On November 27, 2020 Genetron Holdings Limited ("Genetron Health" or the "Company", Nasdaq: GTH), a leading precision oncology platform company in China that specializes in offering molecular profiling tests, early cancer screening products and companion diagnostics development, reported an update for HCCscreenTM, its blood-based early screening test for hepatocellular carcinoma ("HCC"), in China (Press release, Genetron Health Technologies, NOV 27, 2020, View Source [SID1234571850]).

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Led by the Wuxi municipal government ("Wuxi") and administered by the National Cancer Center (NCC) in China, the "Liver Cancer Early Screening Comprehensive Prevention and Control Project" is a public health initiative (the "Project"). The goal of the Project is to increase the awareness of liver cancer early screening, and to become a pilot city model in China. For the Project, Wuxi has selected HCCscreenTM for local residents who are high-risk individuals for HCC, and is committed to administering 150,000 tests over a period of three years. Wuxi had entered into a small-scale collaboration agreement with Genetron Health in 2019, and the Project represents an expanded collaboration between the parties. Wuxi is a city in the southern part of Jiangsu Province in eastern China with a population of over six million people, and has emerged as a biopharma innovation hub in recent years.

Separately, Genetron Health has formed a new operating center through a joint venture agreement with Wuxi, in which the parties will closely collaborate on advancing the liver cancer early screening market in China, through the adoption of HCCscreenTM. Under this joint venture agreement, both parties will contribute capital, and Genetron Health will own 90% of the joint venture. In addition to the commitment of using HCCscreenTM for its residents, Wuxi will also provide Genetron Health with other supportive measures including rental, R&D subsidies and tax benefits.

"We are thrilled about this strategic partnership with Wuxi. It represents a major milestone for HCCscreenTM as it will be broadly used in a real-world setting, reflecting its clinical value that both the NCC and Wuxi recognized. Wuxi’s investment and other supportive measures also highlight its commitment to advancing the liver cancer early screening in China," commented Sizhen Wang, Genetron Health’s co-founder and CEO. "This partnership provides Genetron Health with near term revenue opportunities, as well as a cost-effective structure to build another world-class lab, manufacturing facility and an operating center for future developments. Beyond the financial benefits, the strategic value from this partnership is tremendous. It enables large-scale, real-world adoption of HCCscreenTM, representing an important step for our early screening product development, as well as potentially serving as a pilot model as we navigate the broader commercialization and reimbursement roadmaps in the future. Overall, we expect this initiative to ultimately help drive faster adoption of early cancer detection products in China."

About HCCscreenTM and Liver Cancer

In September 2020, Genetron Health received the U.S. Food and Drug Administration ("FDA")’s Breakthrough Device designation for HCCscreenTM, and the product has been commercialized recently as a lab developed test ("LDT") in China.

Globally, liver cancer is the fourth most common cause of cancer-related death and the sixth in terms of incidence1. China represents the largest market, accounting for almost half of the global incidences. New incidence in China was estimated to be around 393,000 per year, with 369,000 deaths2. Market data by Frost and Sullivan estimated that as of 2019, among the 120 million high risk liver cancer population in China, around 74 million were HBV carriers.

Powered by Genetron Health’s innovative and proprietary Mutation CapsuleTM technology, which enables detection of multiple methylation alterations in parallel with mutations in cell-free DNA from peripheral blood specimens, HCCscreenTM is currently being tested in its ongoing prospective study with 4,500 HBsAg+ individuals in HCC. As of the date of this announcement, 2,000 patients have already completed the study, and preliminary data from 297 patients at one center has demonstrated over 92% sensitivity, 93% specificity, compared to 67% and 99%, respectively in the ultrasound plus alpha-fetoprotein (AFP) arm. HCCscreenTM also achieved a 35% positive predictive value and 99.6% negative predictive value. Furthermore, stratifying by tumor sizes, of the 12 patients identified with HCC in the preliminary dataset, 10 patients had tumor sizes of less than 5 centimeters. Of these, seven patients had tumor sizes of less than 3 centimeters, and HCCscreen successfully detected them all, indicating its ability in detecting early-stage HCC.

