On April 2, 2019 Molecular Templates, Inc., (Nasdaq: MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), a new class of targeted biologic therapies that possess unique mechanisms of action in oncology, reported highlights from the four poster presentations on its pipeline programs that were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, taking place March 29 – Apr 3, 2019 at the Georgia World Congress Center in Atlanta, Georgia (Press release, Molecular Templates, APR 2, 2019, View Source [SID1234534887]). Copies of the posters presented at AACR (Free AACR Whitepaper) can be found in the Presentations section of Molecular Templates’ website at View Source

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"We believe that ETBs represent an important advance in immunotoxins as a therapeutic class of drugs. MT-3724 has demonstrated forced internalization of CD20 and has driven responses in heavily pretreated DLBCL patients. While MT-3724 development continues in Phase II, our presentations at AACR (Free AACR Whitepaper) highlight next generation pipeline programs that show key improvements in the ETB platform," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "These advances include enhanced potency, improved tolerability, potential to dose weekly or bi-weekly, and the ability to alter the immunophenotype of tumors through antigen seeding to redirect a T-cell response to the tumor."

Poster Title: TAK-169, an Exceptionally Potent CD38 Targeted Engineered Toxin Body, as a Novel Direct Cell Kill Approach for the Treatment of Multiple Myeloma
Poster highlights:

TAK-169 is able to efficiently internalize and directly kill CD38-expressing cells with potency seen at picomolar or sub-picomolar concentrations.
Preclinical data suggest that TAK-169 may provide benefit to patients who have progressed after or are unlikely to respond to CD38-targeted antibody therapy.
TAK-169 has demonstrated potent cytotoxicity across a range of myeloma cell lines with a range of CD38 expression in vitro as well as in patient-derived samples including those with previous exposure to daratumumab.
TAK-169 retains activity in the presence of daratumumab.
In xenograft models, complete regressions were observed using both once-weekly and bi-weekly schedules of TAK-169.
TAK-169 was tolerated in cynomolgus monkeys (highest non-severely toxic dose [HNSTD] of 750 mcg/kg weekly) at doses where evidence of pharmacodynamic effect (NK cell depletion) was observed. In comparison, the HNSTD of MT-3724 was 150 mcg/kg with visible signs of capillary leak syndrome (CLS); dosing MT-3724 at 450 mcg/kg showed severe CLS in cynomolgus monkeys.
Poster Title: The Safety and efficacy Profile of a PD-L1-Directed, Engineered Toxin Body, as a Novel Targeted Direct-Cell Kill Approach for the Treatment of PD-L1-Expressing Cancers
Poster highlights:

Molecular Templates has developed PD-L1-targeting ETBs as an approach to directly target tumor cells and overcome resistance mechanisms against PD-1 and PD-L1 antibodies.
MT-6020, a human and cynomolgus cross-reactive, PD-L1-targeted, ETB binds to cell lines expressing non-human primate PD-L1 and elicits cytotoxic responses comparable to those observed on human tumor target cells.
MT-6035 is built upon the MT-6020 scaffold and can also deliver a viral peptide for cell surface presentation and targeting by a specific antiviral CTL population for a second and complementary mechanism for tumor cell destruction, referred to as antigen seeding.
MT-6020 and MT-6035 represent a novel approach to targeting and destroying tumors expressing PD-L1 that is unlikely to be inhibited by resistance mechanisms to current checkpoint inhibitors, is well tolerated in relevant toxicity models, and has the capacity for activity in indications where standard of care has failed.
Poster Title: Combination of CD20-targeted Engineered Toxin Body, MT-3724, with Chemotherapy or IMiDs for the Treatment of Non-Hodgkin’s Lymphoma
Poster highlights:

MT-3724, a CD20-targeted ETB, has demonstrated single agent anti-tumor activity in heavily pre-treated relapsed/refractory (R/R) non-Hodgkin’s lymphoma (NHL) patients in a Phase I clinical study.
The combination of MT-3724 with chemotherapeutic agents (doxorubicin, gemcitabine, bendamustine, and vincristine) or an immunomodulatory (IMiD) agent (lenalidomide) all demonstrated additive or synergistic cytotoxicity of NHL cell lines.
Clinical studies to evaluate MT-3724 as single agent and in combination with gemcitabine and oxaliplatin (GEMOX) or lenalidomide are underway and expected to generate data in 2019.
Poster Title: Design and Characterization of Bispecific Engineered Toxin Bodies for Targeted Cancer Therapy
Poster highlights:

Bispecific ETBs that target two epitopes on the same receptor, or two distinct cell surface molecules both expressed on cancer cells, may allow for enhanced activity profiles. These possibilities include:
activity in the presence of a competitive binding protein
sustained activity when one target molecule is shed or downregulated
synergistic binding events to increase overall potency
increased specificity towards cancer over normal tissue.
Bispecific ETBs have been generated to engage a variety of target combinations, relevant to both solid and hematologic cancer treatment.
MTEM is exploring therapeutically relevant target combinations to facilitate the development of a bispecific clinical lead.

