On December 7, 2018 GenFleet Therapeutics Co. Ltd. (Shanghai, China) reported that it raised RMB120 million ($17.4 million) in an untranched series A round to bring its first therapy into clinic next year (Press release, GenFleet Therapeutics, DEC 7, 2018, http://www.genfleet.com/en/pc/NewsDetials.aspx?Ttext=NTY= [SID1234574440]).

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Ally Bridge Group led the round, which saw participation from Sinopharm Capital and CSPC, and existing investors HighLight Capital, Qian Long Yu Han and TF Capital.

GenFleet’s most advanced compound, GFH018, is a small molecule inhibitor of transforming growth factor β receptor 1 (TGFβR1; ALK5). The therapy is being developed for hepatocellular carcinoma (HCC) and other "China-prevalent" cancers, co-founder and Chairman Qiang Lu told BioCentury. A first-in-human trial is expected to start in mid-2019.

GenFleet’s seven other undisclosed programs are in preclinical development for cancer or autoimmune disease.

While Lu said GenFleet’s eight programs will not yield "first-in-class therapies per se," they are higher risk and, according to Lu, no therapy against the targets have reached clinical proof of concept elsewhere. "We’re not pursuing another IDO and EGFR," Lu added.

GenFleet’s executive team brings with it a history of drug discovery in China. Lu and GenFleet co-founder and CEO Jiong Lan built the new drug discovery team at Yangtze River Pharmaceutical Group Co. Ltd. (Shanghai, China), Lu said, where he was CSO and VP and Lan was VP and general manager of the Yangtze River subsidiary Shanghai Haiyan Pharmaceutical Technology Co. Ltd. Lu was most recently SVP of operations at CStone Pharmaceuticals Co. Ltd. (Suzhou, China), and before that CSO and VP of Harbin Gloria Pharmaceuticals Co. Ltd. (Beijing, China).
GenFleet CSO Biao Zheng was a VP at Johnson & Johnson (NYSE:JNJ) and led immunology-focused collaborations out of the J&J Innovation Center in Shanghai. He also headed immunology discovery sciences in Shanghai for the GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) subsidiary GlaxoSmithKline Pharma GmbH.

According to BioCentury’s BCIQ database, there are two other TGFβR1 inhibitors in clinical development: galunisertib (LY2157299) from Eli Lilly and Co. (NYSE:LLY), which is in Phase II testing for multiple cancers; and vactosertib (TEW-7197, NOV1301, NOV130101) from MedPacto Inc. (Suwon, South Korea), which is in Phase I/II testing for myelodysplastic syndrome (MDS) and Phase I testing for metastatic gastric cancer and advanced solid tumors.

The target has recently generated partnership interest. In July, MedPacto teamed up with Merck & Co. Inc. (NYSE:MRK) and AstraZeneca plc (LSE:AZN; NYSE:AZN) to test vactosertib in Phase Ib/IIa trials in combination with PD-1 inhibitor Keytruda pembrolizumab in metastatic or locally advanced colorectal, gastric and gastroesophageal junction cancer or with PD-L1 inhibitor Imfinzi durvalumab for metastatic non-small cell lung cancer (NSCLC).

In 2015, Lilly announced a pair of partnerships to test galunisertib in combination studies with agents from Immunocore Ltd. (Abingdon, U.K.) and Bristol-Myers Squibb Co. (NYSE:BMY).

Lu said not including reserves, the series A will give GenFleet 18-24 months of runway. "Down the road we expect [to submit] two INDs per year," he added.

The early stage investment is a rarity for Ally Bridge. According to BCIQ, the firm has not invested in a round classified as a series A since 2015.

On December 7, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported overall survival (OS) results for the Phase III EAGLE trial. EAGLE is a randomised, open-label, multi-centre trial evaluating Imfinzi (durvalumab) monotherapy or Imfinzi in combination with tremelimumab, an anti-CTLA4 antibody, versus standard-of-care (SoC) chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who experienced disease progression following platinum-based chemotherapy, regardless of their PD-L1 tumour status (Press release, AstraZeneca, DEC 7, 2018, View Source [SID1234531946]).