In August 2020, Genetron Health announced its participation in the launch of a major national research project for early screening of lung and digestive system cancers led by China’s Ministry of Science and Technology. The project is designed to include a multi-center, prospective cohort study in lung cancer of 120,000 high-risk individuals in 20 provinces, as well as a cohort study in digestive system cancer of more than 100,000 patients in urban areas in China. Genetron Health is the only company in China involved in national key research and development projects for liver, lung and digestive cancer early screening.

References:

Villanueva, A. Hepatocellular Carcinoma. N. Engl. J. Med. 2019, 380, 1450–1462.
Globocan 2018. View Source Information on this website is not incorporated into this update and should not be considered part of this update. We have included any website as an inactive textual reference only.

On November 27, 2020 Exelixis, Inc. (NASDAQ: EXEL) reported that Takeda Pharmaceutical Company Limited (Takeda), its partner responsible for the clinical development and commercialization of CABOMETYX (cabozantinib) in Japan, received approval from the Japanese Ministry of Health, Labor and Welfare to manufacture and market CABOMETYX as a treatment for patients with unresectable hepatocellular carcinoma (HCC) that has progressed after prior systemic therapy (Press release, Exelixis, NOV 27, 2020, View Source [SID1234571848]).

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Takeda’s application is based on the results of two clinical trials in patients with advanced HCC who had received prior systemic therapy: CELESTIAL (XL184-309), a global, randomized, placebo-controlled, double-blind phase 3 clinical trial, and Cabozantinib-2003, a phase 2 clinical trial conducted in Japan. The CELESTIAL trial was the basis for the CABOMETYX approvals in the U.S. and the EU for the treatment of patients with HCC who have been previously treated with sorafenib.

"Hepatocellular carcinoma causes approximately 30,000 deaths in Japan each year and is a leading cause of cancer-related death worldwide," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "The approval of CABOMETYX in Japan is an exciting next step toward bringing this treatment to liver cancer patients who otherwise have limited treatment options following prior systemic therapy. We’re proud to collaborate with Takeda as we work to bring this treatment to patients in Japan."

Per the terms of Exelixis and Takeda’s collaboration and license agreement, Exelixis is eligible to receive a $15 million milestone payment from Takeda upon the first commercial sale of CABOMETYX for unresectable HCC, which is expected to occur in the fourth quarter of 2020. In January 2020, Takeda’s application for approval to manufacture and sell CABOMETYX as a treatment for patients with unresectable HCC that had progressed after prior systemic therapy in Japan triggered a $10 million milestone payment. Exelixis continues to be eligible to receive additional development, regulatory and first-sale milestones for potential future cabozantinib indications and is also eligible for sales revenue milestones and royalties on net sales of cabozantinib in Japan.

Takeda fully funds cabozantinib development activities that are exclusively for the benefit of Japan and has the opportunity to share the costs associated with global cabozantinib clinical trials, providing the company opts into those trials.

About HCC

Liver cancer is a leading cause of cancer death worldwide, accounting for more than 700,000 deaths and 800,000 new cases each year.1 In the U.S., the incidence of liver cancer has more than tripled since 1980.2 HCC is the most common form of liver cancer, making up about three-fourths of the estimated 43,000 new cases in the U.S. in 2020.2 HCC is the fastest-rising cause of cancer-related death in the U.S.3 Without treatment, patients with advanced HCC usually survive less than 6 months.4

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

U.S. Important Safety Information

Warnings and Precautions

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.

Drug Interactions

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

On November 27, 2020 Advaxis, Inc. (Nasdaq: ADXS) (the "Company"), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported the closing of an underwritten public offering of 26,666,666 shares of common stock and warrants to purchase up to 13,333,333 shares of common stock, along with an additional 3,999,999 shares of common stock and 1,999,999 warrants pursuant to the full exercise of the underwriters’ option (Press release, Advaxis, NOV 27, 2020, View Source [SID1234571842]). The shares of common stock and warrants were sold together at a combined public offering price of $0.30 per share for total gross proceeds of approximately $9.2 million, before underwriting commissions and estimated expenses.

