On March 21, 2019 In an article published today by SAGE Publishing, investigators from The Nagourney Cancer Institute and The Albert Einstein Israelite Hospital in São Paulo, Brazil, reported a new approach to identifying effective treatments for patients with advanced metastatic cancers (Press release, Nagourney Cancer Institute, MAR 21, 2019, View Source [SID1234534558]). A drug commonly used to treat kidney and liver cancer was discovered effective for breast cancer, which may open new drug therapies to patients regardless of tumor type. The full article can be found at View Source

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The study reports the use of 3-dimensional-human-tumor derived organoids that were isolated directly from a patient’s drug resistant breast cancer. The drug identified, sorafenib (Nexavar), is widely used for the treatment of kidney and liver cancers but has not been found active, used, nor approved for patients with breast cancer.

"The finding of sorafenib activity was unexpected," said Dr. Robert Nagourney, one of the authors of the paper and the director for the laboratory where the studies were conducted.

When the patient with disease that had spread throughout her body had a near complete remission with only two months of oral therapy, a remission that lasted for over a year, the researchers examined possible mechanism for the response and believe that it reflects an entirely new form of cancer cell death known as "ferroptosis." This iron-mediated process of cancer cell death is uniquely activated by sorafenib.

"Of the many targeted drugs that we tested on the cancer cells from a woman who had few options remaining, it was only sorafenib that had this effect, prompting our colleagues in São Paulo to begin therapy immediately," said Dr. Nagourney. "We are fortunate to have fantastic collaborators in Brazil who tested this therapy to such good effect."

The results could not have been more dramatic as the patient showed compete metabolic response by PET/CT only weeks later.

"We are witness to a new concept in cancer medicine where drugs can be identified and selected for individual patients in the laboratory regardless of the tumor type, that is, breast versus kidney versus lung. Drugs do not know what disease for which they were invented," he added.

The drug selection technique employed by Dr. Nagourney was developed by scientists in his laboratory in California. It uses fresh biopsies removed directly from patients to study each cancer patient’s biology to select from amongst dozens of drugs and combinations, those that will work the best. This is but one more example of what is known as repurposing drugs, allowing physicians to outsmart cancers by going around their defenses.

"It is the availability of the EVA/PCD testing platform that for this first time is making it possible to make rational drug choices for cancer patients based upon each individual’s unique features," Nagourney concluded.

On March 21, 2019, MabVax Therapeutics Holdings, Inc. (the "Company") reported that it filed a voluntary petition for reorganization relief under Chapter 11 of Title 11 of the United States Bankruptcy Code (the "Bankruptcy Code") in the United States Bankruptcy Court for the District of Delaware (the "Bankruptcy Court") (Case No. 19-10603 (CSS)) (Press release, Blueprint Medicines, MAR 21, 2019, View Source [SID1234537257]). The Company continues to manage and operate its business as a debtor in possession pursuant to Bankruptcy Code Sections 1107 and 1108. The Company intends to sell substantially all of its assets pursuant to Section 363 of the Bankruptcy Code in the sixty days following the filing of its Chapter 11 petition under a Bankruptcy Court supervised sales process and, subject to sales proceeds and remaining assets, could convert its case to Chapter 7, at which point a Chapter 7 trustee will be appointed by the Bankruptcy Court.

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On March 21, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology corporation, reported its financial and operational results for year ending December 31, 2018 (Press release, IMV, MAR 21, 2019, View Source [SID1234534539]).

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"IMV made significant advances in 2018," said Frederic Ors, Chief Executive Officer. "Foundational changes, including shifting the name of the corporation to IMV and listing on Nasdaq, are enabling us to access to a larger pool of investors and allow us to better communicate our value proposition globally. However, the evolution of our clinical program is an even more important accomplishment: we entered into a collaboration with Merck across five tumor types; opted, based on DECIDE clinical data, to pursue DPX-Survivac as a monotherapy in ovarian cancer; and published studies clearly demarcating the T cell-activating novel mechanism of action of our DPX platform. With these milestones achieved, we are looking forward to a strong 2019 in which we will continue to advance our pipeline, drive value for investors, and support unmet patient needs."

IMV will host a conference call and webcast tomorrow at 8 a.m. ET. The dial-in number for the conference call is (844) 461-9932 (U.S. and Canada) or (636) 812-6632 (international) using the conference ID: 9647179. A live audio webcast will be available through IMV’s website on the ‘Events and Presentations’ page at View Source The webcast will be recorded and available on the IMV website for 30 days following the call.

