On January 17, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) for Tecentriq (atezolizumab) in combination with Abraxane [albumin-bound paclitaxel; nab-paclitaxel]) and carboplatin for the initial (first-line) treatment of people with metastatic non-squamous non-small cell lung cancer (NSCLC) who do not have EGFR or ALK genomic tumour aberrations (Press release, Hoffmann-La Roche, JAN 17, 2019, View Source [SID1234532700]). The FDA is expected to make a decision on approval by 2 September 2019.

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"We look forward to working with the FDA in order to bring this Tecentriq-based combination to people with non-squamous non-small cell lung cancer as soon as possible," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Lung cancer is a challenging disease to treat, and this review takes us one step closer towards offering a new treatment option that has shown a clinically meaningful survival benefit in the treatment of this type of disease."

This sBLA is based on results from the Phase III IMpower130 study, which met its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) in the initial treatment of people with metastatic non-squamous NSCLC.

The FDA recently approved Tecentriq in combination with Avastin, paclitaxel and carboplatin (chemotherapy) for the initial treatment of people with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations. Tecentriq is also approved by the FDA to treat people with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on FDA approved therapy for NSCLC harbouring these aberrations prior to receiving Tecentriq.

About the IMpower130 study
IMpower130 is a Phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and nab-paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone for chemotherapy-naïve patients with stage IV non-squamous NSCLC. The study enrolled 724 people who were randomised in a 2:1 ratio to receive:

Tecentriq plus nab-paclitaxel and carboplatin (Arm A), or
Nab-paclitaxel and carboplatin (Arm B, control arm)
During the treatment-induction phase, people in Arm A received Tecentriq and carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurred first. People in Arm A received Tecentriq during the maintenance treatment phase until loss of clinical benefit was observed.

During the treatment-induction phase, people in Arm B received carboplatin on day 1 and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurred first. People in Arm B received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover following disease progression to receive Tecentriq as monotherapy until further disease progression.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in people without EGFR or ALK mutations, assessed in the ITT-WT population
OS in the ITT-WT population
The IMpower130 study met its OS and PFS co-primary endpoints as per the study protocol. The interim analysis showed that Tecentriq plus chemotherapy helped people live significantly longer compared with chemotherapy alone (median OS=18.6 versus 13.9 months; hazard ratio [HR]=0.79; 95% CI: 0.64–0.98; p=0.033) in the intention-to-treat wild-type (ITT-WT) population.[1] The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (PFS) compared with chemotherapy alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95% CI: 0.54–0.77; p<0.0001) in the ITT-WT population.[1] Safety for the Tecentriq plus chemotherapy combination appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. Grade 3-4 treatment-related adverse events (AEs) were reported in 73.2% of people receiving Tecentriq plus chemotherapy compared to 60.3% of people receiving chemotherapy alone.

About NSCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.[2] Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.[3] NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.[3]

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has nine Phase III lung cancer studies evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 85 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC). Tecentriq was also recently approved in the United States for the initial treatment of people with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients

On January 16, 2019 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that the first patient has been dosed in its Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-601 in patients with selected solid tumors that are locally advanced or metastatic (Press release, ADC Therapeutics, JAN 16, 2019, View Source [SID1234596066]).

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ADCT-601 is an ADC composed of a humanized monoclonal antibody against human AXL, conjugated using GlycoConnect site specific conjugation technology to a pyrrolobenzodiazepine (PBD) dimer toxin. In preclinical studies, ADCT-601 demonstrated potent and specific in vitro and in vivo anti-tumor activity in multiple cancer-derived models with different levels of AXL expression, and was stable and well tolerated.

Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said, "AXL is a novel and ideal target for an ADC approach, as it is overexpressed in many solid tumor types. We look forward to exploring the effect of ADCT-601 on patients with selected advanced solid tumors who have failed or are intolerant to any established therapy. With five ADCs in eight ongoing clinical trials for multiple indications, we believe our highly targeted therapies have the potential to meaningfully improve outcomes for patients with solid tumors and hematological cancers."

