On February 21, 2022 AIGEN Sciences, an artificial intelligence-based new drug development biotech, reported that it signed a joint research agreement with Incurix to develop new anticancer drugs based on artificial intelligence (AI) (Press release, AIGEN Sciences, FEB 21, 2022, View Source [SID1234643551]).

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 contract applies artificial intelligence technology based on transcriptome profiles based on Eisen Science’s protein structure to develop new anticancer drugs based on transcription factor inhibitors, which are attracting attention as major anticancer targets but are known to be difficult to develop. The goal is joint development.

Eisen Science plans to derive new substances that can regulate transcription factors based on its artificial intelligence platform. Afterwards, Incurix will be responsible for verification of effective substances and lead substances and follow-up development of final candidate substances by utilizing the new substances derived from Eisen Science using the transcription factor direct inhibitor new drug development technology platform. The terms of the contract will be kept confidential as agreed between the two companies, and the profits secured through commercialization, such as third-party technology transfer, will be shared in a certain ratio according to the stage of candidate material development at the time of profit generation.

Accordingly, AIGEN Science uses its platform ‘AIGEN Discovery’ to initially select about 10,000 ‘focused library’ compounds that show the effect of regulating transcription factors at the cellular level from a library of 3 billion compounds. Next, we plan to use the protein structure of the transcription factor to discover effective substances that bind with high affinity, and then proceed with optimization using ‘AIGEN Optimizer’ to discover leading substances.

Kang Jae-woo, CEO of Eisen Science, said, "Through joint development with Incurix, which specializes in developing anticancer drugs that directly inhibit transcription factors, we will successfully lead the development of new drugs for transcription factor targets (difficult-to-target) that were difficult to access through traditional methods. "As Eisen Science’s artificial intelligence platform is a model based on transcriptome data, synergy is expected with Incurix, which has expertise in developing transcription factor inhibitors, and we have high expectations for future joint development."

On February 21, 2022 AstraZeneca reported that Positive high-level results from the pivotal DESTINY-Breast04 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer regardless of hormone receptor (HR) status versus physician’s choice of chemotherapy (Press release, AstraZeneca, FEB 21, 2022, View Source [SID1234608350]).

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!

Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

All patients in the trial received a HER2 test, and the results were centrally confirmed. HER2-low status was defined as an immunohistochemistry (IHC) score of 1+ or IHC 2+ with a negative in-situ hybridisation (ISH) score.

Up to 55% of all patients with breast cancer have tumours with a HER2 IHC score of 1+, or 2+ in combination with a negative ISH test, a level of HER2 expression not currently eligible for HER2-targeted therapy.1,2 HER2-low expression occurs in both HR-positive and HR-negative disease.3

HER2 testing is well established to determine an appropriate treatment strategy in metastatic breast cancer. Targeting the lower range of HER2 expression may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer.4 Currently, chemotherapy remains the only treatment option both for patients with HR-positive tumours following progression on endocrine (hormone) therapy, and for those who are HR-negative.5

DESTINY-Breast04 met its primary endpoint, where Enhertu demonstrated superior PFS in previously treated patients with HR-positive HER2-low metastatic breast cancer compared to the standard-of-care chemotherapy. The trial met the key secondary endpoint of PFS in patients with HER2-low metastatic breast cancer regardless of HR status (HR-positive or HR-negative). The trial also met the key secondary endpoints of OS in patients with HR-positive disease and in patients regardless of HR status at interim analysis.

The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified. Overall interstitial lung disease (ILD) rates were consistent with that observed in late-line HER2-positive breast cancer trials of Enhertu, with a lower rate of Grade 5 ILD observed as determined by an independent adjudication committee.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said: "Today’s historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated. A HER2-directed therapy has never-before shown a benefit in patients with HER2-low metastatic breast cancer. These results for Enhertu are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorise and treat breast cancer."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo said: "Enhertu continues to redefine the treatment of HER2-targetable cancers. DESTINY-Breast04 is the first ever Phase III trial of a HER2-directed therapy in patients with HER2-low metastatic breast cancer to show statistically significant and clinically meaningful benefit in progression-free and overall survival compared to standard treatment. We look forward to sharing the detailed findings of DESTINY-Breast04 with the medical community and initiating discussions with regulatory agencies globally with the goal of bringing Enhertu to patients with metastatic breast cancer previously considered to be HER2-negative."

