Context Therapeutics Announces New Preclinical Data on Apristor at San Antonio Breast Cancer Symposium

On December 8, 2018 Context Therapeutics, a clinical-stage biotechnology company, reported new preclinical data on Apristor (onapristone extended release), its first-in-class full progesterone receptor antagonist, showing that the investigational medicine inhibits tumor cell line growth in hormone receptor positive (HR+) breast cancer cell lines (Press release, Context Therapeutics, DEC 8, 2018, View Source [SID1234531939]). Additionally, it was shown that Apristor is synergistic with current standard of care therapies for HR+ metastatic breast cancer, including the Cdk4/6 inhibitor Ibrance (palbociclib) and the selective estrogen receptor degrader Faslodex (fulvestrant).

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"Progesterone receptor is the forgotten target", said Carol Lange, PhD, Professor of Medicine at the University of Minnesota and principal investigator of the research presentation. "HR+ breast cancer is driven by two hormones, estrogen and progesterone. While there are over half a dozen approved medicines to block estrogen and estrogen-related signaling, there are no FDA approved medicines in cancer to block progesterone. The data presented shows that blocking progesterone-related signaling via Apristor is not only active alone in tumor models but it also enhances the activity of medicines that either directly or indirectly target estrogen."

The data presented shows that:

Progesterone / progesterone peceptor (PR) is a unique target distinct from estrogen / estrogen receptor

PR is critical for in vitro growth of HR+ breast cancer cells

PR antagonism via Apristor reduces the expression of cancer promoting genes

PR antagonism is synergistic with Cdk4/6 inhibitors and a SERD

"We are encouraged by these new preclinical data, which speak to the important role PR plays in facilitating HR+ breast cancer disease progression," said Deepak Lala, PhD, Chief Technology Officer of Context. "This is the first study to show that PR antagonism is synergistic with new treatment modalities, including Cdk4/6 inhibition. "

About Apristor

Apristor (onapristone extended release) is Context’s wholly owned, first-in-class, orally active extended release formulation of onapristone, a full progesterone receptor antagonist. Progesterone receptor [PR] plays a critical role in facilitating breast cancer disease progression as well as therapeutic resistance to first line antiestrogen and/or Cdk4/6 inhibitor therapies. Apristor is the only full PR antagonist that is being developed to target breast cancer. Apristor has the potential to transform the treatment of breast cancer, through the potent inhibition of PR signaling thereby blocking breast cancer cell proliferation and overcoming resistance to first line antiestrogen and Cdk4/6 inhibitor therapy.

AFTER ALLY BRIDGE-BACKED SERIES A, SHANGHAI’S GENFLEET LOOKS TO CLINIC

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.

Syros Announces New Preclinical Data on SY-1365 at San Antonio Breast Cancer Symposium

On December 7, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported new preclinical data on SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, showing that it inhibits tumor cell growth in hormone receptor-positive (HR-positive) breast cancer cell lines that are resistant to treatment with CDK4/6 inhibitors and that it has synergistic activity in combination with fulvestrant in these treatment-resistant cells (Press release, Syros Pharmaceuticals, DEC 7, 2018, View Source [SID1234531956]). These data are being presented by Syros’ collaborators from Dana-Farber Cancer Institute at the San Antonio Breast Cancer Symposium (SABCS).

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"While CDK4/6 inhibitors have emerged as an important class of treatments for HR-positive metastatic breast cancer, patients eventually develop resistance," said Rinath M. Jeselsohn, M.D., Instructor in Medicine at Dana-Farber and principal investigator of the research presentation. "These data shed light on potential mechanisms behind resistance to CDK4/6 inhibitors, pointing to CDK7 as one of the genes critical to the growth of treatment-resistant HR-positive breast cancer cells and selective CDK7 inhibition as a promising new approach for the treatment of HR-positive breast cancer. I look forward to the continuing to evaluate SY-1365 in the ongoing Phase 1 trial focused on breast and ovarian cancers."

Researchers from Dana-Farber characterized an HR-positive breast cancer cell line that is resistant to treatment with CDK4/6 inhibitors, and they demonstrated that these cells have alterations in the RB-pathway, including loss of the retinoblastoma (Rb) protein, higher levels of p107, CDK2 and cyclin E2, and lower levels of the estrogen receptor.

The aim of this study was to identify genes critical for the growth and survival of these cells by evaluating both resistant and sensitive cell lines. The researchers also tested SY-1365 in these resistant cell lines as a single agent and in combination with fulvestrant, an estrogen receptor degrader. The data, highlighted in a Spotlight poster discussion session, show that:

