAF mutations (wild-type).

Enlituo (cetuximab beta, originally known as CMAB009) is a recombinant EGFR monoclonal antibody developed independently in China. Classified as a 2.4 class modified biological new drug, cetuximab beta is prepared using a proprietary protein expression technique, effectively avoiding glycosylation modification that may lead to hypersensitivity.

Enlituo received approval based on robust evidence from a phase 2/3 study and a phase 3 confirmatory clinical trial. In an open-label, randomized, controlled, multicenter, prospective phase 3 study, 505 subjects with RAS/BRAF wild-type mCRC were treated and analyzed. Clinical data revealed that combining cetuximab beta with FOLFIRI significantly extended progression-free survival (PFS) compared to FOLFIRI alone (13.133 months vs. 9.567 months, P = 0.004). Additionally, the combination increased the objective response rate (ORR) (69.1% vs. 42.3%, P < 0.001) and overall survival (OS) (2.322 years vs. 1.900 years, P = 0.024).

Dr. Renhong Tang, Chairman of Simcere Zaiming, emphasized Enlituo’s unique clinical value in targeted therapy: "Its initial indication for colorectal cancer addresses a large patient population. The product synergizes well with Simcere Zaiming’s existing offerings, and efforts are underway to accelerate its commercialization, benefiting more cancer patients."

Dr. Hao Wang, Chief Executive Officer of Mabpharm, expressed excitement as Enlituo bridged the gap in colorectal cancer treatment with domestically developed EGFR-targeted drugs. "This provides clinicians and patients with updated therapeutic options. By collaborating with Simcere Zaiming’s Marketing Team, we are able to rapidly realize the clinical value of Enlituo, benefiting hundreds of thousands of patients in China with an effective and affordable biological new drug. "

Enlituo represents the first EGFR monoclonal antibody drug developed in China with independent intellectual property rights that are approved for the first-line treatment of mCRC. The successful launch of Enlituo will provide high quality and affordable biological targeted remedy for Chinese cancer patients.

In March 2023, the drug marketing application of Enlituo was accepted by the NMPA. On August 18, 2023, the Group entered into a cooperation agreement with Mabpharm, pursuant to which the Group obtained the exclusive commercial rights in respect of Enlituo in Chinese mainland.

On June 26, 2024 AbbVie (NYSE: ABBV) reported that the U.S. Food and Drug Administration (FDA) has approved EPKINLY (epcoritamab-bysp) as the first and only T-cell engaging bispecific antibody administered subcutaneously for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of prior therapy (Press release, AbbVie, JUN 26, 2024, View Source [SID1234644557]). This indication is approved under the FDA’s Accelerated Approval program based on overall response rate (ORR) and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

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"The FDA approval of EPKINLY offers a new treatment option for relapsed or refractory follicular lymphoma, particularly following failure of other therapies," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "EPKINLY treatment has shown deep and durable responses for many patients. Subcutaneous dosing offers convenience, and EPKINLY can be given to patients without mandatory hospitalization using a 3-step-up dosing regimen. We believe that EPKINLY has the potential to be a core therapy in the treatment of multiple B-cell malignancies and furthers our company mission to advance research to raise standards of care for patients with cancer."

Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization.

FL is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30% of all cases.2 About 15,000 people develop FL each year in the U.S.3 and it is considered incurable with current standard of care therapies.4 Patients often relapse and, with each relapse the remission and time to next treatment is shorter.5 Over time, transformation to DLBCL, an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.6

"Patients with relapsed or refractory follicular lymphoma face significant treatment challenges, and there is currently no clear standard of care treatment available across practice settings," said Jeff Sharman, M.D., Disease Chair, Hematology Research, Sarah Cannon Research Institute (SCRI) at Willamette Valley Cancer Institute in Eugene, Oregon. "The responses observed in the follicular lymphoma cohort of the EPCORE NHL-1 clinical trial, as well as in patients with relapsed or refractory DLBCL from the trial, show the potential of EPKINLY to serve as an important treatment option for these patients."

"People living with follicular lymphoma are in need of additional options when their cancer returns," said Lee Greenberger, Ph.D., Chief Scientific Officer at The Leukemia & Lymphoma Society. "Today’s approval is welcome news for patients, as it provides another tool in the physician arsenal for this difficult-to-treat form of cancer."

