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.

On January 16, 2019 Mirati Therapeutics, Inc. (Nasdaq: MRTX) reported that it intends to offer and sell, subject to market and other conditions, $75.0 million of shares of its common stock in an underwritten public offering (Press release, Mirati, JAN 16, 2019, View Source [SID1234532703]). Mirati expects to grant the underwriters a 30-day option to purchase up to an additional $11.25 million of shares of its common stock. All of the shares are being offered by Mirati. There can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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J.P. Morgan Securities LLC, Citigroup Global Markets Inc., Cowen and Company, LLC, Barclays Capital Inc. and Credit Suisse Securities (USA) LLC are acting as joint book-running managers in the offering.

The securities described above are being offered by Mirati pursuant to a shelf registration statement filed by Mirati with the Securities and Exchange Commission ("SEC") that became automatically effective upon filing. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; from Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (800) 831-9146; from Cowen and Company, LLC, c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department, or by calling (631) 274-2806; from Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by calling (888) 603-5847, or by email at [email protected]; or from Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, One Madison Avenue, New York, NY 10010, or by telephone at (800) 221-1037, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other 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 other jurisdiction.

On January 16, 2019 Surface Oncology (Nasdaq:SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the publication of a paper describing the biological activity of IL-27, an immunosuppressive cytokine (Press release, Surface Oncology, JAN 16, 2019, View Source [SID1234532698]). Previously, IL-27 has been referred to as a key regulator for the expression of checkpoint proteins.1

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The paper, "IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors," was published in ImmunoHorizons, a peer-reviewed, open access, online-only journal committed to advancing the knowledge of immunology. Among the findings in the paper, results indicate that the local production of IL-27 at sites of ongoing toxoplasmosis-induced inflammation contributes to expression of PD-L1, LAG-3, CTLA-4, and TIGIT, all key checkpoint proteins in the downregulation of immune responses.

IL-27 is understood to play an important role in turning off an immune response following viral and parasitic infections. Beyond the role of IL-27 in restoring immunostasis, Surface Oncology believes it has identified several cancers where IL-27 may prevent the immune system from recognizing and killing cancer cells.

"This paper is yet another validation of the role of IL-27 as a regulatory cytokine for the upregulation of checkpoint proteins. We are rapidly working toward filing an IND for our IL-27 antibody, SRF388, which we believe will be the first IL-27 antibody for the treatment of cancer. We applaud this additional work in the field and are privileged to work alongside thought leaders such as Dr. Chris Hunter, one of our SAB members and senior author of this paper," said Jeff Goater, chief executive officer of Surface Oncology.

"We have now known for more than 15 years that IL-27 can have remarkable suppressive activities," said Christopher Hunter, B.Sc., Ph.D., chairman, Department of Pathobiology, University of Pennsylvania, and member of Surface Oncology’s Scientific Advisory Board. "However, the ability of IL-27 to promote inhibitory receptor expression in the context of infection, autoimmune inflammation, and cancer may help to explain how it tempers T cell responses."

Surface Oncology is currently conducting IND-enabling studies for its IL-27 antibody, SRF388. IND submission for SRF388 is projected for Q4 2019. SRF388 is believed to be the only IL-27 antibody in late-preclinical development.

1 Kuchroo, Et al. Nature 558, pages 454–459 (2018)

ABOUT SRF388
SRF388 is a fully human anti-IL-27 antibody. In preclinical studies, treatment with SRF388 was observed to block IL-27 signaling and its downstream immunosuppressive signaling effects. Preclinical combination with a PD-1 inhibitor increased the production of key inflammatory cytokines. SRF388 also demonstrates preclinical anti-metastatic tumor activity.

Under Surface’s collaboration agreement with Novartis, Novartis has the right to purchase an option to the SRF388 program.