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Argos Therapeutics Announces Initiation of a Phase 2 Clinical Trial of AGS-003 for the Treatment of Non-small Cell Lung Cancer in Combination with Standard-of-Care Chemotherapy

On March 23, 2016 Argos Therapeutics, Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of truly individualized immunotherapies for the treatment of cancer based on the Arcelis technology platform, reported the initiation of an investigator-sponsored Phase 2 clinical trial of AGS-003 in combination with standard platinum-doublet chemotherapy with or without radiation in patients with newly diagnosed Stage 3 non-small cell lung cancer (NSCLC) (Press release, Argos Therapeutics, MAR 23, 2016, View Source [SID:1234509835]).

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The study is being conducted at the Cancer Research Network of Nebraska (CRNN) and is expected to enroll 20 patients. AGS-003 will be administered either concurrently with chemotherapy and with or without radiation or sequentially with chemotherapy and with or without radiation, according to the subject’s assigned treatment arm.

"The standard of treatment of NSCLC has been chemotherapy after surgery, but now we can offer this exciting new option of individualized immunotherapy," said Dr. Stephen Lemon, co-principal investigator and president of Oncology Associates, Omaha, Nebraska, a CRNN collaborating practice. "We are thrilled to participate in this exciting study and are hopeful that AGS-003 will be safe and effective, and help our patients fight this terrible disease."

AGS-003 is an individualized immunotherapy designed to induce a memory T-cell response specific to each patient’s cancer, including the unique tumor mutations (or neoantigens). It is produced using a small sample of RNA from a patient’s own tumor, and dendritic cells derived from a cell collection procedure from the patient.

The research team at CRNN will evaluate the impact of AGS-003 on the toxicity of standard chemotherapy as the primary safety endpoint. Researchers will also measure the activation of memory T-cells in patients who complete the Induction Phase and receive five or more doses of AGS-003 to determine the immunologic response.

"We are excited that this trial has opened for enrollment. This is the first clinical trial of AGS-003 outside of metastatic renal cell carcinoma and we can now explore the potential activity of this novel immunotherapy in other solid tumors. NSCLC is interesting because it is a tumor type reported to have a high number of mutated targets for the immune system, and therefore represents an important opportunity to integrate treatment with AGS-003 during or following standard-of-care chemotherapy," said Lee F. Allen, M.D., Ph.D., chief medical officer at Argos. "The CRNN team is among the most prominent and experienced oncology research groups in the Midwest, and we look forward to their efforts to rapidly advance this important clinical research and expand the potential indications for the use of AGS-003."

To learn more about the clinical trial visit View Source, call 402-697-2229, or send an e-mail to [email protected].

About Lung Cancer

American Cancer Society estimated that in 2016 approximately 224,000 Americans would be diagnosed with lung cancer resulting in nearly 160,000 deaths. It is the second most common cancer and the leading cause of cancer death for men and women; about 1 out of 4 cancer deaths result from lung cancer. Between 85 and 90% of these are non-small cell lung cancer (NSCLC) histology, which includes squamous cell, adenocarcinoma, and large cell (undifferentiated) cancers. Despite early detection screening efforts, the majority of NSCLC patients continue to present with advanced stage disease (Stage III, IV) at the time of diagnosis. The mainstay of treatment for Stage IV NSCLC is limited to systemic therapies.

Expanded IgG Lineages in Lung Cancer Non-Progressors Reveal Anti-Tumor Antibodies

