On August 9, 2021 Seagen Inc. (Nasdaq: SGEN), a world leader and pioneer in antibody-drug conjugate (ADC) therapies, and RemeGen Co., Ltd. (9995.HK), a leading innovative biopharmaceutical company in China, reported that the two companies have entered into an exclusive worldwide licensing agreement to develop and commercialize disitamab vedotin, a novel HER2-targeted ADC (Press release, Seagen, AUG 9, 2021, View Source [SID1234586075]).

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Disitamab vedotin combines the drug-linker technology originally developed by Seagen with RemeGen’s novel HER2 antibody exhibiting higher affinity and an increased internalization rate as compared to trastuzumab in preclinical models.1, 2 As monotherapy, disitamab vedotin has demonstrated antitumor activity in clinical trials in several solid tumor types, including urothelial, gastric and breast cancer, as well as across a spectrum of HER2 expression levels. In addition, promising combination activity was demonstrated with a PD-1 inhibitor in urothelial cancer.3 It is believed that vedotin-based immunogenic cell death (ICD) may differentiate this class of ADC’s when combined with checkpoint inhibitors.

"This collaboration leverages Seagen’s world-class expertise and knowledge of ADC development, manufacturing and commercialization to maximize the potential of disitamab vedotin. It also complements our existing franchises and our deep and diverse portfolio of innovative anti-cancer therapies for patients in need," said Clay Siegall, Ph.D., President and CEO, Seagen. "The addition of disitamab vedotin as a late-stage asset with multiple development opportunities aligns strategically with our plans to continue expanding our global footprint and deliver meaningful therapies to patients around the world."

Disitamab vedotin received U.S. Food and Drug Administration (FDA) Breakthrough Therapy designation in 2020 for use in second-line treatment of patients with HER2-expressing, locally advanced or metastatic urothelial cancer (mUC) who have previously received platinum-containing chemotherapy. In the same year, RemeGen announced FDA’s clearance of an Investigational New Drug (IND) application for a Phase II clinical trial in mUC. Disitamab vedotin is conditionally approved for treating locally advanced metastatic gastric cancer in China, and in July 2021 the National Medical Products Administration (NMPA) of China also accepted a New Drug Application for disitamab vedotin in mUC.

"Disitamab vedotin has demonstrated robust antitumor activity in multiple advanced cancers where no effective therapy is available," said Jianmin Fang, Ph.D., Co-founder, CEO and CSO, RemeGen. "Seagen is a well-known global biotechnology company recognized for its capabilities in the field of oncology and ADC therapies. We are delighted to partner with Seagen to maximize the potential of disitamab vedotin and to make it available to patients worldwide. We believe this license agreement highlights the global potential of disitamab vedotin in the ADC arena and is a major milestone for us as we begin the journey to transform from a domestic to a global biopharmaceutical company."

Under the terms of the agreement, Seagen will make a $200 million upfront payment to exclusively license rights to disitamab vedotin for global development and commercialization, outside of RemeGen’s territory. RemeGen will retain development and commercialization rights for Asia, excluding Japan and Singapore. Seagen will lead global development and RemeGen will fund and operationalize the portion of global clinical trials attributable to its territory. RemeGen will also be responsible for all clinical development and regulatory submissions specific to its territory.

Seagen will pay RemeGen up to $2.4 billion in potential total milestone payments based upon the achievement of specified development, regulatory and commercialization goals across multiple indications and products. RemeGen will be entitled to a tiered, high single digit to mid-teen percentage royalty based on net sales of disitamab vedotin in Seagen’s territory.

About Disitamab Vedotin (RC48)

Disitamab vedotin is a novel ADC that selectively delivers the anti-cancer agent monomethyl auristatin E (MMAE) into HER2-expressing tumor cells. The novel antibody component of the ADC exhibits a higher affinity and increased internalization rate as compared to trastuzumab in preclinical models, and in animal models, demonstrates promising antitumor activity. It is the first domestically developed ADC in China to receive marketing approval. In June 2021, disitamab vedotin received conditional approval by the NMPA of China to treat locally advanced or metastatic gastric cancer (GEJ carcinoma). In July 2021, the NMPA accepted the New Drug Application for disitamab vedotin in locally advanced or metastatic urothelial carcinoma. In addition, disitamab vedotin has shown significant antitumor activity in clinical trials of a number of HER2-expressing cancers, including those with low HER2 expression. It is currently being studied in multiple late-stage clinical trials across several solid tumor types.

