On October 27, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported receipt of a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for a patent application entitled "Combinations of IRS/STAT3 Dual Modulators and Anti-Cancer Agents for Treating Cancer" (Press release, Kitov Pharmaceuticals , OCT 27, 2020, View Source [SID1234569112]). The patent, which expires in 2036, covers Kitov’s NT219, a dual inhibitor, novel small molecule targeting IRS1/2 and STAT3, important oncogenic drivers and major drug resistance pathways in many hard-to-treat cancers.

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The patent application covers the various combinations of NT219 with multiple 2nd and 3rd generation EGFR inhibitors, including osimertinib (TAGRISSO), a 3rd generation EGFR inhibitor approved in the U.S. for first-line treatment of EGFR-mutated non-small-cell lung carcinoma (NSCLC) with annual sales of more than $3 billion worldwide. In in-vitro studies using NSCLC cells with mutated EGFR (T790M), NT219 was shown to downregulate IRS1 and STAT3, and to synergize with osimertinib in suppressing cell proliferation. In addition, in a preclinical PDX model originated from osimertinib-resistant metastatic NSCLC, NT219 has demonstrated significant single-agent activity, and the combination of NT219 with osimertinib resulted in a synergistic effect, showing strong and statistically significant inhibition of tumor growth, compared to the use of osimertinib alone. These encouraging results suggest a potentially promising therapeutic avenue for NT219 that Kitov intends to explore in future clinical trials.

"We are very pleased with this new addition to our patent coverage in the U.S. for NT219, a potential treatment for many hard-to-treat cancers," said Isaac Israel, Kitov’s Chief Executive Officer. "This is an important milestone that has strengthened our extensive IP portfolio and supports our goal of establishing a potential key market for NT219 in the U.S. We expect top-line data readout from our Phase 1/2 trial with NT219 in the second half of 2021."

Kitov recently initiated a Phase 1/2 trial evaluating NT219 as monotherapy treatment of advanced solid tumors, as well as in combination with cetuximab for the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) or colorectal adenocarcinoma. Preliminary data from part one of the study encompasses a dose-escalation evaluation of NT219 monotherapy administered weekly in patients with refractory advanced solid tumors and is expected in the second half of 2021.

On October 27, 2020 Phosplatin Therapeutics LLC, a clinical-stage pharmaceutical company focused on oncology therapeutics, presented new data showing that glycolytic tumor cells with mitochondrial dysfunction were more sensitive to cell death induced by PT-112, the company’s lead clinical agent, compared to cells with an intact oxidative phosphorylation pathway (Press release, Phosplatin, OCT 27, 2020, View Source [SID1234569110]). The type of cell death induced by PT-112 was also shown to involve autophagy, which is a known pre-cursor of immunogenic cell death (ICD). Such findings reinforce PT-112’s divergence from the canonical expectations surrounding cell death mechanisms of platinum-containing agents. Data were presented at the 32nd Symposium of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) (Free AACR Whitepaper), which took place virtually October 24-25.

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"PT-112’s selectivity to glycolysis-dependent cells over those able to conduct aerobic respiration, and its initiation of autophagy, are promising mechanistic findings that tie in well with PT-112’s ability to induce ICD. These findings may offer opportunity for subsequent clinical applications," said Tyler Ames, PhD, SVP of Research and Development, Phosplatin Therapeutics.

Led by Professor Alberto Anel, PhD of the University of Zaragoza Aragón Health Research Institute of Zaragoza, Spain, the study used the lab’s proprietary cellular models to demonstrate high sensitivity to PT-112 exposure of glycolysis-dependent cancerous cells harboring mitochondrial DNA mutations and high expression of HIF-1a, and a degree of selectivity not observed with cisplatin control. The study authors attributed the variance in response to differences in cellular targets and/or reactive oxygen species (ROS) generation by PT-112. Initial validation of these data in human cancer cells is ongoing. ROS generation is also known from the literature as a pre-cursor to ICD.

"As we continue to learn more about PT-112 and its unique set of cellular effects, we gain greater insight into its pleiotropic mechanism of action, the possible causes of its robust ICD induction, and its breadth of potential clinical application," said Matthew Price, co-founder and Chief Operating Officer, Phosplatin Therapeutics. "We are grateful for our collaboration with the Anel lab. Our hope is that such collaborative lab research, as well as our ongoing clinical correlative studies, will further illuminate ways in which we can continue successfully to treat cancer patients who have few available treatment options."

The abstract "PT-112, A First-In-Class Pyrophosphate-Platinum Conjugate, Selectively Targets Highly Glycolytic Tumor Cells" is available along with a narrated poster presentation at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) symposium site and on the Phosplatin Therapeutics website.

