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Nucleix Announces Publication of Data on Methylation-Based Assay for Detecting High-Risk Non-Muscle Invasive Bladder Cancer in Journal of Clinical Pathology

On June 29, 2020 Nucleix, a liquid biopsy company revolutionizing cancer treatment by detecting the disease earlier, reported the publication of an independent study in the Journal of Clinical Pathology evaluating the company’s urine-based Bladder EpiCheck in patients diagnosed with high-grade non-muscle invasive bladder cancer (NMIBC) (Press release, Nucleix, JUN 29, 2020, View Source [SID1234561540]). The findings support the use of the Bladder EpiCheck methylation biomarkers to detect bladder cancer recurrence in NMIBC patient populations that have undergone instillations.

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The study evaluated 374 patients with a history of high-grade NMIBC who were followed for one year with voided urine cytology and white-light cystoscopy and biopsies, which is standard clinical practice according to European Association of Urology Guidelines. All patients were undergoing treatment with instillations and were selected for cystoscopy based on cytology results. In this study, patients were referred for cystoscopy and biopsies when within cytology categories of high-grade urothelial carcinoma (HGUC), suspicious for high-grade urothelial carcinoma (SHGUC) and atypical urothelial cells (AUC). One hundred and twenty-seven patients in the study (34%) had a pathologically proven recurrence.

"Monitoring for recurrence in patients with high-grade NMIBC undergoing instillations currently requires routine invasive cystoscopies, which are painful procedures for patients and require substantial resources from healthcare providers. Cytology is a routine urine test used in combination with cystoscopy to detect high-grade recurrences; however, it has inherent limitations, such as reader dependency and low sensitivity," said Aharona Shuali, M.D., vice president of medical at Nucleix. "The purpose of this study was to determine if the Bladder EpiCheck test could perform similar to, or better than, cytology in identifying, at a molecular level, which patients have high probability of recurrence and should undergo a cystoscopy and biopsies, and which might be able to avoid these invasive procedures."

The Bladder EpiCheck test was performed together with cytology in all cases and demonstrated a sensitivity of 95%, specificity of 85%, negative predictive value (NPV) of 97% and positive predictive value (PPV) of 76%. Bladder EpiCheck had approximately 90% concordance with HGUC and NHGUC categories, and a high EpiScore (≥90) was strongly correlated with HGUC category (41% vs. 3% in SHGUC, p=0.0001).

The study found that 33% of the negative patients were unnecessarily referred to cystoscopy and biopsy, a finding reflecting cytology’s specificity of 67%. The study demonstrates that if Bladder EpiCheck had been used to select patients for cystoscopy, instead of cytology, this number could have been reduced to 15%, as Bladder EpiCheck specificity was much higher (85%) while detecting 95% of the recurrences.

"These data demonstrate excellent performance of the Bladder EpiCheck test in accurately identifying recurrence vs. non-recurrence in the high-risk NMIBC patient populations without being impacted by the side effects of instillations," said Dr. Francesco Pierconti, associate professor at the Agostino Gemelli University Hospital in Rome, Italy, and lead author of the study. "After two years of experience with Bladder EpiCheck in clinical routine with consistent excellent performance, we are now using it, instead of cytology, to select high-risk NMIBC patients for further workup with cystoscopy and biopsies, allowing us to safely avoid unnecessary procedures," continued Dr. Pierconti, who also serves as professor in the Division of Anatomic Pathology and Histology at the Catholic University of the Sacred Heart in Rome, Italy.

The study titled, "Methylation study of the Paris system for reporting urinary (TPS) categories" has been published online and can be accessed here.

About Bladder EpiCheck

Bladder EpiCheck provides patients and clinicians with a simple, objective urine test to detect recurrence of bladder tumors. The test analyzes subtle disease-specific changes in DNA methylation markers, allowing for the detection of 92% of the high-risk (non Ta-LG) cancers. Bladder EpiCheck demonstrated negative predictive value (NPV) of 99% for high-risk cancer, meaning that when receiving a negative Bladder EpiCheck result, there is 99% chance that no high-risk cancer is present. Bladder EpiCheck is intended for use as a noninvasive method for monitoring of tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer. Bladder EpiCheck is CE-marked and available in Europe. The test is not available for sale in the United States.

Cancer Prevention Pharmaceuticals Submits New Drug Application to the FDA for CPP-1X/sul for Treatment of Familial Adenomatous Polyposis

On June 29, 2020 Cancer Prevention Pharmaceuticals, Inc. (CPP), a private biotech company developing novel therapeutics to prevent cancer and other diseases, reported that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for CPP-1X/sul for treatment of adults with familial adenomatous polyposis (FAP) (Press release, Cancer Prevention Pharmaceuticals, JUN 29, 2020, View Source [SID1234561539]).

