On January 15, 2019 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported PharmaCyte’s partner, Austrianova, has successfully encapsulated the live cells used in PharmaCyte’s therapy for its planned clinical trial in patients with locally advanced, non-metastatic, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, JAN 15, 2019, View Source [SID1234532656]). The cells are now growing and dividing inside the Cell-in-a-Box capsules.

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PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said, "We are now in the process of monitoring the growth and division of the live cells as they spend more time in a ‘nutrient bath.’ This will allow the cells to continue to grow and divide and then completely fill the capsules. Once the capsules are completely full of live cells, they will be placed into syringes and frozen. Austrianova will then commence testing the capsules in the frozen syringes to finalize PharmaCyte’s clinical trial material."

Since its pre-production "engineering runs" in late 2018, Austrianova has further enhanced the manufacturing process and equipment. Once the testing of the syringes is successfully completed, the data and reports generated from this process will allow the completion of the Investigational New Drug application (IND) that must be submitted to the U.S. Food and Drug Administration (FDA) to apply for approval to begin a clinical trial in LAPC.

On January 15, 2019 Seres Therapeutics, Inc. (Nasdaq: MCRB) reported the appointment of Eric D. Shaff as President and Chief Executive Officer (Press release, Seres Therapeutics, JAN 15, 2019, View Source [SID1234532657]). Mr. Shaff, who is currently Chief Operating and Financial Officer, succeeds Roger J. Pomerantz, M.D. Mr. Shaff has also joined Seres’ Board of Directors and will continue to serve as Seres’ principal financial officer on an interim basis. Dr. Pomerantz will continue as Chairman of Seres’ Board of Directors.

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Noubar Afeyan, Ph.D., Lead Director and Co-Founder of Seres Therapeutics and CEO of Flagship Pioneering, commented, "Eric is an experienced business leader with exceptional strategic and operational acumen, and the Board has great confidence in his ability to successfully lead Seres. We are pleased to continue to work with Roger as he returns to his original role as Board Chair. We thank him for his important contributions to the development and growth of Seres since it spun out from Flagship Pioneering in 2014 and look forward to our additional collaborations."

"Seres continues to be the leader in the research and development of microbiome therapeutics, and I am honored and privileged to lead the Company’s next phase of development," said Mr. Shaff. "I look forward to executing the most effective path forward for the Company’s strategy, seeking to create value for shareholders, and most importantly, developing meaningful new medicines for patients in need."

Said Dr. Pomerantz, "I am proud of the significant progress that the Seres team has made during the last five years. The Company has developed leading microbiome drug discovery capabilities, unparalleled manufacturing competencies and a number of promising therapeutic candidates for difficult-to-treat diseases. I look forward to Eric’s leadership of the company and a bright future for Seres and its microbiome therapeutics."

Mr. Shaff has served as Seres’ Chief Financial Officer, Executive Vice President and Treasurer since November 2014, and in January 2018, he was appointed to the additional role of Chief Operating Officer. Mr. Shaff also serves on the Board of Directors for Sigilon Therapeutics and has extensive experience in the biotechnology field, having worked at Momenta Pharmaceuticals and Genzyme Corporation, where he was Vice President of Finance for the Personalized Genetic Health division. Mr. Shaff received his B.A. from the University of Pennsylvania and his MBA from Cornell University.

On January 15, 2019 Pierre Fabre reported updated safety and efficacy results, including mature overall survival (OS), from the safety lead-in of the Phase 3 BEACON CRC trial evaluating the triplet combination of BRAFTOVI (encorafenib), a BRAF inhibitor, MEKTOVI (binimetinib), a MEK inhibitor and ERBITUX (cetuximab), an anti-EGFR antibody, in patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC) (Press release, Pierre Fabre, JAN 15, 2019, View Source [SID1234532658]). The results showed that mature median OS was 15.3 months (95% CI, 9.6–not reached) for patients treated with the triplet combination therapy. These data will be presented on Saturday 19 January at the ASCO (Free ASCO Whitepaper) 2019 Gastrointestinal Cancers Symposium in San Francisco, California.

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Updated median progression-free survival (mPFS) and updated confirmed overall response rate (ORR) results for patients treated with the triplet in the safety lead-in remain the same, as previously reported, with 8 months mPFS (95% CI, 5.6–9.3) and a 48% ORR (95% CI, 29.4–67.5). Among the 17 patients who received only one prior line of therapy, the ORR was 62%.

"We are delighted to see such encouraging data from the BEACON CRC trial, where the mature median overall survival of 15.3 months represents a marked improvement in comparison with the current standards of care for patients with BRAF-mutant mCRC," said Josep Tabernero, MD, PhD, BEACON CRC trial lead investigator and director of the Vall d’Hebron Institute of Oncology in Barcelona, Spain. "These latest data bring us one step closer to understanding the full potential of this triplet therapy, as a possible new treatment option for these patients."