About PT-112

PT-112 is a novel small molecule conjugate of pyrophosphate that possesses a unique pleiotropic mechanism of action that promotes immunogenic cell death (ICD), through the release of damage associated molecular patterns (DAMPs) that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 represents the best-in-class small molecule inducer of this immunological form of cancer cell death and is currently under Phase II development. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and won "Best Poster" within the Developmental Therapeutics category at the ESMO (Free ESMO Whitepaper) 2018 Annual Congress. The novelty of PT-112’s pyrophosphate moiety also results in osteotropism, or the propensity of the drug to reach the mineralized bone. This property is of interest in cancer types that originate in or metastasize to the bone. The combination Phase Ib study of PT-112 with PD-L1 immune checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO (Free ESMO Whitepaper) 2020 Virtual Congress.

On October 27, 2020 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, reported the Company will release its third quarter 2020 financial results before the market opens on Thursday, November 5, 2020 (Press release, Synlogic, OCT 27, 2020, View Source [SID1234569106]). The press release will be followed by a conference call at 8:30 am ET, which will be open to the public via telephone and webcast. During the conference call, the Company will review its financial results and provide a corporate update.

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The conference call dial-in numbers are (844) 815-2882 for domestic callers and (213) 660-0926 for international callers. The conference ID number for the call is 8557525. Participants may access the live webcast via a link on the Synlogic website in the Events Calendar of the Investors and Media section. For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Company’s website.

On October 27, 2020 Exact Sciences Corp. (Nasdaq: EXAS) reported that the company generated revenue of $408.4 million for the third quarter ended September 30, 2020, compared to $218.8 million for the same period of 2019 (Press release, Exact Sciences, OCT 27, 2020, View Source [SID1234569105]).

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"The Exact Sciences team delivered a strong quarter and made significant progress towards our vision," said Kevin Conroy, Chairman and CEO. "We’re confident in the long-term growth outlook for both Cologuard and Oncotype DX and are excited about our extensive pipeline of liquid biopsy tests. Our team and the depth and breadth of our capabilities position us at the forefront of advanced cancer diagnostics."

Third Quarter 2020 Financial Results

For the three-month period ended September 30, 2020, as compared to the same period of 2019 (where applicable):

Total revenue was $408.4 million, compared to $218.8 million
Screening revenue was $214.6 million, a decrease of 2 percent
Precision Oncology revenue was $91.6 million
COVID-19 testing revenue was $102.2 million
Gross margin including amortization of acquired intangible assets was 72 percent, and non-GAAP gross margin excluding amortization of acquired intangible assets was 77 percent
Intangible asset impairment of $209.7 million was primarily related to a one-time impairment of certain in-process research and development assets related to an in vitro diagnostic version of Oncotype DX
Net loss was $219.9 million, or $1.46 per share, compared to a net loss of $40.5 million, or $0.31 per share
EBITDA was $(160.2) million and adjusted EBITDA was $94.5 million
Non-cash interest expense related to convertible debt was $20.6 million, compared to $11.0 million
Cash, cash equivalents, and marketable securities were $1.3 billion at the end of the quarter
Screening includes laboratory service revenue from Cologuard and revenue from Biomatrica products. Precision Oncology includes laboratory service revenue from global Oncotype DX products.

Non-GAAP Disclosure
In addition to the company’s financial results determined in accordance with U.S. GAAP, the company provides non-GAAP measures that it determines to be useful in evaluating its operating performance. The company presents EBITDA, adjusted EBITDA, as well as non-GAAP gross margin and non-GAAP gross profit. EBITDA and adjusted EBITDA consist of net loss after adjustment for those items shown in the table below. The company defines non-GAAP gross profit and non-GAAP gross margin as GAAP gross profit and GAAP gross margin, respectively, excluding amortization of acquired intangible assets. The amortization of acquisition-related intangible assets used in the calculation of non-GAAP gross profit and non-GAAP gross margin pertain only to the amortization associated with developed technology acquired and recorded through purchase accounting transactions. The amortization of these intangible assets will recur in future periods until such intangible assets have been fully amortized. The company believes that these non-GAAP measures are useful in evaluating the company’s operating performance. The company uses this non-GAAP financial information to evaluate ongoing operations and for internal planning and forecasting purposes. Non-GAAP financial information, when taken collectively, may be helpful to investors because it provides consistency and comparability with past financial performance. However, non-GAAP financial information is presented for supplemental information purposes only, has limitations as an analytical tool and should not be considered in isolation or as a substitute for financial information presented in accordance with U.S. GAAP. For example, non-GAAP gross margin and non-GAAP gross profit exclude the amortization of acquired intangible assets although such measures include the revenue associated with the acquisitions. For a reconciliation of these non-GAAP measures to GAAP, see below "EBITDA and Adjusted EBITDA Reconciliations" and "Non-GAAP Gross Profit and Non-GAAP Gross Margin Reconciliations."