On August 9, 2021 Prescient Therapeutics’ (ASX: PTX) reported that strong cash position will enable it to advance its multiple cancer programs, with work to follow on from what managing director Steven Yatomi-Clarke describes as "tremendous" FY 2021 (Press release, Prescient Therapeutics, AUG 9, 2021, View Source;utm_medium=rss&utm_campaign=after-tremendous-fy-2021-prescient-therapeutics-well-funded-to-advance-cancer-fighting-therapies [SID1234586069]).

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The company develops personalised medicinal approaches to cancer, including targeted and cellular therapies.

Its targeted therapy candidates PTX-100 and PTX-200 are designed to inhibit cancer growth and tumour survival, while OmniCAR is a universal immune receptor platform being developed for next-generation CAR-T therapies for acute myeloid leukemia, HER2-positive solid tumours including breast, ovarian and gastric cancers, and glioblastoma multiforme (brain cancer).

Prescient ended the June quarter with $16.1 million cash in the bank after spending $280,000 on research and development activities in Australia and the United States, particularly related to the development of OmniCAR and cell therapy enhancements, and the ongoing clinical studies of PTX-100 and PTX-200.

Recent accomplishments include successful results from a phase 1b trial of PTX-100, announced after 30 June, which has led to an expanded study of the drug candidate to treat T cell lymphoma, and trial and manufacturing milestones achieved in the development of the OmniCAR platform.

PTX-100 trial progress
At the end of July, Prescient reported results from the PTX-100 phase 1b basket trial in solid and hematological cancers that demonstrated the drug was very well tolerated at all dose levels.

Early clinical activity was also observed in two patients with aggressive disease, in which prior therapies had failed to stop its progression. One of the patients experienced a partial response (a reduction in cancer burden) from the therapy with no disease progression for 17 months so far, while the other patient experienced a reduction in cancerous lesions and symptomatic .

"In both cases, such patients with refractory T cell lymphoma on standard-of-care therapies would typically be expected to have disease progression within four months, highlighting the encouraging nature of these responses," Prescient reported.

Owing to these encouraging phase 1b results, the company is now progressing development of PTX-100 as a monotherapy in an expansion cohort study in relapsed and refractory T cell lymphoma.

If the expansion cohort is successful, Prescient could advance directly to a separate registration study which may only require small trials compared to typical phase three trials.

Prescient’s other targeted therapy, PTX-200 is currently undergoing a phase 1b clinical trial in patients with acute myeloid leukemia. Updates from this study is expected in coming months.

OmniCAR milestones
To expedite its OmniCAR milestones, Prescient expanded its research partnership with the world-renowned Peter MacCallum Cancer Centre during the June quarter.

The partnership will fast-track development of Prescient’s next generation CAR-T therapy using the OmniCAR platform.

also recently announced "excellent" results from independent in silico immunogenicity testing of OmniCAR’s key binding components, SpyTag and SpyCatcher.

According to the company, this is a key milestone that substantially de-risks the entire platform and is important for progressing Prescient’s in-house programs and external collaborations.

Immunogenicity testing evaluates the immune response against a new therapy. In the case of CAR-T cell therapies, high levels of immunogenicity can adversely impact CAR-T cell expansion and persistence, which can impact the overall safety and clinical response of the treatment.

OmniCAR’s binding system components SpyTag and SpyCatcher were independently tested by a US research provider with results demonstrating that both components have very low immunogenicity – on par with circulating human antibodies.

Prescient chief executive officer and managing director Steven Yatomi-Clarke said the results "could not have been better".

"It gives us confidence that if these therapies are ultimately delivered to patients, their immune systems will not impair the therapy itself."

"This is essential not only for Prescient’s three in-house OmniCAR programs, but also for potential external collaborators, who consider immunogenicity very stringently," he added.

The development followed the successful completion of manufacturing and delivery of critical components of the OmniCAR platform including cell binders for several cancer targets and lentiviral vectors used to produce CAR-T cells.

On August 9, 2021 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) reported that Positive high-level results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the HER2-directed antibody drug conjugate (ADC), demonstrated superiority over trastuzumab emtansine (T-DM1) (Press release, AstraZeneca, AUG 9, 2021, View Source [SID1234586068]).

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At a planned interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that DESTINY-Breast03 met the primary endpoint of progression-free survival (PFS) showing a highly statistically significant and clinically meaningful improvement for patients with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

In DESTINY-Breast03, Enhertu also showed a strong trend toward improved overall survival (OS) compared to T-DM1 in a key secondary endpoint, although the OS data are still immature. The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.