FAP is a rare genetic disease that if left untreated progresses to colorectal cancer in nearly 100% of patients. The clinical development of CPP-1X/sul was designed to establish this fixed dose combination product as a potential pharmaco-preventive drug treatment specifically for FAP patients.

"The NDA submission for our lead drug candidate, CPP-1X/sul, represents a significant milestone for FAP patients and their families," said CPP CEO Jeff Jacob. "For most FAP patients, current medical practice involves a lifetime of periodic monitoring as well as highly invasive surgical procedures. If approved, CPP-1X/sul could provide an alternative to surgery for many patients, significantly improving their quality of life."

The FDA’s accelerated approval process allows the agency to approve drugs which address a serious or life-threatening condition based on an intermediate or surrogate endpoint that is likely to predict a clinical long-term benefit. The FDA takes into account such factors as the severity, rarity, or the lack of effective current treatments. The designation has been frequently applied to cancer drugs.

In addition, CPP-1X/sul received an orphan drug designation from the FDA. Among the benefits are eligibility for seven years of market exclusivity upon approval of a drug and tax credits for various costs of clinical testing.

CPP also recently submitted a Marketing Authorization Application (MAA) with the European Union (EU) for CPP-1X/sul for the same indication. The drug received an orphan medicinal product designation for FAP following a favorable assessment provided by the European Medicines Agency’s Committee for Orphan Medicinal Products.

About CPP-1X/sul

CPP-1X/sul is a combination of CPP-1X (eflornithine) and sulindac (CPP-1X/sul). In a clinical trial in patients with large bowel polyps, the CPP-1X/sul combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Based on the close biologic similarities with FAP, a Phase 3 pivotal trial compared this same combination to each drug alone (CPP FAP-310).

"With up to four years of treatment, the combination appears to greatly delay the need for major surgeries in the colon, rectum or surgical pouch. We hope that this new drug regimen will soon be available as an adjunct in the management of FAP patients facing large bowel surgery," said Dr. Alfred Cohen, Chief Medical Officer of CPP.

The CPP FAP-310 trial enrolled 171 FAP patients at 17 research institutes in the U.S., Canada, and Europe. It was the largest ever prospective, controlled study performed in FAP and treated patients for up to 48 months, much longer than any other clinical trial in this population. The study was designed to determine if CPP-1X/sul is superior to sulindac or eflornithine as single agents in delaying time to the first occurrence of any FAP-related event, such as surgical removal of the colon, rectum, surgical pouch, duodenum and/or high-risk adenomas. The trial design included FAP patients with varying lower and upper GI disease. CPP-1X/sul did not demonstrate statistical significance in outperforming the single agents in the overall population; however, further analysis of the data showed key differential effects of the agents in the lower vs upper GI anatomy. Focusing on lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), the data showed statistically significant benefit for CPP-1X/sul vs both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. Also, the safety profile of the combination did not significantly differ from that already known for the single agents to support the overall safety assessment of the fixed combination product for long-term therapeutic use.

Oncology Venture signs agreement to out-license two pipeline assets as part of prioritized portfolio strategy

On June 29, 2020 Oncology Venture A/S ("OV" or the "Company") reported that it has signed a definitive agreement out-licensing two clinical pipeline assets, LiPlaCis and 2X-111, to Smerud Medical Research International for further clinical and commercial development (Press release, Oncology Venture, JUN 29, 2020, View Source [SID1234561538]). Under the terms of the agreement, OV will receive regulatory milestone fees of nearly US $30M plus royalties on sales for each drug payable to OV if all the milestones are met . OV also terminated its prior license agreement with Cadila Pharmaceuticals for the development of LiPlaCis in India.

In September 2019, OV announced a significant restructuring, including a new executive management team and a streamlined, prioritized focus on advancing its top three clinical-stage oncology programs towards approval and commercialization. The Company has worked towards establishing partnerships to advance the portfolio while monetizing the value for the Company as part of this ongoing effort.

Smerud Medical Research International AS ("Smerud") is a leading European-based clinical contract research organization (CRO) with expertise in the development of precision cancer drugs. Smerud has previously worked with OV on its LiPlaCis program as well as several other clinical programs. Under their new agreement, Smerud will advance the specific development of LiPlaCis in late stage metastatic breast cancer and 2X-111 in glioblastoma multiforme, in connection with each program’s DRP companion diagnostic.