Third Quarter Conference Call & Webcast
Company management will host a conference call and webcast on Tuesday, October 27, 2020, at 8 a.m. ET to discuss third quarter 2020 results. The webcast will be available at www.exactsciences.com. Domestic callers should dial 833-235-7650 and international callers should dial +1-647-689-4171. The access code for both domestic and international callers is 9947369.

An archive of the webcast will be available at www.exactsciences.com. A replay of the conference call will be available by calling 800-585-8367 domestically or 416-621-4642 internationally. The access code for the replay of the call is 9947369. The webcast, conference call and replay are open to all interested parties.

About Cologuard
Cologuard was approved by the FDA in August 2014, and results from Exact Sciences’ prospective 90-site, point-in-time, 10,000-patient pivotal trial were published in the New England Journal of Medicine in March 2014. Cologuard is included in the American Cancer Society’s (2018) colorectal cancer screening guidelines and the recommendations of the U.S. Preventive Services Task Force (2016) and National Comprehensive Cancer Network (2016). Cologuard is indicated to screen adults 45 years of age and older who are at average risk for colorectal cancer by detecting certain DNA markers and blood in the stool. Do not use Cologuard if you have had precancer, have inflammatory bowel disease and certain hereditary syndromes, or have a personal or family history of colorectal cancer. Cologuard is not a replacement for colonoscopy in high risk patients. Cologuard performance in adults ages 45-49 is estimated based on a large clinical study of patients 50 and older. Cologuard performance in repeat testing has not been evaluated.

The Cologuard test result should be interpreted with caution. A positive test result does not confirm the presence of cancer. Patients with a positive test result should be referred for diagnostic colonoscopy. A negative test result does not confirm the absence of cancer. Patients with a negative test result should discuss with their doctor when they need to be tested again.

Medicare and most major insurers cover Cologuard. For more information about Cologuard, visit www.cologuardtest.com. Rx only.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. In breast cancer, the Oncotype DX Breast Recurrence Score test is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention, and the Oncotype DX AR-V7 Nucleus Detect test helps determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are resistant to androgen receptor (AR)-targeted therapies. The Oncotype DX AR-V7 Nucleus Detect test is performed by Epic Sciences at its centralized, CLIA-certified laboratory in San Diego and offered exclusively by Exact Sciences. With more than 1 million patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatment.org.

On October 27, 2020 Exact Sciences Corp. (Nasdaq: EXAS) and Thrive Earlier Detection Corp. ("Thrive"), a healthcare company dedicated to incorporating earlier cancer detection into routine medical care, reported they have entered into a definitive agreement under which Exact Sciences will acquire Thrive for cash and stock consideration of up to $2.15 billion (Press release, Exact Sciences, OCT 27, 2020, View Source [SID1234569104]). The transaction was unanimously approved by both companies’ Boards of Directors and is anticipated to close during the first quarter of 2021, subject to regulatory approval and the satisfaction of other conditions.

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Combining Thrive’s pioneering early-stage screening test, CancerSEEK, with Exact Sciences’ best-in-class scientific platform, clinical organization, and commercial infrastructure will establish Exact Sciences as a leading competitor in blood-based, multi-cancer screening. Thrive, with an early version of CancerSEEK, has conducted a first-of-its-kind 10,000-patient, prospective, interventional study in a real-world clinical setting. In this landmark study, using its mutation and protein biomarker approach, CancerSEEK achieved promising results detecting 10 different types of cancer, including seven with no recommended screening guidelines, with very few false positives. Bringing together highly complementary scientific approaches and the strengths of both organizations, Exact Sciences expects to develop a more accurate test and accelerate the widespread adoption of this potentially life-saving advancement.

"The acquisition of Thrive is a giant leap toward ensuring blood-based, multi-cancer screening becomes a reality and eventually, the standard of care. We couldn’t be more excited that Exact Sciences will be at the forefront of this incredible opportunity to serve patients," said Kevin Conroy, Chairman and CEO of Exact Sciences. "We have long respected the Thrive team for their rigorous scientific approach, having participated in both funding rounds as an investor. We are proud to take our partnership to the next level by leveraging Exact Sciences’ established R&D team and highly accurate testing platform to augment development of CancerSEEK and accelerate its commercialization. By combining the expertise of both organizations, we believe we can bring this powerful technology to patients faster."

