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PharmaCyte Biotech Successfully Completes Another Study on the Encapsulated Cells Used in Its Pancreatic Cancer Therapy

On July 23, 2018 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a clinical stage biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has successfully completed a study on the stability after "hand thawing" syringes of the Cell-in-a-Box encapsulated cells that will be used, in combination with low doses of the cancer prodrug ifosfamide, for the treatment of locally advanced, non-metastatic, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, JUL 23, 2018, View Source [SID1234528930]). The data obtained from this "hand thawing" study is required by the U.S. Food and Drug Administration (FDA).

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The filing of an Investigational New Drug Application (IND) requires that the clinical product, as well as the product’s use, should be well characterised. PharmaCyte’s Cell-in-a-Box is a cutting edge Advanced Therapy Medicinal Product (ATMP). Therefore, numerous studies are needed since such a product has never been tested before in the United States. The laboratory scale "thawing" study previously conducted (View Source) determined how long the once-frozen Cell-in-a-Box encapsulated cells are still fit for use after thawing, as would occur in a clinical setting before the Cell-in-a-Box capsules are implanted into a patient with LAPC. That study defined one of the important parameters for the upcoming planned clinical trial for LAPC.

At individual study sites, the frozen cells in the Cell-in-a-Box capsules within syringes will be hand-thawed and then kept at room temperature until they are implanted into a patient with LAPC. The results of the "hand thawing" study announced today show that the viability of the cells remains essentially the same for at least 30 minutes at room temperature. This serves to define the time that the interventional radiologist has to implant the Cell-in-a-Box capsules after thawing to ensure cellular viability within the patient.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, explained the significance of the study saying, "This is yet another important study that PharmaCyte has completed to comply with the FDA’s requirements for our planned, upcoming clinical trial in LAPC. The Cell-in-a-Box encapsulated cells are in a frozen state before they are administered to the patient. This study was designed to determine how long after unfreezing the Cell-in-a-Box encapsulated cells can they be held at room temperature before being introduced into the patient without losing their effectiveness.

"This is important since the treatment depends on the viability of our genetically engineered live human cells in order to produce the cytochrome P450 enzyme for the activation of the chemotherapy prodrug ifosfamide. The study’s goal was to determine how long the cells remained viable at room temperature after thawing; thus, mimicking how long the clinicians and interventional radiologists will have to administer the capsules to the patient in the hospital. The newly completed studies show how long that Cell-in-a-Box encapsulated cells can be kept at room temperature for optimal activity."

Leap Therapeutics Announces Collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer to Evaluate Combination of TRX518, Avelumab, and Chemotherapy in Advanced Solid Tumors

On July 23, 2018 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, reported it has entered into a collaboration agreement with Merck KGaA, Darmstadt, Germany, and Pfizer to evaluate Leap’s GITR agonist, TRX518, in combination with avelumab*, a human anti-PD-L1 IgG1 monoclonal antibody, and chemotherapy (Press release, Leap Therapeutics, JUL 23, 2018, View Source;p=RssLanding&cat=news&id=2359396 [SID1234528762]).

Under the terms of the collaboration, Leap will be conducting a Phase I/II clinical trial in advanced solid tumors including expansion populations in patients with relapsed/refractory ovarian, breast, and prostate cancers. The study is expected to begin enrolling patients in the first quarter of 2019.

"The combination of TRX518 with anti-PD-L1 immunotherapy and cyclophosphamide has a solid scientific rationale and we look to build upon our early clinical and preclinical data highlighting the potential benefits of such a combination," commented Cynthia Sirard, M.D., Vice President, Clinical Development of Leap Therapeutics.

"TRX518 has demonstrated encouraging potential with early clinical activity in patients with advanced solid tumors," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "This collaboration with Leap Therapeutics to evaluate TRX518 in combination with avelumab gives us the opportunity to investigate a potential novel immunotherapy treatment regimen as we pursue our mission of improving outcomes for patients living with hard-to-treat cancers."

"Combination therapy remains a major focus in our clinical development program for avelumab in an effort to advance the treatment landscape for patients with challenging cancers," said Alise Reicin, Head of Global Clinical Development at the Biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "Through our collaboration with Leap Therapeutics, we are eager to further understand the potential of this novel immunotherapy combination in this patient population."

Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.

*Avelumab is under clinical investigation for treatment of solid tumors and hematological malignancies in combination with TRX518 and has not been demonstrated to be safe and effective for these uses. There is no guarantee that avelumab will be approved for solid tumors or hematological malignancies by any health authority worldwide.

About Avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials, and over 8,600 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.

Approved Indications in the US**

The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) mMCC in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications were approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information from the US FDA Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.

Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.