Imfinzi monotherapy and the combination of Imfinzi plus tremelimumab did not meet the primary endpoints of improving OS compared to SoC chemotherapy in these hard-to-treat patients. The safety and tolerability profiles for Imfinzi and the combination with tremelimumab were consistent with previous experience.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "The prognosis for recurrent or metastatic head and neck squamous cell cancer is very poor and new treatments for this group of cancers are urgently needed. While these results are disappointing, we remain committed to evaluating the potential of Imfinzi and other innovative medicines for patients with head and neck cancer. We look forward to seeing the results of the Phase III KESTREL trial of Imfinzi and tremelimumab in patients who have not received prior chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma in the first half of 2019."

AstraZeneca will submit the results from the Phase III EAGLE trial for presentation at a forthcoming medical meeting.

About EAGLE
The EAGLE trial is a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi (durvalumab) monotherapy or Imfinzi in combination with tremelimumab compared to standard-of-care chemotherapy in patients with recurrent or metastatic HNSCC who experienced progression following platinum-based chemotherapy, regardless of their PD-L1 tumour status.

The trial was conducted at 169 centres across 24 countries including the US, Europe, South America, Japan, Korea, Taiwan, Israel and Australia. The primary endpoint of the trial was OS, and secondary endpoints included progression-free survival, landmark OS, objective response rate and duration of response.

About HNSCC
Approximately 880,000 patients were diagnosed with head and neck cancer around the world in 2018. Two-thirds of patients diagnosed with head and neck cancer are in advanced stages (Stage III or IV), while the remaining one third are in the early stages of disease (Stage I or II). More than 90% of all head and neck cancers start in the squamous cells that line the mouth, nose and throat called head and neck squamous cell carcinomas (HNSCC).

About Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved for unresectable, Stage III non-small cell lung cancer (NSCLC) in more than 40 countries including the US, EU, and Japan based on the Phase III PACIFIC trial. Imfinzi is also approved for previously-treated patients with advanced bladder cancer in the US, Canada, Brazil, Israel, India, United Arab Emirates, Australia and Hong Kong.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small-cell lung cancer (SCLC), bladder cancer, head and neck cancer and other solid tumours.

About tremelimumab
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation and boosting the immune response to cancer. Tremelimumab is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and neck squamous cell carcinoma, liver cancer and blood cancers.

About AstraZeneca’s approach to immuno-oncology
IO is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies offer the potential for life-changing cancer treatments for the clear majority of patients.

We are pursuing a comprehensive clinical-trial programme that includes Imfinzi (anti-PDL1) as monotherapy and in combination with tremelimumab (anti-CTLA4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our Oncology pipeline, and from our research partners, may provide new treatment options across a broad range of tumours.

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On December 7, 2018 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that on December 6, it received a letter from the U.S. Food and Drug Administration (FDA) indicating that a partial clinical hold has been placed on its Phase 1 monotherapy study of MGD009, a B7-H3 × CD3 bispecific DART molecule, as well as on a combination study of MGD009 and MGA012 (anti-PD-1) (Press release, MacroGenics, DEC 7, 2018, View Source [SID1234531963]). Under the partial clinical hold, no new patients will be enrolled in either study until the partial hold is lifted by the FDA. Current study participants may continue to receive drug at their pre-assigned dose.

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The partial clinical hold was initiated following MacroGenics’ reporting of hepatic adverse events on the MGD009 monotherapy trial to the FDA, including reversible elevations of transaminases with or without concurrent elevations of bilirubin. Although these events have been otherwise uncomplicated and short-lived in duration, MacroGenics also communicated to the FDA the company’s plans to amend the existing MGD009 studies with additional supportive care to mitigate these events. The FDA has placed the trials on partial clinical hold, pending review of additional details regarding these events, and satisfactory review of the planned amendments to the monotherapy and combination study protocols and related documents. MacroGenics will be working closely with the FDA to review these events and seek to resolve this clinical hold.