"Thrive is driven by the knowledge that if cancer is caught early enough, it can be more effectively treated or even cured, and every patient deserves a chance for a better outcome," said David Daly, CEO of Thrive. "Our team has made significant progress toward our mission and we are eager to collaborate with and benefit from Exact Sciences’ expertise, and believe that together we will enable broader, quicker adoption of our test. With the support of our ongoing partnership with Johns Hopkins University, we are energized to contribute meaningfully to our shared mission of advancing the fight against cancer and providing life-changing answers to patients in need."

Creating a Leader in Blood-Based, Multi-Cancer Screening

Transforming the Future of Cancer Diagnostics with a Premier R&D Team: The Exact Sciences R&D team has robust clinical and evidence generation capabilities. This powerful team will be complemented and enhanced by the addition of Thrive’s R&D groups specializing in next-generation sequencing and bioinformatics in liquid biopsy. The combined R&D team’s impact will be amplified by Exact Sciences’ database of proprietary biomarkers, extensive blood sample biorepository, financial strength, and each company’s established partnerships with leading institutions, including Mayo Clinic and Johns Hopkins University.
Accelerating the Approval, Availability, and Adoption of Multi-Cancer Screening: Exact Sciences is uniquely positioned to support the development of Thrive’s CancerSEEK product and facilitate its success. By leveraging Exact Sciences’ proven clinical and regulatory teams, scaled laboratory and IT capabilities, and well-established primary care sales team and direct-to-consumer marketing experience, the Company expects to bring blood-based, multi-cancer screening to patients faster and with greater certainty.
Positioning Exact Sciences as a Leader in a $25 Billion+ Market and Demonstrating Capabilities as a Research and Commercialization Partner-of-Choice: The need to detect the deadliest cancers at earlier, more treatable stages is urgent, and multi-cancer screening can be an impactful solution. Thrive has conducted a large study in a real-world clinical setting, with promising results at a low false positive rate. By joining with Thrive, Exact Sciences would be well-positioned to compete in a significant U.S. market, estimated to be at least $25 billion. Exact Sciences is already home to two of the strongest and fastest-growing brands in cancer diagnostics, Cologuard and Oncotype DX. With the addition of Thrive, Exact Sciences would have the scientific rigor necessary to bring tests to patients at every step of their cancer journey, from screening to minimal residual disease, recurrence monitoring, and therapy selection. This rigor and Exact Sciences’ existing commercial strength further distinguish the Company as a leading developer and provider of innovative products across the cancer continuum.
Transaction Terms and Additional Information
Under the terms of the agreement, Thrive will receive total consideration of up to $2.15 billion, of which $1.7 billion would be payable at closing, comprised of 65% in Exact Sciences common stock and 35% in cash, subject to certain adjustments. An additional $450 million would be payable based upon the achievement of certain milestones related to the development and commercialization of a blood-based, multi-cancer screening test. The transaction is subject to customary closing conditions and regulatory approvals and is anticipated to close during the first quarter of 2021. XMS Capital is serving as financial advisor to Exact Sciences, and K&L Gates is serving as legal advisor. Goldman Sachs & Co. LLC is serving as financial advisor to Thrive, and Goodwin Procter LLP is serving as legal advisor.

Exact Sciences also Acquires Base Genomics to Extend its DNA Methylation Capabilities
Exact Sciences also announced today that it has acquired Base Genomics, an epigenetics company working to set a new standard in DNA methylation analysis, one of the most promising approaches to detecting cancer in its earliest stages. Base Genomics has a talented team and innovative technology enabling highly accurate DNA methylation analysis. It also allows for the analysis of DNA methylation and mutations in a single sample. Base Genomics’ differentiated technology is highly complementary to Exact Sciences’ existing methylation expertise and multi-marker approach. This acquisition will enhance Exact Sciences’ efforts in cancer diagnostics across the continuum. The terms of this transaction were disclosed in Form 10-Q, filed with the U.S. Securities and Exchange Commission earlier today. XMS Capital is serving as financial advisor to Exact Sciences, and K&L Gates is serving as legal advisor. William Blair is serving as financial advisor to Base Genomics, and Bristows LLP is serving as legal advisor.

Conference Call & Third Quarter 2020 Earnings Results
In a separate press release issued today, the Company announced its earnings results for the third quarter of 2020.

Exact Sciences will host a conference call today at 8:00 a.m. ET to discuss the transaction, as well as its third quarter 2020 earnings results. Associated presentation materials and an infographic regarding the transaction will be available on the investor relations section of Exact Sciences website at exactsciences.com/investor-relations/events-and-presentations/.