The data will be presented at a forthcoming medical meeting and shared with global health authorities.

Enhertu (5.4mg/kg) is approved in more than 40 countries 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 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.

Notes

Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.6 More than two million cases of breast cancer were diagnosed in 2020 resulting in nearly 685,000 deaths globally.6

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, and is one of many biomarkers expressed in breast cancer tumours.7 HER2 expression is currently defined as either positive or negative, and is determined by an IHC test which measures the amount of HER2 protein in a cancer cell, and/or an ISH test which counts the copies of the HER2 gene in cancer cells.7,8 HER2-positive cancers are defined as IHC 3+ or IHC 2+/ISH+, and HER2-negative cancers are currently defined as IHC 0, IHC 1+ or IHC 2+/ISH-.7

DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive (n=480) or HR-negative (n=60) HER2-low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomised 2:1 to receive either Enhertu or chemotherapy.

The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomised patients (regardless of HR status), OS in patients with HR-positive disease and OS in all randomised patients (regardless of HR status). Other secondary endpoints include PFS based on BICR and investigator assessment, duration of response based on BICR and safety.

DESTINY-Breast04 enrolled approximately 540 patients at multiple sites in Asia, Europe and North 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 more than 40 countries 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 based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) 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.

Regulatory applications for Enhertu are currently under review in Europe, Japan, the US and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

Enhertu also is currently under review in Europe for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2 based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (referred to as 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 selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. Lynparza has also demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival versus placebo in the adjuvant treatment of patients with germline BRCA-mutated HER2-negative early breast cancer. 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, 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, evaluating 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.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

On February 21, 2022 Oxilio Ltd is a privately held pharmaceutical development company reported that focused on repurposing known drugs for the treatment of cancer through a programme of corporate alliances coupled with rapid proof of concept clinical development (Press release, Quotient Sciences, FEB 21, 2022, View Source [SID1234621608]).

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!

Oxilio signed an exclusive global licensing agreement with TRx Biosciences on 20th October 2021 for the use of their platform technology to support the development of Oxilio’s formulation, OXL001. Oxilio has since progressed the product and now signed a significant service contract with Quotient Sciences, a drug development and manufacturing accelerator, to support the formulation development and preparation of clinical trials for OXL001.

Mark Egerton, CEO of Quotient Sciences said, "By leveraging our integrated development and clinical testing platform, Translational Pharmaceutics, Oxilio and TRx Biosciences will have the flexibility to adjust formulations based on emerging clinical data within their study, enabling us to improve their likelihood of success, reduce their development time and ultimately get new medicines to patients faster. We look forward to working with both companies as we prepare to take OXL001 into the clinic later this year."

Commenting, Oxilio Director Dr Simon Yaxley said: "Quotient has significant capabilities for scientific innovation and adaptation which will further complement Oxilio’s already substantial scientific capacity. We look forward to taking Oxilio’s highly promising formulation OXL001 into the clinic later this year which, if successful, offers tremendous near-term potential benefit for cancer patients."

On February 21, 2022 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Medigene AG (FSE: MDG1, Prime Standard, "Medigene"), a clinical-stage immuno-oncology company focusing on the development of T cell immunotherapies, reported that they have entered a multi-target research collaboration to develop T cell receptor (TCR) based immunotherapies against cancer (Press release, BioNTech, FEB 21, 2022, View Source [SID1234608351]). The initial term of the collaboration is three years.

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!

Medigene will contribute its proprietary TCR discovery platform for the development of TCRs against multiple solid tumor targets nominated by BioNTech. Medigene’s automated, high throughput TCR discovery platform is designed to bypass central tolerance to yield high affinity TCRs. T cell therapy has become a disruptive medical innovation in the treatment of patients with cancer. Engineered TCR-modified T cells (TCR-T cells) are reprogrammed to express a TCR that can recognize specific antigens only present on tumor cells, thereby enabling a precise and potent immune response to attack a patient’s tumor.

"This collaboration with Medigene expands our cell therapy portfolio and TCR discovery capabilities, and further strengthens our ability to be a leader in the rapidly emerging field of engineered cell therapies," said Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech. "We look forward to working closely with Medigene to develop new treatments which address solid tumors with high unmet medical need."