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The Company plans to use the net proceeds from the offering to fund its continued research and development initiatives in connection with expanding its product pipeline including, but not limited to, investment in its ADXS-HOT program and for general corporate purposes. The Company may also use a portion of the net proceeds to acquire or invest in other businesses, products and technologies.

A.G.P./Alliance Global Partners acted as sole book-running manager for the offering.

This offering was made pursuant to an effective shelf registration statement on Form S-3 (File No. 333-226988) previously filed with the U.S. Securities and Exchange Commission (the "SEC"), which became effective upon filing on August 30, 2018. A prospectus supplement describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. Electronic copies of the prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022 or via telephone at 212-624-2060 or email: [email protected].

No securities regulatory authority has either approved or disapproved of the contents of this press release. This press release is for information purposes only and shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 26, 2020 ImmuPharma PLC (LSE:IMM | Euronext Growth: ALIMM), the specialist drug discovery and development company, reported the approval of the grant of options over a total of 9,625,000 ordinary shares of 10p each in the Company ("Ordinary Shares") to Directors, employees and consultants representing 3.8% of ImmuPharma’s Ordinary Shares and total voting rights (the "Options") (Press release, ImmuPharma, NOV 26, 2020, View Source [SID1234571783]). ImmuPharma currently has 250,221,297 Ordinary Shares in issue.

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Upon the recommendation of the Company’s remuneration committee, the Company has granted the Options pursuant to the Company’s Share Option Plan which was adopted on 30 March 2017 (the "2017 Plan").

The exercise price for the Options is 20p being a 54% premium to the closing middle market share price of 13p on 25 November 2020. The Options will vest after three years and are exercisable between three and ten years from the date of grant.

On November 26, 2020 Merck, a leading science and technology company, reported that the European Medicines Agency (EMA) has validated for review, the application for tepotinib for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations (Press release, Merck & Co, NOV 26, 2020, View Source [SID1234571845]). With this validation, the application is complete, and the EMA will now begin the review procedure.

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Tepotinib is a highly selective oral MET inhibitor that is administered once daily.1 The application to the EMA is based on results from the pivotal Phase II VISION study (NCT02864992) evaluating tepotinib as monotherapy in patients with advanced NSCLC with METex14 skipping alterations, prospectively assessed by liquid biopsy or tissue biopsy. In the ongoing study, the patient population is generally characterized as elderly, with a median age of 74.0 years, and as having poor clinical prognosis typical of NSCLC with METex14 skipping alterations. Data from the primary analysis of the VISION study were published in The New England Journal of Medicine (NEJM) on May 29, 2020.2

Lung cancer is estimated to be the second most common cancer in Europe, and the leading cause of cancer-related mortality, responsible for 388,000 deaths in 2018.3 METex14 skipping occurs in approximately 3–4% of NSCLC cases and correlates with aggressive tumor behavior and poor clinical prognosis.4 Currently, there are no treatments available in Europe for patients with advanced NSCLC harboring METex14 skipping alterations.

Tepotinib became the first oral MET inhibitor indicated for the treatment of advanced NSCLC harboring MET gene alterations to receive a regulatory approval globally, with its approval in Japan in March 2020 through the SAKIGAKE program. Recently, the FDA granted Orphan Drug Designation (ODD) to tepotinib and the FDA is reviewing the application under Priority Review and through the Real-Time Oncology Review pilot program.

About Tepotinib

Tepotinib is an oral MET inhibitor that inhibits the oncogenic MET receptor signaling caused by MET (gene) alterations. Discovered and developed in-house at Merck, it has a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.1

Additional Clinical Investigations: Tepotinib is also being investigated in the Phase II INSIGHT 2 study in combination with osimertinib in MET amplified, advanced or metastatic NSCLC harboring activating EGFR mutations that has progressed following first-line treatment with osimertinib, and in the Phase II PERSPECTIVE study in combination with cetuximab in RAS/BRAF wild-type left-sided metastatic colorectal cancer patients having acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.

References

Bladt F, et al. Clin Cancer Res. 2013;19:2941-2951.
Paik PK et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020 May 29; [e-pub]. (View Source)
Ferlay J, et al. Eur J Cancer. 2018;103:356–387.
Reungwetwattana T, et al. Lung Cancer. 2017;103:27–37.
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