On August 19, 2024 Daiichi Sankyo (TSE: 4568) reported that the European Medicines Agency (EMA) has validated the Type II Variation application for ENHERTU (trastuzumab deruxtecan) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting (Press release, AstraZeneca, AUG 19, 2024, View Source [SID1234645999]).

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 specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. This application is based on data from the DESTINY-Breast06 phase 3 trial presented as a late-breaking oral session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO24) Annual Meeting.

"This submission builds on our existing indication for ENHERTU in patients with HER2 low metastatic breast cancer and an expanded approval would enable the potential for use in an earlier disease setting as well as in a broader patient population that now includes HER2 ultralow," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We look forward to working closely with the EMA to potentially bring this medicine to more patients in the EU."

Additional regulatory submissions for ENHERTU in this indication are underway globally.

About DESTINY-Breast06

DESTINY-Breast06 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab paclitaxel) in patients with HR positive, HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months.

The primary endpoint is progression-free survival (PFS) in the HR positive, HER2 low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2 low and HER2 ultralow), overall survival (OS) in patients in the HER2 low patient population and OS in the overall trial population. Other secondary endpoints include objective response rate, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. Analysis of the HER2 ultralow subgroup was not powered to demonstrate statistical significance.

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and n=153 for HER2 ultralow) at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

About Breast Cancer and HER2 Expression

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 In Europe, approximately 557,000 cases of breast cancer are diagnosed annually.2 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.3

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer.4 Patients with high levels of HER2 expression (IHC 3+ or IHC2+/ISH+) are classified as HER2 positive and treated with HER2 targeted therapies, representing approximately 15 to 20% percent of all breast cancers.5 Historically, tumors that were not classified as HER2 positive were classified as HER2 negative, despite the fact that many of these tumors still carry some level of HER2 expression.6 It is estimated that approximately 60% to 65% of HR positive, HER2 negative breast cancers are HER2 low and potentially an additional 25% may be HER2 ultralow.7,8

Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer.9 However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited.9 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.9,10,11,12

Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2 low expression.13 There are no targeted therapies specifically approved for patients with HER2 ultralow expression.14

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) 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 program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Full approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population.

ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial.

On August 19, 2024 ImmunoPrecise Antibodies Ltd. (the "Company" or "IPA") (NASDAQ: IPA), an AI-driven biotherapeutics company, reported a groundbreaking achievement: the ability to engineer antibodies entirely through computer simulations using LENSai (Press release, ImmunoPrecise Antibodies, AUG 19, 2024, View Source [SID1234645982]). This marks a significant milestone for the biotechnology industry. Additionally, the antibodies produced by IPA are highly specific to a challenging oncology target located within the Tumor Microenvironment (TME).

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 achievement was made possible by the patented LENSai technologies, which began from an exceptionally challenging starting point: the target protein had no previously known structural information. Despite this, the LENSai platform was able to model the protein’s structure and accurately engineer antibodies specifically tailored to bind to it. This is particularly significant because designing effective therapeutics without prior structural knowledge of the target is a major hurdle in drug discovery, often requiring extensive experimentation and resources. LENSai’s ability to overcome this challenge entirely in silico highlights its advanced capabilities in computational biology and its potential to revolutionize the field of antibody engineering.

The potential therapies were engineered to bind exclusively to the oncology target under specific conditions. Importantly, it was demonstrated that these therapies do not bind to similar proteins known to be present on healthy cells and tissues, which is crucial because such binding typically leads to the negative side effects seen in chemotherapy. These findings highlight LENSai’s ability to address one of the toughest challenges in optimizing antibodies for oncology.

"This marks a significant milestone for the biotechnology industry, demonstrating LENSai’s ability to engineer highly specific and validated antibodies for the exceedingly difficult environment around tumors, and doing so entirely on a computer," said Dr. Jennifer Bath, President and CEO of IPA. "This success, elevated by the fact that important details of the protein being targeted were unknown, represents a major feat in the application of LENSai in generating targeted and specific therapies for the potential treatment of cancer. Moreover, our continuous advancements and integrations have significantly enhanced our ability to develop these therapies faster, more efficiently, and at a reduced cost compared to traditional methods."

Historically, biologic drug discovery has been a risky, time-consuming, and expensive endeavor, with failure rates exceeding 90%. Recent data indicates that it now costs approximately $1.3 billion and takes an average of 10 to 15 years to bring a single new drug to market, with costs potentially rising even higher depending on the complexity of the drug and therapeutic area​. The market has seen major successes like Humira, which has shown potential in the tumor microenvironment and has generated over $20 billion in annual sales. Similarly, Keytruda has demonstrated effectiveness in modulating the tumor microenvironment and has generated over $14 billion annually. However, the time, cost, and risk associated with developing such biologics have historically limited the number of these therapies that can be pursued, creating a bottleneck in the availability of life-saving treatments.