Abstract: Analyzing anti-cancer immune responses is key to understanding cancer immunotherapy mechanisms. We used Immune Repertoire Capture (IRC) technology to sequence the full length variable regions of natively paired immunoglobulin heavy and light chain genes expressed by over 5000 blood plasmablasts (activated B cells) from a patient with Stage 4 lung adenocarcinoma during a period of long term non-progression (2+ years). There was extensive diversity of germline gene usage and elevated levels of somatic hypermutation (SHM) among the individual B cells. Sequences were grouped into putative clonal families based on immunoglobulin gene usage and other sequence features. Over 1500 putative antibody clonal families were identified, including families observed across blood collection time points and similar to families from another lung adenocarcinoma patient. The full length variable regions of IRC sequences were directly gene synthesized to generate recombinant antibodies representing over 150 large and small putative families. Antibodies showed a range of staining patterns on tumor and normal tissues, including some antibodies that bound tumor types other than lung tumor and some that bound tumor much better than normal tissue. Over one third of the antibodies bound lung cancer-derived cell lines. Some antibodies mediated ADCC killing in vitro. Human proteome arrays are being used to identify the targets of the antibodies. Analyses identified clones with differing SHM from the same putative family that bind the same target with varying potencies, indicating that the mutational differences between sibling antibodies reveal structure-activity information.

Commencement of First-in-Human Clinical Trial for New Molecular Targeting Drug, Co-Developed with The University of Tokyo and National Cancer Center, to Treat Malignant Lymphoma (Including Adult T-cell Leukemia-Lymphoma)

On March 22, 2016 The National Cancer Center, The University of Tokyo, and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported a collaboration to develop a histone methylation enzyme EZH1/2 dual inhibitor (DS-3201), as a new molecular targeting agent for hematologic malignancy, and the commencement of Phase 1*1 clinical trial in patients with malignant lymphoma and adult T-cell leukemia-lymphoma (ATL) (Press release, Daiichi Sankyo, MAR 22, 2016, View Source [SID:1234511231]).

One contributing factor to the poor prognosis for malignant lymphoma is the existence of Cancer Stem Cells*2 capable of regenerating cancer cells and thought to persist after treatment, making the eradication of Cancer Stem Cells essential to the cure of hematologic malignancy. National Cancer Center Research Institute, Division of Hematological Malignancy research group led by Issay Kitabayashi discovered that EZH1/2 are essential enzymes in the maintenance of Cancer Stem Cells, and produced research results suggesting that inhibiting both enzymes may eradicate Cancer Stem Cells to overcome drug-resistance and suppress recurrence. To date, several preclinical studies suggest that this may be an effective treatment for acute myeloid leukemia (AML) and malignant lymphoma.

Searching for an effective ATL treatment, a research group chiefly led by Professor Toshiki Watanabe and Project Research Assistant, Makoto Yamagishi, of The University of Tokyo, Graduate School of Frontier Sciences, discovered an abnormal accumulation of epigenetic changes*3 due to inappropriate activation of EZH1/2 in ATL cells. Also, as ATL cells are more strongly dependent on epigenetic changes caused by EZH1/2 compared to normal cells, the research developed a new compound that simultaneously inhibits the function of both EZH1 and EZH2. This dual inhibitor reversed inappropriate methylation of histones in ATL cells and also selectively eliminated ATL cells and HTLV-1-infected immortalized cells in the peripheral blood.

Malignant lymphoma
Malignant lymphoma is the most prevalent hematologic malignancy. Malignant lymphoma is classified into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Recent advances in the management have led to the improvement in therapeutic outcomes of patients with malignant lymphoma, especially Hodgkin lymphoma and B-cell non-Hodgkin lymphoma. However, relapsed or refractory patients with both diseases and T-cell lymphoma patients are still of unfavorable prognosis. Among various subtypes of T-cell lymphoma, ATL is the disease caused by human T-cell leukemia virus type I (HTLV-1) with the poorest prognosis. About 1,000 patients suffer from ATL every year in Japan, where approximately 1.2 million individuals are infected by HTLV-1. The number of HTLV-1-infected individuals (carriers) is estimated to be about 10 to 20 million in the world. About 5 percent of carriers develop ATL during their lifetimes. However, no onset prevention methods or effective treatments of ATL have been established. The prognosis of ATL is very poor mainly because of the high frequency of drug resistance. As the only HTLV-1 endemic country among developed nations, the world expects Japan to lead global efforts to develop new treatments towards onset prevention and effective treatments of ATL.

Clinical trial
This Phase I is the multicenter, study conducted by the National Cancer Center Hospital (Chuo-ku, Tokyo), and other facilities in Japan.