A BRAF mutation is present in up to 15% of all patients with mCRC, and V600E is the most common BRAF mutation.1–5 BRAFV600E-mutant mCRC patients have a mortality risk more than double that of mCRC patients without the mutation, and currently there are no European Commission (EC)-approved therapies specifically indicated for this high unmet need population.3–10

The most common grade 3 or 4 adverse events seen in at least 10% of patients were fatigue (13%), anaemia (10%), increased creatine phosphokinase (10%), increased aspartate aminotransferase (10%) and urinary tract infections (10%). The rate of grade 3 or 4 skin toxicities continued to be lower than generally observed with ERBITUX in mCRC.

"The encouraging OS data from the updated BEACON CRC safety lead-in trial clearly demonstrate the therapeutic potential of the triplet combination of BRAFTOVI, MEKTOVI and ERBITUX for the treatment patients with BRAFV600E-mutant mCRC, a notoriously difficult-to-treat cancer," said Frédéric Duchesne, President & CEO of the Pierre Fabre Pharmaceuticals Division. "We are extremely delighted with these recent results, which are in line with our R&D strategy to target those cancers where the greatest patient need exists through an emphasis on biomarker-driven treatments."

On 20 September 2018, the EC granted marketing authorisation for the combination of BRAFTOVI and MEKTOVI for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test.11,12 The EC decision is applicable to all 28 European Union member states plus Liechtenstein, Iceland and Norway.

On 7 August 2018, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to BRAFTOVI, in combination with MEKTOVI and ERBITUX, for the treatment of patients with BRAFV600E-mutant mCRC as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease.13

The triplet combination of BRAFTOVI, MEKTOVI and ERBITUX for the treatment of patients with BRAFV600E-mutant mCRC is investigational and not approved by the EC.

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer.14 In the US alone, an estimated 140,250 patients will be diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease.15 BRAF mutations are estimated to occur in 10% to 15% of patients with mCRC and represent a poor prognosis for these patients.1–5 The V600 mutation is the most common BRAF mutation and the risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF.1,10,16 Several irinotecan and cetuximab-containing regimens, similar to the BEACON CRC control arm, have established observed historical published benchmarks in BRAFV600E-mutant mCRC patients, whose disease has progressed after one or two prior lines of therapy. These benchmarks include ORR of 4% to 8%, mPFS of 2 to 3 months and median OS of 4 to 6 months.

About BEACON CRC
BEACON CRC is a randomised, open-label, global trial evaluating the efficacy and safety of BRAFTOVI, MEKTOVI and ERBITUX in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combination targeted therapy in BRAFV600E-mutant mCRC. Thirty patients were treated in the safety lead-in and received the triplet combination (BRAFTOVI 300 mg daily, MEKTOVI 45 mg twice daily and ERBITUX per label). Of the 30 patients, 29 had a BRAFV600 mutation. MSI-H, resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomised portion of the trial. The randomised portion of the BEACON CRC trial is designed to assess the efficacy of BRAFTOVI in combination with ERBITUX with or without MEKTOVI compared with ERBITUX and irinotecan-based therapy. Approximately 615 patients are expected to be randomised 1:1:1 to receive triplet combination, doublet combination (BRAFTOVI and ERBITUX) or the control arm (irinotecan-based therapy and ERBITUX). The study has been amended to include an interim analysis of endpoints including ORR. The primary overall survival endpoint is a comparison of the triplet combination to the control arm. Secondary endpoints address efficacy of the doublet combination compared with the control arm, and the triplet combination compared with the doublet therapy. Other secondary endpoints include PFS, duration of response, safety and tolerability. Health-related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia-Pacific region. Trial recruitment was completed in 2018. The BEACON CRC trial is being conducted with support from Ono Pharmaceutical Co., Pierre Fabre and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).

About BRAFTOVI (encorafenib) and MEKTOVI (binimetinib)
BRAFTOVI (encorafenib) is an oral small-molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral small-molecule MEK inhibitor that targets key enzymes in the MAPK signalling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and others.

In Europe, the combination is approved for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test. On 27 June 2018, Pierre Fabre’s partner Array BioPharma, which has exclusive rights for these medicines in the United States (US), announced that the combination of BRAFTOVI and MEKTOVI was approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.18,19 BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma. BRAFTOVI and MEKTOVI have also received regulatory approval in Japan. The Swiss Medicines Agency (Swissmedic) is currently reviewing the Marketing Authorization Applications for BRAFTOVI and MEKTOVI submitted by Pierre Fabre.

On January 15, 2019 KitovPharma (NASDAQ/TASE:KTOV), an innovative pharmaceutical company, reported new findings from its ongoing collaboration with researchers from the Hebrew University of Jerusalem (Press release, Kitov Pharmaceuticals , JAN 15, 2019, View Source [SID1234532770]). The data reveal NT219’s high affinity and selective binding to its target proteins.