Recent Clinical Updates & Expected Milestones

Phase 1b/2 DPX-Survivac monotherapy and combination trial in ovarian cancer (DECIDE)

The first 13 patients with advanced recurrent ovarian cancer have been enrolled in the phase 2 portion of the study. Six patients were randomized on DPX-Survivac monotherapy and seven were randomized on the DPX-Survivac/epacadostat combination. The Corporation is planning to provide an update on the preliminary clinical data by the end of Q1 2019.

Enrollment of an additional 15 patients in a population with lower tumor burden is ongoing and the corporation is planning to provide another clinical update on this cohort in Q2 2019.

Phase 2 Study in Combination with KEYTRUDA in Relapsed/Refractory DLBCL (SPIREL)

Seven patients have been enrolled and treated across four different clinical sites in Canada. Additional patients are being screened and IMV expects to report updated clinical data in Q2 2019.

Phase 2 Basket Trial in Combination with KEYTRUDA in Multiple Solid Tumors

Screening and enrollment of patients is ongoing at multiple clinical sites across the U.S. and Canada for patients with bladder, liver (hepatocellular carcinoma), ovarian, or non-small cell lung (NSCLC) cancers as well as tumors shown to be positive for the microsatellite instability high (MSI-H) biomarker. The first patients have been dosed in the ovarian and lung cancer cohorts. IMV expects to report preliminary clinical results on several of the solid tumor indications before the end of 2019.

2018 Highlights

Clinical Programs – DECIDE1/2 Advanced Ovarian Cancer Trial

Updated Phase 1b data shared via an oral presentation at the 2018 ASCO (Free ASCO Whitepaper) Meeting and topline data from the first two Phase 1b dosing cohorts highlighted at the 2018 ESMO (Free ESMO Whitepaper)-IO Meeting
Based on these data, IMV opted to develop DPX-Survivac as a monotherapy in certain ovarian cancer patients defined by BTB (baseline tumor burden), an indication of tumour size
Additional analyses were conducted that correlated DPX-Survivac’s novel MOA – the level of T cell infiltration – with clinical response
Met with the U.S. Food and Drug Administration (FDA) and submitted an updated DECIDE trial protocol; in addition, IMV discussed with the FDA the need for accelerated approvals in advanced ovarian cancer and received guidance on clinical design considerations for different lines of therapy and platinum-sensitive and resistant patients
Additional Clinical Highlights

First clinical data obtained from the combination of DPX-Survivac and mCPA with Keytruda (SPIREL Trial), which came from an investigator-sponsored phase 2 trial in patients with persistent or recurrent/refractory DLBCL; data from the combination signaled significant anti-cancer activity in three of the first four evaluable patients as well as a tolerable safety profile
Announced a collaboration with Merck in a phase 2 basket trial evaluating the safety and efficacy of DPX-Survivac, low-dose cyclophosphamide, and Keytruda (pembrolizumab) in patients with select advanced or recurrent solid tumors across five different indications: bladder, liver (hepatocellular carcinoma), ovarian, or non-small cell lung (NSCLC) cancers as well as tumors with the microsatellite instability high (MSI-H) biomarker
R&D Milestones

Research published in the Journal of Biomedical Science demonstrated the association between IMV’s proprietary immune-targeted delivery technology and enhanced efficacy in slowing tumor progression
New data presented at the 2018 AACR (Free AACR Whitepaper) Meeting highlighted the novel MOA underscoring the Corporation’s T cell-activating DPX technology and the potential for heightened anti-cancer activity of combination therapies based on IMV’s proprietary delivery platform
Operational Highlights:

Completion of two public offerings: In February 2018 and in March 2019 for a total of approximately $43.9 million
Nasdaq listing and share consolidation: IMV’s common shares commenced trading on the Nasdaq Stock Market LLC on June 1, 2018
Corporate name change: Because the MOA of DPX-based candidates signals a new class of immunotherapies that is differentiated from vaccines, IMV leadership changed the corporation’s name from Immunovaccine to IMV to better reflect the true potential of its therapeutic candidates
Addition of Julia P. Gregory and Dr. Markus Warmuth to the Corporation’s Board of Directors: Ms. Gregory is a seasoned biotechnology executive, having served as Chief Executive Officer and of ContraFect Corporation and the immuno-oncology company Five Prime. Dr. Warmuth brings to the Board more than 20 years of drug discovery experience with a strong focus on targeted therapy and immuno-oncology programs
Expansion of management team: IMV named Joseph Sullivan as the Corporation’s first Senior Vice-President, Business Development. Mr. Sullivan brings with him over 25 years of global pharmaceutical experience with Merck & Co. Inc. to IMV
Opening of new facility in Dartmouth, Nova Scotia: Nearly tripling the functional workspace, the new premises feature upgraded facilities and equipment as well as increased laboratory size to support long-term growth
Cash position: As of December 31, 2018, cash and cash equivalents and short-term investments were $14.9 million (excluding the $29.5 million financing completed in March 2019) compared to $14.9 million as of December 31, 2017
Overview of Year-End 2018 Financial Results

The net loss and comprehensive loss of $21,935,000 ($0.50 per share) the year ended December 31, 2018 was $9,908,000 higher than the net loss and comprehensive loss for the year ended December 31, 2017.