FDA approval is based on results from the Phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and efficacy of EPKINLY in 127 adult patients with R/R FL who previously received a median of three lines of therapy and with 70% having double refractory disease. Results and safety findings include:

The study results showed an ORR – the study’s primary endpoint − of 82%, a complete response (CR) rate of 60% and a partial response (PR) rate of 22%.
At a median follow-up of 14.8 months among responders, more than half of patients who responded to treatment in the study remained responsive to treatment (i.e., median duration of response was not reached).
Safety was evaluated in a total of 213 patients:
The safety of EPKINLY at a target dose of 48 mg was evaluated in EPCORE NHL-1, a single-arm study of 127 patients who received a 2-step up dosage schedule.
The most common (≥20%) adverse reactions were injection site reactions, cytokine release syndrome (CRS), COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache.
A separate dose optimization cohort evaluated 86 patients at the recommended 3-step dosage schedule for CRS mitigation. For the first full dose of this 3-step regimen, mandatory hospitalization was not required. There were no grade 3 CRS observed in patients with FL who received EPKINLY with the 3 step-up dosage schedule.
The prescribing information has a Boxed Warning for serious or life-threatening CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. Please see additional Important Safety Information, below.

About the Phase 1/2 EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part; an expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (B-NHL), including FL after two or more lines of systemic therapy. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. This cohort generated pivotal data from patients with FL and DLBCL. The optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 cytokine release syndrome (CRS) and mitigate Grade ≥3 CRS. The primary endpoint of the expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab.

NCCN Clinical Practice Guidelines
The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for "B-Cell Lymphomas" were recently updated (Version 2.2024) to add EPKINLY as a Category 2A, preferred recommendation for third-line and subsequent therapy for patients with FL.

About EPKINLY (epcoritamab-bysp)
EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, or follicular lymphoma (FL) that has come back or that did not respond to previous treatment after receiving 2 or more treatments. EPKINLY is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.

Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.7

Epcoritamab (approved under the brand name EPKINLY in the United States and TEPKINLY in the European Union) has received regulatory approval in certain lymphoma indications in several countries.

AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets. Both Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy and in combination across lines of therapy in a range of hematologic malignancies. Please visit clinicaltrials.gov for more information.

EPKINLY (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
Neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.
People with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after receiving their first full dose of EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic problems.

Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. If you have any symptoms that impair consciousness, do not drive or use heavy machinery or do other dangerous activities until your symptoms go away.

EPKINLY can cause other serious side effects, including:

Infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment and treat you as needed if you develop an infection. You should receive medicines from your healthcare provider before you start treatment to help prevent infection. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts, which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.

In DLBCL or high-grade B-cell lymphoma, the most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. The most common severe abnormal laboratory test results include decreased white blood cells, decreased red blood cells, and decreased platelets.

In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract infections, muscle and bone pain, rash, diarrhea, fever, cough, and headache. The most common severe abnormal laboratory test results include decreased white blood cells and decreased red blood cells.

These are not all of the possible side effects of EPKINLY. Call your doctor for medical advice about side effects. You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see Medication Guide, including Important Warnings.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, and bi-specific and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.

Today, our expansive oncology portfolio is comprised of approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines across some of the world’s most widespread and debilitating cancers. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit us at View Source

On June 26, 2024 Merck & Co reported the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) seeking accelerated approval of Daiichi Sankyo (TSE: 4568) and Merck’s (known as MSD outside of the United States and Canada) patritumab deruxtecan (HER3-DXd) for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies (Press release, Merck & Co, JUN 26, 2024, View Source [SID1234644554]).

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The CRL results from findings pertaining to an inspection of a third-party manufacturing facility. The CRL did not identify any issues with the efficacy or safety data submitted.

Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck.

"We will work closely with the FDA and the third-party manufacturer to address the feedback as quickly as possible in order to bring the first HER3 directed medicine to patients with previously-treated EGFR-mutated non-small cell lung cancer." said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We remain confident in the ability to develop this medicine to its full potential."

