On December 16, 2019 Sysmex Inostics reported that new data presented by Dr. Ben Ho Park, Professor of Medicine and Director of Precision Oncology at Vanderbilt University and colleagues at the recent San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas demonstrated a potential utility for monitoring tumor-specific mutations (TSMs) in the circulation of early stage triple-negative breast cancer patients (Press release, Sysmex Inostics, DEC 16, 2019, View Source [SID1234552414]). The investigators utilized Sysmex Inostics’ highly sensitive SafeSEQ technology to detect rare variants down to 0.05% mutant allele fraction (MAF) to explore the rate of detection of ctDNA variants independent of the need for a tissue biopsy.

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This initial data was generated as a pilot investigation as part of the PREDICT DNA trial ("Pathologic Response Evaluation and Detection In Circulating Tumor DNA"), the first prospective, multi-center study designed to verify cell-free circulating tumor DNA (ctDNA) as a biomarker for treatment response and recurrence in early stage breast cancer, with the primary aim of determining the negative predictive value of a negative ctDNA result after neoadjuvant therapy for the achievement of pathologic complete response. Essentially the trial measures whether patients who undergo neoadjuvant chemotherapy to treat tumors prior to surgery still have ctDNA in their blood after the therapy but before surgery. Dr. Park shared, "We give chemotherapy to early stage breast cancer patients and probably 70 percent of those patients don’t need it, but we generally can’t define who has micro-metastatic disease and who doesn’t." The PREDICT DNA trial is aiming to understand whether ultrasensitive next-generation sequencing with a SafeSEQ targeted cancer mutation panel can identify and monitor ctDNA of early-stage breast cancer patients to more precisely administer neoadjuvant therapy and surgery in newly diagnosed patients.

A total of 228 patients with Stage II and III triple-negative or HER2-positive breast cancer have been enrolled at 22 sites, of which 77 with matched pre- and post-neoadjuvant therapy samples were available at the time of the pilot study. Using SafeSEQ, tumor-specific mutations were identified in 48% (37/77) of the pre therapy samples, of which 89% had detectable plasma TP53 mutations, 11% had PIK3CA mutations, and 11% had co-occurring TP53 and PIK3CA mutations. A cohort of patient plasma specimens underwent orthogonal testing with OncoBEAM digital PCR technology, with 100% concordance of results with SafeSEQ.

The authors of the study concluded that SafeSEQ’s ultrasensitive detection of ctDNA has ‘significant clinical implications as an affordable and non-invasive first-pass assay in patients with sparse tumor biopsy tissue’. This preliminary data also demonstrates clinical feasibility of identifying tumor-specific mutations in individuals using minimally-invasive liquid biopsy before neoadjuvant treatment for personalized disease response monitoring without the need for biopsy tissue for NGS analysis.

"There is a paramount need for prospective studies using liquid biopsy," said Dr. Ben Ho Park, Professor of Medicine and Director of Precision Oncology, Vanderbilt University Medical Center. "These exciting preliminary results from the PREDICT DNA Trial represent an important first step in understanding the role of liquid biopsy testing for the management of early stage breast cancer and helping the medical community map out a path to make precision medicine a reality for patients across the continuum of care."

Presentation Details: Saturday 14 December 2019 7am – 9am, Poster Session 6, P6-10-05

Hunter, N. et al (2019) Pathologic Response Evaluation and Detection In Circulating Tumor DNA (PREDICT DNA): Initial results piloting a tissue-biopsy independent method of identifying and monitoring tumor-specific mutations in early stage breast cancer: TBCRC 040 Presented at the San Antonio Breast Cancer Symposium in San Antonio, Texas. ClinicalTrials.gov Identifier: NCT02743910

This work supported by the Translational Breast Cancer Research Consortium.

On December 16, 2019 Zimmer Biomet Holdings, Inc. (NYSE and SIX: ZBH), a global leader in musculoskeletal healthcare, reported that its Board of Directors has approved the payment of a quarterly cash dividend to stockholders for the fourth quarter of 2019 (Press release, Zimmer Holdings, DEC 16, 2019, View Source [SID1234552413]).

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The cash dividend of $0.24 per share is payable on January 31, 2020 to stockholders of record as of the close of business on December 27, 2019.

On December 16, 2019 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition") reported an agreement by its subsidiary Belgian Volition SPRL to acquire an epigenetic reagent company, Octamer GmbH ("Octamer"), for approximately $725,000 consisting of cash and shares of restricted common stock of Volition (Press release, VolitionRX, DEC 16, 2019, View Source [SID1234552412]). The closing of the acquisition is subject to customary conditions and is expected to occur in January 2020. This strategic acquisition helps secure the supply of one of the key components of Volition’s Nu.QTM tests, the recombinant nucleosome used as the calibrant.

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Commenting on the announcement Cameron Reynolds, Chief Executive Officer of Volition said, "I could not be happier that through this acquisition we will be working with one of the world’s leading nucleosome experts, Dr. Adrian Schomburg. Not only will this deal secure the supply of a wide range of our key components, but it will also facilitate the transfer of know-how and expertise so that we can develop the capability to manufacture recombinant nucleosomes ourselves. This deal enhances our goal of becoming one of the world’s leading epigenetics companies."