Chi-Med Initiates a Phase Ib/II Proof-of-Concept Trial of Sulfatinib in Pancreatic Neuroendocrine Tumors and Biliary Tract Cancer in the United States

On July 23, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) has initiated a Phase Ib/II proof-of-concept study of sulfatinib in pancreatic neuroendocrine tumors ("NET") patients and in biliary tract cancer ("BTC") patients in the U.S.. Sulfatinib is an oral small molecule angio-immuno kinase inhibitor that can simultaneously block tumor angiogenesis and immune evasion (Press release, Hutchison China MediTech, JUL 23, 2018, https://www.chi-med.com/sulfatinib-poc-pnet-btc-us/ [SID1234528657]). This study follows several trials that are underway in China, including two Phase III studies in pancreatic and non-pancreatic NET that commenced after positive results from a Phase II study, and a Phase II study in BTC patients. In addition, a Phase I dose escalation part of this study in the U.S. was recently completed.

This proof-of-concept study is a multi-center, single-arm, open-label study to evaluate the efficacy and safety of sulfatinib as a monotherapy in (a) patients with advanced BTC that have progressed on standard first-line chemotherapy, and (b) in patients with advanced pancreatic NET. The primary and secondary endpoints include progression-free survival ("PFS") rate, objective response rate ("ORR"), disease control rate ("DCR"), duration of response ("DoR"), time to response, overall survival ("OS"), safety and tolerability. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT02549937.

About Sulfatinib
Sulfatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor ("VEGFR"), fibroblast growth factor receptor ("FGFR") and colony stimulating factor-1 receptor ("CSF-1R"), three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. Inhibition of the VEGFR signaling pathway can act to stop angiogenesis, the growth of the vasculature around the tumor, and thereby starve the tumor of the nutrients and oxygen it needs to grow rapidly. Aberrant activation of the FGFR signaling pathway, which can be increased by anti-VEGFR therapy treatment, is shown to be associated with cancer progression by promoting tumor growth, angiogenesis and formation of the myeloid derived suppressor cells. Inhibition of the CSF-1R signaling pathway blocks the activation of tumor-associated macrophages, which are involved in suppressing immune responses against tumors. Its unique angio-immuno kinase profile supports sulfatinib as a potentially attractive candidate for exploration of possible combinations with checkpoint inhibitors against various cancers.

Sulfatinib is the first oncology candidate that we have taken through proof-of-concept in China and subsequently started clinical development in the U.S. We are currently conducting studies in six target patient populations on sulfatinib and retain all rights to sulfatinib worldwide.

About Sulfatinib Development in China
Sulfatinib is currently in development as a single agent for patients with NET, thyroid cancer and BTC in China.

Pancreatic NET: In March 2016, we initiated the SANET-p study, which is a randomized, double-blind, placebo-controlled, multi-center, Phase III pivotal registration trial to treat about 190 patients with low- or intermediate-grade, advanced pancreatic NET in China. The primary endpoint is PFS, with secondary endpoints including ORR, DCR, DoR, time to response, OS, safety and tolerability. Additional details of the SANET-p study may be found at clinicaltrials.gov, using identifier NCT02589821. We expect to complete enrollment in 2019 and present top-line results thereafter.

Extra-pancreatic NET: The SANET-ep study, which was initiated in December 2015, is similar to the SANET-p study and is targeted at treating about 270 patients with advanced extra-pancreatic NET in China. Additional details of the SANET-ep study may be found at clinicaltrials.gov, using identifier NCT02588170. We expect to complete enrollment in 2019 and present top-line results thereafter.

Thyroid cancer: In March 2016, we initiated Phase II in two target patient populations in China to evaluate the efficacy and safety of sulfatinib in patients with advanced medullary thyroid cancer and iodine-refractory differentiated thyroid cancer. Additional details of this study may be found at clinicaltrials.gov, using identifier NCT02614495.

BTC: In January 2017, we began a Phase II study in patients with BTC (also known as cholangiocarcinoma), a heterogeneous group of rare malignancies arising from the biliary tract epithelia. Gemzar is the currently approved first-line therapy for biliary tract cancer patients, with a total of approximately 18,000 new patients per year in the U.S. according to the National Cancer Institute, but median survival is less than 12 months for patients with unresectable or metastatic disease at diagnosis. As a result, we see a major unmet medical need for patients who have progressed when being treated with Gemzar, and sulfatinib may offer a new targeted treatment option in this tumor type. Additional details of this study may be found at clinicaltrials.gov, using identifier NCT02966821.

10-Q – Quarterly report [Sections 13 or 15(d)]

HedgePath Pharmaceuticals has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, HedgePath Pharmaceuticals, 2018, JUL 23, 2018, View Source [SID1234527811]).

10-Q – Quarterly report [Sections 13 or 15(d)]

MediciNova has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, MediciNova, 2018, JUL 23, 2018, View Source [SID1234527810]).