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]).

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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 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported progress updates for its two lead programs, MRT-2359, an MGD being developed for MYC-driven solid tumors, and MRT-6160, a VAV1-directed MGD in development for systemic and neurological autoimmune diseases (Press release, Monte Rosa Therapeutics, JUN 27, 2024, View Source [SID1234644571]).

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"We are pleased with the progress of our two lead programs," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "We continue to successfully recruit and advance our ongoing MRT-2359 Phase 1/2 study. We are encouraged by our initial safety and pharmacodynamic assessment of the 0.5 mg dose using the 21 days on, 7 days off regimen and, as such, we consider the 0.5mg dose with the 21 days on, 7 days off regimen a potential recommended Phase 2 dose. Importantly, this regimen allows for dosing of MRT-2359 twice as frequently per cycle compared to the 5 days on, 9 days off regimen previously explored in our study. Based on the favorable safety assessment for the 0.5 mg dose, we initiated a 0.75 mg, 21 days on, 7 days off dose cohort, which is currently ongoing. In the second half of the year, we expect to make a determination of our definitive recommended Phase 2 dose, share updated clinical efficacy and safety results from the dose escalation arm of the trial, and initiate enrollment of our Phase 2 expansion cohorts."

Dr. Warmuth continued, "Moreover, today we are excited to announce the submission of our Investigational New Drug (IND) application to the U.S Food and Drug Administration (FDA) for MRT-6160, a highly selective and orally bioavailable MGD directed against VAV1. This milestone positions us to soon have our second highly promising program in the clinic, pending FDA clearance. We believe our IND is the first for a rationally designed MGD for a non-oncology indication, representing a significant step forward for Monte Rosa and the protein degradation field. MRT-6160 has been shown to potently and selectively degrade VAV1 in human T and B cells and has demonstrated encouraging results in multiple preclinical studies of autoimmune disease, including models of inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. We expect to initiate a Phase 1 single ascending dose / multiple ascending dose (SAD/MAD) study later this summer and anticipate sharing initial clinical data for our MRT-6160 program in Q1 2025."

Monte Rosa continues to evaluate MRT-2359 in a Phase 1/2 clinical trial in MYC-driven solid tumors (NCT05546268). The Company has completed enrollment of the 0.5 mg, 21 days on, 7 days off dose escalation cohort, and tolerability has been favorable with an AE profile similar to what has been observed using the 5 days on, 9 days off schedule at the same dose level. Enrollment is ongoing in the 0.75 mg, 21 days on, 7 days off dose escalation cohort. The Company is evaluating possible Phase 2 expansion cohorts, and anticipates utilizing a two-stage design to enroll patients to evaluate responses in each selected expansion cohort before proceeding with further enrollment.

MRT-6160 is on track for initiation of a Phase 1 SAD/MAD study this summer with Phase 1 clinical data expected in Q1 2025. Monte Rosa expects to subsequently initiate proof-of-concept (POC) studies in autoimmune/inflammatory diseases including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies in dermatology, rheumatology, and neurology indications. Preclinical efficacy data in multiple models of autoimmune/inflammatory diseases and preclinical GLP toxicology data suggest the potential for a highly differentiated profile in T-cell, T/B-cell, and Th17-mediated systemic and neurologic autoimmune diseases.

About MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in preclinical studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple systemic and neurological autoimmune indications, such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and dermatological disorders. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in several in vivo autoimmunity models.

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.

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"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 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapeutics for oncology, reported that the Company received productive feedback from its Type C meeting with the U.S. Food and Drug Administration (FDA), supporting the planned potential registration-enabling trial for pelareorep in HR+/HER2- metastatic breast cancer (mBC) (Press release, Oncolytics Biotech, JUN 27, 2024, View Source [SID1234644572]). The FDA supports progression-free survival as the primary endpoint of the study, with overall survival as a key secondary endpoint. The Company’s proposed study will enroll patients who have failed hormonal therapy and have received no more than one line of antibody-drug conjugate (ADC) therapy.

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"Aligning with the FDA on key design elements and objectives of our planned registrational trial for pelareorep marks a critical step towards bringing this innovative treatment to patients," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics. "Our de-risked program builds on compelling data and key learnings from two randomized studies, BRACELET-1 and IND-213, which demonstrated clinically meaningful benefit in patients receiving pelareorep and paclitaxel compared to paclitaxel alone. Additionally, translational data from the AWARE-1 study highlights pelareorep’s immune-mediated mechanism of action in breast cancer patients. We are now well-positioned to deliver on our mission of making pelareorep available to breast cancer patients in need of better treatment options."

Wayne Pisano, Interim CEO and Chair of the Board of Oncolytics, commented, "We are appreciative of the thoughtful dialog with the FDA and are pleased to have reached an important regulatory milestone that provides a clear path forward for pelareorep’s advancement towards registration in HR+/HER2- mBC. Looking ahead, initiating a registration-enabling trial has become a major corporate objective, and in parallel, we remain on track to report survival data from the BRACELET-1 study in HR+/HER2- mBC in the second half of the year. We believe these data will further bolster our compelling data package and underscores the therapeutic potential of pelareorep. We remain committed to improving the standard of care and addressing the high unmet medical needs of these patients."

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.

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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.