On December 11, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported the presentation of new data that suggests treatment with TAVO (tavokinogene telseplasmid) has the ability to improve immune responses in heavily pretreated, inoperable and locally advanced triple negative breast cancers by increasing tumor infiltrating lymphocyte (TIL) density, increasing effector cytokines, and upregulating immune-related gene expression, factors associated with long-term response to anti-PD1 antibodies (Press release, OncoSec Medical, DEC 11, 2018, View Source [SID1234532009]).

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The now completed Pilot TNBC study, OMS-140 (NCT02531425), was designed to determine whether a single cycle of TAVO monotherapy could enhance anti-tumor immune responses in a TNBC salvage setting. Specifically, a comparative analysis of patient’s pre-TAVO tumor and blood samples to the post-TAVO tumor and blood samples demonstrated that, with only a single cycle of TAVO, a treatment-related increase of CD8+ TIL was observed in four of 10 patients, while also demonstrating a relative decrease in immune suppressive cells.

Nanostring analysis (a novel platform for quantification of gene expression) of the tumor microenvironment revealed a meaningful increase of immune-related transcripts while on treatment. The investigator also evaluated the peripheral blood through a longitudinal analysis of PBMCs (peripheral blood mononuclear cells), and, in doing so, noted an increase of both effector and partially exhausted T cells, which complements the reduced frequency of immune-suppressive MDSC (myeloid-derived suppressor cells) reported earlier this year at AACR (Free AACR Whitepaper).

These data, along with increased effector cytokines noted in serum, demonstrate both local and systemic immune responses with only one cycle of TAVO in this difficult to treat patient population. Additionally, as observed in other clinical trials with TAVO, this study showed that TAVO is safe and well tolerated in this patient population.

These data, as well as other clinical and immunological data, were presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) taking place December 4-8 in San Antonio, Texas.

"The immunological signatures described here, including conversion of non-immunogenic tumors into immunologically active lesions, are very encouraging, especially when considering that patients with very advanced disease received only one cycle of TAVO," said Dr. Christopher Twitty, Chief Scientific Officer of OncoSec. "Late-stage triple negative breast cancer patients have very few treatment options, and those that are available, come with serious toxicities and limited effectiveness. Recent data suggest that some patients with triple negative tumors will benefit from treatment with PD-1 checkpoint inhibitors, but only if the patient’s tumor is immunologically active," continued Dr. Twitty. "This study represents the potential of a safe and effective immunotherapy to turn non-immunogenic tumors into an immunologically active tissue, expanding the benefits of PD-1 checkpoint inhibitors to a much broader subset of women with triple negative breast cancer, which would be an important advance for the treatment of these patients."

As previously reported, a subset of patients that completed a single cycle of TAVO in this study, were sequentially treated with an anti-PD-1 checkpoint therapy (nivolumab). Importantly, some of these patients, one with prior disease progression on anti-PD-L1 antibody monotherapy, experienced robust clinical responses beyond the TAVO treated lesions. One of these patients continues to be treated with TAVO under a compassionate use protocol.

Based on these findings, OncoSec and Merck initiated a second TAVO Phase 2 study in TNBC, KEYNOTE-890, to evaluate the combination of TAVO with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in approximately 25 patients with treatment-refractory, inoperable or metastatic triple negative breast cancer (NCT03567720).

Since KEYNOTE-890 opened in October, investigators have already enrolled five patients into the trial. The KEYNOTE-890 study is testing the combination in patients with inoperable locally advanced or metastatic TNBC who have progressed on more than one line of prior therapy. Patients will be treated with the combination of TAVO with pembrolizumab. The primary endpoint is to assess efficacy as measured by objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

On December 11, 2018 PharmaCyte Biotech, Inc. (OTCQB: PMCB), reported a biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, released an interview with Lyon Gleich, M.D., of Medpace, a global full-service clinical contract research organization (CRO) (Press release, PharmaCyte Biotech, DEC 11, 2018, View Source [SID1234532010]). Dr. Gleich serves as the Medical Monitor and key team member of PharmaCyte’s planned clinical trial in locally advanced, inoperable pancreatic cancer (LAPC).

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Dr. Gleich is Vice President, Medical Oncology, at Medpace headquartered in Cincinnati, Ohio. Dr. Gleich has provided medical leadership over oncology trials at Medpace for nearly 15 years. He has extensive expertise in new drug development in oncology—specifically, pancreatic cancer.

Why is Medpace well suited to conduct PharmaCyte’s clinical trial in locally advanced, non-metastatic, inoperable pancreatic cancer?