On April 2, 2019 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that the first patient treated with FT500 successfully completed an initial safety assessment (Press release, Fate Therapeutics, APR 2, 2019, View Source [SID1234534903]). The patient received three once weekly doses of FT500, and the treatment cycle was well-tolerated with no dose-limiting toxicities or serious adverse events reported during the initial 28-day observation period. The universal, off-the-shelf natural killer (NK) cell product candidate is the first-ever cell therapy derived from an induced pluripotent stem cell (iPSC) administered to a patient in the U.S.

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"The ability to effectively and efficiently deliver multiple doses of a cellular immunotherapy ‘on demand’ brings us closer to our goal of transforming the treatment of cancer for more patients. This initial observation of tolerability from the first-ever cancer patient to receive multiple doses of a universal, off-the-shelf cell product derived from a clonal master iPSC line provides early clinical validation of our proprietary iPSC product platform for off-the-shelf cancer immunotherapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "In addition to our clinical progress with FT500, our engineered iPSC-derived NK cell product candidates continue to exhibit a highly-differentiated therapeutic profile in preclinical models and we look forward to generating initial clinical data with FT516 and FT596 in 2019."

Two additional patients have also been treated with FT500 as a monotherapy in the first dose cohort of 1×108 cells per dose and are currently within the initial 28-day observation period. The FT500 clinical trial is a two-arm study in up to 64 patients for the treatment of advanced solid tumors. The study is designed to assess the safety and activity of three once weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved checkpoint inhibitor therapies – nivolumab, pembrolizumab or atezolizumab – in patients that have failed or have confirmed disease progression on checkpoint inhibitor therapy. Patients that are clinically stable following the initial 28-day observation period are eligible to receive a second treatment cycle.

FT516 Novel CD16 Receptor Promotes High-Affinity Engagement with Monoclonal Antibody Therapy
Today the Company presented preclinical data for FT516, its universal, off-the-shelf NK cell product candidate derived from a clonal master iPSC line engineered to express a novel CD16 Fc (hnCD16) receptor, at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Atlanta, Georgia. FT516 is the first-ever cell therapy derived from a genetically engineered pluripotent stem cell cleared for clinical testing in the world, and the Company is preparing to initiate clinical investigation of FT516 in the U.S. in patients with certain relapsed/refractory hematologic malignancies, including acute myelogenous leukemia as a monotherapy, non-Hodgkin’s lymphoma in combination with rituximab, and multiple myeloma in combination with elotuzumab.

While CD16 is naturally expressed on NK cells and mediates antibody-dependent cellular cytotoxicity, numerous clinical studies with FDA-approved tumor-targeting antibodies have demonstrated that patients with CD16 high-affinity variant 158V have improved clinical outcomes. However, only about 15% of humans are homozygous for 158V. Additionally, the expression of CD16 on NK cells in cancer patients can undergo considerable down-regulation, which significantly inhibits the cell’s anti-tumor activity. The novel CD16 Fc receptor expressed by FT516 has been designed to overcome these inherent deficiencies: it is comprised of the high-affinity 158V variant and is resistant to down-regulation.

In preclinical studies using a B-cell lymphoma line, the Company showed that approximately 70% of peripheral blood NK cells down-regulated CD16 expression upon co-culture with rituximab, while CD16 expression on FT516 remained resistant to down-regulation. These differences resulted in a significant anti-tumor benefit in vivo where, in a human lymphoma cancer model, mice treated with peripheral blood NK cells and rituximab had a median survival time of 39 days as compared to mice treated with FT516 and rituximab, where the median survival time was not yet reached at 100 days.

FT596 CAR and CD16 Modalities Exert Synergistic Anti-Tumor Activity
The Company also presented today at AACR (Free AACR Whitepaper) new preclinical data for FT596, the Company’s first iPSC-derived chimeric antigen receptor (CAR) NK cell product candidate that is designed to concurrently target multiple tumor-associated antigens. FT596 is derived from a clonal master iPSC line engineered to express a proprietary CAR targeting CD19, a hnCD16 Fc receptor, and a novel IL-15 receptor fusion.