"The successful application of LENSai, along with laboratory validation of these novel antibodies, underscores LENSai’s potential to accelerate the development of precision-targeted treatments, aimed at more effective cancer therapies with fewer side effects," stated Dr. Dirk Van Hyfte, MD, PhD, Co-Founder and Head of Innovation at BioStrand, an IPA subsidiary. "What LENSai has accomplished today is just one of the reasons we firmly believe in its ability to bring potentially life-changing biologics to patients with the power of our AI."

On August 19, 2024 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported that enrollment has resumed for the Company’s ongoing VISTA-101 Phase 1/2 clinical trial, effective immediately (Press release, Kineta, AUG 19, 2024, View Source;utm_medium=rss&utm_campaign=kineta-reopens-enrollment-for-the-vista-101-clinical-trial-evaluating-kva12123-in-patients-with-advanced-solid-tumor-cancer [SID1234645983]). As previously announced on March 12, 2024, patient enrollment in the clinical trial was suspended due to certain investors indicating that they would not fulfill their funding obligation due in April 2024 pursuant to the previously disclosed private placement financing.

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!

To date, KVA12123 has cleared the fifth of six monotherapy dose levels and two of the four cohorts in combination with pembrolizumab. Initial results demonstrating partial response and stable disease in the combination cohorts and durable stable disease in the monotherapy cohorts were reported earlier this year at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024. Additionally, the initial results of KVA12123 showed a favorable clinical safety and tolerability profile with no dose limiting toxicities and no evidence of CRS-associated cytokines at any dose level.

"We are very pleased to resume enrollment for VISTA-101. KVA12123 has been well tolerated with no dose limiting toxicities and no cytokine release syndrome and we continue to be encouraged by the initial data demonstrated. With enrollment now recommenced, we are focused on successful execution and working towards completing enrollment which we expect to do by the end of 2024," said Thierry Guillaudeux, Chief Scientific Officer of Kineta.

On July 8, Kineta announced that it had entered into an exclusivity and right of first offer agreement (the "Agreement") with TuHURA Biosciences, Inc. ("TuHURA"), a Phase 3 registration-stage immuno-oncology company developing novel technologies to overcome resistance to cancer immunotherapy. As part of the Agreement, Kineta received a concurrent $5 million nonrefundable payment from TuHURA. Kineta and TuHURA are cooperating on the reinitiation of patient enrollment into this trial.

"KVA12123 is a novel, differentiated new treatment alternative for patients with cancer. The completion of the enrollment in the Phase 1 portion of the trial this year is an important milestone for this exciting development program and we are pleased to work closely with the Kineta team to resume enrollment," said James A. Bianco, Chief Executive Officer of TuHURA.

Pursuant to the Agreement, among other things, Kineta has granted TuHURA an exclusive right to acquire Kineta’s worldwide patents, patent rights, patent applications, product and development program assets, technical and business information, and other rights and assets associated with and derived from its development program related to KVA12123, Kineta’s VISTA blocking immunotherapy. This exclusive right shall continue through the first to occur of (a) the execution of any definitive agreement with respect to a potential transaction by TuHURA or one or more of its affiliates and (b) 11:59 PM Eastern Time on October 1, 2024, subject to extension.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On August 19, 2024 Peptomyc S.L., a company developing foundational mini-protein therapeutics for the treatment of cancer, reported that the Company has been issued a patent by the Hong Kong Patent Office protecting its Methods and Composition of Matter (Press release, Peptomyc, AUG 19, 2024, View Source [SID1234645985]).

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!

"We are delighted to announce further protection of our mini-protein therapeutics in Hong Kong. This patent grant strengthens our patent portfolio that protects our unique mini-protein therapeutics, which are able to inhibit MYC, the most dysregulated oncogene in human cancer, in the major geographical areas in oncology," said Laura Soucek, CEO at Peptomyc S.L.

The Company currently maintains over 10 different patent families worldwide covering applications protecting Peptomyc S.L. first-in-modality mini-protein therapeutics in multiple oncological indications, and counts on the services of ABG Intellectual Property and Dechert LLP for the protection of its IP assets.

On August 19, 2024 Purple biotech presented its corporate presentation (Presentation, Purple Biotech, AUG 19, 2024, View Source [SID1234645986]).

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!