On February 9, 2021 Foundation Medicine, Inc. and its collaborators reported results from a prostate cancer study evaluating the landscape of genomic alterations identified by liquid biopsy in over 3,000 patients, as well as assessing concordance of liquid and tissue biopsy in over 800 patients (Press release, Foundation Medicine, FEB 9, 2021, View Source [SID1234574803]). The study demonstrated high concordance between targetable alterations identified using circulating tumor DNA (ctDNA) and tissue-based comprehensive genomic profiling (CGP) in patients with metastatic castration-resistant prostate cancer (mCRPC). It also found that, in many patients, liquid biopsy detects more acquired resistance mechanisms than tissue biopsy. The study, "Genomic analysis of circulating tumor DNA (ctDNA) in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms," was published online in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). These data will also be presented as a poster highlight on Feb. 11 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU).

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Prostate cancer is the second most common cancer in men; 1 in 9 will be diagnosed during their lifetime.1 mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.2 Because there have previously been limited treatment options for this specific disease area, there is generally a high mortality rate. In this study, genomic analysis of plasma collected from 3,334 patients with advanced prostate cancer (including 1,674 samples collected from Clovis Oncology’s TRITON2 and TRITON3 trials in which Foundation Medicine’s liquid biopsy test was utilized to screen patients for enrollment) demonstrated that nearly all (94%) of patients had detectable ctDNA.

"One of the most important findings in this study is that the majority of patients with advanced prostate cancer have abundant circulating tumor DNA that can be tested using comprehensive genomic profiling to support doctors as they consider targeted therapies for their patients," said Geoff Oxnard, M.D., VP, Global Medical Lead, Liquid Franchise at Foundation Medicine. "When tumor tissue is difficult to obtain, as is often the case in patients in mCRPC, liquid biopsy is a proven, minimally-invasive method to secure genomic insights, with the option to reflex to a tissue biopsy if ctDNA turns out to be insufficient to analyze."

Using the collected samples, researchers profiled the landscape of genomic alterations detected in ctDNA and assessed concordance with tissue-based CGP. Using Foundation Medicine’s liquid biopsy test, study investigators detected 93% of the BRCA1/2 mutations that had also been detected using tissue CGP. Additionally, they found that ctDNA harbored some BRCA1/2 alterations not identified by tissue testing. They concluded that the large percentage of mCRPC patients in the study with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations, positions liquid biopsy as a compelling clinical complement to tissue CGP for these patients.

Further, a diverse variety of potential androgen receptor resistance alterations were detected in 42% of patients, which is higher than the percentage detected in the same patients’ tissue biopsies. This points to ctDNA’s capacity to provide a more comprehensive picture of the development of acquired resistance anywhere in the body than the testing of one lesion.

The poster highlight presentation will be available to ASCO (Free ASCO Whitepaper) GU registrants on Feb. 11 at 8 a.m.:

Abstract 25 – Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.

On February 9, 2021 InteRNA Technologies reported the closing of an extended Series B financing round amounting to EUR 18.5M in total (Press release, InteRNA Technologies, FEB 9, 2021, View Source [SID1234574802]). This Series B round was led by AurorA Science, an Italian biotech investment company, along with existing investor Waterman Ventures. Current shareholders Aglaia Oncology Funds and OostNL also contributed to the financing round. The funding will enable the clinical evaluation of the Company’s microRNA lead candidate, INT-1B3, in patients with advanced solid tumors. Furthermore, the proceeds will be used to develop and advance additional proprietary preclinical drug candidates adressing a variety of cancer indications thereby expanding the Company’s pipeline. As part of the Series B financing, Gabriele Campi, PhD, of AurorA Science will join the Board of Directors.

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"This successful extension of the Series B financing round validates the unique potential that microRNAs offer as a therapeutic modality for hard-to-treat cancers," said Dr. Roel Schaapveld, CEO of InteRNA Technologies. "We thank AurorA Science, Waterman Ventures and our other long-term investors for their support in bringing our microRNA technology into the clinic and look forward to evaluate INT-1B3’s unique mode of action, targeting not only the tumor cells themselves but also the disease-promoting tumor microenvironment."