In a mixed co-culture assay, the Company showed that the concurrent activation of the CAR and hnCD16 targeting modalities of FT596 exert synergistic anti-tumor activity. Increased degranulation (CD107a) and cytokine release (interferon-gamma and TNF-alfa) were observed upon concurrent activation of both the CAR and CD16 receptors in CD19+CD20+ Raji cancer cells with rituximab as compared to activation of each receptor alone, suggestive that dual antigen engagement may elicit a deeper and more durable response. Additionally, in a cellular cytotoxicity assay designed to model CD19 antigen escape, FT596 combined with rituximab was able to effectively eliminate leukemia and lymphoma cancer cells that were positive for CD19 antigen expression as well as those that were null for CD19 antigen expression.

About FT500
FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. FT500 is being investigated in an open-label, repeat-dose Phase 1 clinical trial for the treatment of advanced solid tumors in up to 64 patients, both as a monotherapy and in combination with FDA-approved checkpoint inhibitor therapy. Despite the favorable response rates observed with checkpoint inhibitor therapy, the majority of patients do not respond and many responders relapse. One common mechanism of resistance to checkpoint inhibitor therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations.

On April 2, 2019 AngioDynamics, Inc. (NASDAQ:ANGO), a leading provider of innovative, minimally invasive medical devices for vascular access, peripheral vascular disease, and oncology, reported financial results for the third quarter of fiscal year 2019, which ended February 28, 2019 (Press release, AngioDynamics, APR 2, 2019, View Source [SID1234534920]).

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"While we had pockets of softness in our financial performance during the third quarter, our overall performance remains strong, and we are confident that we will achieve our full-year guidance. We saw strong growth contributions during the quarter from AngioVac and Solero, as well as from Fluid Management," commented Jim Clemmer, President and Chief Executive Officer of AngioDynamics, Inc. "Additionally, I am very excited that the FDA has approved the IDE for our NanoKnife DIRECT Clinical Study, which is the next step toward this incredible technology improving the standard of care for patients afflicted with Stage III pancreatic cancer. The IDE approval also represents a milestone for AngioDynamics as we transform into an evidence-based Company focused on therapies and outcomes facilitated by our unique technologies."

Third Quarter 2019 Financial Results

Net sales for the third quarter of fiscal 2019 were $86.3 million, an increase of 3.0%, compared to $83.9 million a year ago. Foreign currency translation did not have a significant impact on the Company’s sales in the quarter.

Oncology net sales were $13.9 million, an increase of 15.1% from $12.1 million a year ago, as strong sales of Solero, as well as the recent BioSentry and RadiaDyne acquisitions, more than offset weaker than anticipated NanoKnife capital sales during the quarter.
Vascular Interventions and Therapies net sales in the third quarter of fiscal 2019 were $50.1 million, an increase of 3.3%, compared to $48.5 million a year ago, as strong growth in AngioVac was partially offset by a decelerating decline in the Venous Insufficiency business.
Vascular Access net sales were $22.3 million, a decrease of 4.0% from $23.3 million a year ago, as lower sales of midlines, PICCs, and ports were somewhat offset by strong dialysis sales.
U.S. net sales in the third quarter of fiscal 2019 were $68.3 million, an increase of 3.9% from $65.8 million a year ago, and International net sales were $18.0 million, a decrease of 0.3% from $18.1 million a year ago.

Gross margin for the third quarter of fiscal 2019 declined 10 basis points to 54.1% from 54.2% a year ago. This reflects temporary headwinds related to FX and a one-time positive impact from plant closures recognized last year. The Company continues to see gains in gross margin related to operational and supply-chain improvements.

The Company recorded net income of $0.8 million, or $0.02 per share, in the third quarter of fiscal 2019. This compares to net income of approximately $14.0 million, or $0.37 per share, a year ago.

Excluding the items shown in the non-GAAP reconciliation table below, adjusted net income for the third quarter of fiscal 2019 was $7.4 million, or $0.19 per share, compared to adjusted net income of $8.7 million, or $0.23 per share, in the third quarter of fiscal 2018.

Adjusted EBITDAS in the third quarter of fiscal 2019, excluding the items shown in the reconciliation table below, was $14.9 million, compared to $16.8 million in the third quarter of fiscal 2018.

In the third quarter of fiscal 2019, the Company generated $8.3 million in operating cash flow and had capital expenditures of $0.9 million. As of February 28, 2019, the Company had $41.7 million in cash and cash equivalents and $133.8 million in debt, excluding the impact of deferred financing costs.

