On June 1, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that it has held its pre-New Drug Application ("NDA") meeting with the U.S. Food and Drug Administration ("FDA") for surufatinib for the treatment of patients with advanced neuroendocrine tumors ("NET") (Press release, Hutchison China MediTech, JUN 1, 2020, View Source [SID1234558780]). Chi-Med has reached an agreement with the FDA that the completed SANET-ep (non-pancreatic NET) and SANET-p (pancreatic NET) studies, along with existing data from surufatinib in U.S. non-pancreatic and pancreatic NET patients, could form the basis to support a U.S. NDA submission.

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The FDA granted Fast Track Designation status to surufatinib for the non-pancreatic and pancreatic NET development programs in April 2020. Chi-Med has initiated preparatory work for the U.S. NDA and intends to utilize a rolling submission under Fast Track Designation Status. The rolling NDA allows completed portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. Filing acceptance of the NDA is subject to FDA review of the complete application. The planned start of the NDA submission is late 2020.

About Surufatinib

Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Chi-Med currently retains all rights to surufatinib worldwide.

NET in the U.S., Europe and Japan: In the U.S., surufatinib was granted Fast Track Designations for development in pancreatic and non-pancreatic (extra-pancreatic) NET in April 2020, and Orphan Drug Designation for pancreatic NET in November 2019. A U.S. FDA NDA submission is being prepared. Regulatory interactions in Europe and Japan are also underway to confirm the clinical development strategy and potential path to registration. All such interactions are based on the robust data from the two positive Phase III studies of surufatinib in NET in China, and the ongoing multi-cohort Phase Ib study in the U.S. that began in November 2015 (clinicaltrials.gov identifier: NCT02549937).

Non-pancreatic neuroendocrine tumors in China: In November 2019, a NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was accepted for review by the China National Medical Products Administration (NMPA) and granted Priority Review status in December 2019. The NDA is supported by data from the successful SANET-ep study, a Phase III study of surufatinib in patients with advanced non-pancreatic neuroendocrine tumors in China for whom there is no effective therapy. A 198-patient interim analysis was conducted in June 2019, leading the Independent Data Monitoring Committee ("IDMC") to determine that the study met the pre-defined primary endpoint of progression-free survival ("PFS") and should be stopped early. The positive results of this trial were highlighted in an oral presentation at the 2019 European Society for Medical Oncology Congress (clinicaltrials.gov identifier: NCT02588170).

Pancreatic neuroendocrine tumors in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic NET in China. A second NDA for surufatinib for the treatment of patients with advanced pancreatic NET is being prepared for submission, following an interim analysis review conducted in January 2020 by the IDMC that recommended the registrational study be terminated early as the pre-defined primary endpoint of PFS had already been met (clinicaltrials.gov identifier: NCT02589821). Study results will be submitted for presentation at an upcoming scientific conference.

Biliary tract cancer in China: In March 2019, we initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is overall survival (OS) (clinicaltrials.gov identifier NCT03873532).

Immunotherapy combinations: We have entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317), Tuoyi (toripalimab) and Tyvyt (sintilimab), which are approved in China.

On June 1, 2020 Synlogic, Inc., (Nasdaq: SYBX) a clinical stage company applying synthetic biology to beneficial microbes to develop novel, living medicines, reported the publication in Nature Communications of preclinical data supporting its first clinical immuno-oncology program, SYNB1891, which is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors or lymphoma (Press release, Synlogic, JUN 1, 2020, View Source [SID1234558779]). Data described in the publication demonstrate that SYNB1891 treatment cleared tumors and stimulated antitumor immunity in preclinical models of cancer.

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"The targeted delivery and dual immune stimulatory activity of SYNB1891 offer distinct advantages over other approaches," said Aoife Brennan, M.B., Ch. B., Synlogic’s president and chief executive officer. "The preclinical data published today highlight the transformative potential of SYNB1891. Together with the early experience in the clinic demonstrating feasibility and tolerability in the initial cohorts of the clinical trial, these data provide support for the continued development of SYNB1891 as a potential therapeutic option to expand the benefits of immunotherapy to more patients with cancer."

The publication titled, "Immunotherapy with an engineered bacteria by targeting the STING pathway for anti-tumor immunity," details the engineering and characterization of SYNB1891. The work describes preclinical studies that demonstrate anti-tumor activity and generation of immunological memory by SYNB1891 in mouse models of cancer, as well as its robust activation of human antigen presenting cells (APCs) that are key to the generation of an anti-tumoral immune response.

SYNB1891 is an engineered strain of E. coli Nissle, that produces cyclic di-AMP (CDA), a stimulator of the STING (STimulator of INterferon Genes) pathway. This mechanism can play a critical role in the initiation of an anti-tumor immune response via activation of APCs and presentation of tumor antigens. The bacterial chassis of SYNB1891 also stimulates the innate immune system by several other mechanisms, including via Toll-like receptors (TLRs), potentially adding to the magnitude of the overall immune response. A notable advantage of SYNB1891 is that the STING agonist is not released by the bacteria until they have been engulfed by the target cells (APCs) and so there is less risk of deleterious effects on other immune cells such as T-cells. Also, while SYNB1891 has been engineered with safety features that are designed to prevent its replication unless supplemented with specific nutrients, the bacteria remain active for several days within the injected tumor to stimulate a local immune response.