Steve Carchedi, CEO of Oncology Venture, stated, "Partnering with Smerud allows us to continue development of these two clinical therapeutics together with their DRP companion diagnostics, and to monetize our clinical assets for the benefit of our Company and our shareholders. We remain enthusiastic about the therapeutic potential of both LiPlaCis and 2X-111 together with their DRP companion diagnostics, and we are very pleased to reach this important step towards value creation with these two portfolio assets, and, if all milestones are met, will bring us more than US $30M in regulatory milestone fees plus royalties on future drug sales. Furthermore, this provides us with the opportunity to focus on driving our most advanced programs towards commercialization."

Knut Smerud, CEO of Smerud Medical Research, stated, "Over the past few years, we have been closely involved in advancing the LiPlaCis clinical trial in Denmark through a joint EUROSTARS grant obtained together with OV, and we have seen the benefits that the DRP technology can bring to drug development and, most importantly, to patients. It is not often we get the chance to take over both the full financial and operational responsibility of an ongoing clinical development program, which has already shown very promising interim data, and which addresses the needs of a very high number of patients across the world. Our expectation is that 2X-111 will be just as exciting as LiPlaCis, and therefore we are very enthusiastic about now having the chance to lead the advancement of both of these unique personalized cancer treatments."

Gan & Lee Raises $360 Million in Shanghai IPO; Trades up 44%

On June 29, 2020 Gan & Lee Pharma reported that it completed a Shanghai IPO that raised $360 million for the company, which specializes in insulin treatments (Press release, Gan and Lee Pharmaceuticals, JUN 29, 2020, View Source [SID1234561536]). In initial trading, the stock was halted after it moved up to the Shanghai Exchange’s 44% daily limit, a market capitalization of over $5 billion. The Beijing company’s products consist of recombinant insulin analogues (third-generation insulin) and APIs that it markets in China and in foreign countries. The company’s founder, Dr. Zhongru Gan, said Gan & Lee plans to develop R&D for oncology drugs, eukaryotic and prokaryotic protein engineering, and products for cardiovascular and metabolic diseases.

Genmab Announces Very Favorable Topline Results from Phase 2 Clinical Trial of Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer

On June 29, 2020 Genmab A/S (Nasdaq: GMAB) reported very favorable topline results from the Phase 2 single-arm clinical trial known as innovaTV 204 evaluating tisotumab vedotin administered every three weeks for the treatment of patients who have relapsed or progressed on or after prior treatment for recurrent or metastatic cervical cancer (Press release, Genmab, JUN 29, 2020, View Source [SID1234561535]). Results from the trial showed a 24 percent confirmed objective response rate (ORR) by independent central review (95% Confidence Interval: 15.9% – 33.3%) with a median duration of response (DOR) of 8.3 months. The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia, epistaxis (nose bleeds), nausea, conjunctivitis, fatigue and dry eye. The data will be submitted for presentation at an upcoming medical meeting.

Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor, which is expressed on cervical cancer and can promote tumor growth, angiogenesis and metastases.1 Standard therapies for previously treated recurrent and/or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent with median overall survival ranging from 6.0 to 9.4 months, in an all-comers population.1-8 Tisotumab vedotin is being developed in collaboration with Seattle Genetics.

"After treatment with first-line chemotherapy regimens, there is a high unmet need for new effective and tolerable treatment options for women with advanced cervical cancer, regardless of biomarkers and histology," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "These promising topline data from innovaTV 204 will be the basis of further engagement with the U.S. FDA as we continue to progress and expand our tisotumab vedotin development program in solid tumors with our partner."

Additional clinical trials of tisotumab vedotin are currently enrolling patients, including in combination with pembrolizumab, carboplatin or bevacizumab, and with a weekly dosing schedule in patients with locally advanced or metastatic cervical cancer. Tisotumab vedotin is also being evaluated in other tissue factor expressing tumor types, including ovarian and other solid tumors.

About innovaTV 204 Trial
The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with bevacizumab if eligible per local standards. Additionally, patients were eligible if they had received up to two prior lines of therapy in the metastatic setting. In the study operationalized by Genmab, 101 patients were treated with tisotumab vedotin at multiple centers in the U.S. and Europe. The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review. Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

The study was conducted by Genmab in collaboration with Seattle Genetics Inc., European Network of Gynaecological Oncological Trial Groups (ENGOT) and Gynecologic Oncology Group (GOG). For more information about the Phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Cervical Cancer
Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with invasive cervical cancer in the U.S. in 2020, with approximately 4,200 deaths.9 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.10 Routine medical examinations and the human papillomavirus (HPV) vaccine have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic.

About Tisotumab Vedotin
Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab’s fully human monoclonal antibody specific for tissue factor and Seattle Genetics’ ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a protein that can promote tumor growth, angiogenesis and metastases.1 Based on its high expression on many solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seattle Genetics, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

Tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in a range of solid tumors, including recurrent and/or metastatic cervical cancer, ovarian cancer and in combination with other commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three weeks dosing schedule.