Regarding the transaction, Dr. Adrian Schomburg, Founder and CEO of Octamer said, "I believe that the progress that Volition has made to date on nucleosomes in circulation is very exciting and have confidence that this deal is a good convergence of our two technologies and companies. I look forward to working together to bring these transformative diagnostic agents into everyday diagnostic practice."

In addition to nucleosomes, Octamer manufactures and sells histones, octamers and DNA templates. These reagents can be used for custom applications in epigenetic research and drug discovery. Octamer is already revenue generating and has many business development opportunities that Volition plans to exploit in 2020 and beyond.

About the Acquisition

The aggregate purchase price is €650,000 Euros (approximately $725,000), consisting of €350,000 cash and approximately 73,000 shares of common stock of Volition, for 100% of the outstanding shares of Octamer. The shares of common stock will be issued by Volition to the seller in a private placement in reliance on an exemption from the registration requirements of the Securities Act of 1933, as amended, and the rules and regulations promulgated thereunder. The shares of common stock will not be registered under the Securities Act or any state securities laws and unless so registered may not be offered or sold in the United States except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws. In connection with the transaction, the parties will also enter into a five-year royalty agreement the provides for single-digit royalties based on the sales by Octamer of recombinant nucleosomes to pharmaceutical companies for use in the development, manufacture and screening of molecules for use as therapeutic drugs, as well as a consulting arrangement with Dr. Schomburg. The acquisition includes the transfer of Standard Operating Procedures and key assets in addition to onsite training for Belgian Volition scientists.

On December 16, 2019 ORIC Pharmaceuticals, a privately held, clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that new preclinical data on its lead program, ORIC-101, a selective and potent glucocorticoid receptor (GR) antagonist currently being investigated in a Phase 1b clinical trial in combination with nab-paclitaxel in patients with advanced solid tumors, at the 2019 San Antonio Breast Cancer Symposium (Press release, ORIC Pharmaceuticals, DEC 16, 2019, https://www.prnewswire.com/news-releases/oric-pharmaceuticals-presents-preclinical-data-on-glucocorticoid-receptor-antagonist-at-2019-san-antonio-breast-cancer-symposium-300974917.html [SID1234552411]).

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The ORIC-101 preclinical data were presented in a poster titled, "ORIC-101 Robustly Inhibits the Glucocorticoid Pathway and Overcomes Chemoresistance in TNBC" (Program Number: P6-03-24, Abstract #2507).

GR is highly expressed in a variety of cancers including prostate, pancreatic, ovarian, triple-negative breast cancer (TNBC) and endometrial cancers. Preclinical studies have indicated that activation of GR reduces the efficacy of chemotherapy, while inhibition of GR with the antagonist ORIC-101 enhances the efficacy of chemotherapy in multiple solid tumor models.

ORIC-101 potently sensitizes TNBC cells to chemotherapy by reversing GR-mediated resistance through the epithelial-to-mesenchymal transition and anti-apoptosis pathways, in both in vitro and in vivo preclinical models. The poster presented a GR activation signature developed at ORIC that includes the direct GR transcriptional targets FKBP5 and GILZ and subsequently validated both genes as ORIC-101 pharmacodynamic (PD) biomarkers. The relationship between PD biomarkers, pharmacokinetics and efficacy in preclinical models was also assessed. The data demonstrated that ORIC-101 robustly inhibits the transcriptional induction of PD biomarkers and fully reverses GR-mediated chemoresistance in vitro and in vivo.

In addition to its ongoing Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel, ORIC is also conducting a second Phase 1b clinical trial of ORIC-101 in combination with enzalutamide in patients with metastatic prostate cancer.

On December 16, 2019 Medivir AB (Nasdaq Stockholm: MVIR) reported that the independent safety committee (IDMC) for the phase II study of birinapant in combination with pembrolizumab (Keytruda) in patients with MSS colorectal cancer has performed the planned futility analysis (Press release, Medivir, DEC 16, 2019, View Source [SID1234552410]). The primary objective of the phase II study was an improved clinical response to treatment measured as 20% ORR (Overall Response Rate). IDMC’s recommendation is that the study should be terminated as the analysis indicates that it is unlikely that the study’s objectives will be met. Medivir has therefore decided to discontinue the recruitment of patients and to end the study.

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"We are disappointed that the combination therapy with birinapant and pembrolizumab did not work better in this difficult-to-treat patient group where monotherapy with pembrolizumab has very limited effect", said Dr Uli Hacksell, CEO of Medivir. "But we still see a potential for other combination therapies where birinapant could offer patients improved treatment. One example is the ongoing phase I study of a combination of birinapant and radiation therapy in patients with head and neck cancer."

A total of 15 patients with advanced MSS colorectal cancer were recruited in the phase II study, 14 of which were included in the futility analysis. The combination therapy was considered acceptable from a safety perspective, but none of the patients showed a clear clinical efficacy response. Four patients were judged to have stable disease while 10 were judged to have disease progression.

The phase II study was conducted as a collaboration between Medivir and MSD, who provided pembrolizumab.

For further information, please contact:
Uli Hacksell, CEO, Medivir AB, phone: +46-(0)-8-5468-3100.

Medivir AB is obliged to make this information public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 16.00 CET on 16 December, 2019.

About Birinapant

Birinapant is being developed to enhance responses, and extend survival, of patients with solid tumors where existing treatments do not provide sufficient survival benefit, or where patients no longer have treatment options. Based on its unique design and mechanism, birinapant has the potential to enhance patients’ responses in combination with other treatments.