The open-label, multicenter, single-arm trial will include a Phase Ia dose-escalation part followed by a Phase Ib dose-expansion part. The dose-escalation part is designed to determine the maximum tolerated dose of ADCT-601. The identified dose will be evaluated in the dose-expansion part. Approximately 75 patients will be enrolled in the trial. For more information, please visit www.clinicaltrials.gov (identifier NCT03700294).

About ADCT-601

ADCT-601 is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human AXL, conjugated using GlycoConnect technology to a linker with a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to an AXL-expressing cell, ADCT-601 is internalized into the cell where enzymes release the PBD-based warhead. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and ultimately killing the cancer cell. ADCT-601 is being evaluated in a Phase I clinical trial in patients with advanced solid tumors (NCT03700294).

On January 16, 2019 Phoenix Molecular Designs (PhoenixMD), a privately-held biotechnology company designing precise cancer therapeutics by targeting essential kinases, reported that it has entered into a collaboration with Roche to develop a diagnostic (CDx) in triple-negative breast cancer (TNBC) (Press release, PhoenixMD, JAN 16, 2019, View Source [SID1234553816]). The Roche CDx identifies RSK2 activation in human tumors. In cancer, the PDK-1 and MAPK pathways converge on RSK2 to activate it, moving it from the cytoplasm into the nucleus. Measuring nuclear RSK2 signifies activation and abundance of this emerging drug target.

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Complementing its diagnostic efforts, PhoenixMD has also developed PMD-026, which is the first orally available small molecule inhibitor that targets RSK2, a prime drug target in multiple cancers. The leading focus for PhoenixMD is in the treatment of triple-negative breast cancer (TNBC) given the companies’ core expertise in developing breast cancer therapeutics.

The diagnostic assay developed through the Roche/PhoenixMD collaboration will relay information on how active the RSK2 pathway is in TNBC and other cancers. Preliminary data indicates that 80 percent of cases (52/65 TNBC cases) express activated RSK2. More broadly, researchers have investigated more than 300 biopsies and found that RSK2 is activated in 65 percent of tumors from a study of 13 different tumor types. RSK2 was also detected in breast cancer metastases using this method. Over the coming months, Roche will establish a CAP/CLIA certified protocol as a gateway into clinical tumor analyses. In upcoming clinical trials, PhoenixMD will further refine the precision of the RSK2 CDx in identifying patients that may ultimately benefit from PMD-026. In the near term, PhoenixMD expects to file an IND for PMD-026 and initiate a Phase I/Ib study in women with TNBC.

"By working together, PhoenixMD and Roche are at the forefront of innovation in TNBC, the most deadly breast cancer type with no approved therapies. Creating our diagnostic assay and identifying disease biomarkers, such as RSK2 for TNBC, will dramatically reduce the development time needed to create targeted drugs and will improve a drug’s chance of advancing through clinical trials," said Dr. Sandra E. Dunn, CEO of PhoenixMD. "The top-line data generated from our CDx is encouraging, and we look forward to applying these learnings to identify TNBC patients that may benefit from PMD-026 in our upcoming Phase I/Ib study."

About Triple Negative Breast Cancer (TNBC) and RSK Kinases

Approximately 400,000 cases of TNBC are diagnosed every year worldwide and it is one of the most difficult breast cancer subtypes to treat due to lack of effective, targeted therapies. TNBC also claims the lives of young women more than any other type of breast cancer due to a lack of understanding around the therapeutic bullseye. It is also a very heterogeneous disease, therefore a common denominator across TNBC types was necessary to identify the bullseye. Through genome-wide screens, RSK was identified as the prime target for TNBC by scientists at PhoenixMD. Currently, there are no approved targeted therapies available for TNBC.

There are four types of RSK involved in cancer, known as RSK1-4, and each type has a unique role in the development of the disease. RSK1 is responsible for cancer cell invasion and is an important driver in the spread of cancer. RSK2 controls cancer cell growth, and RSK3 and RSK4 are associated with drug resistance.

RSK1 and RSK2 have been proven critical to the survival of patients with TNBC. Over 90 percent of primary TNBC cases express high levels of RSK1 and RSK2. Inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence. PhoenixMD, with its novel, targeted approach, is focused on creating patented cancer RSK inhibitors and companion diagnostics for cancer indications – initially in breast cancer – with the potential to treat blood, brain, ovarian, lung, skin, prostate, colon, head and neck cancers.

