On June 27, 2024 Oncopeptides, a biotech company focused on difficult-to-treat cancers, reported that the first candidate drug based on the company´s unique platform for Small Polypeptide based innate Killer Engagers (SPiKE) has been selected (Press release, Oncopeptides, JUN 27, 2024, View Source [SID1234646776]).

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!

The SPiKE platform uses multi-specific constructs, able to bind to multiple targets simultaneously. The first drug candidate, OPSP1, is a bi-specific construct designed to both engage natural killer cells, a type of immune cell, and target cancer cells. The goal of OPSP1 is to prove the ability of the SPiKE platform to activate these natural killer cells. To do this, OPSP1 targets a specific protein called BCMA that is expressed in some cancers including multiple myeloma. By targeting this protein, Oncopeptides will be able to assess how well the SPiKE platform can activate natural killer cells to fight cancer, a crucial step before continued clinical development of the SPiKE platform.

"There is significant potential in NK cell-mediated therapy for difficult-to-treat cancers," says Dr. Karl-Johan Malmberg, professor at Oslo University and Karolinska Institutet. "Despite the substantial advancements in current treatments, the reality is that resistance to these therapies often develops. This underscores the urgent need for new and innovative treatment options to address this unmet medical need."

NK cell-mediated therapy represents a promising avenue in cancer immunotherapy, with ongoing research aimed at overcoming existing challenges and enhancing its therapeutic potential. As a next step for Oncopeptides, a first-in-human clinical trial will be designed to evaluate the safety, efficacy, and overall therapeutic potential of OPSP1.

"The ability to show a promising product pipeline behind its flagship product is important for a growing biotech company. Following the accomplishments we have seen with our first technology platform PDC, where we have an approved product, we are excited to also announce progress with SPiKE, our second technology platform," says Sofia Heigis, CEO of Oncopeptides. "This milestone is a major step forward in our ambition to ensure that Oncopeptides can continue to provide hope for patients suffering from difficult-to-treat cancers, and value to shareholders investing in our science."

A pre-clinical project for the SPiKE platform has received a financial grant from the Eurostars 3-program, co-financed by the European Union research and innovation program "Horizon Europe" and is driven by an international research consortium that includes world-leading expertise from the department of Cancer Immunology at Oslo University Hospital, Pharmatest Services Ltd in Turku, Finland and the Royal Institute of Technology in Stockholm (KTH), from where the technology originally stems. With this grant, Sweden’s Innovation Agency, Vinnova, has provided Oncopeptides resources to develop pre-clinical proof of concept for a novel synthetic small polypeptide for the treatment of multiple myeloma.

On June 27, 2024, Coherus BioSciences, Inc. (the "Company") entered into an exclusive license and distribution agreement (the "License Agreement") with Apotex, Inc. ("Apotex"), pursuant to which, the Company has granted to Apotex an exclusive license under the Company’s rights to toripalimab to commercialize toripalimab within Canada (Filing, 8-K, Coherus Biosciences, JUN 27, 2024, View Source [SID1234644648]). As previously disclosed, on February 1, 2021, Coherus BioSciences, Inc. (the "Company") announced that it had entered into the exclusive license and commercialization agreement (the "Collaboration Agreement") with Shanghai Junshi Biosciences Co., Ltd. ("Junshi Biosciences") for the co-development and commercialization of toripalimab, Junshi Biosciences’ anti-PD-1 antibody, in the United States and Canada. Pursuant to the Collaboration Agreement, the Company has the right to grant sublicenses to third parties to commercialize toripalimab within Canada.

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!

Pursuant to the License Agreement, Apotex agreed to pay to the Company an upfront payment of $6.25 million United States Dollars ("USD"). In addition, Apotex agreed to pay to the Company the USD equivalent of up to an aggregate of up to $51.5 million Canadian Dollars ("CAD") in milestone payments in connection with the achievement of certain regulatory and sales milestones with respect to toripalimab in Canada. Finally, Apotex agreed to pay to the Company a low double-digit percentage of any future net sales of toripalimab in Canada that the Company will subsequently pay to Junshi Biosciences pursuant to the Collaboration Agreement.

The License Agreement term continues until the tenth year after the first commercial sale of toripalimab in Canada, subject to an extension for a subsequent ten year term at the option of Apotex. Apotex may terminate the License Agreement for any reason after a specified notice period, the License Agreement will terminate automatically if the rights granted to the Company by the Collaboration Agreement are terminated, if there is material breach that is not cured, if there are certain challenges to licensed patents by Apotex and in the case of certain insolvency events.

The foregoing description of the material terms of the License Agreement is qualified in its entirety by reference to the full text of the License Agreement, which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024.