"MacroGenics’ top concern in conducting clinical trials is the safety of study participants," said Scott Koenig, M.D., Ph.D. "As we’ve identified to the FDA, we believe that transaminitis observed in patients administered MGD009 was likely a cytokine-mediated event. We are working with the FDA and will provide an update when we have additional information. This partial clinical hold does not impact ongoing clinical studies for enoblituzumab and MGC018, our other B7-H3-targeted molecules."
About MGD009
MGD009 is a humanized, bispecific DART molecule that recognizes both B7-H3 and CD3 and has a prolonged serum half-life. B7-H3 is a member of the B7 family of molecules involved in immune regulation and is over-expressed on a wide variety of cancer cells, including cancer stem cells, as well as on the supporting tumor vasculature and underlying tissues, or stroma. The intended mechanism of action of MGD009 is its ability to redirect T cells, via their CD3 component, to kill B7-H3-expressing cells.

In addition to MGD009, MacroGenics’ comprehensive B7-H3 franchise includes enoblituzumab, an Fc-optimized monoclonal antibody, as well as MGC018, an antibody-drug conjugate (ADC). These clinical molecules target B7-H3. MacroGenics retains worldwide rights to its franchise of three B7-H3-based molecules.

On December 6, 2018 QIAGEN N.V. (NYSE: QGEN; Frankfurt Prime Standard: QIA) reported that a clinical development program is underway with Novartis to bring to market a molecular test as a companion diagnostic to guide the use of the investigational compound BYL719 (alpelisib) in combination with fulvestrant for men and postmenopausal women living with PIK3CA mutated hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (Press release, Qiagen, DEC 6, 2018, View Source [SID1234531932]).

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The Novartis drug candidate is in late-stage development, and QIAGEN expects to provide its companion diagnostic to clinical laboratory partners who will then be ready to offer immediate access to the test upon potential regulatory approvals of BYL719 and QIAGEN’s test.

Novartis has completed a Phase III clinical trial (SOLAR), testing BYL719 in combination with fulvestrant for patients with PIK3CA mutated HR+/HER2- advanced breast cancer.

QIAGEN’s companion diagnostic for PIK3CA mutations will provide a complete Sample to Insight workflow, from DNA extraction to detection of the clinically relevant mutations and final reporting. The test will be clinically validated for analysis of both FFPE tissue and liquid biopsy samples using plasma. The companion diagnostic will run on the Rotor-Gene Q MDx cycler, which is part of the modular QIAsymphony family of automation solutions, established in numerous pathology laboratories worldwide.

On December 6, 2018 Moderna, Inc. (Nasdaq: MRNA), a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported the pricing of its initial public offering of 26,275,993 shares of common stock at a public offering price of $23.00 per share, before underwriting discounts and commissions (Press release, Moderna Therapeutics, DEC 6, 2018, View Source [SID1234531949]). Moderna’s common stock is expected to begin trading on The Nasdaq Global Select Market on December 7, 2018 under the ticker symbol "MRNA." All of the common stock is being offered by Moderna. The gross proceeds of the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Moderna, are expected to be $604.3 million, excluding any exercise of the underwriters’ option to purchase additional shares. The offering is expected to close on December 11, 2018, subject to satisfaction of customary closing conditions. Moderna has granted the underwriters a 30-day option to purchase up to an additional 3,941,398 shares of Moderna’s common stock at the initial public offering price, less underwriting discounts and commissions.

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Morgan Stanley, Goldman Sachs & Co. LLC and J.P. Morgan are acting as joint lead book-running managers for the offering. BofA Merrill Lynch, Barclays Capital Inc. and Piper Jaffray & Co. are acting as book-running managers for the offering. Oddo BHF SCA, Oppenheimer & Co. Inc., Needham & Company, LLC and Chardan are acting as co-managers for the offering.

Registration statements relating to the shares being sold in this offering have been filed with the Securities and Exchange Commission and were declared effective on December 6, 2018. The offering is being made only by means of a prospectus. Copies of the final prospectus may be obtained, when available, from Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014; from Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, telephone: 1-866-471-2526, facsimile: 212-902-9316, or email: [email protected]; or from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, telephone: 1-866- 803-9204, or email: [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, 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 law of any such state or jurisdiction.