8-K – Current report

On March 22, 2016 IntelGenx Corp. (TSX-V: IGX) (OTCQX: IGXT) (the "Company" or "IntelGenx") reported financial results for the three and twelve-month periods ended December 31, 2015. All amounts are in U.S. Dollars unless otherwise stated (Filing, Q4/Annual, IntelGenx, 2015, MAR 22, 2016, View Source [SID:1234509840]).

2015 Fourth Quarter Financial Highlights:

• Revenues reached $1.5 million, an increase of 82% over the same period last year

• Net comprehensive income was $233 thousand, compared to a net comprehensive loss of ($339 thousand) over the same period last year

• Adjusted EBITDA was $429 thousand, compared to a negative ($225 thousand) over the same period last year

• Cash and cash equivalents totaled $2.87 million as at December 31, 2015

2015 Twelve-Month Financial Highlights:

• Revenue was $5.1 million, an increase of 207% over the same period last year

• Net comprehensive income was $800 thousand, compared to a net comprehensive loss of ($2.2 million) over the same period last year

• Adjusted EBITDA was $1.7 million, compared to a negative ($1.6 million) over the same period last year

Recent Operational Highlights:

• Net sales of Forfivo XL continued to improve significantly in the fourth quarter of 2015 by 24% to $3 million ($5.4 million gross) compared to the third quarter of 2015

• For the past twelve months, net sales of Forfivo XL totaled $9.3 million ($17.4 million gross), an increase of 102% compared to the twelve-month period in 2014

• Received the remaining $2 million milestone payment from Edgemont Pharmaceuticals

• Construction completed of IntelGenx’ new state-of-the-art manufacturing and laboratory facilities which are expected to be fully operational by 2017

"We are most pleased with the record results and progress we have made as an organization in 2015," said Dr. Horst G. Zerbe, President and CEO of IntelGenx. "Our continued sales growth of Forfivo has enabled us to achieve two consecutive quarters of profitability. We have invested these profits back into transforming IntelGenx by building a stronger management team with the clear goal of accelerating the execution of our business plan coupled with the completion of the construction of our state-of-the-art manufacturing facilities. Both these strategic initiatives will enable us to become a global leader in pharmaceutical oral film development and manufacturing."

Financial Results:

Total revenues for the three-month period ended December 31, 2015 amounted to $1.5 million, representing an increase of $677 thousand or 82% compared to $825 thousand for the three-month period ended December 31, 2014. Total revenues for the twelve-month period ended December 31, 2015 amounted to $5.1 million representing an increase of $3.4 million or 207% compared to $1.7 million for the twelve-month period ended December 31, 2014. The increases for the three-month and twelve-month periods ended December 31, 2015 compared to the last year’s corresponding periods are mainly attributable to the attainment of milestones, totaling $2.7 million from IntelGenx’ licensing partner Edgemont. The milestone was triggered by Edgemont reaching in July 2015, $7 million of cumulative net trade sales of Forfivo XL over the preceding 12 months. From the $2.7 million milestones, $1 million was received in the third quarter. From the remaining balance, $1 million was received in the fourth quarter and $1 million was received in the first quarter of 2016, with revenue to be recognized in the first quarter of 2016 of $333 thousand. Nevertheless, 3/6 of the $2 million was recognized as revenue in the fourth quarter and 5/6 of the $2 million was recognized as revenue in the twelve-month period ended December 31, 2015.

Operating costs and expenses were $3.71 million for the twelve-month period of 2015, versus $3.44 million for the corresponding period of 2014.

For the twelve-month period of 2015, the Company generated operating income of $1.4 million compared to an operating loss of ($1.8 million) for the comparable period of 2014.

Net comprehensive income was $800 thousand or $0.01 on a basic and diluted per share basis for the twelve-month period of 2015 compared to a net comprehensive loss of ($2.2 million) or ($0.03) on a basic and diluted per share basis for the comparable period of 2014.