On June 27, 2024 Tubulis reported that the U.S. Food and Drug Administration ("FDA") has granted Fast Track designation to its lead antibody-drug conjugate (ADC) TUB-040 for the treatment of patients with platinum-resistant ovarian cancer (Press release, Tubulis, JUN 27, 2024, View Source [SID1234644591]). TUB-040 is a next-generation NaPi2b-targeting Exatecan ADC based on Tubulis’ proprietary P5 technology with superior biophysical properties that demonstrated effective and durable responses in a range of preclinical models, including ovarian cancer. The candidate is currently being evaluated in a multicenter Phase I/IIa study (NAPISTAR 1-01, NCT06303505) in patients with platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC), who have exhausted other available treatment options.

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!

"Almost all patients with ovarian cancer who are not cured by initial therapy will develop resistance to platinum-based therapy over time. Once platinum-resistant, therapeutic options for these patients are poor with highly unsatisfactory outcomes. The FDA´s Fast Track designation of TUB-040 is an important step in the development of TUB-040 to provide these women with urgently needed new therapeutic options," said Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer of Tubulis. "The FDA decision brings us one step closer to our goal of delivering the true value of ADCs to patients in need, and we are grateful for the agency’s support on this path to develop TUB-040 fast and efficiently.

The Fast Track status granted by the FDA is designed to facilitate the development and expedite the review of new therapies that are intended to treat serious conditions and have the potential to address an unmet medical need. Programs granted Fast Track designation are subject to more frequent interactions with the FDA during clinical development and may be eligible for accelerated approval and/or priority review if certain criteria are met.

TUB-040 is currently being evaluated in a multicenter, first-in-human, dose-escalation and optimization Phase I/IIa study. The trial is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as monotherapy and is being conducted in the US, UK, Spain, Belgium and Germany. Phase Ia includes dose escalation and will determine the safety and the maximum tolerated dose or identified dose for optimization, while Phase IIa will focus on dose optimization, safety, and preliminary efficacy of TUB-040.

About Platinum-resistant Ovarian Cancer

Ovarian cancer (OC) is the leading cause of death among women diagnosed with gynecological cancers. While early-stage disease has a high survival rate, OC is often diagnosed at later stages due to its non-specific clinical symptoms and lack of preventive screening methods.2 The current standard of care is platinum-based therapy, but approximately 20% of patients are platinum-resistant during each treatment line.3,4 Platinum-resistant OC is defined as disease recurrence during or within 6 months after completing the platinum-based chemotherapy. Platinum-resistant OC is associated with poor disease outcomes and low response rates to subsequent chemotherapy treatment. The median survival for these patients is 12-16 months, highlighting the high unmet medical need of this patient population. 5,6

About TUB-040 and the P5 Technology

Tubulis’ lead antibody-drug conjugate (ADC) TUB-040 is directed against Napi2b, an antigen highly overexpressed in ovarian cancer and lung adenocarcinoma. It consists of an IgG1 antibody targeting Napi2b connected to the Topoisomerase I inhibitor Exatecan through a cleavable linker system based on the company’s proprietary P5 conjugation technology with a homogeneous DAR of 8. P5 conjugation is a novel chemistry for cysteine-selective conjugation that enables ADC generation with unprecedented linker stability and biophysical properties. It originated from the fundamental work of Prof. Christian Hackenberger at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), which unlocked the use of phosphorus chemistry for superior bioconjugation. Preclinical pharmacokinetic analysis also demonstrated that TUB-040 efficiently delivers its payload to the tumor while reducing off-site toxicities. The candidate is currently being investigated in a multicenter Phase I/IIa study (NAPISTAR 1-01, NCT06303505) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy.

On June 27, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA (cfDNA) and genetic testing, reported a new gastroesophageal cancer trial, DECIPHER, that will utilize the company’s personalized and tumor-informed molecular residual disease (MRD) test, Signatera, to guide patient selection and assess the rate of MRD clearance in patients being treated for gastroesophageal cancer (Press release, Natera, JUN 27, 2024, View Source [SID1234644590]).

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!

DECIPHER (Developing ctDNA Guided Adjuvant Therapy for Gastroesophageal Cancer) is a single-arm, open-label phase II trial, and the first trial to evaluate the efficacy of a HER2-directed antibody-drug conjugate in gastroesophageal adenocarcinoma (EGC) patients in the adjuvant setting. The study plans to enroll 25 patients from more than 10 sites across the United Kingdom. Patients who are Signatera-positive following neoadjuvant chemotherapy and surgery will forgo standard-of-care adjuvant chemotherapy and receive the investigational therapy for a maximum of eight cycles. Signatera will be used to measure MRD-positivity following surgery and serially thereafter, with MRD clearance serving as the primary endpoint.

"With an adaptive approach aimed at eliminating MRD, DECIPHER is designed to offer patients a second chance at a cure when they have not responded to standard of care therapies," said Dr. Elizabeth Smyth, M.D., consultant in medical oncology at Oxford University Hospitals NHS Foundation Trust l and chief investigator of the trial. "Signatera’s personalized, tumor-informed approach, which has demonstrated high sensitivity across several different cancer types including EGC, will be a key component of this study."