Susan Galbraith, Executive Vice President, Oncology R&D, said: "There is a continued need for new options and better outcomes for patients with HER2-positive metastatic breast cancer who often experience disease progression after initial treatment with available standards of care. These transformative progression-free survival results demonstrate the superiority of Enhertu compared to T-DM1, and the encouraging safety data may open future opportunities to bring this benefit to patients in earlier treatment settings."

Ken Takeshita, Global Head, Research and Development, Daiichi Sankyo, said: "DESTINY-Breast03 is the first global Phase III head-to-head trial of Enhertu against an active control and supports the potential of this medicine to become the new standard of care for patients with HER2-positive metastatic breast cancer following initial treatment with trastuzumab and a taxane. We believe this highly sophisticated and specifically engineered ADC is fulfilling its promise to reshape the treatment of HER2-positive metastatic breast cancer, with the goal to move into earlier lines of treatment for HER2-positive breast cancer and many other HER2-expressing tumour types across our broad clinical trial programme."

The data will be presented at an upcoming medical meeting and shared with health authorities.

Enhertu is approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting in the US, Japan, the EU and several other countries based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.1 More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 Approximately one in five patients with breast cancer are considered HER2-positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.4

Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.5 More effective options are needed to further delay progression and extend survival.5-7

DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary efficacy endpoints include OS, objective response rate, duration of response, clinical benefit rate, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in Canada, the EU, Israel, Japan, the UK and the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4mg/kg) is also approved in Israel, Japan and the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

In May 2020, Enhertu also received Breakthrough Therapy Designation for the treatment of patients with metastatic NSCLC whose tumours have a HER2-mutation and with disease progression on or after platinum-based therapy.

Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral SERD and potential new medicine AZD9833.

PARP inhibitor, Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings. To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, investigating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On August 9, 2021 Targovax ASA (OSE: TRVX) reported that it will announce its second quarter and first half 2021 results on Wednesday 18 August 2021 (Press release, Targovax, AUG 9, 2021, View Source [SID1234586067]). An online presentation by Targovax’s management to investors, analysts and the press will take place at 10:00 am CET.

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The results report and the presentation will be available at www.targovax.com in the Investors section from 07:00 am CET.

Presentation

As a consequence of the Corona situation, there will only be a virtual presentation of the results with a live webcast 18 August at 10.00 am CET. You can join the webcast here. It will be possible to ask questions during the presentation.

On August 8, 2021 ImmVira reported that MVR-C5252 targeting Glioblastoma has received the U.S. FDA clearance to proceed with clinical trial on August 6, 2021 (Press release, Immvira, AUG 8, 2021, View Source [SID1234586063]).

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Glioma is the most common type of CNS tumors. Glioblastoma ("GBM"), as the most aggressive type of Gliomas, displays the highest grade of malignancy and can occur in the brain or spinal cord with median survival of less than two years. The lack of availability in treatment therapies except surgery and radiation, especially the limited options of drugs, indicate an urgent need for development of a novel therapeutic strategy, particularly for recurrent GBM.

On June 11, 2021, Daiichi Sankyo Company, Limited announced that it has received conditional and time-limited approval from the Japan Ministry of Health, Labour and Welfare (MHLW) for DELYTACT (teserpaturev/G47∆), an oncolytic virus("OV"), for the treatment of patients with GBM, becoming the world’s first OV therapy approved for brain tumors. The approval of DELYTACT in Japan is a validation of oHSV-1 modality. Moreover, FDA’s approval on Breakthrough Therapy Status of two OV products targeting GBM in recent years symbolizes the favorable forward-looking for OV modalities over the same indication.

Leveraging ImmVira’s OvPENS development platform, MVR-C5252 is designed specifically for the treatment of malignant glioma. This product has been further genetically engineered on the basis of MVR-T3011 (also known as T3011) by specific attenuation to achieve on-target malignant gliocyte killing while maintaining safety profile. MVR-C5252 also carries exogenous genes that express IL-12 and PD-1 mAb to promote the immune response of tumor microenvironment for further anti-tumor activity.

The IND clearance of MVR-C5252 in the United States highlights ImmVira’s strong and sustainable research and development capability in designing and synthesizing viral vector with functional specificity, and marks another important step for ImmVira’s pipeline expansion. ImmVira’s OvPENS, the systematic next-generation cancer therapy development platform, is expected to drive more pipelines into clinical stage, expand pipelines to cover broader indications, and capture the large and evolving market of oncolytic virotherapy.