On December 15, 2017 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) has reported that it initiated the United States Phase I bridging clinical trial of fruquintinib. Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors ("VEGFR") 1, 2 and 3, that has met its primary endpoint in several Phase II and III clinical trials in China for the treatment of colorectal, lung and gastric cancers (Press release, Hutchison China MediTech, DEC 15, 2017, http://www.chi-med.com/chi-med-initiates-fruquintinib-u-s-clinical-trials/ [SID1234522660]). The clinical study in the U.S. is a multi-center, open-label, Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors. The first drug dose was administered earlier this month. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT03251378.

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About Fruquintinib Development in China
Colorectal cancer: The China Food and Drug Administration ("CFDA") acknowledged acceptance of the New Drug Application ("NDA") for fruquintinib for the treatment of patients with advanced colorectal cancer ("CRC") in June 2017. Fruquintinib was subsequently awarded priority review status in view of its significant clinical value, according to a CFDA announcement in September 2017. The NDA is supported by data from the successful FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with CRC in China, which was highlighted in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held on June 5, 2017 (clinicaltrials.gov identifier NCT02314819). The FRESCO study followed an initial Phase I trial in 40 solid tumor patients, a Phase Ib study in 62 CRC patients, and a Phase II clinical trial in 71 CRC patients.

Lung cancer: Fruquintinib is being studied in a Phase III pivotal trial in approximately 520 third-line non-small cell lung cancer ("NSCLC") patients, known as the FALUCA study (clinicaltrials.gov identifier NCT02691299), following a Phase II clinical trial in 91 third-line NSCLC patients. Fruquintinib is concurrently being studied in a Phase II study in combination with Iressa (gefitinib) in first-line setting for patients with advanced or metastatic NSCLC (clinicaltrials.gov identifier NCT02976116).

Gastric cancer: In October 2017, Chi-Med initiated a pivotal Phase III clinical trial of fruquintinib in combination with Taxol (paclitaxel), known as the FRUTIGA study, for the treatment of over 500 patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (clinicaltrials.gov identifier NCT03223376).

In China, fruquintinib is jointly developed with Eli Lilly and Company.

About Fruquintinib
Fruquintinib (HMPL-013) is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, with lower off-target toxicities compared to other targeted therapies. Its tolerability, along with its clean drug-drug interaction profile demonstrated to date, may enable rational combination with other cancer therapies such as chemotherapy and other targeted therapies, which are being studied in our ongoing clinical trials of fruquintinib.

At an advanced stage, tumors secrete large amounts of vascular endothelial growth factor ("VEGF"), a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumor to provide greater blood flow, oxygen, and nutrients to the tumor. VEGF and VEGFR play pivotal roles in tumor-related angiogenesis, and fruquintinib inhibits the VEGF/VEGFR pathway. This represents an important therapeutic strategy in blocking the development of new blood vessels essential for tumors to grow and invade.

On December 15, 2017 Cancer Research UK reported the signing of a five-year drug-discovery collaboration between its subsidiary, Cancer Research Technology (CRT), and Celgene Corporation (link is external), to discover, develop and commercialise new anti-cancer treatments (Press release, Cancer Research UK, DEC 15, 2017, View Source [SID1234522659]).

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This arrangement represents an expansion of Cancer Research Technology’s theme-based translational model that now encompasses six industry partnerships, including this new collaboration with Celgene.

The collaboration is centred on mRNA translation, the cellular process of assembling proteins, which is a promising area of research with the potential to produce treatments that can target a fundamental characteristic of cancer cells.

Dr Iain Foulkes, Cancer Research Technology’s CEO, said: "This bold and exciting collaboration between one of industry’s leading innovators, Celgene, and CRT is part of our theme-based drug discovery approach and helps leverage our understanding of cancer biology and the needs of patients to drive the most promising discoveries into the clinic.

"This is our largest drug discovery collaboration to date and represents a major endorsement of the reputation and scale of our capacity and expertise in both drug discovery and clinical development by a leading industry partner."

Cancer Research Technology will lead drug discovery R&D activity and can progress clinical candidates through phase one trials.

Under the terms of the agreement*, Celgene will pay an upfront fee to Cancer Research Technology, and have the option to secure US rights to projects resulting from the collaboration, subject to the payment of additional option fees. Celgene will also have the option to secure Global rights to such projects at the end of phase one clinical trials, subject to the payment of additional option fees.

Cancer Research Technology can receive downstream royalties and development milestones from licensed programs.

On December 15, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that ZEJULA (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, is now available by prescription in Germany (Press release, TESARO, DEC 15, 2017, View Source [SID1234522658]). ZEJULA is also currently available for patients in the United Kingdom (UK) who have private insurance. On November 16, the European Commission (EC) approved ZEJULA as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response (CR) or partial response (PR) to platinum-based chemotherapy. ZEJULA is the first once-daily, oral PARP inhibitor to be approved in Europe that does not require BRCA mutation or biomarker testing.

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"As we continue to globalize our mission, we remain committed to enabling access to this important therapy for patients who have completed platinum-based chemotherapy and have limited treatment options. In the U.S., where ZEJULA has been approved since March, it is the most frequently prescribed PARP inhibitor for patients with ovarian cancer," said Orlando Oliveira, Senior Vice President and General Manager of TESARO International. "The introductions of ZEJULA in Germany and the UK are significant milestones for TESARO as we bring transformative therapies to patients with cancer around the globe. With two approved products in Europe, we are working quickly to make our medicines available in the 17 European countries where we have a direct presence."