While there are currently no approved targeted therapies for TNBC, several drugs are involved in research studies and clinical trials. PhoenixMD is addressing this unmet medical need through a novel, targeted approach by inhibiting critical kinases, such as RSK1-4, a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. For this target, PhoenixMD developed PMD-026, a first-in-class, specific RSK inhibitor that blocks downstream signaling of RSK and induces apoptosis.

On January 16, 2019 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that the first patient has been dosed in its Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-601 in patients with selected solid tumors that are locally advanced or metastatic (Press release, Synaffix, JAN 16, 2019, View Source [SID1234532771]).

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ADCT-601 is an ADC composed of a humanized monoclonal antibody against human AXL, conjugated using GlycoConnect site specific conjugation technology to a pyrrolobenzodiazepine (PBD) dimer toxin. In preclinical studies, ADCT-601 demonstrated potent and specific in vitro and in vivo anti-tumor activity in multiple cancer-derived models with different levels of AXL expression, and was stable and well tolerated.

Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said, "AXL is a novel and ideal target for an ADC approach, as it is overexpressed in many solid tumor types. We look forward to exploring the effect of ADCT-601 on patients with selected advanced solid tumors who have failed or are intolerant to any established therapy. With five ADCs in eight ongoing clinical trials for multiple indications, we believe our highly targeted therapies have the potential to meaningfully improve outcomes for patients with solid tumors and hematological cancers."

The open-label, multicenter, single-arm trial will include a Phase Ia dose-escalation part followed by a Phase Ib dose-expansion part. The dose-escalation part is designed to determine the maximum tolerated dose of ADCT-601. The identified dose will be evaluated in the dose-expansion part. Approximately 75 patients will be enrolled in the trial. For more information, please visit www.clinicaltrials.gov (identifier NCT03700294).

About ADCT-601

ADCT-601 is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human AXL, conjugated using GlycoConnect technology to a linker with a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to an AXL-expressing cell, ADCT-601 is internalized into the cell where enzymes release the PBD-based warhead. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and ultimately killing the cancer cell. ADCT-601 is being evaluated in a Phase I clinical trial in patients with advanced solid tumors (NCT03700294).

On January 16, 2019 Kitov Pharma Ltd. (NASDAQ/TASE:KTOV), an innovative biopharmaceutical company, reported that it has entered into definitive agreements with institutional investors providing for the issuance of 3,428,572 American Depositary Shares (ADS) at a purchase price of $1.75 per ADS in a registered direct offering (Press release, Kitov Pharmaceuticals , JAN 16, 2019, View Source [SID1234532769]).

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Kitov will also issue unregistered warrants to purchase up to 2,571,430 ADSs. The warrants will have a term of 5.5 years, be exercisable immediately following the issuance date and have an exercise price of $2.00 per ADS. The offering is expected to result in gross proceeds of approximately $6 million.

H.C. Wainwright & Co. is acting as the exclusive placement agent in connection with this offering.

The closing of the sale of the securities is expected to take place on or about January 18, 2019, subject to satisfaction of customary closing conditions.

The ADSs described above were offered pursuant to a shelf registration statement on Form F-3 (File No. 333-215037), which was declared effective by the United States Securities and Exchange Commission (the "SEC") on December 14, 2016. Such ADSs may be offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement.

When filed with the SEC, copies of the prospectus supplement and the accompanying prospectus relating to the registered direct offering may be obtained at the SEC’s website at View Source Copies of the prospectus supplement and accompanying prospectus relating to the registered direct offering may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by calling (646) 975-6996 or emailing [email protected].

The warrants described above were offered in a private placement pursuant to an applicable exemption from the registration requirements of the Securities Act of 1933, as amended (the "Act"), and, along with the ADSs issuable upon their exercise, have not been registered under the Act, and may not be offered or sold in the United States absent registration with the SEC or an applicable exemption from such registration requirements.

This press release shall not constitute an offer to sell or a 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 the registration or qualification under the securities laws of any such state or jurisdiction.