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Hadas Reuveni, Ph.D., Chief Technology Officer at Kitov’s subsidiary, TyrNovo Ltd., in collaboration with Dr. Galia Blum and Dr. Ofra Moshel from the Hebrew University demonstrated that NT219 binds directly to Insulin Receptor Substrates (IRS) 1/2 and to the Signal Transducer and Activator of Transcription 3 (STAT3), both known modulators of tumor survival, metastasis and drug resistance. Data showed that a short exposure of cancerous cells to NT219 was sufficient to trigger irreversible shutdown of these pathways, resulting in a long-term anti-cancer effect.

Based on these latest findings, Kitov and Yissum, the Technology Transfer company of the Hebrew University of Jerusalem, have extended their collaboration agreement in order to deepen the understanding of NT219’s efficacy in overcoming tumors’ resistance to immunotherapy.

As previously reported (Reuveni et al, Cancer Research, 2013) upon binding to IRS1/2 a three-step mechanism is activated. IRS1/2 dissociates from the cell membrane, undergoes serine phosphorylation which prevents rebinding to the receptor, and is finally degraded by the proteasome. This sequence of events leads to the blockage of AKT – a major cancer cell survival pathway.

"We are excited about the new data which demonstrate NT219’s unique mechanism of action. NT219, a new and promising concept in cancer therapy, is designed to prevent, reverse, and delay resistance to anti-cancer drugs. We are developing NT219 as a drug to be used in combination with other therapies that has a potential to overcome cancer drug resistance and to boost the efficacy of numerous oncology drugs on the market today," stated Kitov CEO, Isaac Israel.

About NT219

NT219 is a small molecule that presents a new concept in cancer therapy by promoting the degradation and inhibiting the phosphorylation of two oncology-related signal transducers, Insulin Receptor Substrates (IRS) 1/2 and signal transducer and activator of transcription 3 (STAT3), respectively. While targeted anti-cancer drugs inhibit the "ON" signal, NT219 activates the "OFF" switch, extensively blocking major oncogenic pathways. In pre-clinical trials, NT219, in combination with several approved cancer drugs, displayed potent anti-tumor effects and increased survival in various cancers, including sarcoma, melanoma, pancreatic, lung, head & neck, prostate and colon cancers, by preventing the tumors from developing drug resistance and reversing resistance after it had been acquired. NT219 is licensed from Yissum, the technology transfer company of the Hebrew University of Jerusalem.

On January 14, 2019 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines, reported that the first patient has been successfully dosed in a phase I clinical trial of anti-CD47 monoclonal antibody (IBI188) for patients with advanced malignancies (Press release, Innovent Biologics, JAN 14, 2019, View Source [SID1234532643]).

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The study is a phase I clinical study conducted in China to evaluate the safety, tolerability, and efficacy of IBI188 in the treatment of patients with advanced malignancies. The primary objectives are to evaluate the safety, tolerability, and phase II recommended doses of IBI188 as a monotherapy and in combination with other agents in subjects with advanced malignancy.

"CD47 is a ‘don’t eat me’ signal; the CD47-SIRPα mechanism is hijacked in many malignant tumors to escape immune mediated clearance. Based on the promising safety and efficacy data from literature, we hope to validate the therapeutic value of IBI188 monoclonal antibody in advanced malignancies," said Professor Jun Zhu, from the Beijing Cancer Hospital.

"IBI188 is a pivotal product in our pipeline of cancer immunotherapies. CD47 is an important component of a critical inhibitory immune pathway but is different from T cell check point inhibitors such as PD-1, PD-L1 and CTLA-4. CD47 targets macrophages and suppresses phagocytosis by interacting and activating the inhibitory receptor SIRPα. Anti-CD47 mono therapy and combination therapy has shown promising efficacy in several types of solid tumor and in refractory/relapsed non-Hodgkin Lymphoma. We are preparing to advance IBI188 into subsequent clinical trials in a variety of cancers once its safety, tolerability and the recommended phase II dose are confirmed. We hope our efforts will give more patients the opportunity for tumor control or even cure," said Michael Yu, Founder, Chief Executive Officer and Chairman of Innovent.

About IBI188

IBI188 is a fully human monoclonal antibody targeting CD47. In vitro and in vivo experiments have shown that IBI188 can bind to the CD47 antigen on the surface of tumor cells, block the CD47-SIRPα signaling pathway, inhibit the "Don’t Eat Me" signal, and promote the phagocytosis of tumor cells by macrophages, thereby exerting an anti-tumor effect. Innovent will launch several clinical trials to assess its safety and efficacy in multiple tumor types, including non-Hodgkin’s lymphoma and ovarian cancer.

About CIBI188A101

The CIBI188A101 study is a Phase I clinical study conducted in China to evaluate the safety, tolerability, and efficacy of IBI188 in the treatment of patients with advanced malignancies. The primary objectives are to evaluate the safety, tolerability, and phase II recommended doses of IBI188 as a monotherapy and in combination with other agents in subjects with advanced malignancy. The phase 1a study explores the priming and maintenance dose of IBI188 as monotherapy.