The EC approval of ZEJULA was based on data from the clinically rigorous ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study of ZEJULA that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. The primary endpoint of the trial was progression free survival (PFS). Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by a robust, unbiased, blinded central review to be the earlier of radiographic or clinical progression. ZEJULA significantly increased PFS in patients with or without germline BRCA mutations as compared to the control arm. Treatment with ZEJULA reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (hazard ratio (HR) 0.27) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.

In the ENGOT-OV16/NOVA trial, the most common grade 3/4 adverse reactions to ZEJULA included thrombocytopenia (34%), anemia (25%), neutropenia (20%), and hypertension (8%). Following dose adjustment based on individual tolerability, the incidence of grade 3/4 thrombocytopenia was low, approximately 1% after month three. The majority of hematologic adverse events were successfully managed via dose modification, and discontinuation of therapy due to thrombocytopenia, neutropenia and anemia occurred in 3%, 2% and 1% of patients, respectively.

The approved starting dose of ZEJULA is 300 milligrams once per day. According to the European summary of product characteristics (SmPC), in patients below 58 kilograms, a starting dose of 200 milligrams once per day may be considered. The most commonly administered dose of ZEJULA over the course of the Phase 3 NOVA clinical trial was 200 milligrams once per day, following dose modification. Further exploratory analyses of the NOVA study indicated that individual dose modification maintained efficacy and reduced the rate of new adverse events1.

About Ovarian Cancer in Europe
Europe has one of the highest incidences of ovarian cancer in the world with approximately 45,000 women diagnosed each year2,3. In the European Union, ovarian cancer is the sixth-most common cancer and the fifth-most frequent cause of cancer death among women there2,4. Despite high initial response rates to platinum-based chemotherapy, approximately 85% of women with advanced ovarian cancer will experience a recurrence of the disease after first-line treatment5. The efficacy of chemotherapy also diminishes over time.

About ZEJULA (niraparib)
ZEJULA is a once-daily, oral poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor that is indicated in the European Union as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in 1.4% of patients receiving ZEJULA vs. 1.1% of patients receiving placebo in the Phase 3 NOVA trial, and 0.9% of patients treated with ZEJULA in all clinical studies. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Monitor complete blood counts (CBCs) weekly for the first month of treatment and modify the dose as needed. After the first month, it is recommended to monitor CBCs for the next 10 months of treatment, and periodically after this time. Based on individual laboratory values, weekly monitoring for the second month may be warranted.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Pre-existing hypertension should be adequately controlled before starting ZEJULA. Monitor blood pressure monthly for the first year and periodically thereafter during treatment with ZEJULA. ZEJULA should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the possible risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.

In clinical studies, the most common adverse reactions included: thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, abdominal pain, diarrhea, dyspepsia, urinary tract infection, fatigue/asthenia, decreased appetite, headache, dizziness, dysgeusia, palpitations, insomnia, nasopharyngitis, dyspnea, cough, and hypertension.

On December 14, 2017 Jnana Therapeutics Inc. reported a $50 million Series A financing (Press release, Jnana Therapeutics, DEC 14, 2017, View Source [SID1234529783]). The company is building the first drug discovery platform dedicated to targeting the solute carrier (SLC) family of transporters, the cell’s metabolic gates. Jnana’s proprietary small molecule platform allows the company to address therapeutic targets rapidly and comprehensively across the SLC transporter family.

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"SLC transporters provide cells with knowledge about their environment. These proteins are amongst the oldest in biology, and afford avenues to address virtually all major diseases. After 50 years of drug development, only a handful of SLCs have been harnessed to treat disease, leaving over 400 members unstudied. Our proprietary chemistry and biology platform allows us to systematically advance medicines based on the biology of these ancient information gathering systems," said Amir Nashat, Ph.D., Managing Partner with Polaris Partners and Chief Executive at Jnana. "We are targeting a broad range of medical conditions with significant unmet need, and we are fortunate to have the support of leaders in medicine and biotechnology."

Jnana is focusing on immunometabolism, lysosomal function and mucosal defense, important disease pathways where SLC transporters provide novel targets for immuno-oncology, inflammatory disorders and neurological diseases.

Seed funders Polaris Partners and Avalon Ventures were joined in the Series A syndicate by Versant Ventures, AbbVie Ventures, and Pfizer R&D Innovate.

Jnana’s founding team includes recognized leaders at the forefront of chemistry, drug discovery and development, translational medicine and company building. The company’s founders are:

Stuart Schreiber, Ph.D., Morris Loeb Professor at Harvard University, Howard Hughes Medical Institute Investigator and Cofounder of Broad Institute and biotech companies including Vertex, Ariad and H3 Biomedicine.
Ramnik Xavier, M.D., Ph.D., Chief of Gastroenterology at Massachusetts General Hospital, Professor at Harvard Medical School and Institute Member at Broad Institute.
Joanne Kotz, Ph.D., President at Jnana, previously Director at Broad Institute.
Joel Barrish, Ph.D., Chief Scientific Officer at Jnana and former VP and Head of Discovery Chemistry at Bristol-Myers Squibb.
Dr. Nashat of Polaris Partners will be joined on Jnana’s board of directors by Kevin Kinsella, founder of Avalon Ventures, and Carlo Rizzuto, Ph.D. Partner at Versant.

Generex has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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