Dr. Lyon Gleich: "Medpace is experienced in managing oncology trials of new molecular entities for our biotech partners and our full-service, scientific-model aligns well with innovative companies such as PharmaCyte. Oncology is a clear and well-established focus of Medpace with multiple recent trials in pancreatic cancer. We have strong relationships with oncology sites and site investigators who will help us recruit the best site investigators for this trial. This will also provide patients access to the trial by having multiple sites throughout the United States. Medpace will work with the Principle Investigator and site investigators to maximize their regional referral networks, as well as to support recruitment for PharmaCyte’s study.

"Conducting a pancreatic cancer study is not like managing a study in more benign conditions, where you can advertise for patients. Working with established cancer centers of excellence that have access to pancreatic cancer patients will be critical to the trial’s success. Our relationships with these sites and site investigators, as well as our processes, will enable us to support the site relationships while making sure that the data quality is high and that the trial is run correctly. Medpace will also support the site’s recruitment efforts and trial management to make it as easy as possible for each site and its patients to participate in the trial."

What is unique about PharmaCyte’s signature live-cell encapsulation technology, Cell-in-a-Box?

Dr. Lyon Gleich: "Given the severe mortality rate associated with pancreatic cancer as well as the morbidity of the locally advanced disease, we are eager to work with PharmaCyte to advance their live-cell encapsulation therapy that can potentially improve local morbidity as well as impact survival for patients suffering from this aggressive disease. The Cell-in-a-Box or ‘CypCaps’ capsules that are implanted into each patient will activate the chemotherapy agent ifosfamide in the pancreatic tumor bed specifically, which will permit an infusion of only a low dose of the chemotherapeutic agent PharmaCyte uses for its pancreatic cancer therapy. This is a novel way to take an older and effective chemotherapeutic product and make it even more efficacious. PharmaCyte’s therapy offers LAPC patients a drug with proven anti-cancer activity that is delivered locally to their advanced cancer.

"The CypCaps will require angiographic administration into the pancreatic cancer feeding vessel. Medpace will train each trial site regarding the implantation of the capsules into the patient to ensure proper and consistent methodologies across the study. This will help ensure that the implantation is done without any adverse events and maximize the potential for efficacy of the chemotherapy agent ifosfamide."

What are your thoughts about PharmaCyte and Medpace teaming up with well-known and respected pancreatic cancer experts such as Dr. Manuel Hidalgo?

Dr. Lyon Gleich: "PharmaCyte and the experience of Medpace with pancreatic cancer experts will be key to driving success in this trial. It is important to have the support of the thought leaders in pancreatic cancer that have already been involved with PharmaCyte so that the best sites are recruiting appropriate patients for the study and the quality of the CypCaps administration is done consistently.

"Manuel Hidalgo, M.D., of Beth Israel Deaconess Medical Center, is the Principal Investigator and a well-known expert in pancreatic cancer with whom Medpace is experienced. This is an excellent example of teaming and collaborating with the best resources in treating pancreatic cancer."

How do the CRO and the PI work together during clinical trials?

Dr. Lyon Gleich: "Medpace works to be as supportive and transparent as possible with the Principle Investigator and the site investigators alike. This includes providing training on all protocol procedures and helping sites understand the purpose and details of the study to present it accurately to potential patients. Medpace physicians and staff are readily available to the sites to support and answer trial-related questions and concerns, and thereby help continuously with enrollment and patient treatment in accordance with the protocol. Of course, one of our main responsibilities is also site monitoring to ensure that data is entered in a timely manner and supported at all times by proper site documentation to support any future applications for Marketing Authorization."

What are some of the biggest challenges you anticipate and are planning for in this trial?

Dr. Lyon Gleich: "Any trial in pancreatic cancer is a difficult trial because of the severity and morbidity of the disease. Many patients enrolled in these studies, even if they have a good performance status and high activity level, are patients with advanced cancer with a very high mortality rate. Patients can turn the corner at any moment, in a very negative way, in terms of having a severe worsening of their disease such as an increase in ascites, a blockage of their biliary duct, and even in some cases, a quick descent to death. This is a huge hurdle for any trial in pancreatic cancer. Even during the couple of weeks during the screening period, LAPC patients can see a rapid progression of the disease and are no longer able to respond to any therapy.

"In this trial, we are hopeful that we won’t experience too much of that. The trial is designed for patients with locally advanced non-metastatic unresectable pancreatic cancer. Many patients with pancreatic cancer do have metastatic disease, meaning the spread of the cancer elsewhere in the body, not just a locally advanced disease. This therapy won’t offer a benefit to those patients and is designed for the non-metastatic locally advanced patient. We need to find locally advanced patients without metastases who still have an acceptable performance status and haven’t, so to speak, gone over the precipice where the disease takes off in a way that therapies can no longer help.

"The support of the patients by the treating physicians, their teams and nurses are key to this. Medpace will work closely with PharmaCyte to provide support and education to the teams so that they can provide that needed support and education to the patients to help them through this terrible disease.