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: "Medigene is at the forefront of the development of TCR-T therapies for oncology. The sale and licensing deal with BioNTech is an important validation from a global leading biotech company of our proprietary technologies to discover and characterize highly specific TCRs and empower resulting TCR-T cells to fight solid tumors. This partnership provides Medigene with meaningful financial resources to fuel our next generation development programs targeting potentially novel tumor-specific "dark matter" antigens, further tools to enhance T-cell-based immunotherapies, as well as additional potential strategic deals with future milestone payments and royalties."

BioNTech will acquire Medigene’s next generation preclinical TCR program, which combines TCR-4 of Medigene’s MDG10XX program targeting PRAME with Medigene’s proprietary PD1-41BB switch receptor technology. BioNTech will also obtain the exclusive option to acquire additional existing TCRs in Medigene’s discovery pipeline and will receive licenses to the company’s PD1-41BB switch receptor and precision pairing library. This has the potential to augment TCR cell therapy efficacy and can be applied to all BioNTech cell therapy programs.

Under the terms of the agreement, Medigene will receive EUR 26 million upfront, as well as research funding for the period of the collaboration. BioNTech will be responsible for global development and hold exclusive worldwide commercialization rights on all TCR therapies resulting from this research collaboration. Medigene will be eligible to receive development, regulatory and commercial milestone payments up to a triple digit million EUR amount per program in addition to tiered deferred option payments on global net sales for products based on TCRs arising from the collaboration and royalties on products utilizing at least one of the licensed technologies.

On Feb. 21, 2022, Applied Pharmaceutical Science, Inc. reported that APS03118, a next-generation selective RET inhibitor, has recently been granted Fast Track Designation by U.S. Food and Drug Administration (FDA) for the treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC) previously-treated with a selective RET inhibitor (Press release, Applied Pharmaceutical Science, FEB 21, 2022, View Source [SID1234613100]). The Fast Track Designation is based on preclinical data of APS03118, which will be presented as an electronic poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2022. Investigational New Drug (IND) application of APS03118 was approved by FDA in January 2022, the global clinical trials are in initiation.

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!

RET aberrances contain fusions and mutations, which can lead to over-activation of RET signaling pathways and uncontrolled cell growth. Because RET oncogene is present in lung cancer, thyroid cancer, rectal cancer, breast cancer, pancreatic cancer and other solid tumors, and it has become an important target of "unlimited cancer" therapy. Cancers with RET alterations primarily rely on abnormal activation of this kinase to promote their proliferation and growth, therefore RET positive cancers are sensitive to RET inhibitors.

NSCLC patients with RET gene alterations are not rarely seen in clinic, particularly in younger, non‐smoking patients with adenocarcinoma histology, with an incidence of 7%-17%. In addition, the brain metastases often occur in lung cancer patients which is highly related with RET fusion, and the cumulative incidence is more than 60% within 24 months. Although first-generation selective RET inhibitors have achieved great success in the therapy of RET positive of NSCLC, patients inevitably acquire resistance.

APS03118 is a next-generation RET inhibitor with innovative chemical structure, and this breakthrough progresses expected to accelerate its registration process and bring new hope to RET aberrance patients. The FDA Fast Track Designation is based on preclinical data:APS03118 showed significant nanomolar level potent antitumor activity in inhibition to various RET fusion and mutations including RET gatekeeper V804M/L/E and solvent frontier G810R/S/C mutations which lead to resistance to selective RET inhibitors. In a brain tumor model, APS03118 completely eliminated brain tumors and all animals survived after dosing, demonstrating the therapeutic advantages of APS03118 for patients with brain metastases.

Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. A drug that receives Fast Track Designation is eligible for some or all of the following: More frequent meetings with FDA to discuss the drug’s development plan; Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, and the opportunities of Rolling Review.APS03118 is granted Fast Track Designation for the treatment of metastatic NSCLC previously-treated with a selective RET inhibitor, which will help to strengthen the communication with FDA, and accelerate the progress of clinical trials and reach the market expeditiously.

Applied Pharmaceutical Science, Inc. is a biopharmaceutical high-tech company specialized on innovative cancer precision therapy, focusing on small molecule precision cancer therapy. Dr. Jun Zhong, R&D vice president of APS, stated, APS03118 granted the Fast Track Designation of FDA, which is another breakthrough of APS in precision cancer therapy. Meanwhile, RET alterations is related to multiple malignant tumors, and we expect to extend APS03118 to other cancer therapies and reach the global market.