Research and development expenses increased by $6,914,000 for the year ended December 31, 2018, compared to 2017. These increases are mainly due to higher enrollment in the phase 1b/2 Incyte trial in ovarian cancer; milestone payments for the phase 2 study in DLBCL; and expenses related to the initiation of the basket trial. The increase is also attributable to manufacturing activities to support the increased clinical activity, which included purchasing raw materials and contract manufacturing organization costs.

General and administrative expenses increased by $2,039,000 for the year ended December 31, 2018 compared to 2017. This increase is mainly due to the various expenses related to the Nasdaq listing (legal, audit and consulting fees as well as listing fees) that are non-recurring expenses, the filing of a shelf prospectus, the increase in insurance premiums following the Nasdaq listing, consulting and professional fees, regulatory fees, the increase of the rent, lease interest accretion, and utilities related to the new facility.

Business development and investor relations expenses increased by $781,000 for the year ended December 31, 2018 compared to 2017. These increases are mainly explained by the hiring of a Senior Vice President, Business Development in January 2018 and a Senior Director of Investor Relations and Communications in November 2018.

At December 31, 2018, the Corporation had cash and cash equivalents of $14,895,000 (excluding the $29.5 million financing completed in March 2019) and working capital of $12,247,000, compared with $14,909,000 and $13,627,000, respectively at December 31, 2017. For the year ended December 31, 2018, IMV’s cash burn rate, defined as net loss for the period adjusted for operations not involving cash (interest on lease obligation, depreciation, accretion of long-term debt, stock-based compensation and DSU compensation), was $18.4 million. IMV expects research and development expenditures to increase over time due to the continuing development of product candidates and other clinical, preclinical, and regulatory activities.

As of March 21, 2019, the number of issued and outstanding common shares was 50,594,260 and a total of 2,008,057 stock options, warrants, and deferred share units were outstanding.

The Corporation’s audited annual consolidated results of operations, financial condition and cash flows for the year ended December 31, 2018 and the related management’s discussion and analysis (MD&A) are available on SEDAR at www.sedar.com and on EDGAR at www.sec.gov/edgar.

On March 20, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM), reported that preclinical data from the novel combination of its CD33 ARC or Antibody Radiation-Conjugate Actimab-A (lintzumab-Ac-225) with venetoclax has been accepted for poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), or AACR (Free AACR Whitepaper), Annual Meeting 2019 (Press release, Actinium Pharmaceuticals, MAR 20, 2019, View Source [SID1234534505]). The data to be presented builds on research by Actinium that demonstrated a synergy between Actimab-A and venetoclax, which resulted in greater cancer cell killing. This research supported the initiation of a Phase 1/2 doublet clinical trial studying Actimab-A and venetoclax and a planned Phase 1/2 triplet combination trial of Actimab-A and venetoclax with a hypomethylating agent, both for patients with relapsed or refractory AML or Acute Myeloid Leukemia. Actinium is conducting these trials with the goal of improving outcomes for patients with the addition of Actimab-A to address patients who do not respond, have suboptimal responses, no longer respond and patients who relapse after treatment with venetoclax.

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Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor jointly developed and marketed by AbbVie and Genentech. BCL-2 is one of several proteins encoded by the BCL2 gene that regulates apoptosis or programmed cell death. MCL-1 is another protein encoded by the BCL2 gene that has been found to be overexpressed in relapsed or refractory AML patients, that prevents apoptosis and promotes resistance to venetoclax which does not bind to MCL-1. It has been observed that MCL-1 levels can be depleted with radiation, but only external radiation was used in these studies. Actinium believes that the targeted internalized radiation from Actimab-A can more effectively deplete MCL-1 levels thereby removing the AML cells’ resistance mechanism and rendering them more susceptible to venetoclax. Actinium has filed a patent on the combination of a targeted alpha-emitting therapeutic such as Actimab-A together with a BCL-2 inhibitor, which includes venetoclax, as a method to treat cancer. The details on Actinium’s poster are as follows:

