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 21, 2019 BioInvent International AB (OMXS: BINV), focused on the discovery and development of novel and first-in-class immuno-regulatory antibody-based medicines generated by its proprietary platforms, reported a comprehensive program to target TNFR2 for therapy of cancer (Press release, BioInvent, MAR 21, 2019, View Source [SID1234534525]). Using the n-CoDeR & F.I.R.S.T. platforms, the company has generated a broad panel of highly specific anti-TNFR2 antibodies, including the lead candidate antibody BI-1808, that may have broad utility in the treatment of solid cancers. BI-1808 is currently in preclinical development, and expected to enter clinical trials in the first half of 2020.

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Tumor necrosis factor 2 (TNFR2) is viewed as a highly promising receptor to target to overcome immune resistance in the tumor microenvironment. TNFR2 is found predominantly on regulatory T cells (Treg cells) in tumor tissue and has in several studies been associated with the most suppressive Treg cells. TNFR2 is known to play an important role both in the proliferation and function, as well as phenotypic stability of Treg cells. TNFR2 is also strongly associated with so called myeloid derived suppressor cells (MDSCs) in the tumor milieu and has been shown to both drive their accumulation and suppressive function. Its relatively selective expression together with its important function in the overall immune suppressive tumor microenvironment make TNFR2 a very compelling immune oncology target. Supporting preclinical data are expected to be submitted for publication in a peer-reviewed journal late 2019.

Björn Frendéus, CSO of BioInvent, said, "We believe targeting TNFR2 for cancer therapy holds great promise. Thanks to our proprietary n-CoDeR & F.I.R.S.T. platforms we have been able to generate first-in class anti-TNRF2 antibodies that are highly specific. We are pushing our first lead candidate BI-1808 towards the clinic, and are on track to commence clinical development in the first half of 2020."

On March 21, 2019 CStone Pharmaceuticals ("CStone"; HKEX: 2616) reported that China’s National Medical Products Administration (NMPA) has approved the clinical trial application to begin a Phase 1 trial in China for BLU-667 (CS3009), a highly selective and potent RET inhibitor discovered by CStone’s partner Blueprint Medicines (Press release, CStone Pharmaceauticals, MAR 21, 2019, View Source [SID1234534561]). The study is part of Blueprint Medicines’ ongoing, global Phase 1 ARROW clinical trial for patients with RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other advanced solid tumors. Trial objectives include overall clinical response, duration of response, pharmacokinetics, pharmacodynamics and safety.

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In June 2018, CStone and Blueprint Medicines entered into a license and collaboration agreement in which Blueprint Medicines granted CStone exclusive rights to develop and commercialize BLU-667 and two other drug candidates in Mainland China, Hong Kong, Macau and Taiwan.

Recently, BLU-667 was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of RET-mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Based on the early clinical data and regulatory feedback, Blueprint Medicines has announced plans to submit a New Drug Application (NDA) to the U.S. FDA for BLU-667 in the first half of 2020.

"BLU-667 has already demonstrated its potential to produce clinical responses in several RET-altered tumor types, and there are currently no selective RET inhibitors approved globally," noted CStone Chairman and CEO Dr. Frank Jiang. "If the data generated in Chinese patients are consistent with global results, we plan to use the global and China data from the ARROW study to support NDA filings in China."

CStone’s Chief Medical Officer Dr. Jason Yang commented: "Currently available data show that non-small cell lung cancer and medullary thyroid cancer patients with RET altered tumors may benefit from BLU-667, with the potential to advance standards of care in these genetically defined populations. We will move forward on development of BLU-667 in China and hope to make this drug candidate available to Chinese patients as quickly as possible."

About BLU-667

BLU-667 is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. In preclinical studies, BLU-667 consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, BLU-667 demonstrated markedly improved selectivity for RET compared to approved multi-kinase inhibitors, including more than 80-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, BLU-667 has the potential to overcome and prevent the emergence of clinical resistance. This approach is expected to enable durable clinical responses across the range of RET alterations, with a favorable safety profile.

BLU-667 was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. Blueprint Medicines is developing BLU-667 for the treatment of people with RET-altered NSCLC, MTC and other solid tumors. The U.S. FDA has granted Breakthrough Therapy Designation to BLU-667 for the treatment of RET-mutation-positive MTC.