Intra-tumorally administered SYNB1891 is being evaluated as a monotherapy in an ongoing Phase 1 open-label, multicenter, dose escalation clinical trial (NCT04167137) in patients with advanced solid tumors or lymphoma. Synlogic expects to release data from the monotherapy arm of this study in late 2020. After establishing a maximum tolerated dose for SYNB1891 as monotherapy, Synlogic expects to initiate a second arm of the trial in which subjects will receive escalating dose levels of SYNB1891 in combination with a fixed dose of the checkpoint inhibitor, atezolizumab (Tecentriq), to establish a recommended dose for the combination regimen.

The DOI for the paper is 10.1038/s41467-020-16602-0.

On June 1, 2020 AbbVie (NYSE:ABBV), a research-based global biopharmaceutical company, and Jacobio Pharmaceuticals, a clinical-stage pharmaceutical company, reported a global, strategic collaboration to develop and commercialize SHP2 inhibitors, which target a key node in cancer and immune cells (Press release, AbbVie, JUN 1, 2020, View Source [SID1234558778]).

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SHP2 is an important protein mediator of cellular signaling through RAS/MAP kinase pathway. Many tumors have genetic mutations, driving abnormal cancer cell growth which relies on SHP2 activity. SHP2 also plays a key role to control cytokine production and immune cell response. Therefore, inhibition of SHP2 is believed to have dual effects by potentially reducing cancer cell growth and modulating immune responses to generate anti-tumor activities. Jacobio’s early clinical stage SHP2 assets, JAB-3068 and JAB-3312, are oral small molecules designed to specifically inhibit SHP2 activity.

"Identifying promising new targeted approaches for solid tumor patients is a high priority for us," said Mohit Trikha, Ph.D., vice president and head, early development oncology and Bay Area site head, AbbVie. "Jacobio’s SHP2 program has the potential to treat cancer patients across many tumor types. By targeting a key node in both cancer and immune cell signaling pathways, SHP2 inhibition, both as a monotherapy and potentially in combination with other agents, may rapidly advance new treatment options for cancer patients."

"We are excited to expand our efforts in global development of delivering breakthrough innovation to not just Chinese, but global patients with cancer," said Yinxiang Wang, Ph.D., CEO and Chairman, Jacobio. "We look forward to a productive collaboration with AbbVie focused on rapidly advancing this novel SHP2 first-in-class therapy as a new approach for multiple cancer types. I am confident that this partnership will strengthen our R&D capabilities and ultimately bring benefits to cancer patients."

Under the terms of the agreement, AbbVie will be granted an exclusive license to the SHP2 portfolio. Jacobio will continue to conduct early global clinical trials of JAB-3068 and JAB-3312 with AbbVie covering R&D expenses. Upon completion, AbbVie will assume global development and commercialization responsibilities. Jacobio has an option, exercisable before the initiation of registrational trials, to exclusively develop and commercialize the SHP2 program in mainland China, Hong Kong, and Macau. Financial terms were not disclosed and the transaction is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

On June 1, 2020 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that patients in the OCEAN study stay on treatment longer than previously estimated (Press release, Oncopeptides, JUN 1, 2020, View Source [SID1234558777]). As a consequence, top-line results are estimated for H1 2021 instead of previously communicated Q4 2020. Patient recruitment in OCEAN will remain open to ensure that the 339 disease progression events needed to complete the study can be reached within a reasonable timeframe.

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OCEAN is a randomized, comparative study between melflufen and pomalidomide in patients with relapsed refractory multiple myeloma (RRMM). The patients enrolled in the study have previously been treated with at least an immunomodulator (IMiD) and a proteasome inhibitor (PI) and have all developed resistance to their last line of therapy and to lenalidomide (IMiD), the most commonly used drug for the treatment of multiple myeloma. The primary endpoint of the phase 3 study is Progression Free Survival (PFS). The results will be evaluated once 339 patients have progressed in their disease.

"A recent analysis indicates that patients enrolled in the OCEAN-study continue treatment for a longer period of time than originally estimated, which speaks to the potential benefit patients can have by participating in this trial", says Jakob Lindberg, CEO of Oncopeptides. "However, this most likely increases the time required to reach the number of disease progression events needed to complete the study. We will continue patient enrollment to enable an analysis of results within a reasonable timeframe."

Oncopeptides is preparing an application for accelerated approval in Q2 2020 based on the results from the ongoing pivotal phase 2 study HORIZON, evaluating melflufen in RRMM patients. Data from the pivotal phase 3 study OCEAN, will form the basis for a submission of a supplemental New Drug Application (sNDA) to the US FDA in H2 2021, followed by a submission of a Marketing Authorization Application (MAA) in Europe.

The information in the press release is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person above, on June 1, 2020 at 08.00 (CET).

About melflufen
Melflufen (melphalan flufenamide) is a first-in-class anti-cancer peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.