"We are focused on a strong financial discipline in managing our expenses and ensuring high standards of financial controls be implemented throughout the organization," said Mr. Andre Godin, Executive Vice-President and CFO of IntelGenx. "We are committed to working at building the visibility of the corporation in the marketplace."

Cash on hand as at December 31, 2015 was $2.87 million, representing a decrease of ($1.53 million) compared with the balance of $4.4 million as at December 31, 2014. The decrease in cash relates primarily to the investments made into our state-of-the-art manufacturing and laboratory facilities.

Verastem Announces Oral Presentation of Data Supporting the Preferential Targeting of Ovarian Cancer Stem Cells at the Society of Gynecologic Oncology’s 2016 Annual Meeting on Women’s Cancer

On March 22, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported the presentation of scientific data at the Society of Gynecologic Oncology’s 2016 Annual Meeting on Women’s Cancer being held March 19-22, 2016 in San Diego, CA (Press release, Verastem, MAR 22, 2016, View Source;p=RssLanding&cat=news&id=2150260 [SID:1234509826]).

"The data presented today at SGO 2016 are important because they provide further scientific evidence that chemotherapy can lead to an increase in ovarian cancer stem cells (CSCs), making the tumor more aggressive and resistant to further treatment," said Dr. Jonathan Pachter, Verastem Head of Research. "At Verastem, we believe that our compounds in development may be especially beneficial as therapeutics when used in combination with other agents, including current and emerging standard of care treatments and immunotherapies, and have the potential to create a more durable clinical response. We look forward to the initiation of a Phase 1/1b clinical trial of the combination of VS-6063 and avelumab, in collaboration with Pfizer and Merck KGaA, for patients with ovarian cancer in the second half of this year."

Verastem, and its collaborators, are presenting these scientific data in support of Verastem’s development programs which utilize a multi-faceted approach to treat cancer by reducing cancer stem cells, enhancing anti-tumor immunity, and modulating the local tumor microenvironment. The Company’s most advanced clinical product candidates are the Focal Adhesion Kinase inhibitors, VS-6063 and VS-4718, and the dual PI3K/mTOR inhibitor, VS-5584. Research on the FAK and PI3K/mTOR signaling pathways has revealed critical roles for each in cancer stem cell survival and disease progression.

Details for the SGO presentation are as follows:

Oral Presentation

Title: Standard chemotherapy for ovarian cancer increases expression of cancer stem cell biomarkers which is predictive of survival

Session: Scientific Plenary IX: Ovary

Date and time: Tuesday, March 22, 2016 at 8:30 – 10:05 AM

Location: Hall A

Summary: In ovarian cancer, certain molecular mediators are thought to possess CSC characteristics and the presence of these mediators, which is linked to earlier recurrence and shorter survival, is possibly brought about by chemotherapy. The aim of this study was to explore the effect of chemotherapy on ovarian cancer stem-like mediators and to determine if there was a relationship to survival. Researchers obtained matched pre- and post-chemotherapy tumor specimens from stage IIIC/IV ovarian cancer patients (n=22) who all underwent neoadjuvant chemotherapy with interval debulking surgery. Samples were then analyzed for expression of 27 CSC markers. CSC markers were then validated in tumorsphere model and in vivo tumor initiating studies.

All 27 CSC markers demonstrated a mean increase in gene expression after exposure to chemotherapy. A 3-fold or greater increase in gene expression after exposure to chemotherapy was seen in 8 of 27 (30%) markers: ABCG2, ALDH1A1, CTGF, DPP4, MYC, CD133, SOX2, and POSTN. Three markers demonstrated a significant fold increase that correlated with platinum resistance: POSTN (4.1-fold), ALDH1A1 (5-fold), and SOX2 (14.5-fold). When implanted into immunocompromised mice, SOX2(hi) cells exhibited significantly higher levels of tumorsphere forming potential than SOX2(lo) cells and were more tumorigenic. High gene expression in these 3 markers demonstrated shorter progression free survival, compared to low expression. These results support the further investigation of directed agents to inhibit these CSC markers to potentially extend survival for patients with ovarian cancer.

A copy of the oral presentation will be available at http://bit.ly/R3M6wc