CDK7 and ESR1 are critical for in vitro cell growth in both CDK4/6 inhibitor-sensitive and CDK4/6 inhibitor-resistant cells.
SY-1365 significantly arrests cell cycle progression and reduces the expression of cancer-promoting genes in both CDK4/6 inhibitor-sensitive and -resistant cell lines.
SY-1365 in combination with fulvestrant demonstrates synergistic activity in CDK4/6 inhibitor resistant cells.
"We are encouraged by these new preclinical data, which speak both to the importance of CDK7 inhibition in HR-positive breast cancer and to the specific potential of this approach in patients who develop resistance to CDK 4/6 inhibitors.," said David Roth, M.D., Chief Medical Officer of Syros. "We are particularly pleased by the data for SY-1365 in combination with fulvestrant, which demonstrate synergistic activity in CDK4/6 inhibitor-resistant HR-positive breast cancer cells. These data support the ongoing clinical evaluation of SY-1365 in combination with fulvestrant in HR-positive breast cancer patients who progress after treatment with a CDK 4/6 inhibitor. We are actively enrolling patients in the Phase 1 trial and are committed to exploring the full potential of CDK7 inhibition with SY-1365 for people with difficult-to-treat cancers."

The ongoing Phase 1 trial of SY-1365 is a multi-center, open-label trial designed to evaluate the safety, tolerability and anti-tumor activity of SY-1365 in patients with advanced solid tumors. Following completion of the dose escalation portion of the trial, Syros opened expansion cohorts to further assess the potential of SY-1365 in multiple ovarian and breast cancer patient populations. The expansion cohorts are evaluating SY-1365: as a single agent in primary platinum-refractory ovarian cancer patients; as a single agent in ovarian cancer patients who have relapsed after three or more therapies; in combination with carboplatin in ovarian cancer patients who have relapsed after one or more prior therapies; and in combination with fulvestrant in patients with HR+ metastatic breast cancer who have progressed after treatment with a CDK4/6 inhibitor. An additional cohort is enrolling patients with any solid tumor accessible for biopsy to further evaluate the mechanism of action of SY-1365. Additional details about the trial can be found using the identified NCT03134638 at www.clinicaltrials.gov.

Navidea Biopharmaceuticals Announces Patent Extension for Lymphoseek®

On December 7, 2018 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported that on November 23, 2018 the U.S. Food and Drug Administration ("FDA") released a letter to the U.S. Patent and Trademark Office ("USPTO") indicating that the USPTO is allowed to extend the patent duration of U.S. patent 6,409,990 for an additional 5 years or until May 12, 2025 (Press release, Navidea Biopharmaceuticals, DEC 7, 2018, View Source [SID1234531972]).

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This patent claims Lymphoseek (technetium (Tc 99m) tilmanocept) and has been exclusively licensed with varying geographical and medical indication coverages to Cardinal Health and Navidea. Allowance of this patent extension will permit Cardinal Health and Navidea to extend their exclusive rights to manufacture and commercialize Lymphoseek until the end of the extended patent term in 2025.

"I am pleased the FDA has taken positive action to extend the Lymphoseek patent until May 12, 2025," said Jed Latkin, CEO of Navidea. "We are excited that this extension allows us to continue advancing the science as Navidea prepares for the many other indications for which Tilmanocept can be used."

Chugai Files for Additional Indication of Anti-PD-L1 Antibody TECENTRIQ® for Small Cell Lung Cancer

On December 7, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed an application for humanized anti-PD-L1 monoclonal antibody TECENTRIQ Intravenous Infusion 1200 mg [generic name: atezolizumab (genetical recombination)], to the Ministry of Health, Labour and Welfare (MHLW) for an additional indication of the first line treatment of extensive-stage small cell lung cancer (ES-SCLC) (Press release, Chugai, DEC 7, 2018, View Source [SID1234531971]).

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"I am very pleased that we have completed filing for the line extension of TECENTRIQ. TECENTRIQ is the first cancer immunotherapy treatment to extend overall survival and progression-free survival in the first line treatment of ES-SCLC, and has recently been designated as an orphan drug by MHLW," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "Chugai is committed to seek approval so that we may deliver TECENTRIQ to ES-SCLC patients who have limited treatment options as early as possible."

This application is based on the results from a global phase I/III clinical study (IMpower133 study). This study is a multicenter, double-blind, randomized, placebo-controlled, global clinical study evaluating the efficacy and safety of TECENTRIQ in combination with chemotherapy (carboplatin and etoposide) which was compared with chemotherapy alone (carboplatin and etoposide) in chemotherapy-naive ES-SCLC patients. TECENTRIQ in combination with chemotherapy met the primary endpoint of overall survival (OS) as compared with chemotherapy alone in the intent to treat (ITT) analysis (median OS, 12.3 vs 10.3 months; hazard ratio=0.70, 95% confidence interval, 0.54-0.91; p=0.0069). The study also met co-primary endpoint of progression-free survival (PFS) (median PFS, 5.2 vs 4.3 months; hazard ratio=0.77, 95% confidence interval, 0.62-0.96; p=0.017). Safety of TECENTRIQ in combination with chemotherapy was consistent with the known safety profile of individual medicines, and no new safety signals were identified with the combination therapy.

About TECENTRIQ

In Japan, TECENTRIQ was approved for "unresectable and advanced/recurrent non-small cell lung cancer" in January 2018 and launched in April. An application for additional indication, first line treatment of non-small cell lung cancer was filed in March 2018.