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 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 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer and other indications, reported the presentation of preclinical data for PRS-342, a GPC3/4-1BB immuno-oncology bispecific drug candidate, at a poster session at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Pieris Pharmaceuticals, APR 2, 2019, View Source [SID1234534885]).

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The poster, titled "Costimulatory T-cell engagement by PRS-342, a GPC3/4-1BB bispecific molecule, leads to activation of T cells and tumor growth inhibition in a HCC humanized mouse model," demonstrated that T-cell activation by PRS-342 led to NF-kB activation, increased production of IL-2 and dose-dependent cytolysis of GPC3-expressing tumor cells. PRS-342 also demonstrated a localized increase of tumor-infiltrating lymphocyte (TIL) levels in a humanized hepatocellular carcinoma (HCC) xenograft mouse model. The data presented suggest potent T-cell activation that is strictly dependent on the presence of GPC3-positive tumor cells. A copy of the poster presentation is available on the publications section of the Pieris website.

On April 2, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its CEO, Jan van de Winkel, Ph.D., will present a company update at the H.C. Wainwright & Co. Global Life Sciences Conference in London at 11:30 AM BST on April 9, 2019 (12:30 PM CEST) (Press release, Genmab, APR 2, 2019, https://ir.genmab.com/news-releases/news-release-details/genmab-present-hc-wainwright-co-global-life-sciences-conference [SID1234534883]). A webcast of the presentation will be available on Genmab’s website at View Source

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On April 2, 2019 NewLink Genetics Corporation (NASDAQ:NLNK) reported results from a Phase 2 study of NLG207, a nanoparticle formulation of the topoisomerase 1 inhibitor camptothecin, conducted in conjunction with The GOG Foundation, Inc. (GOG-3008), in patients with refractory ovarian cancer (Press release, NewLink Genetics, APR 2, 2019, View Source [SID1234534881]). The data were presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, Georgia.

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AACR Annual Meeting 2019 – April 2, 2019
Abstract CT151 A Phase 2 Study of NLG207 in Combination with Weekly Paclitaxel in Patients with Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer, Duska L, et al.

"We are encouraged by the responses observed in this Phase 2 trial of NLG207 in combination with weekly paclitaxel for patients with recurrent ovarian, fallopian tube or primary peritoneal cancer, with good results seen in the cohort of platinum resistant and refractory patients," said Linda R. Duska, MD, Professor of Obstetrics and Gynecology at the University of Virginia School of Medicine. "Equally encouraging is how well tolerated this regimen was in women who have already had multiple lines of therapy. The results from this trial demonstrate the potential for NLG207 as a component of a treatment regimen for women with recurrent ovarian cancer, especially for those resistant to platinum therapy, an area of unmet need."

Background:

NLG207 (formerly CRLX101), a nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase 1 inhibitor, was previously observed to have single agent activity in both preclinical1 and clinical studies.2 A previous Phase 2 trial evaluating NLG207 administered as monotherapy enrolled 29 patients with ovarian, fallopian tube, or primary peritoneal cancer, 22 of which were classified as platinum resistant. Of these 22 patients, 19 were evaluable for efficacy with follow-ups using computerized tomography (CT) scans performed every two cycles. Of these 19 evaluable patients, 17 (74%) demonstrated a net tumor reduction and three (16%) achieved durable partial responses per RECIST.2

In the study reported on today, NLG207 was administered in combination with paclitaxel to patients with recurrent ovarian, fallopian tube, or peritoneal cancer in a Phase 1b/2, single-arm, open label expansion study. Thirty patients were enrolled, and all received at least one cycle of treatment: 3 patients received the lower lead-in Phase 1b dosing schedule of 12 mg/m2 i.v. (every two weeks) plus weekly paclitaxel 80 mg/m2 i.v. (three weeks on, one week off) and 27 patients received the recommended Phase II dose NLG207 15 mg/m2 i.v. (every two weeks) plus weekly paclitaxel 80 mg/m2 i.v. (three weeks on, one week off). The primary objective of the study was overall response rate (ORR = complete response [CR] + partial response [PR]) per RECIST 1.1. Secondary objectives included evaluation of progression-free survival (PFS), PFS at 6 months (PFS6), and duration of response (DOR) in patients with recurrent platinum resistant cancer, and safety.

Results:

N = 30 patients, with all completing at least one cycle (27/30 at Phase 2 dosing schedule; 3/30 at lower lead-in Phase 1b dosing schedule)
57% received ≥ 3 prior therapies
ORR 26.7% (8/30) confirmed, including one CR
Median DOR was 6.0 months
Median PFS was 5.4 months
PFS6 was 41%
Patients with platinum resistant cancer: N = 17
ORR 23.5% (4/17) confirmed
Best response (including unconfirmed) 41.2% (7/17), all PRs
Stable disease (SD) 29.4% (5/17)
Patients with platinum sensitive cancer: N = 13
ORR 30.8% (4/13) confirmed and best response
SD 53.8% (7/13)
Most common treatment related grade 3 / 4 adverse events: decreased neutrophil count 43% (13/30), anemia 10% (3/30), hematuria 7% (2/30)
Conclusions:

NLG207 is a potentially best-in-class topoisomerase 1 inhibitor with demonstrated antitumor activity in recurrent ovarian cancer, including cancer resistant to platinum therapy. The combination therapy of NLG207 plus weekly paclitaxel was well tolerated in heavily pretreated patients with most adverse events consistent with those observed for paclitaxel as a single agent. Prior single agent activity observed in both preclinical and clinical studies, along with Phase 2 results in combination with paclitaxel reported here, support further investigation of NLG207 as a single agent and in combination treatment regimens for patients with recurrent ovarian, fallopian tube or primary peritoneal cancers, particularly those which are platinum resistant.

"We were excited by the single agent activity of NLG207 observed in prior trials and are encouraged by the Phase 2 data presented today at AACR (Free AACR Whitepaper) that support the potential for this drug candidate to improve upon current therapies in ovarian cancer, particularly given its favorable safety profile," said Charles J. Link, Jr, MD, Chairman and Chief Executive Officer of NewLink Genetics. "We wish to thank the patients, their families, and the investigators who participated in this trial as we continue our efforts to better the lives of individuals suffering from cancer."

Abstract CT151 (Poster 17) entitled, A phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer, Duska, L., et al, was presented during the poster session entitled, "Phase II-III Clinical Trials: Part 1," in Exhibit Hall B, Poster Section 16 from 8:00 a.m. – 12:00 p.m. ET. The poster presentation is also available on NewLink Genetics’ website in the "Investors & Media" section, under "Posters & Publications."

1 Pham E, et al. Clin Can Res.2014; 21(4); 808–18.
Lin CJ, et al. Oncotarget.2016 Jul 5;7(27):42408-42421.

2 Pham E, et al. Clin Can Res. 2014; 21(4); 808-818.
Weiss GJ, et al. Invest New Drugs. 2013;31:986-1000.
Krasner CN, wet al. J Clin Oncol. 2014; 32:Abstract 5581.
About NLG207

NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone conjugated to camptothecin, a topoisomerase 1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. Topoisomerase 1 inhibitors are a class of drugs that modify DNA damage responses in cancer cells. NewLink Genetics is evaluating NLG207 in a series of clinical trials in advanced refractory ovarian cancer patients.