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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).

"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]).

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]).

"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.

FDA approves Roche’s Tecentriq in combination with Avastin and chemotherapy for the initial treatment of people with a specific type of metastatic lung cancer

On December 7, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) approved Tecentriq (atezolizumab) in combination with Avastin (bevacizumab), paclitaxel and carboplatin (chemotherapy), for the initial (first-line) treatment of people with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumour aberrations (Press release, Hoffmann-La Roche, DEC 7, 2018, View Source [SID1234531970]).

"This Tecentriq regimen has demonstrated a significant survival benefit in the initial treatment of metastatic non-squamous non-small cell lung cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Today’s approval supports our combination approach for Tecentriq in lung cancer and our vision to develop medicines that improve outcomes for patients with this complex disease."

This approval is based on results from the Phase III IMpower150 study, which showed that Tecentriq in combination with Avastin and chemotherapy helped people live significantly longer, compared to Avastin and chemotherapy (median overall survival [OS]=19.2 versus 14.7 months; hazard ratio [HR]=0.78; 95%, CI: 0.64–0.96; p=0.016) in the intention-to-treat wild-type (ITT–WT) population.[1] The safety profile of the Tecentriq combination was consistent with that observed in previous studies.

Roche is working with the FDA on post-marketing commitments (PMCs) to better understand and characterise the potential effects of Tecentriq-related anti-drug antibodies (ADAs) and neutralising antibodies (NAbs) across all of our studies. An analysis of ADAs in the IMpower150 study showed no impact on the efficacy of Tecentriq.

Tecentriq is also approved by the FDA to treat people with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK genetic alterations.

About the IMpower150 study
IMpower150 is a multicentre, open-label, randomised, controlled Phase III study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV or recurrent metastatic non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease.

It enrolled 1,202 people, of whom 1,045 were in the ITT-WT subpopulation, which excluded those people with EGFR and ALK mutations. People were randomised (1:1:1) to receive:

Tecentriq plus carboplatin and paclitaxel (Arm A), or
Tecentriq and Avastin plus carboplatin and paclitaxel (Arm B), or
Avastin plus carboplatin and paclitaxel (Arm C, control arm).
The co-primary endpoints comparing Arms B and C were OS and progression-free survival (PFS), as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) and assessed in the ITT-WT subpopulation. Key secondary endpoints included investigator-assessed PFS, OS and safety in the ITT population.

A summary of the ITT-WT data from the IMpower150 study that support this approval is included below:[1]

Tecentriq in combination with Avastin and chemotherapy helped people live significantly longer, compared to Avastin and chemotherapy (median OS=19.2 versus 14.7 months; HR=0.78; 95%, CI: 0.64–0.96; p=0.016).
In addition, Tecentriq in combination with Avastin and chemotherapy reduced risk of disease worsening or death (PFS) by 29%, compared to Avastin and chemotherapy (HR: 0.71; 95%, CI: 0.59–0.85, p=0.0002).
Tecentriq in combination with Avastin and chemotherapy shrank tumours (overall response rate [ORR]) in 55% of people (95%, CI: 49–60) compared to 42 percent of people (95 percent CI: 37-48) on Avastin and chemotherapy.
4% of people receiving Tecentriq in combination with Avastin and chemotherapy experienced a complete response (CR), and 51% of people experienced a partial response (PR).
The median duration of response (DoR) for people receiving Tecentriq in combination with Avastin and chemotherapy was 10.8 months (95%, CI: 8.4–13.9) compared to 6.5 months (95 percent CI: 5.6-7.6) for people on Avastin and chemotherapy.
The most common adverse reactions (≥20%) in people receiving Tecentriq in combination with Avastin and chemotherapy were fatigue and lack of energy (asthenia; 50%), hair loss (alopecia; 48%), nausea (39%), diarrhoea (32%), constipation (30%), decreased appetite (29%), joint pain (arthralgia; 26%), hypertension (25%), and pain from nerve damage (peripheral neuropathy; 24%).
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 the Tecentriq (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat first-line advanced NSCLC. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T cell tumour infiltration and enabling priming and activation of T cell responses against tumour antigens.

About Tecentriq (atezolizumab)
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 underway, evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 80 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Avastin (bevacizumab)
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

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.