Title: 225Ac-CD33 Radioimmunotherapy potently increases the sensitivity of resistant acute myeloid leukemia lines to the Bcl-2 inhibitor venetoclax by mediating a reduction in cellular Mcl-1 levels

Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Resistance 5
Session Date and Time: Tuesday Apr 2, 2019 1:00 PM – 5:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 10
Poster Board Number: 13
Abstract Number: 3808

Dr. Dale Ludwig, Actinium’s Chief Scientific Officer said, "We are excited to present new data from this Actimab-A ARC and venetoclax combination to further support our recently initiated clinical study and prior work. We have high confidence in the mechanistic rationale of the Actimab-A and venetoclax combination and are encouraged by the results we have seen thus far. With radiation being used in the treatment of up to 60% of cancer patients and a growing body of literature supporting the synergies of radiation therapy with other modalities, we are motivated to capitalize on numerous opportunities that can leverage our AWE or Antibody Warhead Enabling technology platform to exploit radiation’s synergistic effects. Indeed, our AWE technology platform is a tool for innovation that has the potential to expand our pipeline and facilitate collaborations and partnerships."

Actimab-A delivers the potent alpha-particle emitting radioisotope Ac-225 or Actinium-225 to cells with the CD33 antigen, which is expressed in the vast majority of patients with AML, MDS or Myelodysplastic Syndrome, and 25-35% of patients with Multiple Myeloma, or MM. Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor that is jointly developed and marketed by AbbVie and Genentech that is approved for patients with AML, Chronic Lymphocytic Leukemia, and Small Lymphocytic Leukemia. Actinium has initiated a Phase 1/2 trial that is studying Actimab-A in combination with venetoclax for patients with relapsed or refractory AML and is planning a Phase 1/2 trial that is expected to study Actimab-A and venetoclax with a hypomethylating agent also for patients with relapsed or refractory AML.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "Our Actimab-A venetoclax combination trials are a strategic priority within our CD33 program that demonstrate our ability to rapidly translate research from our AWE technology platform to our clinical pipeline. Our preclinical data demonstrating a synergy between targeted radiation from Actimab-A and venetoclax, together with Actimab-A’s single agent activity and minimal extramedullary toxicities was well received by investigators, allowing us to develop two distinct clinical trials with this novel combination. As a result, we have created multiple opportunities to advance the treatment of patients with unmet needs with our ARC approach."

On March 20, 2019 PDC*line Pharma, a biotech company developing a new class of potent and scalable antigen presenting cell, based on a proprietary cell line of Plasmacytoid Dendritic cells (PDC*line), reported that it has signed an exclusive licensing and option agreement with LG Chem Life Sciences Company, the life sciences division of LG Chem Ltd (Press release, PDC Line Pharma, MAR 20, 2019, View Source [SID1234553824]). This agreement, which includes a development and commercialization collaboration agreement, opens new markets to PDC*line Pharma and expands the global footprint of its PDC*line-based cancer vaccine.

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Under the terms of the agreements, PDC*line Pharma will co-operate with LG Chem, who will have the full rights in South Korea and an exclusive option for other Asian countries, to develop and commercialize the company’s drug candidate, PDC*lung, in lung cancer. PDC*lung is constituted of a PDC*line loaded with HLA-A2 restricted peptides derived from six shared tumor antigens.

PDC*line Pharma is eligible for upfront and near-term milestone payments, plus longerterm clinical development and regulatory milestones totaling up to €108M ($123M). The company will also receive royalties based on net sales of the licensed product in LG Chem’s Asian markets.

Under the terms of the agreement, PDC*line Pharma will continue developing its PDC*lung candidate in the EU, US and global markets outside of Asia, and LG Chem will be responsible for future development and commercialization in its territories.

Eric Halioua, president & CEO of PDC*line Pharma, said: "We are very pleased to cooperate with LG Chem and to start the development of our PDC*lung cancer vaccine in Asia. This licensing agreement is a great opportunity for PDC*line Pharma to expand the scope of its immuno-oncology clinical programs and bring our technology to numerous patients around the world. Furthermore, the agreement with LG-Chem Life Sciences Company, a leading pharmaceutical company in Korea, is a major endorsement for our unique PDC*line approach and its potential."

Dr. Jeewoong Son, president of LG-Chem Life Sciences, said: " We are delighted to start this strategic collaboration with PDC*line Pharma, a great partnership to further expand LG Chem’s cell-based cancer immunotherapy portfolio. PDC*line Pharma’s technology is backed by cutting-edge science and we believe we can extend its reach by bringing this novel therapy to a greater number of cancer patients."