"Patients with previously treated EGFR-mutated non-small cell lung cancer often experience recurrence and have limited treatment options." said Marjorie Green, MD, Senior Vice President and Head of Oncology, Global Clinical Development, Merck Research Laboratories. We are committed to working with Daichi Sankyo and the FDA to prioritize making patritumab deruxtecan available to these patients in need."

The BLA is based on the primary results from the HERTHENA-Lung01 pivotal phase 2 trial that were presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) and simultaneously published in the Journal of Clinical Oncology.

In HERTHENA-Lung01, patritumab deruxtecan was studied in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy, which demonstrated an objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2), including one complete response and 66 partial responses. The median duration of response (DoR) was 6.4 months (95% CI: 4.9-7.8).

The safety profile of patritumab deruxtecan observed in HERTHENA-Lung01 was consistent with previous phase 1 clinical trials in NSCLC with a treatment discontinuation rate of 7.1% due to treatment-emergent adverse events (TEAEs). Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (≥5%) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%). Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. One grade 5 ILD event was observed.

About HERTHENA-Lung01
HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population.

The primary endpoint of HERTHENA-Lung01 was ORR as assessed by blinded independent central review (BICR). Secondary endpoints included DoR, progression-free survival, disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, overall survival, safety and tolerability.

HERTHENA-Lung01 enrolled patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.

About EGFR-mutated non-small cell lung cancer
Approximately 226,000 lung cancer cases were diagnosed in the U.S. in 2022. Lung cancer is the third most common cancer and the leading cause of cancer-related deaths in the U.S. NSCLC accounts for approximately 81% of all lung cancers in the U.S., with 52% having distant spread at diagnosis. EGFR mutations occur in approximately 1 in 5 patients with NSCLC in Western populations.

About HER3
HER3 is a member of the EGFR family of receptor tyrosine kinases. It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment. HER3 is associated with poor treatment outcomes, including shorter relapse-free survival and significantly reduced survival. There is currently no HER3 directed therapy approved for the treatment of any cancer.

About patritumab deruxtecan
Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Patritumab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in December 2021 for the treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies.

Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other therapies in a global development program, which includes HERTHENA-Lung02, a phase 3 trial evaluating the efficacy and safety of patritumab deruxtecan versus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on or after treatment with a third-generation EGFR TKI; HERTHENA-Lung01, a phase 2 trial in metastatic or locally advanced NSCLC with an activating EGFR mutation previously treated with at least one EGFR TKI and one platinum-based chemotherapy-containing regimen; HERTHENA-PanTumor01, a phase 2 trial in locally advanced or metastatic solid tumors, including melanoma, gastric and head and neck cancer, among other types of cancer, previously treated with at least one prior systemic therapy; a phase 1 trial in combination with osimertinib in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial in previously treated patients with advanced NSCLC. A phase 1/2 trial in HER3 expressing metastatic breast cancer also has been completed.

About the Daiichi Sankyo and Merck collaboration
Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.

About the DXd ADC portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

On June 26, 2024 Oragenics, Inc., a company focused on developing unique, intranasal pharmaceuticals for the treatment of neurological disorders, reported the closing of its public offering of 1,100,000 shares of its common stock at an offering price of $1.00 per share (Press release, Oragenics, JUN 26, 2024, View Source [SID1234644553]).

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The gross proceeds of the offering are approximately $1.1 million before deducting placement agent fees and other estimated offering expenses payable by the Company. The Company intends to use the net proceeds from the offering to fund the continued development of its ONP-002 product candidate and for general corporate purposes and working capital.

Dawson James Securities, Inc. acted as the sole placement agent for the offering.

Shumaker, Loop & Kendrick, LLP, represented the Company in connection with the offering, and ArentFox Schiff LLP, Washington, DC, represented the placement agent.

The offering was made pursuant to a shelf registration statement on Form S-3 (File No. 333-269225), including a base prospectus, filed with the U.S. Securities and Exchange Commission (the "SEC") on January 13, 2023, and declared effective on January 25, 2023. The offering will be made only by means of a written prospectus. A preliminary prospectus supplement and accompanying prospectus describing the terms of the offering has been or will be filed with the SEC and will be available on its website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering may also be obtained from Dawson James Securities, Inc., 101 North Federal Highway, Suite 600, Boca Raton, FL 33432 or by telephone at (561) 391-5555, 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.