Nine Months Financial Results

For the nine months ended February 28, 2019:

Net sales were $263.2 million, an increase of 2.8%, compared to $256.0 million for the same period a year ago.
The Company’s net income was $2.5 million, or $0.06 per share, compared to net income of $14.2 million, or $0.38 per share, a year ago.
Gross margin improved 270 basis points to 53.3% from 50.6% a year ago.
Excluding the items shown in the non-GAAP reconciliation table below, adjusted net income was $22.0 million, or $0.57 per share, compared to adjusted net income of $19.9 million, or $0.53 per share, a year ago.
Adjusted EBITDAS, excluding the items shown in the reconciliation table below, was $43.9 million, compared to $41.5 million for the same period a year ago.
Fiscal Year 2019 Financial Guidance

The Company reiterates its previously announced financial guidance, continuing to expect fiscal year 2019 net sales in the range of $354 to $359 million and free cash flow in the range of $26 to $31 million. Additionally, the Company continues to expect adjusted earnings per share in the range of $0.82 to $0.86.

Conference Call

The Company’s management will host a conference call today at 8:00 a.m. ET to discuss its third quarter 2019 results.

To participate in the conference call, dial 1-877-407-0784 (domestic) or 1-201-689-8560 (international) and refer to the passcode 13688664.

This conference call will also be webcast and can be accessed from the "Investors" section of the AngioDynamics website at www.angiodynamics.com. The webcast replay of the call will be available at the same site approximately one hour after the end of the call.

A recording of the call will also be available from 11:00 a.m. ET on Tuesday, April 2, 2019, until 11:59 p.m. ET on Tuesday, April 9, 2019. To hear this recording, dial 1-844-512-2921 (domestic) or 1-412-317-6671 (international) and enter the passcode 13688664.

Use of Non-GAAP Measures

Management uses non-GAAP measures to establish operational goals and believes that non-GAAP measures may assist investors in analyzing the underlying trends in AngioDynamics’ business over time. Investors should consider these non-GAAP measures in addition to, not as a substitute for or as superior to, financial reporting measures prepared in accordance with GAAP. In this news release, AngioDynamics has reported adjusted EBITDAS, adjusted net income, adjusted earnings per share and free cash flow. Management uses these measures in its internal analysis and review of operational performance. Management believes that these measures provide investors with useful information in comparing AngioDynamics’ performance over different periods. By using these non-GAAP measures, management believes that investors get a better picture of the performance of AngioDynamics’ underlying business. Management encourages investors to review AngioDynamics’ financial results prepared in accordance with GAAP to understand AngioDynamics’ performance taking into account all relevant factors, including those that may only occur from time to time but have a material impact on AngioDynamics’ financial results. Please see the tables that follow for a reconciliation of non-GAAP measures to measures prepared in accordance with GAAP.

On April 2, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that first patient has been dosed in Cohort 4, the pivotal cohort of the innovaTIL-01 (C-144-01) study of lifileucel (Press release, Iovance Biotherapeutics, APR 2, 2019, View Source;p=RssLanding&cat=news&id=2393137 [SID1234534888]). Cohort 4 is designed to enroll 75 patients with advanced melanoma.

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"Dosing of the first patient in Cohort 4, the pivotal arm of our melanoma program, is a significant step toward registration of TIL therapy," commented Maria Fardis, Ph.D., president and chief executive officer of Iovance. "Complete enrollment of this cohort is expected in early 2020 and we remain on track to file a Biologics License Application for regulatory approval of lifileucel in late 2020."

InnovaTIL-01 (NCT02360579) is a pivotal phase 2 global multicenter study evaluating the safety and efficacy of Iovance’s autologous lifileucel TIL therapy for treatment of patients with metastatic melanoma. The study is currently enrolling in the United States and Europe. To date, Iovance has activated 39 clinical sites in the United States and Europe. Additional information on this study is available at View Source

On April 2, 2019 Savara Inc. (NASDAQ:SVRA), an orphan lung disease company, reported that Rob Neville, Chief Executive Officer, will present at the H.C. Wainwright Global Life Sciences conference on Tuesday, April 9, 2019 at 1:50 PM GMT / 8:50 AM EST (Press release, Savara, APR 2, 2019, View Source [SID1234534904]). The conference will be held at the JW Marriott Grosvenor House London.

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Interested parties can access a live audio webcast on the Investors page of the Savara website at www.savarapharma.com/investors/events-presentations/. Please connect to the company’s website at least 15 minutes prior to the start of the presentation to ensure sufficient time for any software download that may be required for the webcast. An archived presentation will be available on Savara’s website for 30 days.