"With this participation in InteRNA Technologies, AurorA Science continues its strong commitment into front-edge science," commented Guido Guidi, Chairman at AurorA Science. "We believe InteRNA has developed a promising innovative technology in this area and look forward to supporting the team on their path forward."

microRNAs are naturally occurring, non-coding strands of RNA that trigger the RNA interference pathway and regulate gene expression by controlling the efficiency of messenger RNA (mRNA) translation into functional proteins. InteRNA designs breakthrough therapies tackling cancer by using the inherent characteristic of microRNAs to simultaneously inhibit multiple mRNA targets in a coordinated fashion, e.g. by blocking activated cancer signaling pathways and preventing activation of alternative disease-promoting pathways.

About INT-1B3

INT-1B3’s unique mechanism of action addresses multiple hallmarks of cancer simultaneously. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components across the PTEN tumor suppressor pathway and the oncogenic PI3K/Akt and Ras/MAPK pathways resulting in inhibition of proliferation and migration and induction of cell cycle arrest and apoptosis. The triggering of the immunogenic tumor cell death (ICD) process as well as downregulation of the adenosine-A2A receptor pathway through inhibition of CD39/CD73 leads to a decrease in immunosuppressive FoxP3/Lag3 regulatory T cells and monocytic myeloid-derived suppressor cells (mMDSCs). As a result, the immune system is activated, and long-term immunity is triggered by recruitment of CD8+ effector T cells leading to decreased metastasis development and improved animal survival compared to anti-PD1 treatment. The created T cell-mediated immune response activity is also transferrable to naive mice via adoptive T cell transfer.

On February 9, 2021 Janssen Pharmaceutica NV (Janssen) announced today results from the final analysis of the Phase 3 TITAN study, which demonstrated the continued statistically significant benefit of apalutamide plus androgen deprivation therapy (ADT) in overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) when compared to placebo plus ADT.1 Results will be featured in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary (ASCO GU) Cancers Symposium, taking place virtually February 11-13, 2021 (Abstract #11; Rapid Abstract Session: Prostate Cancer, February 11 9:30 PM-10:15 PM CET).

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With nearly four years of median follow-up, data from the final analysis of the Phase 3 TITAN study confirmed that apalutamide plus ADT provided statistically significant improvement in OS with a 35 percent reduction in risk of death compared to ADT alone (HR 0.65; p<0.0001).1 This result was almost similar to the OS results in the primary analysis of TITAN despite the subsequent crossover rate of almost 40 percent of the placebo-controlled group to the apalutamide arm.1 The improvement in OS increased to a 48 percent reduction in risk of death after adjusting for patients who crossed over (HR 0.52; p<0.0001).1

"Janssen is committed to uncovering new solutions for patients with prostate cancer as until very recently, there has been little advancement in treatment options for people with metastatic hormone-sensitive prostate cancer,"2 said Dr Catherine Taylor, Vice-president, Medical Affairs, Therapeutic Area Strategy for Europe, Middle East and Africa, Johnson & Johnson Middle East FZ-LLC. "The results of the TITAN final analysis demonstrate that apalutamide with ADT provides a new therapeutic option for people living with advanced, hormone-sensitive prostate cancer."

There was consistent benefit across other endpoints, including improved second progression-free survival (PFS2) (HR 0.62; p<0.0001) and delayed time to castration resistance (HR 0.34; p<0.0001).1 In addition, health-related quality of life (HRQoL), per total Functional Assessment of Cancer Therapy–Prostate (FACT-P), continued to be maintained in both groups. Safety of apalutamide was consistent with previously reported studies.1 Observed adverse events included skin rash, fracture, and falls.1

"The TITAN final analysis is a welcome development for the management of metastatic hormone-sensitive-prostate cancer2 as the data show us that apalutamide with ADT improves long-term clinical benefit and prolonged overall survival, without compromising health-related quality of life for these patients," said Professor Axel Merseburger, Chairman of the Clinic of Urology, Universitatsklinikum Schleswig-Holstein and investigator of the TITAN study. "The results also demonstrate an established safety profile which is encouraging for the management of patients living with advanced forms of prostate cancer."