This launch of DECIPHER follows data from the PLAGAST study presented last month at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The data showed that EGC patients who were Signatera-positive following neoadjuvant FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy and surgical resection were at an extremely high risk of disease progression by 12 months, despite standard of care adjuvant treatment, and had a 24-month overall survival rate of zero.1

Gastroesophageal cancer is a common global cancer that has sustained a nearly 2.5-fold increase in incidence over the last two decades.1 Patients with early-stage disease are typically treated with neoadjuvant chemotherapy, followed by surgery and adjuvant chemotherapy. Despite this aggressive and multimodal approach, treatment is curative in less than 50 percent of patients.2

"We are pleased to work with leading investigators in the UK on the first interventional trial for Signatera in gastroesophageal cancer," said Adham Jurdi, M.D., senior medical director of oncology at Natera. "With DECIPHER, we aim to demonstrate how the pairing of Signatera with innovative therapies can potentially enable new personalized treatment options and ultimately improve outcomes for EGC patients."

DECIPHER will be featured today, June 27, 2024, in a poster at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2024 in Munich, Germany. The poster is entitled, "A single arm phase II trial of trastuzumab deruxtecan in patients with gastro-oesophageal adenocarcinoma cancer who are ctDNA and HER2 positive: DECIPHER".

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 60 peer-reviewed papers.

On June 27, 2024 REVEAL GENOMICS, S.L., a Barcelona-based biotechnology start-up seeking to revolutionize precision oncology through biomarker innovation, reported the results of the study "HER2DX ERBB2 mRNA assay Following Trastuzumab-Based Chemotherapy in HER2-Positive Advanced Gastric Cancer" presented at ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2024 in Munich, showing that HER2DX genomic test demonstrates significant potential in refining patient selection for trastuzumab-based chemotherapy in HER2-positive advanced gastric cancer (Press release, REVEAL GENOMICS, JUN 27, 2024, View Source [SID1234644589]).

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!

HER2+ advanced gastric cancer treatment shows variable response to trastuzumab plus chemotherapy, indicating the need for precise biomarkers. The HER2DX is a promising tool for enhancing patient selection by quantifying ERBB2 mRNA expression levels, and classifying tumor samples into different groups: low, medium, and high.

Patricia Villagrasa, REVEAL GENOMICS’ CEO, says, "This study marks the first time that HER2DX has been applied outside of breast cancer, illustrating its precision and potential across different oncological applications. Our findings underscore the test’s capability to improve patient selection, fundamentally transforming the treatment approach for those battling advanced gastric cancer. This represents a significant milestone in our ongoing commitment to advance personalized medicine."

Dr. Tamara Saurí, medical oncologist, coordinator of upper- gastrointestinal cancers, and principal investigator of the study at Hospital Clinic of Barcelona, stresses: "Advanced HER2+ gastric cancer treatment shows variable response to trastuzumab plus chemotherapy, indicating the need for precise biomarkers. HER2DX not only addresses a crucial unmet need but also explains why HER2-positive gastric cancers often have poorer responses compared to HER2-positive breast cancers. By revealing tumor diversity and expression patterns, the test might guide the development of more effective, personalized treatment strategies. This insight is crucial as we explore novel anti-HER2 therapies alone or in combination, aiming to improve patient outcomes."

HER2DX: beyond breast cancer
The study utilized the HER2DX genomic test with a focus on the ERBB2 score to evaluate its association with survival outcomes. The HER2DX genomic test was evaluated in 60 patients with HER2+ advanced gastric cancer treated at two hospitals in Spain (Hospital Clinic of Barcelona and Hospital General Granollers).

The study highlighted the test’s effectiveness, showing a hazard ratio of 0.38 for PFS, indicating a 62% reduction in the risk of progression for patients with high ERBB2 mRNA levels compared to those with low levels. Additionally, the hazard ratio for OS was 0.53, reflecting a 47% reduction in the risk of death for patients in the high ERBB2 mRNA group compared to the low group.

Comparative Analysis with Breast Cancer
The study also included a comparative analysis of ERBB2 expression between gastric and breast cancers, revealing generally lower levels of ERBB2 in gastric cancer, including within the HER2 +3 immunohistochemical category. This comparison further highlights the nuanced role of ERBB2 across different cancers and the need for better methods to quantify this target.

About HER2DX️
HER2DX️ is the world’s first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS️ since January 2022, the HER2DX is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX️ is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e., tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX️ predicts:

Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2+ breast cancer.
About GASTRIC CANCER
According to the article "The current and future incidence and mortality of gastric cancer in 185 countries, 2020−40: A population-based modeling study" published online by eClinicalMedicine in 2022: "In total, approximately 1.1 million new cases and 770,000 deaths of gastric cancer were estimated in 2020. Incidence rates were on average 2-fold higher in males than females (15.8 and 7.0 per 100,000, respectively) with variation across countries. The annual burden of gastric cancer is predicted to increase to approximately 1.8 million new cases and 1.3 million deaths by 2040."