"Based on Medpace’s experience in trials with pancreatic cancer and our experience in working with sites in similar difficult studies for late stage advanced pancreatic cancer, we are well positioned to know what the sites expect from us regarding support. Through this important trial, our hope is being able to advance the treatment of pancreatic cancer, which is greatly needed."

About Medpace

Medpace is a scientifically-driven, global, full-service clinical contract research organization (CRO) providing Phase I-IV clinical development services to the biotechnology, pharmaceutical, and medical device industries. The mission of Medpace is to accelerate the global development of safe and effective medical therapeutics through its high-science and disciplined operating approach that leverages local regulatory and deep therapeutic expertise across all major areas including oncology, cardiology, metabolic disease, endocrinology, central nervous system and anti-viral and anti-infective

On December 11, 2018 NexImmune, an emerging leader in the field of antigen-directed immunotherapy, reported that the United States Patent and Trademark Office has issued a new method of use patent to Johns Hopkins University related to the Company’s E+E (T cell Enrichment and Enhancement) technology for which NexImmune holds an exclusive license from Johns Hopkins (Press release, NexImmune, DEC 11, 2018, View Source [SID1234554955]). This further enhances the company’s AIM technology intellectual property portfolio and provides broad intellectual property rights protecting key aspects of the company’s lead product AIM ACT, an adoptive T cellular therapy for the treatment of cancer.

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"Using our proprietary E+E technology to generate antigen-specific T cells represents a uniquely differentiated approach to expanding polyclonal T cells that are highly antigen-specific, highly polyfunctional and with a phenotypic composition optimized for anti-tumor cytotoxicity, proliferative capacity and long-term immunologic memory. We believe our AIM E+E generated T cell products have the potential to address some of the clinical limitations observed with currently available genetically modified T cell therapies. Our hope is that these differences translate into meaningful benefit for patients suffering from a variety of hematological malignancies," commented Scott Carmer, Chief Executive Officer of NexImmune. "Ensuring a robust intellectual property position around E+E is inherent to advancing the program and the claims granted in this patent exemplify the novel science behind this exciting technology."

U.S. patent 10,098,939 adds to previously issued U.S. and international counterpart patents and patent applications that form NexImmune’s AIM patent portfolio. Claims were granted on the ability of E+E to expand large numbers of antigen-specific T cells from the body’s endogenous T cell repertoire. Preclinical studies have demonstrated that cells generated using E+E have a large proportion of highly functional central and effector memory T cells which the company believes will provide both a potent immediate therapeutic benefit for cancer patients and an enhanced durability of response compared to currently approved adoptive T cell therapies. NexImmune plans to advance its AIM ACT platform into early phase clinical trials in 2019.

On December 11, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported that it has commenced an underwritten public offering of 3,000,000 shares of its common stock (Press release, Tocagen, DEC 11, 2018, View Source [SID1234532011]). All shares of common stock to be sold in the offering will be offered by Tocagen. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Citigroup and Leerink Partners are acting as joint book-running managers for the offering. Tocagen expects to grant the underwriters of the offering a 30-day option to purchase up to an additional 450,000 shares of its common stock at the public offering price, less the underwriting discounts and commissions.

The securities described above are being offered by Tocagen pursuant to a shelf registration statement on Form S-3 filed by Tocagen with the Securities and Exchange Commission (SEC), which was declared effective on May 23, 2018. A preliminary prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC and will be available for free on the SEC’s website at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus related to this offering, when available, may be obtained from: Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (800) 831-9146; or Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, or by telephone at (800) 808-7525, ext. 6132, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 11, 2018 Cellectar Biosciences, Inc. (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted treatments for cancer, reported that the Japan Patent Office has granted the patent titled "Phospholipid Analogs as Diapeutic Agents and Methods of Use Thereof" with application number 2016135920 (Press release, Cellectar Biosciences, DEC 11, 2018, View Source [SID1234532012]). The patent provides composition of matter and use protection for the company’s proprietary phospholipid ether (PLE) analogs and specifically CLR 131 in breast, brain, leukemias and a variety of other cancers.

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"Certain cancers such as pediatric lymphomas and leukemias have a higher prevalence in Asia and represent unmet need both within and outside the region," said Jim Caruso, president and chief executive officer of Cellectar Biosciences. "The issuance of this patent enhances our growing intellectual property portfolio in this strategically important market and provides incremental value to CLR 131 and our PLE delivery franchise."

About Phospholipid Drug Conjugates

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized phospholipid ether-drug conjugates (PDCs) to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary PLE and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in relapsed/refractory multiple myeloma (R/R MM) and a range of B-cell malignancies, and a Phase 1b clinical study in patients with R/R MM exploring fractionated dosing. The objective of the multicenter, open-label, Phase 1b dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2 as well as a fractionated dose of 15.625 mCi/m2 given twice over seven days in Cohort 5. All study doses and regimens have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma as well as a second Phase 1 study in combination with external beam radiation for head and neck cancer.