Initial results from the TITAN study presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) and simultaneously published in The New England Journal of Medicine showed the addition of apalutamide to ADT compared to placebo plus ADT significantly improved the dual primary endpoints of OS and radiographic progression-free survival (rPFS) in patients with mHSPC.3

To date, published results on apalutamide include data from more than 2,000 patients across Phase 3 clinical studies.3 Apalutamide has shown a statistically significant improvement in OS with a consistent safety profile in both approved indications of mHSPC (TITAN) and non-metastatic castration-resistant prostate cancer or nmCRPC (SPARTAN).3

*Professor Axel Merseburger is an investigator of the TITAN study and has been compensated for media work.

About the TITAN Study3,4

TITAN (NCT02489318) is a Phase 3, randomised, placebo-controlled, double-blind study in patients with mHSPC. The study included 1,052 patients in 23 countries across 260 sites in North America, Latin America, South America, Europe, and Asia Pacific. Patients with mHSPC were randomised 1:1 and received either apalutamide (240 mg) plus ADT (n=525), or placebo plus ADT (n=527). The recruitment period for the study spanned from December 2015 to July 2017.3,4 The study included patients with mHSPC with both low- and high-volume disease, those who were newly diagnosed, and those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel for mHSPC.3,4

An Independent Data-Monitoring Committee was commissioned by the sponsor to monitor safety and efficacy.5 Dual primary endpoints of the study were OS and rPFS.1 Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use, and time to skeletal-related events.3,4 Exploratory endpoints included time to prostate specific antigen (PSA) progression, PFS2 and time to symptomatic progression.3,4 For additional study information, visit ClinicalTrials.gov.

About Metastatic Hormone-Sensitive Prostate Cancer

Metastatic hormone-sensitive prostate cancer, also known as metastatic castration-sensitive prostate cancer (mCSPC), refers to prostate cancer that still responds to hormonal therapy and has spread beyond the prostate to other parts of the body.5

About apalutamide

Apalutamide is an orally administered, selective androgen receptor (AR) inhibitor approved in Europe and is indicated in:

adult men for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease, and
in adult men for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC), also known as metastatic castration-sensitive prostate cancer (mCSPC), in combination with androgen deprivation therapy (ADT).6
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

On February 9, 2021 CohBar, Inc. (NASDAQ: CWBR), a clinical stage biotechnology company developing mitochondria based therapeutics to treat chronic diseases and extend healthy lifespan, reported that its Chief Executive Officer, Steven Engle, will present a company overview at the BIO CEO & Investor Digital Conference, being held virtually on February 16 – 18, 2021 (Press release, CohBar, FEB 9, 2021, View Source [SID1234574799]). This presentation will be available on demand for registered attendees.

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On February 9, 2021 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company primarily focused on developing proprietary therapeutics designed to extend life and improve the quality of life for cancer patients, reported the issuance of a patent covering composition of matter for MNPR-101 in Canada, adding to its existing protection in key markets around the world including the US, Europe and Japan (Press release, Monopar Therapeutics, FEB 9, 2021, https://ir.monopartx.com/news/detail/24/monopar-announces-issuance-of-patent-covering-composition-of-matter-for-mnpr-101-in-canada [SID1234574798]).

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"This is an important advancement in our efforts to broaden our global patent estate for MNPR-101," said Chandler Robinson, MD, Chief Executive Officer of Monopar. "MNPR-101 is a novel, first-in-class humanized monoclonal antibody to the urokinase Plasminogen Activator Receptor (uPAR). uPAR is a well credentialed target that appears to be overexpressed in certain aberrantly activated cells, but does not appear much, if at all, in healthy tissue."

In June 2020, Monopar entered into a collaboration with NorthStar Medical Radioisotopes, LLC to utilize MNPR-101 to create a radio-immuno-therapeutic (RIT) to potentially treat severe COVID-19 by targeting and eradicating the aberrantly activated immune cells causing cytokine storm. uPAR targeting by MNPR-101 has wide potential in treating other diseases as well, including cancers, as uPAR is over-expressed in multiple cancer types such as pancreatic and ovarian.

"We are excited about the approval of this composition of matter patent in Canada as it further enables us to explore the potential of MNPR-101 on a global scale," said Andrew Mazar, PhD, Chief Scientific Officer of Monopar.